Reduction of NADPH-oxidase activity ameliorates the cardiovascular phenotype in a mouse model of Williams-Beuren Syndrome.

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Victoria Campuzano

2012-02-01

Full Text Available A hallmark feature of Williams-Beuren Syndrome (WBS is a generalized arteriopathy due to elastin deficiency, presenting as stenoses of medium and large arteries and leading to hypertension and other cardiovascular complications. Deletion of a functional NCF1 gene copy has been shown to protect a proportion of WBS patients against hypertension, likely through reduced NADPH-oxidase (NOX-mediated oxidative stress. DD mice, carrying a 0.67 Mb heterozygous deletion including the Eln gene, presented with a generalized arteriopathy, hypertension, and cardiac hypertrophy, associated with elevated angiotensin II (angII, oxidative stress parameters, and Ncf1 expression. Genetic (by crossing with Ncf1 mutant and/or pharmacological (with ang II type 1 receptor blocker, losartan, or NOX inhibitor apocynin reduction of NOX activity controlled hormonal and biochemical parameters in DD mice, resulting in normalized blood pressure and improved cardiovascular histology. We provide strong evidence for implication of the redox system in the pathophysiology of the cardiovascular disease in a mouse model of WBS. The phenotype of these mice can be ameliorated by either genetic or pharmacological intervention reducing NOX activity, likely through reduced angII-mediated oxidative stress. Therefore, anti-NOX therapy merits evaluation to prevent the potentially serious cardiovascular complications of WBS, as well as in other cardiovascular disorders mediated by similar pathogenic mechanism.

The continuum of monocyte phenotypes: Experimental evidence and prognostic utility in assessing cardiovascular risk.

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Cignarella, Andrea; Tedesco, Serena; Cappellari, Roberta; Fadini, Gian Paolo

2018-03-30

The monocyte-macrophage cell lineage represents a major player in innate immunity, and is involved in many physiologic and pathologic conditions. Particularly, monocyte-macrophages play a very important role in atherosclerosis and cardiovascular disease. Monocyte heterogeneity is well recognized but the biologic and clinical meaning of the various monocyte subtypes is not entirely understood. Traditionally, monocytes can be divided in classical, intermediate, and nonclassical based on expression of the surface antigens CD14 and CD16. While macrophage diversity is now well recognized to organize as a continuum, monocyte subsets have long been considered as separated entities. However, mounting evidence obtained by tracking the ontology of human monocytes help clarifying that monocytes mature from classical to nonclassical ones, through an intermediate phenotype. This concept is therefore best depicted as a continuum, whereas the subdivision into discrete CD14/CD16 subsets appears an oversimplification. In this review, we discuss the evidence supporting the existence of a monocyte continuum along with the technical challenges of monocyte characterization. In particular, we describe the advantage of considering monocytes along a continuous distribution for the evaluation of cardiovascular risk. We make the point that small transition along the monocyte continuum better reflects cardiovascular risk than a simplified analysis of discrete monocyte subsets. Recognizing the monocyte continuum can be helpful to model other pathophysiologic conditions where these cells are involved. ©2018 Society for Leukocyte Biology.

Longitudinal and transverse right ventricular function in pulmonary hypertension: cardiovascular magnetic resonance imaging study from the ASPIRE registry.

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Swift, Andrew J; Rajaram, Smitha; Capener, Dave; Elliot, Charlie; Condliffe, Robin; Wild, Jim M; Kiely, David G

2015-09-01

Right ventricular (RV) function is a strong predictor of outcome in cardiovascular diseases. Two components of RV function, longitudinal and transverse motion, have been investigated in pulmonary hypertension (PH). However, their individual clinical significance remains uncertain. The aim of this study was to determine the factors associated with transverse and longitudinal RV motion in patients with PH. In 149 treatment-naive patients with PH and 16 patients with suspected PH found to have mean pulmonary arterial pressure of transverse motion (fractional septum to free wall distance [f-SFD]; P = 0.002). In patients without PH, no significant difference between f-SFD and f-TAAD was identified (P = 0.442). Longitudinal RV motion was singularly associated with RV ejection fraction independent of age, invasive hemodynamics, and cardiac magnetic resonance measurements (P = 0.024). In contrast, transverse RV motion was independently associated with left ventricular eccentricity (P = 0.036) in addition to RV ejection fraction (P = 0.014). In conclusion, RV motion is significantly greater in the longitudinal direction in patients with PH, whereas patients without PH have equal contributions of transverse and longitudinal motion. Longitudinal RV motion is primarily associated with global RV pump function in PH. Transverse RV motion not only reflects global pump function but is independently influenced by ventricular interaction in patients with PH.

CardioBengo study protocol: a population based cardiovascular longitudinal study in Bengo Province, Angola

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João M. Pedro

2016-03-01

regions and countries, this study will constitute a useful tool for the surveillance of cardiovascular diseases. Like all longitudinal studies, a strong concern exists regarding dropouts, but strategies like regular visits to selected participants and a strong community involvement are in place to minimize these occurrences.

CardioBengo study protocol: a population based cardiovascular longitudinal study in Bengo Province, Angola.

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Pedro, João M; Rosário, Edite; Brito, Miguel; Barros, Henrique

2016-03-01

the surveillance of cardiovascular diseases. Like all longitudinal studies, a strong concern exists regarding dropouts, but strategies like regular visits to selected participants and a strong community involvement are in place to minimize these occurrences.

Cardiovascular events and mortality in patients with adrenal incidentalomas that are either non-secreting or associated with intermediate phenotype or subclinical Cushing's syndrome: a 15-year retrospective study.

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Di Dalmazi, Guido; Vicennati, Valentina; Garelli, Silvia; Casadio, Elena; Rinaldi, Eleonora; Giampalma, Emanuela; Mosconi, Cristina; Golfieri, Rita; Paccapelo, Alexandro; Pagotto, Uberto; Pasquali, Renato

2014-05-01

Incidental discovery of adrenal masses has increased over the past few years. Mild alterations in cortisol secretion without clinical signs of overt hypercortisolism (subclinical Cushing's syndrome) are a common finding in patients with these tumours. Although metabolic alterations and increased cardiovascular risk have been noted in patients with subclinical Cushing's syndrome, incidence of cardiovascular events and mortality in the long term have not been assessed. We aimed to ascertain the frequency of new cardiovascular events and mortality in patients with non-secreting adrenal incidentalomas, tumours of intermediate phenotype, or those causing subclinical Cushing's syndrome. From January, 1995, to September, 2010, consecutive outpatients with adrenal incidentalomas who were referred to the endocrinology unit of S Orsola-Malpighi Hospital, Bologna, Italy, were enrolled into our study. Individuals were assessed every 18-30 months for the first 5 years (mean follow-up 7·5 [SD 3·2] years, range 26 months to 15 years). Cortisol concentrations after the 1 mg dexamethasone suppression test (DST) were used to define non-secreting (+50 nmol/L) and intermediate phenotype (50-138 nmol/L) adrenal incidentalomas and subclinical Cushing's syndrome (+138 nmol/L). At the end of follow-up, patients were reclassified as having either unchanged or worsened secreting patterns from baseline. 198 outpatients were assessed; at the end of follow-up, 114 patients had stable non-secreting adrenal incidentalomas, 61 had either a stable intermediate phenotype or subclinical Cushing's syndrome, and 23 had a pattern of secretion that had worsened. By comparison with patients with stable non-secreting adrenal incidentalomas, the incidence of cardiovascular events was higher in individuals with a stable intermediate phenotype or subclinical Cushing's syndrome (6·7% vs 16·7%; p=0·04) and in those with worsened secreting patterns (6·7% vs 28·4%; p=0·02). Cardiovascular events were

The nature of stable insomnia phenotypes.

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Pillai, Vivek; Roth, Thomas; Drake, Christopher L

2015-01-01

We examined the 1-y stability of four insomnia symptom profiles: sleep onset insomnia; sleep maintenance insomnia; combined onset and maintenance insomnia; and neither criterion (i.e., insomnia cases that do not meet quantitative thresholds for onset or maintenance problems). Insomnia cases that exhibited the same symptom profile over a 1-y period were considered to be phenotypes, and were compared in terms of clinical and demographic characteristics. Longitudinal. Urban, community-based. Nine hundred fifty-four adults with Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition based current insomnia (46.6 ± 12.6 y; 69.4% female). None. At baseline, participants were divided into four symptom profile groups based on quantitative criteria. Follow-up assessment 1 y later revealed that approximately 60% of participants retained the same symptom profile, and were hence judged to be phenotypes. Stability varied significantly by phenotype, such that sleep onset insomnia (SOI) was the least stable (42%), whereas combined insomnia (CI) was the most stable (69%). Baseline symptom groups (cross-sectionally defined) differed significantly across various clinical indices, including daytime impairment, depression, and anxiety. Importantly, however, a comparison of stable phenotypes (longitudinally defined) did not reveal any differences in impairment or comorbid psychopathology. Another interesting finding was that whereas all other insomnia phenotypes showed evidence of an elevated wake drive both at night and during the day, the 'neither criterion' phenotype did not; this latter phenotype exhibited significantly higher daytime sleepiness despite subthreshold onset and maintenance difficulties. By adopting a stringent, stability-based definition, this study offers timely and important data on the longitudinal trajectory of specific insomnia phenotypes. With the exception of daytime sleepiness, few clinical differences are apparent across stable phenotypes. �

Circulating brain-derived neurotrophic factor and indices of metabolic and cardiovascular health: data from the Baltimore Longitudinal Study of Aging.

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Erin Golden

2010-04-01

Full Text Available Besides its well-established role in nerve cell survival and adaptive plasticity, brain-derived neurotrophic factor (BDNF is also involved in energy homeostasis and cardiovascular regulation. Although BDNF is present in the systemic circulation, it is unknown whether plasma BDNF correlates with circulating markers of dysregulated metabolism and an adverse cardiovascular profile.To determine whether circulating BDNF correlates with indices of metabolic and cardiovascular health, we measured plasma BDNF levels in 496 middle-age and elderly subjects (mean age approximately 70, in the Baltimore Longitudinal Study of Aging. Linear regression analysis revealed that plasma BDNF is associated with risk factors for cardiovascular disease and metabolic syndrome, regardless of age. In females, BDNF was positively correlated with BMI, fat mass, diastolic blood pressure, total cholesterol, and LDL-cholesterol, and inversely correlated with folate. In males, BDNF was positively correlated with diastolic blood pressure, triglycerides, free thiiodo-thyronine (FT3, and bioavailable testosterone, and inversely correlated with sex-hormone binding globulin, and adiponectin.Plasma BDNF significantly correlates with multiple risk factors for metabolic syndrome and cardiovascular dysfunction. Whether BDNF contributes to the pathogenesis of these disorders or functions in adaptive responses to cellular stress (as occurs in the brain remains to be determined.

Preeclampsia, prematurity and cardiovascular health in adult life.

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Lewandowski, Adam J; Leeson, Paul

2014-11-01

Investigations into how perinatal growth and intrauterine environment may 'programme' risk of later cardiovascular disease have been ongoing for over two decades. One of the more recent outcomes of these studies is the observation that certain pregnancy-related conditions, such as preterm birth, have an unusually large impact on the long-term cardiovascular health of the offspring. In the present paper, we review the current literature of how preterm birth affects the long-term cardiovascular structure and function of the offspring, considering three major areas of investigation: firstly, outlining the long-term cardiovascular phenotypic changes in preterm-born individuals; secondly, investigating factors related to preterm birth that may be modifying cardiovascular phenotype, such as preeclampsia, perinatal interventions, and physiological disturbances; and thirdly, the expected clinical relevance of these cardiovascular changes. This review discusses the importance of continued research focused on the mechanistic understanding of these cardiovascular alterations in order to develop specific primary prevention strategies. Copyright © 2014 Elsevier Ltd. All rights reserved.

The Nature of Stable Insomnia Phenotypes

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Pillai, Vivek; Roth, Thomas; Drake, Christopher L.

2015-01-01

Study Objectives: We examined the 1-y stability of four insomnia symptom profiles: sleep onset insomnia; sleep maintenance insomnia; combined onset and maintenance insomnia; and neither criterion (i.e., insomnia cases that do not meet quantitative thresholds for onset or maintenance problems). Insomnia cases that exhibited the same symptom profile over a 1-y period were considered to be phenotypes, and were compared in terms of clinical and demographic characteristics. Design: Longitudinal. Setting: Urban, community-based. Participants: Nine hundred fifty-four adults with Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition based current insomnia (46.6 ± 12.6 y; 69.4% female). Interventions: None. Measurements and results: At baseline, participants were divided into four symptom profile groups based on quantitative criteria. Follow-up assessment 1 y later revealed that approximately 60% of participants retained the same symptom profile, and were hence judged to be phenotypes. Stability varied significantly by phenotype, such that sleep onset insomnia (SOI) was the least stable (42%), whereas combined insomnia (CI) was the most stable (69%). Baseline symptom groups (cross-sectionally defined) differed significantly across various clinical indices, including daytime impairment, depression, and anxiety. Importantly, however, a comparison of stable phenotypes (longitudinally defined) did not reveal any differences in impairment or comorbid psychopathology. Another interesting finding was that whereas all other insomnia phenotypes showed evidence of an elevated wake drive both at night and during the day, the “neither criterion” phenotype did not; this latter phenotype exhibited significantly higher daytime sleepiness despite subthreshold onset and maintenance difficulties. Conclusions: By adopting a stringent, stability-based definition, this study offers timely and important data on the longitudinal trajectory of specific insomnia phenotypes. With

Cardiovascular and metabolic profiles amongst different polycystic ovary syndrome phenotypes: who is really at risk?

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Daan, Nadine M P; Louwers, Yvonne V; Koster, Maria P H; Eijkemans, Marinus J C; de Rijke, Yolanda B; Lentjes, Eef W G; Fauser, Bart C J M; Laven, Joop S E

2014-11-01

To study the cardiometabolic profile characteristics and compare the prevalence of cardiovascular (CV) risk factors between women with different polycystic ovary syndrome (PCOS) phenotypes. A cross-sectional multicenter study analyzing 2,288 well phenotyped women with PCOS. Specialized reproductive outpatient clinic. Women of reproductive age (18-45 years) diagnosed with PCOS. Women suspected of oligo- or anovulation underwent a standardized screening consisting of a systematic medical and reproductive history taking, anthropometric measurements, and transvaginal ultrasonography followed by an extensive endocrinologic/metabolic evaluation. Differences in cardiometabolic profile characteristics and CV risk factor prevalence between women with different PCOS phenotypes, i.e., obesity/overweight, hypertension, insulin resistance, dyslipidemia, and metabolic syndrome. Women with hyperandrogenic PCOS (n=1,219; 53.3% of total) presented with a worse cardiometabolic profile and a higher prevalence of CV risk factors, such as obesity and overweight, insulin resistance, and metabolic syndrome, compared with women with nonhyperandrogenic PCOS. In women with nonhyperandrogenic PCOS overweight/obesity (28.5%) and dyslipidemia (low-density lipoprotein cholesterol≥3.0 mmol/L; 52.2%) were highly prevalent. Women with hyperandrogenic PCOS have a worse cardiometabolic profile and higher prevalence of CV risk factors compared with women with nonhyperandrogenic PCOS. However, all women with PCOS should be screened for the presence of CV risk factors, since the frequently found derangements at a young age imply an elevated risk for the development of CV disease later in life. Copyright © 2014 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Association of heme oxygenase-1 GT-repeat polymorphism with blood pressure phenotypes and its relevance to future cardiovascular mortality risk: an observation based on arsenic-exposed individuals.

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Wu, Meei-Maan; Chiou, Hung-Yi; Chen, Chi-Ling; Hsu, Ling-I; Lien, Li-Ming; Wang, Chih-Hao; Hsieh, Yi-Chen; Wang, Yuan-Hung; Hsueh, Yu-Mei; Lee, Te-Chang; Cheng, Wen-Fang; Chen, Chien-Jen

2011-12-01

Heme oxygenase (HO)-1 is up-regulated as a cellular defense responding to stressful stimuli in experimental studies. A GT-repeat length polymorphism in the HO-1 gene promoter was inversely correlated to HO-1 induction. Here, we reported the association of GT-repeat polymorphism with blood pressure (BP) phenotypes, and their interaction on cardiovascular (CV) mortality risk in arsenic-exposed cohorts. Associations of GT-repeat polymorphism with BP phenotypes were investigated at baseline in a cross-sectional design. Effect of GT-repeat polymorphism on CV mortality was investigated in a longitudinal design stratified by hypertension. GT-repeat variants were grouped by S (accounting for CV covariates. Totally, 894 participants were recruited and analyzed. At baseline, carriers with HO-1 S alleles had lower diastolic BP (L/S genotypes, P = 0.014) and a lower possibility of being hypertensive (L/S genotypes, P = 0.048). After follow-up, HO-1 S allele was significantly associated with a reduced CV risk in hypertensive participants [relative mortality ratio (RMR) 0.27 (CI 0.11, 0.69), P = 0.007] but not in normotensive. Hypertensive participants without carrying the S allele had a 5.23-fold increased risk [RMR 5.23 (CI 1.99, 13.69), P = 0.0008] of CV mortality compared with normotensive carrying the S alleles. HO-1 short GT-repeat polymorphism may play a protective role in BP regulation and CV mortality risk in hypertensive individuals against environmental stressors. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Excess Metabolic and Cardiovascular Risk is not Manifested in all Phenotypes of Polycystic Ovary Syndrome: Implications for Diagnosis and Treatment.

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Daskalopoulos, Georgios; Karkanaki, Artemis; Piouka, Athanasia; Prapas, Nikolaos; Panidis, Dimitrios; Gkeleris, Paraschos; Athyros, Vasilios G

2015-01-01

To assess the potential differences in the metabolic and cardiovascular disease (CVD) risk between the distinct phenotypes of the Polycystic Ovary Syndrome (PCOS) according to the Rotterdam definition regardless of body mass index (BMI). The study included 300 women; 240 women with PCOS, according to the Rotterdam criteria and 60 controls without PCOS. All women were further subdivided, according to their BMI, into normal-weight and overweight/obese and PCOS women were furthermore subdivided to the 4 phenotypes of the syndrome. A complete hormonal and metabolic profile as well as the levels of high sensitivity C reactive protein (hsCRP) and lipoprotein-associated phospholipase A2 (Lp-PLA2) were measured. Levels of surrogate markers of subclinical atherosclerosis (hsCRP and Lp-PLA2), levels of evaluated CVD risk score using risk engines, and several correlations of CVD risk factors. hsCRP levels were higher but not significantly so in PCOS women compared with controls. In lean PCOS patients, Lp-PLA2 levels were significantly higher, compared with lean controls, mainly in the 2 classic phenotypes. Overweight/obese patients in all 4 phenotypes had significantly higher Lp-PLA2 levels compared with overweight/obese controls. Evaluated CVD risk according to 4 risk engines was not different among phenotypes and between PCOS patients and controls. There were several correlations of risk factors with metabolic syndrome and non-alcoholic fatty liver disease requiring appropriate treatment. Only 2 of 4 Rotterdam phenotypes, identical with those of the classic PCOS definition, have excess cardiometabolic risk. These need to be treated to prevent CVD events.

Oxidative stress and hemoglobin-cholesterol adduct in renal patients with different LDL phenotypes.

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Miljkovic, Milica; Kotur-Stevuljevic, Jelena; Stefanovic, Aleksandra; Zeljkovic, Aleksandra; Vekic, Jelena; Gojkovic, Tamara; Bogavac-Stanojevic, Natasa; Nikolic, Milan; Simic-Ogrizovic, Sanja; Spasojevic-Kalimanovska, Vesna; Jelic-Ivanovic, Zorana

2016-10-01

Unfavorable lipid profile is a major risk factor for cardiovascular disease in renal pathology. In this study, we compared chronic renal patients and healthy controls with different LDL phenotypes (A or B) in respect of various biochemical parameters related to cardiovascular disease. Oxidative stress and anti-oxidative defense parameters [thiobarbituric acid-reacting substances (TBARS), total oxidative status (TOS), total anti-oxidative status (TAS), total protein sulfhydryl (-SH) groups], as well as red blood cell cholesterol distribution were assessed in 40 renal patients and 40 control subjects by standardized assays. LDL particle diameters were determined by polyacrylamide gradient gel electrophoresis. LDL particles are subdivided according to their size into large LDL A phenotype (diameter >25.5 nm) and small LDL B phenotype (diameter ≤25.5 nm). Renal patients with LDL A phenotype had increased oxidative stress (TOS: p LDL phenotype. A notable decrease in hemoglobin-cholesterol adduct was detected in patients with LDL A phenotype (p LDL B phenotype (p LDL B phenotype was characterized with increased TBARS (p LDL A phenotype in control group. Increased oxidative stress, decreased anti-oxidative defense followed with unfavorable changes in hemoglobin-cholesterol binding capacity, could have important influence on cardiovascular disease risk in renal patients regardless of LDL phenotype.

Ultra-high frequency ultrasound biomicroscopy and high throughput cardiovascular phenotyping in a large scale mouse mutagenesis screen

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Liu, Xiaoqin; Francis, Richard; Tobita, Kimimasa; Kim, Andy; Leatherbury, Linda; Lo, Cecilia W.

2013-02-01

Ultrasound biomicroscopy (UBM) is ideally suited for phenotyping fetal mice for congenital heart disease (CHD), as imaging can be carried out noninvasively to provide both hemodynamic and structural information essential for CHD diagnosis. Using the UBM (Vevo 2100; 40Hz) in conjunction with the clinical ultrasound system (Acuson Sequioa C512; 15Hz), we developed a two-step screening protocol to scan thousands fetuses derived from ENU mutagenized pedigrees. A wide spectrum of CHD was detected by the UBM, which were subsequently confirmed with follow-up necropsy and histopathology examination with episcopic fluorescence image capture. CHD observed included outflow anomalies, left/right heart obstructive lesions, septal/valvular defects and cardiac situs anomalies. Meanwhile, various extracardiac defects were found, such as polydactyly, craniofacial defects, exencephaly, omphalocele-cleft palate, most of which were associated with cardiac defects. Our analyses showed the UBM was better at assessing cardiac structure and blood flow profiles, while conventional ultrasound allowed higher throughput low-resolution screening. Our study showed the integration of conventional clinical ultrasound imaging with the UBM for fetal mouse cardiovascular phenotyping can maximize the detection and recovery of CHD mutants.

Longitudinal Patterns of Change in Systolic Blood Pressure and Incidence of Cardiovascular Disease: The Atherosclerosis Risk in Communities Study.

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Petruski-Ivleva, Natalia; Viera, Anthony J; Shimbo, Daichi; Muntner, Paul; Avery, Christy L; Schneider, Andrea L C; Couper, David; Kucharska-Newton, Anna

2016-06-01

Elevated blood pressure in midlife contributes significantly to the risk of cardiovascular disease. However, patterns of blood pressure increase may differ among individuals and may result in differential risk. Our goal was to examine the contribution of longitudinal patterns of blood pressure change to incidence of heart failure, coronary heart disease, stroke, and cardiovascular disease mortality. Latent class growth models were used to identify patterns of change in blood pressure across 4 clinical examinations (1987-1998) among 9845 Atherosclerosis Risk in Communities (ARIC) cohort participants (mean age, 53.7 [SD 5.7] years). Patterns of change in systolic blood pressure included slowly and steeply increasing, a decreasing and a sustained elevated blood pressure. Changes in diastolic and mid-blood pressure (½ systolic+½ diastolic) were less pronounced. The association of blood pressure pattern group membership with incidence of clinical outcomes was examined in follow-up from the fourth clinical examination (1996-1998) to December 31, 2011, using Poisson regression models adjusted for demographic and metabolic characteristics, and hypertension medication use. A gradient of rates of all events was observed across the identified patterns. Associations were attenuated after adjustment for covariates. Cumulative systolic blood pressure load, rather than the temporal pattern of change in systolic blood pressure itself, plays a role in determining the risk of cardiovascular disease, in particular, of heart failure and cardiovascular disease mortality, independent of blood pressure level measured at one point in time. © 2016 American Heart Association, Inc.

Women with polycystic ovary syndrome demonstrate worsening markers of cardiovascular risk over the short-term despite declining hyperandrogenaemia: Results of a longitudinal study with community controls.

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Huddleston, Heather G; Quinn, Molly M; Kao, Chia-Ning; Lenhart, Nikolaus; Rosen, Mitchell P; Cedars, Marcelle I

2017-12-01

To compare age-associated changes in cardiovascular risk markers in lean and obese reproductive-aged women with polycystic ovary syndrome (PCOS) with community controls. Longitudinal study at an academic medical centre PATIENTS: Patients diagnosed with PCOS by 2004 Rotterdam criteria in a multidisciplinary clinic were systematically enrolled from 2006-2014 in a PCOS cohort study and subsequently agreed to participate in a longitudinal study. The comparison controls were from the prospective, longitudinal Ovarian Aging (OVA) study, which consists of healthy women with regular menstrual cycles recruited from 2006 to 2011. Cardiovascular risk markers and hormone parameters at baseline and follow-up. Obese and lean PCOS (n = 38) and control women (n = 296) completed two study visits. The follow-up time (3.5 ± 1.5 vs 4.0 ± 0.8 years, P = .06) and magnitude of BMI gain (+0.1 kg/m 2 /y [-0.11, 0.36] vs +0.26 [-0.18, 0.87] P = .19) did not differ between obese and lean PCOS and controls. In PCOS subjects, total testosterone decreased in both obese and lean, but the decrease was greater in obese subjects (-0.09 nmol/L per year; 95% CI: -0.16, -0.02 vs -0.04 nmol/L per year; 95%CI: -0.11, 0.03). Compared to their respective controls, obese and lean PCOS saw worsening triglyceride (TG) levels (P women with PCOS demonstrated declines in biochemical hyperandrogenaemia over time. Despite this, PCOS subjects experienced steeper increases in cardiovascular risk factors associated with insulin resistance, including triglycerides and HOMA-IR. © 2017 John Wiley & Sons Ltd.

Selenistasis: Epistatic Effects of Selenium on Cardiovascular Phenotype

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Joseph Loscalzo

2013-01-01

Full Text Available Although selenium metabolism is intricately linked to cardiovascular biology and function, and deficiency of selenium is associated with cardiac pathology, utilization of selenium in the prevention and treatment of cardiovascular disease remains an elusive goal. From a reductionist standpoint, the major function of selenium in vivo is antioxidant defense via its incorporation as selenocysteine into enzyme families such as glutathione peroxidases and thioredoxin reductases. In addition, selenium compounds are heterogeneous and have complex metabolic fates resulting in effects that are not entirely dependent on selenoprotein expression. This complex biology of selenium in vivo may underlie the fact that beneficial effects of selenium supplementation demonstrated in preclinical studies using models of oxidant stress-induced cardiovascular dysfunction, such as ischemia-reperfusion injury and myocardial infarction, have not been consistently observed in clinical trials. In fact, recent studies have yielded data that suggest that unselective supplementation of selenium may, indeed, be harmful. Interesting biologic actions of selenium are its simultaneous effects on redox balance and methylation status, a combination that may influence gene expression. These combined actions may explain some of the biphasic effects seen with low and high doses of selenium, the potentially harmful effects seen in normal individuals, and the beneficial effects noted in preclinical studies of disease. Given the complexity of selenium biology, systems biology approaches may be necessary to reach the goal of optimization of selenium status to promote health and prevent disease.

Cannabis exposure as an interactive cardiovascular risk factor and accelerant of organismal ageing: a longitudinal study.

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Reece, Albert Stuart; Norman, Amanda; Hulse, Gary Kenneth

2016-11-07

Many reports exist of the cardiovascular toxicity of smoked cannabis but none of arterial stiffness measures or vascular age (VA). In view of its diverse toxicology, the possibility that cannabis-exposed patients may be ageing more quickly requires investigation. Cross-sectional and longitudinal, observational. Prospective. Single primary care addiction clinic in Brisbane, Australia. 11 cannabis-only smokers, 504 tobacco-only smokers, 114 tobacco and cannabis smokers and 534 non-smokers. known cardiovascular disease or therapy or acute exposure to alcohol, amphetamine, heroin or methadone. Radial arterial pulse wave tonometry (AtCor, SphygmoCor, Sydney) performed opportunistically and sequentially on patients between 2006 and 2011. Algorithmically calculated VA. other central haemodynamic variables. Differences between group chronological ages (CA, 30.47±0.48 to 40.36±2.44, mean±SEM) were controlled with linear regression. Between-group sex differences were controlled by single-sex analysis. Mean cannabis exposure among patients was 37.67±7.16 g-years. In regression models controlling for CA, Body Mass Index (BMI), time and inhalant group, the effect of cannabis use on VA was significant in males (p=0.0156) and females (p=0.0084). The effect size in males was 11.84%. A dose-response relationship was demonstrated with lifetime exposure (pcannabis was robust to adjustment and was unrelated to its acute effects. Significant power interactions between cannabis exposure and the square and cube of CA were demonstrated (from pCannabis is an interactive cardiovascular risk factor (additional to tobacco and opioids), shows a prominent dose-response effect and is robust to adjustment. Cannabis use is associated with an acceleration of the cardiovascular age, which is a powerful surrogate for the organismal-biological age. This likely underlies and bi-directionally interacts with its diverse toxicological profile and is of considerable public health and regulatory

Life satisfaction and longitudinal changes in physical activity, diabetes and obesity among patients with cardiovascular diseases.

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Baumann, Michèle; Tchicaya, Anastase; Lorentz, Nathalie; Le Bihan, Etienne

2017-12-02

Patients with cardiovascular disease who underwent coronary angiography at the National Institute of Cardiac Surgery and Cardiological Intervention (INCCI) in Luxembourg were surveyed for cardiovascular risk factors (CVRF) (hypertension, hypercholesterolemia, diabetes, obesity, physical inactivity, tobacco consumption). In 2013/14, their life satisfaction (LS) was also assessed. Our aim was to analyse the relationships between LS on one hand and longitudinal changes in CVRF between 2008/09 and 2013/14 and socioeconomic factors on the other. 1289 patients completed a self-administered questionnaire. Life Satisfaction, originally recorded on a 1 to 10 scale of complete satisfaction was dichotomized into two groups: ≤ 7 and. >7. We then performed logistic multiple regressions. The event on which the probability was modelled, was LS > 7. Data were adjusted on age, sex and income. Longitudinal changes in CVRF were assessed by their presence or absence in 2008/09 and 2013/14 (categories: 'no-no'; 'no-yes'; 'yes-no'; 'yes-yes'). Physical activity in 2008/09 and 2013/14 was associated with a lower LS (OR = 0.469). The same pattern was observed for obesity and physical inactivity: lower LS was related to the presence of these risks (yes-yes; no-yes) in 2013/14 (mean OR for obesity and physical inactivity in 2013/14: 0.587 and 0.485 respectively), whereas their presence or absence in 2008/09 was not related to LS. Finally, patients who suffered from diabetes in 2008 were more likely to experience a decline in LS, particularly if their diabetes was less severe in 2013/14 (OR = 0.462). The lowest LS was observed when obesity or physical inactivity was present in 2013/14, newly or otherwise. The same trend was seen in diabetes among patients who had it in 2008/9, but were less severely affected in 2013/14. In secondary prevention, CVD-related upheavals could be minimised if professionals and patients became 'Partners in Healthcare' to better adhere to healthy

Observed versus predicted cardiovascular events and all-cause death in HIV infection: a longitudinal cohort study.

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De Socio, Giuseppe Vittorio; Pucci, Giacomo; Baldelli, Franco; Schillaci, Giuseppe

2017-06-12

The aim of the study was to assess the applicability of an algorithm predicting 10-year cardiovascular disease (CVD) generated in the setting of the Framingham Heart Study to a real-life, contemporary Italian cohort of HIV-positive subjects. The study was an observational longitudinal cohort study. The probability for 10-year CVD events according to the Framingham algorithm was assessed in 369 consecutive HIV-positive participants free from overt CVD enrolled in 2004, who were followed for a median of 10.0 years (interquartile range, 9.1-10.1). Cardiovascular events included myocardial infarction, hospitalized heart failure, revascularized angina, sudden cardiac death, stroke, peripheral arterial disease. Over 3097 person-years of observation, we observed a total of 34 CVD events, whereas Framingham algorithm predicted the occurrence of 34.3 CVD events. CVD event rate was 11.0/1000 person-years of follow-up. In a receiver operating characteristics curve analysis, Framingham risk equation showed an excellent predictive value for incident CVD events (c-statistics, 0.83; 95% confidence interval, 0.76-0.90). In a multivariable Cox analysis, age, smoking and diabetes were independent predictors of CVD events. All-cause death rate was 20.0/1000 person-years of follow-up (n = 62 deaths). Causes of death included liver diseases (18), malignancies (14), AIDS-related (11); cardiovascular (9) and others (10). In a Cox analysis, age, AIDS diagnosis and chronic hepatitis were independent predictors of death. Observed CVD events in HIV-infected patients were well predicted by Framingham algorithm. Established major CVD risk factors are the strongest determinants of CVD morbidity in an Italian contemporary cohort of HIV-positive subjects. Interventions to modify traditional risk factors are urgently needed in HIV people.

Advances in Understanding Air Pollution and Cardiovascular Diseases: The Multi-Ethnic Study of Atherosclerosis and Air Pollution (MESA Air)

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Kaufman, Joel D.; Spalt, Elizabeth W.; Curl, Cynthia L.; Hajat, Anjum; Jones, Miranda R.; Kim, Sun-Young; Vedal, Sverre; Szpiro, Adam A.; Gassett, Amanda; Sheppard, Lianne; Daviglus, Martha L.; Adar, Sara D.

2016-01-01

The Multi-Ethnic Study of Atherosclerosis and Air Pollution (MESA Air) leveraged the platform of the MESA cohort into a prospective longitudinal study of relationships between air pollution and cardiovascular health. MESA Air researchers developed fine-scale, state-of-the-art air pollution exposure models for the MESA Air communities, creating individual exposure estimates for each participant. These models combine cohort-specific exposure monitoring, existing monitoring systems, and an extensive database of geographic and meteorological information. Together with extensive phenotyping in MESA—and adding participants and health measurements to the cohort—MESA Air investigated environmental exposures on a wide range of outcomes. Advances by the MESA Air team included not only a new approach to exposure modeling but also biostatistical advances in addressing exposure measurement error and temporal confounding. The MESA Air study advanced our understanding of the impact of air pollutants on cardiovascular disease and provided a research platform for advances in environmental epidemiology. PMID:27741981

Childhood asthma-predictive phenotype.

Science.gov (United States)

Guilbert, Theresa W; Mauger, David T; Lemanske, Robert F

2014-01-01

Wheezing is a fairly common symptom in early childhood, but only some of these toddlers will experience continued wheezing symptoms in later childhood. The definition of the asthma-predictive phenotype is in children with frequent, recurrent wheezing in early life who have risk factors associated with the continuation of asthma symptoms in later life. Several asthma-predictive phenotypes were developed retrospectively based on large, longitudinal cohort studies; however, it can be difficult to differentiate these phenotypes clinically as the expression of symptoms, and risk factors can change with time. Genetic, environmental, developmental, and host factors and their interactions may contribute to the development, severity, and persistence of the asthma phenotype over time. Key characteristics that distinguish the childhood asthma-predictive phenotype include the following: male sex; a history of wheezing, with lower respiratory tract infections; history of parental asthma; history of atopic dermatitis; eosinophilia; early sensitization to food or aeroallergens; or lower lung function in early life. Copyright © 2014 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

GWAS with longitudinal phenotypes : performance of approximate procedures

NARCIS (Netherlands)

Sikorska, Karolina; Mostafavi, Nahid; Uitterlinden, André; Rivadeneira, Fernando; Eilers, Paul HC; Lesaffre, Emmanuel

2015-01-01

Analysis of genome-wide association studies with longitudinal data using standard procedures, such as linear mixed model (LMM) fitting, leads to discouragingly long computation times. There is a need to speed up the computations significantly. In our previous work (Sikorska et al: Fast linear mixed

GWAS with longitudinal phenotypes: Performance of approximate procedures

NARCIS (Netherlands)

K. Sikorska (Karolina); N.M. Montazeri (Nahid Mostafavi); A.G. Uitterlinden (André); F. Rivadeneira Ramirez (Fernando); P.H.C. Eilers (Paul); E.M.E.H. Lesaffre (Emmanuel)

2015-01-01

textabstractAnalysis of genome-wide association studies with longitudinal data using standard procedures, such as linear mixed model (LMM) fitting, leads to discouragingly long computation times. There is a need to speed up the computations significantly. In our previous work (Sikorska et al: Fast

Estimating Longitudinal Risks and Benefits From Cardiovascular Preventive Therapies Among Medicare Patients: The Million Hearts Longitudinal ASCVD Risk Assessment Tool: A Special Report From the American Heart Association and American College of Cardiology.

Science.gov (United States)

Lloyd-Jones, Donald M; Huffman, Mark D; Karmali, Kunal N; Sanghavi, Darshak M; Wright, Janet S; Pelser, Colleen; Gulati, Martha; Masoudi, Frederick A; Goff, David C

2017-03-28

The Million Hearts Initiative has a goal of preventing 1 million heart attacks and strokes-the leading causes of mortality-through several public health and healthcare strategies by 2017. The American Heart Association and American College of Cardiology support the program. The Cardiovascular Risk Reduction Model was developed by Million Hearts and the Center for Medicare & Medicaid Services as a strategy to assess a value-based payment approach toward reduction in 10-year predicted risk of atherosclerotic cardiovascular disease (ASCVD) by implementing cardiovascular preventive strategies to manage the "ABCS" (aspirin therapy in appropriate patients, blood pressure control, cholesterol management, and smoking cessation). The purpose of this special report is to describe the development and intended use of the Million Hearts Longitudinal ASCVD Risk Assessment Tool. The Million Hearts Tool reinforces and builds on the "2013 ACC/AHA Guideline on the Assessment of Cardiovascular Risk" by allowing clinicians to estimate baseline and updated 10-year ASCVD risk estimates for primary prevention patients adhering to the appropriate ABCS over time, alone or in combination. The tool provides updated risk estimates based on evidence from high-quality systematic reviews and meta-analyses of the ABCS therapies. This novel approach to personalized estimation of benefits from risk-reducing therapies in primary prevention may help target therapies to those in whom they will provide the greatest benefit, and serves as the basis for a Center for Medicare & Medicaid Services program designed to evaluate the Million Hearts Cardiovascular Risk Reduction Model. Copyright © 2017 American Heart Association, Inc., and the American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Longitudinal Associations of Leptin and Adiponectin with Heart Rate Variability in Children

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Roos Van De Wielle

2017-07-01

Full Text Available For early prevention of cardiovascular disease, early detection and risk factor insights are necessary. The autonomic balance reflects cardiovascular risk and can be measured by heart rate variability (HRV. Therefore, our purpose is to examine associations between HRV and the energy-related biomarkers leptin and adiponectin in children. Participants of this study were Belgian children recruited for the longitudinal ChiBS study (year 2010–2012. HRV was measured and fasting blood samples were taken in 249 children at baseline (4.4–11.0 y and 223 children at follow-up (6.7–12.2 y. Cross-sectional and longitudinal linear regression analyses were separated by sex and adjusted for age, socio-economic status, body fat%, negative emotions, puberty, and mean heart rate. Leptin was a negative cross-sectional and longitudinal predictor of parasympathetic activity in boys; while leptin in girls was cross-sectionally associated with higher LF and LF/HF suggesting sympathetic predominance. Adiponectin was a negative cross-sectional and longitudinal predictor of parasympathetic activity in boys; but when adjusting for mean heart rate, this effect disappeared and adiponectin was a positive cross-sectional and longitudinal predictor of parasympathetic activity in girls. These results stress the importance of considering sex differences and adjustment for heart rate in testing HRV predictors. Leptin seemed disadvantageous for the autonomic balance, while adiponectin seemed advantageous for the autonomic balance in girls only. More research is needed to see whether leptin and adiponectin are interesting in cardiovascular screening/prevention or in determining the cardiovascular gain during weight loss follow-up.

Structural, biochemical and non-traditional cardiovascular risk markers in PCOS.

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Christakou, Charikleia; Diamanti-Kandarakis, Evanthia

2013-01-01

Polycystic ovary syndrome (PCOS) is a heterogeneous syndrome of reproductive and metabolic derangements. The combination of anovulation and hyperandrogenism signifies the classic form of PCOS which displays the adverse metabolic phenotype of the syndrome. This phenotype includes visceral obesity and insulin resistance as well as a constellation of other traditional cardiovascular risk factors, mainly low grade inflammation, disturbances of glucose metabolism and dyslipidemia. The resultant increased risk for cardiovascular disease may affect not only obese but also lean women with classic PCOS. The mechanisms underlying the increased cardiovascular risk in the context of PCOS may include not only metabolic aberrations, but also hormonal factors, in particular hyperandrogenemia. However, the consequences in terms of CV morbidity remain questionable due to the difficulties in conducting long-term, prospective studies aimed at identifying potential late-arriving clinical outcomes.

Paraoxonase 1 Phenotype and Mass in South Asian versus Caucasian Renal Transplant Recipients

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Philip W. Connelly

2012-01-01

Full Text Available South Asian renal transplant recipients have a higher incidence of cardiovascular disease compared with Caucasian renal transplant recipients. We carried out a study to determine whether paraoxonase 1, a novel biomarker for cardiovascular risk, was decreased in South Asian compared with Caucasian renal transplant recipients. Subjects were matched two to one on the basis of age and sex for a total of 129 subjects. Paraoxonase 1 was measured by mass, arylesterase activity, and two-substrate phenotype assay. Comparisons were made by using a matched design. The frequency of PON1 QQ, QR and RR phenotype was 56%, 37%, and 7% for Caucasian subjects versus 35%, 44%, and 21% for South Asian subjects (χ2=7.72, P=0.02. PON1 mass and arylesterase activity were not significantly different between South Asian and Caucasian subjects. PON1 mass was significantly associated with PON1 phenotype (P=0.0001, HDL cholesterol (P=0.009, LDL cholesterol (P=0.02, and diabetes status (P<0.05. Arylesterase activity was only associated with HDL cholesterol (P=0.003. Thus the frequency of the PON1 RR phenotype was higher and that of the QQ phenotype was lower in South Asian versus Caucasian renal transplant recipients. However, ethnicity was not a significant factor as a determinant of PON1 mass or arylesterase activity, with or without analysis including PON1 phenotype. The two-substrate method for determining PON1 phenotype may be of value for future studies of cardiovascular complications in renal transplant recipients.

Paraoxonase 1 Phenotype and Mass in South Asian versus Caucasian Renal Transplant Recipients.

Science.gov (United States)

Connelly, Philip W; Maguire, Graham F; Nash, Michelle M; Rapi, Lindita; Yan, Andrew T; Prasad, G V Ramesh

2012-01-01

South Asian renal transplant recipients have a higher incidence of cardiovascular disease compared with Caucasian renal transplant recipients. We carried out a study to determine whether paraoxonase 1, a novel biomarker for cardiovascular risk, was decreased in South Asian compared with Caucasian renal transplant recipients. Subjects were matched two to one on the basis of age and sex for a total of 129 subjects. Paraoxonase 1 was measured by mass, arylesterase activity, and two-substrate phenotype assay. Comparisons were made by using a matched design. The frequency of PON1 QQ, QR and RR phenotype was 56%, 37%, and 7% for Caucasian subjects versus 35%, 44%, and 21% for South Asian subjects (χ(2) = 7.72, P = 0.02). PON1 mass and arylesterase activity were not significantly different between South Asian and Caucasian subjects. PON1 mass was significantly associated with PON1 phenotype (P = 0.0001), HDL cholesterol (P = 0.009), LDL cholesterol (P = 0.02), and diabetes status (P < 0.05). Arylesterase activity was only associated with HDL cholesterol (P = 0.003). Thus the frequency of the PON1 RR phenotype was higher and that of the QQ phenotype was lower in South Asian versus Caucasian renal transplant recipients. However, ethnicity was not a significant factor as a determinant of PON1 mass or arylesterase activity, with or without analysis including PON1 phenotype. The two-substrate method for determining PON1 phenotype may be of value for future studies of cardiovascular complications in renal transplant recipients.

Longitudinal Relationship Between Loneliness and Social Isolation in Older Adults: Results From the Cardiovascular Health Study.

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Petersen, Johanna; Kaye, Jeffrey; Jacobs, Peter G; Quinones, Ana; Dodge, Hiroko; Arnold, Alice; Thielke, Stephen

2016-08-01

To understand the longitudinal relationship between loneliness and isolation. Participants included 5,870 adults 65 years and older (M = 72.89 ± 5.59 years) from the first 5 years of the Cardiovascular Health Study. Loneliness was assessed using a dichotomized loneliness question. Social isolation was assessed using six items from the Lubben Social Network Scale. Yearly life events were included to assess abrupt social network changes. Mixed effects logistic regression was employed to analyze the relationship between isolation and loneliness. Higher levels of social isolation were associated with higher odds of loneliness, as was an increase (from median) in level of social isolation. Life events such as a friend dying were also associated with increased odds of loneliness. These results suggest that average level of isolation and increases in the level of isolation are closely tied to loneliness, which has implications for future assessment or monitoring of loneliness in older adult populations. © The Author(s) 2015.

Association between alcohol and cardiovascular disease

DEFF Research Database (Denmark)

Holmes, Michael V; Dale, Caroline E; Zuccolo, Luisa

2014-01-01

OBJECTIVE: To use the rs1229984 variant in the alcohol dehydrogenase 1B gene (ADH1B) as an instrument to investigate the causal role of alcohol in cardiovascular disease. DESIGN: Mendelian randomisation meta-analysis of 56 epidemiological studies. PARTICIPANTS: 261 991 individuals of European...... descent, including 20 259 coronary heart disease cases and 10 164 stroke events. Data were available on ADH1B rs1229984 variant, alcohol phenotypes, and cardiovascular biomarkers. MAIN OUTCOME MEASURES: Odds ratio for coronary heart disease and stroke associated with the ADH1B variant in all individuals...... disease than those without the genetic variant. This suggests that reduction of alcohol consumption, even for light to moderate drinkers, is beneficial for cardiovascular health....

Adiposity Indexes as Phenotype-Specific Markers of Preclinical Metabolic Alterations and Cardiovascular Risk in Polycystic Ovary Syndrome: A Cross-Sectional Study.

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Mario, Fernanda Missio; Graff, Scheila Karen; Spritzer, Poli Mara

2017-05-01

Polycystic ovary syndrome (PCOS) is a common condition in women of reproductive age. 2 PCOS phenotypes (classic and ovulatory) are currently recognized as the most prevalent, with important differences in terms of cardiometabolic features. We studied the performance of different adiposity indexes to predict preclinical metabolic alterations and cardiovascular risk in 234 women with PCOS (173 with classic and 61 with ovulatory PCOS) and 129 controls. Performance of waist circumference, waist-to-height ratio, conicity index, lipid accumulation product, and visceral adiposity index was assessed based on HOMA-IR ≥ 3.8 as reference standard for screening preclinical metabolic alterations and cardiovascular risk factors in each group. Lipid accumulation product had the best accuracy for classic PCOS, and visceral adiposity index had the best accuracy for ovulatory PCOS. By applying the cutoff point of lipid accumulation productcardiometabolic alterations (Prisk for hypertension, dyslipidemia, and impaired glucose tolerance. In ovulatory PCOS, visceral adiposity index ≥ 1.32 was capable of detecting women with significantly higher blood pressure and less favorable glycemic and lipid variables as compared to ovulatory PCOS with lower visceral adiposity index (Pcardiometabolic risk and secure early interventions. © Georg Thieme Verlag KG Stuttgart · New York.

Cardiovascular disease among people with drug use disorders

DEFF Research Database (Denmark)

Thylstrup, Birgitte; Clausen, Thomas; Hesse, Morten

2015-01-01

Objectives To present the prevalence and incidence of cardiovascular disease (CVD) in a national cohort of patients seeking treatment for drug use disorders (DUD). Methods This is a longitudinal record linkage study of consecutive DUD treatment admissions between 2000 and 2006 from Denmark. Results...... treatment (SHR = 1.15, p = 0.022). The use of amphetamines was negatively associated with the risk of CVD within this cohort (SHR = 0.75, p = 0.001). Conclusions Patients injecting drugs using prescribed methadone were at elevated risk for cardiovascular disease and should be monitored for CVD. Opioid...... medications should be evaluated in terms of their cardiovascular sequelae....

Association between Cardiovascular Health Score and Carotid Intima-Media Thickness: Cross-Sectional Analysis of the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) Baseline Assessment.

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Santos, Itamar S; Goulart, Alessandra C; Pereira, Alexandre C; Lotufo, Paulo A; Benseñor, Isabela M

2016-12-01

The American Heart Association aims to reduce the burden of cardiovascular disease in this decade by improving seven ideal cardiovascular health (CVH) characteristics in the population. The aim of this study was to quantify the association between the American Heart Association's CVH score and values for carotid intima-media thickness (CIMT) in the Brazilian Longitudinal Study of Adult Health baseline assessment. The Brazilian Longitudinal Study of Adult Health is a multicenter cohort study of civil servants aged 35 to 74 years in Brazil. In this study, the investigators analyzed 9,662 individuals with no previous cardiovascular disease. The distribution of CIMT values (categorized into age-, sex-, and race-specific quartiles) was analyzed according to CVH scores using χ 2 trend tests. Linear and multinomial regression models were built to evaluate the association between CIMT and CVH score. A significant increase was observed in the proportion of individuals within the first and second CIMT quartiles, as well as a decrease within the fourth quartile with higher CVH score strata (P for trend < .001). A 1-point increase in CVH score was associated in adjusted models with a decrease of 0.011 mm in CIMT and an odds ratio of 0.79 (95% CI, 0.77-0.81) of having CIMT in the fourth quartile. However, nearly 16% of individuals with optimal CVH scores had CIMT values in the highest quartile. In this study, significant associations were found between CIMT and CVH score in a large sample of middle-aged adults. However, a high CVH score did not warrant the absence of a significant subclinical atherosclerotic burden. Copyright © 2016 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.

Artificial Intelligence in Precision Cardiovascular Medicine.

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Krittanawong, Chayakrit; Zhang, HongJu; Wang, Zhen; Aydar, Mehmet; Kitai, Takeshi

2017-05-30

Artificial intelligence (AI) is a field of computer science that aims to mimic human thought processes, learning capacity, and knowledge storage. AI techniques have been applied in cardiovascular medicine to explore novel genotypes and phenotypes in existing diseases, improve the quality of patient care, enable cost-effectiveness, and reduce readmission and mortality rates. Over the past decade, several machine-learning techniques have been used for cardiovascular disease diagnosis and prediction. Each problem requires some degree of understanding of the problem, in terms of cardiovascular medicine and statistics, to apply the optimal machine-learning algorithm. In the near future, AI will result in a paradigm shift toward precision cardiovascular medicine. The potential of AI in cardiovascular medicine is tremendous; however, ignorance of the challenges may overshadow its potential clinical impact. This paper gives a glimpse of AI's application in cardiovascular clinical care and discusses its potential role in facilitating precision cardiovascular medicine. Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Critical Windows of Cardiovascular Susceptibility to Developmental Hypoxia in Common Snapping Turtle (Chelydra serpentina) Embryos.

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Tate, Kevin B; Kohl, Zachary F; Eme, John; Rhen, Turk; Crossley, Dane A

2015-01-01

Environmental conditions fluctuate dramatically in some reptilian nests. However, critical windows of environmental sensitivity for cardiovascular development have not been identified. Continuous developmental hypoxia has been shown to alter cardiovascular form and function in embryonic snapping turtles (Chelydra serpentina), and we used this species to identify critical periods during which hypoxia modifies the cardiovascular phenotype. We hypothesized that incubation in 10% O2 during specific developmental periods would have differential effects on the cardiovascular system versus overall somatic growth. Two critical windows were identified with 10% O2 from 50% to 70% of incubation, resulting in relative heart enlargement, either via preservation of or preferential growth of this tissue, while exposure to 10% O2 from 20% to 70% of incubation resulted in a reduction in arterial pressure. The deleterious or advantageous aspects of these embryonic phenotypes in posthatching snapping turtles have yet to be explored. However, identification of these critical windows has provided insight into how the developmental environment alters the phenotype of reptiles and will also be pivotal in understanding its impact on the fitness of egg-laying reptiles.

Identification of quantitative trait loci for fibrin clot phenotypes: the EuroCLOT study

DEFF Research Database (Denmark)

Williams, Frances M K; Carter, Angela M; Kato, Bernet

2009-01-01

OBJECTIVE: Fibrin makes up the structural basis of an occlusive arterial thrombus, and variability in fibrin phenotype relates to cardiovascular risk. The aims of the current study from the EU consortium EuroCLOT were to (1) determine the heritability of fibrin phenotypes and (2) identify QTLs as...

Hypertriglyceridemic waist phenotype in primary health care: comparison of two cutoff points

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Braz MAD

2017-09-01

Full Text Available Marina Augusta Dias Braz,1 Jallyne Nunes Vieira,1 Flayane Oliveira Gomes,1 Priscilla Rafaella da Silva,1 Ohanna Thays de Medeiros Santos,1 Ilanna Marques Gomes da Rocha,2 Iasmin Matias de Sousa,2 Ana Paula Trussardi Fayh2 1Faculdade de Ciências da Saúde do Trairi, Universidade Federal do Rio Grande do Norte (UFRN, Santa Cruz, 2Department of Nutrition, Centro de Ciências da Saúde, UFRN, Natal, Rio Grande do Norte, Brazil Objective: We aimed to evaluate the prevalence of hypertriglyceridemic waist (HTGW phenotype among users of primary health care using two different cutoff points used in the literature. Methods: We evaluated adults and elderly individuals of both sexes who attended the same level of primary health care. HTGW phenotype was determined with measurements of waist circumference (WC and triglyceride levels and compared using cutoff points proposed by the National Cholesterol Education Program – NCEP/ATP III (WC ≥102 cm for men and ≥88 cm for women; triglyceride levels ≥150 mg/dL for both sexes and by Lemieux et al (WC ≥90 cm for men and ≥85 cm for women; triglyceride levels ≥177 mg/dL for both. Results: Within the sample of 437 individuals, 73.7% was female. The prevalence of HTGW phenotype was high and statistically different with the use of different cutoff points from the literature. The prevalence was higher using the NCEP/ATP III criteria compared to those proposed by Lemieux et al (36.2% and 32.5%, respectively, p<0.05. Individuals with the presence of the phenotype also presented alterations in other traditional cardiovascular risk markers. Conclusion: The HTGW phenotype identified high prevalence of cardiovascular risk in the population, with higher cutoff points from the NCEP/ATP III criteria. The difference in frequency of risk alerts us to the need to establish cutoff points for the Brazilian population. Keywords: abdominal obesity, cardiovascular disease, dyslipidemia, cardiovascular risk

Body Mass Index below Obesity Threshold Implies Similar Cardiovascular Risk among Various Polycystic Ovary Syndrome Phenotypes.

Science.gov (United States)

Bagir, Gulay Simsek; Bakiner, Okan S; Bozkirli, Emre; Cavlak, Gulhan; Serinsoz, Hulya; Ertorer, M Eda

2016-01-01

The aim of this study was to determine the cardiometabolic risk factors in different polycystic ovary syndrome (PCOS) phenotypes. This cross-sectional study was performed between 2010 and 2011. Eighty-nine patients with PCOS and 25 age- and weight-matched healthy controls were included in the study. Patients were grouped using the Rotterdam 2003 criteria as: group 1, oligomenorrhea and/or anovulation (ANOV) and hyperandrogenemia (HA) and/or hyperandrogenism (n = 23); group 2, ANOV and polycystic ovaries (PCO; n = 22); group 3, HA and PCO (n = 22); group 4, ANOV, HA and PCO (n = 22); group 5, controls (n = 25). Laboratory blood tests for diagnosis and cardiometabolic risk assessments were performed. Insulin resistance (IR) was calculated in all patients with the homeostasis model assessment of IR (HOMA-IR) formula. An euglycemic hyperinsulinemic clamp test was performed on 5 randomly selected cases in each subgroup, making 25 cases in total, and indicated as the 'M' value (mg/kg/min), which is the total body glucose disposal rate. The mean BMl values of the groups were: group 1, 26.1 ± 5.3; group 2, 27.9 ± 5.2; group 3, 24.3 ± 4.2; group 4, 27.9 ± 7.5; group 5, 24.7 ± 5.2 (p > 0.05). There were no differences in the lipid profile, plasma glucose, HOMA-IR, insulin and M values between the groups (p > 0.05). Phenotypes with oligomenorrhea/anovulation (groups 1, 2 and 4) were more obese than group 3 (p = 0.039). The cardiometabolic risk profile was similar among the PCOS subgroups. This finding could be attributed to the mean BMl values, which, being below 30, were not within the obesity range. Obesity appeared to be an important determinant of high cardiovascular risk in PCOS. © 2015 S. Karger AG, Basel.

Secular change in 13 metabolic phenotypes: A Chinese longitudinal twin study

DEFF Research Database (Denmark)

Li, Shuxia; Pang, Zengchang; Zhang, Dongfeng

in prospective investigations. Based on Chinese twin data collected from Danish-Chinese collaboration research, we perform twin modeling on 13 metabolic phenotypes (total cholesterol; triglyceride; high density lipoprotein (HDL); low density lipoprotein (LDL); urine acid (UA); glucose; weight; body mass index...... fitted to the secular changes in each of the 13 phenotypes with best fitting model selected based on model performance. Age and sex were included as covariates in the models to adjust for their effects on secular trend. Results: Variations in secular change in 3 lipids (total cholesterol; triglyceride...

Functional identification of the promoter of SLC4A5, a gene associated with cardiovascular and metabolic phenotypes in the HERITAGE Family Study.

Science.gov (United States)

Stütz, Adrian M; Teran-Garcia, Margarita; Rao, D C; Rice, Treva; Bouchard, Claude; Rankinen, Tuomo

2009-11-01

The sodium bicarbonate cotransporter gene SLC4A5, associated earlier with cardiovascular phenotypes, was tested for associations in the HERITAGE Family Study, and possible mechanisms were investigated. Twelve tag-single nucleotide polymorphisms (SNPs) covering the SLC4A5 gene were analyzed in 276 Black and 503 White healthy, sedentary subjects. Associations were tested using a variance components-based (QTDT) method with data adjusted for age, sex and body size. In Whites, rs6731545 and rs7571842 were significantly associated with resting and submaximal exercise pulse pressure (PP) (0.0004 HERITAGE Family Study are likely due to neither variation in the promoter nor known coding SNPs of SLC4A5.

Longitudinal Study of Hypertensive Subjects With Type 2 Diabetes Mellitus: Overall and Cardiovascular Risk.

Science.gov (United States)

Safar, Michel E; Gnakaméné, Jean-Barthélémy; Bahous, Sola Aoun; Yannoutsos, Alexandra; Thomas, Frédérique

2017-06-01

Despite adequate glycemic and blood pressure control, treated type 2 diabetic hypertensive subjects have a significantly elevated overall/cardiovascular risk. We studied 244 816 normotensive and 99 720 hypertensive subjects (including 7480 type 2 diabetics) attending medical checkups between 1992 and 2011. We sought to identify significant differences in overall/cardiovascular risk between hypertension with and without diabetes mellitus. Mean follow-up was 12.7 years; 14 050 all-cause deaths were reported. From normotensive to hypertensive populations, a significant progression in overall/cardiovascular mortality was observed. Mortality was significantly greater among diabetic than nondiabetic hypertensive subjects (all-cause mortality, 14.05% versus 7.43%; and cardiovascular mortality, 1.28% versus 0.7%). No interaction was observed between hemodynamic measurements and overall/cardiovascular risk, suggesting that blood pressure factors, even during drug therapy, could not explain the differences in mortality rates between diabetic and nondiabetic hypertensive patients. Using cross-sectional regression models, a significant association was observed between higher education levels, lower levels of anxiety and depression, and reduced overall mortality in diabetic hypertensive subjects, while impaired renal function, a history of stroke and myocardial infarction, and increased alcohol and tobacco consumption were significantly associated with increased mortality. Blood pressure and glycemic control alone cannot reverse overall/cardiovascular risk in diabetics with hypertension. Together with cardiovascular measures, overall prevention should include recommendations to reduce alcohol and tobacco consumption and improve stress, education levels, and physical activity. © 2017 American Heart Association, Inc.

Is cardiovascular risk in women with PCOS a real risk? Current insights.

Science.gov (United States)

Papadakis, Georgios; Kandaraki, Eleni; Papalou, Olga; Vryonidou, Andromachi; Diamanti-Kandarakis, Evanthia

2017-12-01

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in reproductive aged women. PCOS incorporates not only symptoms related to the reproductive system but also a clustering of systemic metabolic abnormalities that are linked with increased risk for cardiovascular disease (CVD). More specifically, metabolic aberrations such as impaired glucose and lipid metabolism, accompanied by increased low-grade inflammation as well as elevated coagulation factors appear to contribute to the increased cardiovascular risk. Even though many studies have indicated a rise in surrogate biomarkers of CVD in women with PCOS, it is still doubtful to what extent and magnitude this elevation can be translated to real cardiovascular events. Furthermore, the cardiovascular risk factors appear to vary significantly in the different phenotypes of the syndrome. Women with PCOS have the potential for early atherosclerosis, myocardial and endothelial dysfunction. Whether PCOS women are at real cardiovascular risk compared to controls remains between the verge of theoretical and real threat for the PCOS women at any age but particularly in the post-menopausal state. Interestingly, although the presence of the CVD risk factors is well documented in PCOS women, their combination on different phenotypes may play a role, which eventually results in a spectrum of clinical manifestations of CVD with variable degree of severity. The present manuscript aims to review the interaction between PCOS and the combination of several cardiovascular risk factors.

Cardiovascular outcomes and systemic anti-inflammatory drugs in patients with severe psoriasis

DEFF Research Database (Denmark)

Ahlehoff, O; Skov, L; Gislason, G

2014-01-01

BACKGROUND: Psoriasis is a common disease and is associated with cardiovascular diseases. Systemic anti-inflammatory drugs may reduce risk of cardiovascular events. We therefore examined the rate of cardiovascular events, i.e. cardiovascular death, myocardial infarction and stroke, in patients...... with severe psoriasis treated with systemic anti-inflammatory drugs. METHODS: Individual-level linkage of administrative registries was used to perform a longitudinal nationwide cohort study. Time-dependent multivariable adjusted Cox regression was used to estimate hazard ratios (HRs) with 95% confidence...... intervals (CIs) of cardiovascular events associated with use of biological drugs, methotrexate, cyclosporine, retinoids and other antipsoriatic therapies, including topical treatments, phototherapy and climate therapy. RESULTS: A total of 6902 patients (9662 treatment exposures) with a maximum follow...

Characteristic cardiac phenotypes are detected by cardiovascular magnetic resonance in patients with different clinical phenotypes and genotypes of mitochondrial myopathy.

Science.gov (United States)

Florian, Anca; Ludwig, Anna; Stubbe-Dräger, Bianca; Boentert, Matthias; Young, Peter; Waltenberger, Johannes; Rösch, Sabine; Sechtem, Udo; Yilmaz, Ali

2015-05-22

Mitochondrial myopathies (MM) are a heterogeneous group of inherited conditions resulting from a primary defect in the mitochondrial respiratory chain with consecutively impaired cellular energy metabolism. Small sized studies using mainly electrocardiography (ECG) and echocardiography have revealed cardiac abnormalities ranging from conduction abnormalities and arrhythmias to hypertrophic or dilated cardiomyopathy in these patients. Recently, characteristic patterns of cardiac involvement were documented by cardiovascular magnetic resonance (CMR) in patients with chronic progressive external ophthalmoplegia (CPEO)/Kearns-Sayre syndrome (KSS) and with mitochondrial encephalopathy with lactic acidosis and stroke-like episodes (MELAS). The present study aimed to characterize the prevalence and pattern of cardiac abnormalities and to test the additional diagnostic value of CMR in this patient population. The hypothesis that different neuromuscular MM syndromes present with different cardiac disease phenotypes was evaluated. Sixty-four MM patients (50 ± 15 years, 44% male) and 25 matched controls (52 ± 14 years, 36% male) prospectively underwent cardiac evaluations including CMR (comprising cine- and late-gadolinium-enhancement (LGE) imaging). Based on the neuromuscular phenotype and genotype, the patients were grouped: (a) CPEO/KSS (N = 33); (b) MELAS/-like (N = 11); c) myoclonic epilepsy with ragged-red fibers (MERRF) (N = 3) and d) other non-specific MM forms (N = 17). Among the 64 MM patients, 34 (53%) had at least one abnormal CMR finding: 18 (28%) demonstrated an impaired left ventricular ejection-fraction (LV-EF patients showed significantly higher maximal wall thickness (10 ± 3 vs. 8 ± 2 mm, p = 0.005) and concentricity (LV mass to end-diastolic volume: 0.84 ± 0.27 vs. 0.67 ± 0.11, p patients showed the highest frequency of cardiac disease (in 10/11 (91%)), a mostly concentric LV hypertrophy (6/9; 67%) with or

Phenotype Development in Adolescents With Tourette Syndrome

DEFF Research Database (Denmark)

Groth, Camilla; Debes, Nanette Mol; Skov, Liselotte

2017-01-01

Tourette syndrome (TS) is a neurodevelopmental disorder characterized by frequent comorbidities and a wide spectrum of phenotype presentations. This study aimed to describe the development of phenotypes in TS and tic-related impairment in a large longitudinal study of 226 children and adolescents...... followed up after 6 years. The participants were clinically examined to assess tic severity and impairment, obsessive compulsive disorder (OCD), and attention-deficit/hyperactivity disorder (ADHD). The development in phenotypes changed toward less comorbidity with 40% TS-only (no OCD or ADHD) (TS without...... OCD or ADHD) at baseline and 55% at follow-up.Tic-related impairment was expected to improve with an age-related tic decline, but surprisingly the impairment score did not reflect the tic decline. Sex, vocal and motor tics, and OCD and ADHD severity were highly significantly correlated...

Association of an INSIG2 obesity allele with cardiovascular phenotypes is gender and age dependent

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Erdman Robert

2010-09-01

Full Text Available Abstract Background The INSIG2 gene has been implicated in cholesterol metabolism and a single nucleotide polymorphism (SNP near INSIG2 has been shown to be associated with obesity. We sought to determine the relationship of the INSIG2 SNP to cardiovascular disease (CVD related phenotypes. Methods and Results Nine hundred forty six patients undergoing percutaneous coronary intervention (PCI in wave 5 of the multicenter NHLBI Dynamic Registry were genotyped using RT-PCR/TaqMan/allelic discrimination for the rs7566605 SNP near the INSIG2 gene. Clinical variables analyzed include demographics, medical history, and procedural details. The prevalence of peripheral vascular disease (PVD was significantly higher in older men (≥65 years who were either homozygous or carriers of the obesity/lipid risk allele ("C" compared to non-carriers (odds ratio 3.4, p = 0.013 using a logistic regression model incorporating history of hypercholesterolemia, history of hypertension, cerebrovascular disease, history of diabetes, and BMI. A similar relationship with cerebrovascular disease was found in older (>65 women (odds ratio 3.4, p = 0.013. The INSIG2 SNP was not associated with BMI, nor with other clinical variables. Conclusion Age and gender may influence the association of the INSIG2 obesity SNP with PVD and cerebrovascular disease in patients with pre-existing CVD.

Two-level mixed modeling of longitudinal pedigree data for genetic association analysis

DEFF Research Database (Denmark)

Tan, Q.

2013-01-01

of follow-up. Approaches have been proposed to integrate kinship correlation into the mixed effect models to explicitly model the genetic relationship which have been proven as an efficient way for dealing with sample clustering in pedigree data. Although useful for adjusting relatedness in the mixed...... assess the genetic associations with the mean level and the rate of change in a phenotype both with kinship correlation integrated in the mixed effect models. We apply our method to longitudinal pedigree data to estimate the genetic effects on systolic blood pressure measured over time in large pedigrees......Genetic association analysis on complex phenotypes under a longitudinal design involving pedigrees encounters the problem of correlation within pedigrees which could affect statistical assessment of the genetic effects on both the mean level of the phenotype and its rate of change over the time...

Clustering high-dimensional mixed data to uncover sub-phenotypes: joint analysis of phenotypic and genotypic data.

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McParland, D; Phillips, C M; Brennan, L; Roche, H M; Gormley, I C

2017-12-10

The LIPGENE-SU.VI.MAX study, like many others, recorded high-dimensional continuous phenotypic data and categorical genotypic data. LIPGENE-SU.VI.MAX focuses on the need to account for both phenotypic and genetic factors when studying the metabolic syndrome (MetS), a complex disorder that can lead to higher risk of type 2 diabetes and cardiovascular disease. Interest lies in clustering the LIPGENE-SU.VI.MAX participants into homogeneous groups or sub-phenotypes, by jointly considering their phenotypic and genotypic data, and in determining which variables are discriminatory. A novel latent variable model that elegantly accommodates high dimensional, mixed data is developed to cluster LIPGENE-SU.VI.MAX participants using a Bayesian finite mixture model. A computationally efficient variable selection algorithm is incorporated, estimation is via a Gibbs sampling algorithm and an approximate BIC-MCMC criterion is developed to select the optimal model. Two clusters or sub-phenotypes ('healthy' and 'at risk') are uncovered. A small subset of variables is deemed discriminatory, which notably includes phenotypic and genotypic variables, highlighting the need to jointly consider both factors. Further, 7 years after the LIPGENE-SU.VI.MAX data were collected, participants underwent further analysis to diagnose presence or absence of the MetS. The two uncovered sub-phenotypes strongly correspond to the 7-year follow-up disease classification, highlighting the role of phenotypic and genotypic factors in the MetS and emphasising the potential utility of the clustering approach in early screening. Additionally, the ability of the proposed approach to define the uncertainty in sub-phenotype membership at the participant level is synonymous with the concepts of precision medicine and nutrition. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

Validation of candidate genes associated with cardiovascular risk factors in psychiatric patients

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Windemuth, Andreas; de Leon, Jose; Goethe, John W.; Schwartz, Harold I.; Woolley, Stephen; Susce, Margaret; Kocherla, Mohan; Bogaard, Kali; Holford, Theodore R.; Seip, Richard L.; Ruaño, Gualberto

2016-01-01

The purpose of this study was to identify genetic variants predictive of cardiovascular risk factors in a psychiatric population treated with second generation antipsychotics (SGA). 924 patients undergoing treatment for severe mental illness at four US hospitals were genotyped at 1.2 million single nucleotide polymorphisms. Patients were assessed for fasting serum lipid (low density lipoprotein cholesterol [LDLc], high density lipoprotein cholesterol [HDLc], and triglycerides) and obesity phenotypes (body mass index, BMI). Thirteen candidate genes from previous studies of the same phenotypes in non-psychiatric populations were tested for association. We confirmed 8 of the 13 candidate genes at the 95% confidence level. An increased genetic effect size was observed for triglycerides in the psychiatric population compared to that in the cardiovascular population. PMID:21851846

Diet assessment in the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil: Development of a food frequency questionnaire

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Maria del Carmen Bisi Molina

2013-04-01

Full Text Available OBJECTIVE: The objective of this article is to present the development of the Food Frequency Questionaire used in the Longitudinal Study of Adult Health-Brazil and analyze how diet exposes individuals to cardiovascular diseases and type 2 diabetes Mellitus. METHODS: The Longitudinal Study of Adult Health-Brazil dietary assessment instrument is based on a previously validated Food Frequency Questionaire and the final list of items took into consideration a study done in the six Longitudinal Study of Adult Health-Brazil investigation centers. RESULTS: New foods/preparations were included in the Food Frequency Questionaire with their respective portions, totaling 114 items. The perspectives of dietary analysis and cardiovascular diseases and diabetes are presented in Longitudinal Study of Adult Health-Brazil. CONCLUSION: A new instrument was developed to cover the regional particularities of the study population.

Midlife cardiovascular fitness and dementia: A 44-year longitudinal population study in women.

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Hörder, Helena; Johansson, Lena; Guo, XinXin; Grimby, Gunnar; Kern, Silke; Östling, Svante; Skoog, Ingmar

2018-04-10

To investigate whether greater cardiovascular fitness in midlife is associated with decreased dementia risk in women followed up for 44 years. A population-based sample of 1,462 women 38 to 60 years of age was examined in 1968. Of these, a systematic subsample comprising 191 women completed a stepwise-increased maximal ergometer cycling test to evaluate cardiovascular fitness. Subsequent examinations of dementia incidence were done in 1974, 1980, 1992, 2000, 2005, and 2009. Dementia was diagnosed according to DSM-III-R criteria on the basis of information from neuropsychiatric examinations, informant interviews, hospital records, and registry data up to 2012. Cox regressions were performed with adjustment for socioeconomic, lifestyle, and medical confounders. Compared with medium fitness, the adjusted hazard ratio for all-cause dementia during the 44-year follow-up was 0.12 (95% confidence interval [CI] 0.03-0.54) among those with high fitness and 1.41 (95% CI 0.72-2.79) among those with low fitness. High fitness delayed age at dementia onset by 9.5 years and time to dementia onset by 5 years compared to medium fitness. Among Swedish women, a high cardiovascular fitness in midlife was associated with a decreased risk of subsequent dementia. Promotion of a high cardiovascular fitness may be included in strategies to mitigate or prevent dementia. Findings are not causal, and future research needs to focus on whether improved fitness could have positive effects on dementia risk and when during the life course a high cardiovascular fitness is most important. Copyright © 2018 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.

Human neonatal cardiovascular progenitors: unlocking the secret to regenerative ability.

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Tania I Fuentes

Full Text Available Although clinical benefit can be achieved after cardiac transplantation of adult c-kit+ or cardiosphere-derived cells for myocardial repair, these stem cells lack the regenerative capacity unique to neonatal cardiovascular stem cells. Unraveling the molecular basis for this age-related discrepancy in function could potentially transform cardiovascular stem cell transplantation. In this report, clonal populations of human neonatal and adult cardiovascular progenitor cells were isolated and characterized, revealing the existence of a novel subpopulation of endogenous cardiovascular stem cells that persist throughout life and co-express both c-kit and isl1. Epigenetic profiling identified 41 microRNAs whose expression was significantly altered with age in phenotypically-matched clones. These differences were correlated with reduced proliferation and a limited capacity to invade in response to growth factor stimulation, despite high levels of growth factor receptor on progenitors isolated from adults. Further understanding of these differences may provide novel therapeutic targets to enhance cardiovascular regenerative capacity.

Using trajectory analyses to refine phenotype for genetic association: conduct problems and the serotonin transporter (5HTTLPR).

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Sakai, Joseph T; Boardman, Jason D; Gelhorn, Heather L; Smolen, Andrew; Corley, Robin P; Huizinga, David; Menard, Scott; Hewitt, John K; Stallings, Michael C

2010-10-01

Conduct disorder is a serious, relatively common disorder of childhood and adolescence. Findings from genetic association studies searching for genetic determinants of the liability toward such behaviors have been inconsistent. One possible explanation for differential results is that most studies define phenotype from a single assessment; for many adolescents conduct problems decrease in severity over time, whereas for others such behaviors persist. Therefore, longitudinal datasets offer the opportunity to refine phenotype. We used Caucasians that were first assessed during adolescence from the National Youth Survey Family Study. Nine waves of data were used to create latent growth trajectories and test for associations between trajectory class and 5HTTLPR genotype. For the full sample, 5HTTLPR was not associated with conduct problem phenotypes. However, the short (s) allele was associated with chronic conduct problems in females; a nominally significant sex by 5HTTLPR genotype interaction was noted. Longitudinal studies provide unique opportunities for phenotypic refinement and such techniques, with large samples, may be useful for phenotypic definition with other study designs, such as whole genome association studies.

The interplay between adipose tissue and the cardiovascular system: is fat always bad?

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Akoumianakis, Ioannis; Antoniades, Charalambos

2017-07-01

Obesity is a risk factor for cardiovascular disease (CVD). However, clinical research has revealed a paradoxically protective role for obesity in patients with chronic diseases including CVD, suggesting that the biological 'quality' of adipose tissue (AT) may be more important than overall AT mass or body weight. Importantly, AT is recognised as a dynamic organ secreting a wide range of biologically active adipokines, microRNAs, gaseous messengers, and other metabolites that affect the cardiovascular system in both endocrine and paracrine ways. Despite being able to mediate normal cardiovascular function under physiological conditions, AT undergoes a phenotypic shift characterised by acquisition of pro-oxidant and pro-inflammatory properties in cases of CVD. Crucially, recent evidence suggests that AT depots such as perivascular AT and epicardial AT are able to modify their phenotype in response to local signals of vascular and myocardial origin, respectively. Utilisation of this unique property of certain AT depots to dynamically track cardiovascular biology may reveal novel diagnostic and prognostic tools against CVD. Better understanding of the mechanisms controlling the 'quality' of AT secretome, as well as the communication links between AT and the cardiovascular system, is required for the efficient management of CVD. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For Permissions, please email: journals.permissions@oup.com.

Does present use of cardiovascular medication reflect elevated cardiovascular risk scores estimated ten years ago? A population based longitudinal observational study

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Straand Jørund

2011-03-01

Full Text Available Abstract Background It is desirable that those at highest risk of cardiovascular disease should have priority for preventive measures, eg. treatment with prescription drugs to modify their risk. We wanted to investigate to what extent present use of cardiovascular medication (CVM correlates with cardiovascular risk estimated by three different risk scores (Framingham, SCORE and NORRISK ten years ago. Methods Prospective logitudinal observational study of 20 252 participants in The Hordaland Health Study born 1950-57, not using CVM in 1997-99. Prescription data obtained from The Norwegian Prescription Database in 2008. Results 26% of men and 22% of women aged 51-58 years had started to use some CVM during the previous decade. As a group, persons using CVM scored significantly higher on the risk algorithms Framingham, SCORE and NORRISK compared to those not treated. 16-20% of men and 20-22% of women with risk scores below the high-risk thresholds for the three risk scores were treated with CVM, while 60-65% of men and 25-45% of women with scores above the high-risk thresholds received no treatment. Among women using CVM, only 2.2% (NORRISK, 4.4% (SCORE and 14.5% (Framingham had risk scores above the high-risk values. Low education, poor self-reported general health, muscular pains, mental distress (in females only and a family history of premature cardiovascular disease correlated with use of CVM. Elevated blood pressure was the single factor most strongly predictive of CVM treatment. Conclusion Prescription of CVM to middle-aged individuals by large seems to occur independently of estimated total cardiovascular risk, and this applies especially to females.

Polycystic ovary syndrome: Cardiovascular risk factors according to specific phenotypes

DEFF Research Database (Denmark)

Aziz, Mubeena; Sidelmann, Johannes Jakobsen; Faber, Jens

2015-01-01

INTRODUCTION: Polycystic ovary syndrome (PCOS) is associated with obesity and insulin resistance. The objective of this cross-sectional study was to investigate the impact of insulin resistance and body mass index (BMI) on inflammatory and hemostatic variables associated with long-term risk...... of cardiovascular disease in women with PCOS. MATERIAL AND METHODS: 149 premenopausal women with PCOS were recruited consecutively from April 2010 to February 2012 at three Danish University Hospitals. The study was conducted at the Department of Gynecology and Obstetrics, Herlev University Hospital, Denmark. PCOS...

Cardiac Phenotype of Prehypertrophic Fabry Disease.

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Nordin, Sabrina; Kozor, Rebecca; Baig, Shanat; Abdel-Gadir, Amna; Medina-Menacho, Katia; Rosmini, Stefania; Captur, Gabriella; Tchan, Michel; Geberhiwot, Tarekegn; Murphy, Elaine; Lachmann, Robin; Ramaswami, Uma; Edwards, Nicola C; Hughes, Derralynn; Steeds, Richard P; Moon, James C

2018-06-01

Fabry disease (FD) is a rare and treatable X-linked lysosomal storage disorder. Cardiac involvement determines outcomes; therefore, detecting early changes is important. Native T1 by cardiovascular magnetic resonance is low, reflecting sphingolipid storage. Early phenotype development is familiar in hypertrophic cardiomyopathy but unexplored in FD. We explored the prehypertrophic cardiac phenotype of FD and the role of storage. A prospective, international multicenter observational study of 100 left ventricular hypertrophy-negative FD patients (mean age: 39±15 years; 19% male) and 35 age- and sex-matched healthy volunteers (mean age: 40±14 years; 25% male) who underwent cardiovascular magnetic resonance, including native T1 and late gadolinium enhancement, and 12-lead ECG. In FD, 41% had a low native T1 using a single septal region of interest, but this increased to 59% using a second slice because early native T1 lowering was patchy. ECG abnormalities were present in 41% and twice as common with low native T1 (53% versus 24%; P =0.005). When native T1 was low, left ventricular maximum wall thickness, indexed mass, and ejection fraction were higher (maximum wall thickness 9±1.5 versus 8±1.4 mm, P gadolinium enhancement was more likely when native T1 was low (27% versus 6%; P =0.01). FD had higher maximal apical fractal dimensions compared with healthy volunteers (1.27±0.06 versus 1.24±0.04; P <0.005) and longer anterior mitral valve leaflets (23±2 mm versus 21±3 mm; P <0.005). There is a detectable prehypertrophic phenotype in FD consisting of storage (low native T1), structural, functional, and ECG changes. © 2018 The Authors.

Cardiovascular events in patients with atherothrombotic disease: a population-based longitudinal study in Taiwan.

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Wen-Hsien Lee

Full Text Available BACKGROUND: Atherothrombotic diseases including cerebrovascular disease (CVD, coronary artery disease (CAD, and peripheral arterial disease (PAD, contribute to the major causes of death in the world. Although several studies showed the association between polyvascular disease and poor cardiovascular (CV outcomes in Asian population, there was no large-scale study to validate this relationship in this population. METHODS AND RESULTS: This retrospective cohort study included patients with a diagnosis of CVD, CAD, or PAD from the database contained in the Taiwan National Health Insurance Bureau during 2001-2004. A total of 19954 patients were enrolled in this study. The atherothrombotic disease score was defined according to the number of atherothrombotic disease. The study endpoints included acute coronary syndrome (ACS, all strokes, vascular procedures, in hospital mortality, and so on. The event rate of ischemic stroke (18.2% was higher than that of acute myocardial infarction (5.7% in our patients (P = 0.0006. In the multivariate Cox regression analyses, the adjusted hazard ratios (HRs of each increment of atherothrombotic disease score in predicting ACS, all strokes, vascular procedures, and in hospital mortality were 1.41, 1.66, 1.30, and 1.14, respectively (P≦0.0169. CONCLUSIONS: This large population-based longitudinal study in patients with atherothrombotic disease demonstrated the risk of subsequent ischemic stroke was higher than that of subsequent AMI. In addition, the subsequent adverse CV events including ACS, all stroke, vascular procedures, and in hospital mortality were progressively increased as the increase of atherothrombotic disease score.

Clinical phenotype in relation to the distance-to-index-patient in familial hypercholesterolemia

NARCIS (Netherlands)

Besseling, Joost; Huijgen, Roeland; Martin, Seth S.; Hutten, Barbara A.; Kastelein, John J. P.; Hovingh, G. Kees

2016-01-01

We evaluated whether the severity of the familial hypercholesterolemia (FH) phenotype, i.e. increased levels of low-density lipoprotein cholesterol (LDL-C) and cardiovascular disease (CVD) risk, decreases in more distantly related patients within one family. We included heterozygous FH patients

Genotype and Phenotype of 101 Dutch Patients with Congenital Stationary Night Blindness

NARCIS (Netherlands)

Bijveld, M.M.C.; Florijn, R.J.; Bergen, A.A.B.; van den Born, L.I.; Kamermans, M.; Prick, L.; Riemslag, F.C.C.; van Schooneveld, M.J.; Kappers, A.M.L.; van Genderen, M.M.

2013-01-01

Objective: To investigate the relative frequency of the genetic causes of the Schubert-Bornschein type of congenital stationary night blindness (CSNB) and to determine the genotype-phenotype correlations in CSNB1 and CSNB2. Design: Clinic-based, longitudinal, multicenter study. Participants: A total

Big data in Parkinson's disease: using smartphones to remotely detect longitudinal disease phenotypes.

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Prince, John; Arora, Siddharth; de Vos, Maarten

2018-04-26

To better understand the longitudinal characteristics of Parkinson's disease (PD) through the analysis of finger tapping and memory tests collected remotely using smartphones. Using a large cohort (312 PD subjects and 236 controls) of participants in the mPower study, we extract clinically validated features from a finger tapping and memory test to monitor the longitudinal behaviour of study participants. We investigate any discrepancy in learning rates associated with motor and non-motor tasks between PD subjects and healthy controls. The ability of these features to predict self-assigned severity measures is assessed whilst simultaneously inspecting the severity scoring system for floor-ceiling effects. Finally, we study the relationship between motor and non-motor longitudinal behaviour to determine if separate aspects of the disease are dependent on one another. We find that the test performances of the most severe subjects show significant correlations with self-assigned severity measures. Interestingly, less severe subjects do not show significant correlations, which is shown to be a consequence of floor-ceiling effects within the mPower self-reporting severity system. We find that motor performance after practise is a better predictor of severity than baseline performance suggesting that starting performance at a new motor task is less representative of disease severity than the performance after the test has been learnt. We find PD subjects show significant impairments in motor ability as assessed through the alternating finger tapping (AFT) test in both the short- and long-term analyses. In the AFT and memory tests we demonstrate that PD subjects show a larger degree of longitudinal performance variability in addition to requiring more instances of a test to reach a steady state performance than healthy subjects. Our findings pave the way forward for objective assessment and quantification of longitudinal learning rates in PD. This can be particularly

Longitudinal Investigation into Genetics in the Conservation of Metabolic Phenotypes in Danish and Chinese Twins

DEFF Research Database (Denmark)

Li, Shuxia; Kyvik, Kirsten Ohm; Duan, Haiping

2016-01-01

twin study on long-term stability of metabolic phenotypes in Danish and Chinese twins identified a common pattern of high genetic control over phenotype conservation, and at the same time revealed population-specific patterns of genetic and common environmental regulation on the variance as well...

OBESITY PHENOTYPES IN URBAN MIDDLE-CLASS COHORTS; THE PRIT-LINDAVISTA MERGING EVIDENCE IN MEXICO: THE OPUS PRIME STUDY.

Science.gov (United States)

Fanghänel-Salmón, Guillermo; Gutiérrez-Salmeán, Gabriela; Samaniego, Virginia; Meaney, Alejandra; Sánchez-Reyes, Leticia; Navarrete, Ulises; Alcocer, Luis; Olivares-Corichi, Ivonne; Najera, Nayeli; Ceballos, Guillermo; Meaney, Eduardo

2015-07-01

even though overweight and obesity (O/O) are stated diseases, there is still a claim for a so-called "healthy obese" phenotype. Only few reports have explored the presence of different metabolic phenotypes along the body mass index (BMI) range and their corresponding associations to cardiovascular risks. as of BMI, and according to the presence of metabolic syndrome (MS) features (waist circumference, blood pressure, fasting glycemia, and lipid profile), phenotypes were determined. Cardiovascular risk was estimated with atherogenic quotients: total cholesterol/ HDL-c, LDL-c/HDL-c and the triglycerides (TG)/HDL-c index. in 8 405 mexican adults, 36% lean, 43% overweighed and 21% obese, nine phenotypes were identified: for each weight category there were subjects with normal metabolism (none MS factors), intermediate (≤ 2) and dysmetabolic (≥ 3). Only 10.8% of O/O had normal metabolism, and 5.8% of the lean persons were dysmetabolic. Atherogenic risk was higher in dysmetabolic obese persons, but the risk was high among all dysmetabolic people, independently of the weight status. TG/HDL-c showed the same trend. elevated cardiometabolic risk derives from the high prevalence of O/O. A great proportion of non-obese people have intermediate dysmetabolism. A genetic predisposition to obesity, insulin resistance, diabetes and dyslipidemia in Mexican population is blended to an unhealthy lifestyle, yielding to a catastrophic epidemic of diabetes, and cardiovascular diseases. Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.

Cardiovascular functioning, personality, and the social world: the domain of hierarchical power.

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Newton, Tamara L

2009-02-01

The present paper considers connections between cardiovascular functioning (i.e., disease status and acute stress responses) and social dominance, and its counterpart, social submissiveness, both of which are part of the broader domain of "hierarchical power" [Bugental, D.B., 2000. Acquisition of the algorithms of social life: a domain-based approach. Psychological Bulletin 126, 187-219]. Empirical research on connections between dominance/submissiveness and cardiovascular morbidity and mortality in humans is reviewed, as is research on dominance/submissiveness and cardiovascular reactivity to, and recovery from, acute stressors. Three general conclusions are established. First, in both cross-sectional and longitudinal investigations, trait and behavioral indicators of dominance have been positively associated with cardiovascular disease severity, incidence, and progression, whereas preliminary evidence from two studies suggests that trait submissiveness may protect against poorer disease outcomes. Second, among men and women, trait dominance is associated with reactivity to and recovery from acute stressors, particularly social challenges. Third, linkages between dominance/submissiveness and cardiovascular functioning, especially cardiovascular reactivity, are characterized by gender-specific patterning, and this patterning emerges as a function of social context. Implications for the next generation of research concerning social dominance, gender, and cardiovascular functioning are discussed.

Chocolate intake is associated with better cognitive function: The Maine-Syracuse Longitudinal Study.

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Crichton, Georgina E; Elias, Merrill F; Alkerwi, Ala'a

2016-05-01

Chocolate and cocoa flavanols have been associated with improvements in a range of health complaints dating from ancient times, and has established cardiovascular benefits. Less is known about the effects of chocolate on neurocognition and behaviour. The aim of this study was to investigate whether chocolate intake was associated with cognitive function, with adjustment for cardiovascular, lifestyle and dietary factors. Cross-sectional analyses were undertaken on 968 community-dwelling participants, aged 23-98 years, from the Maine-Syracuse Longitudinal Study (MSLS). Habitual chocolate intake was related to cognitive performance, measured with an extensive battery of neuropsychological tests. More frequent chocolate consumption was significantly associated with better performance on the Global Composite score, Visual-Spatial Memory and Organization, Working Memory, Scanning and Tracking, Abstract Reasoning, and the Mini-Mental State Examination. With the exception of Working Memory, these relations were not attenuated with statistical control for cardiovascular, lifestyle and dietary factors. Prospective analyses revealed no association between cognitive function and chocolate intake measured up to 18 years later. Further intervention trials and longitudinal studies are needed to explore relations between chocolate, cocoa flavanols and cognition, and the underlying causal mechanisms. Copyright © 2016 Elsevier Ltd. All rights reserved.

PhenoLines: Phenotype Comparison Visualizations for Disease Subtyping via Topic Models.

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Glueck, Michael; Naeini, Mahdi Pakdaman; Doshi-Velez, Finale; Chevalier, Fanny; Khan, Azam; Wigdor, Daniel; Brudno, Michael

2018-01-01

PhenoLines is a visual analysis tool for the interpretation of disease subtypes, derived from the application of topic models to clinical data. Topic models enable one to mine cross-sectional patient comorbidity data (e.g., electronic health records) and construct disease subtypes-each with its own temporally evolving prevalence and co-occurrence of phenotypes-without requiring aligned longitudinal phenotype data for all patients. However, the dimensionality of topic models makes interpretation challenging, and de facto analyses provide little intuition regarding phenotype relevance or phenotype interrelationships. PhenoLines enables one to compare phenotype prevalence within and across disease subtype topics, thus supporting subtype characterization, a task that involves identifying a proposed subtype's dominant phenotypes, ages of effect, and clinical validity. We contribute a data transformation workflow that employs the Human Phenotype Ontology to hierarchically organize phenotypes and aggregate the evolving probabilities produced by topic models. We introduce a novel measure of phenotype relevance that can be used to simplify the resulting topology. The design of PhenoLines was motivated by formative interviews with machine learning and clinical experts. We describe the collaborative design process, distill high-level tasks, and report on initial evaluations with machine learning experts and a medical domain expert. These results suggest that PhenoLines demonstrates promising approaches to support the characterization and optimization of topic models.

Sleep apnea and cardiovascular risk.

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Floras, John S

2014-01-01

Sleep apnea is evident in approximately 10% of adults in the general population, but in certain cardiovascular diseases, and in particular those characterized by sodium and water retention, its prevalence can exceed 50%. Although sleep apnea is not as yet integrated into formal cardiovascular risk assessment algorithms, there is increasing awareness of its importance in the causation or promotion of hypertension, coronary artery disease, heart failure, atrial arrhythmias, and stroke, and thus, not surprisingly, as a predictor of premature cardiovascular death. Sleep apnea manifests as two principal phenotypes, both characterized by respiratory instability: obstructive (OSA), which arises when sleep-related withdrawal of respiratory drive to the upper airway dilator muscles is superimposed upon a narrow and highly compliant airway predisposed to collapse, and central (CSA), which occurs when the partial pressure of arterial carbon dioxide falls below the apnea threshold, resulting in withdrawal of central drive to respiratory muscles. The present objectives are to: (1) review the epidemiology and patho-physiology of OSA and CSA, with particular emphasis on the role of renal sodium retention in initiating and promoting these processes, and on population studies that reveal the long-term consequences of untreated OSA and CSA; (2) illustrate mechanical, autonomic, chemical, and inflammatory mechanisms by which OSA and CSA can increase cardiovascular risk and event rates by initiating or promoting hypertension, atherosclerosis, coronary artery disease, heart failure, arrhythmias, and stroke; (3) highlight insights from randomized trials in which treating sleep apnea was the specific target of therapy; (4) emphasize the present lack of evidence that treating sleep apnea reduces cardiovascular risk and the current clinical equipoise concerning treatment of asymptomatic patients with sleep apnea; and (5) consider clinical implications and future directions of clinical

Are women with polycystic ovary syndrome at increased cardiovascular disease risk later in life?

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Gunning, M N; Fauser, B C J M

2017-06-01

To date, the world's leading cause of death amongst women is cardiovascular disease. Polycystic ovary syndrome (PCOS) is associated with an unfavorable cardiometabolic profile in early life. Apart from dyslipidemia, obesity and onset of type 2 diabetes mellitus, androgens are thought to influence cardiovascular health. The question rises whether women with PCOS are truly at risk for cardiovascular disease in later life. In this review paper, we aim to reflect on this assumed relation based on studies in different stages of life in women with PCOS. Cardiovascular risk factors (type 2 diabetes mellitus, obesity and metabolic syndrome), surrogate outcomes (flow-mediated dilation, carotid intima-media thickness and coronary artery calcium) and clinical long-term outcomes (cardiovascular disease and mortality) will be summarized. Data on cardiovascular disease and mortality in peri- and postmenopausal women with PCOS appear to be controversial. Whether androgens have a protective or unfavorable influence on the manifestation of cardiovascular disease remains uncertain. The need for large, prospective, well-phenotyped cohort studies of women with PCOS is high. Only then will we be able to answer this research question.

The LifeLines Cohort Study: Prevalence and treatment of cardiovascular disease and risk factors

OpenAIRE

van der Ende, M. Yldau; Hartman, Minke H. T.; Hagemeijer, Yanick; Meems, Laura M. G.; de Vries, Hendrik Sierd; Stolk, Ronald P.; de Boer, Rudolf A.; Sijtsma, Anna; van der Meer, Peter; Rienstra, Michiel; van der Harst, Pim

2017-01-01

Background: The LifeLines Cohort Study is a large three-generation prospective study and Biobank. Recruitment and data collection started in 2006 and follow-up is planned for 30 years. The central aim of LifeLines is to understand healthy ageing in the 21st century. Here, the study design, methods, baseline and major cardiovascular phenotypes of the LifeLines Cohort Study are presented. Methods and results: Baseline cardiovascular phenotypeswere defined in 9700 juvenile (8-18 years) and 152,1...

The impact of metabolic syndrome and CRP on vascular phenotype in type 2 diabetes mellitus

NARCIS (Netherlands)

Alizadeh Dehnavi, R.; Beishuizen, E.D.; Ree, M.A. van de; Le Cessie, S.; Huisman, M.V.; Kluft, C.; Princen, H.M.G.; Tamsma, J.T.

2008-01-01

Background: The burden of cardiovascular disease in diabetes mellitus type 2 (DM2) patients is variable. We hypothesize that metabolic syndrome (MS) and low-grade systemic inflammation modify the extent of atherosclerosis in DM2. Methods: Vascular phenotype was determined using the following

The Role of Alcohol Consumption in the Aetiology of Different Cardiovascular Disease Phenotypes: a CALIBER Study

Science.gov (United States)

2013-05-28

Chronic Stable Angina; Unstable Angina; Coronary Heart Disease Not Otherwise Specified; Acute Myocardial Infarction; Heart Failure; Ventricular Arrhythmias; Cardiac Arrest; Abdominal Aortic Aneurysm; Peripheral Arterial Disease; Ischaemic Stroke; Subarachnoid Haemorrhagic Stroke; Intracerebral Haemorrhagic Stroke; Stroke Not Otherwise Specified; Sudden Cardiac Death; Unheralded Coronary Death; Mortality; Coronary Heart Disease (CHD); Cardiovascular Disease (CVD); Fatal Cardiovascular Disease (Fatal CVD); ST Elevation Myocardial Infarction (STEMI); Non-ST Elevation Myocardial Infarction (nSTEMI); Myocardial Infarction Not Otherwise Specified (MI NOS)

Arterial stiffness is increased in asymptomatic nondiabetic postmenopausal women with a polycystic ovary syndrome phenotype.

Science.gov (United States)

Armeni, Eleni; Stamatelopoulos, Kimon; Rizos, Demetrios; Georgiopoulos, George; Kazani, Maria; Kazani, Aikaterini; Kolyviras, Athanasios; Stellos, Konstantinos; Panoulis, Konstantinos; Alexandrou, Andreas; Creatsa, Maria; Papamichael, Christos; Lambrinoudaki, Irene

2013-10-01

The metabolic dysfunction accompanying the polycystic ovary syndrome (PCOS) may increase the risk of hypertension and cardiovascular disease (CVD). Although menopause per se may be an additional risk factor of CVD, the association between PCOS in postmenopausal women and cardiovascular risk has not been adequately investigated. We aimed to evaluate the effect of PCOS on markers of subclinical atherosclerosis in nondiabetic postmenopausal women. This cross-sectional study included 286 postmenopausal women with intact ovaries. PCOS phenotype was defined if three of the following were present: insulin resistance, current hyperandrogenism or history of clinical androgen excess, history of infertility, central obesity and history of irregular menses. Traditional CVD risk factors, as well as indices of arterial structure (intima-media thickness, atheromatous plaques presence) and function [flow-mediated dilation, pulse wave velocity (PWV), augmentation index] were compared between women with a PCOS phenotype and the rest of the sample, who served as controls. Women with the PCOS phenotype (N=43) had higher SBP and triglycerides and lower high-density lipoprotein (HDL)-cholesterol than controls. Mean values of PWV differed significantly between PCOS cases and controls (9.46±1.74 vs. 8.60±1.51 m/s, P=0.001, univariate). Multivariate regression analysis showed that the PCOS phenotype, age and SBP were the only independent predictors of PWV. Arterial stiffness is increased in asymptomatic, nondiabetic women with a putative PCOS phenotype, independently of age, BMI or blood pressure. This might present one mechanism through which PCOS increases the risk of CVD and hypertension later in life.

Genetic Modifiers of Cardiovascular Phenotype Caused by Elastin Haploinsufficiency Act by Extrinsic Noncomplementation*

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Kozel, Beth A.; Knutsen, Russell H.; Ye, Li; Ciliberto, Christopher H.; Broekelmann, Thomas J.; Mecham, Robert P.

2011-01-01

Elastin haploinsufficiency causes the cardiovascular complications associated with Williams-Beuren syndrome and isolated supravalvular aortic stenosis. Significant variability exists in the vascular pathology in these individuals. Using the Eln+/− mouse, we sought to identify the source of this variability. Following outcrossing of C57Bl/6J Eln+/−, two backgrounds were identified whose cardiovascular parameters deviated significantly from the parental strain. F1 progeny of the C57Bl/6J; Eln+/−x129X1/SvJ were more hypertensive and their arteries less compliant. In contrast, Eln+/− animals crossed to DBA/2J were protected from the pathologic changes associated with elastin insufficiency. Among the crosses, aortic elastin and collagen content did not correlate with quantitative vasculopathy traits. Quantitative trait locus analysis performed on F2 C57; Eln+/−x129 intercrosses identified highly significant peaks on chromosome 1 (LOD 9.7) for systolic blood pressure and on chromosome 9 (LOD 8.7) for aortic diameter. Additional peaks were identified that affect only Eln+/−, including a region upstream of Eln on chromosome 5 (LOD 4.5). Bioinformatic analysis of the quantitative trait locus peaks revealed several interesting candidates, including Ren1, Ncf1, and Nos1; genes whose functions are unrelated to elastic fiber assembly, but whose effects may synergize with elastin insufficiency to predispose to hypertension and stiffer blood vessels. Real time RT-PCR studies show background-specific increased expression of Ncf1 (a subunit of the NOX2 NAPDH oxidase) that parallel the presence of increased oxidative stress in Eln+/− aortas. This finding raises the possibility that polymorphisms in genes affecting the generation of reactive oxygen species alter cardiovascular function in individuals with elastin haploinsufficiency through extrinsic noncomplementation. PMID:22049077

Longitudinal relationship of parental hypertension with body mass index, blood pressure, and cardiovascular reactivity in children.

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Li, Rongling; Alpert, Bruce S; Walker, Sammie S; Somes, Grant W

2007-05-01

To investigate whether parental hypertension (HTN) affects children's body mass index (BMI) and cardiovascular reactivity (CVR) over time. A longitudinal study of 315 students (black: 23 females, 19 males; white: 142 females, 131 males) was conducted in the public schools of Obion County, Tennessee, between 1987 and 1992. BMI and BMI z scores were calculated. The CVR task was a series of video games (taking approximately 10 minutes to play) given to the same students in their third-, fourth-, fifth-, seventh-, and eighth-grade years. CVR was defined as the change in blood pressure (delta_BP) or heart rate (delta_HR) between before playing and while playing the video game. Positive parental history of HTN (27.6%) was defined as at least 1 parent with HTN. Multivariable regression analyses were performed to estimate the effects of parental HTN on children's BMI and CVR over time. Children with parental HTN had significant higher BMI, BMI z score, and R_BP than did children without parental HTN (BMI: 21.6 vs 19.9, P = .001; BMI z score: 1.6 vs 1.1, P = .003; R_SBP: 112.6 vs 110.4 mm Hg, P = .01; R_DBP 62.7 vs 60.6 mm Hg, P = .003) after adjustment for covariates. Increased CVR was observed in children with parental HTN compared with children without parental HTN but was statistically significant only for SBP (delta_SBP: 17.2 vs 14.9 mm Hg; P = .01) after adjustment for covariates. Parental HTN independently predicted children's BMI, BMI z score, resting BP, and BP reactivity.

Credit scores, cardiovascular disease risk, and human capital.

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Israel, Salomon; Caspi, Avshalom; Belsky, Daniel W; Harrington, HonaLee; Hogan, Sean; Houts, Renate; Ramrakha, Sandhya; Sanders, Seth; Poulton, Richie; Moffitt, Terrie E

2014-12-02

Credit scores are the most widely used instruments to assess whether or not a person is a financial risk. Credit scoring has been so successful that it has expanded beyond lending and into our everyday lives, even to inform how insurers evaluate our health. The pervasive application of credit scoring has outpaced knowledge about why credit scores are such useful indicators of individual behavior. Here we test if the same factors that lead to poor credit scores also lead to poor health. Following the Dunedin (New Zealand) Longitudinal Study cohort of 1,037 study members, we examined the association between credit scores and cardiovascular disease risk and the underlying factors that account for this association. We find that credit scores are negatively correlated with cardiovascular disease risk. Variation in household income was not sufficient to account for this association. Rather, individual differences in human capital factors—educational attainment, cognitive ability, and self-control—predicted both credit scores and cardiovascular disease risk and accounted for ∼45% of the correlation between credit scores and cardiovascular disease risk. Tracing human capital factors back to their childhood antecedents revealed that the characteristic attitudes, behaviors, and competencies children develop in their first decade of life account for a significant portion (∼22%) of the link between credit scores and cardiovascular disease risk at midlife. We discuss the implications of these findings for policy debates about data privacy, financial literacy, and early childhood interventions.

Italian cardiovascular mortality charts of the CUORE project: are they comparable with the SCORE charts?

LENUS (Irish Health Repository)

Donfrancesco, Chiara

2010-08-01

The aim of this study was to build risk charts for the assessment of cardiovascular mortality of the CUORE project, an Italian longitudinal study, and to compare them with the systematic coronary risk evaluation (SCORE) project charts for low risk European countries.

Prenatal Air Pollution Exposure and Early Cardiovascular Phenotypes in Young Adults.

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Carrie V Breton

Full Text Available Exposure to ambient air pollutants increases risk for adverse cardiovascular health outcomes in adults. We aimed to evaluate the contribution of prenatal air pollutant exposure to cardiovascular health, which has not been thoroughly evaluated. The Testing Responses on Youth (TROY study consists of 768 college students recruited from the University of Southern California in 2007-2009. Participants attended one study visit during which blood pressure, heart rate and carotid artery arterial stiffness (CAS and carotid artery intima-media thickness (CIMT were assessed. Prenatal residential addresses were geocoded and used to assign prenatal and postnatal air pollutant exposure estimates using the U.S. Environmental Protection Agency's Air Quality System (AQS database. The associations between CAS, CIMT and air pollutants were assessed using linear regression analysis. Prenatal PM10 and PM2.5 exposures were associated with increased CAS. For example, a 2 SD increase in prenatal PM2.5 was associated with CAS indices, including a 5% increase (β = 1.05, 95% CI 1.00-1.10 in carotid stiffness index beta, a 5% increase (β = 1.05, 95% CI 1.01-1.10 in Young's elastic modulus and a 5% decrease (β = 0.95, 95% CI 0.91-0.99 in distensibility. Mutually adjusted models of pre- and postnatal PM2.5 further suggested the prenatal exposure was most relevant exposure period for CAS. No associations were observed for CIMT. In conclusion, prenatal exposure to elevated air pollutants may increase carotid arterial stiffness in a young adult population of college students. Efforts aimed at limiting prenatal exposures are important public health goals.

Association between carotid intima-media thickness and adiponectin in participants without diabetes or cardiovascular disease of the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil).

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de Almeida-Pititto, Bianca; Ribeiro-Filho, Fernando Flexa; Santos, Itamar S; Lotufo, Paulo A; Bensenor, Isabela M; Ferreira, Sandra Rg

2017-01-01

Objective The study assessed the association of adiponectin concentration with carotid intima-media thickness (CIMT) in middle-aged participants of the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) without diabetes or cardiovascular disease. Design Cross-sectional analyses. Methods A sample of 687 individuals (35-54 years old) without diabetes or cardiovascular disease was stratified into two categories according to CIMT (< or ≥ 75th percentile). Traditional risk factors, C-reactive protein and adiponectin values were compared between categories by Student's t-test and frequencies by chi-square test. In linear regression models, associations of CIMT with adiponectin, adjusted for adiposity, blood pressure, C-reactive protein and homeostasis model assessment-insulin resistance were tested. Mean CIMT values were compared across quartiles of adiponectin concentrations using analysis of variance. Results Three hundred and forty-one individuals (49.6%) were women and 130 (19.0%) had three traditional cardiovascular risk factors. Those with elevated CIMT (21.8%) had greater mean values of body mass index (26.2(3.8) vs. 27.7(4.0)kg/m 2 , p < 0.001), waist circumference (86.9(10.1) vs. 90.1(10.8) cm, p = 0.001), systolic blood pressure (116.2(13.6) vs.121.2(16.1) mmHg, p < 0.001), homeostasis model assessment index (1.4(0.9-2.4) vs. 1.8(1.1-2.9), p = 0.011), C-reactive protein (1.2 (0.6-2.6) vs. 1.4(0.8-3.2) mg/l, p = 0.054) and adiponectin (9.9 (6.0-14.7) vs. 8.9 (5.3-13.8) µg/ml, p = 0.002) levels than the counterpart, while plasma glucose and lipids were not different between groups. In the adjusted model, blood pressure (directly) and adiponectin (inversely) persisted associated with high CIMT. Mean CIMT was greater in the first quartile of adiponectin when compared with the other three quartiles ( p = 0.019). Conclusions Lower adiponectin levels together with higher blood pressure were independently associated with

Beneficial impact on cardiovascular risk profile of water buffalo meat consumption.

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Giordano, G; Guarini, P; Ferrari, P; Biondi-Zoccai, G; Schiavone, B; Giordano, A

2010-09-01

Meat is a good source of proteins and irons, yet its consumption has been associated with unfavorable cardiovascular effects. Whether this applies to all types of meat is unclear. We thus aimed to appraise the impact of water buffalo meat consumption on cardiovascular risk profile with an observational longitudinal study. Several important cardiovascular risk features were appraised at baseline and at 12-month follow-up in 300 adult subjects divided in groups: recent consumers of water buffalo meat vs subjects who had never consumed water buffalo meat. In addition, long-standing consumers of water buffalo meat were evaluated. Age, gender, height, body weight, and the remaining diet (with the exception of cow meat consumption) were similar across groups. From baseline to follow-up, recent consumers of water buffalo meat change their intake of water buffalo meat from none to 600+/-107 g per week (Pconsumption from 504+/-104 to 4+/-28 (PConsumption of buffalo meat seems to be associated with several beneficial effects on cardiovascular risk profile. Awaiting further randomized clinical trials, this study suggests that a larger consumption of water buffalo meat could confer significant cardiovascular benefits, while continuing to provide a substantial proportion of the recommended daily allowance of protein.

Novel R pipeline for analyzing Biolog Phenotypic MicroArray data.

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Minna Vehkala

Full Text Available Data produced by Biolog Phenotype MicroArrays are longitudinal measurements of cells' respiration on distinct substrates. We introduce a three-step pipeline to analyze phenotypic microarray data with novel procedures for grouping, normalization and effect identification. Grouping and normalization are standard problems in the analysis of phenotype microarrays defined as categorizing bacterial responses into active and non-active, and removing systematic errors from the experimental data, respectively. We expand existing solutions by introducing an important assumption that active and non-active bacteria manifest completely different metabolism and thus should be treated separately. Effect identification, in turn, provides new insights into detecting differing respiration patterns between experimental conditions, e.g. between different combinations of strains and temperatures, as not only the main effects but also their interactions can be evaluated. In the effect identification, the multilevel data are effectively processed by a hierarchical model in the Bayesian framework. The pipeline is tested on a data set of 12 phenotypic plates with bacterium Yersinia enterocolitica. Our pipeline is implemented in R language on the top of opm R package and is freely available for research purposes.

Analysis of baseline, average, and longitudinally measured blood pressure data using linear mixed models.

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Hossain, Ahmed; Beyene, Joseph

2014-01-01

This article compares baseline, average, and longitudinal data analysis methods for identifying genetic variants in genome-wide association study using the Genetic Analysis Workshop 18 data. We apply methods that include (a) linear mixed models with baseline measures, (b) random intercept linear mixed models with mean measures outcome, and (c) random intercept linear mixed models with longitudinal measurements. In the linear mixed models, covariates are included as fixed effects, whereas relatedness among individuals is incorporated as the variance-covariance structure of the random effect for the individuals. The overall strategy of applying linear mixed models decorrelate the data is based on Aulchenko et al.'s GRAMMAR. By analyzing systolic and diastolic blood pressure, which are used separately as outcomes, we compare the 3 methods in identifying a known genetic variant that is associated with blood pressure from chromosome 3 and simulated phenotype data. We also analyze the real phenotype data to illustrate the methods. We conclude that the linear mixed model with longitudinal measurements of diastolic blood pressure is the most accurate at identifying the known single-nucleotide polymorphism among the methods, but linear mixed models with baseline measures perform best with systolic blood pressure as the outcome.

Genetics of variation in HOMA-IR and cardiovascular risk factors in Mexican-Americans.

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Voruganti, V Saroja; Lopez-Alvarenga, Juan C; Nath, Subrata D; Rainwater, David L; Bauer, Richard; Cole, Shelley A; Maccluer, Jean W; Blangero, John; Comuzzie, Anthony G

2008-03-01

Insulin resistance is a major biochemical defect underlying the pathogenesis of cardiovascular disease (CVD). Mexican-Americans are known to have an unfavorable cardiovascular profile. Thus, the aim of this study was to investigate the genetic effect on variation in HOMA-IR and to evaluate its genetic correlations with other phenotypes related to risk of CVD in Mexican-Americans. The homeostatic model assessment method (HOMA-IR) is one of several approaches that are used to measure insulin resistance and was used here to generate a quantitative phenotype for genetic analysis. For 644 adults who had participated in the San Antonio Family Heart Study (SAFHS), estimates of genetic contribution were computed using a variance components method implemented in SOLAR. Traits that exhibited significant heritabilities were body mass index (BMI) (h (2) = 0.43), waist circumference (h (2) = 0.48), systolic blood pressure (h (2) = 0.30), diastolic blood pressure (h (2) = 0.21), pulse pressure (h (2) = 0.32), triglycerides (h (2) = 0.51), LDL cholesterol (h (2) = 0.31), HDL cholesterol (h (2) = 0.24), C-reactive protein (h (2) = 0.17), and HOMA-IR (h (2) = 0.33). A genome-wide scan for HOMA-IR revealed significant evidence of linkage on chromosome 12q24 (close to PAH (phenylalanine hydroxylase), LOD = 3.01, p HOMA-IR with BMI (rho (G) = 0.36), waist circumference (rho (G) = 0.47), pulse pressure (rho (G) = 0.39), and HDL cholesterol (rho (G) = -0.18). Identification of significant linkage for HOMA-IR on chromosome 12q replicates previous family-based studies reporting linkage of phenotypes associated with type 2 diabetes in the same chromosomal region. Significant genetic correlations between HOMA-IR and phenotypes related to CVD risk factors suggest that a common set of gene(s) influence the regulation of these phenotypes.

Phenotype- and genotype-specific structural alterations in spasmodic dysphonia.

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Bianchi, Serena; Battistella, Giovanni; Huddleston, Hailey; Scharf, Rebecca; Fleysher, Lazar; Rumbach, Anna F; Frucht, Steven J; Blitzer, Andrew; Ozelius, Laurie J; Simonyan, Kristina

2017-04-01

Spasmodic dysphonia is a focal dystonia characterized by involuntary spasms in the laryngeal muscles that occur selectively during speaking. Although hereditary trends have been reported in up to 16% of patients, the causative etiology of spasmodic dysphonia is unclear, and the influences of various phenotypes and genotypes on disorder pathophysiology are poorly understood. In this study, we examined structural alterations in cortical gray matter and white matter integrity in relationship to different phenotypes and putative genotypes of spasmodic dysphonia to elucidate the structural component of its complex pathophysiology. Eighty-nine patients with spasmodic dysphonia underwent high-resolution magnetic resonance imaging and diffusion-weighted imaging to examine cortical thickness and white matter fractional anisotropy in adductor versus abductor forms (distinct phenotypes) and in sporadic versus familial cases (distinct genotypes). Phenotype-specific abnormalities were localized in the left sensorimotor cortex and angular gyrus and the white matter bundle of the right superior corona radiata. Genotype-specific alterations were found in the left superior temporal gyrus, supplementary motor area, and the arcuate portion of the left superior longitudinal fasciculus. Our findings suggest that phenotypic differences in spasmodic dysphonia arise at the level of the primary and associative areas of motor control, whereas genotype-related pathophysiological mechanisms may be associated with dysfunction of regions regulating phonological and sensory processing. Identification of structural alterations specific to disorder phenotype and putative genotype provides an important step toward future delineation of imaging markers and potential targets for novel therapeutic interventions for spasmodic dysphonia. © 2017 International Parkinson and Movement Disorder Society. © 2017 International Parkinson and Movement Disorder Society.

The International Childhood Cardiovascular Cohort (i3C) consortium outcomes study of childhood cardiovascular risk factors and adult cardiovascular morbidity and mortality: Design and recruitment.

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Sinaiko, Alan R; Jacobs, David R; Woo, Jessica G; Bazzano, Lydia; Burns, Trudy; Hu, Tian; Juonala, Markus; Prineas, Ronald; Raitakari, Olli; Steinberger, Julia; Urbina, Elaine; Venn, Alison; Jaquish, Cashell; Dwyer, Terry

2018-04-22

Although it is widely thought that childhood levels of cardiovascular (CV) risk factors are related to adult CV disease, longitudinal data directly linking the two are lacking. This paper describes the design and organization of the International Childhood Cardiovascular Cohort Consortium Outcomes Study (i3C Outcomes), the first longitudinal cohort study designed to locate adults with detailed, repeated, childhood biological, physical, and socioeconomic measurements and a harmonized database. I3C Outcomes uses a Heart Health Survey (HHS) to obtain information on adult CV endpoints, using mail, email, telephone, and clinic visits in the United States (U.S.) and Australia and a national health database in Finland. Microsoft Access, REsearch Data Capture (REDCap) (U.S.), LimeSurvey (Australia), and Medidata™ Rave data systems are used to collect, transfer and organize data. Self-reported CV events are adjudicated via hospital and doctor-released medical records. After the first two study years, participants (N = 10,968) were more likely to be female (56% vs. 48%), non-Hispanic white (90% vs. 80%), and older (10.4 ± 3.8 years vs. 9.4 ± 3.3 years) at their initial childhood study visit than the currently non-recruited cohort members. Over 48% of cohort members seen during both adulthood and childhood have been found and recruited, to date, vs. 5% of those not seen since childhood. Self-reported prevalences were 0.7% Type 1 Diabetes, 7.5% Type 2 Diabetes, 33% hypertension, and 12.8% CV event. 32% of CV events were judged to be true. I3C Outcomes is uniquely able to establish evidence-based guidelines for child health care and to clarify relations to adult CV disease. Copyright © 2018 Elsevier Inc. All rights reserved.

A broad phenotypic screen identifies novel phenotypes driven by a single mutant allele in Huntington's disease CAG knock-in mice.

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Sabine M Hölter

Full Text Available Huntington's disease (HD is an autosomal dominant neurodegenerative disorder caused by the expansion of a CAG trinucleotide repeat in the HTT gene encoding huntingtin. The disease has an insidious course, typically progressing over 10-15 years until death. Currently there is no effective disease-modifying therapy. To better understand the HD pathogenic process we have developed genetic HTT CAG knock-in mouse models that accurately recapitulate the HD mutation in man. Here, we describe results of a broad, standardized phenotypic screen in 10-46 week old heterozygous HdhQ111 knock-in mice, probing a wide range of physiological systems. The results of this screen revealed a number of behavioral abnormalities in HdhQ111/+ mice that include hypoactivity, decreased anxiety, motor learning and coordination deficits, and impaired olfactory discrimination. The screen also provided evidence supporting subtle cardiovascular, lung, and plasma metabolite alterations. Importantly, our results reveal that a single mutant HTT allele in the mouse is sufficient to elicit multiple phenotypic abnormalities, consistent with a dominant disease process in patients. These data provide a starting point for further investigation of several organ systems in HD, for the dissection of underlying pathogenic mechanisms and for the identification of reliable phenotypic endpoints for therapeutic testing.

Phenotypic heterogeneity associated with a novel mutation (Gly112Glu) in the Norrie disease protein.

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Allen, R C; Russell, S R; Streb, L M; Alsheikheh, A; Stone, E M

2006-02-01

To determine the molecular pathology and clinical severity of two pedigrees with a history of early retinal detachment and peripheral retinal vascular abnormalities. Longitudinal cohort study. A longitudinal clinical study and DNA analysis was performed on 49 family members of two pedigrees. Nine individuals were found to be hemizygous for a mutation at codon 112 (Gly112Glu) of the Norrie disease protein (NDP) in one pedigree. Significant phenotypic heterogeneity was found. The proband presented with a unilateral subtotal retinal detachment at the age of 3 years, and subsequently developed a slowly progressive tractional retinal detachment involving the macula in the contralateral eye at the age of 4 years. One individual had only mild peripheral retinal pigmentary changes with normal vision at the age of 79 years. The remaining seven individuals had varying degrees of peripheral retinal vascular abnormalities and anterior segment findings. Seven affected members of a second pedigree affected by a previously reported mutation, Arg74Cys, also demonstrated wide ocular phenotypic variation. A novel mutation (Gly112Glu), which represents the most carboxy located, NDP mutation reported, results in significant phenotypic heterogeneity. These data support the contention that the spectrum of ocular disease severity associated with these NDP mutations is broad. Use of terms that characterize this entity by phenotypic appearance, such as familial exudative vitreoretinopathy, do not adequately communicate the potential spectrum of severity of this disorder to affected or carrier family members.

Association analysis of whole genome sequencing data accounting for longitudinal and family designs.

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Hu, Yijuan; Hui, Qin; Sun, Yan V

2014-01-01

Using the whole genome sequencing data and the simulated longitudinal phenotypes for 849 pedigree-based individuals from Genetic Analysis Workshop 18, we investigated various approaches to detecting the association of rare and common variants with blood pressure traits. We compared three strategies for longitudinal data: (a) using the baseline measurement only, (b) using the average from multiple visits, and (c) using all individual measurements. We also compared the power of using all of the pedigree-based data and the unrelated subset. The analyses were performed without knowledge of the underlying simulating model.

Cardiovascular risk in postmenopausal women with the polycystic ovary syndrome.

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Lambrinoudaki, Irene

2011-01-01

Polycystic ovary syndrome (PCOS) is one of the commonest endocrine disorders, affecting 5-10% of the female population of reproductive age. "Classic" PCOS is characterized by clinical or biochemical hyperandrogenism and oligo-ovulation. According to the 2003 Rotterdam criteria, two additional phenotypes are recognized: (1) the ovulatory patient with androgen excess and polycystic ovarian morphology and (2) the anovulatory patient with polycystic ovarian morphology without androgen excess. PCOS is associated with an adverse cardiometabolic profile, consisting of increased total or central adiposity, increased blood pressure, a pro-atherogenic lipid profile, increased inflammatory markers, insulin resistance and abnormal glucose metabolism. Furthermore, the incidence of overt or gestational diabetes mellitus, as well as of preeclampsia is significantly higher in PCOS patients. Among the various PCOS phenotypes, those with evidence of androgen excess have the highest burden of cardiovascular risk. Studies evaluating the incidence of cardiovascular disease in postmenopausal women with PCOS are extremely sparse. The available data so far indicate that coronary heart disease, as well as cerebrovascular disease is more common in postmenopausal PCOS patients. Persisting high androgen levels through the menopause, obesity and maturity onset diabetes mellitus are proposed as the main mechanisms accounting for the increased risk. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

Effects of prediabetes mellitus alone or plus hypertension on subsequent occurrence of cardiovascular disease and diabetes mellitus: longitudinal study.

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Qiu, Miaoyan; Shen, Weili; Song, Xiaomin; Ju, Liping; Tong, Wenxin; Wang, Haiyan; Zheng, Sheng; Jin, Yan; Wu, Yixin; Wang, Weiqing; Tian, Jingyan

2015-03-01

Whether prediabetes mellitus alone or combined with other disorders means a higher risk for cardiovascular disease (CVD) is still controversial. This study aimed to investigate the association between prediabetes mellitus and CVD and diabetes mellitus and to explore whether prediabetes mellitus alone or combined with other syndromes, such as hypertension, could promote CVD risks significantly. This longitudinal population-based study of 1609 residents from Shanghai in Southern China was conducted between 2002 and 2014. Participants with a history of CVD at baseline were excluded from analysis. Multivariate log-binomial regression models were used to adjust possible coexisting factors. Incidence of CVD during follow-up was 10.1%. After adjusting for age, sex, and other factors, the association between prediabetes mellitus and CVD was not observed. When hypertension was incorporated in stratifying factors, adjusted CVD risk was elevated significantly (odds ratio, 2.41; 95% confidence interval, 1.25-4.64) in prediabetes mellitus and hypertension combined group, and coexistence of diabetes mellitus and hypertension made CVD risk highly significantly increased, reaching 3.43-fold higher than the reference group. Blood glucose level within prediabetic range is significantly associated with elevated risks for diabetes mellitus after multivariable adjustment, but only when it is concurrent with other disorders, such as hypertension, it will significantly increase CVD risk. © 2015 American Heart Association, Inc.

C-reactive protein and cardiovascular risk in bipolar disorder patients: A systematic review.

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Marshe, Victoria S; Pira, Shamira; Mantere, Outi; Bosche, Bert; Looper, Karl J; Herrmann, Nathan; Müller, Daniel J; Rej, Soham

2017-10-03

New research is revealing a strong association between inflammatory markers with bipolar disorder (BD), potentially due to the high prevalence of cardiovascular disease and cardiovascular risk factors in BD. We aimed to synthesize the literature examining the association between the clinically most relevant inflammatory marker, C-reactive protein (CRP) and cardiovascular disease and cardiovascular risk factors in patients with BD. MEDLINE, Embase and PsychInfo were systematically searched for all relevant English language articles published prior to April 2017. Articles were included if they examined the association between CRP and cardiovascular risk factors/disease in BD. Fifteen relevant articles were retrieved. Studies were mostly cross-sectional and heterogeneous in the cardiovascular risk factors investigated. Overall, elevated CRP was associated with increased risk of metabolic syndrome, elevated body mass index, higher waist circumference, and obesity. CRP was inconsistently associated with elevated fasting glucose, insulin levels, serum triglycerides, total cholesterol levels, and low high density lipoprotein (HDL) levels. Atypical antipsychotic use may mediate some of these effects. No study examined CRP's association with actual cardiovascular disease (e.g. coronary artery disease) in BD. In BD, CRP is associated with increases in several cardiovascular risk factors, suggesting that systemic inflammation could be a shared driving force for both outcomes of BD and cardiovascular risk. Further longitudinal research is needed in this area to verify causality, including an examination of actual cardiovascular disease. Non-pharmacological and pharmacological treatments with anti-inflammatory effects should also be investigated, particularly in patients with increased CRP, for their potential to reduce cardiovascular risk in BD. Copyright © 2017 Elsevier Inc. All rights reserved.

NIH Mouse Metabolic Phenotyping Centers: the power of centralized phenotyping.

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Laughlin, Maren R; Lloyd, K C Kent; Cline, Gary W; Wasserman, David H

2012-10-01

The Mouse Metabolic Phenotyping Centers (MMPCs) were founded in 2001 by the National Institutes of Health (NIH) to advance biomedical research by providing the scientific community with standardized, high-quality phenotyping services for mouse models of diabetes, obesity, and their complications. The intent is to allow researchers to take optimum advantage of the many new mouse models produced in labs and in high-throughput public efforts. The six MMPCs are located at universities around the country and perform complex metabolic tests in intact mice and hormone and analyte assays in tissues on a fee-for-service basis. Testing is subsidized by the NIH in order to reduce the barriers for mouse researchers. Although data derived from these tests belong to the researcher submitting mice or tissues, these data are archived after publication in a public database run by the MMPC Coordinating and Bioinformatics Unit. It is hoped that data from experiments performed in many mouse models of metabolic diseases, using standard protocols, will be useful in understanding the nature of these complex disorders. The current areas of expertise include energy balance and body composition, insulin action and secretion, whole-body and tissue carbohydrate and lipid metabolism, cardiovascular and renal function, and metabolic pathway kinetics. In addition to providing services, the MMPC staff provides expertise and advice to researchers, and works to develop and refine test protocols to best meet the community's needs in light of current scientific developments. Test technology is disseminated by publications and through annual courses.

Cardiometabolic Risk in PCOS: More than a Reproductive Disorder.

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Torchen, Laura C

2017-11-11

Polycystic ovary syndrome (PCOS) is diagnosed by its characteristic reproductive features. However, PCOS is also associated with metabolic abnormalities, including insulin resistance and β-cell dysfunction. The severity of these abnormalities varies according to the reproductive phenotype, with the so-called NIH or classic phenotype conferring the greatest metabolic risk. The increased risk for type 2 diabetes (T2D) is well established among affected women with the NIH phenotype, but whether PCOS also confers an increased risk for cardiovascular events remains unknown. Recent studies in daughters of affected women have found evidence for pancreatic β-cell dysfunction prior to menarche. Further, genetic analyses have provided evidence that metabolic abnormalities such as obesity and insulin resistance contribute to the pathogenesis of PCOS. PCOS increases the risk for T2D. However, the risk for cardiovascular disease has not been quantified, and prospective, longitudinal studies are still critically needed.

Marfan syndrome--a diagnostic challenge caused by phenotypic and genetic heterogeneity.

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Baumgartner, C; Mátyás, G; Steinmann, B; Baumgartner, D

2005-01-01

Marfan syndrome (MFS) is an autosomal dominant inherited connective tissue disorder caused by mutations in the fibrillin-1 (FBN1) gene with variable clinical manifestations in the cardiovascular, musculoskeletal and ocular systems. Data of moleculor genetic analysis and a catalogue of clinical manifestations including aortic elastic parameters were mined in order to (i) assess aortic abnormality before and during medical treatment, and to (ii) identify novel correlations between the genotype and phenotype of the disease using hierarchical cluster analysis and logistic regression analysis. A score measure describing the similarity between a patient's clinical symptoms and a characteristic phenotype class was introduced. A probabilistic model for monitoring the loss of aortic elasticity was built on merely aortic parameters of 34 patients with classic MFS and 43 control subjects showing a sensitivity of 82% and a specificity of 96%. The clinical phenotypes of 100 individuals with classical or suspected MFS were clustered yielding four different phenotypic expressions. The highest correlation was found between FBN1 missense mutations, which manifested as ectopia lentis, skeletal major and skin minor criteria, and two out of four clustered phenotypes. The probability of the presence of a missense mutation in both phenotype classes is approximately 70%. Monitoring of aortic elastic properties during medical treatment may serve as additional criterion to indicate elective surgical interventions. Genotype-phenotype correlation may contribute to anticipate the clinical consequences of specific FBN1 mutations more comprehensively and may be helpful to identify MFS patients at risk at on early stage of disease.

Imaging techniques for visualizing and phenotyping congenital heart defects in murine models.

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Liu, Xiaoqin; Tobita, Kimimasa; Francis, Richard J B; Lo, Cecilia W

2013-06-01

Mouse model is ideal for investigating the genetic and developmental etiology of congenital heart disease. However, cardiovascular phenotyping for the precise diagnosis of structural heart defects in mice remain challenging. With rapid advances in imaging techniques, there are now high throughput phenotyping tools available for the diagnosis of structural heart defects. In this review, we discuss the efficacy of four different imaging modalities for congenital heart disease diagnosis in fetal/neonatal mice, including noninvasive fetal echocardiography, micro-computed tomography (micro-CT), micro-magnetic resonance imaging (micro-MRI), and episcopic fluorescence image capture (EFIC) histopathology. The experience we have gained in the use of these imaging modalities in a large-scale mouse mutagenesis screen have validated their efficacy for congenital heart defect diagnosis in the tiny hearts of fetal and newborn mice. These cutting edge phenotyping tools will be invaluable for furthering our understanding of the developmental etiology of congenital heart disease. Copyright © 2013 Wiley Periodicals, Inc.

Low HDL cholesterol as a cardiovascular risk factor in rural, urban, and rural-urban migrants: PERU MIGRANT cohort study.

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Lazo-Porras, María; Bernabe-Ortiz, Antonio; Málaga, Germán; Gilman, Robert H; Acuña-Villaorduña, Ana; Cardenas-Montero, Deborah; Smeeth, Liam; Miranda, J Jaime

2016-03-01

Whilst the relationship between lipids and cardiovascular mortality has been well studied and appears to be controversial, very little has been explored in the context of rural-to-urban migration in low-resource settings. Determine the profile and related factors for HDL-c patterns (isolated and non-isolated low HDL-c) in three population-based groups according to their migration status, and determine the effect of HDL-c patterns on the rates of cardiovascular outcomes (i.e. non-fatal stroke and non-fatal myocardial infarction) and mortality. Cross-sectional and 5-year longitudinal data from the PERU MIGRANT study, designed to assess the effect of migration on cardiovascular risk profiles and mortality in Peru. Two different analyses were performed: first, we estimated prevalence and associated factors with isolated and non-isolated low HDL-c at baseline. Second, using longitudinal information, relative risk ratios (RRR) of composite outcomes of mortality, non-fatal stroke and non-fatal myocardial infarction were calculated according to HDL-c levels at baseline. Data from 988 participants, rural (n = 201), rural-to-urban migrants (n = 589), and urban (n = 199) groups, was analysed. Low HDL-c was present in 56.5% (95%CI: 53.4%-59.6%) without differences by study groups. Isolated low HDL-c was found in 36.5% (95%CI: 33.5-39.5%), with differences between study groups. In multivariable analysis, urban group (vs. rural), female gender, overweight and obesity were independently associated with isolated low HDL-c. Only female gender, overweight and obesity were associated with non-isolated low HDL-c. Longitudinal analyses showed that non-isolated low HDL-c increased the risk of negative cardiovascular outcomes (RRR = 3.46; 95%CI: 1.23-9.74). Isolated low HDL-c was the most common dyslipidaemia in the study population and was more frequent in rural subjects. Non-isolated low HDL-c increased three-to fourfold the 5-year risk of cardiovascular outcomes. Copyright © 2015 The

New cardiovascular targets to prevent late onset Alzheimer disease.

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Claassen, Jurgen A H R

2015-09-15

The prevalence of dementia rises to between 20% and 40% with advancing age. The dominant cause of dementia in approximately 70% of these patients is Alzheimer disease. There is no effective disease-modifying pharmaceutical treatment for this neurodegenerative disease. A wide range of Alzheimer drugs that appeared effective in animal models have recently failed to show clinical benefit in patients. However, hopeful news has emerged from recent studies that suggest that therapeutic strategies aimed at reducing cardiovascular disease may also reduce the prevalence of dementia due to Alzheimer disease. This review summarizes the evidence for this link between cardiovascular disease and late onset Alzheimer dementia. Only evidence from human research is considered here. Longitudinal studies show an association between high blood pressure and pathological accumulation of the protein amyloid-beta42, and an even stronger association between vascular stiffness and amyloid accumulation, in elderly subjects. Amyloid-beta42 accumulation is considered to be an early marker of Alzheimer disease, and increases the risk of subsequent cognitive decline and development of dementia. These observations could provide an explanation for recent observations of reduced dementia prevalence associated with improved cardiovascular care. Copyright © 2015 Elsevier B.V. All rights reserved.

Phenotypic characteristics of early Wolfram syndrome.

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Marshall, Bess A; Permutt, M Alan; Paciorkowski, Alexander R; Hoekel, James; Karzon, Roanne; Wasson, Jon; Viehover, Amy; White, Neil H; Shimony, Joshua S; Manwaring, Linda; Austin, Paul; Hullar, Timothy E; Hershey, Tamara

2013-04-27

Wolfram Syndrome (WFS:OMIM 222300) is an autosomal recessive, progressive, neurologic and endocrinologic degenerative disorder caused by mutations in the WFS1 gene, encoding the endoplasmic reticulum (ER) protein wolframin, thought to be involved in the regulation of ER stress. This paper reports a cross section of data from the Washington University WFS Research Clinic, a longitudinal study to collect detailed phenotypic data on a group of young subjects in preparation for studies of therapeutic interventions. Eighteen subjects (ages 5.9-25.8, mean 14.2 years) with genetically confirmed WFS were identified through the Washington University International Wolfram Registry. Examinations included: general medical, neurologic, ophthalmologic, audiologic, vestibular, and urologic exams, cognitive testing and neuroimaging. Seventeen (94%) had diabetes mellitus with the average age of diabetes onset of 6.3 ± 3.5 years. Diabetes insipidus was diagnosed in 13 (72%) at an average age of 10.6 ± 3.3 years. Seventeen (94%) had optic disc pallor and defects in color vision, 14 (78%) had hearing loss and 13 (72%) had olfactory defects, eight (44%) had impaired vibration sensation. Enuresis was reported by four (22%) and nocturia by three (17%). Of the 11 tested for bladder emptying, five (45%) had elevated post-void residual bladder volume. WFS causes multiple endocrine and neurologic deficits detectable on exam, even early in the course of the disease. Defects in olfaction have been underappreciated. The proposed mechanism of these deficits in WFS is ER stress-induced damage to neuronal and hormone-producing cells. This group of subjects with detailed clinical phenotyping provides a pool for testing proposed treatments for ER stress. Longitudinal follow-up is necessary for establishing the natural history and identifying potential biomarkers of progression.

Mutational analysis and genotype-phenotype relation in familial hypercholesterolemia: The SAFEHEART registry.

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Bourbon, Mafalda; Alves, Ana Catarina; Alonso, Rodrigo; Mata, Nelva; Aguiar, Pedro; Padró, Teresa; Mata, Pedro

2017-07-01

Familial hypercholesterolemia (FH) is an autosomal dominant disease of cholesterol metabolism that confers an increased risk of premature atherosclerotic cardiovascular disease (ASCVD). Therefore, early identification and treatment of these patients can improve prognosis and reduce the burden of cardiovascular mortality. The aim of this work was to perform the mutational analysis of the SAFEHEART (Spanish Familial Hypercholesterolaemia Cohort Study) registry. The study recruited 2938 individuals with genetic diagnosis of FH belonging to 775 families. Statistical analysis was performed using SPSS v23. A total of 194 variants have been detected in this study, 24 of them were never described before. About 88% of the patients have a pathogenic or likely pathogenic variant. Patients with null variants have a more severe phenotype than patients with defective variants, presenting with significantly higher levels of atherogenic particles (total cholesterol, LDL-cholesterol and apolipoprotein B). This study shows the molecular characteristics of the FH patients included in the SAFEHEART registry and the relationship with the phenotypic expression. The majority of the genetic variants are considered to be pathogenic or likely pathogenic, which confers a high level of confidence to the entry and follow-up data analysis performed with this registry concerning FH patients' prognosis, treatment and survival. Copyright © 2017 Elsevier B.V. All rights reserved.

The association between disease activity and NT-proBNP in 238 patients with rheumatoid arthritis: a 10-year longitudinal study

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Provan, Sella A; Angel, Kristin; Ødegård, Sigrid; Mowinckel, Petter; Atar, Dan; Kvien, Tore K

2008-01-01

Introduction Disease activity in patients with rheumatoid arthritis (RA) is associated with increased cardiovascular morbidity and mortality, of which N-terminal pro-brain natriuretic peptide (NT-proBNP) is a predictor. Our objective was to examine the cross-sectional and longitudinal associations between markers of inflammation, measures of RA disease activity, medication used in the treatment of RA, and NT-proBNP levels (dependent variable). Methods Two hundred thirty-eight patients with RA of less than 4 years in duration were followed longitudinally with three comprehensive assessments of clinical and radiographic data over a 10-year period. Serum samples were frozen and later batch-analyzed for NT-proBNP levels and other biomarkers. Bivariate, multivariate, and repeated analyses were performed. Results C-reactive protein (CRP) levels at baseline were cross-sectionally associated with NT-proBNP levels after adjustment for age and gender (r2 adjusted = 0.23; P < 0.05). At the 10-year follow-up, risk factors for cardiovascular disease were recorded. Duration of RA and CRP levels were independently associated with NT-proBNP in the final model that was adjusted for gender, age, and creatinine levels (r2 adjusted = 0.38; P < 0.001). In the longitudinal analyses, which adjusted for age, gender, and time of follow-up, we found that repeated measures of CRP predicted NT-proBNP levels (P < 0.001). Conclusion CRP levels are linearly associated with levels of NT-proBNP in cross-sectional and longitudinal analyses of patients with RA. The independent associations of NT-proBNP levels and markers of disease activity with clinical cardiovascular endpoints need to be further investigated. PMID:18573197

Interaction between Social/Psychosocial Factors and Genetic Variants on Body Mass Index: A Gene-Environment Interaction Analysis in a Longitudinal Setting.

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Zhao, Wei; Ware, Erin B; He, Zihuai; Kardia, Sharon L R; Faul, Jessica D; Smith, Jennifer A

2017-09-29

Obesity, which develops over time, is one of the leading causes of chronic diseases such as cardiovascular disease. However, hundreds of BMI (body mass index)-associated genetic loci identified through large-scale genome-wide association studies (GWAS) only explain about 2.7% of BMI variation. Most common human traits are believed to be influenced by both genetic and environmental factors. Past studies suggest a variety of environmental features that are associated with obesity, including socioeconomic status and psychosocial factors. This study combines both gene/regions and environmental factors to explore whether social/psychosocial factors (childhood and adult socioeconomic status, social support, anger, chronic burden, stressful life events, and depressive symptoms) modify the effect of sets of genetic variants on BMI in European American and African American participants in the Health and Retirement Study (HRS). In order to incorporate longitudinal phenotype data collected in the HRS and investigate entire sets of single nucleotide polymorphisms (SNPs) within gene/region simultaneously, we applied a novel set-based test for gene-environment interaction in longitudinal studies (LGEWIS). Childhood socioeconomic status (parental education) was found to modify the genetic effect in the gene/region around SNP rs9540493 on BMI in European Americans in the HRS. The most significant SNP (rs9540488) by childhood socioeconomic status interaction within the rs9540493 gene/region was suggestively replicated in the Multi-Ethnic Study of Atherosclerosis (MESA) ( p = 0.07).

Interaction between Social/Psychosocial Factors and Genetic Variants on Body Mass Index: A Gene-Environment Interaction Analysis in a Longitudinal Setting

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Wei Zhao

2017-09-01

Full Text Available Obesity, which develops over time, is one of the leading causes of chronic diseases such as cardiovascular disease. However, hundreds of BMI (body mass index-associated genetic loci identified through large-scale genome-wide association studies (GWAS only explain about 2.7% of BMI variation. Most common human traits are believed to be influenced by both genetic and environmental factors. Past studies suggest a variety of environmental features that are associated with obesity, including socioeconomic status and psychosocial factors. This study combines both gene/regions and environmental factors to explore whether social/psychosocial factors (childhood and adult socioeconomic status, social support, anger, chronic burden, stressful life events, and depressive symptoms modify the effect of sets of genetic variants on BMI in European American and African American participants in the Health and Retirement Study (HRS. In order to incorporate longitudinal phenotype data collected in the HRS and investigate entire sets of single nucleotide polymorphisms (SNPs within gene/region simultaneously, we applied a novel set-based test for gene-environment interaction in longitudinal studies (LGEWIS. Childhood socioeconomic status (parental education was found to modify the genetic effect in the gene/region around SNP rs9540493 on BMI in European Americans in the HRS. The most significant SNP (rs9540488 by childhood socioeconomic status interaction within the rs9540493 gene/region was suggestively replicated in the Multi-Ethnic Study of Atherosclerosis (MESA (p = 0.07.

Identification of extreme motor phenotypes in Huntington's disease.

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Braisch, Ulrike; Hay, Birgit; Muche, Rainer; Rothenbacher, Dietrich; Landwehrmeyer, G Bernhard; Long, Jeffrey D; Orth, Michael

2017-04-01

The manifestation of motor signs in Huntington's disease (HD) has a well-known inverse relationship with HTT CAG repeat length, but the prediction is far from perfect. The probability of finding disease modifiers is enhanced in individuals with extreme HD phenotypes. We aimed to identify extreme HD motor phenotypes conditional on CAG and age, such as patients with very early or very late onset of motor manifestation. Retrospective data were available from 1,218 healthy controls and 9,743 HD participants with CAG repeats ≥40, and a total of about 30,000 visits. Boundaries (2.5% and 97.5% quantiles) for extreme motor phenotypes (UHDRS total motor score (TMS) and motor age-at-onset) were estimated using quantile regression for longitudinal data. More than 15% of HD participants had an extreme TMS phenotype for at least one visit. In contrast, only about 4% of participants were consistent TMS extremes at two or more visits. Data from healthy controls revealed an upper cut-off of 13 for the TMS representing the extreme of motor ratings for a normal aging population. In HD, boundaries of motor age-at-onset based on diagnostic confidence or derived from the TMS data cut-off in controls were similar. In summary, a UHDRS TMS of more than 13 in an individual carrying the HD mutation indicates a high likelihood of motor manifestations of HD irrespective of CAG repeat length or age. The identification of motor phenotype extremes can be useful in the search for disease modifiers, for example, genetic or environmental such as medication. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

ALK7 Gene Polymorphism is Associated with Metabolic Syndrome Risk and Cardiovascular Remodeling

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Zhang, Wenchao; Wang, Hui; Zhang, Wei [Key Laboratory of Cardiovascular Remodeling and Function Research Chinese Ministry of Education and Chinese Ministry of Public Health, Qilu Hospital of Shandong University, Jinan (China); Lv, Ruijuan [Department of Emergency, Qilu Hospital of Shandong University, Jinan (China); Wang, Zhihao [Key Laboratory of Cardiovascular Remodeling and Function Research Chinese Ministry of Education and Chinese Ministry of Public Health, Qilu Hospital of Shandong University, Jinan (China); Department of Geriatrics, Qilu Hospital of Shandong University, Jinan (China); Shang, Yuanyuan; Zhang, Yun; Zhong, Ming [Key Laboratory of Cardiovascular Remodeling and Function Research Chinese Ministry of Education and Chinese Ministry of Public Health, Qilu Hospital of Shandong University, Jinan (China); Chen, Yuguo; Tang, Mengxiong, E-mail: tangmengxiongsdu8@163.com [Key Laboratory of Cardiovascular Remodeling and Function Research Chinese Ministry of Education and Chinese Ministry of Public Health, Qilu Hospital of Shandong University, Jinan (China); Department of Emergency, Qilu Hospital of Shandong University, Jinan (China)

2013-08-15

Activin receptor-like kinase 7 (ALK7) is a type I receptor for the TGF-β superfamily and has recently been demonstrated to play an important role in the maintenance of metabolic homeostasis. To investigate the association of the ALK7 gene polymorphism with metabolic syndrome (MetS) and cardiovascular remodeling in MetS patients. The single nucleotide polymorphism rs13010956 in the ALK7 gene was genotyped in 351 Chinese subjects undergoing carotid and cardiac ultrasonography. The associations of the ALK7 gene polymorphism with the MetS phenotype, MetS parameters, and cardiovascular ultrasonic features were analyzed. The rs13010956 polymorphism in the ALK7 gene was found to be significantly associated with the MetS phenotype in females (p < 0.05) and was also significantly associated with blood pressure in the total (p < 0.05) and female populations (p < 0.01). Further analysis revealed that rs13010956 was associated with mean intima-media thickness of the carotid arteries in females (p < 0.05). After control for body mass index, blood pressure, fasting blood glucose, and triglycerides, rs13010956 was also found to be significantly associated with left ventricular mass index in the total (p < 0.05) and female populations (p < 0.05). Our findings suggested that the ALK7 gene polymorphism rs13010956 was significantly associated with MetS risk in females and may be involved in cardiovascular remodeling in MetS patients.

ALK7 Gene Polymorphism is Associated with Metabolic Syndrome Risk and Cardiovascular Remodeling

International Nuclear Information System (INIS)

Zhang, Wenchao; Wang, Hui; Zhang, Wei; Lv, Ruijuan; Wang, Zhihao; Shang, Yuanyuan; Zhang, Yun; Zhong, Ming; Chen, Yuguo; Tang, Mengxiong

2013-01-01

Activin receptor-like kinase 7 (ALK7) is a type I receptor for the TGF-β superfamily and has recently been demonstrated to play an important role in the maintenance of metabolic homeostasis. To investigate the association of the ALK7 gene polymorphism with metabolic syndrome (MetS) and cardiovascular remodeling in MetS patients. The single nucleotide polymorphism rs13010956 in the ALK7 gene was genotyped in 351 Chinese subjects undergoing carotid and cardiac ultrasonography. The associations of the ALK7 gene polymorphism with the MetS phenotype, MetS parameters, and cardiovascular ultrasonic features were analyzed. The rs13010956 polymorphism in the ALK7 gene was found to be significantly associated with the MetS phenotype in females (p < 0.05) and was also significantly associated with blood pressure in the total (p < 0.05) and female populations (p < 0.01). Further analysis revealed that rs13010956 was associated with mean intima-media thickness of the carotid arteries in females (p < 0.05). After control for body mass index, blood pressure, fasting blood glucose, and triglycerides, rs13010956 was also found to be significantly associated with left ventricular mass index in the total (p < 0.05) and female populations (p < 0.05). Our findings suggested that the ALK7 gene polymorphism rs13010956 was significantly associated with MetS risk in females and may be involved in cardiovascular remodeling in MetS patients

Association of various blood pressure variables and vascular phenotypes with coronary, stroke and renal deaths: Potential implications for prevention.

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Harbaoui, Brahim; Courand, Pierre-Yves; Milon, Hughes; Fauvel, Jean-Pierre; Khettab, Fouad; Mechtouff, Laura; Cassar, Emmanuel; Girerd, Nicolas; Lantelme, Pierre

2015-11-01

The relationship between blood pressure (BP) and cardiovascular diseases has been extensively documented. However, the benefit of anti-hypertensive drugs differs according to the type of cardiovascular event. Aortic stiffness is tightly intertwined with BP and aorta cross-talk with small arteries. We endeavored to elucidate which BP component and type of vessel remodeling was predictive of the following outcomes: fatal myocardial infarction (MI), fatal stroke, renal -, coronary- or cerebrovascular-related deaths. Large vessel remodeling was estimated by an aortography-based aortic atherosclerosis score (ATS) while small vessel disease was documented by the presence of a hypertensive retinopathy. We included 1031 subjects referred for hypertension workup and assessed outcomes 30 years later. After adjustment for major risk factors, ATS and pulse pressure (PP) were predictive of coronary events while mean BP (MBP) and retinopathy were not. On the contrary, MBP was predictive of cerebrovascular and renal related deaths while ATS and PP were not. Retinopathy was only predictive of cerebrovascular related deaths. Lastly, the aortic atherosclerosis phenotype and increased PP identified patients prone to develop fatal MI whereas the retinopathy phenotype and increased MBP identified patients at higher risk of fatal stroke. These results illustrate the particular feature of the resistive coronary circulation comparatively to the brain and kidneys' low-resistance circulation. Our results advocate for a rational preventive strategy based on the identification of distinct clinical phenotypes. Accordingly, decreasing MBP levels could help preventing stroke in retinopathy phenotypes whereas targeting PP is possibly more efficient in preventing MI in atherosclerotic phenotypes. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Tourette syndrome in a longitudinal perspective. Clinical course of tics and comorbidities, coexisting psychopathologies, phenotypes and predictors.

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Groth, Camilla

2018-04-01

Tourette syndrome (TS) is a childhood onset neurodevelopmental disorder characterised by motor and vocal tics and frequent associated comorbidities. The developmental trajectory of tic shows tic-onset in the age of 4-6, peak in the age of 10-12 and decline during adolescence, although only few and small longitudinal studies form the basis of this evidence. Recent studies suggest that comorbid obsessive-compulsive disorder (OCD), attention deficit-hyperactivity disorder (ADHD) and coexisting psychopathologies tend to persist and become more dominant in adolescence. This large prospective follow-up study want to examine the clinical course of TS: tic and comorbidities during adolescence, the prevalence of coexisting psychopathologies, the tic-related impairment, development in phenotype expression and find predictors for the expected course of TS. 
Method: This study is examining a large clinical cohort recruited at the Danish National Tourette Clinic during the period 2005-2007 and 2011-2013. At baseline, 314 participants aged 5-19 years were included and at follow-up 6 years later 227 participated, aged 11-26. All participants were uniformly clinically examined at basis and follow-up with a clinical interview and validated measurements to assess comorbidities. The Yale Global Tic Severity Scale was used to asses tic severity and tic-related impairment. At follow-up a cross-sectional diagnostic evaluation was made with the Development and Well-Being Assessment to assess coexisting psychopathologies.
 Results: A significant decline in tic and the most frequent comorbidities OCD and ADHD was found although some variation existed and some subclinical and partial remissions persisted. Tic-related impairment was not reflected in the tic-decline as expected but influenced by several parameters. The phenotype expression was found to be dynamic but overall changed toward TS without comorbidities. Several predictors were found to predict the clinical course of TS in

Musculoskeletal phenotype through the life course: the role of nutrition.

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Ward, Kate

2012-02-01

This review considers the definition of a healthy bone phenotype through the life course and the modulating effects of muscle function and nutrition. In particular, it will emphasise that optimal bone strength (and how that is regulated) is more important than simple measures of bone mass. The forces imposed on bone by muscle loading are the primary determinants of musculoskeletal health. Any factor that changes muscle loading on the bone, or the response of bone to loading results in alterations of bone strength. Advances in technology have enhanced the understanding of a healthy bone phenotype in different skeletal compartments. Multiple components of muscle strength can also be quantified. The critical evaluation of emerging technologies for assessment of bone and muscle phenotype is vital. Populations with low and moderate/high daily Ca intakes and/or different vitamin D status illustrate the importance of nutrition in determining musculoskeletal phenotype. Changes in mass and architecture maintain strength despite low Ca intake or vitamin D status. There is a complex interaction between body fat and bone which, in addition to protein intake, is emerging as a key area of research. Muscle and bone should be considered as an integrative unit; the role of body fat requires definition. There remains a lack of longitudinal evidence to understand how nutrition and lifestyle define musculoskeletal health. In conclusion, a life-course approach is required to understand the definition of healthy skeletal phenotype in different populations and at different stages of life.

Cardiometabolic Risk in PCOS: More than a Reproductive Disorder

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Torchen, Laura C.

2018-01-01

Purpose of Review Polycystic ovary syndrome (PCOS) is diagnosed by its characteristic reproductive features. However, PCOS is also associated with metabolic abnormalities, including insulin resistance and β-cell dysfunction. The severity of these abnormalities varies according to the reproductive phenotype, with the so-called NIH or classic phenotype conferring the greatest metabolic risk. The increased risk for type 2 diabetes (T2D) is well-established among affected women with the NIH phenotype, but whether PCOS also confers an increased risk for cardiovascular events remains unknown. Recent Findings Recent studies in daughters of affected women have found evidence for pancreatic β-cell dysfunction prior to menarche. Further, genetic analyses have provided evidence that metabolic abnormalities such as obesity and insulin resistance contribute to the pathogenesis of PCOS. Summary PCOS increases the risk for T2D. However, the risk for cardiovascular disease has not been quantified, and prospective, longitudinal studies are still critically needed. PMID:29128916

Effects of Estrogen in Gender-dependent Fetal Programming of Adult Cardiovascular Dysfunction.

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Chen, Zewen; Wang, Lei; Ke, Jun; Xiao, DaLiao

2018-03-01

Epidemiological studies and experimental studies have demonstrated that intrauterine adverse environment increases the risk of cardiovascular disease (CVD) in adulthood. However, whether an individual develops a cardiovascular dysfunctional phenotype may depend on genetic background, age, and sex. In this review, we summarize some of the recent experimental animal studies in the developmental programming of adult CVD with an emphasis on sex differences and the potential role of estrogen in mediating sexual dimorphism. Few epidemiological studies report the effect of sex on the developmental programming of CVD. However, numerous experimental animal studies have shown a sex difference in fetal programming of adult cardiovascular dysfunction. Most of the animal studies indicate that male offspring develop cardiovascular dysfunction and CVD in adulthood, whereas adult females appear to be protected. Estrogen is one of the key factors that contributes to the sex difference of adult CVD. Estrogen/its receptor (ER) may interact with the RAS system by changes of DNA methylation patterns at the target gene promoter, serve as an antioxidant to counteract the prenatal insults-induced heightened ROS, and function as an eNOS activator to increase vasodilation, resulting in the protection of female offspring from the development of hypertension and other CVDs. These studies suggest that estrogen/ER may contribute to sex differences in cardiovascular response to an adverse intrauterine environment and play a significant role in modulating the cardiovascular response in adulthood. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Recent advances in cardiovascular aspects of polycystic ovary syndrome.

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Sathyapalan, T; Atkin, S L

2012-04-01

Polycystic ovary syndrome (PCOS) has been associated with increased cardiovascular risk (CVR) markers, but population studies have not clarified whether there is an increase in cardiovascular morbidity and mortality. Four different PCOS phenotypes resulted from the Rotterdam criteria that may differ in their CVR potential, thus introducing further complexity. This has led to studies using surrogate CVR markers including biomarkers in blood and imaging such as flow-mediated vasodilatation. In PCOS, both peripheral and central insulin resistance (IR) have been shown. Weight loss has been shown to improve IR and visceral fat, while insulin sensitizer therapies with metformin or thiazolidinediones improve IR and endothelial dysfunction. IR is also found in non-alcoholic fatty liver disease that in turn is very common in PCOS; studies have suggested that IR may be improved by treatment with metformin and omega-3 fish oils. PCOS patients have a more dyslipidemic phenotype that is worse in 'classical PCOS' associated with a higher CVR. Studies with atorvastatin and simvastatin have reported a decrease in the lipid parameters and an improvement in CVR indices including IR, but it is unclear whether this is due to their lipid-lowering action or a pleiotropic effect of the statin. In this expert opinion review, the relevant literature published during the last 2 years was considered. It focuses on some recent important data that has emerged while also exposing the gaps that remain in our knowledge that need to be addressed.

Prevalence of comorbidities according to predominant phenotype and severity of chronic obstructive pulmonary disease

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Camiciottoli G

2016-09-01

Full Text Available Gianna Camiciottoli,1,2 Francesca Bigazzi,1 Chiara Magni,1 Viola Bonti,1 Stefano Diciotti,3 Maurizio Bartolucci,4 Mario Mascalchi,5 Massimo Pistolesi1 1Section of Respiratory Medicine, Department of Clinical and Experimental Medicine, 2Department of Clinical and Experimental Biomedical Sciences, University of Florence, Florence, 3Department of Electrical, Electronic, and Information Engineering “Guglielmo Marconi,” University of Bologna, Cesena, 4Department of Diagnostic Imaging, Careggi University Hospital, 5Radiodiagnostic Section, Department of Clinical and Experimental Biomedical Sciences, University of Florence, Florence, Italy Background: In addition to lung involvement, several other diseases and syndromes coexist in patients with chronic obstructive pulmonary disease (COPD. Our purpose was to investigate the prevalence of idiopathic arterial hypertension (IAH, ischemic heart disease, heart failure, peripheral vascular disease (PVD, diabetes, osteoporosis, and anxious depressive syndrome in a clinical setting of COPD outpatients whose phenotypes (predominant airway disease and predominant emphysema and severity (mild and severe diseases were determined by clinical and functional parameters. Methods: A total of 412 outpatients with COPD were assigned either a predominant airway disease or a predominant emphysema phenotype of mild or severe degree according to predictive models based on pulmonary functions (forced expiratory volume in 1 second/vital capacity; total lung capacity %; functional residual capacity %; and diffusing capacity of lung for carbon monoxide % and sputum characteristics. Comorbidities were assessed by objective medical records. Results: Eighty-four percent of patients suffered from at least one comorbidity and 75% from at least one cardiovascular comorbidity, with IAH and PVD being the most prevalent ones (62% and 28%, respectively. IAH prevailed significantly in predominant airway disease, osteoporosis prevailed

Circulating 25-hydroxyvitamin D and insulin resistance in older adults: The Cardiovascular Health Study

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Danziger, John; Biggs, Mary L.; Niemi, Matt; Ix, Joachim H.; Kizer, Jorge R.; Djoussé, Luc; de Boer, Ian H.; Siscovick, David S.; Kestenbaum, Bryan; Mukamal, Kenneth J.

2014-01-01

Background Despite extensive study, the role of vitamin D in insulin resistance and secretion remains unclear. Objective To examine the cross-sectional and longitudinal relationships between 25-hydroxyvitamin D (25(OH)D) concentrations and indices of insulin resistance and secretion in older adults. Methods and Results Among 2134 participants of the Cardiovascular Health Study who were free from cardiovascular disease, we measured serum 25(OH)D concentrations in samples collected in 1992–1993. We examined insulin resistance and secretion using Homeostasis Model Assessment (HOMA) estimates cross-sectionally and among 1469 participants who had repeated HOMA measures four years later (1996–1997). In cross-sectional analysis, each 10 ng/mL increment in 25(OH)D concentration was associated with a 0.09 lower adjusted HOMA-IR [95%CI (−0.17, −0.02), p=0.01]. However, baseline 25(OH)D concentrations were not associated with change in HOMA-IR over 4 years of follow up (p=0.48). 25(OH)D concentrations were not associated with insulin secretion, as determined by HOMA-β, in either cross-sectional or longitudinal analysis. Conclusions Circulating 25(OH)D concentrations are associated with lower insulin resistance in cross-sectional but not longitudinal analyses. Whether this reflects residual confounding in cross-sectional analyses or the short-term nature of the relationship between vitamin D and insulin sensitivity will require trials with repeated measures of these factors. PMID:23987236

Lipoprotein profile, lipoprotein-associated phospholipase A2 and cardiovascular risk in hemodialysis patients.

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Rolla, Roberta; De Mauri, Andreana; Valsesia, Ambra; Vidali, Matteo; Chiarinotti, Doriana; Bellomo, Giorgio

2015-12-01

Cardiovascular disease is the leading cause of morbidity and mortality in hemodialysis patients; the increased risk of cardiovascular disease is due to accelerated atherosclerosis, inflammation and impaired lipoprotein metabolism. We aimed to evaluate lipoprotein-associated phospholipase A2 (Lp-PLA2) and some pro-inflammatory aspects of the lipoprotein profile in dialyzed patients in order to evaluate the relationship with the accelerated atherosclerosis and vascular accidents. In 102 dialysis patients and 40 non-uremic controls, we investigated the lipoprotein plasma profile, high sensitivity C-reactive protein (CRP), ceruloplasmin and serum amyloid A protein (SAA), and followed patients for 1 year to analyze the risk of acute cardiovascular events. Total cholesterol, low-density lipoprotein and high-density lipoprotein plasma levels were significantly lower in uremic patients than controls, whereas CRP, SAA, ceruloplasmin, Lp-PLA2 and their ratio with apolipoprotein A1 were significantly higher. Patients with Lp-PLA2 levels >194 nmol/min/ml had more acute cardiovascular events than patients with lower values. Our results show that in dialysis subjects: (1) low-density lipoproteins show a more atherogenic phenotype than in the general population; (2) high-density lipoproteins are less anti-inflammatory; (3) Lp-PLA2 could potentially be used to evaluate cardiovascular risk.

Is Sex Good for Your Health? A National Study on Partnered Sexuality and Cardiovascular Risk among Older Men and Women.

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Liu, Hui; Waite, Linda J; Shen, Shannon; Wang, Donna H

2016-09-01

Working from a social relationship and life course perspective, we provide generalizable population-based evidence on partnered sexuality linked to cardiovascular risk in later life using national longitudinal data from the National Social Life, Health and Aging Project (NSHAP) (N = 2,204). We consider characteristics of partnered sexuality of older men and women, particularly sexual activity and sexual quality, as they affect cardiovascular risk. Cardiovascular risk is defined as hypertension, rapid heart rate, elevated C-reactive protein (CRP), and general cardiovascular events. We find that older men are more likely to report being sexually active, having sex more often, and more enjoyably than are older women. Results from cross-lagged models suggest that high frequency of sex is positively related to later risk of cardiovascular events for men but not women, whereas good sexual quality seems to protect women but not men from cardiovascular risk in later life. We find no evidence that poor cardiovascular health interferes with later sexuality for either gender. © American Sociological Association 2016.

Leisure-Time Physical Activity, but not Commuting Physical Activity, is Associated with Cardiovascular Risk among ELSA-Brasil Participants.

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Pitanga, Francisco José Gondim; Matos, Sheila M A; Almeida, Maria da Conceição; Barreto, Sandhi Maria; Aquino, Estela M L

2018-01-01

Despite reports in the literature that both leisure-time physical activity (LTPA) and commuting physical activity (CPA) can promote health benefits, the literature lacks studies comparing the associations of these domains of physical activity with cardiovascular risk scores. To investigate the association between LTPA and CPA with different cardiovascular risk scores in the cohort of the Longitudinal Study of Adult Health ELSA-Brasil. Cross-sectional study with data from 13,721 participants of both genders, aged 35-74 years, free of cardiovascular disease, from ELSA Brazil. Physical activity was measured using the International Physical Activity Questionnaire (IPAQ). Five cardiovascular risk scores were used: Framingham score - coronary heart disease (cholesterol); Framingham score - coronary heart disease (LDL-C); Framingham score - cardiovascular disease (cholesterol); Framingham score - cardiovascular disease (body mass index, BMI); and pooled cohort equations for atherosclerotic cardiovascular disease (ASCVD). Associations adjusted for confounding variables between physical activity and different cardiovascular risk scores were analyzed by logistic regression. Confidence interval of 95% (95%CI) was considered. LTPA is inversely associated with almost all cardiovascular risk scores analyzed, while CPA shows no statistically significant association with any of them. Dose-response effect in association between LTPA and cardiovascular risk scores was also found, especially in men. LTPA was shown to be associated with the cardiovascular risk scores analyzed, but CPA not. The amount of physical activity (duration and intensity) was more significantly associated, especially in men, with cardiovascular risk scores in ELSA-Brasil.

Association of hyperandrogenemic and metabolic phenotype with carotid intima-media thickness in young women with polycystic ovary syndrome.

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Vryonidou, Andromachi; Papatheodorou, Athanasios; Tavridou, Anna; Terzi, Thomais; Loi, Vasiliki; Vatalas, Ioannis-Anastasios; Batakis, Nikolaos; Phenekos, Constantinos; Dionyssiou-Asteriou, Amalia

2005-05-01

Polycystic ovary syndrome (PCOS), a common endocrinopathy of women of reproductive age, is associated with the early appearance of multiple risk factors for cardiovascular disease, such as abdominal obesity, dyslipidemia, and diabetes mellitus. However, premature atherosclerosis of the carotid artery has not yet been demonstrated in young women with PCOS. Measurement of carotid intima-media thickness (IMT) is considered an easy and reliable index of subclinical atherosclerosis, which is predictive of subsequent myocardial infarction and stroke. To evaluate the cardiovascular risk of PCOS and the participation of the hyperandrogenemic and metabolic pattern, we measured carotid IMT by B-mode ultrasound as well as hormonal and several cardiovascular disease-associated parameters in 75 young women with PCOS and 55 healthy, age- and body mass index-matched women. The PCOS women had significantly increased carotid IMT (0.58 vs. 0.47 mm, P PCOS status, age, body mass index, and parental history of coronary heart disease were strong positive predictors of carotid IMT, whereas dehydroepiandrosterone sulfate was a strong negative predictor. In PCOS patients lower delta4-androstenedione and high-density lipoprotein-cholesterol levels were additionally strong positive predictors of carotid IMT, whereas in control women only total cholesterol was the additional positive predictor of carotid IMT. In conclusion, young women with PCOS have an early increase of cardiovascular risk factors and greater carotid IMT, both of which may be responsible for subclinical atherosclerosis. The hyperandrogenemic phenotype of the syndrome may attenuate the consequences of the dysmetabolic phenotype on the vascular wall.

The association between serum brain-derived neurotrophic factor and a cluster of cardiovascular risk factors in adolescents

DEFF Research Database (Denmark)

Pedersen, Natascha Holbæk; Tarp, Jakob; Andersen, Lars Bo

2017-01-01

.034) and HOMA-IR (Std. β = 0.19, P = 0.004), and negatively associated with CRF (Std. β = -0.15, P = 0.026). In females, BDNF was positively associated with TG (Std. β = 0.14, P = 0.030) and negatively associated with waist circumference (WC) (Std. β = -0.16, P = 0.012). Conclusion: Serum BDNF was positively...... associated with a composite z-score of cardiovascular risk factors. This association seems to be mainly driven by the association between TG, HOMA-IR and serum BDNF, and particularly for males. Further longitudinal research is warranted to determine the temporal relationship between BDNF and cardiovascular...

Comparing Analytic Methods for Longitudinal GWAS and a Case-Study Evaluating Chemotherapy Course Length in Pediatric AML. A Report from the Children’s Oncology Group.

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Marijana Vujkovic

2016-08-01

Full Text Available Regression analysis is commonly used in genome-wide association studies (GWAS to test genotype-phenotype associations but restricts the phenotype to a single observation for each individual. There is an increasing need for analytic methods for longitudinally collected phenotype data. Several methods have been proposed to perform longitudinal GWAS for family-based studies but few methods are described for unrelated populations. We compared the performance of three statistical approaches for longitudinal GWAS in unrelated subjectes: (1 principal component-based generalized estimating equations (PC-GEE; (2 principal component-based linear mixed effects model (PC-LMEM; (3 kinship coefficient matrix-based linear mixed effects model (KIN-LMEM, in a study of single-nucleotide polymorphisms (SNPs on the duration of 4 courses of chemotherapy in 624 unrelated children with de novo acute myeloid leukemia (AML genotyped on the Illumina 2.5M OmniQuad from the COG studies AAML0531 and AAML1031.In this study we observed an exaggerated type I error with PC-GEE in SNPs with minor allele frequencies < 0.05, wheras KIN-LMEM produces more than expected type II errors. PC-MEM showed balanced type I and type II errors for the observed versus expected P-values in comparison to competing approaches. In general, a strong concordance was observed between the P-values with the different approaches, in particular among P-values < 0.01 where the between-method AUCs exceed 99%. PC-LMEM accounts for genetic relatedness and correlations among repeated phenotype measures, shows minimal genome-wide inflation of type I errors, and yields high power. We therefore recommend PC-LMEM as a robust analytic approach for GWAS of longitudinal data in unrelated populations.

Influence of arterial hypertension, type 2 diabetes and cardiovascular risk factors on ALS outcome: a population-based study.

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Moglia, Cristina; Calvo, Andrea; Canosa, Antonio; Bertuzzo, Davide; Cugnasco, Paolo; Solero, Luca; Grassano, Maurizio; Bersano, Enrica; Cammarosano, Stefania; Manera, Umberto; Pisano, Fabrizio; Mazzini, Letizia; Dalla Vecchia, Laura A; Mora, Gabriele; Chiò, Adriano

2017-11-01

To assess the prognostic influence of pre-morbid type 2 diabetes mellitus, arterial hypertension and cardiovascular (CV) risk profile on ALS phenotype and outcome in a population-based cohort of Italian patients. A total of 650 ALS patients from the Piemonte/Valle d'Aosta Register for ALS, incident in the 2007-2011 period, were recruited. Information about premorbid presence of type 2 diabetes mellitus, arterial hypertension was collected at the time of diagnosis. Patients' CV risk profile was calculated according to the Joint British Societies' guidelines on prevention of cardiovascular disease in clinical practice (JBS2). At the univariate analysis, the presence of pre-morbid arterial hypertension was associated with a higher age at onset of ALS and a shorter survival, and patients with a high CV risk profile had a worse prognosis than those with a low CV risk profile. The Cox multivariable analysis did not confirm such findings. Type 2 diabetes mellitus did not modify either the phenotype or the prognosis of ALS patients. This study performed on a large population-based cohort of ALS patients has demonstrated that arterial hypertension, type 2 diabetes and CV risk factors, calculated using the Framingham equation, do not influence ALS phenotype and prognosis.

Prevention and Treatment of Cardiovascular Disease in Adolescents and Adults through the Transcendental Meditation® Program: A Research Review Update

Science.gov (United States)

Barnes, Vernon A.; Orme-Johnson, David W.

2012-01-01

The pathogenesis and progression of cardiovascular diseases are thought to be exacerbated by stress. Basic research indicates that the Transcendental Meditation® technique produces acute and longitudinal reductions in sympathetic tone and stress reactivity. In adolescents at risk for hypertension, the technique has been found to reduce resting and ambulatory blood pressure, left ventricular mass, cardiovascular reactivity, and to improve school behavior. Research on adults with mild or moderate essential hypertension has reported decreased blood pressure and reduced use of anti-hypertensive medication. The technique has also been reported to decrease symptoms of angina pectoris and carotid atherosclerosis, to reduce cardiovascular risk factors, including alcohol and tobacco use, to markedly reduce medical care utilization for cardiovascular diseases, and to significantly decrease cardiovascular and all-cause morbidity and mortality. These findings have important implications for inclusion of the Transcendental Meditation program in efforts to prevent and treat cardiovascular diseases and their clinical consequences. ®Transcendental Meditation and TM are trademarks registered in the US. Patent and Trademark Office, licensed to Maharishi Vedic Education Development Corporation and are used with permission. PMID:23204989

Prevention and Treatment of Cardiovascular Disease in Adolescents and Adults through the Transcendental Meditation(®) Program: A Research Review Update.

Science.gov (United States)

Barnes, Vernon A; Orme-Johnson, David W

2012-08-01

The pathogenesis and progression of cardiovascular diseases are thought to be exacerbated by stress. Basic research indicates that the Transcendental Meditation(®) technique produces acute and longitudinal reductions in sympathetic tone and stress reactivity. In adolescents at risk for hypertension, the technique has been found to reduce resting and ambulatory blood pressure, left ventricular mass, cardiovascular reactivity, and to improve school behavior. Research on adults with mild or moderate essential hypertension has reported decreased blood pressure and reduced use of anti-hypertensive medication. The technique has also been reported to decrease symptoms of angina pectoris and carotid atherosclerosis, to reduce cardiovascular risk factors, including alcohol and tobacco use, to markedly reduce medical care utilization for cardiovascular diseases, and to significantly decrease cardiovascular and all-cause morbidity and mortality. These findings have important implications for inclusion of the Transcendental Meditation program in efforts to prevent and treat cardiovascular diseases and their clinical consequences.(®)Transcendental Meditation and TM are trademarks registered in the US. Patent and Trademark Office, licensed to Maharishi Vedic Education Development Corporation and are used with permission.

Cardiovascular disease risk factors for women. A life course-events perspective

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Arora Chander P.

2010-04-01

Full Text Available Cardiovascular disease (CVD in women is the most common cause of death and in 2009 accounted for one third of all deaths. The purpose of this paper is to present what conditions during pregnancy and during the pre-menopause period lead to a greater risk of CVD. The early recognition and the application of interventions may decrease this risk. To emphasize this point we have taken a «Life course-events perspective». Current data suggests that genetic predisposition to disease in conjunction with behavior and environmental factors during fetal life is related to permanent changes in fetalplacental-maternal physiology and function, resulting in fetal programming characterizing the phenotype of the child which may persist into adulthood. Longitudinal studies have identified biological, behavioral and environmental factors related to childhood diseases such as hypertension, insulin resistance and mental health disorders. Gender differences have been identified and animal studies have suggested that estrogens in women are protective and when the risk of CVD in men is considered, the risk in women is delayed by 10 years. Thus, a normal pregnancy may be protective and reduce the risk of CVD in women. However, hypertension developing in women before or during pregnancy is a significant risk factor for women and diabetes further increases this risk of CVD, as does smoking. It is very clear that an «intervention action plan» must be developed. It is the current opinion of the authors that this action plan must be implemented early in life to decrease the risk for the development of CVS in women.

Trajectories of the healthy ageing phenotype among middle-aged and older Britons, 2004-2013.

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Tampubolon, Gindo

2016-06-01

Since the ageing population demands a response to ensure older people remain healthy and active, we studied the dynamics of a recently proposed healthy ageing phenotype. We drew the phenotype's trajectories and tested whether their levels and rates of change are influenced by health behaviours, comorbidities and socioeconomic positions earlier in the life course. The English Longitudinal Ageing Study, a prospective, nationally representative sample of people aged ≥50 years, measured a set of eight biomarkers which make up the outcome of the healthy ageing phenotype three times over nearly a decade (N2004=5009, N2008=5301, N2013=4455). A cluster of health behaviours, comorbidities and socioeconomic positions were also measured repeatedly. We assessed the phenotype's distribution non-parametrically, then fitted linear mixed models to phenotypic change and further examined time interactions with gender and socioeconomic position. We ran additional analyses to test robustness. Women had a wider distribution of the healthy ageing phenotype than men had. The phenotype declined annually by -0.242 (95% confidence interval [CI]: -0.352, -0.131). However, there was considerable heterogeneity in the levels and rates of phenotypic change. Women started at higher levels, then declined more steeply by -0.293 (CI: -0.403, -0.183) annually, leading to crossover in the trajectories. Smoking and physical activity assessed on the Allied Dunbar scale were strongly associated with the trajectories. Though marked by secular decline, the trajectories of the healthy ageing phenotype showed distinct socioeconomic gradients. The trajectories were also susceptible to variations in health behaviours, strengthening the case for serial interventions to attain healthy and active ageing. Copyright © 2016 The Author. Published by Elsevier Ireland Ltd.. All rights reserved.

Effects of the Multidisciplinary Risk Assessment and Management Program for Patients with Diabetes Mellitus (RAMP-DM) on biomedical outcomes, observed cardiovascular events and cardiovascular risks in primary care: a longitudinal comparative study.

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Jiao, Fang Fang; Fung, Colman Siu Cheung; Wong, Carlos King Ho; Wan, Yuk Fai; Dai, Daisy; Kwok, Ruby; Lam, Cindy Lo Kuen

2014-08-21

To assess whether the Multidisciplinary Risk Assessment and Management Program for Patients with Diabetes Mellitus (RAMP-DM) led to improvements in biomedical outcomes, observed cardiovascular events and predicted cardiovascular risks after 12-month intervention in the primary care setting. A random sample of 1,248 people with diabetes enrolled to RAMP-DM for at least 12 months was selected and 1,248 people with diabetes under the usual primary care were matched by age, sex, and HbA1c level at baseline as the usual care group. Biomedical and cardiovascular outcomes were measured at baseline and at 12-month after the enrollment. Difference-in-differences approach was employed to measure the effect of RAMP-DM on the changes in biomedical outcomes, proportion of subjects reaching treatment targets, observed and predicted cardiovascular risks. Compared to the usual care group, RAMP-DM group had lower cardiovascular events incidence (1.21% vs 2.89%, P = 0.003), and net decrease in HbA1c (-0.20%, P risks (total CVD risk, -2.06%, P risk, -1.43%, P risk, -0.71%, P risks. The RAMP-DM resulted in greater improvements in HbA1c and reduction in observed and predicted cardiovascular risks at 12 months follow-up, which indicated a risk-stratification multidisciplinary intervention was an effective strategy for managing Chinese people with diabetes in the primary care setting. ClinicalTrials.gov, NCT02034695.

Cardiovascular Safety of Stimulants in Children with Attention-Deficit/Hyperactivity Disorder

DEFF Research Database (Denmark)

Dalsgaard, S.; Kvist, A. P.; Leckman, J. F.

2014-01-01

Objective: The purpose of this study was to determine whether stimulant users are at higher risk of a later cardiovascular event than are non-users, examining this association in both a national cohort and a population-based sample of children and adolescents diagnosed with attention-deficit/hyperactivity...... disorder (ADHD). We also aim to examine a possible dose-response relationship in such an association. Methods: We conducted a longitudinal, prospective cohort study of all children born in Denmark between 1990 and 1999. Within this cohort, children with ADHD were identified. Data from national health...... using Cox regression, adjusted for other known risk factors. Results: In the total population (n = 714,258 contributing a total of 6,767,982 person-years) use of stimulants increased the risk of a cardiovascular event; adjusted HR = 1.83 (1.10-3.04). In children with ADHD (n = 8300) stimulant treatment...

Investigation of the 5q33.3 longevity locus and age-related phenotypes

DEFF Research Database (Denmark)

Nygaard, Marianne; Thinggaard, Mikael; Christensen, Kaare

2017-01-01

A large meta-analysis recently found the 5q33.3 locus to be associated with survival to ≥ 90 years and lower all-cause mortality, thus suggesting it as a third human longevity locus alongside APOE and FOXO3A. The 5q33.3 locus has previously been associated with blood pressure regulation and cardi......A large meta-analysis recently found the 5q33.3 locus to be associated with survival to ≥ 90 years and lower all-cause mortality, thus suggesting it as a third human longevity locus alongside APOE and FOXO3A. The 5q33.3 locus has previously been associated with blood pressure regulation...... and cardiovascular diseases in middle-aged individuals. However, part of the influence on mortality appears to be independent of cardiovascular phenotypes, and the role of the 5q33.3 locus in longevity and survival is therefore still partly unknown. We investigated the association between the longevity......-associated variant rs2149954 on chromosome 5q33.3 and age-related phenotypes in two cohorts of 1,588 and 1,271 long-lived individuals (mean ages 93.1 and 95.9 years, respectively) as well as in 700 middle-aged and 677 elderly individuals (mean ages 52.5 and 78.7 years). Altogether, nominally significant associations...

Riesgo cardiovascular, una herramienta útil para la prevención de las enfermedades cardiovasculares Cardiovascular risk, a useful tool for prevention of cardiovascular diseases

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Jorge Vega Abascal

2011-03-01

Full Text Available El riesgo cardiovascular se define como la probabilidad de padecer un evento cardiovascular en un determinado período. Mejorar la exactitud en la predicción del riesgo requiere la evaluación y el tratamiento de múltiples factores de riesgo cardiovascular, los que tienen un efecto sinérgico, más que aditivo, sobre el riesgo cardiovascular total. El cálculo utilizando métodos cuantitativos es más preciso que el obtenido con métodos cualitativos. La predicción del riesgo cardiovascular ha constituido, en los últimos años, la piedra angular en las guías clínicas de prevención cardiovascular, y deviene una herramienta útil del Médico de Familia para establecer prioridades en la atención primaria, mejorando la atención a los pacientes y eligiendo más eficazmente la terapéutica a seguir, con el objetivo de acercarnos más a la realidad multifactorial de las enfermedades cardiovasculares y a su prevención.The cardiovascular risk is defined like a probability of suffering a cardiovascular event in a determined period. To improve the accuracy in risk prediction requires the assessment and treatment of different cardiovascular risk factors, which have a synergistic effect more than additive on the total cardiovascular risk. The calculus using quantitative methods is more accurate than that obtained with qualitative methods. The prediction of cardiovascular risk has been in past years the cornerstone in clinical guidances of cardiovascular prevention and becomes an useful tool for Family Physician to establish priorities in the primary care, improving the patients care and selecting in a more effective way the therapy to be followed to bring closer more to multifactor reality of cardiovascular diseases and its prevention.

Right Ventricular Volumes and Systolic Function by Cardiac Magnetic Resonance and the Impact of Sex, Age, and Obesity in a Longitudinally Followed Cohort Free of Pulmonary and Cardiovascular Disease: The Framingham Heart Study.

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Foppa, Murilo; Arora, Garima; Gona, Philimon; Ashrafi, Arman; Salton, Carol J; Yeon, Susan B; Blease, Susan J; Levy, Daniel; O'Donnell, Christopher J; Manning, Warren J; Chuang, Michael L

2016-03-01

Cardiac magnetic resonance is uniquely well suited for noninvasive imaging of the right ventricle. We sought to define normal cardiac magnetic resonance reference values and to identify the main determinants of right ventricular (RV) volumes and systolic function using a modern imaging sequence in a community-dwelling, longitudinally followed cohort free of clinical cardiovascular and pulmonary disease. The Framingham Heart Study Offspring cohort has been followed since 1971. We scanned 1794 Offspring cohort members using steady-state free precession cardiac magnetic resonance and identified a reference group of 1336 adults (64±9 years, 576 men) free of prevalent cardiovascular and pulmonary disease. RV trabeculations and papillary muscles were considered cavity volume. Men had greater RV volumes and cardiac output before and after indexation to body size (all Pheart rate account for most of the variability in RV volumes and function in this community-dwelling population. We report sex-specific normative values for RV measurements among principally middle-aged and older adults. RV ejection fraction is greater in women. RV volumes increase with body size, are greater in men, and are smaller in older people. Body surface area seems to be appropriate for indexation of cardiac magnetic resonance-derived RV volumes. © 2016 American Heart Association, Inc.

Lipid accumulation product as a marker of cardiometabolic susceptibility in women with different phenotypes of polycystic ovary syndrome.

Science.gov (United States)

Božić-Antić, Ivana; Ilić, Dušan; Bjekić-Macut, Jelica; Bogavac, Tamara; Vojnović-Milutinović, Danijela; Kastratovic-Kotlica, Biljana; Milić, Nataša; Stanojlović, Olivera; Andrić, Zoran; Macut, Djuro

2016-12-01

There are limited data on cardiometabolic risk factors and the prevalence of metabolic syndrome (MetS) across the different PCOS phenotypes in Caucasian population. Lipid accumulation product (LAP) is a clinical surrogate marker that could be used for evaluation of MetS in clinical practice. The aim of the study was to analyze metabolic characteristics and the ability of LAP to predict MetS in different PCOS phenotypes. Cross-sectional clinical study analyzing 365 women with PCOS divided into four phenotypes according to the ESHRE/ASRM criteria, and 125 healthy BMI-matched controls. In all subjects, LAP was determined and MetS was diagnosed according to the National Cholesterol Education Program/Adult Treatment Panel III (NCEP-ATP III), the International Diabetes Federation (IDF) and the Joint Interim Statement (JIS) criteria. Logistic regression and ROC curve analyses were used to determine predictors of MetS in each PCOS phenotype. All analyses were performed with age and BMI adjustment. All PCOS phenotypes in comparison to controls had higher prevalence of MetS assessed by NCEP-ATP III criteria, and only classic phenotypes when IDF and JIS criteria were used. All phenotypes had the same prevalence of MetS irrespective of used definition. LAP and exhibited the highest diagnostic accuracy and was an independent predictor of MetS in all phenotypes. LAP is an independent and accurate clinical determinant of MetS in all PCOS phenotypes in our Caucasian population. All PCOS phenotypes, including non-classic ones, are metabolically challenged and with cardiovascular risk, particularly phenotype B. © 2016 European Society of Endocrinology.

Longitudinal Changes in Thyroid Function in the Oldest Old and Survival: The Cardiovascular Health Study All-Stars Study

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Waring, Avantika C.; Arnold, Alice M.; Newman, Anne B.; Bùžková, Petra; Hirsch, Calvin

2012-01-01

Context: Data on thyroid function in the oldest old are sparse, and existing studies show conflicting evidence on the relationship between thyroid function and mortality in this age group. Objective: We describe longitudinal changes in thyroid function in a cohort of elderly individuals and determine the relationship between thyroid function and mortality. Design, Setting, and Participants: Eight hundred forty-three participants in the Cardiovascular Health Study All Stars Study who were not taking thyroid medications and had thyroid function testing in 2005–2006 (mean age 85 yr). Main Outcome Measure: Thyroid-stimulating hormone (TSH), free T4 (FT4), total T3, and thyroid peroxidase antibody status were measured in 1992–1993 and 2005–2006. Deaths were ascertained through February 2011. Results: There was a statistically significant 13% increase in TSH, 1.7% increase in FT4, and 13% decrease in total T3 over the 13-yr period. Two hundred eighty-seven deaths occurred over a median follow-up of 5.1 yr. There was no association between subclinical hypothyroidism[hazard ratio (HR) 0.97, 95% confidence interval (CI) 0.66–1.43], TSH level (HR per milliunits per liter 0.94, 95% CI 0.88–1.01), or persistent thyroid peroxidase antibody positivity (HR 1.09, 95% CI 0.62–1.92), and death. However, FT4 was positively associated with death (HR per nanograms per deciliter 2.57, 95% CI 1.32–5.02). Conclusions: TSH increased over time in these older individuals. This elevation was not associated with increased or decreased mortality, although higher FT4 levels were associated with death. These findings raise concern for treatment of mild elevations of TSH in advanced age. Further studies are needed to determine the potential benefit of treating age-related changes in thyroid function. PMID:22879629

Calpain 1 inhibitor BDA-410 ameliorates α-klotho-deficiency phenotypes resembling human aging-related syndromes.

Science.gov (United States)

Nabeshima, Yoko; Washida, Miwa; Tamura, Masaru; Maeno, Akiteru; Ohnishi, Mutsuko; Shiroishi, Toshihiko; Imura, Akihiro; Razzaque, M Shawkat; Nabeshima, Yo-ichi

2014-08-01

Taking good care of elderly is a major challenge of our society, and thus identification of potential drug targets to reduce age-associated disease burden is desirable. α-klotho(-/-) (α-kl) is a short-lived mouse model that displays multiple phenotypes resembling human aging-related syndromes. Such ageing phenotype of α-kl(-/-) mice is associated with activation of a proteolytic enzyme, Calpain-1. We hypothesized that uncontrolled activation of calpain-1 might be causing age-related phenotypes in α-kl-deficient mice. We found that daily administration of BDA-410, a calpain-1 inhibitor, strikingly ameliorated multiple aging-related phenotypes. Treated mice showed recovery of reproductive ability, increased body weight, reduced organ atrophy, and suppression of ectopic calcifications, bone mineral density reduction, pulmonary emphysema and senile atrophy of skin. We also observed ectopic expression of FGF23 in calcified arteries of α-kl(-/-) mice, which might account for the clinically observed association of increased FGF23 level with increased risk of cardiovascular mortality. These findings allow us to propose that modulation of calpain-1 activity is a potential therapeutic option for delaying age-associated organ pathology, particularly caused by the dysregulation of mineral ion homeostasis.

Major dietary patterns and cardiovascular risk factors from childhood to adulthood. The Cardiovascular Risk in Young Finns Study.

Science.gov (United States)

Mikkilä, Vera; Räsänen, Leena; Raitakari, Olli T; Marniemi, Jukka; Pietinen, Pirjo; Rönnemaa, Tapani; Viikari, Jorma

2007-07-01

Studies on the impact of single nutrients on the risk of CVD have often given inconclusive results. Recent research on dietary patterns has offered promising information on the effects of diet as a whole on the risk of CVD. The Cardiovascular Risk in Young Finns Study is an ongoing, prospective cohort study with a 21-year follow-up to date. The subjects were children and adolescents at baseline (3-18 years, n 1768) and adults at the latest follow-up study (24-39 years, n 1037). We investigated the associations between two major dietary patterns and several risk factors for CVD. In longitudinal analyses with repeated measurements, using multivariate mixed linear regression models, the traditional dietary pattern (characterised by high consumption of rye, potatoes, butter, sausages, milk and coffee) was independently associated with total and LDL cholesterol concentrations, apolipoprotein B and C-reactive protein concentrations among both genders, and also with systolic blood pressure and insulin levels among women and concentrations of homocysteine among men (P health-conscious food choices (such as high consumption of vegetables, legumes and nuts, tea, rye, cheese and other dairy products, and alcoholic beverages) was inversely, but less strongly associated with cardiovascular risk factors. Our results support earlier findings that dietary patterns have a role in the development of CVD.

Age-related left ventricular remodeling and associated risk for cardiovascular outcomes: the Multi-Ethnic Study of Atherosclerosis.

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Cheng, Susan; Fernandes, Verônica R S; Bluemke, David A; McClelland, Robyn L; Kronmal, Richard A; Lima, João A C

2009-05-01

Age-related alterations of left ventricular (LV) structure and function that may predispose to cardiovascular events are not well understood. We used cardiac MRI to examine age-related differences in LV structure and function in 5004 participants without overt cardiovascular disease when enrolled in the Multi-Ethnic Study of Atherosclerosis; 1099 participants received additional strain analyses by MRI tagging. We also assessed the relation of age-associated remodeling with cardiovascular outcomes using Cox proportional hazard models adjusting for cardiovascular risk factors. Although LV mass decreased with age (-0.3 g per year), the mass-to-volume ratio markedly increased (+5 mg/mL per year, Pfall in stroke volume (-0.4 mL per year, P or =65 years; hazard ratio, 1.68 [CI 0.77 to 3.68]) individuals with the highest compared to lowest mass-to-volume ratio quintile (P(interaction)=0.013). Age is associated with a phenotype of LV remodeling marked by increased mass-to-volume ratio and accompanied by systolic as well as diastolic myocardial dysfunction that is not reflected by preserved ejection fraction. This pattern of ventricular remodeling confers significant cardiovascular risk, particularly when present earlier in life.

Phenotype expression in women with CMT1X.

LENUS (Irish Health Repository)

Siskind, Carly E

2011-06-01

Charcot-Marie-Tooth disease type 1X (CMT1X) is the second most common inherited peripheral neuropathy. Women with CMT1X typically have a less severe phenotype than men, perhaps because of X-inactivation patterns. Our objective was to determine the phenotype of women with CMT1X and whether X-inactivation patterns in white blood cells (WBCs) differ between females with CMT1X and controls. Thirty-one women with CMT1X were evaluated using the CMT neuropathy score (CMTNS) and the CMT symptom score in cross-sectional and longitudinal analyses. Lower scores correspond to less disability. WBCs were analyzed for X-inactivation pattern by androgen receptor X-inactivation assay in 14 patients and 23 controls. The 31 women\\'s mean CMTNS was 8.35. Two-thirds of the cohort had a mild CMTNS (mean 4.85) and one-third had a moderate CMTNS (mean 14.73). Three patients had a CMTNS of 0. The pattern of X-inactivation did not differ between the affected and control groups. Women with CMT1X presented with variable impairment independent of age, type of mutation, or location of mutation. No evidence supported the presence of a gap junction beta-1 (GJB1) mutation affecting the pattern of X-inactivation in blood. Further studies are planned to determine whether X-inactivation is the mechanism for CMT1X females\\' variable phenotypes.

Postsystolic Shortening by Speckle Tracking Echocardiography Is an Independent Predictor of Cardiovascular Events and Mortality in the General Population

DEFF Research Database (Denmark)

Brainin, Philip; Biering-Sørensen, Sofie Reumert; Møgelvang, Rasmus

2018-01-01

BACKGROUND: Postsystolic shortening (PSS) has been proposed as a novel marker of contractile dysfunction in the myocardium. Our objective was to assess the prognostic potential of PSS on cardiovascular events and death in the general population. METHODS AND RESULTS: The study design consisted...... of a prospective cohort study of 1296 low-risk participants from the general population, who were examined by speckle tracking echocardiography. The primary end point was the composite of heart failure, myocardial infarction, and cardiovascular death, defined as major adverse cardiovascular events (MACEs...... as having MACEs and 236 participants (18%) died. Increasing number of walls with PSS predicted both end points, an association that persisted after adjustment for age, sex, estimated glomerular filtration rate, global longitudinal strain, hypertension, heart rate, left ventricular ejection fraction, LV mass...

Redox signaling in cardiovascular pathophysiology: A focus on hydrogen peroxide and vascular smooth muscle cells

Directory of Open Access Journals (Sweden)

Chang Hyun Byon

2016-10-01

Full Text Available Oxidative stress represents excessive intracellular levels of reactive oxygen species (ROS, which plays a major role in the pathogenesis of cardiovascular disease. Besides having a critical impact on the development and progression of vascular pathologies including atherosclerosis and diabetic vasculopathy, oxidative stress also regulates physiological signaling processes. As a cell permeable ROS generated by cellular metabolism involved in intracellular signaling, hydrogen peroxide (H2O2 exerts tremendous impact on cardiovascular pathophysiology. Under pathological conditions, increased oxidase activities and/or impaired antioxidant systems results in uncontrolled production of ROS. In a pro-oxidant environment, vascular smooth muscle cells (VSMC undergo phenotypic changes which can lead to the development of vascular dysfunction such as vascular inflammation and calcification. Investigations are ongoing to elucidate the mechanisms for cardiovascular disorders induced by oxidative stress. This review mainly focuses on the role of H2O2 in regulating physiological and pathological signals in VSMC.

Systemic Hemodynamic Atherothrombotic Syndrome and Resonance Hypothesis of Blood Pressure Variability: Triggering Cardiovascular Events.

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Kario, Kazuomi

2016-07-01

Blood pressure (BP) exhibits different variabilities and surges with different time phases, from the shortest beat-by-beat to longest yearly changes. We hypothesized that the synergistic resonance of these BP variabilites generates an extraordinarily large dynamic surge in BP and triggers cardiovascular events (the resonance hypothesis). The power of pulses is transmitted to the peripheral sites without attenuation by the large arteries, in individuals with stiffened arteries. Thus, the effect of a BP surge on cardiovascular risk would be especially exaggerated in high-risk patients with vascular disease. Based on this concept, our group recently proposed a new theory of systemic hemodynamic atherothromboltic syndrome (SHATS), a vicious cycle of hemodynamic stress and vascular disease that advances organ damage and triggers cardiovascular disease. Clinical phenotypes of SHATS are large-artery atherothombotic diseases such as stroke, coronary artery disease, and aortic and pheripheral artery disease; small-artery diseases, and microcirculation-related disease such as vascular cognitive dysfunction, heart failure, and chronic kidney disease. The careful consideration of BP variability and vascular diseases such as SHATS, and the early detection and management of SHATS, will achieve more effective individualized cardiovascular protection. In the near future, information and communication technology-based 'anticipation medicine' predicted by the changes of individual BP values could be a promising approach to achieving zero cardiovascular events.

Text mining applied to electronic cardiovascular procedure reports to identify patients with trileaflet aortic stenosis and coronary artery disease.

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Small, Aeron M; Kiss, Daniel H; Zlatsin, Yevgeny; Birtwell, David L; Williams, Heather; Guerraty, Marie A; Han, Yuchi; Anwaruddin, Saif; Holmes, John H; Chirinos, Julio A; Wilensky, Robert L; Giri, Jay; Rader, Daniel J

2017-08-01

Interrogation of the electronic health record (EHR) using billing codes as a surrogate for diagnoses of interest has been widely used for clinical research. However, the accuracy of this methodology is variable, as it reflects billing codes rather than severity of disease, and depends on the disease and the accuracy of the coding practitioner. Systematic application of text mining to the EHR has had variable success for the detection of cardiovascular phenotypes. We hypothesize that the application of text mining algorithms to cardiovascular procedure reports may be a superior method to identify patients with cardiovascular conditions of interest. We adapted the Oracle product Endeca, which utilizes text mining to identify terms of interest from a NoSQL-like database, for purposes of searching cardiovascular procedure reports and termed the tool "PennSeek". We imported 282,569 echocardiography reports representing 81,164 individuals and 27,205 cardiac catheterization reports representing 14,567 individuals from non-searchable databases into PennSeek. We then applied clinical criteria to these reports in PennSeek to identify patients with trileaflet aortic stenosis (TAS) and coronary artery disease (CAD). Accuracy of patient identification by text mining through PennSeek was compared with ICD-9 billing codes. Text mining identified 7115 patients with TAS and 9247 patients with CAD. ICD-9 codes identified 8272 patients with TAS and 6913 patients with CAD. 4346 patients with AS and 6024 patients with CAD were identified by both approaches. A randomly selected sample of 200-250 patients uniquely identified by text mining was compared with 200-250 patients uniquely identified by billing codes for both diseases. We demonstrate that text mining was superior, with a positive predictive value (PPV) of 0.95 compared to 0.53 by ICD-9 for TAS, and a PPV of 0.97 compared to 0.86 for CAD. These results highlight the superiority of text mining algorithms applied to electronic

Marijuana Use and Cardiovascular Disease.

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Franz, Christopher A; Frishman, William H

2016-01-01

Marijuana is currently the most used illicit substance in the world. With the current trend of decriminalization and legalization of marijuana in the US, physicians in the US will encounter more patients using marijuana recreationally over a diverse range of ages and health states. Therefore, it is relevant to review marijuana's effects on human cardiovascular physiology and disease. Compared with placebo, marijuana cigarettes cause increases in heart rate, supine systolic and diastolic blood pressures, and forearm blood flow via increased sympathetic nervous system activity. These actions increase myocardial oxygen demand to a degree that they can decrease the time to exercise-induced angina in patients with a history of stable angina. In addition, marijuana has been associated with triggering myocardial infarctions (MIs) in young male patients. Smoking marijuana has been shown to increase the risk of MI onset by a factor of 4.8 for the 60 minutes after marijuana consumption, and to increase the annual risk of MI in the daily cannabis user from 1.5% to 3% per year. Human and animal models suggest that this effect may be due to coronary arterial vasospasm. However, longitudinal studies have indicated that marijuana use may not have a significant effect on long-term mortality. While further research is required to definitively determine the impact of marijuana on cardiovascular disease, it is reasonable to recommend against recreational marijuana use, especially in individuals with a history of coronary artery disorders.

Distinctive Risk Factors and Phenotype of Younger Patients With Resistant Hypertension: Age Is Relevant.

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Ghazi, Lama; Oparil, Suzanne; Calhoun, David A; Lin, Chee Paul; Dudenbostel, Tanja

2017-05-01

Resistant hypertension, defined as blood pressure >140/90 mm Hg despite using ≥3 antihypertensive medications, is a well-recognized clinical entity. Patients with resistant hypertension are at an increased risk of cardiovascular disease compared with those with more easily controlled hypertension. Coronary heart disease mortality rates of younger adults are stagnating or on the rise. The purpose of our study was to characterize the phenotype and risk factors of younger patients with resistant hypertension, given the dearth of data on cardiovascular risk profile in this cohort. We conducted a cross-sectional analysis with predefined age groups of a large, ethnically diverse cohort of 2170 patients referred to the Hypertension Clinic at the University of Alabama at Birmingham. Patients (n=2068) met the inclusion criteria and were classified by age groups, that is, ≤40 years (12.7% of total cohort), 41 to 55 years (32.1%), 56 to 70 years (36.1%), and ≥71 years (19.1%). Patients aged ≤40 years compared with those aged ≥71 years had significantly earlier onset of hypertension (24.7±7.4 versus 55.0±14.1 years; P hypertension, younger individuals have a distinct phenotype characterized by overlapping risk factors and comorbidities, including obesity, high aldosterone, and high dietary sodium intake compared with elderly. © 2017 American Heart Association, Inc.

Job burnout predicts decline of health-related quality of life among employees with cardiovascular disease: A one-year follow-up study in female nurses.

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Zhang, Min; Loerbroks, Adrian; Li, Jian

To examine whether job burnout is associated with health-related quality of life (HRQOL) in employees with cardiovascular disease. In this longitudinal study, we included 305 female hospital nurses with cardiovascular disease. Job burnout was measured by the 6-item Copenhagen Burnout Inventory at baseline. We categorized study participants into low, intermediate and high levels of job burnout based on tertiles. HRQOL at baseline and at one-year follow-up was operationalized in terms of the physical and mental functioning summary scores of the short form 8-item health survey (SF-8), which is an abbreviated version of the widely used SF-36 with score ranges of 0-100. Linear regression was applied to examine longitudinal associations. After taking into account relevant socio-demographic, behavioral, and work-related covariates as well as HRQOL scores at baseline, we found that both physical functioning and mental functioning declined (by 2.53 points and 3.02 points respectively, pburnout group compared with the low job burnout group. Dose-response relationships were also observed (pburnout predicts decline of HRQOL one year later among employees with cardiovascular disease. Copyright © 2017 Elsevier Inc. All rights reserved.

[Breastfeeding as a method to prevent cardiovascular diseases in the mother and the child].

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Aguilar Cordero, María José; Madrid Baños, Nayra; Baena García, Laura; Mur Villar, Norma; Guisado Barrilao, Rafael; Sánchez López, Antonio Manuel

2015-05-01

Breastfeeding is a recommended practice from all health institutions, both national and international, due to the benefits that it provides for both the nursling's and the mother's health. It has been proved that mothers who breastfeed their children suffer from less cardiovascular disorders, including hypertension, than those women who have never done it. The goal of this review is to analyse the studies that have done some research on breastfeeding as a protection from cardiovascular diseases in the mother and the infant. A systematic search has been carried out and 10 meta-analysis or reviews, 8 original articles of clinical studies, 31 longitudinal or cohort studies and 7 correlational studies of large sample and descriptive were selected. Cardiovascular disease is the main cause of death for women all over the world. Diet, exercise, quitting smoking and blood pressure control are well-known methods to prevent cardiovascular diseases. It has been shown that breastfeeding has a positive impact on the mother and child's blood pressure level, both in the short term and the long term. It is, thus, necessary to provide further information for the population so as to promote breastfeeding and know its benefits. Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.

Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes Afford New Opportunities in Inherited Cardiovascular Disease Modeling

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Daniel R. Bayzigitov

2016-01-01

Full Text Available Fundamental studies of molecular and cellular mechanisms of cardiovascular disease pathogenesis are required to create more effective and safer methods of their therapy. The studies can be carried out only when model systems that fully recapitulate pathological phenotype seen in patients are used. Application of laboratory animals for cardiovascular disease modeling is limited because of physiological differences with humans. Since discovery of induced pluripotency generating induced pluripotent stem cells has become a breakthrough technology in human disease modeling. In this review, we discuss a progress that has been made in modeling inherited arrhythmias and cardiomyopathies, studying molecular mechanisms of the diseases, and searching for and testing drug compounds using patient-specific induced pluripotent stem cell-derived cardiomyocytes.

klf2ash317 Mutant Zebrafish Do Not Recapitulate Morpholino-Induced Vascular and Haematopoietic Phenotypes.

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Peter Novodvorsky

Full Text Available The zinc-finger transcription factor Krϋppel-like factor 2 (KLF2 transduces blood flow into molecular signals responsible for a wide range of responses within the vasculature. KLF2 maintains a healthy, quiescent endothelial phenotype. Previous studies report a range of phenotypes following morpholino antisense oligonucleotide-induced klf2a knockdown in zebrafish. Targeted genome editing is an increasingly applied method for functional assessment of candidate genes. We therefore generated a stable klf2a mutant zebrafish and characterised its cardiovascular and haematopoietic development.Using Transcription Activator-Like Effector Nucleases (TALEN we generated a klf2a mutant (klf2ash317 with a 14bp deletion leading to a premature stop codon in exon 2. Western blotting confirmed loss of wild type Klf2a protein and the presence of a truncated protein in klf2ash317 mutants. Homozygous klf2ash317 mutants exhibit no defects in vascular patterning, survive to adulthood and are fertile, without displaying previously described morphant phenotypes such as high-output cardiac failure, reduced haematopoetic stem cell (HSC development or impaired formation of the 5th accessory aortic arch. Homozygous klf2ash317 mutation did not reduce angiogenesis in zebrafish with homozygous mutations in von Hippel Lindau (vhl, a form of angiogenesis that is dependent on blood flow. We examined expression of three klf family members in wildtype and klf2ash317 zebrafish. We detected vascular expression of klf2b (but not klf4a or biklf/klf4b/klf17 in wildtypes but found no differences in expression that might account for the lack of phenotype in klf2ash317 mutants. klf2b morpholino knockdown did not affect heart rate or impair formation of the 5th accessory aortic arch in either wildtypes or klf2ash317 mutants.The klf2ash317 mutation produces a truncated Klf2a protein but, unlike morpholino induced klf2a knockdown, does not affect cardiovascular development.

Obesity and Cardiovascular Disease.

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Ortega, Francisco B; Lavie, Carl J; Blair, Steven N

2016-05-27

The prevalence of obesity has increased worldwide over the past few decades. In 2013, the prevalence of obesity exceeded the 50% of the adult population in some countries from Oceania, North Africa, and Middle East. Lower but still alarmingly high prevalence was observed in North America (≈30%) and in Western Europe (≈20%). These figures are of serious concern because of the strong link between obesity and disease. In the present review, we summarize the current evidence on the relationship of obesity with cardiovascular disease (CVD), discussing how both the degree and the duration of obesity affect CVD. Although in the general population, obesity and, especially, severe obesity are consistently and strongly related with higher risk of CVD incidence and mortality, the one-size-fits-all approach should not be used with obesity. There are relevant factors largely affecting the CVD prognosis of obese individuals. In this context, we thoroughly discuss important concepts such as the fat-but-fit paradigm, the metabolically healthy but obese (MHO) phenotype and the obesity paradox in patients with CVD. About the MHO phenotype and its CVD prognosis, available data have provided mixed findings, what could be partially because of the adjustment or not for key confounders such as cardiorespiratory fitness, and to the lack of consensus on the MHO definition. In the present review, we propose a scientifically based harmonized definition of MHO, which will hopefully contribute to more comparable data in the future and a better understanding on the MHO subgroup and its CVD prognosis. © 2016 American Heart Association, Inc.

Longitudinal patterns of semantic and episodic memory in frontotemporal lobar degeneration and Alzheimer's disease.

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Xie, Sharon X; Libon, David J; Wang, Xingmei; Massimo, Lauren; Moore, Peachie; Vesely, Luisa; Khan, Alea; Chatterjee, Anjan; Coslett, H Branch; Hurtig, Howard I; Liang, Tsao-Wei; Grossman, Murray

2010-03-01

The longitudinal assessment of episodic and semantic memory was obtained from 236 patients diagnosed with Alzheimer's disease (AD, n = 128) and with frontotemporal lobar degeneration (FTLD, n = 108), including patients with a social comportment/dysexecutive (SOC/EXEC) disorder, progressive nonfluent aphasia (PNFA), semantic dementia (SemD), and corticobasal syndrome (CBS). At the initial assessment, AD patients obtained a lower score on the delayed free recall test than other patients. Longitudinal analyses for delayed free recall found converging performance, with all patients reaching the same level of impairment as AD patients. On the initial evaluation for delayed recognition, AD patients also obtained lower scores than other groups. Longitudinal analyses for delayed recognition test performance found that AD patients consistently produced lower scores than other groups and no convergence between AD and other dementia groups was seen. For semantic memory, there were no initial between-group differences. However, longitudinal analyses for semantic memory revealed group differences over illness duration, with worse performance for SemD versus AD, PNFA, SOC/EXEC, and CBS patients. These data suggest the presence of specific longitudinal patterns of impairment for episodic and semantic memory in AD and FTLD patients suggesting that all forms of dementia do not necessarily converge into a single phenotype.

Cardiovascular disease in patients with osteogenesis imperfecta — a nationwide, register-based cohort study

OpenAIRE

Folkestad, Lars; Hald, Jannie Dahl; Gram, Jeppe; Langdahl, Bente L.; Hermann, Anne Pernille; Diederichsen, Axel CP; Abrahamsen, Bo; Brixen, Kim

2016-01-01

BACKGROUND: Osteogenesis imperfecta (OI) is a hereditary connective tissue disease often due to mutations in genes coding for type 1 collagen. Collagen type 1 is important in the development of the heart and vasculature. Little is known about the risk of cardiovascular disease (CVD) in OI.OBJECTIVE: To investigate the risk of symptomatic CVD in OI.DESIGN: A Danish nationwide, population-based and register-based longitudinal open cohort study.PARTICIPANTS: All patients registered with the diag...

Association of Accelerometry-Measured Physical Activity and Cardiovascular Events in Mobility-Limited Older Adults: The LIFE (Lifestyle Interventions and Independence for Elders) Study.

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Cochrane, Shannon K; Chen, Shyh-Huei; Fitzgerald, Jodi D; Dodson, John A; Fielding, Roger A; King, Abby C; McDermott, Mary M; Manini, Todd M; Marsh, Anthony P; Newman, Anne B; Pahor, Marco; Tudor-Locke, Catrine; Ambrosius, Walter T; Buford, Thomas W

2017-12-02

Data are sparse regarding the value of physical activity (PA) surveillance among older adults-particularly among those with mobility limitations. The objective of this study was to examine longitudinal associations between objectively measured daily PA and the incidence of cardiovascular events among older adults in the LIFE (Lifestyle Interventions and Independence for Elders) study. Cardiovascular events were adjudicated based on medical records review, and cardiovascular risk factors were controlled for in the analysis. Home-based activity data were collected by hip-worn accelerometers at baseline and at 6, 12, and 24 months postrandomization to either a physical activity or health education intervention. LIFE study participants (n=1590; age 78.9±5.2 [SD] years; 67.2% women) at baseline had an 11% lower incidence of experiencing a subsequent cardiovascular event per 500 steps taken per day based on activity data (hazard ratio, 0.89; 95% confidence interval, 0.84-0.96; P =0.001). At baseline, every 30 minutes spent performing activities ≥500 counts per minute (hazard ratio, 0.75; confidence interval, 0.65-0.89 [ P =0.001]) were also associated with a lower incidence of cardiovascular events. Throughout follow-up (6, 12, and 24 months), both the number of steps per day (per 500 steps; hazard ratio, 0.90, confidence interval, 0.85-0.96 [ P =0.001]) and duration of activity ≥500 counts per minute (per 30 minutes; hazard ratio, 0.76; confidence interval, 0.63-0.90 [ P =0.002]) were significantly associated with lower cardiovascular event rates. Objective measurements of physical activity via accelerometry were associated with cardiovascular events among older adults with limited mobility (summary score >10 on the Short Physical Performance Battery) both using baseline and longitudinal data. URL: http://www.clinicaltrials.gov. Unique identifier: NCT01072500. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

The CAPN10 Gene Is Associated with Insulin Resistance Phenotypes in the Spanish Population

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Sáez, María E.; González-Sánchez, José L.; Ramírez-Lorca, Reposo; Martínez-Larrad, María T.; Zabena, Carina; González, Alejandro; Morón, Francisco J.; Ruiz, Agustín; Serrano-Ríos, Manuel

2008-01-01

Cardiovascular disease is the leading cause of morbidity and mortality in the industrialized world. Familial aggregation of cardiovascular risk factors is a frequent finding, but genetic factors affecting its presentation are still poorly understood. The calpain 10 gene (CAPN10) has been associated with type 2 diabetes (T2DM), a complex metabolic disorder with increased risk of cardiovascular disease. Moreover, the CAPN10 gene has been associated with the presence of metabolic syndrome (MS) in T2DM and in polycystic ovary syndrome (PCOS). In this work, we have analysed whether the polymorphisms UCSNP44, -43, -19 and -63 are related to several cardiovascular risk factors in the context of MS. Molecular analysis of CAPN10 gene was performed in 899 individuals randomly chosen from a cross-sectional population-based epidemiological survey. We have found that CAPN10 gene in our population is mainly associated with two indicators of the presence of insulin resistance: glucose levels two hours after a 75-g oral glucose tolerance test (OGTT) and HOMA values, although cholesterol levels and blood pressure values are also influenced by CAPN10 variants. In addition, the 1221/1121 haplogenotype is under-represented in individuals that fulfil the International Diabetes Federation (IDF) diagnostic criteria for MS. Our results suggest that CAPN10 gene is associated with insulin resistance phenotypes in the Spanish population. PMID:18698425

The CAPN10 gene is associated with insulin resistance phenotypes in the Spanish population.

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María E Sáez

Full Text Available Cardiovascular disease is the leading cause of morbidity and mortality in the industrialized world. Familial aggregation of cardiovascular risk factors is a frequent finding, but genetic factors affecting its presentation are still poorly understood. The calpain 10 gene (CAPN10 has been associated with type 2 diabetes (T2DM, a complex metabolic disorder with increased risk of cardiovascular disease. Moreover, the CAPN10 gene has been associated with the presence of metabolic syndrome (MS in T2DM and in polycystic ovary syndrome (PCOS. In this work, we have analysed whether the polymorphisms UCSNP44, -43, -19 and -63 are related to several cardiovascular risk factors in the context of MS. Molecular analysis of CAPN10 gene was performed in 899 individuals randomly chosen from a cross-sectional population-based epidemiological survey. We have found that CAPN10 gene in our population is mainly associated with two indicators of the presence of insulin resistance: glucose levels two hours after a 75-g oral glucose tolerance test (OGTT and HOMA values, although cholesterol levels and blood pressure values are also influenced by CAPN10 variants. In addition, the 1221/1121 haplogenotype is under-represented in individuals that fulfil the International Diabetes Federation (IDF diagnostic criteria for MS. Our results suggest that CAPN10 gene is associated with insulin resistance phenotypes in the Spanish population.

Non-cardiovascular findings in clinical cardiovascular magnetic resonance imaging in children

International Nuclear Information System (INIS)

Ghadimi Mahani, Maryam; Morani, Ajaykumar C.; Lu, Jimmy C.; Dorfman, Adam L.; Fazeli Dehkordy, Soudabeh; Jeph, Sunil; Agarwal, Prachi P.

2016-01-01

With increasing use of pediatric cardiovascular MRI, it is important for all imagers to become familiar with the spectrum of non-cardiovascular imaging findings that can be encountered. This study aims to ascertain the prevalence and nature of these findings in pediatric cardiovascular MRIs performed at our institution. We retrospectively evaluated reports of all cardiovascular MRI studies performed at our institute from January 2008 to October 2012 in patients younger than18 years. Most studies (98%) were jointly interpreted by a pediatric cardiologist and a radiologist. We reviewed the electronic medical records of all cases with non-cardiovascular findings, defined as any imaging finding outside the cardiovascular system. Non-cardiovascular findings were classified into significant and non-significant, based on whether they were known at the time of imaging or they required additional workup or a change in management. In 849 consecutive studies (mean age 9.7 ± 6.3 years), 145 non-cardiovascular findings were found in 140 studies (16.5% of total studies). Overall, 51.0% (74/145) of non-cardiovascular findings were in the abdomen, 30.3% (44/145) were in the chest, and 18.6% (27/145) were in the spine. A total of 19 significant non-cardiovascular findings were observed in 19 studies in individual patients (2.2% of total studies, 47% male, mean age 5.9 ± 6.7 years). Significant non-cardiovascular findings included hepatic adenoma, arterially enhancing focal liver lesions, asplenia, solitary kidney, pelvicaliectasis, renal cystic diseases, gastric distention, adrenal hemorrhage, lung hypoplasia, air space disease, bronchial narrowing, pneumomediastinum and retained surgical sponge. Non-cardiovascular findings were seen in 16.5% of cardiovascular MRI studies in children, of which 2.2% were clinically significant findings. Prevalence and nature of these non-cardiovascular findings are different from those reported in adults. Attention to these findings is important

Non-cardiovascular findings in clinical cardiovascular magnetic resonance imaging in children

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Ghadimi Mahani, Maryam [University of Michigan Health System, C.S. Mott Children' s Hospital, Department of Radiology, Section of Pediatric Radiology, Ann Arbor, MI (United States); Morani, Ajaykumar C. [The University of Texas MD Anderson Cancer Center, Department of Diagnostic Radiology, Houston, TX (United States); Lu, Jimmy C.; Dorfman, Adam L. [University of Michigan Health System, C.S. Mott Children' s Hospital, Department of Pediatrics and Communicable Diseases, Division of Pediatric Cardiology, Ann Arbor, MI (United States); Fazeli Dehkordy, Soudabeh [University of Michigan Health System, C.S. Mott Children' s Hospital, Department of Radiology, Section of Pediatric Radiology, Ann Arbor, MI (United States); Providence Hospital and Medical Centers, Department of Graduate Medical Education, Southfield, MI (United States); Jeph, Sunil [The University of Texas MD Anderson Cancer Center, Department of Diagnostic Radiology, Houston, TX (United States); Geisinger Medical Center, Department of Radiology, Danville, PA (United States); Agarwal, Prachi P. [University of Michigan Health System, Department of Radiology, Division of Cardiothoracic Radiology, Ann Arbor, MI (United States)

2016-04-15

With increasing use of pediatric cardiovascular MRI, it is important for all imagers to become familiar with the spectrum of non-cardiovascular imaging findings that can be encountered. This study aims to ascertain the prevalence and nature of these findings in pediatric cardiovascular MRIs performed at our institution. We retrospectively evaluated reports of all cardiovascular MRI studies performed at our institute from January 2008 to October 2012 in patients younger than18 years. Most studies (98%) were jointly interpreted by a pediatric cardiologist and a radiologist. We reviewed the electronic medical records of all cases with non-cardiovascular findings, defined as any imaging finding outside the cardiovascular system. Non-cardiovascular findings were classified into significant and non-significant, based on whether they were known at the time of imaging or they required additional workup or a change in management. In 849 consecutive studies (mean age 9.7 ± 6.3 years), 145 non-cardiovascular findings were found in 140 studies (16.5% of total studies). Overall, 51.0% (74/145) of non-cardiovascular findings were in the abdomen, 30.3% (44/145) were in the chest, and 18.6% (27/145) were in the spine. A total of 19 significant non-cardiovascular findings were observed in 19 studies in individual patients (2.2% of total studies, 47% male, mean age 5.9 ± 6.7 years). Significant non-cardiovascular findings included hepatic adenoma, arterially enhancing focal liver lesions, asplenia, solitary kidney, pelvicaliectasis, renal cystic diseases, gastric distention, adrenal hemorrhage, lung hypoplasia, air space disease, bronchial narrowing, pneumomediastinum and retained surgical sponge. Non-cardiovascular findings were seen in 16.5% of cardiovascular MRI studies in children, of which 2.2% were clinically significant findings. Prevalence and nature of these non-cardiovascular findings are different from those reported in adults. Attention to these findings is important

The rationale/design of the Guimarães/Vizela study: a multimodal population-based cohort study to determine global cardiovascular risk and disease.

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Cunha, Pedro Guimarães; Cotter, Jorge; Oliveira, Pedro; Vila, Isabel; Sousa, Nuno

2014-06-01

Cardiovascular disease and dementia are growing medical and social problems in aging societies. Appropriate knowledge of cardiovascular disease and cognitive decline risk factors (RFs) are critical for global CVR health preventive intervention. Many epidemiological studies use case definition based on data collected/measured in a single visit, a fact that can overestimate prevalence rates and distant from clinical practice demanding criteria. Portugal displays an elevated stroke mortality rate. However, population's global CV risk characterization is limited, namely, considering traditional/nontraditional RF and new intermediate phenotypes of CV and renal disease. Association of hemodynamic variables (pulse wave velocity and central blood pressure) with global CVR stratification, cognitive performance, and kidney disease are practically inexistent at a dwelling population level. After reviewing published data, we designed a population-based cohort study to analyze the prevalence of these cardiovascular RFs and intermediate phenotypes, using random sampling of adult dwellers living in 2 adjacent cities. Strict definition of phenotypes was planned: subjects were observed twice, and several hemodynamic and other biological variables measured at least 3 months apart. Three thousand thirty-eight subjects were enrolled, and extensive data collection (including central and peripheral blood pressure, pulse wave velocity), sample processing, and biobank edification were carried out. One thousand forty-seven cognitive evaluations were performed. Seeking for CV risk reclassification, early identification of subjects at risk, and evidence of early vascular aging and cognitive and renal function decline, using the strict daily clinical practice criteria, will lead to better resource allocation in preventive measures at a population level.

Cardiovascular assessment of patients with Ullrich-Turner's Syndrome on Doppler echocardiography and magnetic resonance imaging

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Castro Ana Valéria Barros de

2002-01-01

Full Text Available OBJECTIVE: To assess the cardiovascular features of Ullrich-Turner's syndrome using echocardiography and magnetic resonance imaging, and to correlate them with the phenotype and karyotype of the patients. The diagnostic concordance between the 2 methods was also assessed. METHODS: Fifteen patients with the syndrome were assessed by echocardiography and magnetic resonance imaging (cardiac chambers, valves, and aorta. Their ages ranged from 10 to 28 (mean of 16.7 years. The karyotype was analyzed in 11 or 25 metaphases of peripheral blood lymphocytes, or both. RESULTS: The most common phenotypic changes were short stature and spontaneous absence of puberal development (100%; 1 patient had a cardiac murmur. The karyotypes detected were as follows: 45,X (n=7, mosaics (n=5, and deletions (n=3. No echocardiographic changes were observed. In regard to magnetic resonance imaging, coarctation and dilation of the aorta were found in 1 patient, and isolated dilation of the aorta was found in 4 patients. CONCLUSION: The frequencies of coarctation and dilation of the aorta detected on magnetic resonance imaging were similar to those reported in the literature (5.5% to 20%, and 6.3% to 29%, respectively. This confirmed the adjuvant role of magnetic resonance imaging to Doppler echocardiography for diagnosing cardiovascular alterations in patients with Ullrich-Turner's syndrome.

Depression and cardiovascular disease: Epidemiological evidence on their linking mechanisms.

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Penninx, Brenda W J H

2017-03-01

Depression's burden of disease goes beyond functioning and quality of life and extends to somatic health. Results from longitudinal cohort studies converge in illustrating that major depressive disorder (MDD) subsequently increases the risk of cardiovascular morbidity and mortality with about 80%. The impact of MDD on cardiovascular health may be partly explained by mediating mechanisms such as unhealthy lifestyle (smoking, excessive alcohol use, physical inactivity, unhealthy diet, therapy non-compliance) and unfavorable pathophysiological disturbances (autonomic, HPA-axis, metabolic and immuno-inflammatory dysregulations). A summary of the literature findings as well as relevant results from the large-scale Netherlands Study of Depression and Anxiety (N=2981) are presented. Persons with MDD have significantly worse lifestyles as well as more pathophysiological disturbances as compared to healthy controls. Some of these differences seem to be specific for (typical versus 'atypical', or antidepressant treated versus drug-naive) subgroups of MDD patients. Alternative explanations are also present, namely undetected confounding, iatrogenic effects or 'third factors' such as genetics. Copyright © 2016 Elsevier Ltd. All rights reserved.

Metabolic and cardiovascular outcomes of fatherhood: results from a cohort of study in subjects with sexual dysfunction.

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Fisher, Alessandra D; Rastrelli, Giulia; Bandini, Elisa; Corona, Giovanni; Balzi, Daniela; Melani, Cecilia; Monami, Matteo; Matta, Vanessa; Mannucci, Edoardo; Maggi, Mario

2012-11-01

Previous cross-sectional and longitudinal studies reported a negative correlation between fatherhood and testosterone (T) levels, likely due to a centrally mediated downregulation of the hypothalamic-pituitary-gonadal axis. Moreover, epidemiological data indicate that fatherhood might affect metabolic and cardiovascular outcomes, although different results have been reported. Up to now, no studies have evaluated these associations in a population of men seeking treatment for sexual dysfunction (SD). To explore biological and clinical correlates of number of children (NoC) and its possible associations with forthcoming major cardiovascular events (MACE) in a sample of men with SD. A consecutive series of 4,045 subjects (mean age 52 ± 13.1 years old) attending the Outpatient Clinic for SD was retrospectively studied. A subset of the previous sample (N = 1,687) was enrolled in a longitudinal study. Information on MACE was obtained through the City of Florence Registry Office. Among patients studied, 31.6% had no children, while 26.3% reported having one child, 33.4% two, and 8.8% three or more children. Although fatherhood was negatively related with follicle-stimulating hormone levels and positively with testis volume, we found a NoC-dependent, stepwise decrease in T plasma levels, not compensated by a concomitant increase in luteinizing hormone. NoC was associated with a worse metabolic and cardiovascular profile, as well as worse penile blood flows and a higher prevalence of metabolic syndrome (MetS). In the longitudinal study, after adjusting for confounders, NoC was independently associated with a higher incidence of MACE. However, when the presence of MetS was introduced as a further covariate, the association was no longer significant. This study supports the hypothesis that bond maintenance contexts and fatherhood are associated with an adaptive downregulation of the gonadotropin-gonadal axis, even in a sample of men with SD. Moreover, our data suggest that

Influence of somatic state on cardiovascular measurements in pregnancy.

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D'Silva, Lindsay A; Davies, Rhiannon E; Emery, Simon J; Lewis, Michael J

2014-01-01

Normal pregnancy causes marked changes in cardiac and haemodynamic function but there is continuing debate about the patterns of 'normal' change. We believe that this lack of consensus is in large part caused by inappropriate assessment conditions. This study aimed to assess physiological data obtained from pregnant women during multiple steady-states and during between-state changes. The study was a longitudinal characterization of apparently healthy pregnant women aged >18 years with assessments at three antenatal stages (12-16, 26-28 and 34-36 weeks) and at 12 weeks following birth. Cardiovascular and heart rate variability (HRV) measures were quantified non-invasively during a range of states including postural manoeuvre, exercise and respiratory regulation. Cardiovascular and HRV variables were influenced by pregnancy in specific ways: (1) steady-state values were influenced differently to state-change responses; (2) cardiac output (CO) increased progressively throughout pregnancy in all states except supine rest; (3) the ΔCO response to the supine-standing manoeuvre was particularly sensitive to pregnancy stage; (4) blood pressure was unaffected by pregnancy; (6) ΔCO and ΔSBP (systolic blood pressure) were enhanced from mid-pregnancy onwards; (7) ΔHRV responses to state changes were markedly and progressively influenced by pregnancy. This study indicates that cardiovascular function in pregnant women is best quantified during at least one physical state change (in particular during the supine-to-standing manoeuvre) and that assessment during supine rest is inadequate for quantifying antenatal physiological function.

Diet in children with phenylketonuria and risk of cardiovascular disease: A narrative overview.

Science.gov (United States)

Verduci, E; Banderali, G; Moretti, F; Lassandro, C; Cefalo, G; Radaelli, G; Salvatici, E; Giovannini, M

2016-03-01

The aim of this paper is to review the possible relationship of restricted phenylalanine (Phe) diet, a diet primarily comprising low-protein foods and Phe-free protein substitutes, with major cardiovascular risk factors (overweight/obesity, blood lipid profile, plasma levels of homocysteine, adiponectin and free asymmetric dimethylarginine (ADMA), oxidative stress and blood pressure) in PKU children. In PKU children compliant with diet, blood total cholesterol, low-density lipoprotein cholesterol (LDL-C), plasma ADMA levels and diastolic pressure were reported to be lower and plasma adiponectin levels to be higher compared to healthy controls. No difference was observed in overweight prevalence and in high-density lipoprotein cholesterol (HDL-C) levels. Inconsistent results were found for plasma homocysteine levels and antioxidant status. PKU children compliant with diet seem to display non-different cardiovascular risks compared with the healthy population. Well-designed longitudinal studies are required to clarify the potential underlying mechanisms associated with PKU and cardiovascular risk factors. Copyright © 2015 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.

Chemotherapeutic-Induced Cardiovascular Dysfunction: Physiological Effects, Early Detection—The Role of Telomerase to Counteract Mitochondrial Defects and Oxidative Stress

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Quryshi, Nabeel; Norwood Toro, Laura E.; Ait-Aissa, Karima; Kong, Amanda; Beyer, Andreas M.

2018-01-01

Although chemotherapeutics can be highly effective at targeting malignancies, their ability to trigger cardiovascular morbidity is clinically significant. Chemotherapy can adversely affect cardiovascular physiology, resulting in the development of cardiomyopathy, heart failure and microvascular defects. Specifically, anthracyclines are known to cause an excessive buildup of free radical species and mitochondrial DNA damage (mtDNA) that can lead to oxidative stress-induced cardiovascular apoptosis. Therefore, oncologists and cardiologists maintain a network of communication when dealing with patients during treatment in order to treat and prevent chemotherapy-induced cardiovascular damage; however, there is a need to discover more accurate biomarkers and therapeutics to combat and predict the onset of cardiovascular side effects. Telomerase, originally discovered to promote cellular proliferation, has recently emerged as a potential mechanism to counteract mitochondrial defects and restore healthy mitochondrial vascular phenotypes. This review details mechanisms currently used to assess cardiovascular damage, such as C-reactive protein (CRP) and troponin levels, while also unearthing recently researched biomarkers, including circulating mtDNA, telomere length and telomerase activity. Further, we explore a potential role of telomerase in the mitigation of mitochondrial reactive oxygen species and maintenance of mtDNA integrity. Telomerase activity presents a promising indicator for the early detection and treatment of chemotherapy-derived cardiac damage. PMID:29534446

COACH CV: The Seven Clinical Phenotypes of Concussion

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Neil Craton

2017-09-01

Full Text Available Our understanding of the diverse physiological manifestations of concussion is changing rapidly. This has an influence on the clinical assessment of patients who have sustained a concussion. The 2017 Consensus Statement on Concussion in Sport states that numerous post-injury clinical findings, such as cognitive deficits, post-traumatic headaches, dizziness, difficulties with oculomotor function, and depression have all been associated with a poorer prognosis in concussed patients. This demonstrates that there are several potential clinical manifestations after head injury warranting clinical evaluation. We have developed an acronym to guide the office-based assessment of concussed patients to consider each of the potential clinical phenotypes. “COACH CV” prompts the clinician to evaluate for cognitive problems, oculomotor dysfunction, affective disturbances, cervical spine disorders, headaches, and cardiovascular and vestibular anomalies.

Childhood Health Status and Adulthood Cardiovascular Disease Morbidity in Rural China: Are They Related?

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Wang, Qing; Shen, Jay J

2016-06-06

Cardiovascular diseases (CVDs) are among the top health problems of the Chinese population. Although mounting evidence suggests that early childhood health status has an enduring effect on late life chronic morbidity, no study so far has analyzed the issue in China. Using nationally representative data from the 2013 China Health and Retirement Longitudinal Study (CHARLS), a Probit model and Two-Stage Residual Inclusion estimation estimator were applied to analyze the relationship between childhood health status and adulthood cardiovascular disease in rural China. Good childhood health was associated with reduced risk of adult CVDs. Given the long-term effects of childhood health on adulthood health later on, health policy and programs to improve the health status and well-being of Chinese populations over the entire life cycle, especially in persons' early life, are expected to be effective and successful.

Childhood Health Status and Adulthood Cardiovascular Disease Morbidity in Rural China: Are They Related?

Directory of Open Access Journals (Sweden)

Qing Wang

2016-06-01

Full Text Available Cardiovascular diseases (CVDs are among the top health problems of the Chinese population. Although mounting evidence suggests that early childhood health status has an enduring effect on late life chronic morbidity, no study so far has analyzed the issue in China. Using nationally representative data from the 2013 China Health and Retirement Longitudinal Study (CHARLS, a Probit model and Two-Stage Residual Inclusion estimation estimator were applied to analyze the relationship between childhood health status and adulthood cardiovascular disease in rural China. Good childhood health was associated with reduced risk of adult CVDs. Given the long-term effects of childhood health on adulthood health later on, health policy and programs to improve the health status and well-being of Chinese populations over the entire life cycle, especially in persons’ early life, are expected to be effective and successful.

Principal component analysis of cardiovascular risk traits in three generations cohort among Indian Punjabi population

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Badaruddoza

2015-09-01

Full Text Available The current study focused to determine significant cardiovascular risk factors through principal component factor analysis (PCFA among three generations on 1827 individuals in three generations including 911 males (378 from offspring, 439 from parental and 94 from grand-parental generations and 916 females (261 from offspring, 515 from parental and 140 from grandparental generations. The study performed PCFA with orthogonal rotation to reduce 12 inter-correlated variables into groups of independent factors. The factors have been identified as 2 for male grandparents, 3 for male offspring, female parents and female grandparents each, 4 for male parents and 5 for female offspring. This data reduction method identified these factors that explained 72%, 84%, 79%, 69%, 70% and 73% for male and female offspring, male and female parents and male and female grandparents respectively, of the variations in original quantitative traits. The factor 1 accounting for the largest portion of variations was strongly loaded with factors related to obesity (body mass index (BMI, waist circumference (WC, waist to hip ratio (WHR, and thickness of skinfolds among all generations with both sexes, which has been known to be an independent predictor for cardiovascular morbidity and mortality. The second largest components, factor 2 and factor 3 for almost all generations reflected traits of blood pressure phenotypes loaded, however, in male offspring generation it was observed that factor 2 was loaded with blood pressure phenotypes as well as obesity. This study not only confirmed but also extended prior work by developing a cumulative risk scale from factor scores. Till today, such a cumulative and extensive scale has not been used in any Indian studies with individuals of three generations. These findings and study highlight the importance of global approach for assessing the risk and need for studies that elucidate how these different cardiovascular risk factors

Principal component analysis of cardiovascular risk traits in three generations cohort among Indian Punjabi population.

Science.gov (United States)

Badaruddoza; Kumar, Raman; Kaur, Manpreet

2015-09-01

The current study focused to determine significant cardiovascular risk factors through principal component factor analysis (PCFA) among three generations on 1827 individuals in three generations including 911 males (378 from offspring, 439 from parental and 94 from grand-parental generations) and 916 females (261 from offspring, 515 from parental and 140 from grandparental generations). The study performed PCFA with orthogonal rotation to reduce 12 inter-correlated variables into groups of independent factors. The factors have been identified as 2 for male grandparents, 3 for male offspring, female parents and female grandparents each, 4 for male parents and 5 for female offspring. This data reduction method identified these factors that explained 72%, 84%, 79%, 69%, 70% and 73% for male and female offspring, male and female parents and male and female grandparents respectively, of the variations in original quantitative traits. The factor 1 accounting for the largest portion of variations was strongly loaded with factors related to obesity (body mass index (BMI), waist circumference (WC), waist to hip ratio (WHR), and thickness of skinfolds) among all generations with both sexes, which has been known to be an independent predictor for cardiovascular morbidity and mortality. The second largest components, factor 2 and factor 3 for almost all generations reflected traits of blood pressure phenotypes loaded, however, in male offspring generation it was observed that factor 2 was loaded with blood pressure phenotypes as well as obesity. This study not only confirmed but also extended prior work by developing a cumulative risk scale from factor scores. Till today, such a cumulative and extensive scale has not been used in any Indian studies with individuals of three generations. These findings and study highlight the importance of global approach for assessing the risk and need for studies that elucidate how these different cardiovascular risk factors interact with

Beyond the Cholesterol-Lowering Effect of Soy Protein: A Review of the Effects of Dietary Soy and Its Constituents on Risk Factors for Cardiovascular Disease

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D. Dan Ramdath

2017-03-01

Full Text Available The hypocholesterolemic effect of soy is well-documented and this has led to the regulatory approval of a health claim relating soy protein to a reduced risk of cardiovascular disease (CVD. However, soybeans contain additional components, such as isoflavones, lecithins, saponins and fiber that may improve cardiovascular health through independent mechanisms. This review summarizes the evidence on the cardiovascular benefits of non-protein soy components in relation to known CVD risk factors such as hypertension, hyperglycemia, inflammation, and obesity beyond cholesterol lowering. Overall, the available evidence suggests non-protein soy constituents improve markers of cardiovascular health; however, additional carefully designed studies are required to independently elucidate these effects. Further, work is also needed to clarify the role of isoflavone-metabolizing phenotype and gut microbiota composition on biological effect.

MeDALL (Mechanisms of the Development of ALLergy): an integrated approach from phenotypes to systems medicine

DEFF Research Database (Denmark)

Bousquet, J; Anto, J; Auffray, C

2011-01-01

) Building discovery of the relevant mechanisms in IgE-associated allergic diseases in existing longitudinal birth cohorts and Karelian children; (iii) Validation and redefinition of classical and novel phenotypes of IgE-associated allergic diseases; and (iv) Translational integration of systems biology......The origin of the epidemic of IgE-associated (allergic) diseases is unclear. MeDALL (Mechanisms of the Development of ALLergy), an FP7 European Union project (No. 264357), aims to generate novel knowledge on the mechanisms of initiation of allergy and to propose early diagnosis, prevention...... of complementary experts in allergy, epidemiology, allergen biochemistry, immunology, molecular biology, epigenetics, functional genomics, bioinformatics, computational and systems biology. The following steps are proposed: (i) Identification of 'classical' and 'novel' phenotypes in existing birth cohorts; (ii...

Longitudinal analysis of the behavioral phenotype in a novel transgenic rat model of early stages of Alzheimer's disease.

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Galeano, Pablo; Martino Adami, Pamela V; Do Carmo, Sonia; Blanco, Eduardo; Rotondaro, Cecilia; Capani, Francisco; Castaño, Eduardo M; Cuello, A Claudio; Morelli, Laura

2014-01-01

Intraneuronal accumulation of amyloid β (iAβ) has been linked to mild cognitive impairment that may precede Alzheimer's disease (AD) onset. This neuropathological trait was recently mimicked in a novel animal model of AD, the hemizygous transgenic McGill-R-Thy1-APP (Tg(+/-)) rat. The characterization of the behavioral phenotypes in this animal model could provide a baseline of efficacy for earlier therapeutic interventions. The aim of the present study was to undertake a longitudinal study of Aβ accumulation and a comprehensive behavioral evaluation of this transgenic rat model. We assessed exploratory activity, anxiety-related behaviors, recognition memory, working memory, spatial learning and reference memory at 3, 6, and 12 months of age. In parallel, we measured Aβ by ELISA, Western blots and semiquantitative immunohistochemistry in hippocampal samples. SDS-soluble Aβ peptide accumulated at low levels (~9 pg/mg) without differences among ages. However, Western blots showed SDS-resistant Aβ oligomers (~30 kDa) at 6 and 12 months, but not at 3 months. When compared to wild-type (WT), male Tg(+/-) rats exhibited a spatial reference memory deficit in the Morris Water Maze (MWM) as early as 3 months of age, which persisted at 6 and 12 months. In addition, Tg(+/-) rats displayed a working memory impairment in the Y-maze and higher anxiety levels in the Open Field (OF) at 6 and 12 months of age, but not at 3 months. Exploratory activity in the OF was similar to that of WT at all-time points. Spatial learning in the MWM and the recognition memory, as assessed by the Novel Object Recognition Test, were unimpaired at any time point. The data from the present study demonstrate that the hemizygous transgenic McGill-R-Thy1-APP rat has a wide array of behavioral and cognitive impairments from young adulthood to middle-age. The low Aβ burden and early emotional and cognitive deficits in this transgenic rat model supports its potential use for drug discovery purposes in

A longitudinal, population-based twin study of avoidant and obsessive-compulsive personality disorder traits from early to middle adulthood.

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Gjerde, L C; Czajkowski, N; Røysamb, E; Ystrom, E; Tambs, K; Aggen, S H; Ørstavik, R E; Kendler, K S; Reichborn-Kjennerud, T; Knudsen, G P

2015-12-01

The phenotypic stability of avoidant personality disorder (AVPD) and obsessive-compulsive personality disorder (OCPD) has previously been found to be moderate. However, little is known about the longitudinal structure of genetic and environmental factors for these disorders separately and jointly, and to what extent genetic and environmental factors contribute to their stability. AVPD and OCPD criteria were assessed using the Structured Interview for DSM-IV Personality in 2793 young adult twins (1385 pairs, 23 singletons) from the Norwegian Institute of Public Health Twin Panel at wave 1 and 2282 (986 pairs, 310 singletons) of these on average 10 years later at wave 2. Longitudinal biometric models were fitted to AVPD and OCPD traits. For twins who participated at both time-points, the number of endorsed sub-threshold criteria for both personality disorders (PDs) decreased 31% from wave 1 to wave 2. Phenotypic correlations between waves were 0.54 and 0.37 for AVPD and OCPD, respectively. The heritability estimates of the stable PD liabilities were 0.67 for AVPD and 0.53 for OCPD. The genetic correlations were 1.00 for AVPD and 0.72 for OCPD, while the unique environmental influences correlated 0.26 and 0.23, respectively. The correlation between the stable AVPD and OCPD liabilities was 0.39 of which 63% was attributable to genetic influences. Shared environmental factors did not significantly contribute to PD variance at either waves 1 or 2. Phenotypic stability was moderate for AVPD and OCPD traits, and genetic factors contributed more than unique environmental factors to the stability both within and across phenotypes.

Worsening calcification propensity precedes all-cause and cardiovascular mortality in haemodialyzed patients.

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Lorenz, Georg; Steubl, Dominik; Kemmner, Stephan; Pasch, Andreas; Koch-Sembdner, Wilhelm; Pham, Dang; Haller, Bernhard; Bachmann, Quirin; Mayer, Christopher C; Wassertheurer, Siegfried; Angermann, Susanne; Lech, Maciej; Moog, Philipp; Bauer, Axel; Heemann, Uwe; Schmaderer, Christoph

2017-10-17

A novel in-vitro test (T 50 -test) assesses ex-vivo serum calcification propensity which predicts mortality in HD patients. The association of longitudinal changes of T 50 with all-cause and cardiovascular mortality has not been investigated. We assessed T 50 in paired sera collected at baseline and at 24 months in 188 prevalent European HD patients from the ISAR cohort, most of whom were Caucasians. Patients were followed for another 19 [interquartile range: 11-37] months. Serum T 50 exhibited a significant decline between baseline and 24 months (246 ± 64 to 190 ± 68 minutes; p < 0.001). With serum Δ-phosphate showing the strongest independent association with declining T 50 (r = -0.39; p < 0.001) in multivariable linear regression. The rate of decline of T 50 over 24 months was a significant predictor of all-cause (HR = 1.51 per 1SD decline, 95% CI: 1.04 to 2.2; p = 0.03) and cardiovascular mortality (HR = 2.15; 95% CI: 1.15 to 3.97; p = 0.02) in Kaplan Meier and multivariable Cox-regression analysis, while cross-sectional T 50 at inclusion and 24 months were not. Worsening serum calcification propensity was an independent predictor of mortality in this small cohort of prevalent HD patients. Prospective larger scaled studies are needed to assess the value of calcification propensity as a longitudinal parameter for risk stratification and monitoring of therapeutic interventions.

Cardiovascular magnetic resonance in adults with previous cardiovascular surgery.

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von Knobelsdorff-Brenkenhoff, Florian; Trauzeddel, Ralf Felix; Schulz-Menger, Jeanette

2014-03-01

Cardiovascular magnetic resonance (CMR) is a versatile non-invasive imaging modality that serves a broad spectrum of indications in clinical cardiology and has proven evidence. Most of the numerous applications are appropriate in patients with previous cardiovascular surgery in the same manner as in non-surgical subjects. However, some specifics have to be considered. This review article is intended to provide information about the application of CMR in adults with previous cardiovascular surgery. In particular, the two main scenarios, i.e. following coronary artery bypass surgery and following heart valve surgery, are highlighted. Furthermore, several pictorial descriptions of other potential indications for CMR after cardiovascular surgery are given.

Aberrant supracallosal longitudinal bundle: MR features, pathogenesis and associated clinical phenotype

International Nuclear Information System (INIS)

Arrigoni, Filippo; Peruzzo, Denis; Romaniello, Romina; Borgatti, Renato; Righini, Andrea; Parazzini, Cecilia; Colombo, Paola; Bassi, Maria Teresa; Triulzi, Fabio

2016-01-01

To describe the MRI and structural features of a peculiar malformation of the corpus callosum (CC) in a group of young patients with intellectual disability. We studied with conventional MRI and DTI a group of subjects showing an aberrant supracallosal bundle, characterized by the presence of a triangle-shaped bulging above the dorsal surface of CC on the midline. Clinical evaluations, CGH-array and instrumental analysis were also collected. Among 85 patients with malformed CC, we identified 15 subjects that showed the supracallosal bundle. The CC was thickened in five cases, long and thinned in three cases, short and thinned in three cases and it had a ''ribbon-like'' appearance in four subjects. Additional brain anomalies were present in eight cases. DTI colour maps and tractography showed that the bundle had an antero-posterior longitudinal orientation and that the tract bifurcated posteriorly, ending in the posterior hippocampi. Patients had different combinations of neurological symptoms, but all showed mild or severe intellectual disability. Combining radiological and genetic data with embryological knowledge of the development of cerebral commissures, we hypothesize that the supracallosal bundle represents a vestigial structure, the dorsal fornix, present during fetal life. Its persistence is associated with intellectual disability. (orig.)

Influence of somatic state on cardiovascular measurements in pregnancy

International Nuclear Information System (INIS)

D’Silva, Lindsay A; Davies, Rhiannon E; Lewis, Michael J; Emery, Simon J

2014-01-01

Normal pregnancy causes marked changes in cardiac and haemodynamic function but there is continuing debate about the patterns of ‘normal’ change. We believe that this lack of consensus is in large part caused by inappropriate assessment conditions. This study aimed to assess physiological data obtained from pregnant women during multiple steady-states and during between-state changes. The study was a longitudinal characterization of apparently healthy pregnant women aged >18 years with assessments at three antenatal stages (12–16, 26–28 and 34–36 weeks) and at 12 weeks following birth. Cardiovascular and heart rate variability (HRV) measures were quantified non-invasively during a range of states including postural manoeuvre, exercise and respiratory regulation. Cardiovascular and HRV variables were influenced by pregnancy in specific ways: (1) steady-state values were influenced differently to state-change responses; (2) cardiac output (CO) increased progressively throughout pregnancy in all states except supine rest; (3) the ΔCO response to the supine-standing manoeuvre was particularly sensitive to pregnancy stage; (4) blood pressure was unaffected by pregnancy; (6) ΔCO and ΔSBP (systolic blood pressure) were enhanced from mid-pregnancy onwards; (7) ΔHRV responses to state changes were markedly and progressively influenced by pregnancy. This study indicates that cardiovascular function in pregnant women is best quantified during at least one physical state change (in particular during the supine-to-standing manoeuvre) and that assessment during supine rest is inadequate for quantifying antenatal physiological function. (paper)

Hypertriglyceridemic-waist phenotype predicts diabetes: a cohort study in Chinese urban adults

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Zhang Meilin

2012-12-01

Full Text Available Abstract Background Hypertriglycedemic-waist (HTGW phenotype is a simple and inexpensive screening parameter to identify people at increased risk for cardiovascular disease. We evaluated whether the HTGW phenotype predicts prediabetes and diabetes in Chinese urban adults. Methods Two thousand nine hundred and eight (2908 subjects including 1957 men and 951 women, aged 20 years and older, free of prediabetes and diabetes at baseline were enrolled in 2008 and followed for 3 years. Meanwhile, new cases of prediabetes and diabetes were identified via annual physical examination. Cox proportional hazards models were used to assess the association of HTGW phenotype with the incidence of prediabetes and diabetes. Results One thousand five hundred and thirty-three (1533 new prediabetes and 90 new diabetes cases were diagnosed during the follow-up period. The accumulated incidence of prediabetes and diabetes was 52.7% and 3.1%, respectively. Compared with the normal waist normal triglyceride (NWNT group, those in the HTGW group had higher incidence of prediabetes and diabetes for both men and women. The hazard ratio (HR for developing prediabetes in the presence of HTGW phenotype at baseline was 1.51 (95% confidence interval [CI] =1.04-2.19 in women, not in men (HR=1.01; 95% CI = 0.82-1.24, after adjusting for age, body mass index, systolic blood pressure, total cholesterol and low density lipoprotein-cholesterol. The HR for developing diabetes were 4.46 (95% CI = 1.88-10.60 in men and 4.64 (95% CI = 1.20-17.97 in women for people who were HTGW phenotype at baseline, after adjusting for age, body mass index, systolic blood pressure, total cholesterol and low density lipoprotein-cholesterol. Conclusions The HTGW phenotype can be used as a simple screening approach to predict diabetes. By using this approach, it is possible to identify individuals at high-risk for diabetes, which is of great significance in reducing the incidence of diabetes among Chinese

Truncated thioredoxin (Trx-80) promotes pro-inflammatory macrophages of the M1 phenotype and enhances atherosclerosis.

Science.gov (United States)

Mahmood, Dler Faieeq Darweesh; Abderrazak, Amna; Couchie, Dominique; Lunov, Oleg; Diderot, Vimala; Syrovets, Tatiana; Slimane, Mohamed-Naceur; Gosselet, Fabien; Simmet, Thomas; Rouis, Mustapha; El Hadri, Khadija

2013-07-01

Vascular cells are particularly susceptible to oxidative stress that is believed to play a key role in the pathogenesis of cardiovascular disorders. Thioredoxin-1 (Trx-1) is an oxidative stress-limiting protein with anti-inflammatory and anti-apoptotic properties. In contrast, its truncated form (Trx-80) exerts pro-inflammatory effects. Here we analyzed whether Trx-80 might exert atherogenic effects by promoting macrophage differentiation into the M1 pro-inflammatory phenotype. Trx-80 at 1 µg/ml significantly attenuated the polarization of anti-inflammatory M2 macrophages induced by exposure to either IL-4 at 15 ng/ml or IL-4/IL-13 (10 ng/ml each) in vitro, as evidenced by the expression of the characteristic markers, CD206 and IL-10. By contrast, in LPS-challenged macrophages, Trx-80 significantly potentiated the differentiation into inflammatory M1 macrophages as indicated by the expression of the M1 cytokines, TNF-α and MCP-1. When Trx-80 was administered to hyperlipoproteinemic ApoE2.Ki mice at 30 µg/g body weight (b.w.) challenged either with LPS at 30 µg/30 g (b.w.) or IL-4 at 500 ng/30 g (b.w.), it significantly induced the M1 phenotype but inhibited differentiation of M2 macrophages in thymus and liver. When ApoE2.Ki mice were challenged once weekly with LPS for 5 weeks, they showed severe atherosclerotic lesions enriched with macrophages expressing predominantly M1 over M2 markers. Such effect was potentiated when mice received daily, in addition to LPS, the Trx-80. Moreover, the Trx-80 treatment led to a significantly increased aortic lesion area. The ability of Trx-80 to promote differentiation of macrophages into the classical proinflammatory phenotype may explain its atherogenic effects in cardiovascular diseases. Copyright © 2013 Wiley Periodicals, Inc.

Cardiovascular risk factors and events in women with androgen excess.

Science.gov (United States)

Macut, D; Antić, I B; Bjekić-Macut, J

2015-03-01

Androgen excess (AE) was approximated to be present in 7% of the adult population of women. Polycystic ovary syndrome (PCOS) is the most prevalent among them, followed by idiopathic hirsutism (IH), congenital adrenal hyperplasia (CAH), hyperandrogenic insulin-resistant acanthosis nigricans (HAIRAN) syndrome, and androgen-secreting neoplasms (ASNs). Increased cardiovascular risk was implicated in women with AE. Serum testosterone independently increases risk for cardiovascular disease (CVD), and correlates even with indices of subclinical atherosclerosis in various populations of postmenopausal women. Hyperandrogenism in PCOS is closely related to the aggravation of abdominal obesity, and together with insulin resistance forming the metabolic core for the development of CVD. However, phenotypic variability of PCOS generates significant influence on the cardiometabolic risks. Numerous risk factors in PCOS lead to 5-7 times higher risk for CVD and over 2-fold higher risk for coronary heart disease and stroke. However, issue on the cardiometabolic risk in postmenopausal women with hyperandrogenic history is still challenging. There is a significant overlapping in the CVD characteristics of women with PCOS and variants of CAH. Relevant clinical data on the prevalence and cardiometabolic risk and events in women with IH, HAIRAN syndrome or ASNs are scarce. The effects of various oral contraceptives (OCs) and antiandrogenic compounds on metabolic profile are varying, and could be related to the selected populations and different therapy regiments mainly conducted in women with PCOS. It is assumed relation of OCs containing antiandrogenic progestins to the increased risk of cardiovascular and thromboembolic events.

Refractory versus resistant hypertension: Novel distinctive phenotypes

Science.gov (United States)

Dudenbostel, Tanja; Siddiqui, Mohammed; Gharpure, Nitin; Calhoun, David A.

2017-01-01

Resistant hypertension (RHTN) is relatively common with an estimated prevalence of 10-20% of treated hypertensive patients. It is defined as blood pressure (BP) >140/90 mmHg treated with ≥3 antihypertensive medications, including a diuretic, if tolerated. Refractory hypertension is a novel phenotype of severe antihypertensive treatment failure. The proposed definition for refractory hypertension, i.e. BP >140/90 mmHg with use of ≥5 different antihypertensive medications, including a diuretic and a mineralocorticoid receptor antagonist (MRA) has been applied inconsistently. In comparison to RHTN, refractory hypertension seems to be less prevalent than RHTN. This review focuses on current knowledge about this novel phenotype compared with RHTN including definition, prevalence, mechanisms, characteristics and comorbidities, including cardiovascular risk. In patients with RHTN excess fluid retention is thought to be a common mechanism for the development of RHTN. Recently, evidence has emerged suggesting that refractory hypertension may be more of neurogenic etiology due to increased sympathetic activity as opposed to excess fluid retention. Treatment recommendations for RHTN are generally based on use and intensification of diuretic therapy, especially with the combination of a long-acting thiazide-like diuretic and an MRA. Based on findings from available studies, such an approach does not seem to be a successful strategy to control BP in patients with refractory hypertension and effective sympathetic inhibition in such patients, either with medications and/or device based approaches may be needed. PMID:29034321

Associations of Health Club Membership with Physical Activity and Cardiovascular Health.

Directory of Open Access Journals (Sweden)

Elizabeth C Schroeder

Full Text Available This study evaluates whether a health club membership is associated with meeting the US physical activity (PA guidelines and/or favorable cardiovascular health.Using cross-sectional data of health club members (n = 204 and non-members (n = 201 from April to August 2013, this is the first study to our knowledge to examine a health club membership in relation to objectively measured cardiovascular health indicators including resting blood pressure, resting heart rate, body mass index, waist circumference, and cardiorespiratory fitness based on a non-exercise test algorithm. To determine the total PA and sedentary time, this study used a comprehensive PA questionnaire about both aerobic and resistance activities at the health club, as well as lifestyle activities in other settings, which was developed based on the International Physical Activity Questionnaire (IPAQ.The odds ratios (95% confidence interval of meeting either the aerobic, resistance, or both aerobic and resistance PA guidelines for members compared to non-members were 16.5 (9.8-27.6, 10.1 (6.2-16.3, and 13.8 (8.5-22.4, respectively. Significant associations of health club membership with more favorable cardiovascular health outcomes and sedentary behavior were observed for resting heart rate (B: -4.8 b/min, p1 year had more favorable health outcomes, with a smaller waist circumference (men, B: -4.0 cm, p = 0.04; women, B: -3.4 cm, p = 0.06, compared to non-members.Health club membership is associated with significantly increased aerobic and resistance physical activity levels and more favorable cardiovascular health outcomes compared to non-members. However, longitudinal, randomized controlled trials would be clearly warranted as cross-sectional data prohibits causal inferences.

A Distinct DNA Methylation Shift in a Subset of Glioma CpG Island Methylator Phenotypes during Tumor Recurrence

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Camila Ferreira de Souza

2018-04-01

Full Text Available Summary: Glioma diagnosis is based on histomorphology and grading; however, such classification does not have predictive clinical outcome after glioblastomas have developed. To date, no bona fide biomarkers that significantly translate into a survival benefit to glioblastoma patients have been identified. We previously reported that the IDH mutant G-CIMP-high subtype would be a predecessor to the G-CIMP-low subtype. Here, we performed a comprehensive DNA methylation longitudinal analysis of diffuse gliomas from 77 patients (200 tumors to enlighten the epigenome-based malignant transformation of initially lower-grade gliomas. Intra-subtype heterogeneity among G-CIMP-high primary tumors allowed us to identify predictive biomarkers for assessing the risk of malignant recurrence at early stages of disease. G-CIMP-low recurrence appeared in 9.5% of all gliomas, and these resembled IDH-wild-type primary glioblastoma. G-CIMP-low recurrence can be characterized by distinct epigenetic changes at candidate functional tissue enhancers with AP-1/SOX binding elements, mesenchymal stem cell-like epigenomic phenotype, and genomic instability. Molecular abnormalities of longitudinal G-CIMP offer possibilities to defy glioblastoma progression. : IDH-mutant lower-grade glioma glioblastoma often progresses to a more aggressive phenotype upon recurrence. de Souza et al. examines the intra-subtype heterogeneity of initial G-CIMP-high and use this information to identify predictive biomarkers for assessing the risk of recurrence and malignant transformation. Keywords: longitudinal gliomas, DNA methylation, IDH mutation, G-CIMP-high, intra-subtype heterogeneity, malignant transformation and recurrence, G-CIMP-low, stem cell-like glioblastoma, predictive biomarkers

Sympathetic neurons are a powerful driver of myocyte function in cardiovascular disease.

Science.gov (United States)

Larsen, Hege E; Lefkimmiatis, Konstantinos; Paterson, David J

2016-12-14

Many therapeutic interventions in disease states of heightened cardiac sympathetic activity are targeted to the myocytes. However, emerging clinical data highlights a dominant role in disease progression by the neurons themselves. Here we describe a novel experimental model of the peripheral neuro-cardiac axis to study the neuron's ability to drive a myocyte cAMP phenotype. We employed a co-culture of neonatal ventricular myocytes and sympathetic stellate neurons from normal (WKY) and pro-hypertensive (SHR) rats that are sympathetically hyper-responsive and measured nicotine evoked cAMP responses in the myocytes using a fourth generation FRET cAMP sensor. We demonstrated the dominant role of neurons in driving the myocyte ß-adrenergic phenotype, where SHR cultures elicited heightened myocyte cAMP responses during neural activation. Moreover, cross-culturing healthy neurons onto diseased myocytes rescued the diseased cAMP response of the myocyte. Conversely, healthy myocytes developed a diseased cAMP response if diseased neurons were introduced. Our results provide evidence for a dominant role played by the neuron in driving the adrenergic phenotype seen in cardiovascular disease. We also highlight the potential of using healthy neurons to turn down the gain of neurotransmission, akin to a smart pre-synaptic ß-blocker.

Circulating early biomarkers of atherogenesis in participants of the Longitudinal Study of Adult Health (ELSA-Brasil) without diabetes or cardiovascular disease.

Science.gov (United States)

Almeida-Pititto, Bianca de; Ribeiro-Filho, Fernando Flexa; Barreto, Sandhi; Duncan, Bruce B; Schmidt, Maria Inês; Lotufo, Paulo A; Bensenor, Isabela M; Ferreira, Sandra R G

2016-01-01

Our aim was to describe the distribution of selected biomarkers according to age and sex, adjusted for HOMA-IR and adiposity, in a subset of middle-aged individuals of Brazilian Longitudinal Study of Adult Health-ELSA without diabetes mellitus or CVD. This cross-sectional study was conducted in 998 participants of the ELSA-Brasil without diabetes and/or cardiovascular disease. In addition to the traditional risk factors, several biomarkers concentrations were compared according to sex, age groups (35-44; 45-54 yrs) and HOMA-IR tertiles. Linear regression was used to examine independent associations of sex and age with selected novel biomarkers, adjusted for body adiposity and HOMA-IR. Fifty-five percent were women. Men had higher mean values of body mass index, waist circumference, blood pressure, plasma glucose, HOMA-IR, worse lipid profile and higher E-selectin and lower leptin concentrations than women; while women had higher levels of HDL-cholesterol and leptin than men. Mean values of waist circumference, systolic BP, plasma glucose and apolipoprotein B (Apo B) increased with age in both sexes. Leptin and E-selectin concentrations increased across HOMA-IR tertiles. Independent associations of Apo B with age were found only in male sex, while of leptin with body mass index and HOMA-IR, and of E-selectin with HOMA-IR in both sexes. In conclusion, our data indicate age, sex, adiposity and, consequently, insulin resistance, influence circulating levels of Apo B, leptin and E-selectin, suggesting that those aspects should be taken into consideration when assessing these parameters for research or clinical purposes in individuals at relatively low cardiometabolic risk.

HIV and Cardiovascular Disease

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... Select a Language: Fact Sheet 652 HIV and Cardiovascular Disease HIV AND CARDIOVASCULAR DISEASE WHY SHOULD PEOPLE WITH HIV CARE ABOUT CVD? ... OF CVD? WHAT ABOUT CHANGING MEDICATIONS? HIV AND CARDIOVASCULAR DISEASE Cardiovascular disease (CVD) includes a group of problems ...

Postirradiation cardiovascular dysfunction

International Nuclear Information System (INIS)

Hawkins, R.N.; Cockerham, L.G.

1987-01-01

Cardiovascular dysfunction may be defined as the inability of any element of the cardiovascular system to perform adequately upon demand, leading to inadequate performance and nutritive insufficiency of various parts of the body. Exposure to supralethal doses of radiation (accidental and therapeutic) has been show to induce significant alterations in cardiovascular function in man. These findings indicate that, after irradiation, cardiovascular function is a major determinant of continued performance and even survival. For the two persons who received massive radiation doses (45 and 88 Gy, respectively) in criticality accidents, the inability to maintain systematic arterial blood pressure (AP) was the immediate cause of death. In a study of cancer patients given partial-body irradiation, two acute lethalities were attributed to myocardial infarction after an acute hypotensive episode during the first few hours postexposure. Although radiation-induced cardiovascular dysfunction has been observed in many species, its severity, duration, and even etiology may vary with the species, level of exposure, and dose rate. For this reason, our consideration of the effects of radiation on cardiovascular performance is limited to the circulatory derangements that occur in rat, dog, and monkey after supralethal doses and lead to radiation-induced cardiovascular dysfunction in these experimental models. The authors consider other recent data as they pertain to the etiology of cardiovascular dysfunction in irradiated animals

A simple algorithm for the identification of clinical COPD phenotypes

DEFF Research Database (Denmark)

Burgel, Pierre-Régis; Paillasseur, Jean-Louis; Janssens, Wim

2017-01-01

This study aimed to identify simple rules for allocating chronic obstructive pulmonary disease (COPD) patients to clinical phenotypes identified by cluster analyses. Data from 2409 COPD patients of French/Belgian COPD cohorts were analysed using cluster analysis resulting in the identification...... of subgroups, for which clinical relevance was determined by comparing 3-year all-cause mortality. Classification and regression trees (CARTs) were used to develop an algorithm for allocating patients to these subgroups. This algorithm was tested in 3651 patients from the COPD Cohorts Collaborative...... International Assessment (3CIA) initiative. Cluster analysis identified five subgroups of COPD patients with different clinical characteristics (especially regarding severity of respiratory disease and the presence of cardiovascular comorbidities and diabetes). The CART-based algorithm indicated...

Differential association between sarcopenia and metabolic phenotype in Korean young and older adults with and without obesity.

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Hwang, You-Cheol; Cho, In-Jin; Jeong, In-Kyung; Ahn, Kyu Jeung; Chung, Ho Yeon

2017-01-01

To determine whether sarcopenia was associated with metabolic phenotype in subjects with and without obesity. A total of 6,021 participants (2,592 men, 3,429 women) aged 30 to 93 years were assessed using data from the 2009 Korea National Health and Nutrition Examination Survey. Sarcopenia was defined as appendicular skeletal muscle mass divided by weight (%) that is young adults. Metabolically unhealthy was defined as ≥2 components of metabolic syndrome or the presence of hypertension, diabetes, or cardiovascular disease. Obesity was defined as body mass index ≥25.0 kg/m 2 . Sarcopenia was associated with a metabolically unhealthy phenotype in nonobese men independent of age, smoking, regular physical activity, daily energy intake, total body fat, fasting insulin, non-HDL cholesterol, white blood cell count, ferritin level, and 25(OH) vitamin D level (OR per 1 SD increment (95% CI) 1.88 (1.28-2.75), P obesity. Sarcopenia was independently associated with a metabolically unhealthy phenotype in nonobese men, but this association was not evident in nonobese women or subjects with obesity. © 2016 The Obesity Society.

The differential impact of subjective and objective aspects of social engagement on cardiovascular risk factors

LENUS (Irish Health Repository)

Kamiya, Yumiko

2010-11-02

Abstract Background This article provides new insights into the impact of social engagement on CVD risk factors in older adults. We hypothesized that objective (social participation, social ties and marital status) and subjective (emotional support) aspects of social engagement are independently associated with objective measures of cardiovascular risk. Methods Data from the English Longitudinal Study on Ageing (ELSA) were analyzed. The effects of social participation, social ties, marital status, and emotional support on hypertension, obesity, high sensitivity C-reactive protein, and fibrinogen were estimated by logistic regression controlling for age, sex, education, physical function, depression, cardiovascular disease, other chronic diseases, physical activity, and smoking. Results Social participation is a consistent predictor of low risk for four risk factors, even after controlling for a wide range of covariates. Being married is associated with lower risk for hypertension. Social ties and emotional support are not significantly associated with any of the cardiovascular risk factors. Conclusion Our analysis suggests that participation in social activities has a stronger association with CV risk factors than marital status, social ties or emotional support. Different forms of social engagement may therefore have different implications for the biological risk factors involved.

The Putative Role of the Antiageing Protein Klotho in Cardiovascular and Renal Disease

Directory of Open Access Journals (Sweden)

Giuseppe Maltese

2012-01-01

Full Text Available Ageing is a multifactorial process often characterized by a progressive decline in physiological function(s. Ageing can and is often associated with an increased incidence of cardiovascular and renal disease. Klotho is a novel antiageing gene that encodes a protein with multiple pleiotropic functions including an emerging role in cardiorenal disease. Mice deficient for this gene display a phenotype of premature human ageing characterized by diffuse vascular calcification, altered calcium/phosphate metabolism, and shortened lifespan. Klotho is mainly expressed in the renal tubules but it also exists as circulating soluble form detectable in the blood, with systemic effects. Reduction in soluble Klotho has been associated with renal disease, hyperphosphataemia, increased oxidative stress, endothelial dysfunction, and diffuse vascular calcification. Conversely, overexpression of Klotho promotes cardiovascular-renal protection. The majority of the research on Klotho has been conducted in vitro and in animal studies but there is emerging data from human studies which suggest that Klotho may be a modifiable factor involved in the pathogenesis of cardiovascular and renal disease in at-risk populations. Further data is required to confirm if this novel protein can emerge as therapeutic tool that may be used to prevent or slow progression of cardiorenal disease.

Induced pluripotent stem cell-derived cardiomyocytes for cardiovascular disease modeling and drug screening.

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Sharma, Arun; Wu, Joseph C; Wu, Sean M

2013-12-24

Human induced pluripotent stem cells (hiPSCs) have emerged as a novel tool for drug discovery and therapy in cardiovascular medicine. hiPSCs are functionally similar to human embryonic stem cells (hESCs) and can be derived autologously without the ethical challenges associated with hESCs. Given the limited regenerative capacity of the human heart following myocardial injury, cardiomyocytes derived from hiPSCs (hiPSC-CMs) have garnered significant attention from basic and translational scientists as a promising cell source for replacement therapy. However, ongoing issues such as cell immaturity, scale of production, inter-line variability, and cell purity will need to be resolved before human clinical trials can begin. Meanwhile, the use of hiPSCs to explore cellular mechanisms of cardiovascular diseases in vitro has proven to be extremely valuable. For example, hiPSC-CMs have been shown to recapitulate disease phenotypes from patients with monogenic cardiovascular disorders. Furthermore, patient-derived hiPSC-CMs are now providing new insights regarding drug efficacy and toxicity. This review will highlight recent advances in utilizing hiPSC-CMs for cardiac disease modeling in vitro and as a platform for drug validation. The advantages and disadvantages of using hiPSC-CMs for drug screening purposes will be explored as well.

Measurements of Pulmonary Artery Size for Assessment of Pulmonary Hypertension by Cardiovascular Magnetic Resonance and Clinical Application

Directory of Open Access Journals (Sweden)

Fan YANG

2017-02-01

Full Text Available Background and objective Pulmonary hypertension (PH often leads to dilatation of main pulmonary artery (MPA. MPA measurements can be used to predict PH. This aim of this study is to investigate power of MPA vessel indices, which are acquired from cardiovascular magnetic resonance, to evaluate PH. Methods Cardiovascular-magnetic-resonance-determined parameters of MPA were acquired and calculated in 83 PH patients, whose diagnosis were confirmed with right heart catheterization and 49 healthy volunteers; these parameters included MPA diameter (DPA, ratio of DPA and ascending aorta diameter (DPA/DAo, max mean diameter (MDmax, min mean diameter (MDmin, fraction transverse diameter (fTD, fraction longitudinal diameter (fLD, and distensibility. Results Compared with control group, DPA, DPA/DAo, MDmax, and MDmin were significantly higher in patients with PH (P28.4 mm, and MDmax>32.4 mm (area under the curve, AUC=0.979, 0.981 showed best performance in predicting PH, yielding highest specificity at 100%. Conclusion Noninvasive cardiovascular-magnetic-resonance-derived MPA measurements provide excellent and practical reference in clinical settings for detecting PH.

Exosomes as agents of change in the cardiovascular system.

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Poe, A J; Knowlton, A A

2017-10-01

Exosomes have an evolving role in paracrine and autocrine signaling, which is enhanced because these lipid vesicles are quite stable and can deliver miRNA, DNA, protein and other molecules to cells throughout the body. Most cell types release exosomes, and exosomes are found in all biological fluids, making them accessible biomarkers. Significantly, exosomes can carry a biologically potent cargo, which can alter the phenotype of recipient cells. In the cardiovascular system exosomes have been primarily studied for their role in mediating the beneficial effects of mesenchymal stem cells after myocardial injury. Exosomes released by cardiac cells in disease states, such as myocardial ischemia, can potentially have important pathophysiologic effects on other cardiac cells as well as on distant organs. Published by Elsevier Ltd.

Eating competence of elderly Spanish adults is associated with a healthy diet and a favorable cardiovascular disease risk profile.

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Lohse, Barbara; Psota, Tricia; Estruch, Ramón; Zazpe, Itziar; Sorli, José V; Salas-Salvadó, Jordi; Serra, Mercè; Krall, Jodi Stotts; Márquez, Fabiola; Ros, Emilio

2010-07-01

Eating competence (EC), a bio-psychosocial model for intrapersonal approaches to eating and food-related behaviors, is associated with less weight dissatisfaction, lower BMI, and increased HDL-cholesterol in small U.S. studies, but its relationship to nutrient quality and overall cardiovascular risk have not been examined. Prevención con Dieta Mediterránea (PREDIMED) is a 5-y controlled clinical trial evaluating Mediterranean diet efficacy on the primary prevention of cardiovascular diseases (CVD) in Spain. In a cross-sectional study, 638 PREDIMED participants (62% women, mean age 67 y) well phenotyped for cardiovascular risk factors were assessed for food intake and EC using validated questionnaires. Overall, 45.6% were eating-competent. EC was associated with being male and energy intake (P diet (P 5.6 mmol/L (0.71; 95% CI 0.51-0.98) and HDL-cholesterol or =3.4 mmol/L were 0.1). Our findings support further examination of EC as a strategy for enhancing diet quality and CVD prevention.

Semantic Disease Gene Embeddings (SmuDGE): phenotype-based disease gene prioritization without phenotypes

KAUST Repository

AlShahrani, Mona; Hoehndorf, Robert

2018-01-01

In the past years, several methods have been developed to incorporate information about phenotypes into computational disease gene prioritization methods. These methods commonly compute the similarity between a disease's (or patient's) phenotypes and a database of gene-to-phenotype associations to find the phenotypically most similar match. A key limitation of these methods is their reliance on knowledge about phenotypes associated with particular genes which is highly incomplete in humans as well as in many model organisms such as the mouse. Results: We developed SmuDGE, a method that uses feature learning to generate vector-based representations of phenotypes associated with an entity. SmuDGE can be used as a trainable semantic similarity measure to compare two sets of phenotypes (such as between a disease and gene, or a disease and patient). More importantly, SmuDGE can generate phenotype representations for entities that are only indirectly associated with phenotypes through an interaction network; for this purpose, SmuDGE exploits background knowledge in interaction networks comprising of multiple types of interactions. We demonstrate that SmuDGE can match or outperform semantic similarity in phenotype-based disease gene prioritization, and furthermore significantly extends the coverage of phenotype-based methods to all genes in a connected interaction network.

Semantic Disease Gene Embeddings (SmuDGE): phenotype-based disease gene prioritization without phenotypes

KAUST Repository

Alshahrani, Mona

2018-04-30

In the past years, several methods have been developed to incorporate information about phenotypes into computational disease gene prioritization methods. These methods commonly compute the similarity between a disease\\'s (or patient\\'s) phenotypes and a database of gene-to-phenotype associations to find the phenotypically most similar match. A key limitation of these methods is their reliance on knowledge about phenotypes associated with particular genes which is highly incomplete in humans as well as in many model organisms such as the mouse. Results: We developed SmuDGE, a method that uses feature learning to generate vector-based representations of phenotypes associated with an entity. SmuDGE can be used as a trainable semantic similarity measure to compare two sets of phenotypes (such as between a disease and gene, or a disease and patient). More importantly, SmuDGE can generate phenotype representations for entities that are only indirectly associated with phenotypes through an interaction network; for this purpose, SmuDGE exploits background knowledge in interaction networks comprising of multiple types of interactions. We demonstrate that SmuDGE can match or outperform semantic similarity in phenotype-based disease gene prioritization, and furthermore significantly extends the coverage of phenotype-based methods to all genes in a connected interaction network.

Gender aspects of the relationship between migraine and cardiovascular risk factors: A cross-sectional evaluation in the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil).

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Goulart, Alessandra C; Santos, Itamar S; Lotufo, Paulo A; Benseñor, Isabela M

2015-10-01

The relationship between cardiovascular risk factors (CVRF) and migraine is controversial and might be different in both genders. These associations were evaluated in Brazilian middle-aged men and women from the Longitudinal Study of Adult Health (ELSA-Brasil). The cross-sectional relationship between our main outcome, which was migraine headache (definite, probable and overall), and CVRF was evaluated in the total sample and according to gender. We calculated frequencies and odds ratios (95% CI) for this relationship using binary and multinomial logistic regression analyses in crude, age-adjusted and multivariable models adjusted by potential confounders. Of 14,953 individuals who completed the data about headache and CVRF, the frequency of one-year migraine was of 29.5% (22.5% in women and 7.0% in men). In the multivariable-adjusted regression analyses, an inverse association between hypertension (OR, 0.53; 95% CI, 0.36-0.79), metabolic syndrome (OR, 0.65; 95% CI, 0.43-0.99) and definite migraine were confirmed for men, but not for women. In the opposite direction, a positive association between migraine headaches (definite, probable and overall) and dyslipidemia (overall migraine OR, 1.25; 95% CI, 1.13-1.38) was observed only for women, but not for men. A gender influence on the relationship between migraine and CVRF was verified in the ELSA-Brasil. © International Headache Society 2015.

A comparative study on genetic and environmental influences on metabolic phenotypes in Eastern (Chinese) and Western (Danish) populations

DEFF Research Database (Denmark)

Li, Shuxia

2015-01-01

the risk of clinic diseases e.g. diabetes, atherosclerosis, stroke and cardiovascular disease. Metabolic phenotypes, similar to most complex traits, can be influenced by both genetic and environmental factors as well as their interplay. Many family and twin studies have demonstrated both genetic...... and environmental factors play important role in the variation of metabolic phenotypes and intra-individual change over time. Although both genetic and environmental factors are involved the development of metabolic disorders, the role of environment should be emphasized as the expression or function of gene can...... be regulated to adapt to existing environmental circumstance. In other words, adaptive evolution in populations under distinct environmental and cultural circumstances could have resulted in varying genetic basis of metabolic factors and development of metabolic disorders or diseases. Thus, it can...

Anti-atherosclerotic plants which modulate the phenotype of vascular smooth muscle cells.

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Saleh Al-Shehabi, Tuqa; Iratni, Rabah; Eid, Ali H

2016-10-15

Cardiovascular disease (CVD) remains the leading cause of global death, with atherosclerosis being a major contributor to this mortality. Several mechanisms are implicated in the pathogenesis of this disease. A key element in the development and progression of atherosclerotic lesions is the phenotype of vascular smooth muscle cells. Under pathophysiologic conditions such as injury, these cells switch from a contractile to a synthetic phenotype that often possesses high proliferative and migratory capacities. Despite major advances made in the management and treatment of atherosclerosis, mortality associated with this disease remains high. This mandates that other approaches be sought. Herbal medicine, especially for the treatment of CVD, has been gaining more attention in recent years. This is in no small part due to the evidence-based values associated with the consumption of many plants as well as the relatively cheaper prices, easier access and conventional folk medicine "inherited" over generations. Sections: In this review, we provide a brief introduction about the pathogenesis of atherosclerosis then we highlight the role of vascular smooth muscle cells in this disease, especially when a phenotypic switch of these cells arises. We then thoroughly discuss the various plants that show potentially beneficial effects as anti-atherosclerotic, with prime attention given to herbs and plants that inhibit the phenotypic switch of vascular smooth muscle cells. Accumulating evidence provides the justification for the use of botanicals in the treatment or prevention of atherosclerosis. However, further studies, especially clinical ones, are warranted to better define several pharmacological parameters of these herbs, such as toxicity, tolerability, and efficacy. Copyright © 2015 Elsevier Ltd. All rights reserved.

Phenotypic plasticity, costs of phenotypes, and costs of plasticity

DEFF Research Database (Denmark)

Callahan, Hilary S; Maughan, Heather; Steiner, Uli

2008-01-01

Why are some traits constitutive and others inducible? The term costs often appears in work addressing this issue but may be ambiguously defined. This review distinguishes two conceptually distinct types of costs: phenotypic costs and plasticity costs. Phenotypic costs are assessed from patterns...... of covariation, typically between a focal trait and a separate trait relevant to fitness. Plasticity costs, separable from phenotypic costs, are gauged by comparing the fitness of genotypes with equivalent phenotypes within two environments but differing in plasticity and fitness. Subtleties associated with both...... types of costs are illustrated by a body of work addressing predator-induced plasticity. Such subtleties, and potential interplay between the two types of costs, have also been addressed, often in studies involving genetic model organisms. In some instances, investigators have pinpointed the mechanistic...

Genetic and Computational Approaches for Studying Plant Development and Abiotic Stress Responses Using Image-Based Phenotyping

Science.gov (United States)

Campbell, M. T.; Walia, H.; Grondin, A.; Knecht, A.

2017-12-01

The development of abiotic stress tolerant crops (i.e. drought, salinity, or heat stress) requires the discovery of DNA sequence variants associated with stress tolerance-related traits. However, many traits underlying adaptation to abiotic stress involve a suite of physiological pathways that may be induced at different times throughout the duration of stress. Conventional single-point phenotyping approaches fail to fully capture these temporal responses, and thus downstream genetic analysis may only identify a subset of the genetic variants that are important for adaptation to sub-optimal environments. Although genomic resources for crops have advanced tremendously, the collection of phenotypic data for morphological and physiological traits is laborious and remains a significant bottleneck in bridging the phenotype-genotype gap. In recent years, the availability of automated, image-based phenotyping platforms has provided researchers with an opportunity to collect morphological and physiological traits non-destructively in a highly controlled environment. Moreover, these platforms allow abiotic stress responses to be recorded throughout the duration of the experiment, and have facilitated the use of function-valued traits for genetic analyses in major crops. We will present our approaches for addressing abiotic stress tolerance in cereals. This talk will focus on novel open-source software to process and extract biological meaningful data from images generated from these phenomics platforms. In addition, we will discuss the statistical approaches to model longitudinal phenotypes and dissect the genetic basis of dynamic responses to these abiotic stresses throughout development.

Associations of Fitness, Physical Activity, Strength, and Genetic Risk With Cardiovascular Disease: Longitudinal Analyses in the UK Biobank Study.

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Tikkanen, Emmi; Gustafsson, Stefan; Ingelsson, Erik

2018-04-09

Background -Observational studies have shown inverse associations among fitness, physical activity, and cardiovascular disease. However, little is known about these associations in individuals with elevated genetic susceptibility for these diseases. Methods -We estimated associations of grip strength, objective and subjective physical activity, and cardiorespiratory fitness with cardiovascular events and all-cause death in a large cohort of 502635 individuals from the UK Biobank (median follow-up, 6.1 years; interquartile range, 5.4-6.8 years). Then we further examined these associations in individuals with different genetic burden by stratifying individuals based on their genetic risk scores for coronary heart disease and atrial fibrillation. We compared disease risk among individuals in different tertiles of fitness, physical activity, and genetic risk using lowest tertiles as reference. Results -Grip strength, physical activity, and cardiorespiratory fitness showed inverse associations with incident cardiovascular events (coronary heart disease: hazard ratio [HR], 0.79; 95% confidence interval [CI], 0.77- 0.81; HR, 0.95; 95% CI, 0.93-0.97; and HR, 0.68; 95% CI, 0.63-0.74, per SD change, respectively; atrial fibrillation: HR, 0.75; 95% CI, 0.73- 0.76; HR, 0.93; 95% CI, 0.91-0.95; and HR, 0.60; 95% CI, 0.56-0.65, per SD change, respectively). Higher grip strength and cardiorespiratory fitness were associated with lower risk of incident coronary heart disease and atrial fibrillation in each genetic risk score group ( P trend fitness were associated with 49% lower risk for coronary heart disease (HR, 0.51; 95% CI, 0.38-0.69) and 60% lower risk for atrial fibrillation (HR, 0.40; 95%, CI 0.30-0.55) among individuals at high genetic risk for these diseases. Conclusions - Fitness and physical activity demonstrated inverse associations with incident cardiovascular disease in the general population, as well as in individuals with elevated genetic risk for these diseases.

Adverse metabolic phenotype of female offspring exposed to preeclampsia in utero: a characterization of the BPH/5 mouse in postnatal life.

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Sutton, Elizabeth F; Lob, Heinrich E; Song, Jiunn; Xia, YunWei; Butler, Scott; Liu, Chin-Chi; Redman, Leanne M; Sones, Jenny L

2017-04-01

Preeclampsia (PE) is a devastating disorder of pregnancy that classically presents with maternal hypertension and proteinuria after 20 wk of gestation. In addition to being a leading cause of maternal and fetal morbidity/mortality, epidemiological and prospective studies have revealed long-term consequences for both the mother and baby of preeclamptic pregnancies, including chronic hypertension as well as other cardiovascular diseases and metabolic derangements. To better understand the effect of in utero exposure of PE on offspring, we utilized the BPH/5 mouse, a spontaneous model of the maternal and fetal PE syndrome. We hypothesized that young BPH/5 offspring would have altered metabolic and cardiovascular phenotypes. Indeed, BPH/5 growth-restricted offspring showed excess catch-up growth by early adulthood due to hyperphagia and increased white adipose tissue (WAT) accumulation, with inflammation markers isolated to the reproductive WAT depot only. Both excessive WAT accumulation and the inflammatory WAT phenotype were corrected by pair-feeding young BPH/5 female mice. We also found that young BPH/5 female mice showed evidence of leptin resistance. Indeed, chronic hyperleptinemia has been shown to characterize other rodent models of PE; however, the maternal metabolic profile before pregnancy has not been fully understood. Furthermore, we found that these mice show signs of cardiovascular anomalies (hypertension and cardiomegaly) and altered signaling within the reproductive axis in early life. Future studies will involve challenging the physiological metabolic state of BPH/5 mice through pair-feeding to reduce WAT before pregnancy and determining its causal role in adverse pregnancy outcomes. Copyright © 2017 the American Physiological Society.

Mortality of mothers from cardiovascular and non-cardiovascular causes following pregnancy complications in first delivery

DEFF Research Database (Denmark)

Lykke, Jacob Alexander; Langhoff-Roos, Jens; Lockwood, Charles J

2010-01-01

cardiovascular and non-cardiovascular causes following preterm delivery, small-for-gestational-age offspring and hypertensive disorders of pregnancy. We found that preterm delivery and small-for-gestational-age were both associated with subsequent death of mothers from cardiovascular and non...... cardiovascular and non-cardiovascular causes, while hypertensive disorders of pregnancy are markers of early death of mothers from cardiovascular causes....

Longitudinal Associations between Triglycerides and Metabolic Syndrome Components in a Beijing Adult Population, 2007-2012.

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Tao, Li-Xin; Yang, Kun; Liu, Xiang-Tong; Cao, Kai; Zhu, Hui-Ping; Luo, Yan-Xia; Guo, Jin; Wu, Li-Juan; Li, Xia; Guo, Xiu-Hua

2016-01-01

Longitudinal associations between triglycerides (TG) and other metabolic syndrome (MetS) components have rarely been reported. The purpose was to investigate the longitudinal association between TG and other MetS components with time. The longitudinal study was established in 2007 on individuals who attended health check-ups at Beijing Tongren Hospital and Beijing Xiaotangshan Hospital. Data used in this study was based on 7489 participants who had at least three health check-ups over a period of 5-year follow up. Joint model was used to explore longitudinal associations between TG and other MetS components after adjusted for age. There were positive correlations between TG and other MetS components except for high density lipoprotein (HDL), and the correlations increased with time. A negative correlation was displayed between TG and HDL, and the correlation also increased with time. Among all five pairs of TG and other MetS components, the marginal correlation between TG and body mass index (BMI) was the largest for both men and women. The marginal correlation between TG and fasting plasma glucose was the smallest for men, while the marginal correlation between TG and diastolic blood pressure was the smallest for women. The longitudinal association between TG and other MetS components increased with time. Among five pairs of TG and other MetS components, the longitudinal correlation between TG and BMI was the largest. It is important to closely monitor subjects with high levels of TG and BMI in health check-up population especially for women, because these two components are closely associated with development of hypertension, diabetes, cardiovascular disease and other metabolic diseases.

Predictors of healthcare professionals' intention and behaviour to encourage physical activity in patients with cardiovascular risk factors

Directory of Open Access Journals (Sweden)

Kok Gerjo

2011-04-01

Full Text Available Abstract Background Healthcare professionals can play a crucial role in optimizing the health status of patients with cardiovascular risk factors (abdominal obesity, high blood pressure, low HDL cholesterol, elevated triglycerides and elevated blood glucose. In order to do this, it is imperative that we understand the social-cognitive determinants (including habits that underlie healthcare professionals' intention and the corresponding behavior of actually encouraging patients with cardiovascular risk factors to engage in physical activity. Methods In this longitudinal Professionals' Intention and Behavior (PIB study, healthcare professionals (N = 278, aged 20-61 years with approximately 60% having attained an education level exceeding bachelor's degree, types of healthcare professionals 60% in physiotherapy and 40% in nursing completed online surveys measuring the social-cognitive determinants of healthcare professionals' intention and the corresponding behavior of actually encouraging patients with cardiovascular risk factors to engage in physical activity. Results Social-cognitive determinants accounted for 41% (p We explored the congruence between healthcare professionals' intention to encourage patients and the self-reported behavior of encouraging patients. We found that intention and behavior were congruent in 39.7% of the healthcare professionals. Additionally, the intention to encourage and the corresponding behavior of encouraging was incongruent in 31.7% of the healthcare professionals. Conclusions In the prevention of cardiovascular disease, healthcare professionals' intention to encourage physical activity among patients and subsequent behavior of encouraging patients is important for the improvement of patients' cardiovascular risk profiles. We found that the intentions and self-reported behavior of healthcare professionals working with patients with cardiovascular risk factors can be predicted by social-cognitive determinants thus

Presymptomatic and longitudinal neuroimaging in neurodegeneration--from snapshots to motion picture: a systematic review.

Science.gov (United States)

Schuster, Christina; Elamin, Marwa; Hardiman, Orla; Bede, Peter

2015-10-01

Recent quantitative neuroimaging studies have been successful in capturing phenotype and genotype-specific changes in dementia syndromes, amyotrophic lateral sclerosis, Parkinson's disease and other neurodegenerative conditions. However, the majority of imaging studies are cross-sectional, despite the obvious superiority of longitudinal study designs in characterising disease trajectories, response to therapy, progression rates and evaluating the presymptomatic phase of neurodegenerative conditions. The aim of this work is to perform a systematic review of longitudinal imaging initiatives in neurodegeneration focusing on methodology, optimal statistical models, follow-up intervals, attrition rates, primary study outcomes and presymptomatic studies. Longitudinal imaging studies were identified from 'PubMed' and reviewed from 1990 to 2014. The search terms 'longitudinal', 'MRI', 'presymptomatic' and 'imaging' were utilised in combination with one of the following degenerative conditions; Alzheimer's disease, amyotrophic lateral sclerosis/motor neuron disease, frontotemporal dementia, Huntington's disease, multiple sclerosis, Parkinson's disease, ataxia, HIV, alcohol abuse/dependence. A total of 423 longitudinal imaging papers and 103 genotype-based presymptomatic studies were identified and systematically reviewed. Imaging techniques, follow-up intervals and attrition rates showed significant variation depending on the primary diagnosis. Commonly used statistical models included analysis of annualised percentage change, mixed and random effect models, and non-linear cumulative models with acceleration-deceleration components. Although longitudinal imaging studies have the potential to provide crucial insights into the presymptomatic phase and natural trajectory of neurodegenerative processes a standardised design is required to enable meaningful data interpretation. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under

Sortilin and the risk of cardiovascular disease.

Science.gov (United States)

Coutinho, Maria Francisca; Bourbon, Mafalda; Prata, Maria João; Alves, Sandra

2013-10-01

Plasma low-density lipoprotein cholesterol (LDL-C) levels are a key determinant of the risk of cardiovascular disease, which is why many studies have attempted to elucidate the pathways that regulate its metabolism. Novel latest-generation sequencing techniques have identified a strong association between the 1p13 locus and the risk of cardiovascular disease caused by changes in plasma LDL-C levels. As expected for a complex phenotype, the effects of variation in this locus are only moderate. Even so, knowledge of the association is of major importance, since it has unveiled a new metabolic pathway regulating plasma cholesterol levels. Crucial to this discovery was the work of three independent teams seeking to clarify the biological basis of this association, who succeeded in proving that SORT1, encoding sortilin, was the gene in the 1p13 locus involved in LDL metabolism. SORT1 was the first gene identified as determining plasma LDL levels to be mechanistically evaluated and, although the three teams used different, though appropriate, experimental methods, their results were in some ways contradictory. Here we review all the experiments that led to the identification of the new pathway connecting sortilin with plasma LDL levels and risk of myocardial infarction. The regulatory mechanism underlying this association remains unclear, but its discovery has paved the way for considering previously unsuspected therapeutic targets and approaches. Copyright © 2013 Sociedade Portuguesa de Cardiologia. Published by Elsevier España. All rights reserved.

Landscape of Innovation for Cardiovascular Pharmaceuticals: From Basic Science to New Molecular Entities.

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Beierlein, Jennifer M; McNamee, Laura M; Walsh, Michael J; Kaitin, Kenneth I; DiMasi, Joseph A; Ledley, Fred D

2017-07-01

This study examines the complete timelines of translational science for new cardiovascular therapeutics from the initiation of basic research leading to identification of new drug targets through clinical development and US Food and Drug Administration (FDA) approval of new molecular entities (NMEs) based on this research. This work extends previous studies by examining the association between the growth of research on drug targets and approval of NMEs associated with these targets. Drawing on research on innovation in other technology sectors, where technological maturity is an important determinant in the success or failure of new product development, an analytical model was used to characterize the growth of research related to the known targets for all 168 approved cardiovascular therapeutics. Categorizing and mapping the technological maturity of cardiovascular therapeutics reveal that (1) there has been a distinct transition from phenotypic to targeted methods for drug discovery, (2) the durations of clinical and regulatory processes were significantly influenced by changes in FDA practice, and (3) the longest phase of the translational process was the time required for technology to advance from initiation of research to a statistically defined established point of technology maturation (mean, 30.8 years). This work reveals a normative association between metrics of research maturation and approval of new cardiovascular therapeutics and suggests strategies for advancing translational science by accelerating basic and applied research and improving the synchrony between the maturation of this research and drug development initiatives. Copyright © 2017 Elsevier HS Journals, Inc. All rights reserved.

School burnout and heart rate variability: risk of cardiovascular disease and hypertension in young adult females.

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May, Ross W; Seibert, Gregory S; Sanchez-Gonzalez, Marcos A; Fincham, Frank D

2018-05-01

Emerging research documents the relationship between school burnout and some indicators of increased cardiovascular risk. Indicators of cardiovascular functioning assessed via ambulatory blood pressure and heart rate variability (HRV) have not been thoroughly explored in this research domain. Therefore, the current study examined relationships between school burnout and indicators of cardiac functioning via 24 h ambulatory blood pressure (BP) and electrocardiogram monitoring in a sample of young adult female undergraduates (N = 88). Two hypotheses were tested: (1) that independent of related negative affective symptomology (depression and anxiety), increased school burnout would be related to greater systolic and diastolic BP, higher low frequency (LF) HRV and lower very low frequency (VLF) HRV, and (2) that lower VLF would be related to greater school burnout independently of LF HRV. Hierarchical multiple regression analyzes showed that school burnout was significantly related to elevated ambulatory BP (systolic and diastolic) and HRV markers of increased cardiac sympathovagal tone. These findings support the hypotheses and suggest that school burnout might be implicated in the development of pre-hypertension or early cardiovascular disease. Study limitations and the need for future longitudinal research are discussed.

BELFAST nonagenarians: nature or nurture? Immunological, cardiovascular and genetic factors

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Rea I M

2010-05-01

Full Text Available Abstract Nonagenarians are the fastest growing sector of populations across Western European and the developed world. They are some of the oldest members of our societies and survivors of their generation and may help us understand how to age not only longer, but better. The Belfast Longevity Group enlisted the help of 500 community-living, mobile, mentally competent, 'elite' nonagenarians, as part of an ongoing study of ageing. We assessed some immunological, cardiovascular, nutritional and genetic factors and some aspects of their interaction in this group of 'oldest old'. Here we present some of the evidence related to genetic and nutritional factors which seem to be important for good quality ageing in nonagenarians from the Belfast Elderly Longitudinal Free-living Ageing STudy (BELFAST.

Diabetes Drugs and Cardiovascular Safety

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Ji Cheol Bae

2016-06-01

Full Text Available Diabetes is a well-known risk factor of cardiovascular morbidity and mortality, and the beneficial effect of improved glycemic control on cardiovascular complications has been well established. However, the rosiglitazone experience aroused awareness of potential cardiovascular risk associated with diabetes drugs and prompted the U.S. Food and Drug Administration to issue new guidelines about cardiovascular risk. Through postmarketing cardiovascular safety trials, some drugs demonstrated cardiovascular benefits, while some antidiabetic drugs raised concern about a possible increased cardiovascular risk associated with drug use. With the development of new classes of drugs, treatment options became wider and the complexity of glycemic management in type 2 diabetes has increased. When choosing the appropriate treatment strategy for patients with type 2 diabetes at high cardiovascular risk, not only the glucose-lowering effects, but also overall benefits and risks for cardiovascular disease should be taken into consideration.

Geographic differences in allele frequencies of susceptibility SNPs for cardiovascular disease

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Kullo Iftikhar J

2011-04-01

Full Text Available Abstract Background We hypothesized that the frequencies of risk alleles of SNPs mediating susceptibility to cardiovascular diseases differ among populations of varying geographic origin and that population-specific selection has operated on some of these variants. Methods From the database of genome-wide association studies (GWAS, we selected 36 cardiovascular phenotypes including coronary heart disease, hypertension, and stroke, as well as related quantitative traits (eg, body mass index and plasma lipid levels. We identified 292 SNPs in 270 genes associated with a disease or trait at P -8. As part of the Human Genome-Diversity Project (HGDP, 158 (54.1% of these SNPs have been genotyped in 938 individuals belonging to 52 populations from seven geographic areas. A measure of population differentiation, FST, was calculated to quantify differences in risk allele frequencies (RAFs among populations and geographic areas. Results Large differences in RAFs were noted in populations of Africa, East Asia, America and Oceania, when compared with other geographic regions. The mean global FST (0.1042 for 158 SNPs among the populations was not significantly higher than the mean global FST of 158 autosomal SNPs randomly sampled from the HGDP database. Significantly higher global FST (P FST of 2036 putatively neutral SNPs. For four of these SNPs, additional evidence of selection was noted based on the integrated Haplotype Score. Conclusion Large differences in RAFs for a set of common SNPs that influence risk of cardiovascular disease were noted between the major world populations. Pairwise comparisons revealed RAF differences for at least eight SNPs that might be due to population-specific selection or demographic factors. These findings are relevant to a better understanding of geographic variation in the prevalence of cardiovascular disease.

The outbreak fingolimod cardiovascular side effects in relapsing-remitting multiple sclerosis patient: A longitudinal study in an Iranian population

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Morteza Abdar

2017-03-01

Full Text Available BACKGROUND: Fingolimod (FTY-720 has shown efficacy in relapsing multiple sclerosis (MS, while some side effects of this drug have been recognized that the most important is cardiovascular side effects. The aim of this study was to evaluate the cardiovascular side effects of FTY-720. However, the effect of fingolimod on cardiac has not been well recognized. This study was designed to evaluate the cardiovascular side effects of fingolimod in relapsing-remitting multiple sclerosis (RRMS patient in an Iranian population. METHODS: This prospective clinical trial study was performed on 200 RRMS patients. The patients received a single daily oral dose of fingolimod 0.5 mg. During the first 6 hours after the first fingolimod dose, the patients’ vital signs and electrocardiographic traces were continuously monitored. Moreover, the patients followed up over 6 months after receiving fingolimod. RESULTS: The results showed that pulse rate (P < 0.001, systolic blood pressure (BP (P < 0.001, and diastolic BP (P < 0.001 were decreased significantly during 6 hours after receiving the first dose of fingolimod. The most reduction in vital sign was observed in 3 hours. Arrhythmia, bradycardia, and dizziness were the other complications of fingolimod, which were detected in our study. CONCLUSION: All the side effects such as hypotension and bradycardia were happened in first 3 hours after receiving the fingolimod. Indeed, we advise clinicians to monitor the patients for first 6 hours after initiation of fingolimod to decrease worse side effects. 

Mild pituitary phenotype in 3- and 12-month-old Aip-deficient male mice.

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Lecoq, Anne-Lise; Zizzari, Philippe; Hage, Mirella; Decourtye, Lyvianne; Adam, Clovis; Viengchareun, Say; Veldhuis, Johannes D; Geoffroy, Valérie; Lombès, Marc; Tolle, Virginie; Guillou, Anne; Karhu, Auli; Kappeler, Laurent; Chanson, Philippe; Kamenický, Peter

2016-10-01

Germline mutations in the aryl hydrocarbon receptor-interacting protein (AIP) gene predispose humans to pituitary adenomas, particularly of the somatotroph lineage. Mice with global heterozygous inactivation of Aip (Aip(+/-)) also develop pituitary adenomas but differ from AIP-mutated patients by the high penetrance of pituitary disease. The endocrine phenotype of these mice is unknown. The aim of this study was to determine the endocrine phenotype of Aip(+/-) mice by assessing the somatic growth, ultradian pattern of GH secretion and IGF1 concentrations of longitudinally followed male mice at 3 and 12 months of age. As the early stages of pituitary tumorigenesis are controversial, we also studied the pituitary histology and somatotroph cell proliferation in these mice. Aip(+/-) mice did not develop gigantism but exhibited a leaner phenotype than wild-type mice. Analysis of GH pulsatility by deconvolution in 12-month-old Aip(+/-) mice showed a mild increase in total GH secretion, a conserved GH pulsatility pattern, but a normal IGF1 concentration. No pituitary adenomas were detected up to 12 months of age. An increased ex vivo response to GHRH of pituitary explants from 3-month-old Aip(+/-) mice, together with areas of enlarged acini identified on reticulin staining in the pituitary of some Aip(+/-) mice, was suggestive of somatotroph hyperplasia. Global heterozygous Aip deficiency in mice is accompanied by subtle increase in GH secretion, which does not result in gigantism. The absence of pituitary adenomas in 12-month-old Aip(+/-) mice in our experimental conditions demonstrates the important phenotypic variability of this congenic mouse model. © 2016 Society for Endocrinology.

Impact of beverage intake on metabolic and cardiovascular health.

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Helm, Laura; Macdonald, Ian A

2015-09-01

This review is based on a presentation that was made at a meeting concerning hydration. It summarizes the epidemiological evidence for selected beverages in relation to cardiovascular and/or metabolic health. The review focuses on tea, cocoa, milk, orange juice, alcohol, and beverages sweetened with sugars. These beverage types were chosen because of their widespread consumption, with tea, cocoa, orange juice, and milk being of potential benefit while alcohol and sugars may be detrimental. There is reasonably consistent evidence of reduced risk of cardiovascular disease (CVD) in association with high consumption of tea, with the tea flavonoids appearing to be responsible for these benefits. There is also a growing evidence base for cocoa flavanols to have beneficial cardiovascular effects. The bulk of the evidence supporting these conclusions is epidemiological and needs to be confirmed with randomized controlled trials. Milk is associated with reduced risk of CVD, particularly in relation to blood pressure, with certain milk tripeptides being implicated in having effects to reduce angiotensin action. Further work is needed to confirm these potentially beneficial effects. There is some evidence of potentially beneficial effects of orange juice on aspects of cardiovascular function, but this is by no means convincing, and further evidence is needed from randomized controlled trials, together with the elucidation of whether any benefits are linked to the citrus flavanones or simply to the vitamin C content. While there is some evidence that red wine may convey some health benefits, there is also clear evidence that alcoholic beverages can have undesirable effects on blood pressure and increase the risk of CVD. It is possible that low to moderate intakes of alcoholic beverages may be beneficial. There is some evidence that beverages sweetened with sugars may contribute to increased energy intake and weight gain, and there is also an indication from longitudinal cohort

Cardiovascular risk and subclinical cardiovascular disease in polycystic ovary syndrome.

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Bajuk Studen, Katica; Jensterle Sever, Mojca; Pfeifer, Marija

2013-01-01

In addition to its effects on reproductive health, it is now well recognized that polycystic ovary syndrome (PCOS) is a metabolic disorder, characterized by decreased insulin sensitivity which leads to an excess lifetime risk of type 2 diabetes and cardiovascular disease. PCOS patients are often obese, hypertensive, dyslipidemic and insulin resistant; they have obstructive sleep apnea and have been reported to have higher aldosterone levels in comparison to normal healthy controls. These are all components of an adverse cardiovascular risk profile. Many studies exploring subclinical atherosclerosis using different methods (flow-mediated dilatation, intima media thickness, arterial stiffness, coronary artery calcification) as well as assessing circulating cardiovascular risk markers, point toward an increased cardiovascular risk and early atherogenesis in PCOS. The risk and early features of subclinical atherosclerosis can be reversed by non-medical (normalization of weight, healthy lifestyle) and medical (metformin, thiazolidinediones, spironolactone, and statins) interventions. However, the long-term risk for cardiovascular morbidity and mortality as well as the clinical significance of different interventions still need to be properly addressed in a large prospective study. Copyright © 2013 S. Karger AG, Basel.

Association of heart-type fatty acid-binding protein with cardiovascular risk factors and all-cause mortality in the general population: the Takahata study.

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Yoichiro Otaki

Full Text Available Despite many recent advances in medicine, preventing the development of cardiovascular diseases remains a challenge. Heart-type fatty acid-binding protein (H-FABP is a marker of ongoing myocardial damage and has been reported to be a useful indicator for future cardiovascular events. However, it remains to be determined whether H-FABP can predict all-cause and cardiovascular deaths in the general population.This longitudinal cohort study included 3,503 subjects who participated in a community-based health checkup with a 7-year follow-up. Serum H-FABP was measured in registered subjects. The results demonstrated that higher H-FABP levels were associated with increasing numbers of cardiovascular risk factors, including hypertension, diabetes mellitus, obesity, and metabolic syndrome. There were 158 deaths during the follow-up period, including 50 cardiovascular deaths. Deceased subjects had higher H-FABP levels compared to surviving subjects. Multivariate Cox proportional hazard regression analysis revealed that H-FABP is an independent predictor of all-cause and cardiovascular deaths after adjustments for confounding factors. Subjects were divided into four quartiles according to H-FABP level, and Kaplan-Meier analysis demonstrated that the highest H-FABP quartile was associated with the greatest risks for all-cause and cardiovascular deaths. Net reclassification index and integrated discrimination index were significantly increased by addition of H-FABP to cardiovascular risk factors.H-FABP level was increased in association with greater numbers of cardiovascular risk factors and was an independent risk factor for all-cause and cardiovascular deaths. H-FABP could be a useful indicator for the early identification of high-risk subjects in the general population.

Association of the Aspartate Aminotransferase to Alanine Aminotransferase Ratio with BNP Level and Cardiovascular Mortality in the General Population: The Yamagata Study 10-Year Follow-Up

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Miyuki Yokoyama

2016-01-01

Full Text Available Background. Early identification of high risk subjects for cardiovascular disease in health check-up is still unmet medical need. Cardiovascular disease is characterized by the superior increase in aspartate aminotransferase (AST to alanine aminotransferase (ALT. However, the association of AST/ALT ratio with brain natriuretic peptide (BNP levels and cardiovascular mortality remains unclear in the general population. Methods and Results. This longitudinal cohort study included 3,494 Japanese subjects who participated in a community-based health check-up, with a 10-year follow-up. The AST/ALT ratio increased with increasing BNP levels. And multivariate logistic analysis showed that the AST/ALT ratio was significantly associated with a high BNP (≥100 pg/mL. There were 250 all-cause deaths including 79 cardiovascular deaths. Multivariate Cox proportional hazard regression analysis revealed that a high AST/ALT ratio (>90 percentile was an independent predictor of all-cause and cardiovascular mortality after adjustment for confounding factors. Kaplan-Meier analysis demonstrated that cardiovascular mortality was higher in subjects with a high AST/ALT ratio than in those without. Conclusions. The AST/ALT ratio was associated with an increase in BNP and was predictive of cardiovascular mortality in a general population. Measuring the AST/ALT ratio during routine health check-ups may be a simple and cost-effective marker for cardiovascular mortality.

Cardiovascular outcomes of pregnancy in Marfan's syndrome patients: A literature review.

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Kim, So Yeon; Wolfe, Diana S; Taub, Cynthia C

2018-03-01

Pregnancy in patients with Marfan's syndrome (MFS) carries an increased risk of cardiovascular complications, resulting in increased maternal and fetal mortality and morbidity. Literature on MFS pregnant patients is relatively sparse, and there has yet to be a concrete consensus on the management of this unique patient population. The purpose of our paper is to provide a literature review of case reports and studies on MFS during pregnancy (published between 2005 and 2015) and to explore cardiovascular outcomes of patients with MFS. Of the 852 women in our review, there were 1112 pregnancies, with an aortic dissection rate of 7.9% and mortality of 1.2%. Data demonstrated a trend that patients whose aortic diameter ≥40 mm had a greater rate of dissection than MFS patients whose aortic diameter pregnancy or currently pregnant should be carefully counseled about the maternal and fetal risks throughout pregnancy. MFS patients whose aortic diameters ≥40 mm should be advised to ideally await pregnancy until prophylactic aortic surgery. As MFS varies in its phenotypic expression, each patient's risk of adverse cardiac events should be assessed individually through a joint Maternal Fetal Medicine and Cardiology Center. © 2017 Wiley Periodicals, Inc.

Cardiovascular Disease Modeling Using Patient-Specific Induced Pluripotent Stem Cells

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Atsushi Tanaka

2015-08-01

Full Text Available The generation of induced pluripotent stem cells (iPSCs has opened up a new scientific frontier in medicine. This technology has made it possible to obtain pluripotent stem cells from individuals with genetic disorders. Because iPSCs carry the identical genetic anomalies related to those disorders, iPSCs are an ideal platform for medical research. The pathophysiological cellular phenotypes of genetically heritable heart diseases such as arrhythmias and cardiomyopathies, have been modeled on cell culture dishes using disease-specific iPSC-derived cardiomyocytes. These model systems can potentially provide new insights into disease mechanisms and drug discoveries. This review focuses on recent progress in cardiovascular disease modeling using iPSCs, and discusses problems and future perspectives concerning their use.

Cardiovascular radiology

International Nuclear Information System (INIS)

VanAman, M.; Mueller, C.F.

1985-01-01

Soon after Roentgen documented the uses of x-rays in 1895, fluoroscopic and film evaluation of the heart began. Even today the chest roentgenogram remains one of the first and most frequently used studies for the evaluation of the normal and abnormal heart and great vessels. This chapter gives an overview of plain film evaluation of the cardiovascular system and follow up with comments on the newer imaging modalities of computed tomography, and digital subtraction angiography, in the cardiovascular disease workup. The authors present an evaluation of plain films of the chest, which remains their most cost effective, available, simple, and reliable initial screening tool in the evaluation of cardiovascular disease

Physiological Changes to the Cardiovascular System at High Altitude and Its Effects on Cardiovascular Disease.

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Riley, Callum James; Gavin, Matthew

2017-06-01

Riley, Callum James, and Matthew Gavin. Physiological changes to the cardiovascular system at high altitude and its effects on cardiovascular disease. High Alt Med Biol. 18:102-113, 2017.-The physiological changes to the cardiovascular system in response to the high altitude environment are well understood. More recently, we have begun to understand how these changes may affect and cause detriment to cardiovascular disease. In addition to this, the increasing availability of altitude simulation has dramatically improved our understanding of the physiology of high altitude. This has allowed further study on the effect of altitude in those with cardiovascular disease in a safe and controlled environment as well as in healthy individuals. Using a thorough PubMed search, this review aims to integrate recent advances in cardiovascular physiology at altitude with previous understanding, as well as its potential implications on cardiovascular disease. Altogether, it was found that the changes at altitude to cardiovascular physiology are profound enough to have a noteworthy effect on many forms of cardiovascular disease. While often asymptomatic, there is some risk in high altitude exposure for individuals with certain cardiovascular diseases. Although controlled research in patients with cardiovascular disease was largely lacking, meaning firm conclusions cannot be drawn, these risks should be a consideration to both the individual and their physician.

Significance of left ventricular apical-basal muscle bundle identified by cardiovascular magnetic resonance imaging in patients with hypertrophic cardiomyopathy

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Gruner, Christiane; Chan, Raymond H.; Crean, Andrew; Rakowski, Harry; Rowin, Ethan J.; Care, Melanie; Deva, Djeven; Williams, Lynne; Appelbaum, Evan; Gibson, C. Michael; Lesser, John R.; Haas, Tammy S.; Udelson, James E.; Manning, Warren J.; Siminovitch, Katherine

2017-01-01

Aims Cardiovascular magnetic resonance (CMR) has improved diagnostic and management strategies in hypertrophic cardiomyopathy (HCM) by expanding our appreciation for the diverse phenotypic expression. We sought to characterize the prevalence and clinical significance of a recently identified accessory left ventricular (LV) muscle bundle extending from the apex to the basal septum or anterior wall (i.e. apical-basal). Methods and results CMR was performed in 230 genotyped HCM patients (48 ± 15...

Gastric Bypass Surgery Produces a Durable Reduction in Cardiovascular Disease Risk Factors and Reduces the Long-Term Risks of Congestive Heart Failure.

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Benotti, Peter N; Wood, G Craig; Carey, David J; Mehra, Vishal C; Mirshahi, Tooraj; Lent, Michelle R; Petrick, Anthony T; Still, Christopher; Gerhard, Glenn S; Hirsch, Annemarie G

2017-05-23

Obesity and its association with reduced life expectancy are well established, with cardiovascular disease as one of the major causes of fatality. Metabolic surgery is a powerful intervention for severe obesity, resulting in improvement in comorbid diseases and in cardiovascular risk factors. This study investigates the relationship between metabolic surgery and long-term cardiovascular events. A cohort of Roux-en-Y gastric bypass surgery (RYGB) patients was tightly matched by age, body mass index, sex, Framingham Risk Score, smoking history, use of antihypertension medication, diabetes mellitus status, and calendar year with a concurrent cohort of nonoperated control patients. The primary study end points of major cardiovascular events (myocardial infarction, stroke, and congestive heart failure) were evaluated using Cox regression. Secondary end points of longitudinal cardiovascular risk factors were evaluated using repeated-measures regression. The RYGB and matched controls (N=1724 in each cohort) were followed for up to 12 years after surgery (overall median of 6.3 years). Kaplan-Meier analysis revealed a statistically significant reduction in incident major composite cardiovascular events ( P =0.017) and congestive heart failure (0.0077) for the RYGB cohort. Adjusted Cox regression models confirmed the reductions in severe composite cardiovascular events in the RYGB cohort (hazard ratio=0.58, 95% CI=0.42-0.82). Improvements of cardiovascular risk factors (eg, 10-year cardiovascular risk score, total cholesterol, high-density lipoprotein, systolic blood pressure, and diabetes mellitus) were observed within the RYGB cohort after surgery. Gastric bypass is associated with a reduced risk of major cardiovascular events and the development of congestive heart failure. © 2017 The Authors and Geisinger Clinic. Published on behalf of the American Heart Association, Inc., by Wiley.

Dose-response relationship of the cardiovascular adaptation to endurance training in healthy adults: how much training for what benefit?

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Iwasaki, Ken-Ichi; Zhang, Rong; Zuckerman, Julie H; Levine, Benjamin D

2003-10-01

Occupational or recreational exercise reduces mortality from cardiovascular disease. The potential mechanisms for this reduction may include changes in blood pressure (BP) and autonomic control of the circulation. Therefore, we conducted the present long-term longitudinal study to quantify the dose-response relationship between the volume and intensity of exercise training, and regulation of heart rate (HR) and BP. We measured steady-state hemodynamics and analyzed dynamic cardiovascular regulation by spectral and transfer function analysis of cardiovascular variability in 11 initially sedentary subjects during 1 yr of progressive endurance training sufficient to allow them to complete a marathon. From this, we found that 1) moderate exercise training for 3 mo decreased BP, HR, and total peripheral resistance, and increased cardiovascular variability and arterial baroreflex sensitivity; 2) more prolonged and intense training did not augment these changes further; and 3) most of these changes returned to control values at 12 mo despite markedly increased training duration and intensity equivalent to that routinely observed in competitive athletes. In conclusion, increases in R-wave-R-wave interval and cardiovascular variability indexes are consistent with an augmentation of vagal modulation of HR after exercise training. It appears that moderate doses of training for 3 mo are sufficient to achieve this response as well as a modest hypotensive effect from decreasing vascular resistance. However, more prolonged and intense training does not necessarily lead to greater enhancement of circulatory control and, therefore, may not provide an added protective benefit via autonomic mechanisms against death by cardiovascular disease.

Adolescent vulnerability to cardiovascular consequences of chronic social stress: Immediate and long-term effects of social isolation during adolescence.

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Cruz, Fábio C; Duarte, Josiane O; Leão, Rodrigo M; Hummel, Luiz F V; Planeta, Cleopatra S; Crestani, Carlos C

2016-01-01

It has been demonstrated that disruption of social bonds and perceived isolation (loneliness) are associated with an increased risk of cardiovascular morbidity and mortality. Adolescence is proposed as a period of vulnerability to stress. Nevertheless, the impact of chronic social stress during this ontogenic period in cardiovascular function is poorly understood. Therefore, the purpose of this study was to compare the impact in cardiovascular function of social isolation for 3 weeks in adolescent and adult male rats. Also, the long-term effects of social isolation during adolescence were investigated longitudinally. Social isolation reduced body weight in adolescent, but not in adult animals. Disruption of social bonds during adolescence increased arterial pressure without affecting heart rate and pulse pressure (PP). Nevertheless, social isolation in adulthood reduced systolic arterial pressure and increased diastolic arterial pressure, which in turn decreased PP without affecting mean arterial pressure. Cardiovascular changes in adolescents, but not adults, were followed by facilitation of both baroreflex sensitivity and vascular reactivity to the vasodilator agent acetylcholine. Vascular responsiveness to either the vasodilator agent sodium nitroprusside or the vasoconstrictor agent phenylephrine was not affected by social isolation. Except for the changes in body weight and baroreflex sensitivity, all alterations evoked by social isolation during adolescence were reversed in adulthood after moving animals from isolated to collective housing. These findings suggest a vulnerability of adolescents to the effects of chronic social isolation in cardiovascular function. However, results indicate minimal cardiovascular consequences in adulthood of disruption of social bonds during adolescence. © 2015 Wiley Periodicals, Inc.

Longitudinal Cognitive Trajectories of Women Veterans from the Women’s Health Initiative Memory Study

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Padula, Claudia B.; Weitlauf, Julie C.; Rosen, Allyson C.; Reiber, Gayle; Cochrane, Barbara B.; Naughton, Michelle J.; Li, Wenjun; Rissling, Michelle; Yaffe, Kristine; Hunt, Julie R.; Stefanick, Marcia L.; Goldstein, Mary K.; Espeland, Mark A.

2016-01-01

Purpose of the Study: A comparison of longitudinal global cognitive functioning in women Veteran and non-Veteran participants in the Women’s Health Initiative (WHI). Design and Methods: We studied 7,330 women aged 65–79 at baseline who participated in the WHI Hormone Therapy Trial and its ancillary Memory Study (WHIMS). Global cognitive functioning (Modified Mini-Mental State Examination [3MSE]) in Veterans (n = 279) and non-Veterans (n = 7,051) was compared at baseline and annually for 8 years using generalized linear modeling methods. Results: Compared with non-Veterans, Veteran women were older, more likely to be Caucasian, unmarried, and had higher rates of educational and occupational attainment. Results of unadjusted baseline analyses suggest 3MSE scores were similar between groups. Longitudinal analyses, adjusted for age, education, ethnicity, and WHI trial assignment revealed differences in the rate of cognitive decline between groups over time, such that scores decreased more in Veterans relative to non-Veterans. This relative difference was more pronounced among Veterans who were older, had higher educational/occupational attainment and greater baseline prevalence of cardiovascular risk factors (e.g., smoking) and cardiovascular disease (e.g., angina, stroke). Implications: Veteran status was associated with higher prevalence of protective factors that may have helped initially preserve cognitive functioning. However, findings ultimately revealed more pronounced cognitive decline among Veteran relative to non-Veteran participants, likely suggesting the presence of risks that may impact neuropathology and the effects of which were initially masked by Veterans’ greater cognitive reserve. PMID:26615021

Data in support of dyslipidemia-associated alterations in B cell subpopulations frequency and phenotype during experimental atherosclerosis

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Héctor Rincón-Arévalo

2016-06-01

Full Text Available Cardiovascular diseases are the most common cause of death in the world, atherosclerosis being its main underlying disease. Information about the role of B cells during atherosclerotic process is scarce, but both proatherogenic and atheroprotective properties have been described in the immunopathology of this disease. Frequency and phenotype of B cell subpopulations were studied in wild type and apolipoprotein-E-deficient (apoE−/− mice fed or not with high-fat diet (HFD, by flow cytometry. Here, we provide the information about the materials, methods, analysis and additional information related to our study published in Atherosclerosis (DOI: 10.1016/j.atherosclerosis.2015.12.022, article reference: ATH14410 [1]. The data contained in this article shows and supports that mice with advanced atherosclerosis have a variety of alterations in frequency and phenotype of B cell subsets, most of which associated with dyslipidemia.

Data in support of dyslipidemia-associated alterations in B cell subpopulations frequency and phenotype during experimental atherosclerosis

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Rincón-Arévalo, Héctor; Castaño, Diana; Villa-Pulgarín, Janny; Rojas, Mauricio; Vásquez, Gloria; Correa, Luis A.; Ramírez-Pineda, José R.; Yassin, Lina M.

2016-01-01

Cardiovascular diseases are the most common cause of death in the world, atherosclerosis being its main underlying disease. Information about the role of B cells during atherosclerotic process is scarce, but both proatherogenic and atheroprotective properties have been described in the immunopathology of this disease. Frequency and phenotype of B cell subpopulations were studied in wild type and apolipoprotein-E-deficient (apoE−/−) mice fed or not with high-fat diet (HFD), by flow cytometry. Here, we provide the information about the materials, methods, analysis and additional information related to our study published in Atherosclerosis (DOI: 10.1016/j.atherosclerosis.2015.12.022, article reference: ATH14410) [1]. The data contained in this article shows and supports that mice with advanced atherosclerosis have a variety of alterations in frequency and phenotype of B cell subsets, most of which associated with dyslipidemia. PMID:27081674

Association of diastolic blood pressure with cardiovascular events in older people varies upon cardiovascular history

DEFF Research Database (Denmark)

Wijsman, Liselotte W.; Muller, Majon; de Craen, Anton J .M.

2018-01-01

with those with normal DBP. After further adjusting for cardiovascular factors, this association attenuated to 1.05 (0.86; 1.28). A previous history of cardiovascular disease significantly modified the relation between DBP and risk of cardiovascular events (P-interaction 0.042). In participants without......BACKGROUND: In older age, a low DBP has been associated with increased risk of cardiovascular events, especially in frail older people. We tested the hypothesis that low DBP is associated with a high risk of cardiovascular events in people with a previous history of cardiovascular disease......-90 mmHg) or high (>90 mmHg). Cox proportional hazards analyses were used to estimate hazard ratio with 95% confidence intervals (CI); analyses were stratified for cardiovascular history. RESULTS: Participants with low DBP had a 1.24-fold (1.04; 1.49) increased risk of cardiovascular events compared...

Variance decomposition of protein profiles from antibody arrays using a longitudinal twin model

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Kato Bernet S

2011-11-01

Full Text Available Abstract Background The advent of affinity-based proteomics technologies for global protein profiling provides the prospect of finding new molecular biomarkers for common, multifactorial disorders. The molecular phenotypes obtained from studies on such platforms are driven by multiple sources, including genetic, environmental, and experimental components. In characterizing the contribution of different sources of variation to the measured phenotypes, the aim is to facilitate the design and interpretation of future biomedical studies employing exploratory and multiplexed technologies. Thus, biometrical genetic modelling of twin or other family data can be used to decompose the variation underlying a phenotype into biological and experimental components. Results Using antibody suspension bead arrays and antibodies from the Human Protein Atlas, we study unfractionated serum from a longitudinal study on 154 twins. In this study, we provide a detailed description of how the variation in a molecular phenotype in terms of protein profile can be decomposed into familial i.e. genetic and common environmental; individual environmental, short-term biological and experimental components. The results show that across 69 antibodies analyzed in the study, the median proportion of the total variation explained by familial sources is 12% (IQR 1-22%, and the median proportion of the total variation attributable to experimental sources is 63% (IQR 53-72%. Conclusion The variability analysis of antibody arrays highlights the importance to consider variability components and their relative contributions when designing and evaluating studies for biomarker discoveries with exploratory, high-throughput and multiplexed methods.

Worm Phenotype Ontology: Integrating phenotype data within and beyond the C. elegans community

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Yook Karen

2011-01-01

Full Text Available Abstract Background Caenorhabditis elegans gene-based phenotype information dates back to the 1970's, beginning with Sydney Brenner and the characterization of behavioral and morphological mutant alleles via classical genetics in order to understand nervous system function. Since then C. elegans has become an important genetic model system for the study of basic biological and biomedical principles, largely through the use of phenotype analysis. Because of the growth of C. elegans as a genetically tractable model organism and the development of large-scale analyses, there has been a significant increase of phenotype data that needs to be managed and made accessible to the research community. To do so, a standardized vocabulary is necessary to integrate phenotype data from diverse sources, permit integration with other data types and render the data in a computable form. Results We describe a hierarchically structured, controlled vocabulary of terms that can be used to standardize phenotype descriptions in C. elegans, namely the Worm Phenotype Ontology (WPO. The WPO is currently comprised of 1,880 phenotype terms, 74% of which have been used in the annotation of phenotypes associated with greater than 18,000 C. elegans genes. The scope of the WPO is not exclusively limited to C. elegans biology, rather it is devised to also incorporate phenotypes observed in related nematode species. We have enriched the value of the WPO by integrating it with other ontologies, thereby increasing the accessibility of worm phenotypes to non-nematode biologists. We are actively developing the WPO to continue to fulfill the evolving needs of the scientific community and hope to engage researchers in this crucial endeavor. Conclusions We provide a phenotype ontology (WPO that will help to facilitate data retrieval, and cross-species comparisons within the nematode community. In the larger scientific community, the WPO will permit data integration, and

Mortality of mothers from cardiovascular and non-cardiovascular causes following pregnancy complications in first delivery

DEFF Research Database (Denmark)

Lykke, Jacob Alexander; Langhoff-Roos, Jens; Lockwood, Charles J

2010-01-01

The combined effects of preterm delivery, small-for-gestational-age offspring, hypertensive disorders of pregnancy, placental abruption and stillbirth on early maternal death from cardiovascular causes have not previously been described in a large cohort. We investigated the effects of pregnancy...... cardiovascular and non-cardiovascular causes following preterm delivery, small-for-gestational-age offspring and hypertensive disorders of pregnancy. We found that preterm delivery and small-for-gestational-age were both associated with subsequent death of mothers from cardiovascular and non......-cardiovascular causes. Severe pre-eclampsia was associated with death from cardiovascular causes only. There was a less than additive effect on cardiovascular mortality hazard ratios with increasing number of pregnancy complications: preterm delivery 1.90 [95% confidence intervals 1.49, 2.43]; preterm delivery...

Advances in Integrating Traditional and Omic Biomarkers When Analyzing the Effects of the Mediterranean Diet Intervention in Cardiovascular Prevention

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Fitó, Montserrat; Melander, Olle; Martínez, José Alfredo; Toledo, Estefanía; Carpéné, Christian; Corella, Dolores

2016-01-01

Intervention with Mediterranean diet (MedDiet) has provided a high level of evidence in primary prevention of cardiovascular events. Besides enhancing protection from classical risk factors, an improvement has also been described in a number of non-classical ones. Benefits have been reported on biomarkers of oxidation, inflammation, cellular adhesion, adipokine production, and pro-thrombotic state. Although the benefits of the MedDiet have been attributed to its richness in antioxidants, the mechanisms by which it exercises its beneficial effects are not well known. It is thought that the integration of omics including genomics, transcriptomics, epigenomics, and metabolomics, into studies analyzing nutrition and cardiovascular diseases will provide new clues regarding these mechanisms. However, omics integration is still in its infancy. Currently, some single-omics analyses have provided valuable data, mostly in the field of genomics. Thus, several gene-diet interactions in determining both intermediate (plasma lipids, etc.) and final cardiovascular phenotypes (stroke, myocardial infarction, etc.) have been reported. However, few studies have analyzed changes in gene expression and, moreover very few have focused on epigenomic or metabolomic biomarkers related to the MedDiet. Nevertheless, these preliminary results can help to better understand the inter-individual differences in cardiovascular risk and dietary response for further applications in personalized nutrition. PMID:27598147

Longitudinal Cognitive Trajectories of Women Veterans from the Women's Health Initiative Memory Study.

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Padula, Claudia B; Weitlauf, Julie C; Rosen, Allyson C; Reiber, Gayle; Cochrane, Barbara B; Naughton, Michelle J; Li, Wenjun; Rissling, Michelle; Yaffe, Kristine; Hunt, Julie R; Stefanick, Marcia L; Goldstein, Mary K; Espeland, Mark A

2016-02-01

A comparison of longitudinal global cognitive functioning in women Veteran and non-Veteran participants in the Women's Health Initiative (WHI). We studied 7,330 women aged 65-79 at baseline who participated in the WHI Hormone Therapy Trial and its ancillary Memory Study (WHIMS). Global cognitive functioning (Modified Mini-Mental State Examination [3MSE]) in Veterans (n = 279) and non-Veterans (n = 7,051) was compared at baseline and annually for 8 years using generalized linear modeling methods. Compared with non-Veterans, Veteran women were older, more likely to be Caucasian, unmarried, and had higher rates of educational and occupational attainment. Results of unadjusted baseline analyses suggest 3MSE scores were similar between groups. Longitudinal analyses, adjusted for age, education, ethnicity, and WHI trial assignment revealed differences in the rate of cognitive decline between groups over time, such that scores decreased more in Veterans relative to non-Veterans. This relative difference was more pronounced among Veterans who were older, had higher educational/occupational attainment and greater baseline prevalence of cardiovascular risk factors (e.g., smoking) and cardiovascular disease (e.g., angina, stroke). Veteran status was associated with higher prevalence of protective factors that may have helped initially preserve cognitive functioning. However, findings ultimately revealed more pronounced cognitive decline among Veteran relative to non-Veteran participants, likely suggesting the presence of risks that may impact neuropathology and the effects of which were initially masked by Veterans' greater cognitive reserve. © The Author 2015. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Triglycerides and cardiovascular disease

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Nordestgaard, Børge G; Varbo, Anette

2014-01-01

cholesterol might not cause cardiovascular disease as originally thought has now generated renewed interest in raised concentrations of triglycerides. This renewed interest has also been driven by epidemiological and genetic evidence supporting raised triglycerides, remnant cholesterol, or triglyceride......-rich lipoproteins as an additional cause of cardiovascular disease and all-cause mortality. Triglycerides can be measured in the non-fasting or fasting states, with concentrations of 2-10 mmol/L conferring increased risk of cardiovascular disease, and concentrations greater than 10 mmol/L conferring increased risk...... of acute pancreatitis and possibly cardiovascular disease. Although randomised trials showing cardiovascular benefit of triglyceride reduction are scarce, new triglyceride-lowering drugs are being developed, and large-scale trials have been initiated that will hopefully provide conclusive evidence...

Discovering Pediatric Asthma Phenotypes on the Basis of Response to Controller Medication Using Machine Learning.

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Ross, Mindy K; Yoon, Jinsung; van der Schaar, Auke; van der Schaar, Mihaela

2018-01-01

Pediatric asthma has variable underlying inflammation and symptom control. Approaches to addressing this heterogeneity, such as clustering methods to find phenotypes and predict outcomes, have been investigated. However, clustering based on the relationship between treatment and clinical outcome has not been performed, and machine learning approaches for long-term outcome prediction in pediatric asthma have not been studied in depth. Our objectives were to use our novel machine learning algorithm, predictor pursuit (PP), to discover pediatric asthma phenotypes on the basis of asthma control in response to controller medications, to predict longitudinal asthma control among children with asthma, and to identify features associated with asthma control within each discovered pediatric phenotype. We applied PP to the Childhood Asthma Management Program study data (n = 1,019) to discover phenotypes on the basis of asthma control between assigned controller therapy groups (budesonide vs. nedocromil). We confirmed PP's ability to discover phenotypes using the Asthma Clinical Research Network/Childhood Asthma Research and Education network data. We next predicted children's asthma control over time and compared PP's performance with that of traditional prediction methods. Last, we identified clinical features most correlated with asthma control in the discovered phenotypes. Four phenotypes were discovered in both datasets: allergic not obese (A + /O - ), obese not allergic (A - /O + ), allergic and obese (A + /O + ), and not allergic not obese (A - /O - ). Of the children with well-controlled asthma in the Childhood Asthma Management Program dataset, we found more nonobese children treated with budesonide than with nedocromil (P = 0.015) and more obese children treated with nedocromil than with budesonide (P = 0.008). Within the obese group, more A + /O + children's asthma was well controlled with nedocromil than with budesonide (P = 0.022) or with placebo

Applied longitudinal analysis

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Fitzmaurice, Garrett M; Ware, James H

2012-01-01

Praise for the First Edition "". . . [this book] should be on the shelf of everyone interested in . . . longitudinal data analysis.""-Journal of the American Statistical Association   Features newly developed topics and applications of the analysis of longitudinal data Applied Longitudinal Analysis, Second Edition presents modern methods for analyzing data from longitudinal studies and now features the latest state-of-the-art techniques. The book emphasizes practical, rather than theoretical, aspects of methods for the analysis of diverse types of lo

The deleterious effects of arteriovenous fistula-creation on the cardiovascular system: a longitudinal magnetic resonance imaging study

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Dundon BK

2014-09-01

Full Text Available Benjamin K Dundon,1–3 Kim Torpey,3 Adam J Nelson,1 Dennis TL Wong,1,2 Rae F Duncan,1 Ian T Meredith,2 Randall J Faull,1,3 Stephen G Worthley,1,4 Matthew I Worthley1,4 1Cardiology Department, Royal Adelaide Hospital, Central Adelaide Local Health Network, Discipline of Medicine, University of Adelaide, Adelaide, SA, Australia; 2Monash Cardiovascular Research Centre, MonashHEART, Monash Health, Melbourne, Vic, Australia; 3Central Northern Renal and Transplantation Service, Royal Adelaide Hospital, Central Adelaide Local Health Network, Adelaide, SA, Australia; 4South Australian Health and Medical Research Institute, Adelaide, SA, Australia Aim: Arteriovenous fistula-formation remains critical for the provision of hemodialysis in end-stage renal failure patients. Its creation results in a significant increase in cardiac output, with resultant alterations in cardiac stroke volume, systemic blood flow, and vascular resistance. The impact of fistula-formation on cardiac and vascular structure and function has not yet been evaluated via "gold standard" imaging techniques in the modern era of end-stage renal failure care. Methods: A total of 24 patients with stage 5 chronic kidney disease undergoing fistula-creation were studied in a single-arm pilot study. Cardiovascular magnetic resonance imaging was undertaken at baseline, and prior to and 6 months following fistula-creation. This gold standard imaging modality was used to evaluate, via standard brachial flow-mediated techniques, cardiac structure and function, aortic distensibility, and endothelial function. Results: At follow up, left ventricular ejection fraction remained unchanged, while mean cardiac output increased by 25.0% (P<0.0001. Significant increases in left and right ventricular end-systolic volumes (21% [P=0.014] and 18% [P<0.01], left and right atrial area (11% [P<0.01] and 9% [P<0.01], and left ventricular mass were observed (12.7% increase (P<0.01. Endothelial

New insights on the maternal diet induced-hypertension: potential role of the phenotypic plasticity and sympathetic-respiratory overactivity

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JOAO HENRIQUE eDA COSTA SILVA

2015-11-01

Full Text Available Systemic arterial hypertension (SAH is an important risk factor for cardiovascular disease and affects worldwide population. Current environment including life style coupled with genetic programming have been attributed to the rising incidence of hypertension. Besides, environmental conditions during perinatal development such as maternal malnutrition can program changes in the integration among renal, neural and endocrine system leading to hypertension. This phenomenon is termed phenotypic plasticity and refers to the adjustment of a phenotype in response to environmental input without genetic change, following a novel or unusual input during development. Human and animal studies indicate that fetal exposure to an adverse maternal environment may alter the renal morphology and physiology that contribute to the development of hypertension. Recently, it has been shown that the maternal protein restriction alter the central control of SAH by a mechanism that include respiratory dysfunction and enhanced sympathetic-respiratory coupling at early life, which may contribute to adult hypertension. This review will address the new insights on the maternal diet induced-hypertension that include the potential role of the phenotypic plasticity, specifically the perinatal protein malnutrition, and sympathetic-respiratory overactivity.

Understanding cardiovascular disease

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... page: //medlineplus.gov/ency/patientinstructions/000759.htm Understanding cardiovascular disease To use the sharing features on this page, ... lead to heart attack or stroke. Types of Cardiovascular Disease Coronary heart disease (CHD) is the most common ...

Asthma phenotypes in childhood.

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Reddy, Monica B; Covar, Ronina A

2016-04-01

This review describes the literature over the past 18 months that evaluated childhood asthma phenotypes, highlighting the key aspects of these studies, and comparing these studies to previous ones in this area. Recent studies on asthma phenotypes have identified new phenotypes on the basis of statistical analyses (using cluster analysis and latent class analysis methodology) and have evaluated the outcomes and associated risk factors of previously established early childhood asthma phenotypes that are based on asthma onset and patterns of wheezing illness. There have also been investigations focusing on immunologic, physiologic, and genetic correlates of various phenotypes, as well as identification of subphenotypes of severe childhood asthma. Childhood asthma remains a heterogeneous condition, and investigations into these various presentations, risk factors, and outcomes are important since they can offer therapeutic and prognostic relevance. Further investigation into the immunopathology and genetic basis underlying childhood phenotypes is important so therapy can be tailored accordingly.

Elevation of urinary liver-type fatty acid binding protein after cardiac catheterization related to cardiovascular events

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Kamijo-Ikemori A

2015-08-01

Full Text Available Atsuko Kamijo-Ikemori,1,3 Nobuyuki Hashimoto,2 Takeshi Sugaya,1 Katsuomi Matsui,1 Mikako Hisamichi,1 Yugo Shibagaki,1 Fumihiko Miyake,2 Kenjiro Kimura1 1Department of Nephrology and Hypertension, 2Department of Cardiology, 3Department of Anatomy, St Marianna University School of Medicine, Kawasaki, Kanagawa, Japan Purpose: Contrast medium (CM induces tubular hypoxia via endothelial damage due to direct cytotoxicity or viscosity. Urinary liver-type fatty acid binding protein (L-FABP increases along with tubular hypoxia and may be a detector of systemic circulation injury. The aim of this study was to evaluate the clinical usefulness of detecting increases in urinary L-FABP levels due to administration of CM, as a prognostic biomarker for cardiovascular disease in patients without occurrence of CM-induced nephropathy undergoing cardiac catheterization procedure (CCP. Methods: Retrospective longitudinal analyses of the relationship between urinary L-FABP levels and occurrence of cardiovascular events were performed (n=29. Urinary L-FABP was measured by ELISA before CCP, and at 6, 12, 24, and 48 hours after CCP. Results: Urinary L-FABP levels were significantly higher at 12 hours (P<0.05 and 24 hours (P<0.005 after CCP compared with before CCP, only in the patients with occurrence of cardiovascular events (n=17, but not in those without cardiovascular events (n=12. The parameter with the largest area under the curve (0.816 for predicting the occurrence of cardiovascular events was the change in urinary L-FABP at 24 hours after CCP. The difference in urinary L-FABP levels (ΔL-FABP ≥11.0 µg/g creatinine between before CCP and at 24 hours after CCP was a risk factor for the occurrence of cardiovascular events (hazard ratio, 4.93; 95% confidence interval, 1.27–19.13; P=0.021. Conclusion: Measurement of urinary L-FABP before CCP and at 24 hours after CCP in patients with mild to moderate renal dysfunction may be an important indicator for risk

Work-related stress as a cardiovascular risk factor in police officers: a systematic review of evidence.

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Magnavita, N; Capitanelli, I; Garbarino, S; Pira, E

2018-05-01

Several studies suggest that work-related stress in police officers may be associated with an increased risk of cardiovascular diseases. A systematic review of studies is, however, still lacking. According to PRISMA statement, a systematic search of PubMed, ISI Web of Science, Cinahl and PsychInfo electronic databases was undertaken. Studies published in English between 1/1/2000 and 31/12/2016 were included. A studies quality assessment was performed using the Newcastle Ottawa scale (NOS). The preliminary search retrieved 752 records. After selection, 16 studies (total population 17,698) were retrieved. The average quality of studies was low. Exposure to stress in cross-sectional studies was inconstantly associated with hypertension, obesity, dyslipidaemia, and impaired glucose metabolism. In addition, there was a prevalence of positive studies showing an association between stress and cardiovascular disease morbidity. Studies of higher quality, such as longitudinal studies on large sample size, were more supportive of a significant positive association between stress and cardiovascular risk factors. Results were, however, often conflicting and inconsistent with regard to definitions and measurement of stress, features of individual study design, study conduct, and conclusions drawn. A sound precautionary principle would be to adopt worksite health promotion programs designed to implement stress management strategies in this category of workers.

The Human Phenotype Ontology project: linking molecular biology and disease through phenotype data

NARCIS (Netherlands)

Kohler, S.; Doelken, S.C.; Mungall, C.J.; Bauer, S.; Firth, H.V.; Bailleul-Forestier, I.; Black, G.C.M.; Brown, D.L.; Brudno, M.; Campbell, J.; FitzPatrick, D.R.; Eppig, J.T.; Jackson, A.P.; Freson, K.; Girdea, M.; Helbig, I.; Hurst, J.A.; Jahn, J.; Jackson, L.G.; Kelly, A.M.; Ledbetter, D.H.; Mansour, S.; Martin, C.L.; Moss, C.; Mumford, A.; Ouwehand, W.H.; Park, S.M.; Riggs, E.R.; Scott, R.H.; Sisodiya, S.; Vooren, S. van der; Wapner, R.J.; Wilkie, A.O.; Wright, C.F.; Silfhout, A.T. van; Leeuw, N. de; Vries, B. de; Washingthon, N.L.; Smith, C.L.; Westerfield, M.; Schofield, P.; Ruef, B.J.; Gkoutos, G.V.; Haendel, M.; Smedley, D.; Lewis, S.E.; Robinson, P.N.

2014-01-01

The Human Phenotype Ontology (HPO) project, available at http://www.human-phenotype-ontology.org, provides a structured, comprehensive and well-defined set of 10,088 classes (terms) describing human phenotypic abnormalities and 13,326 subclass relations between the HPO classes. In addition we have

Slow breathing and cardiovascular disease

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Ashish Chaddha

2015-01-01

Full Text Available Cardiovascular disease is the leading cause of death for both men and women worldwide. Much emphasis has been placed on the primary and secondary prevention of cardiovascular disease. While depression and anxiety increase the risk of developing cardiovascular disease, cardiovascular disease also increases the risk of developing anxiety and depression. Thus, promoting optimal mental health may be important for both primary and secondary prevention of cardiovascular disease. Like lowering blood pressure, lipids, and body weight, lowering anger and hostility and improving depression and anxiety may also be an important intervention in preventive cardiology. As we strive to further improve cardiovascular outcomes, the next bridge to cross may be one of offering patients nonpharmacologic means for combating daily mental stress and promoting mental health, such as yoga and pranayama. Indeed, the best preventive cardiovascular medicine may be a blend of both Western and Eastern medicine.

The evolution of phenotypic plasticity in fish swimming

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Oufiero, Christopher E.; Whitlow, Katrina R.

2016-01-01

Abstract Fish have a remarkable amount of variation in their swimming performance, from within species differences to diversity among major taxonomic groups. Fish swimming is a complex, integrative phenotype and has the ability to plastically respond to a myriad of environmental changes. The plasticity of fish swimming has been observed on whole-organismal traits such as burst speed or critical swimming speed, as well as underlying phenotypes such as muscle fiber types, kinematics, cardiovascular system, and neuronal processes. Whether the plastic responses of fish swimming are beneficial seems to depend on the environmental variable that is changing. For example, because of the effects of temperature on biochemical processes, alterations of fish swimming in response to temperature do not seem to be beneficial. In contrast, changes in fish swimming in response to variation in flow may benefit the fish to maintain position in the water column. In this paper, we examine how this plasticity in fish swimming might evolve, focusing on environmental variables that have received the most attention: temperature, habitat, dissolved oxygen, and carbon dioxide variation. Using examples from previous research, we highlight many of the ways fish swimming can plastically respond to environmental variation and discuss potential avenues of future research aimed at understanding how plasticity of fish swimming might evolve. We consider the direct and indirect effects of environmental variation on swimming performance, including changes in swimming kinematics and suborganismal traits thought to predict swimming performance. We also discuss the role of the evolution of plasticity in shaping macroevolutionary patterns of diversity in fish swimming. PMID:29491937

Molecular cardiovascular imaging

International Nuclear Information System (INIS)

Schaefers, M.

2007-01-01

Although huge and long-lasting research efforts have been spent on the development of new diagnostic techniques investigating cardiovascular diseases, still fundamental challenges exist; the main challenge being the diagnosis of a suspected or known coronary artery disease or its consequences (myocardial infarction, heart failure etc.). Beside morphological techniques, functional imaging modalities are available in clinical diagnostic algorithms, whereas molecular cardiovascular imaging techniques are still under development. This review summarizes clinical-diagnostical challenges of modern cardiovascular medicine as well as the potential of new molecular imaging techniques to face these. (orig.)

Cardiovascular Diseases and Fat Soluble Vitamins: Vitamin D and Vitamin K.

Science.gov (United States)

Tsugawa, Naoko

2015-01-01

Recently, the associations between insufficiency of fat soluble vitamins and cardiovascular diseases (CVDs) have been reported. Vitamin D affects the cardiovascular system via several pathways, such as suppression of parathyroid hormone, the renin- angiotensin-aldosterone system and vascular endothelial growth and the immune system. Cross-sectional and longitudinal studies have shown the association between the concentration of serum 25-hydroxyvitamin D (25OHD), which is a vitamin D metabolite indicating nutritional vitamin D status, and hypertension, myocardial infarction, heart failure and CVD mortality. On the other hand, the association between vitamin K status and CVDs, especially vascular calcification, has been also reported. Cross-sectional and cohort studies show that high vitamin K status is associated with reduced coronary artery calcification, CVDs and mortality risk. Epidemiological and basic studies indicate that vitamin K possesses a benefit in the prevention of the progression of coronary artery calcification via activation of matrix-gla protein (MGP). While these data in epidemiological and basic studies suggest the protective role of vitamin D and K in CVDs, the benefits of supplementation of both vitamins have not been validated in randomized controlled trials. Further basic and interventional studies are needed to confirm the benefit of both vitamins in protection against CVDs.

Phenotypic equilibrium as probabilistic convergence in multi-phenotype cell population dynamics.

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Da-Quan Jiang

Full Text Available We consider the cell population dynamics with n different phenotypes. Both the Markovian branching process model (stochastic model and the ordinary differential equation (ODE system model (deterministic model are presented, and exploited to investigate the dynamics of the phenotypic proportions. We will prove that in both models, these proportions will tend to constants regardless of initial population states ("phenotypic equilibrium" under weak conditions, which explains the experimental phenomenon in Gupta et al.'s paper. We also prove that Gupta et al.'s explanation is the ODE model under a special assumption. As an application, we will give sufficient and necessary conditions under which the proportion of one phenotype tends to 0 (die out or 1 (dominate. We also extend our results to non-Markovian cases.

Dietary Intake and Cardiovascular Risk Factors in Icelanders Following Voluntarily a Low Carbohydrate Diet.

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Anita S Elidottir

Full Text Available Most studies regarding low-carbohydrate diets (LCDs have been intervention studies. The aim of the current study was to investigate dietary intake and cardiovascular risk factors among individuals who voluntarily follow a LCD.A cross-sectional study was conducted (N = 54, 20-66yrs in Reykjavik, Iceland. Participants recorded food intake for three days. Blood samples were analyzed for cardiovascular risk factors.Nearly half of the participants were obese and around 60% had been on a LCD for ≥ 6 months. Fifty percent claimed they had lost weight during the past month. The median intake of carbohydrate, protein and fat were 8%, 22% and 68% E (hereof 25% saturated fatty acids, respectively. The consumption of bread and wholegrain cereals was very low (<5g/day, including the intake of dietary fiber (11g/day. Median fruit intake was 12 g/day. Intake of red meat and meat products was double that of the general population or ~900 g/week. Median intake of vitamins and minerals were mostly higher than the estimated average requirements. Cardiovascular risk factors were mostly within normal range. Mean blood lipids were slightly elevated although the high density lipoprotein/total cholesterol ratio was normal.Despite poor diet quality and high prevalence of obesity, individuals who voluntarily follow a LCD have cardiovascular risk factors mostly within reference range. These individuals consume very low amounts of carbohydrates and high amounts of fat and saturated fat acids. Intake of red meat and processed meat exceeds recommended intake. Very low intake of whole grain cereals and fruits results in low intake of fiber. Long term health implications need to be examined further in longitudinal studies.

Associations of Dairy Intake with Arterial Stiffness in Brazilian Adults: The Brazilian Longitudinal Study of Adult Health (ELSA-Brasil).

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Ribeiro, Amanda Gomes; Mill, José Geraldo; Cade, Nágela Valadão; Velasquez-Melendez, Gustavo; Matos, Sheila Maria Alvim; Molina, Maria Del Carmen Bisi

2018-05-31

Recent studies have suggested the possible effect of dairy product intake on cardiovascular risk markers, including arterial stiffness. Our aim was to investigate whether dairy food intake is associated with arterial stiffness, which we assessed by carotid-femoral pulse wave velocity (cfPWV) and pulse pressure (PP) in a cross-sectional analysis of baseline data (2008⁻2010; n = 12,892) of the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil). Dairy consumption was evaluated with a validated food-frequency questionnaire (FFQ) by computing servings per day for total and subgroups of dairy products. Dairy consumption was described in four categories (≤1 serving/day to >4 servings/day). Covariance analysis (ANCOVA) was used to compare cfPWV across increasing intake of dairy food, adjusting for confounding factors, including non-dairy food groups. The intake of total dairy was inversely associated with cfPWV and PP (-0.13 m/s and -1.3 mmHg, from the lowest and to the highest category of dairy intake). Low-fat dairy, fermented dairy and cheese showed an inverse relationship with cfPWV and PP. These findings suggest a beneficial effect of dairy consumption to reduce arterial stiffness. However, further evidence from longitudinal studies or long-term intervention is needed to support reduction of cfPWV and PP mediating the beneficial effects of dairy products on cardiovascular health.

Associations of Dairy Intake with Arterial Stiffness in Brazilian Adults: The Brazilian Longitudinal Study of Adult Health (ELSA-Brasil

Directory of Open Access Journals (Sweden)

Amanda Gomes Ribeiro

2018-05-01

Full Text Available Recent studies have suggested the possible effect of dairy product intake on cardiovascular risk markers, including arterial stiffness. Our aim was to investigate whether dairy food intake is associated with arterial stiffness, which we assessed by carotid-femoral pulse wave velocity (cfPWV and pulse pressure (PP in a cross-sectional analysis of baseline data (2008–2010; n = 12,892 of the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil. Dairy consumption was evaluated with a validated food-frequency questionnaire (FFQ by computing servings per day for total and subgroups of dairy products. Dairy consumption was described in four categories (≤1 serving/day to >4 servings/day. Covariance analysis (ANCOVA was used to compare cfPWV across increasing intake of dairy food, adjusting for confounding factors, including non-dairy food groups. The intake of total dairy was inversely associated with cfPWV and PP (−0.13 m/s and −1.3 mmHg, from the lowest and to the highest category of dairy intake. Low-fat dairy, fermented dairy and cheese showed an inverse relationship with cfPWV and PP. These findings suggest a beneficial effect of dairy consumption to reduce arterial stiffness. However, further evidence from longitudinal studies or long-term intervention is needed to support reduction of cfPWV and PP mediating the beneficial effects of dairy products on cardiovascular health.

Cardiac patients who completed a longitudinal psychosocial study had a different clinical and psychosocial baseline profile than patients who dropped out prematurely

DEFF Research Database (Denmark)

Damen, Nikki L; Versteeg, Henneke; Serruys, Patrick W

2013-01-01

drop-outs may have a different cardiovascular risk. We studied a cohort of 1132 consecutive patients undergoing percutaneous coronary intervention (PCI). At baseline, all patients completed the Hospital Anxiety and Depression Scale (HADS) and the Type D Scale (DS14). At 12 months follow-up, 70.8% (n...... cardiovascular medications, including calcium antagonists and angiotensin-converting enzyme inhibitors, as compared with completers. Drop-outs more often had depression, anxiety, and negative affectivity, as compared with completers (all p-values......Non-response is a serious threat to the external validity of longitudinal psychosocial studies. Little is known about potential systematic differences between patients with coronary artery disease who complete a psychosocial study and those who drop out prematurely due to non-response, or whether...

Caffeine and cardiovascular health.

Science.gov (United States)

Turnbull, Duncan; Rodricks, Joseph V; Mariano, Gregory F; Chowdhury, Farah

2017-10-01

This report evaluates the scientific literature on caffeine with respect to potential cardiovascular outcomes, specifically relative risks of total cardiovascular disease (CVD), coronary heart disease (CHD) and acute myocardial infarction (AMI), effects on arrhythmia, heart failure, sudden cardiac arrest, stroke, blood pressure, hypertension, and other biomarkers of effect, including heart rate, cerebral blood flow, cardiac output, plasma homocysteine levels, serum cholesterol levels, electrocardiogram (EKG) parameters, heart rate variability, endothelial/platelet function and plasma/urine catecholamine levels. Caffeine intake has been associated with a range of reversible and transient physiological effects broadly and cardiovascular effects specifically. This report attempts to understand where the delineations exist in caffeine intake and corresponding cardiovascular effects among various subpopulations. The available literature suggests that cardiovascular effects experienced by caffeine consumers at levels up to 600 mg/day are in most cases mild, transient, and reversible, with no lasting adverse effect. The point at which caffeine intake may cause harm to the cardiovascular system is not readily identifiable in part because data on the effects of daily intakes greater than 600 mg is limited. However, the evidence considered within this review suggests that typical moderate caffeine intake is not associated with increased risks of total cardiovascular disease; arrhythmia; heart failure; blood pressure changes among regular coffee drinkers; or hypertension in baseline populations. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

[Strategies for cardiovascular disease prevention].

Science.gov (United States)

Gabus, Vincent; Wuerzner, Grégoire; Saubade, Mathieu; Favre, Lucie; Jacot Sadowski, Isabelle; Nanchen, David

2018-02-28

Atherosclerosis is a disease which develops very gradually over decades. Under the influence of modifiable cardiovascular risk factors, such as blood pressure, LDL-cholesterol level, smoking or lifestyle, clinical symptoms of atherosclerosis manifest more or less early in life. When cardiovascular risk factors accumulate, the risk of having a cardiovascular event increases and the benefits of prevention measures are greater. This article summarizes existing strategies for controlling modifiable cardiovascular risk factors in primary prevention. The physician can rely on an interprofessional network of cardiovascular prevention. Managing risk factors while respecting the autonomy and priorities of the patient will bring the greatest benefit.

Restoration of longitudinal images.

Science.gov (United States)

Hu, Y; Frieden, B R

1988-01-15

In this paper, a method of restoring longitudinal images is developed. By using the transfer function for longitudinal objects, and inverse filtering, a longitudinal image may be restored. The Fourier theory and sampling theorems for transverse images cannot be used directly in the longitudinal case. A modification and reasonable approximation are introduced. We have numerically established a necessary relationship between just-resolved longitudinal separation (after inverse filtering), noise level, and the taking conditions of object distance and lens diameter. An empirical formula is also found to well-fit the computed results. This formula may be of use for designing optical systems which are to image longitudinal details, such as in robotics or microscopy.

Knowledge-based analysis of phenotypes

KAUST Repository

Hoendorf, Robert

2016-01-27

Phenotypes are the observable characteristics of an organism, and they are widely recorded in biology and medicine. To facilitate data integration, ontologies that formally describe phenotypes are being developed in several domains. I will describe a formal framework to describe phenotypes. A formalized theory of phenotypes is not only useful for domain analysis, but can also be applied to assist in the diagnosis of rare genetic diseases, and I will show how our results on the ontology of phenotypes is now applied in biomedical research.

Acute Cardiovascular Care Association Position Paper on Intensive Cardiovascular Care Units

DEFF Research Database (Denmark)

Bonnefoy-Cudraz, Eric; Bueno, Hector; Casella, Gianni

2018-01-01

, the recommended management structure, the optimal number of staff, the need for specially trained cardiologists and cardiovascular nurses, the desired equipment and architecture, and the interaction with other departments in the hospital and other intensive cardiovascular care units in the region...

Phenotypes of sleep-disordered breathing symptoms to two years of age based on age of onset and duration of symptoms.

Science.gov (United States)

Kamal, Muna; Tamana, Sukhpreet K; Smithson, Lisa; Ding, Linda; Lau, Amanda; Chikuma, Joyce; Mariasine, Jennifer; Lefebvre, Diana L; Subbarao, Padmaja; Becker, Allan B; Turvey, Stuart E; Sears, Malcolm R; Pei, Jacqueline; Mandhane, Piush J

2018-05-03

Childhood sleep-disordered breathing (SDB) symptoms may comprise multiple phenotypes depending on craniofacial anatomy, tonsil and adenoid growth, body habitus, and rhinitis symptoms. The primary objective of this study is to identify and characterize the different SDB phenotypes to two years of age. Data from 770 infants in the Edmonton sub-cohort of the Canadian Healthy Infant Longitudinal Study (CHILD) were analyzed to identify SDB phenotypes based on age of onset and duration of symptoms. Parents completed the 22-item sleep-related breathing disorder (SRBD) scale. Children with a SRBD ratio greater than 0.33 were considered positive for SDB at each quarterly assessment between three months and two years. The STATA Proc trajectory extension identified SDB phenotypes based on their age of onset and duration of symptoms and attributed the percentage chance of a participant being assigned to each phenotype. Multivariate linear regression identified factors associated with increased risk of being assigned to each SDB phenotype. Trajectory analysis identified four phenotypes: no SDB (65.7%), early-onset SDB (15.7%) with peak symptoms at nine months, late-onset SDB (14.2%) with peak symptoms at 18 months, and persistent SDB (5.3%) with symptoms from 3 to 24 months. Rhinitis was associated with all three SDB symptom trajectories (p sleep apnea syndrome (OSAS) was associated with persistent (p = 0.01) and late SDB (p < 0.001). Atopy (positive skin prick test at one year) was associated with persistent SDB (p = 0.04). Infants born prior to 36.5 weeks gestational age were more likely to present with late SDB (p = 0.03). Childhood SDB symptoms, rather than being a homogenous disorder, may comprise multiple overlapping phenotypes each with unique risk factors. Copyright © 2018 Elsevier B.V. All rights reserved.

Longitudinal assessment of endothelial function in the microvasculature of mice in-vivo.

Science.gov (United States)

Belch, Jill J F; Akbar, Naveed; Alapati, Venkateswara; Petrie, John; Arthur, Simon; Khan, Faisel

2013-01-01

Endothelial dysfunction is associated with early development of cardiovascular disease, making longitudinal measurements desirable. We devised a protocol using laser Doppler imaging (LDI) and iontophoresis of acetylcholine (ACh) and sodium nitroprusside (SNP) to assess the skin microcirculation longitudinally in mice every 4 weeks for 24 weeks in two groups of C57BL/6 mice, chow versus high-cholesterol diet(known to induce endothelial dysfunction). LDI measurements were compared with vascular function (isometric tension) measured using wire myography in the tail artery in response to ACh and SNP. Microvascular responses to ACh were significantly reduced in cholesterol-fed versus chow-fed mice from week 4 onwards (Phydrochloride (L-NAME) showed a significant reduction in ACh response compared with vehicle-treated animals (P<0.05) at baseline and at 12 weeks. In cholesterol-fed mice, ACh responses were 226 ± 21 and 180 ± 21 AU (P=0.03) before and after L-NAME, respectively. A reduction in ex-vivo ACh response was detected in the tail artery in cholesterol-fed mice, and a significant correlation found between peak microvascular ACh response and maximum ACh response in the tail artery (r=0.699, P=0.017). No changes were found in SNP responses in the microvasculature or tail artery. Using this protocol, we have shown longitudinal decreases in microvascular endothelial function to cholesterol feeding. L-NAME studies confirm that the reduced vasodilatation to ACh in cholesterol-fed mice was mediated partly through reduced NO bioavailability. Wire myography of tail arteries confirmed that in-vivo measurements of microvascular function reflect ex-vivo vascular function in other beds. Longitudinal assessments of skin microvascular function in mice could provide a useful translatable model for assessing early endothelial dysfunction. Copyright © 2012 Elsevier Inc. All rights reserved.

Mortality of mothers from cardiovascular and non-cardiovascular causes following pregnancy complications in first delivery.

Science.gov (United States)

Lykke, Jacob A; Langhoff-Roos, Jens; Lockwood, Charles J; Triche, Elizabeth W; Paidas, Michael J

2010-07-01

The combined effects of preterm delivery, small-for-gestational-age offspring, hypertensive disorders of pregnancy, placental abruption and stillbirth on early maternal death from cardiovascular causes have not previously been described in a large cohort. We investigated the effects of pregnancy complications on early maternal death in a registry-based retrospective cohort study of 782 287 women with a first singleton delivery in Denmark 1978-2007, followed for a median of 14.8 years (range 0.25-30.2) accruing 11.6 million person-years. We employed Cox proportional hazard models of early death from cardiovascular and non-cardiovascular causes following preterm delivery, small-for-gestational-age offspring and hypertensive disorders of pregnancy. We found that preterm delivery and small-for-gestational-age were both associated with subsequent death of mothers from cardiovascular and non-cardiovascular causes. Severe pre-eclampsia was associated with death from cardiovascular causes only. There was a less than additive effect on cardiovascular mortality hazard ratios with increasing number of pregnancy complications: preterm delivery 1.90 [95% confidence intervals 1.49, 2.43]; preterm delivery and small-for-gestational-age offspring 3.30 [2.25, 4.84]; preterm delivery, small-for-gestational-age offspring and pre-eclampsia 3.85 [2.07, 7.19]. Thus, we conclude that, separately and combined, preterm delivery and small-for-gestational-age are strong markers of early maternal death from both cardiovascular and non-cardiovascular causes, while hypertensive disorders of pregnancy are markers of early death of mothers from cardiovascular causes.

Phenotypic subgroups of polycystic ovary syndrome have different intra-renal resistance symptoms.

Science.gov (United States)

Ciftci, Ceylan F; Uckuyu, Ayla; Karadeli, Elif; Turhan, Erdem; Toprak, Erzat; Ozcimen, Emel E

2012-12-01

The polycystic ovary syndrome (PCOS) is known to be related with increased metabolic and cardiovascular risks. Various phenotypic subgroups of PCOS have been proven to have metabolic and endocrine disorders with varying degrees of severity However, intra-renal vascular resistance, which is an indirect indication of atherosclerosis, remains unknown in PCOS subgroups. In this study we examined whether PCOS subgroups have different intra-renal resistance symptoms. 98 PCOS patients (diagnosed according to the Rotterdam criteria) 30 controls were included in the study The diagnosis of PCOS was established in the presence of at least two of the following criteria: 1-oligo and/or amenorrhea (OM); 2-clinic and/or biochemical signs of hyperandrogenism (HA); 3-polycystic ovarian morphology (PCO) detected by transvaginal ultrasonography 37 patients (Group 1) met all three criteria (HA+OM+PCO), 29 patients (Group 2) met two of the criteria including hyperandrogenism (HA+OM or HA+PCO) and the remaining 32 patients (Group 3) had no hyperandrogenism but fulfilled the other two criteria; PCO+OM. Renal Doppler ultrasonography and hormonal/biochemical analyses were carried out. The first outcome measure was designated as the differences in the renal resistive index (RRI) values of the groups, and the second outcome measure was designated as the relation of RRI with the insulin resistance and lipid profile. In Group 1, the RRI and the homeostasis model assessment of insulin resistance (HOMA-IR) values were significantly higher than in Group 3 and controls (P PCOS subgroups have metabolic and endocrine disorders and cardiovascular risks of varying degrees of severity Moreover, we showed that there was no increase of metabolic and cardiovascular risks in PCOS patients without hyperandrogenism.

Factors affecting affect cardiovascular health in Indonesian HIV patients beginning ART.

Science.gov (United States)

Karim, Birry; Wijaya, Ika Praseya; Rahmaniyah, Rizky; Ariyanto, Ibnu; Waters, Shelley; Estiasari, Riwanti; Price, Patricia

2017-08-31

We present a small longitudinal study of how demographic factors and persistent burdens of HIV and cytomegalovirus (CMV) influence cardiovascular health in young adults beginning ART in an inner-city clinic in Jakarta, Indonesia. ART-naïve HIV patients [n = 67; aged 31 (19 to 48) years] were enrolled in the JakCCANDO Project. Echocardiography and carotid Doppler ultrasonography were performed before ART (V0) and after 3, 6, and 12 months (V3-12). Antibodies reactive with CMV lysate or IE-1 protein were assessed at each timepoint and CMV DNA was identified at V0. Markers of adverse cardiovascular prognosis [left ventricular mass index, ejection fraction and carotid intimal media thickness (cIMT)] were similar to healthy controls, but increased at V12. Internal diameters of the carotid arteries and systolic blood pressure correlated with HIV disease severity at V0, but cardiac parameters and cIMT did not. E/A ratios (left ventricular diastolic function) were lower in patients with CMV DNA at V0, but this effect waned by V6. Levels of antibody reactive with CMV IE-1 correlated inversely with CD4 T cell counts at V0, and levels at V6-V12 correlated directly with the right cIMT. Overall the severity of HIV disease and the response to ART have only subtle effects on cardiovascular health in this young Asian population. CMV replication before ART may have a transient effect on cardiac health, whilst antibody reactive with CMV IE-1 may mark a high persistent CMV burden with cumulative effects on the carotid artery.

Multiplatform serum metabolic phenotyping combined with pathway mapping to identify biochemical differences in smokers.

Science.gov (United States)

Kaluarachchi, Manuja R; Boulangé, Claire L; Garcia-Perez, Isabel; Lindon, John C; Minet, Emmanuel F

2016-10-01

Determining perturbed biochemical functions associated with tobacco smoking should be helpful for establishing causal relationships between exposure and adverse events. A multiplatform comparison of serum of smokers (n = 55) and never-smokers (n = 57) using nuclear magnetic resonance spectroscopy, UPLC-MS and statistical modeling revealed clustering of the classes, distinguished by metabolic biomarkers. The identified metabolites were subjected to metabolic pathway enrichment, modeling adverse biological events using available databases. Perturbation of metabolites involved in chronic obstructive pulmonary disease, cardiovascular diseases and cancer were identified and discussed. Combining multiplatform metabolic phenotyping with knowledge-based mapping gives mechanistic insights into disease development, which can be applied to next-generation tobacco and nicotine products for comparative risk assessment.

Advanced phenotyping and phenotype data analysis for the plant growth and development study

Directory of Open Access Journals (Sweden)

Md. Matiur eRahaman

2015-08-01

Full Text Available Due to increase in the consumption of food, feed, fuel and to ensure global food security for rapidly growing human population, there is need to breed high yielding crops that can adapt to future climate. To solve these global issues, novel approaches are required to provide quantitative phenotypes to elucidate the genetic basis of agriculturally import traits and to screen germplasm with super performance in function under resource-limited environment. At present, plant phenomics has offered and integrated suite technologies for understanding the complete set of phenotypes of plants, towards the progression of the full characteristics of plants with whole sequenced genomes. In this aspect, high-throughput phenotyping platforms have been developed that enables to capture extensive and intensive phenotype data from non-destructive imaging over time. These developments advance our view on plant growth and performance with responses to the changing climate and environment. In this paper, we present a brief review on currently developed high-throughput plant phenotyping infrastructures based on imaging techniques and corresponding principles for phenotype data analysis.

Trace Elements in Cardiovascular Diseases

Energy Technology Data Exchange (ETDEWEB)

Masironi, R. [Cardiovascular Diseases Unit, World Health Organization, Geneva (Switzerland)

1970-07-01

Cardiovascular diseases are the leading cause of death in industrialized countries. Their incidence increases, apparently, as a, function of technological progress so that in the future they may become a major public health problem in developing countries too. Early diagnosis and prevention are the tools best suited to curb such an alarming trend, but our knowledge of these topics is unsatisfactory, Valuable information would be obtained through a systematic investigation of trace elements in relation to cardiovascular function and to various types of cardiovascular diseases. Such studies would provide clues to the following questions: 1. Why does the incidence and type of cardiovascular disease differ from one country to another? May this be related to differences in tissue mineral concentrations among various population groups? 2. Which trace elements if any are beneficial to cardiovascular health, and which are harmful ones that may act as aetiological agents for some cardiovascular diseases? 3. Is it possible to utilize measurements of mineral element concentration for diagnostic purposes in cardiovascular disease? (author)

Calcium as a cardiovascular toxin in CKD-MBD.

Science.gov (United States)

Moe, Sharon M

2017-07-01

Disordered calcium balance and homeostasis are common in patients with chronic kidney disease. Such alterations are commonly associated with abnormal bone remodeling, directly and indirectly. Similarly, positive calcium balance may also be a factor in the pathogenesis of extra skeletal soft tissue and arterial calcification. Calcium may directly affect cardiac structure and function through direct effects to alter cell signaling due to abnormal intracellular calcium homeostasis 2) extra-skeletal deposition of calcium and phosphate in the myocardium and small cardiac arterioles, 3) inducing cardiomyocyte hypertrophy through calcium and hormone activation of NFAT signaling mechanisms, and 4) increased aorta calcification resulting in chronic increased afterload leading to hypertrophy. Similarly, calcium may alter vascular smooth muscle cell function and affect cell signaling which may predispose to a proliferative phenotype important in arteriosclerosis and arterial calcification. Thus, disorders of calcium balance and homeostasis due to CKD-MBD may play a role in the high cardiovascular burden observed in patients with CKD. Published by Elsevier Inc.

Asian & Pacific Islanders and Cardiovascular Diseases

Science.gov (United States)

... Fact Sheet 2016 Update Asian & Pacific Islanders and Cardiovascular Diseases Cardiovascular Disease (CVD) (ICD 10 codes I00-I99, Q20- ... of na- tive Hawaiians or oth- A indicates cardiovascular disease plus congenital cardiovascular disease (ICD-10 I00- ...

Fatty acid binding protein 3 (fabp3) is associated with insulin, lipids and cardiovascular phenotypes of the metabolic syndrome through epigenetic modifications in a Northern European family population.

Science.gov (United States)

Zhang, Yi; Kent, Jack W; Lee, Adam; Cerjak, Diana; Ali, Omar; Diasio, Robert; Olivier, Michael; Blangero, John; Carless, Melanie A; Kissebah, Ahmed H

2013-03-19

Fatty acid-binding proteins (FABPs) play regulatory roles at the nexus of lipid metabolism and signaling. Dyslipidemia in clinical manifestation frequently co-occurs with obesity, insulin resistance and hypertension in the Metabolic Syndrome (MetS). Animal studies have suggested FABPs play regulatory roles in expressing MetS phenotypes. In our family cohort of Northern European descent, transcript levels in peripheral white blood cells (PWBCs) of a key FABPs, FABP3, is correlated with the MetS leading components. However, evidence supporting the functions of FABPs in humans using genetic approaches has been scarce, suggesting FABPs may be under epigenetic regulation. The objective of this study was to test the hypothesis that CpG methylation status of a key regulator of lipid homeostasis, FABP3, is a quantitative trait associated with status of MetS phenotypes in humans. We used a mass-spec based quantitative method, EpiTYPER®, to profile a CpG island that extends from the promoter to the first exon of the FABP3 gene in our family-based cohort of Northern European descent (n=517). We then conducted statistical analysis of the quantitative relationship of CpG methylation and MetS measures following the variance-component association model. Heritability of each methylation and the effect of age and sex on CpG methylation were also assessed in our families. We find that methylation levels of individual CpG units and the regional average are heritable and significantly influenced by age and sex. Regional methylation was strongly associated with plasma total cholesterol (p=0.00028) and suggestively associated with LDL-cholesterol (p=0.00495). Methylation at individual units was significantly associated with insulin sensitivity, lipid particle sizing and diastolic blood pressure (pmetabolism (βWHR=-0.72; βLDL-c=-0.53) while positively correlated with plasma adiponectin (β=0.24). Further, we show that differential methylation of FABP3 affects binding activity with

Power Doppler ultrasound phenotyping of expanding versus collapsed popliteal lymph nodes in murine inflammatory arthritis.

Directory of Open Access Journals (Sweden)

Echoe M Bouta

Full Text Available Rheumatoid arthritis is a chronic inflammatory disease manifested by episodic flares in affected joints that are challenging to predict and treat. Longitudinal contrast enhanced-MRI (CE-MRI of inflammatory arthritis in tumor necrosis factor-transgenic (TNF-Tg mice has demonstrated that popliteal lymph nodes (PLN increase in volume and contrast enhancement during the pre-arthritic "expanding" phase of the disease, and then suddenly "collapse" during knee flare. Given the potential of this biomarker of arthritic flare, we aimed to develop a more cost-effective means of phenotyping PLN using ultrasound (US imaging. Initially we attempted to recapitulate CE-MRI of PLN with subcutaneous footpad injection of US microbubbles (DEFINITY®. While this approach allowed for phenotyping via quantification of lymphatic sinuses in PLN, which showed a dramatic decrease in collapsed PLN versus expanding or wild-type (WT PLN, electron microscopy demonstrated that DEFINITY® injection also resulted in destruction of the lymphatic vessels afferent to the PLN. In contrast, Power Doppler (PD US is innocuous to and efficiently quantifies blood flow within PLN of WT and TNF-Tg mice. PD-US demonstrated that expanding PLN have a significantly higher normalized PD volume (NPDV versus collapsed PLN (0.553 ± 0.007 vs. 0.008 ± 0.003; p0.030 and lower (<0.016 quartile NPDVs in this cohort of mice, which serve as conservative thresholds to phenotype PLN as expanding and collapsed, respectively. Interestingly, of the 12 PLN phenotyped by the two methods, there was disagreement in 4 cases in which they were determined to be expanding by CE-MRI and collapsed by PD-US. Since the adjacent knee had evidence of synovitis in all 4 cases, we concluded that the PD-US phenotyping was correct, and that this approach is currently the safest and most cost-effective in vivo approach to phenotype murine PLN as a biomarker of arthritic flare.

Global Longitudinal Strain by Echocardiography Predicts Long-Term Risk of Cardiovascular Morbidity and Mortality in a Low-Risk General Population

DEFF Research Database (Denmark)

Biering-Sørensen, Tor; Biering-Sørensen, Sofie Reumert; Olsen, Flemming Javier

2017-01-01

participants in a general population study underwent a health examination, including echocardiography measurement of GLS. The primary end point was the composite of incident heart failure, acute myocardial infarction, or cardiovascular death. During a median follow-up of 11 years, 149 (12%) participants were...

Deep Phenotyping: Deep Learning For Temporal Phenotype/Genotype Classification

OpenAIRE

Najafi, Mohammad; Namin, Sarah; Esmaeilzadeh, Mohammad; Brown, Tim; Borevitz, Justin

2017-01-01

High resolution and high throughput, genotype to phenotype studies in plants are underway to accelerate breeding of climate ready crops. Complex developmental phenotypes are observed by imaging a variety of accessions in different environment conditions, however extracting the genetically heritable traits is challenging. In the recent years, deep learning techniques and in particular Convolutional Neural Networks (CNNs), Recurrent Neural Networks (RNNs) and Long-Short Term Memories (LSTMs), h...

The effectiveness of mobile-health behaviour change interventions for cardiovascular disease self-management: A systematic review.

Science.gov (United States)

Pfaeffli Dale, Leila; Dobson, Rosie; Whittaker, Robyn; Maddison, Ralph

2016-05-01

Mobile wireless devices (mHealth) have been used to deliver cardiovascular disease self-management interventions to educate and support patients in making healthy lifestyle changes. This systematic review aimed to determine the effectiveness of mHealth interventions on behavioural lifestyle changes and medication adherence for cardiovascular disease self-management. A comprehensive literature search was conducted from inception through to 3 March 2015 using MEDLINE, PubMed, PsycINFO, EMBASE and The Cochrane Library. Eligible studies used an experimental trial design to determine the effectiveness of an mHealth intervention to change lifestyle behaviours in any cardiovascular disease population. Data extracted included intervention and comparison group characteristics with a specific focus on the use of behaviour change techniques. Seven studies met our inclusion criteria and were included in the qualitative synthesis. All interventions were delivered in part by mobile phone text messaging. Three studies were effective at improving adherence to medication and two studies increased physical activity behaviour. No effects were observed on dietary behaviour or smoking cessation, measured in one study each. Simple text messaging interventions appeared to be most effective; however, no clear relationships were found between study findings and intervention dose, duration or behaviour change techniques targeted. Our review found mHealth has the potential to change lifestyle behaviour. Results are still limited to a small number of trials, inconsistent outcome measures and ineffective reporting of intervention characteristics. Large scale, longitudinal studies are now warranted to gain a clear understanding of the effects of mHealth on behaviour change in the cardiovascular disease population. © The European Society of Cardiology 2015.

The Human Phenotype Ontology in 2017

International Nuclear Information System (INIS)

Köhler, Sebastian; Vasilevsky, Nicole A.; Engelstad, Mark; Foster, Erin; McMurry, Julie

2016-01-01

Deep phenotyping has been defined as the precise and comprehensive analysis of phenotypic abnormalities in which the individual components of the phenotype are observed and described. The three components of the Human PhenotypeOntology (HPO; www.human-phenotype-ontology.org) project are the phenotype vocabulary, disease-phenotype annotations and the algorithms that operate on these. These components are being used for computational deep phenotyping and precision medicine as well as integration of clinical data into translational research. The HPO is being increasingly adopted as a standard for phenotypic abnormalities by diverse groups such as international rare disease organizations, registries, clinical labs, biomedical resources, and clinical software tools and will thereby contribute toward nascent efforts at global data exchange for identifying disease etiologies. This update article reviews the progress of the HPO project since the debut Nucleic Acids Research database article in 2014, including specific areas of expansion such as common (complex) disease, new algorithms for phenotype driven genomic discovery and diagnostics, integration of cross-species mapping efforts with the Mammalian Phenotype Ontology, an improved quality control pipeline, and the addition of patient-friendly terminology.

Engagement in Pleasant Leisure Activities and Blood Pressure: A 5-Year Longitudinal Study in Alzheimer Caregivers.

Science.gov (United States)

Mausbach, Brent T; Romero-Moreno, Rosa; Bos, Taylor; von Känel, Roland; Ziegler, Michael G; Allison, Matthew A; Mills, Paul J; Dimsdale, Joel E; Ancoli-Israel, Sonia; Losada, Andrés; Márquez-González, María; Patterson, Thomas L; Grant, Igor

2017-09-01

Elevated blood pressure is a significant public health concern, particularly given its association with cardiovascular disease risk, including stroke. Caring for a loved one with Alzheimer disease has been associated with physical health morbidity, including higher blood pressure. Engagement in adaptive coping strategies may help prevent blood pressure elevation in this population. This 5-year longitudinal study examined whether greater participation in pleasant leisure activities was associated with reduced blood pressure in caregivers. Participants were 126 in-home spousal Alzheimer's caregivers (M [SD] age = 74.2 [7.9] years) that completed five yearly assessments. Linear mixed-effects models analysis was used to examine the longitudinal relationship between pleasant leisure activities and caregivers' blood pressure, after adjusting for demographic and health characteristics. Greater engagement in pleasant leisure activities was associated with reduced mean arterial blood pressure (B = -0.08, SE = 0.04, p = .040). Follow-up analyses indicated that engagement in activities was significantly associated with reduced diastolic (B = -0.07, SE = 0.03, p = .030) but not systolic blood pressure (B = -0.10, SE = 0.06, p = .114). In addition, mean arterial blood pressure was significantly reduced when caregiving duties ended because of placement of care recipients in nursing homes (B = -3.10, SE = 1.11, p = .005) or death of the care recipient (B = -2.64, SE = 1.14, p = .021). Greater engagement in pleasant leisure activities was associated with lowered caregivers' blood pressure over time. Participation in pleasant leisure activities may have cardiovascular health benefits for Alzheimer's caregivers.

Impaired masturbation-induced erections: a new cardiovascular risk factor for male subjects with sexual dysfunction.

Science.gov (United States)

Rastrelli, Giulia; Boddi, Valentina; Corona, Giovanni; Mannucci, Edoardo; Maggi, Mario

2013-04-01

Erectile dysfunction (ED) is considered an early surrogate marker of silent, or even overt, cardiovascular diseases (CVD). However, epidemiological studies take into account only sexual intercourse-related erections. Although autoeroticism is a very common practice, data on masturbation-induced erections as a possible predictor of major adverse cardiovascular events (MACE) are lacking. To evaluate the clinical correlates of impaired masturbation-induced erections and to verify the importance of this sexual aspect in predicting MACE. A consecutive series of 4,031 male patients attending the Outpatient Clinic for sexual dysfunction for the first time was retrospectively studied. Among these subjects, 64% reported autoeroticism during the last 3 months, and only this subset was considered in the following analyses. In the longitudinal study, 862 subjects reporting autoeroticism were enrolled. Several clinical, biochemical, and instrumental (Prostaglandin E1 [PGE1 ] test and penile color Doppler ultrasound) parameters were studied. Subjects with an impaired erection during masturbation (46% of those reporting autoeroticism) had more often a positive personal or family history of CVD, a higher risk of reduced intercourse- and sleep-related erections, hypoactive sexual desire and perceived reduced ejaculate volume, and impaired PGE1 test response. Prolactin levels were lower in those having impaired erection during masturbation. In the longitudinal study, unadjusted incidence of MACE was significantly associated with impaired masturbation-induced erections. When dividing the population according to the median age and diagnosis of diabetes, the association between impaired masturbation-induced erections and incidence of MACE was maintained only in the youngest (masturbation-induced erections, can provide further insights on forthcoming MACE in particular in "low risk" subjects. © 2013 International Society for Sexual Medicine.

Consequências cardiovasculares na SAOS Cardiovascular consequences of obstructive sleep apnea syndrome

Directory of Open Access Journals (Sweden)

Geraldo Lorenzi Filho

2010-06-01

Full Text Available Uma condição clínica muito comum é SAOS, que está associada a várias doenças cardiovasculares, incluindo hipertensão arterial sistêmica, fibrilação atrial e aterosclerose. A associação entre SAOS e doença cardiovascular não é somente uma consequência da sobreposição de fatores de risco, incluindo obesidade, sedentarismo, ser do sexo masculino e ter idade maior. Existem evidências crescentes de que SAOS contribui de forma independente para o aparecimento e a progressão de várias doenças cardiovasculares. Os mecanismos pelos quais SAOS pode afetar o sistema cardiovascular são múltiplos e incluem a ativação do sistema nervoso simpático, inflamação sistêmica, resistência a insulina e geração de estresse oxidativo. Existem evidências que o tratamento de SAOS com CPAP pode reduzir a pressão arterial, sinais precoces de aterosclerose, risco de recorrência de fibrilação atrial e mortalidade, principalmente por acidente vascular cerebral e infarto agudo do miocárdio, em pacientes com SAOS grave.Obstructive sleep apnea syndrome (OSAS is a common condition associated with various cardiovascular diseases, including systemic arterial hypertension, atrial fibrillation, and atherosclerosis. The association between OSAS and cardiovascular disease has been related to the overlapping of risk factors, including obesity, having a sedentary lifestyle, being male, and being older. However, there is mounting evidence that OSAS can also independently contribute to the development and progression of various cardiovascular diseases. The mechanisms by which OSAS can affect the cardiovascular system are multiple, including the activation of the sympathetic nervous system, systemic inflammation, insulin resistance, and oxidative stress. There is also evidence that the treatment of OSAS with CPAP can reduce arterial blood pressure, early signs of atherosclerosis, the risk of atrial fibrillation recurrence, and mortality (principally

14 CFR 67.111 - Cardiovascular.

Science.gov (United States)

2010-01-01

... 14 Aeronautics and Space 2 2010-01-01 2010-01-01 false Cardiovascular. 67.111 Section 67.111 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) AIRMEN MEDICAL STANDARDS AND CERTIFICATION First-Class Airman Medical Certificate § 67.111 Cardiovascular. Cardiovascular...

14 CFR 67.311 - Cardiovascular.

Science.gov (United States)

2010-01-01

... 14 Aeronautics and Space 2 2010-01-01 2010-01-01 false Cardiovascular. 67.311 Section 67.311 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) AIRMEN MEDICAL STANDARDS AND CERTIFICATION Third-Class Airman Medical Certificate § 67.311 Cardiovascular. Cardiovascular...

14 CFR 67.211 - Cardiovascular.

Science.gov (United States)

2010-01-01

... 14 Aeronautics and Space 2 2010-01-01 2010-01-01 false Cardiovascular. 67.211 Section 67.211 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) AIRMEN MEDICAL STANDARDS AND CERTIFICATION Second-Class Airman Medical Certificate § 67.211 Cardiovascular. Cardiovascular...

Genetic and environmental contributions to cardiovascular disease risk in American Indians: the strong heart family study.

Science.gov (United States)

North, Kari E; Howard, Barbara V; Welty, Thomas K; Best, Lyle G; Lee, Elisa T; Yeh, J L; Fabsitz, Richard R; Roman, Mary J; MacCluer, Jean W

2003-02-15

The aims of the Strong Heart Family Study are to clarify the genetic determinants of cardiovascular disease (CVD) risk in American Indians and to map and identify genes for CVD susceptibility. The authors describe the design of the Strong Heart Family Study (conducted between 1998 and 1999) and evaluate the heritabilities of CVD risk factors in American Indians from this study. In the first phase of the study, approximately 950 individuals, aged 18 years or more, in 32 extended families, were examined. The examination consisted of a personal interview, physical examination, laboratory tests, and an ultrasound examination of the carotid arteries. The phenotypes measured during the physical examination included anthropometry, lipoproteins, blood pressure, glycemic status, and clotting factors. Heritabilities for CVD risk factor phenotypes were estimated using a variance component approach and the program SOLAR. After accounting for the effects of covariates, the authors detected significant heritabilities for many CVD risk factor phenotypes (e.g., high density lipoprotein cholesterol (heritability = 0.50) and diastolic blood pressure (heritability = 0.34)). These results suggest that heredity explains a substantial proportion of the variability of CVD risk factors and that these heritabilities are large enough to warrant a search for major risk factor genes.

GGCX-Associated Phenotypes: An Overview in Search of Genotype-Phenotype Correlations

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Eva Y. G. De Vilder

2017-01-01

Full Text Available Gamma-carboxylation, performed by gamma-glutamyl carboxylase (GGCX, is an enzymatic process essential for activating vitamin K-dependent proteins (VKDP with important functions in various biological processes. Mutations in the encoding GGCX gene are associated with multiple phenotypes, amongst which vitamin K-dependent coagulation factor deficiency (VKCFD1 is best known. Other patients have skin, eye, heart or bone manifestations. As genotype–phenotype correlations were never described, literature was systematically reviewed in search of patients with at least one GGCX mutation with a phenotypic description, resulting in a case series of 47 patients. Though this number was too low for statistically valid correlations—a frequent problem in orphan diseases—we demonstrate the crucial role of the horizontally transferred transmembrane domain in developing cardiac and bone manifestations. Moreover, natural history suggests ageing as the principal determinant to develop skin and eye symptoms. VKCFD1 symptoms seemed more severe in patients with both mutations in the same protein domain, though this could not be linked to a more perturbed coagulation factor function. Finally, distinct GGCX functional domains might be dedicated to carboxylation of very specific VKDP. In conclusion, this systematic review suggests that there indeed may be genotype–phenotype correlations for GGCX-related phenotypes, which can guide patient counseling and management.

Interoperability between phenotype and anatomy ontologies.

Science.gov (United States)

Hoehndorf, Robert; Oellrich, Anika; Rebholz-Schuhmann, Dietrich

2010-12-15

Phenotypic information is important for the analysis of the molecular mechanisms underlying disease. A formal ontological representation of phenotypic information can help to identify, interpret and infer phenotypic traits based on experimental findings. The methods that are currently used to represent data and information about phenotypes fail to make the semantics of the phenotypic trait explicit and do not interoperate with ontologies of anatomy and other domains. Therefore, valuable resources for the analysis of phenotype studies remain unconnected and inaccessible to automated analysis and reasoning. We provide a framework to formalize phenotypic descriptions and make their semantics explicit. Based on this formalization, we provide the means to integrate phenotypic descriptions with ontologies of other domains, in particular anatomy and physiology. We demonstrate how our framework leads to the capability to represent disease phenotypes, perform powerful queries that were not possible before and infer additional knowledge. http://bioonto.de/pmwiki.php/Main/PheneOntology.

Maintained intentional weight loss reduces cardiovascular outcomes: results from the Sibutramine Cardiovascular OUTcomes (SCOUT) trial.

Science.gov (United States)

Caterson, I D; Finer, N; Coutinho, W; Van Gaal, L F; Maggioni, A P; Torp-Pedersen, C; Sharma, A M; Legler, U F; Shepherd, G M; Rode, R A; Perdok, R J; Renz, C L; James, W P T

2012-06-01

The Sibutramine Cardiovascular OUTcomes trial showed that sibutramine produced greater mean weight loss than placebo but increased cardiovascular morbidity but not mortality. The relationship between 12-month weight loss and subsequent cardiovascular outcomes is explored. Overweight/obese subjects (N = 10 744), ≥55 years with cardiovascular disease and/or type 2 diabetes mellitus, received sibutramine plus weight management during a 6-week Lead-in Period before randomization to continue sibutramine (N = 4906) or to receive placebo (N = 4898). The primary endpoint was the time from randomization to first occurrence of a primary outcome event (non-fatal myocardial infarction, non-fatal stroke, resuscitated cardiac arrest or cardiovascular death). For the total population, mean weight change during Lead-in Period (sibutramine) was -2.54 kg. Post-randomization, mean total weight change to Month 12 was -4.18 kg (sibutramine) or -1.87 kg (placebo). Degree of weight loss during Lead-in Period or through Month 12 was associated with a progressive reduction in risk for the total population in primary outcome events and cardiovascular mortality over the 5-year assessment. Although more events occurred in the randomized sibutramine group, on an average, a modest weight loss of approximately 3 kg achieved in the Lead-in Period appeared to offset this increased event rate. Moderate weight loss (3-10 kg) reduced cardiovascular deaths in those with severe, moderate or mild cardiovascular disease. Modest weight loss over short-term (6 weeks) and longer-term (6-12 months) periods is associated with reduction in subsequent cardiovascular mortality for the following 4-5 years even in those with pre-existing cardiovascular disease. While the sibutramine group experienced more primary outcome events than the placebo group, greater weight loss reduced overall risk of these occurring in both groups. © 2011 Blackwell Publishing Ltd.

Protective effect of yerba mate intake on the cardiovascular system: a post hoc analysis study in postmenopausal women.

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da Veiga, D T A; Bringhenti, R; Copes, R; Tatsch, E; Moresco, R N; Comim, F V; Premaor, M O

2018-01-01

The prevalence of cardiovascular and metabolic diseases is increased in postmenopausal women, which contributes to the burden of illnesses in this period of life. Yerba mate (Ilex paraguariensis) is a native bush from Southern South America. Its leaves are rich in phenolic components, which may have antioxidant, vasodilating, hypocholesterolemic, and hypoglycemic proprieties. This post hoc analysis of the case-control study nested in the Obesity and Bone Fracture Cohort evaluated the consumption of yerba mate and the prevalence of hypertension, dyslipidemia, and coronary diseases in postmenopausal women. Ninety-five postmenopausal women were included in this analysis. A questionnaire was applied to evaluate the risk factors and diagnosis of cardiovascular diseases and consumption of yerba mate infusion. Student's t-test and chi-square test were used to assess significant differences between groups. The group that consumed more than 1 L/day of mate infusion had significantly fewer diagnoses of coronary disease, dyslipidemia, and hypertension (P<0.049, P<0.048, and P<0.016, respectively). Furthermore, the serum levels of glucose were lower in the group with a higher consumption of yerba mate infusion (P<0.013). The serum levels of total cholesterol, LDL-cholesterol, HDL-cholesterol, and triglycerides were similar between the groups. This pragmatic study points out the benefits of yerba mate consumption for the cardiovascular and metabolic systems. The ingestion of more than 1 L/day of mate infusion was associated with fewer self-reported cardiovascular diseases and lower serum levels of glucose. Longitudinal studies are needed to evaluate the association between yerba mate infusion and reduction of cardiovascular diseases in postmenopausal women.

Insoluble elastin reduces collagen scaffold stiffness, improves viscoelastic properties, and induces a contractile phenotype in smooth muscle cells.

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Ryan, Alan J; O'Brien, Fergal J

2015-12-01

Biomaterials with the capacity to innately guide cell behaviour while also displaying suitable mechanical properties remain a challenge in tissue engineering. Our approach to this has been to utilise insoluble elastin in combination with collagen as the basis of a biomimetic scaffold for cardiovascular tissue engineering. Elastin was found to markedly alter the mechanical and biological response of these collagen-based scaffolds. Specifically, during extensive mechanical assessment elastin was found to reduce the specific tensile and compressive moduli of the scaffolds in a concentration dependant manner while having minimal effect on scaffold microarchitecture with both scaffold porosity and pore size still within the ideal ranges for tissue engineering applications. However, the viscoelastic properties were significantly improved with elastin addition with a 3.5-fold decrease in induced creep strain, a 6-fold increase in cyclical strain recovery, and with a four-parameter viscoelastic model confirming the ability of elastin to confer resistance to long term deformation/creep. Furthermore, elastin was found to result in the modulation of SMC phenotype towards a contractile state which was determined via reduced proliferation and significantly enhanced expression of early (α-SMA), mid (calponin), and late stage (SM-MHC) contractile proteins. This allows the ability to utilise extracellular matrix proteins alone to modulate SMC phenotype without any exogenous factors added. Taken together, the ability of elastin to alter the mechanical and biological response of collagen scaffolds has led to the development of a biomimetic biomaterial highly suitable for cardiovascular tissue engineering. Copyright © 2015 Elsevier Ltd. All rights reserved.

Cardiovascular diseases

International Nuclear Information System (INIS)

Kodama, Kazunori

1992-01-01

This paper is aimed to discuss the involvement of delayed radiation effects of A-bomb exposure in cardiovascular diseases. First, the relationship between radiation and cardiovascular diseases is reviewed in the literature. Animal experiments have confirmed the relationship between ionizing radiation and vascular lesions. There are many reports which describe ischemic heart disease, cervical and cerebrovascular diseases, and peripheral disease occurring after radiation therapy. The previous A-bomb survivor cohort studies, i.e., the RERF Life Span Study and Adult Health Study, have dealt with the mortality rate from cardiovascular diseases, the prevalence or incidence of cardiovascular diseases, pathological findings, clinical observation of arteriosclerosis, ECG abnormality, blood pressure abnormality, and cardiac function. The following findings have been suggested: (1) A-bomb exposure is likely to be involved in the mortality rate and incidence of ischemic heart disease and cerebrovascular diseases; (2) similarly, the involvement of A-bomb exposure is considered in the prevalence of the arch of aorta; (3) ECG abnormality corresponding to ischemic heart disease may reflect the involvement of A-bomb exposure. To confirm the above findings, further studies are required on the basis of more accurate information and the appropriate number of cohort samples. Little evidence has been presented for the correlation between A-bomb exposure and both rheumatic heart disease and congenital heart disease. (N.K.) 88 refs

Nonfasting hyperlipidemia and cardiovascular disease

DEFF Research Database (Denmark)

Nordestgaard, B G; Langsted, A; Freiberg, J J

2009-01-01

, total cholesterol/HDL cholesterol, and apolipoprotein B/apolipoprotein A1 all associate with increased risk of cardiovascular disease. These new data open the possibility that nonfasting rather than fasting lipid profiles can be used for cardiovascular risk prediction. If implemented, this would...... of cardiovascular disease and early death....

Searching for polycystic ovary syndrome in postmenopausal women: evidence of a dose-effect association with prevalent cardiovascular disease.

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Krentz, Andrew J; von Mühlen, Denise; Barrett-Connor, Elizabeth

2007-01-01

To test the hypothesis that polycystic ovary syndrome (PCOS) is associated with an increased risk of atherosclerotic cardiovascular disease (CVD) in older postmenopausal women. Cross-sectional study of community-dwelling non-estrogen-using postmenopausal-white women (N=713; mean+/-SD age, 73.8+/-7.9 years; mean body mass index, 24.0+/-3.5 kg/m) participating in the Rancho Bernardo Study. A putative PCOS phenotype was defined as the presence of three or more of the following features: (1) recalled history of irregular menses, (2) symptomatic premenopausal hyperandrogenism or biochemical evidence of current biochemical hyperandrogenism, (3) history of infertility or miscarriage, (4) central obesity, or (5) insulin resistance. Atherosclerotic CVD was determined from clinical history, electrocardiography, and structured interviews using validated techniques. The analysis was stratified by diabetes status, ascertained from medical history or 75-g oral glucose tolerance tests. The PCOS phenotype was present in 9.3% of the entire cohort and 5.8% of nondiabetic women. The prevalence of CVD was similar between women with the phenotype and unaffected women (27.3% vs 24.4%). Among women with intact ovaries and no diabetes, there was a stepwise graded association between an increasing number of features of the PCOS phenotype (ie, none to three or more) and prevalent CVD (P=0.02). A similar association was also observed for coronary heart disease alone (P=0.03). Among nondiabetic postmenopausal women with intact ovaries, prevalent atherosclerotic CVD is associated with features of a putative PCOS phenotype. This finding supports the thesis that PCOS increases the risk of atherosclerotic CVD after menopause.

Continuity of Genetic and Environmental Influences on Cognition across the Life Span: A Meta-Analysis of Longitudinal Twin and Adoption Studies

Science.gov (United States)

Tucker-Drob, Elliot M.; Briley, Daniel A.

2014-01-01

The longitudinal rank-order stability of cognitive ability increases dramatically over the lifespan. Multiple theoretical perspectives have proposed that genetic and/or environmental mechanisms underlie the longitudinal stability of cognition, and developmental trends therein. However, the patterns of stability of genetic and environmental influences on cognition over the lifespan largely remain poorly understood. We searched for longitudinal studies of cognition that reported raw genetically-informative longitudinal correlations or parameter estimates from longitudinal behavior genetic models. We identified 150 combinations of time points and measures from 15 independent longitudinal samples. In total, longitudinal data came from 4,538 monozygotic twin pairs raised together, 7,777 dizygotic twin pairs raised together, 34 monozygotic twin pairs raised apart, 78 dizygotic twin pairs raised apart, 141 adoptive sibling pairs, and 143 non-adoptive sibling pairs, ranging in age from infancy through late adulthood. At all ages, cross-time genetic correlations and shared environmental correlations were substantially larger than cross-time nonshared environmental correlations. Cross-time correlations for genetic and shared environmental components were low during early childhood, increased sharply over child development, and remained relatively high from adolescence through late adulthood. Cross-time correlations for nonshared environmental components were low across childhood and increased gradually to moderate magnitudes in adulthood. Increasing phenotypic stability over child development was almost entirely mediated by genetic factors. Time-based decay of genetic and shared environmental stability was more pronounced earlier in child development. Results are interpreted in reference to theories of gene-environment interaction and correlation. PMID:24611582

Can genetic pleiotropy replicate common clinical constellations of cardiovascular disease and risk?

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Omri Gottesman

Full Text Available The relationship between obesity, diabetes, hyperlipidemia, hypertension, kidney disease and cardiovascular disease (CVD is established when looked at from a clinical, epidemiological or pathophysiological perspective. Yet, when viewed from a genetic perspective, there is comparatively little data synthesis that these conditions have an underlying relationship. We sought to investigate the overlap of genetic variants independently associated with each of these commonly co-existing conditions from the NHGRI genome-wide association study (GWAS catalog, in an attempt to replicate the established notion of shared pathophysiology and risk. We used pathway-based analyses to detect subsets of pleiotropic genes involved in similar biological processes. We identified 107 eligible GWAS studies related to CVD and its established comorbidities and risk factors and assigned genes that correspond to the associated signals based on their position. We found 44 positional genes shared across at least two CVD-related phenotypes that independently recreated the established relationship between the six phenotypes, but only if studies representing non-European populations were included. Seven genes revealed pleiotropy across three or more phenotypes, mostly related to lipid transport and metabolism. Yet, many genes had no relationship to each other or to genes with established functional connection. Whilst we successfully reproduced established relationships between CVD risk factors using GWAS findings, interpretation of biological pathways involved in the observed pleiotropy was limited. Further studies linking genetic variation to gene expression, as well as describing novel biological pathways will be needed to take full advantage of GWAS results.

Haptoglobin phenotype, preeclampsia risk and the efficacy of vitamin C and E supplementation to prevent preeclampsia in a racially diverse population.

Directory of Open Access Journals (Sweden)

Tracey L Weissgerber

Full Text Available Haptoglobin's (Hp antioxidant and pro-angiogenic properties differ between the 1-1, 2-1, and 2-2 phenotypes. Hp phenotype affects cardiovascular disease risk and treatment response to antioxidant vitamins in some non-pregnant populations. We previously demonstrated that preeclampsia risk was doubled in white Hp 2-1 women, compared to Hp 1-1 women. Our objectives were to determine whether we could reproduce this finding in a larger cohort, and to determine whether Hp phenotype influences lack of efficacy of antioxidant vitamins in preventing preeclampsia and serious complications of pregnancy-associated hypertension (PAH. This is a secondary analysis of a randomized controlled trial in which 10,154 low-risk women received daily vitamin C and E, or placebo, from 9-16 weeks gestation until delivery. Hp phenotype was determined in the study prediction cohort (n = 2,393 and a case-control cohort (703 cases, 1,406 controls. The primary outcome was severe PAH, or mild or severe PAH with elevated liver enzymes, elevated serum creatinine, thrombocytopenia, eclampsia, fetal growth restriction, medically indicated preterm birth or perinatal death. Preeclampsia was a secondary outcome. Odds ratios were estimated by logistic regression. Sampling weights were used to reduce bias from an overrepresentation of women with preeclampsia or the primary outcome. There was no relationship between Hp phenotype and the primary outcome or preeclampsia in Hispanic, white/other or black women. Vitamin supplementation did not reduce the risk of the primary outcome or preeclampsia in women of any phenotype. Supplementation increased preeclampsia risk (odds ratio 3.30; 95% confidence interval 1.61-6.82, p<0.01 in Hispanic Hp 2-2 women. Hp phenotype does not influence preeclampsia risk, or identify a subset of women who may benefit from vitamin C and E supplementation to prevent preeclampsia.

Sex hormone binding globulin phenotypes

DEFF Research Database (Denmark)

Cornelisse, M M; Bennett, Patrick; Christiansen, M

1994-01-01

Human sex hormone binding globulin (SHBG) is encoded by a normal and a variant allele. The resulting SHBG phenotypes (the homozygous normal SHBG, the heterozygous SHBG and the homozygous variant SHBG phenotype) can be distinguished by their electrophoretic patterns. We developed a novel detection....... This method of detection was used to determine the distribution of SHBG phenotypes in healthy controls of both sexes and in five different pathological conditions characterized by changes in the SHBG level or endocrine disturbances (malignant and benign ovarian neoplasms, hirsutism, liver cirrhosis...... on the experimental values. Differences in SHBG phenotypes do not appear to have any clinical significance and no sex difference was found in the SHBG phenotype distribution....

Hierarchical linear modeling of longitudinal pedigree data for genetic association analysis

DEFF Research Database (Denmark)

Tan, Qihua; B Hjelmborg, Jacob V; Thomassen, Mads

2014-01-01

-effect models to explicitly model the genetic relationship. These have proved to be an efficient way of dealing with sample clustering in pedigree data. Although current algorithms implemented in popular statistical packages are useful for adjusting relatedness in the mixed modeling of genetic effects...... associated with blood pressure with estimated inflation factors of 0.99, suggesting that our modeling of random effects efficiently handles the genetic relatedness in pedigrees. Application to simulated data captures important variants specified in the simulation. Our results show that the method is useful......Genetic association analysis on complex phenotypes under a longitudinal design involving pedigrees encounters the problem of correlation within pedigrees, which could affect statistical assessment of the genetic effects. Approaches have been proposed to integrate kinship correlation into the mixed...

Text-based phenotypic profiles incorporating biochemical phenotypes of inborn errors of metabolism improve phenomics-based diagnosis.

Science.gov (United States)

Lee, Jessica J Y; Gottlieb, Michael M; Lever, Jake; Jones, Steven J M; Blau, Nenad; van Karnebeek, Clara D M; Wasserman, Wyeth W

2018-05-01

Phenomics is the comprehensive study of phenotypes at every level of biology: from metabolites to organisms. With high throughput technologies increasing the scope of biological discoveries, the field of phenomics has been developing rapid and precise methods to collect, catalog, and analyze phenotypes. Such methods have allowed phenotypic data to be widely used in medical applications, from assisting clinical diagnoses to prioritizing genomic diagnoses. To channel the benefits of phenomics into the field of inborn errors of metabolism (IEM), we have recently launched IEMbase, an expert-curated knowledgebase of IEM and their disease-characterizing phenotypes. While our efforts with IEMbase have realized benefits, taking full advantage of phenomics requires a comprehensive curation of IEM phenotypes in core phenomics projects, which is dependent upon contributions from the IEM clinical and research community. Here, we assess the inclusion of IEM biochemical phenotypes in a core phenomics project, the Human Phenotype Ontology. We then demonstrate the utility of biochemical phenotypes using a text-based phenomics method to predict gene-disease relationships, showing that the prediction of IEM genes is significantly better using biochemical rather than clinical profiles. The findings herein provide a motivating goal for the IEM community to expand the computationally accessible descriptions of biochemical phenotypes associated with IEM in phenomics resources.

Research in cardiovascular care

DEFF Research Database (Denmark)

Jaarsma, Tiny; Deaton, Christi; Fitzsimmons, Donna

2014-01-01

with the increasing opportunities and challenges in multidisciplinary research, the Science Committee of the Council on Cardiovascular Nursing and Allied Professionals (CCNAP) recognised the need for a position statement to guide researchers, policymakers and funding bodies to contribute to the advancement...... of the body of knowledge that is needed to further improve cardiovascular care. In this paper, knowledge gaps in current research related to cardiovascular patient care are identified, upcoming challenges are explored and recommendations for future research are given....

Erectile dysfunction in the cardiovascular patient.

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Vlachopoulos, Charalambos; Jackson, Graham; Stefanadis, Christodoulos; Montorsi, Piero

2013-07-01

Erectile dysfunction is common in the patient with cardiovascular disease. It is an important component of the quality of life and it also confers an independent risk for future cardiovascular events. The usual 3-year time period between the onset of erectile dysfunction symptoms and a cardiovascular event offers an opportunity for risk mitigation. Thus, sexual function should be incorporated into cardiovascular disease risk assessment for all men. A comprehensive approach to cardiovascular risk reduction (comprising of both lifestyle changes and pharmacological treatment) improves overall vascular health, including sexual function. Proper sexual counselling improves the quality of life and increases adherence to medication. This review explores the critical connection between erectile dysfunction and cardiovascular disease and evaluates how this relationship may influence clinical practice. Algorithms for the management of patient with erectile dysfunction according to the risk for sexual activity and future cardiovascular events are proposed.

Cohort Study of ECG Left Ventricular Hypertrophy Trajectories: Ethnic Disparities, Associations With Cardiovascular Outcomes, and Clinical Utility.

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Iribarren, Carlos; Round, Alfred D; Lu, Meng; Okin, Peter M; McNulty, Edward J

2017-10-05

ECG left ventricular hypertrophy (LVH) is a well-known predictor of cardiovascular disease. However, no prior study has characterized patterns of presence/absence of ECG LVH ("ECG LVH trajectories") across the adult lifespan in both sexes and across ethnicities. We examined: (1) correlates of ECG LVH trajectories; (2) the association of ECG LVH trajectories with incident coronary heart disease, transient ischemic attack, ischemic stroke, hemorrhagic stroke, and heart failure; and (3) reclassification of cardiovascular disease risk using ECG LVH trajectories. We performed a cohort study among 75 412 men and 107 954 women in the Northern California Kaiser Permanente Medical Care Program who had available longitudinal exposures of ECG LVH and covariates, followed for a median of 4.8 (range ECG LVH was measured by Cornell voltage-duration product. Adverse trajectories of ECG LVH (persistent, new development, or variable pattern) were more common among blacks and Native American men and were independently related to incident cardiovascular disease with hazard ratios ranging from 1.2 for ECG LVH variable pattern and transient ischemic attack in women to 2.8 for persistent ECG LVH and heart failure in men. ECG LVH trajectories reclassified 4% and 7% of men and women with intermediate coronary heart disease risk, respectively. ECG LVH trajectories were significant indicators of coronary heart disease, stroke, and heart failure risk, independently of level and change in cardiovascular disease risk factors, and may have clinical utility. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Cardiovascular Disease and Diabetes

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... Peripheral Artery Disease Venous Thromboembolism Aortic Aneurysm More Cardiovascular Disease & Diabetes Updated:Jan 29,2018 The following ... clear that there is a strong correlation between cardiovascular disease (CVD) and diabetes. At least 68 percent ...

Lipoprotein Profile Modifications during Gestation: A Current Approach to Cardiovascular risk surrogate markers and Maternal-fetal Unit Complications.

Science.gov (United States)

Santos, Ana Paula Caires Dos; Couto, Ricardo David

2018-05-16

Several changes occur in lipid metabolism during gestation due to hormonal and metabolic changes, which are essential to satisfy the nutritional demands of the maternal-fetal unit development. The gestation shows two distinct periods that begin with fat accumulation, mainly in maternal adipose tissue, and the late phase, characterized by accelerated catabolism, with the increase of fatty acids in the circulation that causes hyperlipidemia, especially the one characterized as hypertriglyceridemia. Maternal hyperlipidemia may be associated with the development of maternal-fetal complications (preterm birth, preeclampsia, vascular complications) and the development of long-term cardiovascular disease. The cardiovascular risk may not only be related to lipoproteins cholesterol content, but also to the number and functionality of circulating lipoprotein particles. This review reports the major changes that occur in lipoprotein metabolism during pregnancy and that are associated with the development of dyslipidemias, lipoprotein atherogenic phenotype, and maternal-fetal unit complications. Thieme Revinter Publicações Ltda Rio de Janeiro, Brazil.

Cardiovascular Benefits of Moderate Exercise Training in Marfan Syndrome: Insights From an Animal Model.

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Mas-Stachurska, Aleksandra; Siegert, Anna-Maria; Batlle, Monsterrat; Gorbenko Del Blanco, Darya; Meirelles, Thayna; Rubies, Cira; Bonorino, Fabio; Serra-Peinado, Carla; Bijnens, Bart; Baudin, Julio; Sitges, Marta; Mont, Lluís; Guasch, Eduard; Egea, Gustavo

2017-09-25

Marfan syndrome (MF) leads to aortic root dilatation and a predisposition to aortic dissection, mitral valve prolapse, and primary and secondary cardiomyopathy. Overall, regular physical exercise is recommended for a healthy lifestyle, but dynamic sports are strongly discouraged in MF patients. Nonetheless, evidence supporting this recommendation is lacking. Therefore, we studied the role of long-term dynamic exercise of moderate intensity on the MF cardiovascular phenotype. In a transgenic mouse model of MF ( Fbn1 C1039G/+ ), 4-month-old wild-type and MF mice were subjected to training on a treadmill for 5 months; sedentary littermates served as controls for each group. Aortic and cardiac remodeling was assessed by echocardiography and histology. The 4-month-old MF mice showed aortic root dilatation, elastic lamina rupture, and tunica media fibrosis, as well as cardiac hypertrophy, left ventricular fibrosis, and intramyocardial vessel remodeling. Over the 5-month experimental period, aortic root dilation rate was significantly greater in the sedentary MF group, compared with the wild-type group (∆mm, 0.27±0.07 versus 0.13±0.02, respectively). Exercise significantly blunted the aortic root dilation rate in MF mice compared with sedentary MF littermates (∆mm, 0.10±0.04 versus 0.27±0.07, respectively). However, these 2 groups were indistinguishable by aortic root stiffness, tunica media fibrosis, and elastic lamina ruptures. In MF mice, exercise also produced cardiac hypertrophy regression without changes in left ventricular fibrosis. Our results in a transgenic mouse model of MF indicate that moderate dynamic exercise mitigates the progression of the MF cardiovascular phenotype. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Oral health and cardiovascular care: Perceptions of people with cardiovascular disease

Science.gov (United States)

Salamonson, Yenna; Ajwani, Shilpi; Bhole, Sameer; Bishop, Joshua; Lintern, Karen; Nolan, Samantha; Rajaratnam, Rohan; Redfern, Julie; Sheehan, Maria; Skarligos, Fiona; Spencer, Lissa; Srinivas, Ravi

2017-01-01

Main objective The aim of this study was to explore the perception of patients with cardiovascular disease towards oral health and the potential for cardiac care clinicians to promote oral health. Method A needs assessment was undertaken with twelve patients with cardiovascular disease attending cardiac rehabilitation between 2015 and 2016, in three metropolitan hospitals in Sydney, Australia. These patients participated in face-to-face semi-structured interviews. Data was analysed using thematic analysis. Results Results suggested that while oral health was considered relevant there was high prevalence of poor oral health among participants, especially those from socioeconomic disadvantaged background. Awareness regarding the importance of oral health care its impact on cardiovascular outcomes was poor among participants. Oral health issues were rarely discussed in the cardiac setting. Main barriers deterring participants from seeking oral health care included lack of awareness, high cost of dental care and difficulties in accessing the public dental service. Findings also revealed that participants were interested in receiving further information about oral health and suggested various mediums for information delivery. The concept of cardiac care clinicians, especially nurses providing education, assessment and referrals to ongoing dental care was well received by participants who felt the post-acute period was the most appropriate time to receive oral health care advice. The issues of oral health training for non-dental clinicians and how to address existing barriers were highlighted by participants. Relevance to clinical practice The lack of oral health education being provided to patients with cardiovascular disease offers an opportunity to improve care and potentially, outcomes. In view of the evidence linking poor oral health with cardiovascular disease, cardiac care clinicians, especially nurses, should be appropriately trained to promote oral health in

Oral health and cardiovascular care: Perceptions of people with cardiovascular disease.

Directory of Open Access Journals (Sweden)

Paula Sanchez

Full Text Available The aim of this study was to explore the perception of patients with cardiovascular disease towards oral health and the potential for cardiac care clinicians to promote oral health.A needs assessment was undertaken with twelve patients with cardiovascular disease attending cardiac rehabilitation between 2015 and 2016, in three metropolitan hospitals in Sydney, Australia. These patients participated in face-to-face semi-structured interviews. Data was analysed using thematic analysis.Results suggested that while oral health was considered relevant there was high prevalence of poor oral health among participants, especially those from socioeconomic disadvantaged background. Awareness regarding the importance of oral health care its impact on cardiovascular outcomes was poor among participants. Oral health issues were rarely discussed in the cardiac setting. Main barriers deterring participants from seeking oral health care included lack of awareness, high cost of dental care and difficulties in accessing the public dental service. Findings also revealed that participants were interested in receiving further information about oral health and suggested various mediums for information delivery. The concept of cardiac care clinicians, especially nurses providing education, assessment and referrals to ongoing dental care was well received by participants who felt the post-acute period was the most appropriate time to receive oral health care advice. The issues of oral health training for non-dental clinicians and how to address existing barriers were highlighted by participants.The lack of oral health education being provided to patients with cardiovascular disease offers an opportunity to improve care and potentially, outcomes. In view of the evidence linking poor oral health with cardiovascular disease, cardiac care clinicians, especially nurses, should be appropriately trained to promote oral health in their practice. Affordable and accessible

Educational inequality in cardiovascular diseases

DEFF Research Database (Denmark)

Søndergaard, Grethe; Dalton, Susanne Oksbjerg; Mortensen, Laust Hvas

2018-01-01

AIMS: Educational inequality in diseases in the circulatory system (here termed cardiovascular disease) is well documented but may be confounded by early life factors. The aim of this observational study was to examine whether the associations between education and all cardiovascular diseases...... educational status was associated with a higher risk of cardiovascular disease, ischaemic heart disease and stroke. All associations attenuated in the within-sibship analyses, in particular in the analyses on ischaemic heart disease before age 45 years. For instance, in the cohort analyses, the hazard rate...... factors shared by siblings explained the associations between education and the cardiovascular disease outcomes but to varying degrees. This should be taken into account when planning interventions aimed at reducing educational inequalities in the development of cardiovascular disease, ischaemic heart...

A Longitudinal Follow-up of Autoimmune Polyendocrine Syndrome Type 1

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Bruserud, Øyvind; Oftedal, Bergithe E.; Landegren, Nils; Erichsen, Martina M.; Bratland, Eirik; Lima, Kari; Jørgensen, Anders P.; Myhre, Anne G.; Svartberg, Johan; Fougner, Kristian J.; Bakke, Åsne; Nedrebø, Bjørn G.; Mella, Bjarne; Breivik, Lars; Viken, Marte K.; Knappskog, Per M.; Marthinussen, Mihaela C.; Løvås, Kristian; Kämpe, Olle; Wolff, Anette B.

2016-01-01

Context: Autoimmune polyendocrine syndrome type 1 (APS1) is a childhood-onset monogenic disease defined by the presence of two of the three major components: hypoparathyroidism, primary adrenocortical insufficiency, and chronic mucocutaneous candidiasis (CMC). Information on longitudinal follow-up of APS1 is sparse. Objective: To describe the phenotypes of APS1 and correlate the clinical features with autoantibody profiles and autoimmune regulator (AIRE) mutations during extended follow-up (1996–2016). Patients: All known Norwegian patients with APS1. Results: Fifty-two patients from 34 families were identified. The majority presented with one of the major disease components during childhood. Enamel hypoplasia, hypoparathyroidism, and CMC were the most frequent components. With age, most patients presented three to five disease manifestations, although some had milder phenotypes diagnosed in adulthood. Fifteen of the patients died during follow-up (median age at death, 34 years) or were deceased siblings with a high probability of undisclosed APS1. All except three had interferon-ω) autoantibodies, and all had organ-specific autoantibodies. The most common AIRE mutation was c.967_979del13, found in homozygosity in 15 patients. A mild phenotype was associated with the splice mutation c.879+1G>A. Primary adrenocortical insufficiency and type 1 diabetes were associated with protective human leucocyte antigen genotypes. Conclusions: Multiple presumable autoimmune manifestations, in particular hypoparathyroidism, CMC, and enamel hypoplasia, should prompt further diagnostic workup using autoantibody analyses (eg, interferon-ω) and AIRE sequencing to reveal APS1, even in adults. Treatment is complicated, and mortality is high. Structured follow-up should be performed in a specialized center. PMID:27253668

Environmental Factors and Cardiovascular Diseases

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Omer Faruk Tekbas

2008-10-01

Full Text Available Epidemiological and clinical observations have led to the hypothesis that the risk of developing cardiovascular diseases is influenced not only by genetic, lifestyle and major risk factors, but also by environmental factors. Environmental factors are considered key determinants of cardiovascular diseases. Although lifestyle choices such as smoking, diet, and exercise are viewed as major environmental influences, the contribution of pollutants and environmental chemicals is less clear. Accumulating evidence suggests that exposure to physically and chemical pollutants could elevate the risk of cardiovascular diseases. Many epidemiological studies report that exposure to physically, biologically and socio-cultural environmental factors are associated with an increase in cardiovascular mortality. Relationships between environmental factors and coronary arter disease, arhythmias, and cardiomyopathies have been reported. Exposures to arsenic, lead, cadmium, pollutant gases, solvents, and pesticides have also been linked to increased incidence of cardiovascular disease. In this paper, I review that relationships between exposure to physically, chemical, biologically and socio-cultural environmental factors and cardiovascular diseases. [TAF Prev Med Bull 2008; 7(5.000: 435-444

APOE Genotyping, Cardiovascular Disease

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... Resources For Health Professionals Subscribe Search APOE Genotyping, Cardiovascular Disease Send Us Your Feedback Choose Topic At a ... help understand the role of genetic factors in cardiovascular disease . However, the testing is sometimes used in clinical ...

Distinct phenotype, longitudinal changes of numbers and cell-associated virus in blood dendritic cells in SIV-infected CD8-lymphocyte depleted macaques.

Directory of Open Access Journals (Sweden)

Caroline Soulas

Full Text Available Loss of circulating CD123+ plasmacytoid dendritic cells (pDCs during HIV infection is well established. However, changes of myeloid DCs (mDCs are ambiguous since they are studied as a homogeneous CD11c+ population despite phenotypic and functional heterogeneity. Heterogeneity of CD11c+ mDCs in primates is poorly described in HIV and SIV infection. Using multiparametric flow cytometry, we monitored longitudinally cell number and cell-associated virus of CD123+ pDCs and non-overlapping subsets of CD1c+ and CD16+ mDCs in SIV-infected CD8-depleted rhesus macaques. The numbers of all three DC subsets were significantly decreased by 8 days post-infection. Whereas CD123+ pDCs were persistently depleted, numbers of CD1c+ and CD16+ mDCs rebounded. Numbers of CD1c+ mDCs significantly increased by 3 weeks post-infection while numbers of CD16+ mDCs remained closer to pre-infection levels. We found similar changes in the numbers of all three DC subsets in CD8 depleted animals as we found in animals that were SIV infected animals that were not CD8 lymphocyte depleted. CD16+ mDCs and CD123+ pDCs but not CD1c+ mDCs were significantly decreased terminally with AIDS. All DC subsets harbored SIV RNA as early as 8 days and then throughout infection. However, SIV DNA was only detected in CD123+ pDCs and only at 40 days post-infection consistent with SIV RNA, at least in mDCs, being surface-bound. Altogether our data demonstrate that SIV infection differently affects CD1c+ and CD16+ mDCs where CD16+ but not CD1c+ mDCs are depleted and might be differentially regulated in terminal AIDS. Finally, our data underline the importance of studying CD1c+ and CD16+ mDCs as discrete populations, and not as total CD11c+ mDCs.

Cardiovascular and Metabolic Heterogeneity of Obesity: Clinical Challenges and Implications for Management.

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Neeland, Ian J; Poirier, Paul; Després, Jean-Pierre

2018-03-27

The prevalence of obesity has increased globally over the last 2 decades. Although the body mass index has been a convenient and simple index of obesity at the population level, studies have shown that obesity defined by body mass index alone is a remarkably heterogeneous condition with varying cardiovascular and metabolic manifestations across individuals. Adipose tissue is an exquisitely active metabolic organ engaged in cross-talk between various systems; perturbation of adipose tissue results in a pathological response to positive caloric balance in susceptible individuals that directly and indirectly contributes to cardiovascular and metabolic disease. Inadequate subcutaneous adipose tissue expansion in the face of dietary triglycerides leads to visceral and ectopic fat deposition, inflammatory/adipokine dysregulation, and insulin resistance. Conversely, preferential fat storage in the lower body depot may act as a metabolic buffer and protect other tissues from lipotoxicity caused by lipid overflow and ectopic fat. Translational, epidemiological, and clinical studies over the past 30 years have clearly demonstrated a strong link between visceral and ectopic fat and the development of a clinical syndrome characterized by atherogenic dyslipidemia, hyperinsulinemia/glucose intolerance, hypertension, atherosclerosis, and adverse cardiac remodeling/heart failure. This relationship is even more nuanced when clinical entities such as metabolically healthy obesity phenotype and the obesity paradox are considered. Although it is clear that the accumulation of visceral/ectopic fat is a major contributor to cardiovascular and metabolic risk above and beyond the body mass index, implementation of fat distribution assessment into clinical practice remains a challenge. Anthropometric indexes of obesity are easily implemented, but newer imaging-based methods offer improved sensitivity and specificity for measuring specific depots. Lifestyle, pharmacological, and surgical

Multifactorial Prevention of Cardiovascular Disease in Patients with Hypertension : the Cardiovascular Polypill

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Lafeber, M; Spiering, W; Visseren, F L J; Grobbee, D E

2016-01-01

Hypertension is a major, if not the most important, contributor to the disease burden and premature death globally which is largely related to cardiovascular disease. In both the primary and the secondary preventions of cardiovascular disease, blood pressure (BP) targets are often not achieved which

Molecular and phenotypic biomarkers of aging [version 1; referees: 3 approved

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Xian Xia

2017-06-01

Full Text Available Individuals of the same age may not age at the same rate. Quantitative biomarkers of aging are valuable tools to measure physiological age, assess the extent of ‘healthy aging’, and potentially predict health span and life span for an individual. Given the complex nature of the aging process, the biomarkers of aging are multilayered and multifaceted. Here, we review the phenotypic and molecular biomarkers of aging. Identifying and using biomarkers of aging to improve human health, prevent age-associated diseases, and extend healthy life span are now facilitated by the fast-growing capacity of multilevel cross-sectional and longitudinal data acquisition, storage, and analysis, particularly for data related to general human populations. Combined with artificial intelligence and machine learning techniques, reliable panels of biomarkers of aging will have tremendous potential to improve human health in aging societies.

A “Forward Genomics” Approach Links Genotype to Phenotype using Independent Phenotypic Losses among Related Species

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Michael Hiller

2012-10-01

Full Text Available Genotype-phenotype mapping is hampered by countless genomic changes between species. We introduce a computational “forward genomics” strategy that—given only an independently lost phenotype and whole genomes—matches genomic and phenotypic loss patterns to associate specific genomic regions with this phenotype. We conducted genome-wide screens for two metabolic phenotypes. First, our approach correctly matches the inactivated Gulo gene exactly with the species that lost the ability to synthesize vitamin C. Second, we attribute naturally low biliary phospholipid levels in guinea pigs and horses to the inactivated phospholipid transporter Abcb4. Human ABCB4 mutations also result in low phospholipid levels but lead to severe liver disease, suggesting compensatory mechanisms in guinea pig and horse. Our simulation studies, counts of independent changes in existing phenotype surveys, and the forthcoming availability of many new genomes all suggest that forward genomics can be applied to many phenotypes, including those relevant for human evolution and disease.

Characterization of changes in serum anti-glycan antibodies in Crohn's disease--a longitudinal analysis.

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Florian Rieder

Full Text Available INTRODUCTION: Anti-glycan antibodies are a promising tool for differential diagnosis and disease stratification of patients with Crohn's disease (CD. We longitudinally assessed level and status changes of anti-glycan antibodies over time in individual CD patients as well as determinants of this phenomenon. METHODS: 859 serum samples derived from a cohort of 253 inflammatory bowel disease (IBD patients (207 CD, 46 ulcerative colitis (UC were tested for the presence of anti-laminarin (Anti-L, anti-chitin (Anti-C, anti-chitobioside (ACCA, anti-laminaribioside (ALCA, anti-mannobioside (AMCA and anti-Saccharomyces cerevisiae (gASCA antibodies by ELISA. All patients had at least two and up to eleven serum samples taken during the disease course. RESULTS: Median follow-up time for CD was 17.4 months (Interquartile range (IQR 8.0, 31.6 months and for UC 10.9 months (IQR 4.9, 21.0 months. In a subgroup of CD subjects marked changes in the overall immune response (quartile sum score and levels of individual markers were observed over time. The marker status (positive versus negative remained widely stable. Neither clinical phenotype nor NOD2 genotype was associated with the observed fluctuations. In a longitudinal analysis neither changes in disease activity nor CD behavior led to alterations in the levels of the glycan markers. The ability of the panel to discriminate CD from UC or its association with CD phenotypes remained stable during follow-up. In the serum of UC patients neither significant level nor status changes were observed. CONCLUSIONS: While the levels of anti-glycan antibodies fluctuate in a subgroup of CD patients the antibody status is widely stable over time.

The Association of Baseline and Longitudinal Change in Endothelial Microparticle Count with Mortality in Chronic Kidney Disease.

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Green, Darren; Skeoch, Sarah; Alexander, M Yvonne; Kalra, Philip A; Parker, Ben

2017-01-01

Chronic kidney disease (CKD) is associated with a unique milieu of vascular pathology, and effective biomarkers of active vascular damage are lacking. A candidate biomarker is the quantification of circulating endothelial microparticles (EMPs). This study observed baseline and longitudinal EMP change (δEMP) and established the association of these with all-cause mortality and cardiovascular events in CKD. An observational study in adults with CKD (estimated glomerular filtration rate [eGFR] change was not. This may reflect disease-specific EMP behaviour and the limitation of EMP as a generalised biomarker in CKD. © 2017 S. Karger AG, Basel.

Clinical phenotype-based gene prioritization: an initial study using semantic similarity and the human phenotype ontology.

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Masino, Aaron J; Dechene, Elizabeth T; Dulik, Matthew C; Wilkens, Alisha; Spinner, Nancy B; Krantz, Ian D; Pennington, Jeffrey W; Robinson, Peter N; White, Peter S

2014-07-21

Exome sequencing is a promising method for diagnosing patients with a complex phenotype. However, variant interpretation relative to patient phenotype can be challenging in some scenarios, particularly clinical assessment of rare complex phenotypes. Each patient's sequence reveals many possibly damaging variants that must be individually assessed to establish clear association with patient phenotype. To assist interpretation, we implemented an algorithm that ranks a given set of genes relative to patient phenotype. The algorithm orders genes by the semantic similarity computed between phenotypic descriptors associated with each gene and those describing the patient. Phenotypic descriptor terms are taken from the Human Phenotype Ontology (HPO) and semantic similarity is derived from each term's information content. Model validation was performed via simulation and with clinical data. We simulated 33 Mendelian diseases with 100 patients per disease. We modeled clinical conditions by adding noise and imprecision, i.e. phenotypic terms unrelated to the disease and terms less specific than the actual disease terms. We ranked the causative gene against all 2488 HPO annotated genes. The median causative gene rank was 1 for the optimal and noise cases, 12 for the imprecision case, and 60 for the imprecision with noise case. Additionally, we examined a clinical cohort of subjects with hearing impairment. The disease gene median rank was 22. However, when also considering the patient's exome data and filtering non-exomic and common variants, the median rank improved to 3. Semantic similarity can rank a causative gene highly within a gene list relative to patient phenotype characteristics, provided that imprecision is mitigated. The clinical case results suggest that phenotype rank combined with variant analysis provides significant improvement over the individual approaches. We expect that this combined prioritization approach may increase accuracy and decrease effort for

Women's cardiovascular health in India.

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Chow, Clara K; Patel, Anushka A

2012-03-01

Cardiovascular diseases (CVDs) are the leading cause of death among adult women in many parts of India and a major cause of morbidity. In some parts of the world, gender inequities have been observed in cardiovascular healthcare and cardiovascular outcomes. The authors discuss the data for potential disparities in cardiovascular healthcare for women in India. Data on cardiovascular healthcare provision and CVD outcomes among women in India are generally lacking. The little available data suggest that women in rural areas, younger women and girl children with CVD are less likely to receive appropriate management than men, with this disparity most apparent in those of lower socioeconomic status and education. However, there is a particular lack of information about the prevention and management of atherosclerotic heart disease in women from a range of communities that comprise the extremely diverse population of India.

Latent Cognitive Phenotypes in De Novo Parkinson's Disease: A Person-Centered Approach.

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LaBelle, Denise R; Walsh, Ryan R; Banks, Sarah J

2017-08-01

Cognitive impairment is an important aspect of Parkinson's disease (PD), but there is considerable heterogeneity in its presentation. This investigation aims to identify and characterize latent cognitive phenotypes in early PD. Latent class analysis, a data-driven, person-centered, cluster analysis was performed on cognitive data from the Parkinson's Progressive Markers Initiative baseline visit. This analytic method facilitates identification of naturally occurring endophenotypes. Resulting classes were compared across biomarker, symptom, and demographic data. Six cognitive phenotypes were identified. Three demonstrated consistent performance across indicators, representing poor ("Weak-Overall"), average ("Typical-Overall"), and strong ("Strong-Overall") cognition. The remaining classes demonstrated unique patterns of cognition, characterized by "Strong-Memory," "Weak-Visuospatial," and "Amnestic" profiles. The Amnestic class evidenced greater tremor severity and anosmia, but was unassociated with biomarkers linked with Alzheimer's disease. The Weak-Overall class was older and reported more non-motor features associated with cognitive decline, including anxiety, depression, autonomic dysfunction, anosmia, and REM sleep behaviors. The Strong-Overall class was younger, more female, and reported less dysautonomia and anosmia. Classes were unrelated to disease duration, functional independence, or available biomarkers. Latent cognitive phenotypes with focal patterns of impairment were observed in recently diagnosed individuals with PD. Cognitive profiles were found to be independent of traditional biomarkers and motoric indices of disease progression. Only globally impaired class was associated with previously reported indicators of cognitive decline, suggesting this group may drive the effects reported in studies using variable-based analysis. Longitudinal and neuroanatomical characterization of classes will yield further insight into the evolution of cognitive

Crowdfunding for cardiovascular research.

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Krittanawong, Chayakrit; Zhang, HongJu Janet; Aydar, Mehmet; Wang, Zhen; Sun, Tao

2018-01-01

The competition for public cardiovascular research grants has recently increased. Independent researchers are facing increasing competition for public research grant support and ultimately may need to seek alternative funding sources. Crowdfunding, a financing method of raising funds online by pooling together small donations from the online community to support a specific initiative, seems to have significant potential. However, the feasibility of crowdfunding for cardiovascular research remains unknown. Here, we performed exploratory data analysis of the feasibility of online crowdfunding in cardiovascular research. Copyright © 2017 Elsevier B.V. All rights reserved.

Envejecimiento del sistema cardiovascular Cardiovascular system aging

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José M Ocampo

2005-08-01

Full Text Available El envejecimiento del sistema cardiovascular está asociado con un número característico de cambios a nivel bioquímico, histológico y morfológico. Sin embargo, no todas las modificaciones presentadas se asocian con deterioro en la función. Entre los cambios a nivel cardiaco se tienen: disminución en el número de miocitos y en las células del sistema de conducción cardiaca, desarrollo de fibrosis, cambios en el transporte de calcio a través de las membranas y disminución del cronotropismo, inotropismo y lusitropismo mediados por estímulo b-adrenérgico. A nivel vascular, hay incremento en la rigidez de la pared de las arterias, con aumento en la velocidad de la onda de pulso, disfunción endotelial y disminución de la vasodilatación mediada por estímulo b-adrenérgico. Durante el reposo el sistema cardiovascular es capaz de desarrollar mecanismos adaptativos eficientes, pero en situaciones de estrés como el ejercicio, los cambios asociados con el envejecimiento se hacen evidentes ya que está disminuida la capacidad para obtener la frecuencia cardiaca máxima, está incrementada la postcarga y hay disminución de la contractilidad intrínseca. Por lo anterior, los ancianos deben utilizar al máximo el mecanismo de Frank-Starling para mantener el gasto cardiaco. Los cambios estructurales y funcionales asociados con el envejecimiento cardiovascular, disminuyen de forma significativa el umbral en el cual las enfermedades cardiacas llegan a ser evidentes, y deben ser conocidos por el personal de salud encargado de cuidar a los ancianos.Cardiovascular aging is associated with characteristic biochemical, histological and morphological changes. Nevertheless, these changes are not necessarily associated to a deterioration in its function. Among the cardiac changes found, there is a reduction in the number of myocytes and of the cardiac conduction system cells, development of fibrosis, changes in the trans-membrane calcium transport and a

Cardiac dysfunction in Pkd1-deficient mice with phenotype rescue by galectin-3 knockout

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Balbo, Bruno E.; Amaral, Andressa G.; Fonseca, Jonathan M.; de Castro, Isac; Salemi, Vera M.; Souza, Leandro E.; dos Santos, Fernando; Irigoyen, Maria C.; Qian, Feng; Chammas, Roger; Onuchic, Luiz F.

2016-01-01

Alterations in myocardial wall texture stand out among ADPKD cardiovascular manifestations, in hypertensive and normotensive patients. To elucidate their pathogenesis, we analyzed the cardiac phenotype in Pkd1cond/cond:Nestincre (CYG+) cystic mice exposed to increased blood pressure, at 5–6 and 20–24 weeks of age, and Pkd1+/− (HTG+) noncystic mice at 5–6 and 10–13 weeks. Echocardiographic analyses revealed decreased myocardial deformation and systolic function in CYG+ and HTG+ mice, as well as diastolic dysfunction in older CYG+ mice, compared to their Pkd1cond/cond and Pkd1+/+ controls. Hearts from CYG+ and HTG+ mice presented reduced polycystin-1 expression, increased apoptosis and mild fibrosis. Since galectin-3 has been associated with heart dysfunction, we studied it as a potential modifier of the ADPKD cardiac phenotype. Double-mutant Pkd1cond/cond:Nestincre;Lgals3−/− (CYG−) and Pkd1+/−;Lgals3−/− (HTG−) mice displayed improved cardiac deformability and systolic parameters compared to single-mutants, not differing from their controls. CYG− and HTG− showed decreased apoptosis and fibrosis. Analysis of a severe cystic model (Pkd1V/V; VVG+) showed that Pkd1V/V;Lgals3−/− (VVG−) mice have longer survival, decreased cardiac apoptosis and improved heart function compared to VVG+. CYG− and VVG− animals showed no difference in renal cystic burden compared to CYG+ and VVG+ mice. Thus, myocardial dysfunction occurs in different Pkd1-deficient models and suppression of galectin-3 expression rescues this phenotype. PMID:27475230

Doença cardiovascular e fatores de risco cardiovascular em candidatos a transplante renal Cardiovascular disease and risk factors in candidates for renal transplantation

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Luís Henrique Wolff Gowdak

2005-02-01

Full Text Available OBJETIVO: Determinar a prevalência de doença cardiovascular (DCV e de fatores de risco tradicionais em portadores de insuficiência renal crônica em avaliação para inclusão em lista para transplante renal. MÉTODOS: Foram submetidos à avaliação clínica e exames complementares 195 pacientes com insuficiência renal crônica dialítica e comparados a grupo de 334 hipertensos pareados por idade. As equações de Framingham foram usadas para o cálculo do risco absoluto (RA; o risco relativo (RR foi calculado tendo como referência o risco absoluto da coorte de baixo risco de Framingham. RESULTADOS: Do total, 37% apresentaram algum tipo de doença cardiovascular na avaliação inicial, sendo que arteriopatia obstrutiva (23% foi a mais prevalente. Excluídos os pacientes com doença cardiovascular, em relação aos fatores de risco tradicionais, houve diferença significativa quanto à pressão arterial sistólica e colesterol total (maiores no grupo de hipertensos e às prevalências de homens, diabetes e tabagismo, maiores no grupo de insuficiência renal crônica, que apresentou maior grau de hipertrofia ventricular esquerda, menor pressão arterial diastólica e menor prevalência de história familiar de doença cardiovascular e obesidade. O risco relativo para doença cardiovascular dos pacientes com insuficiência renal crônica foi mais elevado em relação à população controle de Framingham porém não diferiu da observada no grupo de hipertensos. CONCLUSÃO: Em candidatos a transplante renal é significativa a prevalência de doença cardiovascular e de fatores de risco tradicionais; as equações de Framingham não quantificam adequadamente o risco cardiovascular real e outros fatores de risco específicos desta população devem contribuir para o maior risco cardiovascular.OBJECTIVE: To determine the prevalence of cardiovascular disease (CVD and traditional risk factors in patients with chronic renal failure undergoing

Mechanistic phenotypes: an aggregative phenotyping strategy to identify disease mechanisms using GWAS data.

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Jonathan D Mosley

Full Text Available A single mutation can alter cellular and global homeostatic mechanisms and give rise to multiple clinical diseases. We hypothesized that these disease mechanisms could be identified using low minor allele frequency (MAF<0.1 non-synonymous SNPs (nsSNPs associated with "mechanistic phenotypes", comprised of collections of related diagnoses. We studied two mechanistic phenotypes: (1 thrombosis, evaluated in a population of 1,655 African Americans; and (2 four groupings of cancer diagnoses, evaluated in 3,009 white European Americans. We tested associations between nsSNPs represented on GWAS platforms and mechanistic phenotypes ascertained from electronic medical records (EMRs, and sought enrichment in functional ontologies across the top-ranked associations. We used a two-step analytic approach whereby nsSNPs were first sorted by the strength of their association with a phenotype. We tested associations using two reverse genetic models and standard additive and recessive models. In the second step, we employed a hypothesis-free ontological enrichment analysis using the sorted nsSNPs to identify functional mechanisms underlying the diagnoses comprising the mechanistic phenotypes. The thrombosis phenotype was solely associated with ontologies related to blood coagulation (Fisher's p = 0.0001, FDR p = 0.03, driven by the F5, P2RY12 and F2RL2 genes. For the cancer phenotypes, the reverse genetics models were enriched in DNA repair functions (p = 2×10-5, FDR p = 0.03 (POLG/FANCI, SLX4/FANCP, XRCC1, BRCA1, FANCA, CHD1L while the additive model showed enrichment related to chromatid segregation (p = 4×10-6, FDR p = 0.005 (KIF25, PINX1. We were able to replicate nsSNP associations for POLG/FANCI, BRCA1, FANCA and CHD1L in independent data sets. Mechanism-oriented phenotyping using collections of EMR-derived diagnoses can elucidate fundamental disease mechanisms.

Lifestyle in Cardiovascular Disease

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J.O. Younge (John)

2015-01-01

markdownabstract__Abstract__ Globally, the burden of cardiovascular disease (CVD) is still increasing. However, in recent decades, better treatment modalities have led to less cardiovascular related deaths. After years of research, we now generally accept that lifestyle factors are the most

A FBN1 mutation association with different phenotypes of Marfan syndrome in a Chinese family.

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Li, Yapeng; Xu, Jianhua; Chen, Mingjie; Du, Binbin; Li, Qiaoli; Xing, Qinghe; Zhang, Yanzhou

2016-09-01

Previous studies demonstrated that patients with different FBN1 mutations often present more considerable phenotypic variation compared to different members of the related family carrying a same mutation. The purpose of our study was to identify pathogenic mutation and provide more information about genotype-phenotypic correlations in a large Chinese family with Marfan syndrome. 15 related family members from a Chinese 4-generation pedigree with Marfan syndrome underwent physical, ophthalmologic, radiological and cardiovascular examinations. The propositus has De Bakey III aortic dissection and didn't fulfill the revised Ghent criteria for Marfan syndrome. Nine family members have ectopia lentis and their echocardiogram was normal. Five other family members have no evidence of Marfan syndrome. Genomic DNA was isolated from blood leukocytes. The exome sequencing was employed on the propositus, then the Sanger sequencing was conducted for mutation verification in other 14 participants of this family. The causative mutation in FBN1 discovered in the propositus was a known heterozygous missense mutation, c.1633T>G (p.R545C), in exon 14 (NM 000138). This same mutation was also identified in all 9 ectopia lentis patients and one unaffected 8-year-old girl. However, the same mutation was not discovered in other 4 unaffected family members. Our data enhance the information of genotype-phenotype correlation owing to FBN1 mutations. To our current knowledge, we firstly reported that the same FBN1 mutation, c. 1633C>T (Arg545Cys), was detected simultaneously in three different cardinal phenotypes (ectopia lentis, aortic dissection and unaffected) within one family. The unaffected girl with FBN1 mutation may presumably represent a rare case of nonpenetrance. Copyright © 2016 Elsevier B.V. All rights reserved.

Prevalence and metabolic characteristics of adrenal androgen excess in hyperandrogenic women with different phenotypes.

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Carmina, E; Lobo, R A

2007-02-01

Serum DHEAS has been found to be elevated in some women with polycystic ovary syndrome (PCOS). We wished to determine whether this prevalence is different in women with androgen excess who have different phenotypes and to correlate these findings with various cardiovascular and metabolic parameters. Two hundred and thirty-eight young hyperandrogenic women categorized into various diagnostic groups were evaluated for elevations in serum DHEAS, testosterone, glucose, insulin, quantitative insulin-sensitivity check index (QUICKI), cholesterol, HDL-C, LDL-C, triglycerides and C-reactive protein (CRP). Data were stratified based on elevations in DHEAS. Serum DHEAS was elevated in 39.5% for the entire group [36.7% in PCOS and 48.3% in idiopathic hyperandrogenism (IHA)]. In classic (C)-PCOS, the prevalence was 39.6% and in ovulatory (OV) PCOS it was 29.1%. These differences were not statistically significant. Women with elevated DHEAS had higher testosterone but lower insulin, higher QUICKI, lower total and LDL-cholesterol and higher HDL-cholesterol, pPCOS. The prevalence of adrenal hyperandrogenism, as determined by elevations in DHEAS, appears to be statistically similar in IHA, C-PCOS and compared to OV-PCOS. Metabolic and cardiovascular parameters were noted to be more favorable in those women who have higher DHEAS levels.

Left ventricular long axis function assessed during cine-cardiovascular magnetic resonance is an independent predictor of adverse cardiac events.

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Rangarajan, Vibhav; Chacko, Satish Jacob; Romano, Simone; Jue, Jennifer; Jariwala, Nikhil; Chung, Jaehoon; Farzaneh-Far, Afshin

2016-06-07

Left ventricular pump function requires a complex interplay involving myocardial fibers orientated in the longitudinal, oblique and circumferential directions. Long axis dysfunction appears to be an early marker for a number of pathological states. We hypothesized that mitral annular plane systolic excursion (MAPSE) measured during cine-cardiovascular magnetic resonance (CMR) reflects changes in long axis function and may be an early marker for adverse cardiovascular outcomes. The aims of this study were therefore: 1) To assess the feasibility and reproducibility of MAPSE measurements during routine cine-CMR; and 2) To assess whether MAPSE, as a surrogate for long axis function, is a predictor of major adverse cardiovascular events (MACE). Four hundred consecutive patients undergoing CMR were prospectively enrolled. MAPSE was measured in the 4-chamber cine view. Patients were prospectively followed for major adverse cardiac events (MACE) - death, non-fatal myocardial infarction, hospitalization for heart failure or unstable angina, and late revascularization. Cox proportional hazards regression modeling was used to identify factors independently associated with MACE. Net reclassification improvement (NRI) was calculated to assess whether addition of MAPSE resulted in improved risk reclassification of MACE. Seventy-two MACE occurred during a median follow-up of 14.5 months. By Kaplan-Meier analysis, patients with lateral MAPSE cine-CMR is an independent predictor of MACE.

Cardiovascular Reactivity, Stress, and Physical Activity

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Chun-Jung eHuang

2013-11-01

Full Text Available Psychological stress has been proposed as a major contributor to the progression of cardiovascular disease (CVD. Acute mental stress can activate the sympathetic-adrenal-medullary (SAM axis, eliciting the release of catecholamines (NE and EPI resulting in the elevation of heart rate (HR and blood pressure (BP. Combined stress (psychological and physical can exacerbate these cardiovascular responses, which may partially contribute to the elevated risk of CVD and increased proportionate mortality risks experienced by some occupations (e.g., firefighting and law enforcement. Studies have supported the benefits of physical activity on physiological and psychological health, including the cardiovascular response to acute stress. Aerobically trained individuals exhibit lower sympathetic nervous system (e.g., HR reactivity and enhanced cardiovascular efficiency (e.g., lower vascular reactivity and decreased recovery time in response to physical and/or psychological stress. In addition, resistance training has been demonstrated to attenuate cardiovascular responses and improve mental health. This review will examine stress-induced cardiovascular reactivity and plausible explanations for how exercise training and physical fitness (aerobic and resistance exercise can attenuate cardiovascular responses to stress. This enhanced functionality may facilitate a reduction in the incidence of stroke and myocardial infarction. Finally, this review will also address the interaction of obesity and physical activity on cardiovascular reactivity and CVD.

Precision Medicine in Cardiovascular Diseases

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Yan Liu

2017-02-01

Full Text Available Since President Obama announced the Precision Medicine Initiative in the United States, more and more attention has been paid to precision medicine. However, clinicians have already used it to treat conditions such as cancer. Many cardiovascular diseases have a familial presentation, and genetic variants are associated with the prevention, diagnosis, and treatment of cardiovascular diseases, which are the basis for providing precise care to patients with cardiovascular diseases. Large-scale cohorts and multiomics are critical components of precision medicine. Here we summarize the application of precision medicine to cardiovascular diseases based on cohort and omic studies, and hope to elicit discussion about future health care.

A longitudinal twin study on IQ, executive functioning, and attention problems during childhood and early adolescence.

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Polderman, Tinca J C; Gosso, M Florencia; Posthuma, Danielle; Van Beijsterveldt, Toos C E M; Heutink, Peter; Verhulst, Frank C; Boomsma, Dorret I

2006-12-01

Variation in human behavior may be caused by differences in genotype and by non-genetic differences ("environment") between individuals. The relative contributions of genotype (G) and environment (E) to phenotypic variation can be assessed with the classical twin design. We illustrate this approach with longitudinal data collected in 5 and 12-year-old Dutch twins. At age 5 data on cognitive abilities as assessed with a standard intelligence test (IQ), working memory, selective and sustained attention, and attention problems were collected in 237 twin pairs. Seven years later, 172 twin pairs participated again when they were 12 years old and underwent a similar protocol. Results showed that variation in all phenotypes was influenced by genetic factors. For IQ the heritability estimates increased from 30% at age 5, to 80% at age 12. For executive functioning performance genetic factors accounted for around 50% of the variance at both ages. Attention problems showed high heritabilities (above 60%) at both ages, for maternal and teacher ratings. Longitudinal analyses revealed that executive functioning during childhood was weakly correlated with IQ scores at age 12. Attention problems during childhood, as rated by the mother and the teacher were stronger predictors (r = -0.28 and -0.36, respectively). This association could be attributed to a partly overlapping set of genes influencing attention problems at age 5 and IQ at age 12. IQ performance at age 5 was the best predictor of IQ at age 12. IQ at both ages was influenced by the same genes, whose influence was amplified during development.

Association Between Leisure Time Physical Activity, Cardiopulmonary Fitness, Cardiovascular Risk Factors, and Cardiovascular Workload at Work in Firefighters.

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Yu, Clare C W; Au, Chun T; Lee, Frank Y F; So, Raymond C H; Wong, John P S; Mak, Gary Y K; Chien, Eric P; McManus, Alison M

2015-09-01

Overweight, obesity, and cardiovascular disease risk factors are prevalent among firefighters in some developed countries. It is unclear whether physical activity and cardiopulmonary fitness reduce cardiovascular disease risk and the cardiovascular workload at work in firefighters. The present study investigated the relationship between leisure-time physical activity, cardiopulmonary fitness, cardiovascular disease risk factors, and cardiovascular workload at work in firefighters in Hong Kong. Male firefighters (n = 387) were randomly selected from serving firefighters in Hong Kong (n = 5,370) for the assessment of cardiovascular disease risk factors (obesity, hypertension, diabetes mellitus, dyslipidemia, smoking, known cardiovascular diseases). One-third (Target Group) were randomly selected for the assessment of off-duty leisure-time physical activity using the short version of the International Physical Activity Questionnaire. Maximal oxygen uptake was assessed, as well as cardiovascular workload using heart rate monitoring for each firefighter for four "normal" 24-hour working shifts and during real-situation simulated scenarios. Overall, 33.9% of the firefighters had at least two cardiovascular disease risk factors. In the Target Group, firefighters who had higher leisure-time physical activity had a lower resting heart rate and a lower average working heart rate, and spent a smaller proportion of time working at a moderate-intensity cardiovascular workload. Firefighters who had moderate aerobic fitness and high leisure-time physical activity had a lower peak working heart rate during the mountain rescue scenario compared with firefighters who had low leisure-time physical activities. Leisure-time physical activity conferred significant benefits during job tasks of moderate cardiovascular workload in firefighters in Hong Kong.

Symptoms of anxiety and depression are related to cardiovascular responses to active, but not passive, coping tasks.

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Yuenyongchaiwat, Kornanong; Baker, Ian S; Sheffield, David

2017-01-01

Anxiety and depression have been linked to blunted blood pressure (BP) and heart rate (HR) reactions to mental stress tests; however, most studies have not included indices of underlying hemodynamics nor multiple stress tasks. This study sought to examine the relationships of anxiety and depression with hemodynamic responses to acute active and passive coping tasks. A total of 104 participants completed the Hospital Anxiety and Depression Scales and mental arithmetic, speech, and cold pressor tasks while BP, HR, total peripheral resistance, and cardiac output (CO) were assessed. After adjustment for traditional risk factors and baseline cardiovascular activity, depression scores were negatively associated with systolic BP, HR, and CO responses to the mental arithmetic task, while anxiety scores were inversely related to the systolic BP response to mental arithmetic. High anxiety or depression scores appear to be associated with blunted cardiac reactions to mental arithmetic (an active coping task), but not to the cold pressor test or speech tasks. Future research should further examine potential mechanisms and longitudinal pathways relating depression and anxiety to cardiovascular reactivity. TCTR20160208004.

Exploring Longitudinal Risk-return Relationships

DEFF Research Database (Denmark)

Andersen, Torben J.; Bettis, Richard A.

2015-01-01

We study a longitudinal fit model of adaptation and its association with the longitudinal risk-return relationship. The model allows the firm to adjust its position in response to partial learning about a changing environment characterized by two path-dependent processes—a random walk and a stoch......We study a longitudinal fit model of adaptation and its association with the longitudinal risk-return relationship. The model allows the firm to adjust its position in response to partial learning about a changing environment characterized by two path-dependent processes—a random walk...... can lead to the inverse longitudinal risk-return relationships observed empirically. We discuss this apparent paradox and the possible resolution between mindless and conscious behavior as plausible causes of the longitudinal Bowman Paradox....

Influenza vaccines for preventing cardiovascular disease.

Science.gov (United States)

Clar, Christine; Oseni, Zainab; Flowers, Nadine; Keshtkar-Jahromi, Maryam; Rees, Karen

2015-05-05

This is an update of the original review published in 2008. The risk of adverse cardiovascular outcomes is increased with influenza-like infection, and vaccination against influenza may improve cardiovascular outcomes. To assess the potential benefits of influenza vaccination for primary and secondary prevention of cardiovascular disease. We searched the following electronic databases on 18 October 2013: The Cochrane Library (including Cochrane Central Register of Controlled Trials (CENTRAL), Database of Abstracts of Reviews of Effects (DARE), Economic Evaluation Database (EED) and Health Technology Assessment database (HTA)), MEDLINE, EMBASE, Science Citation Index Expanded, Conference Proceedings Citation Index - Science and ongoing trials registers (www.controlled-trials.com/ and www.clinicaltrials.gov). We examined reference lists of relevant primary studies and systematic reviews. We performed a limited PubMed search on 20 February 2015, just before publication. Randomised controlled trials (RCTs) of influenza vaccination compared with placebo or no treatment in participants with or without cardiovascular disease, assessing cardiovascular death or non-fatal cardiovascular events. We used standard methodological procedures as expected by The Cochrane Collaboration. We carried out meta-analyses only for cardiovascular death, as other outcomes were reported too infrequently. We expressed effect sizes as risk ratios (RRs), and we used random-effects models. We included eight trials of influenza vaccination compared with placebo or no vaccination, with 12,029 participants receiving at least one vaccination or control treatment. We included six new studies (n = 11,251), in addition to the two included in the previous version of the review. Four of these trials (n = 10,347) focused on prevention of influenza in the general or elderly population and reported cardiovascular outcomes among their safety analyses; four trials (n = 1682) focused on prevention of

Galectin-2 induces a proinflammatory, anti-arteriogenic phenotype in monocytes and macrophages.

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Cansu Yıldırım

Full Text Available Galectin-2 is a monocyte-expressed carbohydrate-binding lectin, for which increased expression is genetically determined and associated with decreased collateral arteriogenesis in obstructive coronary artery disease patients. The inhibiting effect of galectin-2 on arteriogenesis was confirmed in vivo, but the mechanism is largely unknown. In this study we aimed to explore the effects of galectin-2 on monocyte/macrophage phenotype in vitro and vivo, and to identify the receptor by which galectin-2 exerts these effects. We now show that the binding of galectin-2 to different circulating human monocyte subsets is dependent on monocyte surface expression levels of CD14. The high affinity binding is blocked by an anti-CD14 antibody but not by carbohydrates, indicating a specific protein-protein interaction. Galectin-2 binding to human monocytes modulated their transcriptome by inducing proinflammatory cytokines and inhibiting pro-arteriogenic factors, while attenuating monocyte migration. Using specific knock-out mice, we show that galectin-2 acts through the CD14/toll-like receptor (TLR-4 pathway. Furthermore, galectin-2 skews human macrophages to a M1-like proinflammatory phenotype, characterized by a reduced motility and expression of an anti-arteriogenic cytokine/growth factor repertoire. This is accompanied by a switch in surface protein expression to CD40-high and CD206-low (M1. In a murine model we show that galectin-2 administration, known to attenuate arteriogenesis, leads to increased numbers of CD40-positive (M1 and reduced numbers of CD206-positive (M2 macrophages surrounding actively remodeling collateral arteries. In conclusion galectin-2 is the first endogenous CD14/TLR4 ligand that induces a proinflammatory, non-arteriogenic phenotype in monocytes/macrophages. Interference with CD14-Galectin-2 interaction may provide a new intervention strategy to stimulate growth of collateral arteries in genetically compromised cardiovascular

Thoracic and Cardiovascular Surgeons’ Perception of the Concentration of Cardiovascular Operations in Seoul Metropolitan Area’s Hospitals

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Hyo Seon Jeong

2016-12-01

Full Text Available Background: The purpose of this study is to evaluate the concentration of cardiovascular surgical procedures in a metropolitan area and investigate the perception of specialists regarding governmental policies to resolve this imbalance. Methods: From March to May 2015, surveys were distributed to members of the Thoracic and Cardiovascular Surgery Association. The final pool of research subjects consisted of 75 respondents. Subjects were queried regarding the concentration of cardiovascular operations in metropolitan areas, alternatives to the imbalance, and governmental policies to resolve the inequalities. Results: Survey participants responded that South Korea needs governmental policies to alleviate the concentration of cardiovascular surgery patients in large metropolitan hospitals. Participants agreed that the freedom to choose medical institutions and improved accessibility to metropolitan hospitals due to advanced transportation systems were some of the causes for the concentration. A majority (98.7% of respondents thought establishing thoracic and cardiovascular surgery centers in provinces was an appropriate solution to alleviate the concentration. Thoracic and cardiovascular surgery specialists were ranked as the number one group on which to focus development. Conclusion: Developing and carrying out policies to establish thoracic and cardiovascular surgery centers in provinces will alleviate the regional imbalance in available heart surgery services and an overall improvement in cardiovascular disease treatment in South Korea.

Cardiovascular involvement in myositis

DEFF Research Database (Denmark)

Diederichsen, Louise P

2017-01-01

PURPOSE OF REVIEW: The purpose of this review is to provide an update on cardiovascular involvement in idiopathic inflammatory myopathy (IIM). Studies from the past 18 months are identified and reviewed. Finally, the clinical impact of these findings is discussed. RECENT FINDINGS: Epidemiological...... on cardiac magnetic resonance (CMR) imaging suggests that CMR should be considered as a potentially viable diagnostic tool to evaluate the possibility of silent myocardial inflammation in IIM with normal routine noninvasive evaluation. SUMMARY: Updated literature on cardiovascular involvement in IIM has...... identified an increased risk for subclinical and clinical cardiovascular disease in these rare inflammatory muscle diseases....

Cardiovascular complications of cirrhosis

DEFF Research Database (Denmark)

Møller, S; Henriksen, Jens Henrik Sahl

2008-01-01

Cardiovascular complications of cirrhosis include cardiac dysfunction and abnormalities in the central, splanchnic and peripheral circulation, and haemodynamic changes caused by humoral and nervous dysregulation. Cirrhotic cardiomyopathy implies systolic and diastolic dysfunction and electrophysi......Cardiovascular complications of cirrhosis include cardiac dysfunction and abnormalities in the central, splanchnic and peripheral circulation, and haemodynamic changes caused by humoral and nervous dysregulation. Cirrhotic cardiomyopathy implies systolic and diastolic dysfunction....... The clinical significance of cardiovascular complications and cirrhotic cardiomyopathy is an important topic for future research, and the initiation of new randomised studies of potential treatments for these complications is needed....

Longitudinal predictors of health-related quality of life in middle-aged and older adults with hypertension: results of a population-based study.

Science.gov (United States)

Maatouk, Imad; Wild, Beate; Herzog, Wolfgang; Wesche, Daniela; Schellberg, Dieter; Schöttker, Ben; Müller, Heiko; Rothenbacher, Dietrich; Stegmaier, Christa; Brenner, Hermann

2012-07-01

The aim of the study was to assess the longitudinal association between cardiovascular risk factors including albuminuria and other variables (e.g. awareness of hypertension, number of types of antihypertensive drugs, comorbidity), and health-related quality of life (HRQOL) in a large cohort of patients with hypertension, over a follow-up period of 5 years. Nine thousand nine hundred and fifty-three participants of the ESTHER (Epidemiologische Studie zu Chancen der Verhütung, Früherkennung und optimierten Therapie chronischer Erkrankungen) study - a population-based cohort study of middle-aged and older adults aged 50-74 years at baseline - were recruited by general practitioners (GPs) in 2000-2002 and included in the follow-up (2005-2007). HRQOL at baseline and follow-up was measured using the Short-Form General Health Survey (SF-12). Mental component scores (MCS) and physical component scores (PCS) were calculated. Multiple linear regression models were used to determine longitudinal predictors of HRQOL at follow-up. Four thousand, two hundred and three patients with hypertension (98.2%) responded to the SF-12 both at baseline and after 5 years and were therefore included in the study. Smoking status, BMI, diabetes, macroalbuminuria, comorbid diseases, history of depression, and lower HRQOL at baseline predicted lower PCS at the 5-year follow-up. Lower MCS after 5 years was predicted by smoking status, dyslipidaemia, a reported history of depression, and HRQOL at baseline. No significant association was detected between awareness of hypertension and any HRQOL component score after 5 years. Macroalbuminuria and other variables related to increased cardiovascular risk have a negative impact on PCS. Suggestions of a link of treatment and awareness of hypertension with HRQOL from previous cross-sectional studies are not supported by our longitudinal findings.

Chronic Obstructive Pulmonary Disease Biomarkers

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Tatsiana Beiko

2016-04-01

Full Text Available Despite significant decreases in morbidity and mortality of cardiovascular diseases (CVD and cancers, morbidity and cost associated with chronic obstructive pulmonary disease (COPD continue to be increasing. Failure to improve disease outcomes has been related to the paucity of interventions improving survival. Insidious onset and slow progression halter research successes in developing disease-modifying therapies. In part, the difficulty in finding new therapies is because of the extreme heterogeneity within recognized COPD phenotypes. Novel biomarkers are necessary to help understand the natural history and pathogenesis of the different COPD subtypes. A more accurate phenotyping and the ability to assess the therapeutic response to new interventions and pharmaceutical agents may improve the statistical power of longitudinal clinical studies. In this study, we will review known candidate biomarkers for COPD, proposed pathways of pathogenesis, and future directions in the field.

LITTLE FISH, BIG DATA: ZEBRAFISH AS A MODEL FOR CARDIOVASCULAR AND METABOLIC DISEASE.

Science.gov (United States)

Gut, Philipp; Reischauer, Sven; Stainier, Didier Y R; Arnaout, Rima

2017-07-01

The burden of cardiovascular and metabolic diseases worldwide is staggering. The emergence of systems approaches in biology promises new therapies, faster and cheaper diagnostics, and personalized medicine. However, a profound understanding of pathogenic mechanisms at the cellular and molecular levels remains a fundamental requirement for discovery and therapeutics. Animal models of human disease are cornerstones of drug discovery as they allow identification of novel pharmacological targets by linking gene function with pathogenesis. The zebrafish model has been used for decades to study development and pathophysiology. More than ever, the specific strengths of the zebrafish model make it a prime partner in an age of discovery transformed by big-data approaches to genomics and disease. Zebrafish share a largely conserved physiology and anatomy with mammals. They allow a wide range of genetic manipulations, including the latest genome engineering approaches. They can be bred and studied with remarkable speed, enabling a range of large-scale phenotypic screens. Finally, zebrafish demonstrate an impressive regenerative capacity scientists hope to unlock in humans. Here, we provide a comprehensive guide on applications of zebrafish to investigate cardiovascular and metabolic diseases. We delineate advantages and limitations of zebrafish models of human disease and summarize their most significant contributions to understanding disease progression to date. Copyright © 2017 the American Physiological Society.

Clinical phenotypes of asthma

NARCIS (Netherlands)

Bel, Elisabeth H.

2004-01-01

PURPOSE OF REVIEW: Asthma is a phenotypically heterogeneous disorder and, over the years, many different clinical subtypes of asthma have been described. A precise definition of asthma phenotypes is now becoming more and more important, not only for a better understanding of pathophysiologic

Factores de riesgo cardiovasculares e hiperreactividad cardiovascular en jóvenes venezolanos

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Sady Montes Amador

2015-07-01

Full Text Available Fundamento: la hiperreactividad cardiovascular en los jóvenes se ha asociado a diferentes factores de riesgo y a la historia familiar de hipertensión arterial. Objetivo: determinar la asociación entre la historia familiar de hipertensión y los factores de riesgo cardiovasculares, con el estado de hiperreactividad cardiovascular. Método: se realizó un estudio descriptivo, correlacional y de corte transversal con un universo de 77 jóvenes entre 18 y 40 años, de la parroquia Churuguara, Estado Falcón en Venezuela. Se analizaron como variables: edad, sexo, color de la piel, antecedentes familiares de hipertensión arterial, antecedentes personales de hipertensión arterial y de diabetes mellitus, ingestión de bebidas alcohólicas y de sal, actividad física e índice de masa corporal. Se determinaron como variables hemodinámicas: presión arterial diastólica, presión arterial sistólica, antes y después de la respuesta presora desencadenada por la aplicación un ejercicio isométrico Resultados: el 13 % de los individuos presentó reactividad vascular ante la prueba del peso sostenido. Es tres veces mayor la hiperreactividad cardiovascular en las personas con historia familiar de hipertensión arterial, el 60 % de las personas con un índice de masa corporal mayor o igual a 27 kg/m2 son hiperreactivos cardiovasculares, en la medida que se ingiere más alcohol aumenta la respuesta cardiovascular a la prueba del peso sostenido, son hiperreactivos el 33,3 % de los que fuman. Conclusión: existe una asociación significativa entre la historia familiar de hipertensión arterial, la obesidad, la ingestión de sal, el consumo de bebidas alcohólicas y la hiperreactividad vascular.

The Current Landscape of Genetic Testing in Cardiovascular Malformations: Opportunities and Challenges

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Benjamin John Landis

2016-07-01

Full Text Available Human cardiovascular malformations (CVMs frequently have a genetic contribution. Through the application of novel technologies such as next generation sequencing, DNA sequence variants associated with CVMs are being identified at a rapid pace. While clinicians are now able to offer testing with next generation sequencing gene panels or whole exome sequencing to any patient with a CVM, the interpretation of genetic variation remains problematic. Variable phenotypic expression, reduced penetrance, inconsistent phenotyping methods, and the lack of high throughput functional testing of variants, contribute to these challenges. This article elaborates critical issues that impact the decision to broadly implement clinical molecular genetic testing in CVMs. Major benefits of testing include establishing a genetic diagnosis, facilitating cost-effective screening of family members who may have subclinical disease, predicting recurrence risk in offspring, enabling early diagnosis and anticipatory management of CV and non-CV disease phenotypes, predicting long term outcomes, and facilitating the development of novel therapies aimed at disease improvement or prevention. Limitations include financial cost, psychosocial cost, and ambiguity of interpretation of results. Multiplex families and patients with syndromic features are two groups where disease causation could potentially be firmly established. However, these account for the minority of the overall CVM population, and there is increasing recognition that genotypes previously associated with syndromes also exist in patients who lack non-CV findings. In all circumstances, ongoing dialogue between cardiologists and clinical geneticists will be needed to accurately interpret genetic testing and improve these patients’ health. This may be most effectively implemented by the creation and support of CV genetics services at centers committed to pursuing testing for patients.

Stability in symptoms of anxiety and depression as a function of genotype and environment: a longitudinal twin study from ages 3 to 63 years.

Science.gov (United States)

Nivard, M G; Dolan, C V; Kendler, K S; Kan, K J; Willemsen, G; van Beijsterveldt, C E M; Lindauer, R J L; van Beek, J H D A; Geels, L M; Bartels, M; Middeldorp, C M; Boomsma, D I

2015-04-01

The influence of genetic factors on major depressive disorder is lower than on other psychiatric disorders. Heritability estimates mainly derive from cross-sectional studies, and knowledge on the longitudinal aetiology of symptoms of anxiety and depression (SxAnxDep) across the lifespan is limited. We aimed to assess phenotypic, genetic and environmental stability in SxAnxDep between ages 3 and 63 years. We used a cohort-sequential design combining data from 49 524 twins followed from birth to age ⩾20 years, and from adolescence into adulthood. SxAnxDep were assessed repeatedly with a maximum of eight assessments over a 25-year period. Data were ordered in 30 age groups and analysed with longitudinal genetic models. Over age, there was a significant increase during adolescence in mean scores with sex differences (women>men) emerging. Heritability was high in childhood and decreased to 30-40% during adulthood. This decrease in heritability was due to an increase in environmental variance. Phenotypic stability was moderate in children (correlations across ages ~0.5) and high in adolescents (r = 0.6), young adults (r = 0.7), and adults (r = 0.8). Longitudinal stability was mostly attributable to genetic factors. During childhood and adolescence there was also significant genetic innovation, which was absent in adults. Environmental effects contributed to short-term stability. The substantial stability in SxAnxDep is mainly due to genetic effects. The importance of environmental effects increases with age and explains the relatively low heritability of depression in adults. The environmental effects are transient, but the contribution to stability increases with age.

Retinal photography: A window into the cardiovascular-brain link in adolescent bipolar disorder.

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Naiberg, Melanie R; Hatch, Jessica K; Selkirk, Beth; Fiksenbaum, Lisa; Yang, Victor; Black, Sandra; Kertes, Peter J; Goldstein, Benjamin I

2017-08-15

The burden of cardiovascular disease in bipolar disorder (BD) exceeds what can be explained by traditional cardiovascular risk factors (CVRFs), lifestyle, and/or medications. Moreover, neurocognitive deficits are a core feature of BD, and are also related to CVRFs. We examined retinal vascular photography, a proxy for cerebral microvasculature, in relation to CVRFs, peripheral microvascular function, and neurocognition among BD adolescents. Subjects were 30 adolescents with BD and 32 healthy controls (HC). Retinal photography was conducted using a Topcon TRC 50 DX, Type IA camera, following pupil dilation. Retinal arteriolar and venular caliber was measured, from which the arterio-venular ratio (AVR) was computed. All measures were conducted masked to participant diagnosis. Peripheral arterial tonometry measured endothelial function. Neurocognition was assessed using the Cambridge Neuropsychological Tests Automated Battery. AVR was not significantly different between groups (Cohen's d=0.18, p=0.103). Higher diastolic blood pressure (BP) was associated with lower (worse) AVR in BD (r=-0.441, p=0.015) but not HC (r=-0.192, p=0.293). Similarly, in the BD group only, higher (better) endothelial function was associated with higher AVR (r=0.375, p=0.041). Hierarchical regression models confirmed that, independent of covariates, retinal vascular caliber was significantly associated with diastolic BP and endothelial function in BD. Within the BD group, mood scores were significantly negatively correlated with AVR (β=-0.451, p=0.044). This study's limitations include a small sample size, a cross-sectional study design, and a heterogeneous sample. Retinal photography may offer unique insights regarding the cardiovascular and neurocognitive burden of BD. Larger longitudinal studies are warranted. Copyright © 2017. Published by Elsevier B.V.

The relationship between migraine and lipid sub-fractions among individuals without cardiovascular disease: A cross-sectional evaluation in the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil).

Science.gov (United States)

Goulart, Alessandra C; Lotufo, Paulo A; Santos, Itamar S; Bittencourt, Márcio S; Santos, Raul D; Blaha, Michael J; Jones, Steven; Toth, Peter P; Kulkarni, Krishnaji; Benseñor, Isabela M

2018-03-01

Introduction Recent studies have explored the relationship between dyslipidemia and migraine in a cardiovascular context. Thus, we aimed to evaluate the possible association between lipids, lipoprotein subfractions and migraine according to aura symptoms in the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil). Methods 1,560 women and 1,595 men, without CVD or lipid disorders requiring medication, underwent a baseline clinical assessment. Total-cholesterol and its sub-fractions (LDL, VLDL and HDL subclass cholesterol); triglycerides and triglyceride-rich lipoprotein cholesterol [TRL-C (VLDL 1+2 -C VLDL 3 -C + IDL-C)] were determined by vertical auto profile (VAP). We also calculated logarithmic LDL density ratio [LLDR = ln ((LDL 3 -C + LDL 4 -C)/(LDL 1 -C + LDL 2 -C))], T-Chol/HDL-C and triglycerides/HDL-C ratios. Odds ratios (OR) with 95% confidence intervals (CI) were obtained to evaluate the relationship between lipids tertiles and migraine for both sexes. Results Main findings revealed positive associations between migraine without aura (MO) and the highest tertiles of VLDL-C (OR, 1.61; 95%CI, 1.07-2.40) and TRL-C (OR, 1.55; 95% CI, 1.03-2.34) in women. In men, the highest tertile of VLDL 3 -C (OR, 3.87; 95%CI, 1.23-12.19) was positively associated with MO, as well. Conclusions In middle-aged participants without CVD or lipid disorders requiring medication, the worst lipid profile was determined by the highest levels of TRL-C and their cholesterol-rich remnants in migraineurs without aura for both sexes.

Longitudinal changes in visceral and subcutaneous adipose tissue and metabolic syndrome: Results from the Multicultural Community Health Assessment Trial (M-CHAT).

Science.gov (United States)

Tu, Andrew W; Humphries, Karin H; Lear, Scott A

2017-12-01

Few studies have examined whether longitudinal changes in visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT), independent of each other, are associated with the risk of developing metabolic syndrome (MetS). The objective of this study was to examine the longitudinal effects of VAT and SAT on MetS and metabolic risk factors in a multi-ethnic sample of Canadians followed for 5-years. In total, 598 adults of the Multicultural Community Health Assessment Trial (M-CHAT) were included in this study. Assessments of body composition using computed tomography (CT) and metabolic risk factors were conducted at baseline, 3-, and 5-years. Mixed-effects logistic regression was used to model the longitudinal effects of VAT and SAT on MetS and metabolic risk factors. There were significant between-person (cross-sectional) effects such that for every 10cm 2 higher VAT, the odds of MetS, high-risk fasting glucose levels and high-risk HDL-C levels significantly increased by 16% (95% CI: 9-24%), 11% (3-20%), and 7% (0-14%) respectively. Significant within-person (longitudinal) effects were also found such that for every 10cm 2 increase in VAT the odds of MetS and high-risk triglyceride levels significantly increased by 23% (9-39%) and 30% (14-48%), respectively. Cross-sectional or longitudinal changes in SAT were not associated with MetS or metabolic risk factors. This study found a direct relationship between longitudinal change in VAT and MetS risk independent of changes in SAT. Clinical practice should focus on the reduction of VAT to improve cardiovascular health outcomes. Copyright © 2017 Diabetes India. Published by Elsevier Ltd. All rights reserved.

Cardiovascular nuclear medicine and MRI

International Nuclear Information System (INIS)

Reiber, J.H.C.; Wall, E.E. van der

1992-01-01

This book is based on a meeting of the Working Group on Nuclear Cardiology, which held March 22-23,1991 under the auspices of the European Society of Cardiology and the Interuniversity Cardiology Institute of the Netherlands, and on the Second International Symposium on Computer Applications in Nuclear Medicine and Cardiac Magnetic Resonance Imaging, which was held March 20-22,1991 in Rotterdam, the Netherlands. It covers almost every aspect of quantitative cardio-vascular nuclear medicine and magnetic resonance imaging. The main topics are: single photon emission computed tomography (technical aspects); new development in cardiovascular nuclear medicine; advances in cardiovascular imaging; cardiovascular clinical applications; and cardiac magnetic resonance imaging. (A.S.). refs.; figs.; tabs

CYP2D6 phenotypes are associated with adverse outcomes related to opioid medications

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St Sauver JL

2017-07-01

Full Text Available Jennifer L St Sauver,1,2 Janet E Olson,1,3 Veronique L Roger,1,2,4 Wayne T Nicholson,5 John L Black III,3,6 Paul Y Takahashi,7 Pedro J Caraballo,7 Elizabeth J Bell,2 Debra J Jacobson,1,2 Nicholas B Larson,1 Suzette J Bielinski,1,3 1Department of Health Sciences Research, 2Kern Center for the Science of Health Care Delivery, Mayo Clinic, Rochester, 3Center for Individualized Medicine, 4Department of Cardiovascular Diseases, 5Department of Anesthesiology and Perioperative Medicine, 6Department of Laboratory Medicine and Pathology, 7Department of Primary Care Internal Medicine, Mayo Clinic, Rochester, MN, USA Background: Variation in the CYP2D6 gene may affect response to opioids in both poor and ultrarapid metabolizers, but data demonstrating such associations have been mixed, and the impact of variants on toxicity-related symptoms (e.g., nausea is unclear. Therefore, we examined the association between CYP2D6 phenotype and poor pain control or other adverse symptoms related to the use of opioids in a sample of primary care patients.Materials and methods: We identified all patients in the Mayo Clinic RIGHT Protocol who were prescribed an opioid medication between July 01, 2013 and June 30, 2015, and categorized patients into three phenotypes: poor, intermediate to extensive, or ultrarapid CYP2D6 metabolizers. We reviewed the electronic health record of these patients for indications of poor pain control or adverse symptoms related to medication use. Associations between phenotype and outcomes were assessed using Chi-square tests and logistic regression.Results: Overall, 257 (25% of RIGHT Protocol participants patients received at least one opioid prescription; of these, 40 (15% were poor metabolizers, 146 (57% were intermediate to extensive metabolizers, and 71 (28% were ultrarapid metabolizers. We removed patients that were prescribed a CYP2D6 inhibitor medication (n=38. After adjusting for age and sex, patients with a poor or ultrarapid

Cardiovascular investigations of airline pilots with excessive cardiovascular risk.

Science.gov (United States)

Wirawan, I Made Ady; Aldington, Sarah; Griffiths, Robin F; Ellis, Chris J; Larsen, Peter D

2013-06-01

This study examined the prevalence of airline pilots who have an excessive cardiovascular disease (CVD) risk score according to the New Zealand Guideline Group (NZGG) Framingham-based Risk Chart and describes their cardiovascular risk assessment and investigations. A cross-sectional study was performed among 856 pilots employed in an Oceania based airline. Pilots with elevated CVD risk that had been previously evaluated at various times over the previous 19 yr were reviewed retrospectively from the airline's medical records, and the subsequent cardiovascular investigations were then described. There were 30 (3.5%) pilots who were found to have 5-yr CVD risk score of 10-15% or higher. Of the 29 pilots who had complete cardiac investigations data, 26 pilots underwent exercise electrocardiography (ECG), 2 pilots progressed directly to coronary angiograms and 1 pilot with abnormal echocardiogram was not examined further. Of the 26 pilots, 7 had positive or borderline exercise tests, all of whom subsequently had angiograms. One patient with a negative exercise test also had a coronary angiogram. Of the 9 patients who had coronary angiograms as a consequence of screening, 5 had significant disease that required treatment and 4 had either trivial disease or normal coronary arteries. The current approach to investigate excessive cardiovascular risk in pilots relies heavily on exercise electrocardiograms as a diagnostic test, and may not be optimal either to detect disease or to protect pilots from unnecessary invasive procedures. A more comprehensive and accurate cardiac investigation algorithm to assess excessive CVD risk in pilots is required.

Revisiting the association of blood pressure with mortality in oldest old people in China: community based, longitudinal prospective study

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Lv, Yue-Bin; Gao, Xiang; Yin, Zhao-Xue; Chen, Hua-Shuai; Luo, Jie-Si; Brasher, Melanie Sereny; Kraus, Virginia Byers; Li, Tian-Tian; Zeng, Yi

2018-01-01

Abstract Objective To examine the associations of blood pressure with all cause mortality and cause specific mortality at three years among oldest old people in China. Design Community based, longitudinal prospective study. Setting 2011 and 2014 waves of the Chinese Longitudinal Healthy Longevity Survey, conducted in 22 Chinese provinces. Participants 4658 oldest old individuals (mean age 92.1 years). Main outcome measures All cause mortality and cause specific mortality assessed at three year follow-up. Results 1997 deaths were recorded at three year follow-up. U shaped associations of mortality with systolic blood pressure, mean arterial pressure, and pulse pressure were identified; values of 143.5 mm Hg, 101 mm Hg, and 66 mm Hg conferred the minimum mortality risk, respectively. After adjustment for covariates, the U shaped association remained only for systolic blood pressure (minimum mortality risk at 129 mm Hg). Compared with a systolic blood pressure value of 129 mm Hg, risk of all cause mortality decreased for values lower than 107 mm Hg (from 1.47 (95% confidence interval 1.01 to 2.17) to 1.08 (1.01 to 1.17)), and increased for values greater than 154 mm Hg (from 1.08 (1.01 to 1.17) to 1.27 (1.02 to 1.58)). In the cause specific analysis, compared with a middle range of systolic blood pressure (107-154 mm Hg), higher values (>154 mm Hg) were associated with a higher risk of cardiovascular mortality (adjusted hazard ratio 1.51 (95% confidence interval 1.12 to 2.02)); lower values (blood pressure and all cause mortality at three years among oldest old people in China. This association could be explained by the finding that higher systolic blood pressure predicted a higher risk of death from cardiovascular disease, and that lower systolic blood pressure predicted a higher risk of death from non-cardiovascular causes. These results emphasise the importance of revisiting blood pressure management or establishing specific guidelines for management among oldest

Increased susceptibility to cardiovascular effects of dihydrocapcaicin in resuscitated rats. Cardiovascular effects of dihydrocapsaicin

DEFF Research Database (Denmark)

Fosgerau, Keld; Ristagno, Giuseppe; Jayatissa, Magdalena Niepsuj

2010-01-01

Survivors of a cardiac arrest often have persistent cardiovascular derangements following cardiopulmonary resuscitation including decreased cardiac output, arrhythmias and morphological myocardial damage. These cardiovascular derangements may lead to an increased susceptibility towards the extern...

Longitudinal categorical data analysis

CERN Document Server

Sutradhar, Brajendra C

2014-01-01

This is the first book in longitudinal categorical data analysis with parametric correlation models developed based on dynamic relationships among repeated categorical responses. This book is a natural generalization of the longitudinal binary data analysis to the multinomial data setup with more than two categories. Thus, unlike the existing books on cross-sectional categorical data analysis using log linear models, this book uses multinomial probability models both in cross-sectional and longitudinal setups. A theoretical foundation is provided for the analysis of univariate multinomial responses, by developing models systematically for the cases with no covariates as well as categorical covariates, both in cross-sectional and longitudinal setups. In the longitudinal setup, both stationary and non-stationary covariates are considered. These models have also been extended to the bivariate multinomial setup along with suitable covariates. For the inferences, the book uses the generalized quasi-likelihood as w...

21 CFR 870.3375 - Cardiovascular intravascular filter.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Cardiovascular intravascular filter. 870.3375... Cardiovascular intravascular filter. (a) Identification. A cardiovascular intravascular filter is an implant that... and Revision of 2/12/90 (K90-1)” and (ii) “Guidance for Cardiovascular Intravascular Filter 510(k...

National differences in screening programmes for cardiovascular risks could obstruct understanding of cardiovascular prevention studies in Europe

NARCIS (Netherlands)

Thio, S. L.; Twickler, Th B.; Cramer, M. J.; Giral, P.

2011-01-01

In North-West Europe, cardiovascular disease is still a major cause of death and despite several efforts (e.g. European guidelines and conferences) cardiovascular risk factors are still inconsistently diagnosed and treated. We evaluated the first consultations of patients in two cardiovascular

Genotype-phenotype associations in obesity dependent on definition of the obesity phenotype.

Science.gov (United States)

Kring, Sofia Inez Iqbal; Larsen, Lesli Hingstrup; Holst, Claus; Toubro, Søren; Hansen, Torben; Astrup, Arne; Pedersen, Oluf; Sørensen, Thorkild I A

2008-01-01

In previous studies of associations of variants in the genes UCP2, UCP3, PPARG2, CART, GRL, MC4R, MKKS, SHP, GHRL, and MCHR1 with obesity, we have used a case-control approach with cases defined by a threshold for BMI. In the present study, we assess the association of seven abdominal, peripheral, and overall obesity phenotypes, which were analyzed quantitatively, and thirteen candidate gene polymorphisms in these ten genes in the same cohort. Obese Caucasian men (n = 234, BMI >or= 31.0 kg/m(2)) and a randomly sampled non-obese group (n = 323), originally identified at the draft board examinations, were re-examined at median ages of 47.0 or 49.0 years by anthropometry and DEXA scanning. Obesity phenotypes included BMI, fat body mass index, waist circumference, waist for given BMI, intra-abdominal adipose tissue, hip circumference and lower body fat mass (%). Using logistic regression models, we estimated the odds for defined genotypes (dominant or recessive genetic transmission) in relation to z-scores of the phenotypes. The minor (rare) allele for SHP 512G>C (rs6659176) was associated with increased hip circumference. The minor allele for UCP2 Ins45bp was associated with increased BMI, increased abdominal obesity, and increased hip circumference. The minor allele for UCP2 -866G>A (rs6593669) was associated with borderline increased fat body mass index. The minor allele for MCHR1 100213G>A (rs133072) was associated with reduced abdominal obesity. None of the other genotype-phenotype combinations showed appreciable associations. If replicated in independent studies with focus on the specific phenotypes, our explorative studies suggest significant associations between some candidate gene polymorphisms and distinct obesity phenotypes, predicting beneficial and detrimental effects, depending on compartments for body fat accumulation. Copyright 2008 S. Karger AG, Basel.

Influenza vaccines for preventing cardiovascular disease

Directory of Open Access Journals (Sweden)

Christine Clar

Full Text Available ABSTRACTBACKGROUND: This is an update of the original review published in 2008. The risk of adverse cardiovascular outcomes is increased with influenza-like infection, and vaccination against influenza may improve cardiovascular outcomes.OBJECTIVES: To assess the potential benefits of influenza vaccination for primary and secondary prevention of cardiovascular disease.METHODS:Search methods:We searched the following electronic databases on 18 October 2013: The Cochrane Library (including Cochrane Central Register of Controlled Trials (CENTRAL, Database of Abstracts of Reviews of Effects (DARE, Economic Evaluation Database (EED and Health Technology Assessment database (HTA, MEDLINE, EMBASE, Science Citation Index Expanded, Conference Proceedings Citation Index - Science and ongoing trials registers (www.controlled-trials.com/ and www.clinicaltrials.gov. We examined reference lists of relevant primary studies and systematic reviews. We performed a limited PubMed search on 20 February 2015, just before publication.Selection criteria:Randomised controlled trials (RCTs of influenza vaccination compared with placebo or no treatment in participants with or without cardiovascular disease, assessing cardiovascular death or non-fatal cardiovascular events.Data collection and analysis:We used standard methodological procedures as expected by The Cochrane Collaboration. We carried out meta-analyses only for cardiovascular death, as other outcomes were reported too infrequently. We expressed effect sizes as risk ratios (RRs, and we used random-effects models.MAIN RESULTS: We included eight trials of influenza vaccination compared with placebo or no vaccination, with 12,029 participants receiving at least one vaccination or control treatment. We included six new studies (n = 11,251, in addition to the two included in the previous version of the review. Four of these trials (n = 10,347 focused on prevention of influenza in the general or elderly population

Gender bias in cardiovascular advertisements.

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Ahmed, Sofia B; Grace, Sherry L; Stelfox, Henry Thomas; Tomlinson, George; Cheung, Angela M

2004-11-01

Women with cardiovascular disease are treated less aggressively than men. The reasons for this disparity are unclear. Pharmaceutical advertisements may influence physician practices and patient care. To determine if female and male patients are equally likely to be featured in cardiovascular advertisements. We examined all cardiovascular advertisements from US editions of general medical and cardiovascular journals published between 1 January 1996 and 30 June 1998. For each unique advertisement, we recorded the total number of journal appearances and the number of appearances in journals' premium positions. We noted the gender, age, race and role of both the primary figure and the majority of people featured in the advertisement. Nine hundred and nineteen unique cardiovascular advertisements were identified of which 254 depicted a patient as the primary figure. A total of 20%[95% confidence interval (CI) 15.3-25.5%] of these advertisements portrayed a female patient, while 80% (95% CI 74.5-84.7%) depicted a male patient, P advertisements appeared 249 times (13.3%; 95% CI 8.6-18.9%) while male patient advertisements appeared 1618 times (86.7%; 95% CI 81.1-91.4%), P advertisements also had significantly fewer mean appearances than male patient advertisements in journals' premium positions (0.82 vs. 1.99, P=0.02). Similar results were seen when the advertisements were analysed according to predominant gender. Despite increasing emphasis on cardiovascular disease in women, significant under-representation of female patients exists in cardiovascular advertisements. Physicians should be cognizant of this gender bias.

Sugar-sweetened soft drinks are associated with poorer cognitive function in individuals with type 2 diabetes: the Maine-Syracuse Longitudinal Study.

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Crichton, Georgina E; Elias, Merrill F; Torres, Rachael V

2016-04-01

The importance of adequate nutrition on cognitive performance is well recognised. Greater intakes of soft drinks are associated with a higher risk for type 2 diabetes, as well as other cardiometabolic diseases. A few studies have specifically examined whether the intake of soft drinks may be related to cognitive function. The aim of this study was to investigate whether soft drink intakes, including both sugar-sweetened and diet beverages, are associated with cognitive function, with adjustment for cardiovascular, lifestyle and dietary factors, and stratified according to type 2 diabetes status. Cross-sectional analyses were undertaken using 803 community-dwelling participants, aged 23-98 years, from the Maine-Syracuse Longitudinal Study. Cognitive function was measured using an extensive battery of neuropsychological tests. Usual dietary intake of soft drinks was assessed using a FFQ. Stratification by type 2 diabetes indicated that a greater intake of sugar-sweetened soft drinks was significantly associated with poorer performance in visual spatial memory, working memory, scanning and tracking, executive function, the global composite and the Mini-Mental State Examination in diabetic individuals. These relations were not attenuated with statistical control for BMI and other cardiovascular, lifestyle and dietary factors. Diet soft drink intake was unrelated to cognitive performance. Frequent sugar-sweetened soft drink intake was associated with poorer cognitive performance, particularly in individuals with type 2 diabetes, but the underlying causal mechanisms are yet to be determined. Longitudinal studies are needed to clarify these findings and the underlying causal mechanisms.

[Controversies and dilemmas on the use of beta-blockers in treatment of associated cardiovascular disease in patients with chronic obstructive pulmonary disease].

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Pescaru, Camelia; Tudorache, Voicu; Oancea, Cristian

2010-01-01

In the last decade, chronic obstructive pulmonary disease (COPD) has been considered a syndrome with multiple phenotypical facets and systemic components. Chronic diseases are associated, in time, with several comorbidities. Cardiovascular disease represents the most common comorbidity in COPD, increases its handicap and mortality indices. Most entities associated with cardiovascular disease require treatment with beta-blockers. However, beta-blockers are a "two-edged sword" when administered in obstructive pulmonary disorder. The use of beta-blockers should be assessed by their action on three areas: their effect on FEV1, their effect on bronchial hyperreactivity, the result obtained when additionally administering beta-agonists. The result of beta-blocker administration is influenced by the involvement of several other factors: the cardioselectivity of the beta-blocker, the dosage, the concomitant administration of beta-agonists, the stage of the disease (stable or exacerbation of COPD), smoker status etc. Their administration under strict monitoring results in a decreased morbidity and mortality, including in patients who had undergone cardiovascular surgery. The overall conclusion is that beta-blockers may be administered in COPD associated with cardiac comorbidity, but this administration requires utmost care.

Longitudinal Associations between Physical Activity and Educational Outcomes.

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Kari, Jaana T; Pehkonen, Jaakko; Hutri-Kähönen, Nina; Raitakari, Olli T; Tammelin, Tuija H

2017-11-01

This longitudinal study examined the role of leisure-time physical activity in academic achievement at the end of compulsory basic education and educational attainment in adulthood. The data were drawn from the ongoing longitudinal Cardiovascular Risk in Young Finns Study, which was combined with register-based data from Statistics Finland. The study consisted of children who were 12 yr (n = 1723, 49% boys) and 15 yr (n = 2445, 48% boys) of age at the time when physical activity was measured. The children were followed up until 2010, when their mean age was 40 yr. Physical activity was self-reported and included several measurements: overall leisure-time physical activity outside school hours, participation in sports club training sessions, and participation in sports competitions. Individuals' educational outcomes were measured with the self-reported grade point average at age 15 yr and register-based information on the years of completed postcompulsory education in adulthood. Ordinary least squares models and the instrumental variable approach were used to analyze the relationship between physical activity and educational outcomes. Physical activity in adolescence was positively associated with educational outcomes. Both the physical activity level at age 15 yr and an increase in the physical activity level between the ages of 12 and 15 yr were positively related to the grade point average at age 15 yr and the years of postcompulsory education in adulthood. The results were robust to the inclusion of several individual and family background factors, including health endowments, family income, and parents' education. The results provide evidence that physical activity in adolescence may not only predict academic success during compulsory basic education but also boost educational outcomes later in life.

Cardiovascular autonomic neuropathy in diabetes

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Spallone, Vincenza; Ziegler, Dan; Freeman, Roy

2011-01-01

Cardiovascular Autonomic Neuropathy (CAN) Subcommittee of Toronto Consensus Panel on Diabetic Neuropathy worked to update CAN guidelines, with regard to epidemiology, clinical impact, diagnosis, usefulness of CAN testing, and management. CAN is the impairment of cardiovascular autonomic control...... in type 2 diabetes. CAN is a risk marker of mortality and cardiovascular morbidity, and possibly a progression promoter of diabetic nephropathy. Criteria for CAN diagnosis and staging are: 1. one abnormal cardio-vagal test identifies possible or early CAN; 2. at least two abnormal cardio-vagal tests....... diagnosis of CAN clinical forms, 2. detection and tailored treatment of CAN clinical correlates (e.g. tachycardia, OH, nondipping, QT interval prolongation), 3. risk stratification for diabetic complications and cardiovascular morbidity and mortality, and 4. modulation of targets of diabetes therapy...

Hypertriglyceridemic Waist Phenotype and Changes in the Fasting Glycemia and Blood Pressure in Children and Adolescents Over One-Year Follow-Up Period.

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Costa, Priscila Ribas de Farias; Assis, Ana Marlúcia Oliveira; Cunha, Carla de Magalhães; Pereira, Emile Miranda; Jesus, Gabriela Dos Santos de; Silva, Lais Eloy Machado da; Alves, Wilanne Pinheiro de Oliveira

2017-07-01

The hypertriglyceridemic waist (HTW) phenotype is defined as the simultaneous presence of increased waist circumference (WC) and serum triglycerides (TG) levels and it has been associated with cardiometabolic risk in children and adolescents. The objective was to evaluate the influence of HTW phenotype in the fasting glycemia and blood pressure in children and adolescents over one-year follow-up period. It is a cohort study involving 492 children and adolescents from 7 to 15 years old, both genders, who were submitted to anthropometric, biochemical and clinical evaluation at the baseline, and also after 6 and 12 months of follow-up. Generalized Estimating Equation (GEE) models were calculated to evaluate the longitudinal influence of the HTW phenotype in the glycemia and blood pressure over one-year. It was observed a prevalence of 10.6% (n = 52) of HTW phenotype in the students. The GEE models identified that students with HTW phenotype had an increase of 3.87 mg/dl in the fasting glycemia mean (CI: 1.68-6.05) and of 3.67mmHg in the systolic blood pressure (SBP) mean (CI: 1.55-6.08) over one-year follow-up, after adjusting for confounding variables. The results of this study suggest that HTW phenotype is a risk factor for longitudinal changes in glycemia and SBP in children and adolescents over one-year follow-up period. O fenótipo de cintura hipertrigliceridêmica (CHT) é definido como a presença simultânea de circunferência de cintura (CC) e níveis séricos de triglicérides (TG) aumentados e tem sido associado com risco cardiometabólico em crianças e adolescentes. Avaliar a influência do fenótipo CHT na glicemia de jejum e na pressão arterial em crianças e adolescentes em um período de acompanhamento de um ano. Trata-se de um estudo de coorte envolvendo 492 crianças e adolescentes de 7 a 15 anos de ambos os sexos, que foram submetidos à avaliação antropométrica, bioquímica e clínica no início e também após 6 e 12 meses de seguimento. Os

Association between red meat consumption and metabolic syndrome in a Mediterranean population at high cardiovascular risk: cross-sectional and 1-year follow-up assessment.

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Babio, N; Sorlí, M; Bulló, M; Basora, J; Ibarrola-Jurado, N; Fernández-Ballart, J; Martínez-González, M A; Serra-Majem, L; González-Pérez, R; Salas-Salvadó, Jordi

2012-03-01

Little is known about the role that red meat and processed red meat (RM) consumption plays in the development of the metabolic syndrome (MetS). The aim was to assess the relationship between RM consumption and the prevalence or incidence of the MetS and its components in a Mediterranean population at high risk of cardiovascular disease. Cross-sectional analyses were carried out at baseline and at 1-year follow-up and longitudinal analysis were conducted in a cohort of individuals at high risk of cardiovascular disease from the PREDIMED study. A 137-item validated semi-quantitative food frequency questionnaire, anthropometric measurements, blood pressure, fasting plasma glucose and lipid profile were evaluated both at baseline and after 1-year follow-up. The MetS was defined in accordance with the updated ATP III criteria. Subjects in the upper quartile of RM consumption were more likely to meet the criteria for the MetS at baseline (OR, 2.3; 95% CI, 1.4-3.9; P-trend = 0.001) and after 1-year follow-up (OR, 2.2; 95% CI, 1.3-3.7; P-trend = 0.034) compared with those in the quartile of reference, even after adjusting for potential confounders. The longitudinal analyses showed that individuals in the fourth quartile of RM consumption had an increased risk of MetS (OR, 2.7; 95% CI, 1.1-6.8; P-trend = 0.009) or central obesity incidence (OR, 8.1; 95% CI, 1.4-46.0; P-trend = 0.077) at the end of the follow-up compared to the lowest quartile. Higher RM consumption is associated with a significantly higher prevalence and incidence of MetS and central obesity in individuals at high risk of cardiovascular disease. Copyright © 2010 Elsevier B.V. All rights reserved.

Increased burden of cardiovascular disease in carriers of APOL1 genetic variants.

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Ito, Kaoru; Bick, Alexander G; Flannick, Jason; Friedman, David J; Genovese, Giulio; Parfenov, Michael G; Depalma, Steven R; Gupta, Namrata; Gabriel, Stacey B; Taylor, Herman A; Fox, Ervin R; Newton-Cheh, Christopher; Kathiresan, Sekar; Hirschhorn, Joel N; Altshuler, David M; Pollak, Martin R; Wilson, James G; Seidman, J G; Seidman, Christine

2014-02-28

Two distinct alleles in the gene encoding apolipoprotein L1 (APOL1), a major component of high-density lipoprotein, confer protection against Trypanosoma brucei rhodesiense infection and also increase risk for chronic kidney disease. Approximately 14% of Americans with African ancestry carry 2 APOL1 risk alleles, accounting for the high chronic kidney disease burden in this population. We tested whether APOL1 risk alleles significantly increase risk for atherosclerotic cardiovascular disease (CVD) in African Americans. We sequenced APOL1 in 1959 randomly selected African American participants in the Jackson Heart Study (JHS) and evaluated associations between APOL1 genotypes and renal and cardiovascular phenotypes. Previously identified association between APOL1 genotypes and chronic kidney disease was confirmed (P=2.4×10(-6)). Among JHS participants with 2 APOL1 risk alleles, we observed increased risk for CVD (50/763 events among participants without versus 37/280 events among participants with 2 risk alleles; odds ratio, 2.17; P=9.4×10(-4)). We replicated this novel association of APOL1 genotype with CVD in Women's Health Initiative (WHI) participants (66/292 events among participants without versus 37/101 events among participants with 2 risk alleles; odds ratio, 1.98; P=8.37×10(-3); JHS and WHI combined, P=8.5×10(-5); odds ratio, 2.12). The increased risk for CVD conferred by APOL1 alleles was robust to correction for both traditional CVD risk factors and chronic kidney disease. APOL1 variants contribute to atherosclerotic CVD risk, indicating a genetic component to cardiovascular health disparities in individuals of African ancestry. The considerable population of African Americans with 2 APOL1 risk alleles may benefit from intensive interventions to reduce CVD.

Cardiovascular death and manic-depressive psychosis

DEFF Research Database (Denmark)

Weeke, A; Juel, K; Vaeth, M

2013-01-01

In order to study if tricyclic antidepressant drugs (TCA) in therapeutic doses increase the risk of death due to cardiovascular causes, the relative mortality from cardiovascular diseases was studied in two large groups of first hospitalized manic-depressive patients, one from the TCA era...... to the general population. Among 1133 such cases admitted between 1950 and 1956, the rate was 1.87. Our findings do not support the hypothesis that TCA contribute to the cardiovascular mortality in manic-depressives and even support suggestions that TCA treatment may lower the risk of death by cardiovascular...

The Cardiovascular Research Grid (CVRG)

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U.S. Department of Health & Human Services — The CardioVascular Research Grid (CVRG) project is creating an infrastructure for sharing cardiovascular data and data analysis tools. CVRG tools are developed using...

Developmental plasticity and epigenetic mechanisms underpinning metabolic and cardiovascular diseases.

Science.gov (United States)

Low, Felicia M; Gluckman, Peter D; Hanson, Mark A

2011-06-01

The importance of developmental factors in influencing the risk of later-life disease has a strong evidence base derived from multiple epidemiological, clinical and experimental studies in animals and humans. During early life, an organism is able to adjust its phenotypic development in response to environmental cues. Such developmentally plastic responses evolved as a fitness-maximizing strategy to cope with variable environments. There are now increasing data that these responses are, at least partially, underpinned by epigenetic mechanisms. A mismatch between the early and later-life environments may lead to inappropriate early life-course epigenomic changes that manifest in later life as increased vulnerability to disease. There is also growing evidence for the transgenerational transmission of epigenetic marks. This article reviews the evidence that susceptibility to metabolic and cardiovascular disease in humans is linked to changes in epigenetic marks induced by early-life environmental cues, and discusses the clinical, public health and therapeutic implications that arise.

Healthy lifestyle factors and risk of cardiovascular events and mortality in treatment-resistant hypertension: the Reasons for Geographic and Racial Differences in Stroke study.

Science.gov (United States)

Diaz, Keith M; Booth, John N; Calhoun, David A; Irvin, Marguerite R; Howard, George; Safford, Monika M; Muntner, Paul; Shimbo, Daichi

2014-09-01

Few data exist on whether healthy lifestyle factors are associated with better prognosis among individuals with apparent treatment-resistant hypertension, a high-risk phenotype of hypertension. The purpose of this study was to assess the association of healthy lifestyle factors with cardiovascular events, all-cause mortality, and cardiovascular mortality among individuals with apparent treatment-resistant hypertension. We studied participants (n=2043) from the population-based Reasons for Geographic and Racial Differences in Stroke (REGARDS) study with apparent treatment-resistant hypertension (blood pressure ≥140/90 mm Hg despite the use of 3 antihypertensive medication classes or the use of ≥4 classes of antihypertensive medication regardless of blood pressure control). Six healthy lifestyle factors adapted from guidelines for the management of hypertension (normal waist circumference, physical activity ≥4 times/week, nonsmoking, moderate alcohol consumption, high Dietary Approaches to Stop Hypertension diet score, and low sodium-to-potassium intake ratio) were examined. A greater number of healthy lifestyle factors were associated with lower risk for cardiovascular events (n=360) during a mean follow-up of 4.5 years. Multivariable-adjusted hazard ratios [HR (95% confidence interval)] for cardiovascular events comparing individuals with 2, 3, and 4 to 6 versus 0 to 1 healthy lifestyle factors were 0.91 (0.68-1.21), 0.80 (0.57-1.14), and 0.63 (0.41-0.95), respectively (P-trend=0.020). Physical activity and nonsmoking were individual healthy lifestyle factors significantly associated with lower risk for cardiovascular events. Similar associations were observed between healthy lifestyle factors and risk for all-cause and cardiovascular mortality. In conclusion, healthy lifestyle factors, particularly physical activity and nonsmoking, are associated with a lower risk for cardiovascular events and mortality among individuals with apparent treatment

Detection of mild cognitive impairment in people older than 65 years of age and its relationship to cardiovascular risk factors (DECRIVAM

Directory of Open Access Journals (Sweden)

Agudo-Conde Cristina

2011-06-01

Full Text Available Abstract Background Studies centered on the detection of cognitive impairment and its relationship to cardiovascular risk factors in elderly people have gained special relevance in recent years. Knowledge of the cardiovascular risk factors that may be associated to cognitive impairment could be very useful for introducing treatments in early stages - thereby possibly contributing to improve patient quality of life. The present study explores cognitive performance in people over 65 years of age in Salamanca (Spain, with special emphasis on the identification of early symptoms of cognitive impairment, with the purpose of detecting mild cognitive impairment and of studying the relationships between this clinical situation and cardiovascular risk factors. Methods/Design A longitudinal study is contemplated. The reference population will consist of 420 people over 65 years of age enrolled through randomized sampling stratified by healthcare area, and who previously participated in another study. Measurement: a Sociodemographic variables; b Cardiovascular risk factors; c Comorbidity; d Functional level for daily life activities; and e Study of higher cognitive functions based on a neuropsychological battery especially adapted to the evaluation of elderly people. Discussion We hope that this study will afford objective information on the representative prevalence of cognitive impairment in the population over 65 years of age in Salamanca. We also hope to obtain data on the relationship between cognitive impairment and cardiovascular risk factors in this specific population group. Based on the results obtained, we also will be able to establish the usefulness of some of the screening tests applied during the study, such as the Mini-Mental State Examination and the 7 Minute Screen test. Trial registration ClinicalTrials.gov: NCT01327196

Depressive symptoms, physical inactivity and risk of cardiovascular mortality in older adults: the Cardiovascular Health Study

Science.gov (United States)

Win, Sithu; Parakh, Kapil; Eze-Nliam, Chete M; Gottdiener, John S; Kop, Willem J

2011-01-01

Background Depressed older individuals have a higher mortality than older persons without depression. Depression is associated with physical inactivity, and low levels of physical activity have been shown in some cohorts to be a partial mediator of the relationship between depression and cardiovascular events and mortality. Methods A cohort of 5888 individuals (mean 72.8±5.6 years, 58% female, 16% African-American) from four US communities was followed for an average of 10.3 years. Self-reported depressive symptoms (10-item Center for Epidemiological Studies Depression Scale) were assessed annually and self-reported physical activity was assessed at baseline and at 3 and 7 years. To estimate how much of the increased risk of cardiovascular mortality associated with depressive symptoms was due to physical inactivity, Cox regression with time-varying covariates was used to determine the percentage change in the log HR of depressive symptoms for cardiovascular mortality after adding physical activity variables. Results At baseline, 20% of participants scored above the cut-off for depressive symptoms. There were 2915 deaths (49.8%), of which 1176 (20.1%) were from cardiovascular causes. Depressive symptoms and physical inactivity each independently increased the risk of cardiovascular mortality and were strongly associated with each other (all pphysical inactivity had greater cardiovascular mortality than those with either individually (pPhysical inactivity reduced the log HR of depressive symptoms for cardiovascular mortality by 26% after adjustment. This was similar for persons with (25%) and without (23%) established coronary heart disease. Conclusions Physical inactivity accounted for a significant proportion of the risk of cardiovascular mortality due to depressive symptoms in older adults, regardless of coronary heart disease status. PMID:21339320

Immune phenotypes predict survival in patients with glioblastoma multiforme

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Haouraa Mostafa

2016-09-01

Full Text Available Abstract Background Glioblastoma multiforme (GBM, a common primary malignant brain tumor, rarely disseminates beyond the central nervous system and has a very bad prognosis. The current study aimed at the analysis of immunological control in individual patients with GBM. Methods Immune phenotypes and plasma biomarkers of GBM patients were determined at the time of diagnosis using flow cytometry and ELISA, respectively. Results Using descriptive statistics, we found that immune anomalies were distinct in individual patients. Defined marker profiles proved highly relevant for survival. A remarkable relation between activated NK cells and improved survival in GBM patients was in contrast to increased CD39 and IL-10 in patients with a detrimental course and very short survival. Recursive partitioning analysis (RPA and Cox proportional hazards models substantiated the relevance of absolute numbers of CD8 cells and low numbers of CD39 cells for better survival. Conclusions Defined alterations of the immune system may guide the course of disease in patients with GBM and may be prognostically valuable for longitudinal studies or can be applied for immune intervention.

Oral Antidiabetic Agents and Cardiovascular Outcomes

DEFF Research Database (Denmark)

Pareek, Manan; Bhatt, Deepak L

2018-01-01

Cardiovascular disease is the leading cause of morbidity and mortality among patients with type 2 diabetes; however, a direct protective effect of tight glycemic control remains unproven. In fact, until 2008, when concerns related to rosiglitazone prompted regulatory agencies to mandate assessment...... of cardiovascular safety of new antidiabetic agents, little was known about how these medications affected cardiovascular outcomes. Since then, there has been a considerable increase in the number of cardiovascular trials, which employ a noninferiority design and focus on high-risk populations to establish safety...... in the shortest time possible. In this article, we summarize the 4 major cardiovascular outcome trials of oral antidiabetic agents, completed so far. These include 3 dipeptidyl peptidase-4 inhibitors (saxagliptin, alogliptin, and sitagliptin) and 1 sodium-glucose cotransporter-2 inhibitor (empagliflozin). We...

[Cooperative Cardiovascular Disease Research Network (RECAVA)].

Science.gov (United States)

García-Dorado, David; Castro-Beiras, Alfonso; Díez, Javier; Gabriel, Rafael; Gimeno-Blanes, Juan R; Ortiz de Landázuri, Manuel; Sánchez, Pedro L; Fernández-Avilés, Francisco

2008-01-01

Today, cardiovascular disease is the principal cause of death and hospitalization in Spain, and accounts for an annual healthcare budget of more than 4000 million euros. Consequently, early diagnosis, effective prevention, and the optimum treatment of cardiovascular disease present a significant social and healthcare challenge for the country. In this context, combining all available resources to increase the efficacy and healthcare benefits of scientific research is a priority. This rationale prompted the establishment of the Spanish Cooperative Cardiovascular Disease Research Network, or RECAVA (Red Temática de Investigación Cooperativa en Enfermedades Cardiovasculares), 5 years ago. Since its foundation, RECAVA's activities have focused on achieving four objectives: a) to facilitate contacts between basic, clinical and epidemiological researchers; b) to promote the shared use of advanced technological facilities; c) to apply research results to clinical practice, and d) to train a new generation of translational cardiovascular researchers in Spain. At present, RECAVA consists of 41 research groups and seven shared technological facilities. RECAVA's research strategy is based on a scientific design matrix centered on the most important cardiovascular processes. The level of RECAVA's research activity is reflected in the fact that 28 co-authored articles were published in international journals during the first six months of 2007, with each involving contributions from at least two groups in the network. Finally, RECAVA also participates in the work of the Spanish National Center for Cardiovascular Research, or CNIC (Centro Nacional de Investigación Cardiovascular), and some established Biomedical Research Network Centers, or CIBER (Centros de Investigación Biomédica en RED), with the aim of consolidating the development of a dynamic multidisciplinary research framework that is capable of meeting the growing challenge that cardiovascular disease will present

Phenotypic characterization of the Komeda miniature rat Ishikawa, an animal model of dwarfism caused by a mutation in Prkg2.

Science.gov (United States)

Tsuchida, Atsuko; Yokoi, Norihide; Namae, Misako; Fuse, Masanori; Masuyama, Taku; Sasaki, Masashi; Kawazu, Shoji; Komeda, Kajuro

2008-12-01

The Komeda miniature rat Ishikawa (KMI) is a spontaneous animal model of dwarfism caused by a mutation in Prkg2, which encodes cGMP-dependent protein kinase type II (cGKII). This strain has been maintained as a segregating inbred strain for the mutated allele mri. In this study, we characterized the phenotype of the KMI strain, particularly growth traits, craniofacial measurements, and organ weights. The homozygous mutant (mri/mri) animals were approximately 70% to 80% of the size of normal, heterozygous (mri/+) animals in regard to body length, weight, and naso-occipital length of the calvarium, and the retroperitoneal fat of mri/mri rats was reduced greatly. In addition, among progeny of the (BNxKMI-mri/mri)F1xKMI-mri/mri backcross, animals with the KMI phenotype (mri/mri) were easily distinguished from those showing the wild-type phenotype (mri/+) by using growth traits such as body length and weight. Genetic analysis revealed that all of the backcrossed progeny exhibiting the KMI phenotype were homozygous for the KMI allele in the 1.2-cM region between D14Rat5 and D14Rat80 on chromosome 14, suggesting strongly that mri acts in a completely recessive manner. The KMI strain is the first and only rat model with a confirmed mutation in Prkg2 and is a valuable model for studying dwarfism and longitudinal growth traits in humans and for functional studies of cGKII.

The phenotypic variance gradient - a novel concept.

Science.gov (United States)

Pertoldi, Cino; Bundgaard, Jørgen; Loeschcke, Volker; Barker, James Stuart Flinton

2014-11-01

Evolutionary ecologists commonly use reaction norms, which show the range of phenotypes produced by a set of genotypes exposed to different environments, to quantify the degree of phenotypic variance and the magnitude of plasticity of morphometric and life-history traits. Significant differences among the values of the slopes of the reaction norms are interpreted as significant differences in phenotypic plasticity, whereas significant differences among phenotypic variances (variance or coefficient of variation) are interpreted as differences in the degree of developmental instability or canalization. We highlight some potential problems with this approach to quantifying phenotypic variance and suggest a novel and more informative way to plot reaction norms: namely "a plot of log (variance) on the y-axis versus log (mean) on the x-axis, with a reference line added". This approach gives an immediate impression of how the degree of phenotypic variance varies across an environmental gradient, taking into account the consequences of the scaling effect of the variance with the mean. The evolutionary implications of the variation in the degree of phenotypic variance, which we call a "phenotypic variance gradient", are discussed together with its potential interactions with variation in the degree of phenotypic plasticity and canalization.

The broader autism phenotype in infancy: when does it emerge?

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Ozonoff, Sally; Young, Gregory S; Belding, Ashleigh; Hill, Monique; Hill, Alesha; Hutman, Ted; Johnson, Scott; Miller, Meghan; Rogers, Sally J; Schwichtenberg, A J; Steinfeld, Marybeth; Iosif, Ana-Maria

2014-04-01

This study had 3 goals, which were to examine the following: the frequency of atypical development, consistent with the broader autism phenotype, in high-risk infant siblings of children with autism spectrum disorder (ASD); the age at which atypical development is first evident; and which developmental domains are affected. A prospective longitudinal design was used to compare 294 high-risk infants and 116 low-risk infants. Participants were tested at 6, 12, 18, 24, and 36 months of age. At the final visit, outcome was classified as ASD, Typical Development (TD), or Non-TD (defined as elevated Autism Diagnostic Observation Schedule [ADOS] score, low Mullen Scale scores, or both). Of the high-risk group, 28% were classified as Non-TD at 36 months of age. Growth curve models demonstrated that the Non-TD group could not be distinguished from the other groups at 6 months of age, but differed significantly from the Low-Risk TD group by 12 months on multiple measures. The Non-TD group demonstrated atypical development in cognitive, motor, language, and social domains, with differences particularly prominent in the social-communication domain. These results demonstrate that features of atypical development, consistent with the broader autism phenotype, are detectable by the first birthday and affect development in multiple domains. This highlights the necessity for close developmental surveillance of infant siblings of children with ASD, along with implementation of appropriate interventions as needed. Copyright © 2014 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.

Hepatitis C virus and cardiovascular: A review

Directory of Open Access Journals (Sweden)

Salvatore Petta

2017-03-01

Full Text Available Chronic hepatitis C virus (HCV infection is a systemic disease that leads to increased risks of cirrhosis and its complications, as well as extrahepatic disturbances, including immune-related disorders and metabolic alterations such as insulin resistance and steatosis. Recent accumulating evidence suggests that HCV infection can increase cardiovascular risk, and that viral eradication can improve cardiovascular outcomes in the clinical setting. These data are strengthened by evidence identifying potential mechanisms (indirectly linking HCV infection to vascular damage. However, the high prevalence of both HCV infection and cardiovascular alterations, as well as the presence of contrasting results not identifying any association between HCV infection and cardiovascular dysfunction, provides uncertainty about a direct association of HCV infection with cardiovascular risk. Further studies are needed to clarify definitively the role of HCV infection in cardiovascular alterations, as well as the impact of viral eradication on cardiovascular outcomes. These features are now more attractive, considering the availability of new, safe, and very effective interferon-free antiviral agents for the treatment of HCV infection. This review aims to discuss carefully available data on the relationship between HCV infection and cardiovascular risk.

ABO blood group phenotype frequency estimation using molecular phenotyping in rhesus and cynomolgus macaques.

Science.gov (United States)

Kanthaswamy, S; Ng, J; Oldt, R F; Valdivia, L; Houghton, P; Smith, D G

2017-11-01

A much larger sample (N = 2369) was used to evaluate a previously reported distribution of the A, AB and B blood group phenotypes in rhesus and cynomolgus macaques from six different regional populations. These samples, acquired from 15 different breeding and research facilities in the United States, were analyzed using a real-time quantitative polymerase chain reaction (qPCR) assay that targets single nucleotide polymorphisms (SNPs) responsible for the macaque A, B and AB phenotypes. The frequency distributions of blood group phenotypes of the two species differ significantly from each other and significant regional differentiation within the geographic ranges of each species was also observed. The B blood group phenotype was prevalent in rhesus macaques, especially those from India, while the frequencies of the A, B and AB phenotypes varied significantly among cynomolgus macaques from different geographic regions. The Mauritian cynomolgus macaques, despite having originated in Indonesia, showed significant (P ≪ .01) divergence from the Indonesian animals at the ABO blood group locus. Most Mauritian animals belonged to the B blood group while the Indonesian animals were mostly A. The close similarity in blood group frequency distributions between the Chinese rhesus and Indochinese cynomolgus macaques demonstrates that the introgression between these two species extends beyond the zone of intergradation in Indochina. This study underscores the importance of ABO blood group phenotyping of the domestic supply of macaques and their biospecimens. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Elucidating the genotype-phenotype map by automatic enumeration and analysis of the phenotypic repertoire.

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Lomnitz, Jason G; Savageau, Michael A

The gap between genotype and phenotype is filled by complex biochemical systems most of which are poorly understood. Because these systems are complex, it is widely appreciated that quantitative understanding can only be achieved with the aid of mathematical models. However, formulating models and measuring or estimating their numerous rate constants and binding constants is daunting. Here we present a strategy for automating difficult aspects of the process. The strategy, based on a system design space methodology, is applied to a class of 16 designs for a synthetic gene oscillator that includes seven designs previously formulated on the basis of experimentally measured and estimated parameters. Our strategy provides four important innovations by automating: (1) enumeration of the repertoire of qualitatively distinct phenotypes for a system; (2) generation of parameter values for any particular phenotype; (3) simultaneous realization of parameter values for several phenotypes to aid visualization of transitions from one phenotype to another, in critical cases from functional to dysfunctional; and (4) identification of ensembles of phenotypes whose expression can be phased to achieve a specific sequence of functions for rationally engineering synthetic constructs. Our strategy, applied to the 16 designs, reproduced previous results and identified two additional designs capable of sustained oscillations that were previously missed. Starting with a system's relatively fixed aspects, its architectural features, our method enables automated analysis of nonlinear biochemical systems from a global perspective, without first specifying parameter values. The examples presented demonstrate the efficiency and power of this automated strategy.

Genome-wide association analysis identifies 11 risk variants associated with the asthma with hay fever phenotype.

Science.gov (United States)

Ferreira, Manuel A R; Matheson, Melanie C; Tang, Clara S; Granell, Raquel; Ang, Wei; Hui, Jennie; Kiefer, Amy K; Duffy, David L; Baltic, Svetlana; Danoy, Patrick; Bui, Minh; Price, Loren; Sly, Peter D; Eriksson, Nicholas; Madden, Pamela A; Abramson, Michael J; Holt, Patrick G; Heath, Andrew C; Hunter, Michael; Musk, Bill; Robertson, Colin F; Le Souëf, Peter; Montgomery, Grant W; Henderson, A John; Tung, Joyce Y; Dharmage, Shyamali C; Brown, Matthew A; James, Alan; Thompson, Philip J; Pennell, Craig; Martin, Nicholas G; Evans, David M; Hinds, David A; Hopper, John L

2014-06-01

To date, no genome-wide association study (GWAS) has considered the combined phenotype of asthma with hay fever. Previous analyses of family data from the Tasmanian Longitudinal Health Study provide evidence that this phenotype has a stronger genetic cause than asthma without hay fever. We sought to perform a GWAS of asthma with hay fever to identify variants associated with having both diseases. We performed a meta-analysis of GWASs comparing persons with both physician-diagnosed asthma and hay fever (n = 6,685) with persons with neither disease (n = 14,091). At genome-wide significance, we identified 11 independent variants associated with the risk of having asthma with hay fever, including 2 associations reaching this level of significance with allergic disease for the first time: ZBTB10 (rs7009110; odds ratio [OR], 1.14; P = 4 × 10(-9)) and CLEC16A (rs62026376; OR, 1.17; P = 1 × 10(-8)). The rs62026376:C allele associated with increased asthma with hay fever risk has been found to be associated also with decreased expression of the nearby DEXI gene in monocytes. The 11 variants were associated with the risk of asthma and hay fever separately, but the estimated associations with the individual phenotypes were weaker than with the combined asthma with hay fever phenotype. A variant near LRRC32 was a stronger risk factor for hay fever than for asthma, whereas the reverse was observed for variants in/near GSDMA and TSLP. Single nucleotide polymorphisms with suggestive evidence for association with asthma with hay fever risk included rs41295115 near IL2RA (OR, 1.28; P = 5 × 10(-7)) and rs76043829 in TNS1 (OR, 1.23; P = 2 × 10(-6)). By focusing on the combined phenotype of asthma with hay fever, variants associated with the risk of allergic disease can be identified with greater efficiency. Copyright © 2013 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

Editor's Choice - Acute Cardiovascular Care Association Position Paper on Intensive Cardiovascular Care Units: An update on their definition, structure, organisation and function.

Science.gov (United States)

Bonnefoy-Cudraz, Eric; Bueno, Hector; Casella, Gianni; De Maria, Elia; Fitzsimons, Donna; Halvorsen, Sigrun; Hassager, Christian; Iakobishvili, Zaza; Magdy, Ahmed; Marandi, Toomas; Mimoso, Jorge; Parkhomenko, Alexander; Price, Susana; Rokyta, Richard; Roubille, Francois; Serpytis, Pranas; Shimony, Avi; Stepinska, Janina; Tint, Diana; Trendafilova, Elina; Tubaro, Marco; Vrints, Christiaan; Walker, David; Zahger, Doron; Zima, Endre; Zukermann, Robert; Lettino, Maddalena

2018-02-01

Acute cardiovascular care has progressed considerably since the last position paper was published 10 years ago. It is now a well-defined, complex field with demanding multidisciplinary teamworking. The Acute Cardiovascular Care Association has provided this update of the 2005 position paper on acute cardiovascular care organisation, using a multinational working group. The patient population has changed, and intensive cardiovascular care units now manage a large range of conditions from those simply requiring specialised monitoring, to critical cardiovascular diseases with associated multi-organ failure. To describe better intensive cardiovascular care units case mix, acuity of care has been divided into three levels, and then defining intensive cardiovascular care unit functional organisation. For each level of intensive cardiovascular care unit, this document presents the aims of the units, the recommended management structure, the optimal number of staff, the need for specially trained cardiologists and cardiovascular nurses, the desired equipment and architecture, and the interaction with other departments in the hospital and other intensive cardiovascular care units in the region/area. This update emphasises cardiologist training, referring to the recently updated Acute Cardiovascular Care Association core curriculum on acute cardiovascular care. The training of nurses in acute cardiovascular care is additionally addressed. Intensive cardiovascular care unit expertise is not limited to within the unit's geographical boundaries, extending to different specialties and subspecialties of cardiology and other specialties in order to optimally manage the wide scope of acute cardiovascular conditions in frequently highly complex patients. This position paper therefore addresses the need for the inclusion of acute cardiac care and intensive cardiovascular care units within a hospital network, linking university medical centres, large community hospitals, and smaller

Cardiovascular risk profile in women and dementia.

Science.gov (United States)

Dufouil, Carole; Seshadri, Sudha; Chêne, Geneviève

2014-01-01

There is growing evidence for the importance of cardiovascular risk factors in dementia development, including Alzheimer's disease. As cardiovascular risk profiles vary greatly by gender, with men suffering a greater burden of cardiovascular risk in midlife, this could lead to differences in dementia risk. To explore current evidence on the association between components of the cardiovascular risk profile and dementia risk in women and men, we reviewed all studies reporting the risk of dementia associated with cardiovascular risk factors stratified by gender and found 53 eligible articles out of over 4,000 published since the year 2000. Consistent results were found: 1) for exposures acting specifically in women: Overweight/obesity (harmful) and physical activity (protective), and 2) for exposures acting similarly in women and men: Moderate alcohol (protective) and hypertension, diabetes, and depression (harmful). A modified effect of tobacco or high cholesterol/statin use remained controversial. Available data do not allow us to assess whether selection of men with healthier cardiovascular profile (due to cardiovascular death in midlife) could lead in late life either to a difference in the distribution of risk factors or to a differential effect of these risk factors by gender. We recommend that results on dementia risk factors, especially cardiovascular ones, be reported systematically by gender in all future studies. More generally, as cardiovascular risk profiles evolve over time, more attention needs to be paid to the detection and correction of cardiovascular risk factors, as early as possible in the life course, and as actively in women as in men.

Comparison of three lifecourse models of poverty in predicting cardiovascular disease risk in youth.

Science.gov (United States)

Kakinami, Lisa; Séguin, Louise; Lambert, Marie; Gauvin, Lise; Nikiema, Béatrice; Paradis, Gilles

2013-08-01

Childhood poverty heightens the risk of adulthood cardiovascular disease (CVD), but the underlying pathways are poorly understood. Three lifecourse models have been proposed but have never been tested among youth. We assessed the longitudinal association of childhood poverty with CVD risk factors in 10-year-old youth according to the timing, accumulation, and mobility models. The Québec Longitudinal Study of Child Development birth cohort was established in 1998 (n = 2120). Poverty was defined as annual income below the low-income thresholds defined by Statistics Canada. Multiple imputation was used for missing data. Multivariable linear regression models adjusted for gender, pubertal stage, parental education, maternal age, whether the household was a single parent household, whether the child was overweight or obese, the child's physical activity in the past week, and family history. Approximately 40% experienced poverty at least once, 16% throughout childhood, and 25% intermittently. Poverty was associated with significantly elevated triglycerides and insulin according to the timing and accumulation models, although the timing model was superior for predicting insulin and the accumulation model was superior for predicting triglycerides. Early and prolonged exposure to poverty significantly increases CVD risk among 10-year-old youth. Copyright © 2013 Elsevier Inc. All rights reserved.

Gene networks underlying convergent and pleiotropic phenotypes in a large and systematically-phenotyped cohort with heterogeneous developmental disorders.

Directory of Open Access Journals (Sweden)

Tallulah Andrews

2015-03-01

Full Text Available Readily-accessible and standardised capture of genotypic variation has revolutionised our understanding of the genetic contribution to disease. Unfortunately, the corresponding systematic capture of patient phenotypic variation needed to fully interpret the impact of genetic variation has lagged far behind. Exploiting deep and systematic phenotyping of a cohort of 197 patients presenting with heterogeneous developmental disorders and whose genomes harbour de novo CNVs, we systematically applied a range of commonly-used functional genomics approaches to identify the underlying molecular perturbations and their phenotypic impact. Grouping patients into 408 non-exclusive patient-phenotype groups, we identified a functional association amongst the genes disrupted in 209 (51% groups. We find evidence for a significant number of molecular interactions amongst the association-contributing genes, including a single highly-interconnected network disrupted in 20% of patients with intellectual disability, and show using microcephaly how these molecular networks can be used as baits to identify additional members whose genes are variant in other patients with the same phenotype. Exploiting the systematic phenotyping of this cohort, we observe phenotypic concordance amongst patients whose variant genes contribute to the same functional association but note that (i this relationship shows significant variation across the different approaches used to infer a commonly perturbed molecular pathway, and (ii that the phenotypic similarities detected amongst patients who share the same inferred pathway perturbation result from these patients sharing many distinct phenotypes, rather than sharing a more specific phenotype, inferring that these pathways are best characterized by their pleiotropic effects.

Gene networks underlying convergent and pleiotropic phenotypes in a large and systematically-phenotyped cohort with heterogeneous developmental disorders.

Science.gov (United States)

Andrews, Tallulah; Meader, Stephen; Vulto-van Silfhout, Anneke; Taylor, Avigail; Steinberg, Julia; Hehir-Kwa, Jayne; Pfundt, Rolph; de Leeuw, Nicole; de Vries, Bert B A; Webber, Caleb

2015-03-01

Readily-accessible and standardised capture of genotypic variation has revolutionised our understanding of the genetic contribution to disease. Unfortunately, the corresponding systematic capture of patient phenotypic variation needed to fully interpret the impact of genetic variation has lagged far behind. Exploiting deep and systematic phenotyping of a cohort of 197 patients presenting with heterogeneous developmental disorders and whose genomes harbour de novo CNVs, we systematically applied a range of commonly-used functional genomics approaches to identify the underlying molecular perturbations and their phenotypic impact. Grouping patients into 408 non-exclusive patient-phenotype groups, we identified a functional association amongst the genes disrupted in 209 (51%) groups. We find evidence for a significant number of molecular interactions amongst the association-contributing genes, including a single highly-interconnected network disrupted in 20% of patients with intellectual disability, and show using microcephaly how these molecular networks can be used as baits to identify additional members whose genes are variant in other patients with the same phenotype. Exploiting the systematic phenotyping of this cohort, we observe phenotypic concordance amongst patients whose variant genes contribute to the same functional association but note that (i) this relationship shows significant variation across the different approaches used to infer a commonly perturbed molecular pathway, and (ii) that the phenotypic similarities detected amongst patients who share the same inferred pathway perturbation result from these patients sharing many distinct phenotypes, rather than sharing a more specific phenotype, inferring that these pathways are best characterized by their pleiotropic effects.

Delineation of C12orf65-related phenotypes: a genotype-phenotype relationship.

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Spiegel, Ronen; Mandel, Hanna; Saada, Ann; Lerer, Issy; Burger, Ayala; Shaag, Avraham; Shalev, Stavit A; Jabaly-Habib, Haneen; Goldsher, Dorit; Gomori, John M; Lossos, Alex; Elpeleg, Orly; Meiner, Vardiella

2014-08-01

C12orf65 participates in the process of mitochondrial translation and has been shown to be associated with a spectrum of phenotypes, including early onset optic atrophy, progressive encephalomyopathy, peripheral neuropathy, and spastic paraparesis.We used whole-genome homozygosity mapping as well as exome sequencing and targeted gene sequencing to identify novel C12orf65 disease-causing mutations in seven affected individuals originating from two consanguineous families. In four family members affected with childhood-onset optic atrophy accompanied by slowly progressive peripheral neuropathy and spastic paraparesis, we identified a homozygous frame shift mutation c.413_417 delAACAA, which predicts a truncated protein lacking the C-terminal portion. In the second family, we studied three affected individuals who presented with early onset optic atrophy, peripheral neuropathy, and spastic gait in addition to moderate intellectual disability. Muscle biopsy in two of the patients revealed decreased activities of the mitochondrial respiratory chain complexes I and IV. In these patients, we identified a homozygous splice mutation, g.21043 T>A (c.282+2 T>A) which leads to skipping of exon 2. Our study broadens the phenotypic spectrum of C12orf65 defects and highlights the triad of optic atrophy, axonal neuropathy and spastic paraparesis as its key clinical features. In addition, a clear genotype-phenotype correlation is anticipated in which deleterious mutations which disrupt the GGQ-containing domain in the first coding exon are expected to result in a more severe phenotype, whereas down-stream C-terminal mutations may result in a more favorable phenotype, typically lacking cognitive impairment.

Cold Weather and Cardiovascular Disease

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... Venous Thromboembolism Aortic Aneurysm More Cold Weather and Cardiovascular Disease Updated:Sep 16,2015 Th is winter ... and procedures related to heart disease and stroke. Cardiovascular Conditions • Conditions Home • Arrhythmia and Atrial Fibrillation • Cardiac ...

Machine-learning phenotypic classification of bicuspid aortopathy.

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Wojnarski, Charles M; Roselli, Eric E; Idrees, Jay J; Zhu, Yuanjia; Carnes, Theresa A; Lowry, Ashley M; Collier, Patrick H; Griffin, Brian; Ehrlinger, John; Blackstone, Eugene H; Svensson, Lars G; Lytle, Bruce W

2018-02-01

Bicuspid aortic valves (BAV) are associated with incompletely characterized aortopathy. Our objectives were to identify distinct patterns of aortopathy using machine-learning methods and characterize their association with valve morphology and patient characteristics. We analyzed preoperative 3-dimensional computed tomography reconstructions for 656 patients with BAV undergoing ascending aorta surgery between January 2002 and January 2014. Unsupervised partitioning around medoids was used to cluster aortic dimensions. Group differences were identified using polytomous random forest analysis. Three distinct aneurysm phenotypes were identified: root (n = 83; 13%), with predominant dilatation at sinuses of Valsalva; ascending (n = 364; 55%), with supracoronary enlargement rarely extending past the brachiocephalic artery; and arch (n = 209; 32%), with aortic arch dilatation. The arch phenotype had the greatest association with right-noncoronary cusp fusion: 29%, versus 13% for ascending and 15% for root phenotypes (P < .0001). Severe valve regurgitation was most prevalent in root phenotype (57%), followed by ascending (34%) and arch phenotypes (25%; P < .0001). Aortic stenosis was most prevalent in arch phenotype (62%), followed by ascending (50%) and root phenotypes (28%; P < .0001). Patient age increased as the extent of aneurysm became more distal (root, 49 years; ascending, 53 years; arch, 57 years; P < .0001), and root phenotype was associated with greater male predominance compared with ascending and arch phenotypes (94%, 76%, and 70%, respectively; P < .0001). Phenotypes were visually recognizable with 94% accuracy. Three distinct phenotypes of bicuspid valve-associated aortopathy were identified using machine-learning methodology. Patient characteristics and valvular dysfunction vary by phenotype, suggesting that the location of aortic pathology may be related to the underlying pathophysiology of this disease. Copyright © 2017 The American

Cocoa, blood pressure, and cardiovascular health.

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Ferri, Claudio; Desideri, Giovambattista; Ferri, Livia; Proietti, Ilenia; Di Agostino, Stefania; Martella, Letizia; Mai, Francesca; Di Giosia, Paolo; Grassi, Davide

2015-11-18

High blood pressure is an important risk factor for cardiovascular disease and cardiovascular events worldwide. Clinical and epidemiological studies suggest that cocoa-rich products reduce the risk of cardiovascular disease. According to this, cocoa has a high content in polyphenols, especially flavanols. Flavanols have been described to exert favorable effects on endothelium-derived vasodilation via the stimulation of nitric oxide-synthase, the increased availability of l-arginine, and the decreased degradation of NO. Cocoa may also have a beneficial effect by protecting against oxidative stress alterations and via decreased platelet aggregation, decreased lipid oxidation, and insulin resistance. These effects are associated with a decrease of blood pressure and a favorable trend toward a reduction in cardiovascular events and strokes. Previous meta-analyses have shown that cocoa-rich foods may reduce blood pressure. Long-term trials investigating the effect of cocoa products are needed to determine whether or not blood pressure is reduced on a chronic basis by daily ingestion of cocoa. Furthermore, long-term trials investigating the effect of cocoa on clinical outcomes are also needed to assess whether cocoa has an effect on cardiovascular events. A 3 mmHg systolic blood pressure reduction has been estimated to decrease the risk of cardiovascular and all-cause mortality. This paper summarizes new findings concerning cocoa effects on blood pressure and cardiovascular health, focusing on putative mechanisms of action and "nutraceutical " viewpoints.

C-reactive protein, APOE genotype and longitudinal cognitive change in an older population

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Lima, Thomas A. S.; Adler, Amanda L.; Minett, Thais; Matthews, Fiona E.; Brayne, Carol; Marioni, Riccardo E.

2014-01-01

Background: circulating measures of inflammatory markers, such as C-reactive protein (CRP) have been associated with an increased risk of future cognitive decline. However, the nature of the relationship among the very old (>75 years) is unclear. Cross-sectional evidence suggests that elevated CRP may even be protective in this age group. This study examines these associations longitudinally. Methods: logistic regression was used to investigate the association between CRP and drop in cognitive performance (≥3 point change on the Mini-Mental State Examination) over a 4-year period in a population of 266 people, mean age 77 years. Results: increased levels of CRP were associated with a decreased risk of a drop in cognitive performance; however, this association was only seen in those without an APOE e4 allele [odds ratio of decline per unit increase in ln(CRP) 0.57, P = 0.04]. The magnitude of the finding remained consistent after adjustment for cardiovascular confounders (smoking, drinking, MI, stroke, diabetes, education, medication and blood pressure). For those with an e4 allele, the relationship with longitudinal cognitive decline was neither statistically significant nor in a consistent direction after controlling for acute inflammation. Conclusions: this study strengthens previous cross-sectional findings and shows elevated levels of CRP to be linked to a decreased risk of longitudinal cognitive decline in the very old. However, as with prior analyses, this was only observed in those not carrying an APOE e4 allele. Future work on larger APOE e4 allele carrying samples is required to determine the nature of the association in this population. PMID:24305621

Cardiovascular Diseases in HIV-infected Subjects (HIV-HEART Study)

Science.gov (United States)

2010-05-07

Detection of Frequency, Severity and Progression of Cardiovascular Diseases in Patients With HIV-infection.; Effect on Cardiovascular Risk and Life Quality by Age, Gender, Classic Cardiovascular Risk Factors,; HIV-specific Cardiovascular Risk Factors, Cardiovascular Medication, Antiretroviral Medication

Delineation of the Marfan phenotype associated with mutations in exons 23-32 of the FBN1 gene

Energy Technology Data Exchange (ETDEWEB)

Putnam, E.A.; Cho, M.; Milewicz, D.M. [Univ. of Texas-Houston Medical School, Houston, TX (United States)] [and others

1996-03-29

Marfan syndrome is a dominantly inherited connective tissue disorder with a wide range of phenotypic severity. The condition is the result of mutations in FBN1, a large gene composed of 65 exons encoding the fibrillin-1 protein. While mutations causing classic manifestations of Marfan syndrome have been identified throughout the FBN1 gene, the six previously characterized mutations resulting in the severe, perinatal lethal form of Marfan syndrome have clustered in exons 24-32 of the gene. We screened 8 patients with either neonatal Marfan syndrome or severe cardiovascular complications of Marfan syndrome for mutations in this region of the gene. Using intron-based exon-specific primers, we amplified exons 23-32 from genomic DNAs, screened these fragments by single-stranded conformational polymorphism analysis, and sequenced indicated exons. This analysis documented mutations in exons 25-27 of the FBN1 mutations in 6 of these patients. These results, taken together with previously published FBN1 mutations in this region, further define the phenotype associated with mutations in exons 24-32 of the FBN1 gene, information important for the development of possible diagnostic tests and genetic counseling. 49 refs., 4 figs., 2 tabs.

Deep Learning for Plant Phenotyping

OpenAIRE

Mori, Matteo

2016-01-01

Plant Phenotyping is an emerging science which provides us the knowledge to better understand plants. Indeed, the study of the link between genetic background and environment in which plants develop can help us to determine cures for plants’ sicknesses and new ways to improve yields using limited resources. In this regard, one of the main aspects of Plant Phenotyping that were studied in the past, was Root Phenotyping, which is based on the study of the root architectures. In particular, toda...

Machine learning in cardiovascular medicine: are we there yet?

Science.gov (United States)

Shameer, Khader; Johnson, Kipp W; Glicksberg, Benjamin S; Dudley, Joel T; Sengupta, Partho P

2018-01-19

Artificial intelligence (AI) broadly refers to analytical algorithms that iteratively learn from data, allowing computers to find hidden insights without being explicitly programmed where to look. These include a family of operations encompassing several terms like machine learning, cognitive learning, deep learning and reinforcement learning-based methods that can be used to integrate and interpret complex biomedical and healthcare data in scenarios where traditional statistical methods may not be able to perform. In this review article, we discuss the basics of machine learning algorithms and what potential data sources exist; evaluate the need for machine learning; and examine the potential limitations and challenges of implementing machine in the context of cardiovascular medicine. The most promising avenues for AI in medicine are the development of automated risk prediction algorithms which can be used to guide clinical care; use of unsupervised learning techniques to more precisely phenotype complex disease; and the implementation of reinforcement learning algorithms to intelligently augment healthcare providers. The utility of a machine learning-based predictive model will depend on factors including data heterogeneity, data depth, data breadth, nature of modelling task, choice of machine learning and feature selection algorithms, and orthogonal evidence. A critical understanding of the strength and limitations of various methods and tasks amenable to machine learning is vital. By leveraging the growing corpus of big data in medicine, we detail pathways by which machine learning may facilitate optimal development of patient-specific models for improving diagnoses, intervention and outcome in cardiovascular medicine. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Integrating phenotype ontologies with PhenomeNET

KAUST Repository

Rodriguez-Garcia, Miguel Angel

2017-12-19

Background Integration and analysis of phenotype data from humans and model organisms is a key challenge in building our understanding of normal biology and pathophysiology. However, the range of phenotypes and anatomical details being captured in clinical and model organism databases presents complex problems when attempting to match classes across species and across phenotypes as diverse as behaviour and neoplasia. We have previously developed PhenomeNET, a system for disease gene prioritization that includes as one of its components an ontology designed to integrate phenotype ontologies. While not applicable to matching arbitrary ontologies, PhenomeNET can be used to identify related phenotypes in different species, including human, mouse, zebrafish, nematode worm, fruit fly, and yeast. Results Here, we apply the PhenomeNET to identify related classes from two phenotype and two disease ontologies using automated reasoning. We demonstrate that we can identify a large number of mappings, some of which require automated reasoning and cannot easily be identified through lexical approaches alone. Combining automated reasoning with lexical matching further improves results in aligning ontologies. Conclusions PhenomeNET can be used to align and integrate phenotype ontologies. The results can be utilized for biomedical analyses in which phenomena observed in model organisms are used to identify causative genes and mutations underlying human disease.

Diet, life-style and cardiovascular morbidity in the rural, free living population of Elafonisos island

Directory of Open Access Journals (Sweden)

Chris J. Kapelios

2017-02-01

Full Text Available Abstract Background There are about 70 small islands in the Aegean and Ionian Sea, of less than 300 Km2 and 5000 inhabitants each, comprising a total population of more than 75,000 individuals with geographical and socioeconomic characteristics of special interest. The objective of the present study was to assess lifestyle characteristics and the state of cardiovascular risk of the population of a small Eastern Mediterranean island, Elafonisos. Methods PERSEAS (Prospective Evaluation of cardiovascular Risk Surrogates in Elafonisos Area Study is an ongoing, population-based, longitudinal survey of cardiovascular risk factors, life-style characteristics and related morbidity/mortality performed in a small and relatively isolated island of the Aegean Sea, named Elafonisos. Validated, closed-ended questionnaires for demographic, socio-economic, clinical and lifestyle characteristics were distributed and analyzed. The MedDietScore, a validated Mediterranean diet score was also calculated. In addition, all participants underwent measurement of anthropometric parameters, blood pressure and a full blood panel for glucose and lipids. Results The analysis included 596 individuals who represented 74.5% of the target population. The mean age of the population was 49.5 ± 19.6 years and 48.2% were males. Fifty participants (8.4% had a history of cardiovascular disease (CVD. The rates of reported diabetes, hypertension, and hypercholesterolemia were 7.7%, 30.9% and 30.9% respectively, with screen-detection of each condition accounting for an additional 4.0%, 12.9%, and 23.3% of cases, respectively. Four hundred and seven individuals (68.3% were overweight or obese, 25% reported being physically inactive and 36.6% were active smokers. The median MedDietScore was 25 [interquartile range: 6, range 12–47] with higher values significantly associated with older age, better education, increased physical activity, absence of history of diabetes and known

Cardiovascular risk in Turner syndrome.

Science.gov (United States)

Donato, Beatriz; Ferreira, Maria João

2018-06-01

Turner syndrome is a relatively common genetic disorder of female development, characterized by partial or complete absence of an X chromosome, with a variable clinical presentation. Congenital or acquired cardiovascular disease is highly prevalent and a major cause of early death in this syndrome. The most feared complication is aortic dissection, which can occur at a very young age and requires careful assessment of its risk factors. A systematic literature search identified sixty relevant publications. These were reviewed with regard to the increased risk of cardiovascular disease in women with Turner syndrome, especially in pregnancy. The most common congenital cardiovascular defects are presented and illustrated with appropriate iconography. The current recommendations regarding the screening and monitoring of cardiovascular disease in these patients are discussed. Copyright © 2018 Sociedade Portuguesa de Cardiologia. Publicado por Elsevier España, S.L.U. All rights reserved.

HIV INFECTION, ANTIRETROVIRAL THERAPY AND CARDIOVASCULAR RISK

Directory of Open Access Journals (Sweden)

Katleen de Gaetano Donati

2010-11-01

Full Text Available In the last 15 years, highly active antiretroviral therapy (HAART has determined a dramatic reduction of both morbidity and mortality in human immunodeficiency virus (HIV-infected subjects, transforming this infection in a chronic and manageable disease. Patients surviving with HIV in the developed world, in larger number men,  are becoming aged. As it would be expected for a population of comparable age, many HIV-infected individuals report a family history of cardiovascular disease, a small proportion have already experienced a cardiovascular event and an increasing proportion has diabetes mellitus. Smoking rate is very high while an increasing proportion of HIV-infected individuals have dyslipidaemia. Studies suggest that these traditional risk factors could play an important  role in the development of cardiovascular disease in these patients as they do in the general population. Thus, whilst the predicted 10-year cardiovascular disease risk remains relatively low at present, it will likely increase in relation to the progressive aging of  this patient population. Thus, the long-term follow-up of HIV infected patients has to include co-morbidity management such as cardiovascular disease prevention and treatment. Two intriguing aspects related to the cardiovascular risk in patients with HIV infection are the matter of current investigation: 1 while these subjects share many cardiovascular risk factors with the general population, HIV infection itself increases cardiovascular risk; 2 some HAART regimens too influence atherosclerotic profile, partly due to lipid changes. Although the mechanisms involved in the development of cardiovascular complications in HIV-infected patients remain to be fully elucidated, treatment guidelines recommending interventions to prevent cardiovascular disease in these individuals are already available; however, their application is still limited.

Cardiovascular hospitalizations and associations with environmental quality

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Cardiovascular disease has been identified as a condition that may be associated with environmental factors. Air pollution in particular has been demonstrated to be associated with cardiovascular disease and atherosclerosis, which can increase the likelihood of cardiovascular eve...

Sexual phenotype differences in zic2 mRNA abundance in the preoptic area of a protogynous teleost, Thalassoma bifasciatum.

Directory of Open Access Journals (Sweden)

Katherine McCaffrey

Full Text Available The highly conserved members of the zic family of zinc-finger transcription factors are primarily known for their roles in embryonic signaling pathways and regulation of cellular proliferation and differentiation. This study describes sexual phenotype differences in abundances of zic2 mRNA in the preoptic area of the hypothalamus, a region strongly implicated in sexual behavior and function, in an adult teleost, Thalassoma bifasciatum. The bluehead wrasse (Thalassoma bifasciatum is a valuable model for studying neuroendocrine processes because it displays two discrete male phenotypes, initial phase (IP males and territorial, terminal phase (TP males, and undergoes socially-controlled protogynous sex change. Previously generated microarray-based comparisons suggested that zic2 was upregulated in the brains of terminal phase males relative to initial phase males. To further explore this difference, we cloned a 727 bp sequence for neural zic2 from field-collected animals. Riboprobe-based in situ hybridization was employed to localize zic2 signal in adult bluehead brains and assess the relative abundance of brain zic2 mRNA across sexual phenotypes. We found zic2 mRNA expression was extremely abundant in the granular cells of the cerebellum and widespread in other brain regions including in the thalamus, hypothalamus, habenula, torus semicircularis, torus longitudinalis, medial longitudinal fascicle and telencephalic areas. Quantitative autoradiography and phosphorimaging showed zic2 mRNA hybridization signal in the preoptic area of the hypothalamus was significantly higher in terminal phase males relative to both initial phase males and females, and silver grain analysis confirmed this relationship between phenotypes. No significant difference in abundance was found in zic2 signal across phenotypes in the habenula, a brain region not implicated in the control of sexual behavior, or cerebellum.

Reactividad cardiovascular y factores de riesgos cardiovasculares en individuos normotensos menores de 40 años

Directory of Open Access Journals (Sweden)

Benet Rodríguez Mikhail

2003-01-01

Full Text Available Fundamento: Se ha observado que la hiperreactividad cardiovascular está asociada a factores de riesgo cardiovasculares en la población general. El objetivo de este trabajo es conocer si estos factores también se asocian en la población de individuos con menos de 40 años, ya que podría ser importante para modificar estilos de vida e intervenir en la prevención de las enfermedades cardiovasculares. Métodos: Se realizó un estudio comparativo representativo con una muestra de 249 individuos normotensos de ambos sexos entre 18 y 40 años de edad. Se formaron dos grupos a partir de los resultados de la prueba del peso sostenido (PPS, basada en la aplicación de un ejercicio isométrico para producir reactividad cardiovascular. Uno de los grupos estuvo formado por sujetos hiperreactivos cardiovasculares (n=62, con valores de presión arterial (TA 90/140 mmHg después de la prueba del peso sostenido, y el otro, estuvo formado por sujetos normorreactivos cardiovasculares (n=187, con valores de TA < 90/140 mmHg. Mediante un modelo de regresión logística se determinó la asociación entre la edad, sexo, historia familiar de hipertensión arterial (HF de HTA, actividad física (AcF, consumo de cigarros (CC, ingestión de bebidas alcohólicas (IBA, consumo de sal (CS y la raza con el estado de hiperreactividad cardiovascular. Resultados: El riesgo de los individuos con historia familiar de hipertensión arterial de tener hiperreactivad cardiovascular fue 2 veces mayor (OR=2,88 IC 95%: 1,54-5,36. Por cada año de edad el riesgo de hiperreactividad aumentó en 1,08 veces y llegó hasta 1,14 veces. Por otro lado, el índice de masa corporal mostró una relación significativa independiente con el estado de hiperreactividad vascular (OR=1,11 IC 95%: 1,01-1,21. El resto de las variables estudiadas no mostraron asociación con el estado de hiperreactividad cardiovascular. Conclusiones: Los individuos normotensos entre 18 y 40 años de edad tienen un

Elucidating the genotype–phenotype map by automatic enumeration and analysis of the phenotypic repertoire

Science.gov (United States)

Lomnitz, Jason G; Savageau, Michael A

2015-01-01

Background: The gap between genotype and phenotype is filled by complex biochemical systems most of which are poorly understood. Because these systems are complex, it is widely appreciated that quantitative understanding can only be achieved with the aid of mathematical models. However, formulating models and measuring or estimating their numerous rate constants and binding constants is daunting. Here we present a strategy for automating difficult aspects of the process. Methods: The strategy, based on a system design space methodology, is applied to a class of 16 designs for a synthetic gene oscillator that includes seven designs previously formulated on the basis of experimentally measured and estimated parameters. Results: Our strategy provides four important innovations by automating: (1) enumeration of the repertoire of qualitatively distinct phenotypes for a system; (2) generation of parameter values for any particular phenotype; (3) simultaneous realization of parameter values for several phenotypes to aid visualization of transitions from one phenotype to another, in critical cases from functional to dysfunctional; and (4) identification of ensembles of phenotypes whose expression can be phased to achieve a specific sequence of functions for rationally engineering synthetic constructs. Our strategy, applied to the 16 designs, reproduced previous results and identified two additional designs capable of sustained oscillations that were previously missed. Conclusions: Starting with a system’s relatively fixed aspects, its architectural features, our method enables automated analysis of nonlinear biochemical systems from a global perspective, without first specifying parameter values. The examples presented demonstrate the efficiency and power of this automated strategy. PMID:26998346

X-ray cardiovascular examination apparatus

International Nuclear Information System (INIS)

1977-01-01

An X-ray source is mounted in an enclosure for angulating longitudinally about a horizontal axis. An X-ray-permeable, patient-supporting table is mounted on the top of the enclosure for executing lateral and longitudinal movements. An X-ray image-receiving device such as an X-ray image intensifier is mounted above the table on a vertically movable arm which is on a longitudinally movable carriage. Electric control means are provided for angulating the X-ray source and image intensifier synchronously as the image intensifier system is shifted longitudinally or vertically such that the central ray from the X-ray source is kept intensifier

Phenex: ontological annotation of phenotypic diversity.

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James P Balhoff

2010-05-01

Full Text Available Phenotypic differences among species have long been systematically itemized and described by biologists in the process of investigating phylogenetic relationships and trait evolution. Traditionally, these descriptions have been expressed in natural language within the context of individual journal publications or monographs. As such, this rich store of phenotype data has been largely unavailable for statistical and computational comparisons across studies or integration with other biological knowledge.Here we describe Phenex, a platform-independent desktop application designed to facilitate efficient and consistent annotation of phenotypic similarities and differences using Entity-Quality syntax, drawing on terms from community ontologies for anatomical entities, phenotypic qualities, and taxonomic names. Phenex can be configured to load only those ontologies pertinent to a taxonomic group of interest. The graphical user interface was optimized for evolutionary biologists accustomed to working with lists of taxa, characters, character states, and character-by-taxon matrices.Annotation of phenotypic data using ontologies and globally unique taxonomic identifiers will allow biologists to integrate phenotypic data from different organisms and studies, leveraging decades of work in systematics and comparative morphology.

Phenex: ontological annotation of phenotypic diversity.

Science.gov (United States)

Balhoff, James P; Dahdul, Wasila M; Kothari, Cartik R; Lapp, Hilmar; Lundberg, John G; Mabee, Paula; Midford, Peter E; Westerfield, Monte; Vision, Todd J

2010-05-05

Phenotypic differences among species have long been systematically itemized and described by biologists in the process of investigating phylogenetic relationships and trait evolution. Traditionally, these descriptions have been expressed in natural language within the context of individual journal publications or monographs. As such, this rich store of phenotype data has been largely unavailable for statistical and computational comparisons across studies or integration with other biological knowledge. Here we describe Phenex, a platform-independent desktop application designed to facilitate efficient and consistent annotation of phenotypic similarities and differences using Entity-Quality syntax, drawing on terms from community ontologies for anatomical entities, phenotypic qualities, and taxonomic names. Phenex can be configured to load only those ontologies pertinent to a taxonomic group of interest. The graphical user interface was optimized for evolutionary biologists accustomed to working with lists of taxa, characters, character states, and character-by-taxon matrices. Annotation of phenotypic data using ontologies and globally unique taxonomic identifiers will allow biologists to integrate phenotypic data from different organisms and studies, leveraging decades of work in systematics and comparative morphology.

Longitudinal course of cortical thickness decline in amyotrophic lateral sclerosis.

Science.gov (United States)

Schuster, Christina; Kasper, Elisabeth; Machts, Judith; Bittner, Daniel; Kaufmann, Jörn; Benecke, Reiner; Teipel, Stefan; Vielhaber, Stefan; Prudlo, Johannes

2014-10-01

To determine longitudinal rates of cortical atrophy in classical Amyotrophic lateral sclerosis (ALS) and ALS variants. Rates of cortical thinning were determined between 2 scans, 3-15 months apart, in 77 ALS patients: 51 classical, 12 upper motor neuron (UMN), and 14 lower motor neuron (LMN) ALS variants. Cortical thickness at the first assessment was compared with 60 healthy controls matched by age and gender. Atrophy rates were compared between patient sub-groups and correlated with disease duration, progression, and severity. Using a cross-sectional analysis, we found a significant difference in cortical thickness between ALS patients and controls in the motor and extra-motor areas (left medial orbito frontal gyrus, left inferior parietal gyrus, bilateral insular cortex, right fusiform gyrus, bilateral precuneus). Using a longitudinal analysis, we found a significant decline of cortical thickness in frontal, temporal, and parietal regions over the course of the study in ALS patients. Effects were independent of the clinical subtype, with exception of the precentral gyrus (p gyrus, the UMN-dominant subjects exhibited intermediate rates of atrophy, and the classical ALS patients exhibited no such change. Atrophy of the precentral gyrus in classical ALS indicates a floor effect at the first assessment, resulting in a lack of further atrophy over time. Structural loss of the precentral gyrus appears to be an early sign of classical ALS. Over time, patterns of cortical thinning in extra-motor areas can be identified in ALS, regardless of the phenotype.

Cardiovascular risk-benefit profile of sibutramine.

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Scheen, A J

2010-01-01

Sibutramine is a combined norepinephrine and serotonin reuptake inhibitor used as an antiobesity agent to reduce appetite and promote weight loss in combination with diet and exercise. At a daily dose of 10-20 mg, it was initially considered to have a good safety profile, as it does not induce primary pulmonary hypertension or adverse effects on cardiac valves, in contrast to previous reports relating to some other antiobesity agents. However, it exerts disparate effects on cardiovascular risk factors. On the one hand, sibutramine may have antiatherogenic activities, as it improves insulin resistance, glucose metabolism, dyslipidemia, and inflammatory markers, with most of these effects resulting from weight loss rather than from an intrinsic effect of the drug. On the other hand, because of its specific mode of action, sibutramine exerts a peripheral sympathomimetic effect, which induces a moderate increase in heart rate and attenuates the reduction in BP attributable to weight loss or even slightly increases BP. It may also prolong the QT interval, an effect that could induce arrhythmias. Because of these complex effects, it is difficult to conclude what the final impact of sibutramine on cardiovascular outcomes might be. Sibutramine has been shown to exert favorable effects on some surrogate cardiovascular endpoints such as reduction of left ventricular hypertrophy and improvement of endothelial dysfunction. A good cardiovascular safety profile was demonstrated in numerous 1- to 2-year controlled trials, in both diabetic and nondiabetic well selected patients, as well as in several observational studies. However, since 2002, several cardiovascular adverse events (hypertension, tachycardia, arrhythmias, and myocardial infarction) have been reported in sibutramine-treated patients. This led to a contraindication of the use of this antiobesity agent in patients with established coronary heart disease, previous stroke, heart failure, or cardiac arrhythmias. SCOUT

Pharmacogenomics in cardiovascular disorders: Steps in approaching personalized medicine in cardiovascular medicine

Directory of Open Access Journals (Sweden)

Christopher Barone

2009-09-01

Full Text Available Christopher Barone, Shaymaa S Mousa, Shaker A MousaThe Pharmaceutical Research Institute, Albany College of Pharmacy and Health Sciences, Albany, NY, USAAbstract: Some of the most commonly prescribed medications are those for cardiovascular maladies. The beneficial effects of these medications have been well documented. However, there can be substantial variation in response to these medications among patients, which may be due to genetic variation. For this reason pharmacogenomic studies are emerging across all aspects of cardiovascular medicine. The goal of pharmacogenomics is to tailor treatment to an individual’s genetic makeup in order to improve the benefit-to-risk ratio. This review examines the potential pharmacogenomic parameters which may lead to a future of personalized medicine. For example, it has been found that patients with CYP2C9 and VKORC1 gene variations have a different response to warfarin. Other studies looking at β-blockers, ACE inhibitors, ARBs, diuretics and statins have shown some results linking genetic variations to pharmacologic response. However these studies have not impacted clinical use yet, unlike warfarin findings, as the small retrospective studies need to be followed up by larger prospective studies for definitive results.Keywords: cardiovascular, pharmacogenomics, genetics, cardiovascular medicine, personalized medicine, polymorphism

[TECOS: confirmation of the cardiovascular safety of sitaliptin].

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Scheen, A J; Paquot, N

2015-10-01

The cardiovascular safety of sitagliptin has been evaluated in TECOS ("Trial Evaluating Cardiovascular Outcomes with Sitagliptin"). TECOS recruited patients with type 2 diabetes and a history of cardiovascular disease who received, as add-on to their usual therapy, either sitagliptin (n = 7.257) or placebo (n = 7.266), with a median follow-up of 3 years. The primary cardiovascular outcome was a composite of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for unstable angina. Sitagliptin was noninferior to placebo for the primary composite cardiovascular outcome (hazard ratio, 0.98; 95% confidence interval, 0.88 to 1.09; P<0.001). Rates of hospitalization for heart failure did not differ between the two groups (hazard ratio, 1.00; 95% CI, 0.83 to 1.20; P=0.98). The cardiovascular safety of sitagliptin, which was already shown in meta-analyses of phase II-III randomised controlled trials and in observational cohort studies in real life, is now confirmed in the landmark prospective cardiovascular outcome study TECOS.

Associations of maternal iron intake and hemoglobin in pregnancy with offspring vascular phenotypes and adiposity at age 10: findings from the Avon Longitudinal Study of Parents and Children.

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Nisreen A Alwan

Full Text Available Iron deficiency is common during pregnancy. Experimental animal studies suggest that it increases cardiovascular risk in the offspring.To examine the relationship between maternal pregnancy dietary and supplement iron intake and hemoglobin, with offspring's arterial stiffness (measured by carotid-radial pulse wave velocity, endothelial function (measured by brachial artery flow mediated dilatation, blood pressure, and adiposity (measured by body mass index, test for mediation by cord ferritin, birth weight, gestational age, and child dietary iron intake, and for effect modification by maternal vitamin C intake and offspring sex.Prospective data from 2958 mothers and children pairs at 10 years of age enrolled in an English birth cohort, the Avon Longitudinal Study for Parents and Children (ALSPAC, was analysed.2639 (89.2% mothers reported dietary iron intake in pregnancy below the UK reference nutrient intake of 14.8 mg/day. 1328 (44.9% reported taking iron supplements, and 129 (4.4% were anemic by 18 weeks gestation. No associations were observed apart from maternal iron intake from supplements with offspring systolic blood pressure (-0.8 mmHg, 99% CI -1.7 to 0, P = 0.01 in the sample with all relevant data observed, and -0.7 mmHg, 99% CI -1.3 to 0, P = 0.008 in the sample with missing data imputed.There was no evidence of association between maternal pregnancy dietary iron intake, or maternal hemoglobin concentration (which is less likely to be biased by subjective reporting with offspring outcomes. There was a modest inverse association between maternal iron supplement intake during pregnancy with offspring systolic blood pressure at 10 years.

Influenza vaccines for preventing cardiovascular disease

OpenAIRE

Clar,Christine; Oseni,Zainab; Flowers,Nadine; Keshtkar-Jahromi,Maryam; Rees,Karen

2015-01-01

ABSTRACTBACKGROUND: This is an update of the original review published in 2008. The risk of adverse cardiovascular outcomes is increased with influenza-like infection, and vaccination against influenza may improve cardiovascular outcomes.OBJECTIVES: To assess the potential benefits of influenza vaccination for primary and secondary prevention of cardiovascular disease.METHODS:Search methods:We searched the following electronic databases on 18 October 2013: The Cochrane Library (including Coch...

Hypertriglyceridemic waist phenotype and nutritional factors: a study with participants of ELSA-Brasil.

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Andrade, Juliana Rodrigues de; Velasquez-Melendez, Gustavo; Barreto, Sandhi Maria; Pereira, Taísa Sabrina Silva; Mill, José Geraldo; Molina, Maria Del Carmen Bisi

2017-01-01

To investigate the association between fat and fiber intakes and the hypertriglyceridemic waist phenotype (HWP). Cross-sectional survey conducted from the baseline of Brazilian Longitudinal Study of Health Adult (ELSA-Brasil). Anthropometric measurements were conducted and the body mass index was calculated (BMI). Participants were classified according to the presence of HWP when waist circumference ≥ 102 and ≥ 88 cm, respectively, in men and women, and triglycerides ≥ 150 mg/dL. Fat and fiber intakes were assessed using a validated food frequency questionnaire, and socioeconomic, demographic and behavioral variables were collected through a questionnaire. The χ² test, Mann-Whitney and Poisson regression were performed with significance level of 5%. There was no association between fiber and fat intakes with HWP. A lower prevalence of HWP among men was observed (IRR = 0.959; 95%CI 0.948 - 0.969). A higher prevalence of HWP was observed in participants with low physical activity (OR = 1.039, 95%CI 1.021 - 1.057), smoking history (OR = 1.044, 95%CI 1.031 - 1.057), lower per capita income (IRR = 1.035; 95%CI 1.022 - 1.049) and obesity (OR = 1.32, 95%CI 1.305 - 1.341). Fat and fiber intakes were not associated with HWP. A higher prevalence of HWP was found in obese, but no association was found between intake of fat and fiber and phenotype.

Modulation of Malaria Phenotypes by Pyruvate Kinase (PKLR Variants in a Thai Population.

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Rebekah van Bruggen

Full Text Available Pyruvate kinase (PKLR is a critical erythrocyte enzyme that is required for glycolysis and production of ATP. We have shown that Pklr deficiency in mice reduces the severity (reduced parasitemia, increased survival of blood stage malaria induced by infection with Plasmodium chabaudi AS. Likewise, studies in human erythrocytes infected ex vivo with P. falciparum show that presence of host PK-deficiency alleles reduces infection phenotypes. We have characterized the genetic diversity of the PKLR gene, including haplotype structure and presence of rare coding variants in two populations from malaria endemic areas of Thailand and Senegal. We investigated the effect of PKLR genotypes on rich longitudinal datasets including haematological and malaria-associated phenotypes. A coding and possibly damaging variant (R41Q was identified in the Thai population with a minor allele frequency of ~4.7%. Arginine 41 (R41 is highly conserved in the pyruvate kinase family and its substitution to Glutamine (R41Q affects protein stability. Heterozygosity for R41Q is shown to be associated with a significant reduction in the number of attacks with Plasmodium falciparum, while correlating with an increased number of Plasmodium vivax infections. These results strongly suggest that PKLR protein variants may affect the frequency, and the intensity of malaria episodes induced by different Plasmodium parasites in humans living in areas of endemic malaria.

Depression, anxiety and major adverse cardiovascular and cerebrovascular events in patients following coronary artery bypass graft surgery: A five year longitudinal cohort study

NARCIS (Netherlands)

P.J. Tully (Phillip); H.R. Winefield (Helen); R.A. Baker (Robert); J. Denollet (Johan); S.S. Pedersen (Susanne); G.A. Wittert (Gary); D.A. Turnbull (Deborah)

2015-01-01

textabstractBackground: Although depression and anxiety have been implicated in risk for major adverse cardiovascular and cerebrovascular events (MACCE), a theoretical approach to identifying such putative links is lacking. The objective of this study was to examine the association between

Depression, anxiety and major adverse cardiovascular and cerebrovascular events in patients following coronary artery bypass graft surgery : A five year longitudinal cohort study

NARCIS (Netherlands)

Tully, P.J.; Winefield, H.R.; Baker, R.A.; Denollet, Johan; Pedersen, S.S.; Wittert, G.A.; Turnbull, D.

2015-01-01

Background Although depression and anxiety have been implicated in risk for major adverse cardiovascular and cerebrovascular events (MACCE), a theoretical approach to identifying such putative links is lacking. The objective of this study was to examine the association between theoretical

The impact of cardiovascular disease prevalence on women's enrollment in landmark randomized cardiovascular trials: a systematic review.

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Tsang, Wendy; Alter, David A; Wijeysundera, Harindra C; Zhang, Tony; Ko, Dennis T

2012-01-01

Many studies have demonstrated that women are substantially underrepresented in cardiovascular trials, but few have considered that women develop cardiovascular disease at older ages than men. The extent to which observed gender enrollment inequalities persist after accounting for age-gender differences in disease prevalence is unknown. The purpose of the study was to compare observed rates of women participating in cardiovascular clinical trials with expected rates of female participation based on age- and gender-specific population disease prevalence. Publications between 1997 and 2009 in the three leading medical journals were included to calculate observed women's enrollment rates. Population-based data in Canada were used to determine the expected enrollment rates of women. Multicenter, randomized cardiovascular clinical trials that enrolled both men and women were analyzed. Two reviewers independently extracted data on women's enrollment and important clinical trial characteristics. The female enrollment rate was 30% in the included 325 trials, which ranged from 27% in trials of coronary artery disease, 27% in heart failure, 31% in arrhythmia, to 45% in primary prevention. Increased female enrollment correlated strongly with increasing age at recruitment in cardiovascular clinical trials (P disease prevalence, gaps in female enrollment were much lower than the expected enrollment rates estimated by 5% in coronary artery disease, 13% in heart failure, 9% in arrhythmia, and 3% in primary prevention. Only cardiovascular trials were evaluated in our study. Female underrepresentation in cardiovascular clinical trials is smaller than conventionally believed after accounting for age- and gender-specific population disease prevalence. Our findings suggest that greater representation of women in cardiovascular clinical trials can be achieved through the recruitment of older populations.

Burden of cardiovascular risk factors and disease among patients with type 1 diabetes: results of the Australian National Diabetes Audit (ANDA).

Science.gov (United States)

Pease, Anthony; Earnest, Arul; Ranasinha, Sanjeeva; Nanayakkara, Natalie; Liew, Danny; Wischer, Natalie; Andrikopoulos, Sofianos; Zoungas, Sophia

2018-06-02

.4, 11.6). Further, the models for CVD demonstrated good discriminatory ability (area under the ROC curve 0.88; 95% CI 0.84, 0.92). Cardiovascular risk factors were prevalent and strongly associated with CVD among adults with type 1 diabetes attending Australian diabetes centres. Given the approximate J-shaped association between type 1 diabetes duration and CVD, the impact of cardiovascular risk stratification and management before and after 20 years duration needs to be further assessed longitudinally. Diabetes specific cardiovascular risk stratification tools incorporating diabetes duration should be an important consideration in future guideline development.

Resting cardiovascular function improvements in adult men ...

African Journals Online (AJOL)

Impaired cardiovascular function increases the risk for fatal and non-fatal cardiovascular disease, renal disease and all-cause mortality. Research has demonstrated an inverse relationship between these cardiovascular impairments and exercise. However, previous research has mainly focused on aerobic training since ...

Phenotype Instance Verification and Evaluation Tool (PIVET): A Scaled Phenotype Evidence Generation Framework Using Web-Based Medical Literature

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Ke, Junyuan; Ho, Joyce C; Ghosh, Joydeep; Wallace, Byron C

2018-01-01

Background Researchers are developing methods to automatically extract clinically relevant and useful patient characteristics from raw healthcare datasets. These characteristics, often capturing essential properties of patients with common medical conditions, are called computational phenotypes. Being generated by automated or semiautomated, data-driven methods, such potential phenotypes need to be validated as clinically meaningful (or not) before they are acceptable for use in decision making. Objective The objective of this study was to present Phenotype Instance Verification and Evaluation Tool (PIVET), a framework that uses co-occurrence analysis on an online corpus of publically available medical journal articles to build clinical relevance evidence sets for user-supplied phenotypes. PIVET adopts a conceptual framework similar to the pioneering prototype tool PheKnow-Cloud that was developed for the phenotype validation task. PIVET completely refactors each part of the PheKnow-Cloud pipeline to deliver vast improvements in speed without sacrificing the quality of the insights PheKnow-Cloud achieved. Methods PIVET leverages indexing in NoSQL databases to efficiently generate evidence sets. Specifically, PIVET uses a succinct representation of the phenotypes that corresponds to the index on the corpus database and an optimized co-occurrence algorithm inspired by the Aho-Corasick algorithm. We compare PIVET’s phenotype representation with PheKnow-Cloud’s by using PheKnow-Cloud’s experimental setup. In PIVET’s framework, we also introduce a statistical model trained on domain expert–verified phenotypes to automatically classify phenotypes as clinically relevant or not. Additionally, we show how the classification model can be used to examine user-supplied phenotypes in an online, rather than batch, manner. Results PIVET maintains the discriminative power of PheKnow-Cloud in terms of identifying clinically relevant phenotypes for the same corpus with

Contracepção hormonal e sistema cardiovascular Contracepción hormonal y sistema cardiovascular Hormonal contraception and cardiovascular system

Directory of Open Access Journals (Sweden)

Milena Bastos Brito

2011-04-01

Full Text Available A contracepção hormonal é o método mais utilizado para prevenção de gestações não planejadas. A literatura tem demonstrado associação entre risco cardiovascular e uso de hormonioterapia. A fim de melhorar a orientação contraceptiva para mulheres com fatores de risco para doença cardiovascular, realizamos uma revisão da literatura em relação ao assunto. Esta revisão descreve os dados mais recentes da literatura científica acerca da influência dos contraceptivos hormonais em relação a trombose venosa, arterial e hipertensão arterial sistêmica, doenças cada dia mais prevalentes na população feminina jovem.La contracepción hormonal es el método más utilizado para la prevención de los embarazos no planificados. La literatura ha venido demostrando la asociación que existe entre el riesgo cardiovascular y el uso de la hormonoterapia. Con el objetivo de mejorar la orientación en la contracepción en mujeres con factores de riesgo para el desarrollo de enfermedad cardiovascular, realizamos una revisión de la literatura con relación a ese asunto. Esa revisión describe los datos más recientes de la literatura científica acerca de la influencia de los anticonceptivos hormonales con relación a la trombosis venosa, arterial e hipertensión arterial sistémica, enfermedades cada día más prevalentes en la población femenina joven.Hormonal contraception is the most widely used method to prevent unplanned pregnancies. The literature has shown an association between cardiovascular risk and use of hormone therapy. With the purpose of providing better guidelines on contraception methods for women with risk factors for cardiovascular disease, we have reviewed the literature on the subject. This review describes the latest data from the scientific literature concerning the influence of hormonal contraceptives on arterial thrombosis, venous thrombosis and systemic high blood pressure, which are diseases that have become

Natural Selection on Genes Related to Cardiovascular Health in High-Altitude Adapted Andeans.

Science.gov (United States)

Crawford, Jacob E; Amaru, Ricardo; Song, Jihyun; Julian, Colleen G; Racimo, Fernando; Cheng, Jade Yu; Guo, Xiuqing; Yao, Jie; Ambale-Venkatesh, Bharath; Lima, João A; Rotter, Jerome I; Stehlik, Josef; Moore, Lorna G; Prchal, Josef T; Nielsen, Rasmus

2017-11-02

The increase in red blood cell mass (polycythemia) due to the reduced oxygen availability (hypoxia) of residence at high altitude or other conditions is generally thought to be beneficial in terms of increasing tissue oxygen supply. However, the extreme polycythemia and accompanying increased mortality due to heart failure in chronic mountain sickness most likely reduces fitness. Tibetan highlanders have adapted to high altitude, possibly in part via the selection of genetic variants associated with reduced polycythemic response to hypoxia. In contrast, high-altitude-adapted Quechua- and Aymara-speaking inhabitants of the Andean Altiplano are not protected from high-altitude polycythemia in the same way, yet they exhibit other adaptive features for which the genetic underpinnings remain obscure. Here, we used whole-genome sequencing to scan high-altitude Andeans for signals of selection. The genes showing the strongest evidence of selection-including BRINP3, NOS2, and TBX5-are associated with cardiovascular development and function but are not in the response-to-hypoxia pathway. Using association mapping, we demonstrated that the haplotypes under selection are associated with phenotypic variations related to cardiovascular health. We hypothesize that selection in response to hypoxia in Andeans could have vascular effects and could serve to mitigate the deleterious effects of polycythemia rather than reduce polycythemia itself. Copyright © 2017. Published by Elsevier Inc.

Symptoms of anxiety and depression are related to cardiovascular responses to active, but not passive, coping tasks

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Kornanong Yuenyongchaiwat

Full Text Available Objective: Anxiety and depression have been linked to blunted blood pressure (BP and heart rate (HR reactions to mental stress tests; however, most studies have not included indices of underlying hemodynamics nor multiple stress tasks. This study sought to examine the relationships of anxiety and depression with hemodynamic responses to acute active and passive coping tasks. Methods: A total of 104 participants completed the Hospital Anxiety and Depression Scales and mental arithmetic, speech, and cold pressor tasks while BP, HR, total peripheral resistance, and cardiac output (CO were assessed. Results: After adjustment for traditional risk factors and baseline cardiovascular activity, depression scores were negatively associated with systolic BP, HR, and CO responses to the mental arithmetic task, while anxiety scores were inversely related to the systolic BP response to mental arithmetic. Conclusion: High anxiety or depression scores appear to be associated with blunted cardiac reactions to mental arithmetic (an active coping task, but not to the cold pressor test or speech tasks. Future research should further examine potential mechanisms and longitudinal pathways relating depression and anxiety to cardiovascular reactivity. Clinical trial registration number: TCTR20160208004

Cattle phenotypes can disguise their maternal ancestry.

Science.gov (United States)

Srirattana, Kanokwan; McCosker, Kieren; Schatz, Tim; St John, Justin C

2017-06-26

Cattle are bred for, amongst other factors, specific traits, including parasite resistance and adaptation to climate. However, the influence and inheritance of mitochondrial DNA (mtDNA) are not usually considered in breeding programmes. In this study, we analysed the mtDNA profiles of cattle from Victoria (VIC), southern Australia, which is a temperate climate, and the Northern Territory (NT), the northern part of Australia, which has a tropical climate, to determine if the mtDNA profiles of these cattle are indicative of breed and phenotype, and whether these profiles are appropriate for their environments. A phylogenetic tree of the full mtDNA sequences of different breeds of cattle, which were obtained from the NCBI database, showed that the mtDNA profiles of cattle do not always reflect their phenotype as some cattle with Bos taurus phenotypes had Bos indicus mtDNA, whilst some cattle with Bos indicus phenotypes had Bos taurus mtDNA. Using D-loop sequencing, we were able to contrast the phenotypes and mtDNA profiles from different species of cattle from the 2 distinct cattle breeding regions of Australia. We found that 67 of the 121 cattle with Bos indicus phenotypes from NT (55.4%) had Bos taurus mtDNA. In VIC, 92 of the 225 cattle with Bos taurus phenotypes (40.9%) possessed Bos indicus mtDNA. When focusing on oocytes from cattle with the Bos taurus phenotype in VIC, their respective oocytes with Bos indicus mtDNA had significantly lower levels of mtDNA copy number compared with oocytes possessing Bos taurus mtDNA (P cattle with a Bos taurus phenotype. The phenotype of cattle is not always related to their mtDNA profiles. MtDNA profiles should be considered for breeding programmes as they also influence phenotypic traits and reproductive capacity in terms of oocyte quality.

Spice: discovery of phenotype-determining component interplays

Directory of Open Access Journals (Sweden)

Chen Zhengzhang

2012-05-01

Full Text Available Abstract Background A latent behavior of a biological cell is complex. Deriving the underlying simplicity, or the fundamental rules governing this behavior has been the Holy Grail of systems biology. Data-driven prediction of the system components and their component interplays that are responsible for the target system’s phenotype is a key and challenging step in this endeavor. Results The proposed approach, which we call System Phenotype-related Interplaying Components Enumerator (Spice, iteratively enumerates statistically significant system components that are hypothesized (1 to play an important role in defining the specificity of the target system’s phenotype(s; (2 to exhibit a functionally coherent behavior, namely, act in a coordinated manner to perform the phenotype-specific function; and (3 to improve the predictive skill of the system’s phenotype(s when used collectively in the ensemble of predictive models. Spice can be applied to both instance-based data and network-based data. When validated, Spice effectively identified system components related to three target phenotypes: biohydrogen production, motility, and cancer. Manual results curation agreed with the known phenotype-related system components reported in literature. Additionally, using the identified system components as discriminatory features improved the prediction accuracy by 10% on the phenotype-classification task when compared to a number of state-of-the-art methods applied to eight benchmark microarray data sets. Conclusion We formulate a problem—enumeration of phenotype-determining system component interplays—and propose an effective methodology (Spice to address this problem. Spice improved identification of cancer-related groups of genes from various microarray data sets and detected groups of genes associated with microbial biohydrogen production and motility, many of which were reported in literature. Spice also improved the predictive skill of the

Vitamin D, cardiovascular disease and risk factors

DEFF Research Database (Denmark)

Skaaby, Tea; Thuesen, Betina H.; Linneberg, Allan

2017-01-01

of vitamin D effects from a cardiovascular health perspective. It focuses on vitamin D in relation to cardiovascular disease, i.e. ischemic heart disease, and stroke; the traditional cardiovascular risk factors hypertension, abnormal blood lipids, obesity; and the emerging risk factors hyperparathyroidism......, microalbuminuria, chronic obstructive pulmonary diseases, and non-alcoholic fatty liver disease. Meta-analyses of observational studies have largely found vitamin D levels to be inversely associated with cardiovascular risk and disease. However, Mendelian randomization studies and randomized, controlled trials...... (RCTs) have not been able to consistently replicate the observational findings. Several RCTs are ongoing, and the results from these are needed to clarify whether vitamin D deficiency is a causal and reversible factor to prevent cardiovascular disease....

Racism and cardiovascular disease: implications for nursing.

Science.gov (United States)

Jackson, Jennifer; McGibbon, Elizabeth; Waldron, Ingrid

2013-01-01

The social determinants of health (SDH) are recognized as a prominent influence on health outcomes across the lifespan. Racism is identified as a key SDH. In this article, the authors describe the concept of racism as an SDH, its impact in discriminatory actions and inactions, and the implications for cardiovascular nurses. Although research in Canada on the links among racism, stress, and cardiovascular disease is limited, there is growing evidence about the stress of racism and its long-term impact on cardiovascular health. The authors discuss how cardiovascular nursing could be enhanced through an understanding of racism-related stress, and race-based differences in cardiovascular care. The authors conclude with strategies for action to address this nursing concern.

Educational differences in cardiovascular mortality

DEFF Research Database (Denmark)

Kjøllesdal, M. K. R.; Ariansen, I.; Mortensen, L. H.

2016-01-01

Aims: To explore the confounding effects of early family factors shared by siblings and cardiovascular risk factors in midlife on the educational differences in mortality from cardiovascular disease (CVD). Methods: Data from national and regional health surveys in Norway (1974–2003) were linked...

Post-traumatic stress disorder and cardiovascular disease.

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Edmondson, Donald; von Känel, Roland

2017-04-01

In this paper, a first in a Series of two, we look at the evidence for an association of post-traumatic stress disorder with incident cardiovascular disease risk and the mechanisms that might cause this association, as well as the prevalence of post-traumatic stress disorder due to cardiovascular disease events and its associated prognostic risk. We discuss research done after the publication of previous relevant systematic reviews, and survey currently funded research from the two most active funders in the field: the National Institutes of Health and the US Veterans Administration. We conclude that post-traumatic stress disorder is a risk factor for incident cardiovascular disease, and a common psychiatric consequence of cardiovascular disease events that might worsen the prognosis of the cardiovascular disease. There are many candidate mechanisms for the link between post-traumatic stress disorder and cardiovascular disease, and several ongoing studies could soon point to the most important behavioural and physiological mechanisms to target in early phase intervention development. Similarly, targets are emerging for individual and environmental interventions that might offset the risk of post-traumatic stress disorder after cardiovascular disease events. Copyright © 2017 Elsevier Ltd. All rights reserved.

PPARs and the Cardiovascular System

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Hamblin, Milton; Chang, Lin; Fan, Yanbo; Zhang, Jifeng

2009-01-01

Abstract Peroxisome proliferator-activated receptors (PPARs) belong to the nuclear hormone-receptor superfamily. Originally cloned in 1990, PPARs were found to be mediators of pharmacologic agents that induce hepatocyte peroxisome proliferation. PPARs also are expressed in cells of the cardiovascular system. PPARγ appears to be highly expressed during atherosclerotic lesion formation, suggesting that increased PPARγ expression may be a vascular compensatory response. Also, ligand-activated PPARγ decreases the inflammatory response in cardiovascular cells, particularly in endothelial cells. PPARα, similar to PPARγ, also has pleiotropic effects in the cardiovascular system, including antiinflammatory and antiatherosclerotic properties. PPARα activation inhibits vascular smooth muscle proinflammatory responses, attenuating the development of atherosclerosis. However, PPARδ overexpression may lead to elevated macrophage inflammation and atherosclerosis. Conversely, PPARδ ligands are shown to attenuate the pathogenesis of atherosclerosis by improving endothelial cell proliferation and survival while decreasing endothelial cell inflammation and vascular smooth muscle cell proliferation. Furthermore, the administration of PPAR ligands in the form of TZDs and fibrates has been disappointing in terms of markedly reducing cardiovascular events in the clinical setting. Therefore, a better understanding of PPAR-dependent and -independent signaling will provide the foundation for future research on the role of PPARs in human cardiovascular biology. Antioxid. Redox Signal. 11, 1415–1452. PMID:19061437

Cardiovascular Safety Pharmacology of Sibutramine.

Science.gov (United States)

Yun, Jaesuk; Chung, Eunyong; Choi, Ki Hwan; Cho, Dae Hyun; Song, Yun Jeong; Han, Kyoung Moon; Cha, Hey Jin; Shin, Ji Soon; Seong, Won-Keun; Kim, Young-Hoon; Kim, Hyung Soo

2015-07-01

Sibutramine is an anorectic that has been banned since 2010 due to cardiovascular safety issues. However, counterfeit drugs or slimming products that include sibutramine are still available in the market. It has been reported that illegal sibutramine-contained pharmaceutical products induce cardiovascular crisis. However, the mechanism underlying sibutramine-induced cardiovascular adverse effect has not been fully evaluated yet. In this study, we performed cardiovascular safety pharmacology studies of sibutramine systemically using by hERG channel inhibition, action potential duration, and telemetry assays. Sibutramine inhibited hERG channel current of HEK293 cells with an IC50 of 3.92 μM in patch clamp assay and increased the heart rate and blood pressure (76 Δbpm in heart rate and 51 ΔmmHg in blood pressure) in beagle dogs at a dose of 30 mg/kg (per oral), while it shortened action potential duration (at 10 μM and 30 μM, resulted in 15% and 29% decreases in APD50, and 9% and 17% decreases in APD90, respectively) in the Purkinje fibers of rabbits and had no effects on the QTc interval in beagle dogs. These results suggest that sibutramine has a considerable adverse effect on the cardiovascular system and may contribute to accurate drug safety regulation.

Cardiovascular Risk in Primary Hyperaldosteronism.

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Prejbisz, A; Warchoł-Celińska, E; Lenders, J W M; Januszewicz, A

2015-12-01

After the first cases of primary aldosteronism were described and characterized by Conn, a substantial body of experimental and clinical evidence about the long-term effects of excess aldosterone on the cardiovascular system was gathered over the last 5 decades. The prevalence of primary aldosteronism varies considerably between different studies among hypertensive patients, depending on patient selection, the used diagnostic methods, and the severity of hypertension. Prevalence rates vary from 4.6 to 16.6% in those studies in which confirmatory tests to diagnose primary aldosteronism were used. There is also growing evidence indicating that prolonged exposure to elevated aldosterone concentrations is associated with target organ damage in the heart, kidney, and arterial wall, and high cardiovascular risk in patients with primary aldosteronism. Therefore, the aim of treatment should not be confined to BP normalization and hypokalemia correction, but rather should focus on restoring the deleterious effects of excess aldosterone on the cardiovascular system. Current evidence convincingly demonstrates that both surgical and medical treatment strategies beneficially affect cardiovascular outcomes and mortality in the long term. Further studies can be expected to provide better insight into the relationship between cardiovascular risk and complications and the genetic background of primary aldosteronism. © Georg Thieme Verlag KG Stuttgart · New York.

Ideal cardiovascular health and risk of cardiovascular events in the EPIC-Norfolk prospective population study

NARCIS (Netherlands)

Lachman, Sangeeta; Peters, Ron Jg; Lentjes, Marleen Ah; Mulligan, Angela A.; Luben, Robert N.; Wareham, Nicholas J.; Khaw, Kay-Tee; Boekholdt, S. Matthijs

2016-01-01

The American Heart Association has prioritised seven cardiovascular health metrics to reduce the cardiovascular burden, including: body mass index, healthy diet, physical activity, smoking status, blood pressure, glycated haemoglobin A1c and total cholesterol. The aim of the current study was to

Cardiac phenotyping in ex vivo murine embryos using microMRI.

Science.gov (United States)

Cleary, Jon O; Price, Anthony N; Thomas, David L; Scambler, Peter J; Kyriakopoulou, Vanessa; McCue, Karen; Schneider, Jürgen E; Ordidge, Roger J; Lythgoe, Mark F

2009-10-01

Microscopic MRI (microMRI) is an emerging technique for high-throughput phenotyping of transgenic mouse embryos, and is capable of visualising abnormalities in cardiac development. To identify cardiac defects in embryos, we have optimised embryo preparation and MR acquisition parameters to maximise image quality and assess the phenotypic changes in chromodomain helicase DNA-binding protein 7 (Chd7) transgenic mice. microMRI methods rely on tissue penetration with a gadolinium chelate contrast agent to reduce tissue T(1), thus improving signal-to-noise ratio (SNR) in rapid gradient echo sequences. We investigated 15.5 days post coitum (dpc) wild-type CD-1 embryos fixed in gadolinium-diethylene triamine pentaacetic acid (Gd-DTPA) solutions for either 3 days (2 and 4 mM) or 2 weeks (2, 4, 8 and 16 mM). To assess penetration of the contrast agent into heart tissue and enable image contrast simulations, T(1) and T(*) (2) were measured in heart and background agarose. Compared to 3-day, 2-week fixation showed reduced mean T(1) in the heart at both 2 and 4 mM concentrations (p < 0.0001), resulting in calculated signal gains of 23% (2 mM) and 29% (4 mM). Using T(1) and T(*) (2) values from 2-week concentrations, computer simulation of heart and background signal, and ex vivo 3D gradient echo imaging, we demonstrated that 2-week fixed embryos in 8 mM Gd-DTPA in combination with optimised parameters (TE/TR/alpha/number of averages: 9 ms/20 ms/60 degrees /7) produced the largest SNR in the heart (23.2 +/- 1.0) and heart chamber contrast-to-noise ratio (CNR) (27.1 +/- 1.6). These optimised parameters were then applied to an MRI screen of embryos heterozygous for the gene Chd7, implicated in coloboma of the eye, heart defects, atresia of the choanae, retardation of growth, genital/urinary abnormalities, ear abnormalities and deafness (CHARGE) syndrome (a condition partly characterised by cardiovascular birth defects in humans). A ventricular septal defect was readily identified

Association between voluntary/involuntary job loss and the development of stroke or cardiovascular disease: a prospective study of middle-aged to older workers in a rapidly developing Asian country.

Directory of Open Access Journals (Sweden)

Mo-Yeol Kang

Full Text Available The aim of this research was to investigate the association between job loss and the development of stroke or cardiovascular disease among middle-aged to older individuals in Korea. We also examined how this relationship was modified by gender and the nature of the job loss.This study used samples from the first- to fourth-wave datasets from the Korean Longitudinal Study of Aging (KLoSA, which were collected in 2006, 2008, 2010, and 2012. The study collected data from a total of 10,254 subjects aged ≥ 45 years at baseline. After applying exclusion criteria, the final sample size for analysis consisted of 4,000 individuals. Information about employment status, development of stroke or cardiovascular disease, and covariates (age, income level, and behavioral factors was obtained. Cox proportional hazards models were used to evaluate the association between voluntary/involuntary job loss and the development of stroke or cardiovascular disease. We performed these analyses separately according to disease, gender, and the nature of the job loss.Involuntary job loss significantly increased the risk of stroke or cardiovascular disease among males (adjusted hazard ratio [HR]  = 3.560, 95% confidence interval [CI]  = 2.055-6.168. Voluntary retirement also increased the risk of cardiovascular disease or stroke among males (adjusted HR = 2.879, 95% CI = 1.533-5.409. Job loss was more closely associated with stroke than with cardiovascular disease (stroke, adjusted HR = 6.208, 95% CI = 2.417-15.943; cardiovascular disease, adjusted HR = 2.768, 95% CI = 1.402-5.465.Our findings suggest that both voluntary retirement and involuntary job loss increase the risk for stroke or cardiovascular disease in middle-aged to older individuals, especially males.

A Comparison of the Hormonal Profile of Early Androgenetic Alopecia in Men With the Phenotypic Equivalent of Polycystic Ovarian Syndrome in Women.

Science.gov (United States)

Sanke, Sarita; Chander, Ram; Jain, Anju; Garg, Taru; Yadav, Pravesh

2016-09-01

Early androgenetic alopecia (AGA) is patterned hair loss occurring before age 30 years. Early AGA in men is frequently reported as the phenotypic equivalent of polycystic ovarian syndrome (PCOS) in women, which carries the risk of developing obesity, metabolic syndrome, and cardiovascular diseases. Very few studies have been conducted to evaluate this. To study the hormonal profile of men with early AGA and to evaluate if early AGA in men can be considered as the phenotypic equivalent of PCOS, the associated risks of which are well known. This case-control study was conducted from January 1, 2014, to March 31, 2015, in a tertiary care government hospital. Fifty-seven men aged 19 to 30 years presenting with patterned hair loss were recruited as study participants. Thirty-two age-matched men with no evidence of hair loss were recruited as controls. Men who had any established endocrine disorder, diabetes mellitus, or cardiovascular disease and those who took any oral medication or hormonal treatment for hair loss were excluded from the study. The serum concentrations of total testosterone, sex hormone-binding globulin (SHBG), dehydroepiandrosterone sulfate (DHEAS), luteinizing hormone (LH), follicle-stimulating hormone (FSH), prolactin, fasting plasma glucose, and insulin levels were measured. Insulin resistance (IR) and free androgen index (FAI) were calculated and compared with age- and sex-matched controls. The primary outcome was to measure the clinico-endocrinological profiles (LH, FSH, SHBG, DHEAS, and testosterone levels) of men with early AGA and to compare it with the PCOS profile; the secondary outcome was to establish a relationship between this endocrinological profile and IR. Compared with the 32 controls, the 57 participants with AGA showed significantly increased mean (SD) levels of testosterone (24.61 [7.97] vs 20.57 [4.9] nmol/L; P = .04), DHEAS (3.63 [2.19] vs 2.64 [1.49] µg/mL; P = .02), LH (7.78 [3.19] vs 4.56 [2.01] mIU/mL; P PCOS. The

Plant phenomics and the need for physiological phenotyping across scales to narrow the genotype-to-phenotype knowledge gap

Czech Academy of Sciences Publication Activity Database

Grosskinsky, D. K.; Svensgaard, J.; Christensen, S.; Roitsch, Thomas

2015-01-01

Roč. 66, č. 18 (2015), s. 5429-5440 ISSN 0022-0957 Institutional support: RVO:67179843 Keywords : External phenotype * genome–environment–management interaction * genome–phenome map * internal phenotype * phenomics * physiological traits * physiology * plant phenotyping * predictors Subject RIV: EH - Ecology, Behaviour Impact factor: 5.677, year: 2015

Nordic research infrastructures for plant phenotyping

Directory of Open Access Journals (Sweden)

Kristiina Himanen

2018-03-01

Full Text Available Plant phenomics refers to the systematic study of plant phenotypes. Together with closely monitored, controlled climates, it provides an essential component for the integrated analysis of genotype-phenotype-environment interactions. Currently, several plant growth and phenotyping facilities are under establishment globally, and numerous facilities are already in use. Alongside the development of the research infrastructures, several national and international networks have been established to support shared use of the new methodology. In this review, an overview is given of the Nordic plant phenotyping and climate control facilities. Since many areas of phenomics such as sensor-based phenotyping, image analysis and data standards are still developing, promotion of educational and networking activities is especially important. These facilities and networks will be instrumental in tackling plant breeding and plant protection challenges. They will also provide possibilities to study wild species and their ecological interactions under changing Nordic climate conditions.

Intermittent hypoxia, cardiovascular disease and obstructive sleep apnoea.

Science.gov (United States)

Turnbull, Chris D

2018-01-01

Obstructive sleep apnoea (OSA) is a common disorder and is associated with cardiovascular disease. Continuous positive airway pressure (CPAP), whilst reducing blood pressure, has not been shown to reduce cardiovascular events when used as a treatment solely for this purpose in patients with previous cardiovascular disease. Developing a better understanding of the mechanisms underlying cardiovascular disease in OSA is important to develop new treatments. Potential causative mechanisms for cardiovascular disease in OSA include arousal induced sympathetic activation, large intrathoracic pressure swings leading to shear stress on the heart and great vessels, and intermittent hypoxia (IH). This review discusses the role of IH, as a major physiological consequence of OSA, in the development of cardiovascular disease.

Cheese and cardiovascular disease risk

DEFF Research Database (Denmark)

Hjerpsted, Julie Bousgaard; Tholstrup, Tine

2016-01-01

Abstract Currently, the effect of dairy products on cardiovascular risk is a topic with much debate and conflicting results. The purpose of this review is to give an overview of the existing literature regarding the effect of cheese intake and risk of cardiovascular disease (CVD). Studies included...