WorldWideScience

Sample records for human mendelian hypertension

  1. Molecular-Based Mechanisms of Mendelian Forms of Salt-Dependent Hypertension Questioning the Prevailing Theory

    Czech Academy of Sciences Publication Activity Database

    Kurtz, T. W.; Dominiczak, A. F.; DiCarlo, S. E.; Pravenec, Michal; Morris Jr., R. C.

    2015-01-01

    Roč. 65, č. 5 (2015), s. 932-941 ISSN 0194-911X R&D Projects: GA ČR(CZ) GAP301/12/0696 Institutional support: RVO:67985823 Keywords : Mendelian * salt sensitive hypertension * vasodysfunction Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 6.350, year: 2015

  2. Dairy consumption, systolic blood pressure, and risk of hypertension: Mendelian randomization study

    Science.gov (United States)

    This study examined whether previous observed inverse associations of dairy intake with systolic blood pressure and risk of hypertension were causal. A Mendelian randomization study was employed, using the single nucleotide polymorphism rs4988235 related to lactase persistence as an instrumental var...

  3. Vitamin D and risk of pregnancy related hypertensive disorders: mendelian randomisation study.

    Science.gov (United States)

    Magnus, Maria C; Miliku, Kozeta; Bauer, Anna; Engel, Stephanie M; Felix, Janine F; Jaddoe, Vincent W V; Lawlor, Debbie A; London, Stephanie J; Magnus, Per; McGinnis, Ralph; Nystad, Wenche; Page, Christian M; Rivadeneira, Fernando; Stene, Lars C; Tapia, German; Williams, Nicholas; Bonilla, Carolina; Fraser, Abigail

    2018-06-20

    To use mendelian randomisation to investigate whether 25-hydroxyvitamin D concentration has a causal effect on gestational hypertension or pre-eclampsia. One and two sample mendelian randomisation analyses. Two European pregnancy cohorts (Avon Longitudinal Study of Parents and Children, and Generation R Study), and two case-control studies (subgroup nested within the Norwegian Mother and Child Cohort Study, and the UK Genetics of Pre-eclampsia Study). 7389 women in a one sample mendelian randomisation analysis (751 with gestational hypertension and 135 with pre-eclampsia), and 3388 pre-eclampsia cases and 6059 controls in a two sample mendelian randomisation analysis. Single nucleotide polymorphisms in genes associated with vitamin D synthesis (rs10741657 and rs12785878) and metabolism (rs6013897 and rs2282679) were used as instrumental variables. Gestational hypertension and pre-eclampsia defined according to the International Society for the Study of Hypertension in Pregnancy. In the conventional multivariable analysis, the relative risk for pre-eclampsia was 1.03 (95% confidence interval 1.00 to 1.07) per 10% decrease in 25-hydroxyvitamin D level, and 2.04 (1.02 to 4.07) for 25-hydroxyvitamin D levels effect of 25-hydroxyvitamin D on the risk of gestational hypertension or pre-eclampsia: odds ratio 0.90 (95% confidence interval 0.78 to 1.03) and 1.19 (0.92 to 1.52) per 10% decrease, respectively. The two sample mendelian randomisation estimate gave an odds ratio for pre-eclampsia of 0.98 (0.89 to 1.07) per 10% decrease in 25-hydroxyvitamin D level, an odds ratio of 0.96 (0.80 to 1.15) per unit increase in the log(odds) of 25-hydroxyvitamin D level effect of vitamin D status on gestational hypertension or pre-eclampsia. Future mendelian randomisation studies with a larger number of women with pre-eclampsia or more genetic instruments that would increase the proportion of 25-hydroxyvitamin D levels explained by the instrument are needed. Published by the BMJ

  4. Human Mendelian pain disorders: a key to discovery and validation of novel analgesics.

    Science.gov (United States)

    Goldberg, Y P; Pimstone, S N; Namdari, R; Price, N; Cohen, C; Sherrington, R P; Hayden, M R

    2012-10-01

    We have utilized a novel application of human genetics, illuminating the important role that rare genetic disorders can play in the development of novel drugs that may be of relevance for the treatment of both rare and common diseases. By studying a very rare Mendelian disorder of absent pain perception, congenital indifference to pain, we have defined Nav1.7 (endocded by SCN9A) as a critical and novel target for analgesic development. Strong human validation has emerged with SCN9A gain-of-function mutations causing inherited erythromelalgia (IEM) and paroxysmal extreme pain disorder, both Mendelian disorder of spontaneous or easily evoked pain. Furthermore, variations in the Nav1.7 channel also modulate pain perception in healthy subjects as well as in painful conditions such as osteoarthritis and Parkinson disease. On the basis of this, we have developed a novel compound (XEN402) that exhibits potent, voltage-dependent block of Nav1.7. In a small pilot study, we showed that XEN402 blocks Nav1.7 mediated pain associated with IEM thereby demonstrating the use of rare genetic disorders with mutant target channels as a novel approach to rapid proof-of-concept. Our approach underscores the critical role that human genetics can play by illuminating novel and critical pathways pertinent for drug discovery. © 2012 John Wiley & Sons A/S.

  5. Online Mendelian Inheritance in Man (OMIM), a knowledgebase of human genes and genetic disorders.

    Science.gov (United States)

    Hamosh, Ada; Scott, Alan F; Amberger, Joanna S; Bocchini, Carol A; McKusick, Victor A

    2005-01-01

    Online Mendelian Inheritance in Man (OMIM) is a comprehensive, authoritative and timely knowledgebase of human genes and genetic disorders compiled to support human genetics research and education and the practice of clinical genetics. Started by Dr Victor A. McKusick as the definitive reference Mendelian Inheritance in Man, OMIM (http://www.ncbi.nlm.nih.gov/omim/) is now distributed electronically by the National Center for Biotechnology Information, where it is integrated with the Entrez suite of databases. Derived from the biomedical literature, OMIM is written and edited at Johns Hopkins University with input from scientists and physicians around the world. Each OMIM entry has a full-text summary of a genetically determined phenotype and/or gene and has numerous links to other genetic databases such as DNA and protein sequence, PubMed references, general and locus-specific mutation databases, HUGO nomenclature, MapViewer, GeneTests, patient support groups and many others. OMIM is an easy and straightforward portal to the burgeoning information in human genetics.

  6. Mendelian analysis of a metastasis-prone substrain of BALB/c nude mice using a subcutaneously inoculated human tumour

    DEFF Research Database (Denmark)

    Schou, M; Brünner, N; Spang-Thomsen, M

    2006-01-01

    Most nude mice do not allow the formation of metastases after heterotransplantation of human malignant tumours. Here we describe a substrain of BALB/c nude mice (BALB/c/AnNCr) that reproducibly allows some human cancers to metastasize. By Mendelian analysis of hybrids between this substrain and C57...

  7. Taste and hypertension in humans

    DEFF Research Database (Denmark)

    Roura, Eugeni; Foster, Simon; Winklebach, Anja

    2016-01-01

    The association between salty taste and NaCl intake with hypertension is well-established, although it is far from completely understood. Other taste types such as sweet, umami or bitter have also been related to alterations in blood pressure. Here, we review the mutual relationship between taste...... and hypertension to identify potential avenues to better control blood pressure. This review focuses on published data involving humans, with the exception of a section on molecular mechanisms. There is compelling evidence to suggest that changes in salty taste sensitivity can be used to predict the onset...... of hypertension. This goes hand in hand with the medical concept of sodium sensitivity, which also increases with age, particularly in hypertensive patients. The association of hypertension with the loss of taste acuity less definitive with some data/conclusions masked by the use of anti-hypertensive drugs...

  8. OMIM.org: Online Mendelian Inheritance in Man (OMIM®), an online catalog of human genes and genetic disorders.

    Science.gov (United States)

    Amberger, Joanna S; Bocchini, Carol A; Schiettecatte, François; Scott, Alan F; Hamosh, Ada

    2015-01-01

    Online Mendelian Inheritance in Man, OMIM(®), is a comprehensive, authoritative and timely research resource of curated descriptions of human genes and phenotypes and the relationships between them. The new official website for OMIM, OMIM.org (http://omim.org), was launched in January 2011. OMIM is based on the published peer-reviewed biomedical literature and is used by overlapping and diverse communities of clinicians, molecular biologists and genome scientists, as well as by students and teachers of these disciplines. Genes and phenotypes are described in separate entries and are given unique, stable six-digit identifiers (MIM numbers). OMIM entries have a structured free-text format that provides the flexibility necessary to describe the complex and nuanced relationships between genes and genetic phenotypes in an efficient manner. OMIM also has a derivative table of genes and genetic phenotypes, the Morbid Map. OMIM.org has enhanced search capabilities such as genome coordinate searching and thesaurus-enhanced search term options. Phenotypic series have been created to facilitate viewing genetic heterogeneity of phenotypes. Clinical synopsis features are enhanced with UMLS, Human Phenotype Ontology and Elements of Morphology terms and image links. All OMIM data are available for FTP download and through an API. MIMmatch is a novel outreach feature to disseminate updates and encourage collaboration. © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.

  9. Pst I restriction fragment length polymorphism of human placental alkaline phosphatase gene: Mendelian in segregation and localization of mutation site in the gene

    International Nuclear Information System (INIS)

    Tsavaler, L.; Penhallow, R.C.; Sussman, H.H.

    1988-01-01

    The pattern of inheritance of a Pst I restriction fragment length polymorphism (RFLP) of the human placental alkaline phosphatase gene was studied in nine nuclear families by Southern blot hybridization analysis of genomic DNA. The dimorphic RFLP is defined by the presence of allelic fragments 1.0 kilobase and 0.8 kilobase long. The results of this study show that the two alleles of the Pst I RFLP of the placental alkaline phosphatase gene segregate as codominant traits according to Mendelian expectations. For a polymorphism to be useful as a genetic marker the probability that an offspring is informative (PIC) must be at least 0.15. The allelic frequency of the 1.0-kilobase allele is 0.21, which correlates to a probability that an offspring is informative of 0.275 and is indicative of a useful polymorphism. By using probes derived from different regions of the placental alkaline phosphatase cDNA, the mutated Pst I site causing the RFLP was located in the penultimate intron 2497 base pairs downstream from the transcriptional initiation site

  10. Hemorheological abnormalities in human arterial hypertension

    Science.gov (United States)

    Lo Presti, Rosalia; Hopps, Eugenia; Caimi, Gregorio

    2014-05-01

    Blood rheology is impaired in hypertensive patients. The alteration involves blood and plasma viscosity, and the erythrocyte behaviour is often abnormal. The hemorheological pattern appears to be related to some pathophysiological mechanisms of hypertension and to organ damage, in particular left ventricular hypertrophy and myocardial ischemia. Abnormalities have been observed in erythrocyte membrane fluidity, explored by fluorescence spectroscopy and electron spin resonance. This may be relevant for red cell flow in microvessels and oxygen delivery to tissues. Although blood viscosity is not a direct target of antihypertensive therapy, the rheological properties of blood play a role in the pathophysiology of arterial hypertension and its vascular complications.

  11. Hypertension

    Science.gov (United States)

    ... role in the start and continuation of primary hypertension. Secondary hypertension is due to other diseases such as kidney ... the body can greatly improve or even cure secondary hypertension. Obstructive sleep apnea is a potentially serious sleep ...

  12. Online Mendelian Inheritance in Man (OMIM).

    Science.gov (United States)

    Hamosh, A; Scott, A F; Amberger, J; Valle, D; McKusick, V A

    2000-01-01

    Online Mendelian Inheritance In Man (OMIM) is a public database of bibliographic information about human genes and genetic disorders. Begun by Dr. Victor McKusick as the authoritative reference Mendelian Inheritance in Man, it is now distributed electronically by the National Center for Biotechnology Information (NCBI). Material in OMIM is derived from the biomedical literature and is written by Dr. McKusick and his colleagues at Johns Hopkins University and elsewhere. Each OMIM entry has a full text summary of a genetic phenotype and/or gene and has copious links to other genetic resources such as DNA and protein sequence, PubMed references, mutation databases, approved gene nomenclature, and more. In addition, NCBI's neighboring feature allows users to identify related articles from PubMed selected on the basis of key words in the OMIM entry. Through its many features, OMIM is increasingly becoming a major gateway for clinicians, students, and basic researchers to the ever-growing literature and resources of human genetics. Copyright 2000 Wiley-Liss, Inc.

  13. Circulating interleukin-10 levels and human papilloma virus and Epstein-Barr virus-associated cancers: evidence from a Mendelian randomization meta-analysis based on 11,170 subjects.

    Science.gov (United States)

    Qu, Kai; Pang, Qing; Lin, Ting; Zhang, Li; Gu, Mingliang; Niu, Wenquan; Liu, Chang; Zhang, Ming

    2016-01-01

    Recent studies have showed interleukin 10 (IL-10) is a critical cytokine that determines antiviral immune response and is related to virus-associated cancers. However, whether genetically elevated circulating IL-10 levels are associated with the risk of human papilloma virus and Epstein-Barr virus-associated cancers (HEACs) is still unclear. Mendelian randomization method was implemented to meta-analyze available observational studies by employing IL-10 three variants (-592C>A, -819C>T, and -1082A>G) as instruments. A total of 24 articles encompassing 11,170 subjects were ultimately eligible for the meta-analysis. Overall, there was a significant association between IL-10 promoter variant -1082A>G and HEACs under allelic and dominant models (both PG was significant for nasopharyngeal cancer under allelic, homozygous genotypic and dominant models (all P<0.001). Moreover by ethnicity, carriers of -1082G allele had a 74% increased risk for nasopharyngeal cancer in Asians under dominant model (odds ratio [OR] =1.737; 95% confidence interval [CI]: 1.280-2.358; P<0.001). In further Mendelian randomization analysis, the predicted OR for 10 pg/mL increment in IL-10 levels was 1.14 (95% CI: 1.01-16.99) in HEACs. Our findings provided strong evidence for a critical role of genetically elevated circulating IL-10 levels in the development of HEACs, especially in Asian population and for nasopharyngeal cancer.

  14. hypertension

    Directory of Open Access Journals (Sweden)

    Emine Hatipoglu

    2013-05-01

    Full Text Available Hypertension is a common disease associated with important cardiovascular complications. Persistent blood pressure of 140/90 or higher despite combined use of a reninangiotensin system blocker, calcium channel blocker and a diuretic at highest tolerated doses constitutes resistant hypertension. Excess sympathetic activity plays an important pathogenic role in resistant hypertension in addition to contributing to the development of metabolic problems, in particular diabetes. Reduction of renal sympathetic activity by percutaneous catheter-based radiofrequency ablation via the renal arteries has been shown in several studies to decrease blood pressure in patients with resistant hypertension, and importantly is largely free of significant complications. However, longer term follow-up is required to confirm both long-term safety and efficacy.

  15. Hypertension

    Data.gov (United States)

    Allegheny County / City of Pittsburgh / Western PA Regional Data Center — These datasets provide de-identified insurance data for hypertension hyperlipidemia. The data is provided by three managed care organizations in Allegheny County...

  16. Hypertension

    OpenAIRE

    Farrugia, Emanuel

    2004-01-01

    Hypertension is a rapidly moving clinical field with frequent developments in new pharmacologic agents and management strategies. Perhaps more importantly, there have been substantial improvements in our understanding of how best to use the drugs available to us. In this article, I will review some of the more important advances in our understanding of hypertension over the past two years, specifically by reviewing six important trials, one survey and two sets of guidelines, all published bet...

  17. [Histopathological changes in human placentas related to hypertensive disorders].

    Science.gov (United States)

    Artico, Luciano Guimarães; Madi, José Mauro; Godoy, Alessandra Eifler Guerra; Coelho, Celso Piccoli; Rombaldi, Renato Luís; Artico, Graziela Rech

    2009-01-01

    to determine the prevalence of histopathological changes, in human placentas, related to hypertensive syndromes. a transversal study that compares histopathological changes identified in 43 placentae from hypertensive pregnant women (HypPr), with the ones from 33 placentae from normotensive pregnant women (NorPr). The weight, volume and macroscopic and microscopic occurrence of infarctions, clots, hematomas, atherosis (partial obliteration, thickness of layers and presence of blood vessels hyalinization) and Tenney-Parker changes (absent, discreet and prominent), as well as the locating of infarctions and clots (central, peripheral or the association of both) have been analyzed. The chi2 and t Student tests have been used for the statistical analysis, as well as medians, standard deviations and ratios. It has been considered as significant, p<0.05. the macroscopic study of HypPr placentae have presented lower weight (461.1 versus 572.1 g) and volume (437.4 versus 542.0 cm(3)), higher infarction (51.2 versus 45.5%; p<0.05: OR=1.15) and clots (51.2 versus 15.1%; p<0.05; OR=5.4) ratios, as compared to the NorPr's. In the HypPr and NorPr, microscopic clots have occurred in 83.7 versus 45.5% (p<0.05; OR=4.3), respectively. Atherosis and Tenney-Parker changes have been statistically associated to the hypertensive syndromes (p<0.05). the obtained data allow us to associate lower placentary weight and volume, higher ratio of macro and microscopic infarction, clots, atherosis and Tenney-Parker changes to placentae of gestations occurring with hypertensive syndromes.

  18. [Pulmonary arterial hypertension associated to human immunodeficiency virus].

    Science.gov (United States)

    Sandoval-Gutiérrez, José Luis; Santos-Martínez, Luis Efren; Rodríguez-Silverio, Juan; Baranda-Tovar, Francisco Martín; Rivera-Rosales, Rosa María; Flores-Murrieta, Francisco Javier

    2015-01-01

    From the advent of the highly effective antiretroviral treatment, the life expectancy of patients with human immunodeficiency virus has increased significantly. At present, the causes of death are non-infectious complications. Between them, the pulmonary arterial hypertension has a special importance. It is important early detection to establish the therapeutic, with the objective of preventing a fatal outcome to future. Copyright © 2013 Instituto Nacional de Cardiología Ignacio Chávez. Published by Masson Doyma México S.A. All rights reserved.

  19. Women as Mendelians and Geneticists

    Science.gov (United States)

    Richmond, Marsha L.

    2015-01-01

    After the rediscovery of Mendel's laws of heredity in 1900, the biologists who began studying heredity, variation, and evolution using the new Mendelian methodology—performing controlled hybrid crosses and statistically analyzing progeny to note the factorial basis of characters—made great progress. By 1910, the validity of Mendelism was widely recognized and the field William Bateson christened `genetics' was complemented by the chromosome theory of heredity of T. H. Morgan and his group in the United States. Historians, however, have largely overlooked an important factor in the early establishment of Mendelism and genetics: the large number of women who contributed to the various research groups. This article examines the social, economic, and disciplinary context behind this new wave of women's participation in science and describes the work of women Mendelians and geneticists employed at three leading experimental research institutes, 1900-1940. It argues that the key to more women working in science was the access to higher education and the receptivity of emerging interdisciplinary fields such as genetics to utilize the expertise of women workers, which not only advanced the discipline but also provided new opportunities for women's employment in science.

  20. Structural insights into central hypertension regulation by human aminopeptidase A.

    Science.gov (United States)

    Yang, Yang; Liu, Chang; Lin, Yi-Lun; Li, Fang

    2013-08-30

    Hypertension is regulated through both the central and systemic renin-angiotensin systems. In the central renin-angiotensin system, zinc-dependent aminopeptidase A (APA) up-regulates blood pressure by specifically cleaving the N-terminal aspartate, but not the adjacent arginine, from angiotensin II, a process facilitated by calcium. Here, we determined the crystal structures of human APA and its complexes with different ligands and identified a calcium-binding site in the S1 pocket of APA. Without calcium, the S1 pocket can bind both acidic and basic residues through formation of salt bridges with the charged side chains. In the presence of calcium, the binding of acidic residues is enhanced as they ligate the cation, whereas the binding of basic residues is no longer favorable due to charge repulsion. Of the peptidomimetic inhibitors of APA, amastatin has higher potency than bestatin by fitting better in the S1 pocket and interacting additionally with the S3' subsite. These results explain the calcium-modulated substrate specificity of APA in central hypertension regulation and can guide the design and development of brain-targeting antihypertensive APA inhibitors.

  1. Structural Insights into Central Hypertension Regulation by Human Aminopeptidase A*

    Science.gov (United States)

    Yang, Yang; Liu, Chang; Lin, Yi-Lun; Li, Fang

    2013-01-01

    Hypertension is regulated through both the central and systemic renin-angiotensin systems. In the central renin-angiotensin system, zinc-dependent aminopeptidase A (APA) up-regulates blood pressure by specifically cleaving the N-terminal aspartate, but not the adjacent arginine, from angiotensin II, a process facilitated by calcium. Here, we determined the crystal structures of human APA and its complexes with different ligands and identified a calcium-binding site in the S1 pocket of APA. Without calcium, the S1 pocket can bind both acidic and basic residues through formation of salt bridges with the charged side chains. In the presence of calcium, the binding of acidic residues is enhanced as they ligate the cation, whereas the binding of basic residues is no longer favorable due to charge repulsion. Of the peptidomimetic inhibitors of APA, amastatin has higher potency than bestatin by fitting better in the S1 pocket and interacting additionally with the S3′ subsite. These results explain the calcium-modulated substrate specificity of APA in central hypertension regulation and can guide the design and development of brain-targeting antihypertensive APA inhibitors. PMID:23888046

  2. Human podocyte depletion in association with older age and hypertension.

    Science.gov (United States)

    Puelles, Victor G; Cullen-McEwen, Luise A; Taylor, Georgina E; Li, Jinhua; Hughson, Michael D; Kerr, Peter G; Hoy, Wendy E; Bertram, John F

    2016-04-01

    Podocyte depletion plays a major role in the development and progression of glomerulosclerosis. Many kidney diseases are more common in older age and often coexist with hypertension. We hypothesized that podocyte depletion develops in association with older age and is exacerbated by hypertension. Kidneys from 19 adult Caucasian American males without overt renal disease were collected at autopsy in Mississippi. Demographic data were obtained from medical and autopsy records. Subjects were categorized by age and hypertension as potential independent and additive contributors to podocyte depletion. Design-based stereology was used to estimate individual glomerular volume and total podocyte number per glomerulus, which allowed the calculation of podocyte density (number per volume). Podocyte depletion was defined as a reduction in podocyte number (absolute depletion) or podocyte density (relative depletion). The cortical location of glomeruli (outer or inner cortex) and presence of parietal podocytes were also recorded. Older age was an independent contributor to both absolute and relative podocyte depletion, featuring glomerular hypertrophy, podocyte loss, and thus reduced podocyte density. Hypertension was an independent contributor to relative podocyte depletion by exacerbating glomerular hypertrophy, mostly in glomeruli from the inner cortex. However, hypertension was not associated with podocyte loss. Absolute and relative podocyte depletion were exacerbated by the combination of older age and hypertension. The proportion of glomeruli with parietal podocytes increased with age but not with hypertension alone. These findings demonstrate that older age and hypertension are independent and additive contributors to podocyte depletion in white American men without kidney disease. Copyright © 2016 the American Physiological Society.

  3. Arsenic and diabetes and hypertension in human populations: A review

    International Nuclear Information System (INIS)

    Chen, C.-J.; Wang, S.-L.; Chiou, J.-M.; Tseng, C.-H.; Chiou, H.-Y.; Hsueh, Y.-M.; Chen, S.-Y.; Wu, M.-M.; Lai, M.-S.

    2007-01-01

    Long-term exposure to ingested arsenic from drinking water has been well documented to be associated with an increased risk of diabetes mellitus and hypertension in a dose-response relationship among residents of arseniasis-endemic areas in southwestern Taiwan and Bangladesh. An increased risk of self-reported hypertension but not diabetes was reported in a community-based study of residents who consumed drinking water with a low level of arsenic. Increased glycosylated hemoglobin level and systolic blood pressure were observed in workers occupationally exposed to arsenic. Inconsistent findings of arsenic and diabetes in occupational studies may result from the healthy worker effect and the variation in exposure measurement, age composition, number of patients, accuracy in diagnosis and classification of underlying causes of death, competing causes of death, and method to detect diabetes. The dose-response relationship and toxicological mechanisms of arsenic-induced diabetes and hypertension need further elucidation

  4. Metabolic Profiling of Adiponectin Levels in Adults: Mendelian Randomization Analysis.

    Science.gov (United States)

    Borges, Maria Carolina; Barros, Aluísio J D; Ferreira, Diana L Santos; Casas, Juan Pablo; Horta, Bernardo Lessa; Kivimaki, Mika; Kumari, Meena; Menon, Usha; Gaunt, Tom R; Ben-Shlomo, Yoav; Freitas, Deise F; Oliveira, Isabel O; Gentry-Maharaj, Aleksandra; Fourkala, Evangelia; Lawlor, Debbie A; Hingorani, Aroon D

    2017-12-01

    Adiponectin, a circulating adipocyte-derived protein, has insulin-sensitizing, anti-inflammatory, antiatherogenic, and cardiomyocyte-protective properties in animal models. However, the systemic effects of adiponectin in humans are unknown. Our aims were to define the metabolic profile associated with higher blood adiponectin concentration and investigate whether variation in adiponectin concentration affects the systemic metabolic profile. We applied multivariable regression in ≤5909 adults and Mendelian randomization (using cis -acting genetic variants in the vicinity of the adiponectin gene as instrumental variables) for analyzing the causal effect of adiponectin in the metabolic profile of ≤37 545 adults. Participants were largely European from 6 longitudinal studies and 1 genome-wide association consortium. In the multivariable regression analyses, higher circulating adiponectin was associated with higher high-density lipoprotein lipids and lower very-low-density lipoprotein lipids, glucose levels, branched-chain amino acids, and inflammatory markers. However, these findings were not supported by Mendelian randomization analyses for most metabolites. Findings were consistent between sexes and after excluding high-risk groups (defined by age and occurrence of previous cardiovascular event) and 1 study with admixed population. Our findings indicate that blood adiponectin concentration is more likely to be an epiphenomenon in the context of metabolic disease than a key determinant. © 2017 The Authors.

  5. MendelianRandomization: an R package for performing Mendelian randomization analyses using summarized data.

    Science.gov (United States)

    Yavorska, Olena O; Burgess, Stephen

    2017-12-01

    MendelianRandomization is a software package for the R open-source software environment that performs Mendelian randomization analyses using summarized data. The core functionality is to implement the inverse-variance weighted, MR-Egger and weighted median methods for multiple genetic variants. Several options are available to the user, such as the use of robust regression, fixed- or random-effects models and the penalization of weights for genetic variants with heterogeneous causal estimates. Extensions to these methods, such as allowing for variants to be correlated, can be chosen if appropriate. Graphical commands allow summarized data to be displayed in an interactive graph, or the plotting of causal estimates from multiple methods, for comparison. Although the main method of data entry is directly by the user, there is also an option for allowing summarized data to be incorporated from the PhenoScanner database of genotype-phenotype associations. We hope to develop this feature in future versions of the package. The R software environment is available for download from [https://www.r-project.org/]. The MendelianRandomization package can be downloaded from the Comprehensive R Archive Network (CRAN) within R, or directly from [https://cran.r-project.org/web/packages/MendelianRandomization/]. Both R and the MendelianRandomization package are released under GNU General Public Licenses (GPL-2|GPL-3). © The Author 2017. Published by Oxford University Press on behalf of the International Epidemiological Association.

  6. Survivor bias in Mendelian randomization analysis

    DEFF Research Database (Denmark)

    Vansteelandt, Stijn; Dukes, Oliver; Martinussen, Torben

    2017-01-01

    Mendelian randomization studies employ genotypes as experimental handles to infer the effect of genetically modified exposures (e.g. vitamin D exposure) on disease outcomes (e.g. mortality). The statistical analysis of these studies makes use of the standard instrumental variables framework. Many...... of these studies focus on elderly populations, thereby ignoring the problem of left truncation, which arises due to the selection of study participants being conditional upon surviving up to the time of study onset. Such selection, in general, invalidates the assumptions on which the instrumental variables...... analysis rests. We show that Mendelian randomization studies of adult or elderly populations will therefore, in general, return biased estimates of the exposure effect when the considered genotype affects mortality; in contrast, standard tests of the causal null hypothesis that the exposure does not affect...

  7. Involvement of Connective Tissue Growth Factor in Human and Experimental Hypertensive Nephrosclerosis

    NARCIS (Netherlands)

    Ito, Yasuhiko; Aten, Jan; Nguyen, Tri Q.; Joles, Jaap A.; Matsuo, Seiichi; Weening, Jan J.; Goldschmeding, Roel

    2011-01-01

    Background/Aims: Connective tissue growth factor (CTGF; CCN2) has been implicated as a marker and mediator of fibrosis in human and experimental renal disease. Methods: We performed a comparative analysis of CTGF expression in hypertensive patients with and without nephrosclerosis, and in

  8. Ingestion of broccoli sprouts does not improve endothelial function in humans with hypertension

    DEFF Research Database (Denmark)

    Christiansen, Buris; Bellostas Muguerza, Natalia; Petersen, Atheline Major

    2010-01-01

    be the case in humans suffering from essential hypertension. METHODS: 40 hypertensive individuals without diabetes and with normal levels of cholesterol were examined. The participants were randomized either to ingest 10 g dried broccoli sprouts, a natural donor of glucosinolates with high in vitro...... groups. Diastolic blood pressure stayed essentially unchanged in both groups, while the systolic blood pressure showed a small non significant decrease (9 mm Hg) in the interventional group from a value of 153 mm Hg at start. CONCLUSION: Daily ingestion of 10 g dried broccoli sprouts does not improve...

  9. The Hidden Complexity of Mendelian Traits across Natural Yeast Populations

    Directory of Open Access Journals (Sweden)

    Jing Hou

    2016-07-01

    Full Text Available Mendelian traits are considered to be at the lower end of the complexity spectrum of heritable phenotypes. However, more than a century after the rediscovery of Mendel’s law, the global landscape of monogenic variants, as well as their effects and inheritance patterns within natural populations, is still not well understood. Using the yeast Saccharomyces cerevisiae, we performed a species-wide survey of Mendelian traits across a large population of isolates. We generated offspring from 41 unique parental pairs and analyzed 1,105 cross/trait combinations. We found that 8.9% of the cases were Mendelian. Further tracing of causal variants revealed background-specific expressivity and modified inheritances, gradually transitioning from Mendelian to complex traits in 30% of the cases. In fact, when taking into account the natural population diversity, the hidden complexity of traits could be substantial, confounding phenotypic predictability even for simple Mendelian traits.

  10. Human heme oxygenase-1 gene transfer lowers blood pressure and promotes growth in spontaneously hypertensive rats.

    Science.gov (United States)

    Sabaawy, H E; Zhang, F; Nguyen, X; ElHosseiny, A; Nasjletti, A; Schwartzman, M; Dennery, P; Kappas, A; Abraham, N G

    2001-08-01

    Heme oxygenase (HO) catalyzes the conversion of heme to biliverdin, with release of free iron and carbon monoxide. Both heme and carbon monoxide have been implicated in the regulation of vascular tone. A retroviral vector containing human HO-1 cDNA (LSN-HHO-1) was constructed and subjected to purification and concentration of the viral particles to achieve 5x10(9) to 1x10(10) colony-forming units per milliliter. The ability of concentrated infectious viral particles to express human HO-1 (HHO-1) in vivo was tested. A single intracardiac injection of the concentrated infectious viral particles (expressing HHO-1) to 5-day-old spontaneously hypertensive rats resulted in functional expression of the HHO-1 gene and attenuation of the development of hypertension. Rats expressing HHO-1 showed a significant decrease in urinary excretion of a vasoconstrictor arachidonic acid metabolite and a reduction in myogenic responses to increased intraluminal pressure in isolated arterioles. Unexpectedly, HHO-1 chimeric rats showed a simultaneous significant proportionate increase in somatic growth. Thus, delivery of HHO-1 gene by retroviral vector attenuates the development of hypertension and promotes body growth in spontaneously hypertensive rats.

  11. B-Type Natriuretic Peptide Deletion Leads to Progressive Hypertension, Associated Organ Damage, and Reduced Survival: Novel Model for Human Hypertension.

    Science.gov (United States)

    Holditch, Sara J; Schreiber, Claire A; Nini, Ryan; Tonne, Jason M; Peng, Kah-Whye; Geurts, Aron; Jacob, Howard J; Burnett, John C; Cataliotti, Alessandro; Ikeda, Yasuhiro

    2015-07-01

    Altered myocardial structure and function, secondary to chronically elevated blood pressure, are leading causes of heart failure and death. B-type natriuretic peptide (BNP), a guanylyl cyclase A agonist, is a cardiac hormone integral to cardiovascular regulation. Studies have demonstrated a causal relationship between reduced production or impaired BNP release and the development of human hypertension. However, the consequences of BNP insufficiency on blood pressure and hypertension-associated complications remain poorly understood. Therefore, the goal of this study was to create and characterize a novel model of BNP deficiency to investigate the effects of BNP absence on cardiac and renal structure, function, and survival. Genetic BNP deletion was generated in Dahl salt-sensitive rats. Compared with age-matched controls, BNP knockout rats demonstrated adult-onset hypertension. Increased left ventricular mass with hypertrophy and substantially augmented hypertrophy signaling pathway genes, developed in young adult knockout rats, which preceded hypertension. Prolonged hypertension led to increased cardiac stiffness, cardiac fibrosis, and thrombi formation. Significant elongation of the QT interval was detected at 9 months in knockout rats. Progressive nephropathy was also noted with proteinuria, fibrosis, and glomerular alterations in BNP knockout rats. End-organ damage contributed to a significant decline in overall survival. Systemic BNP overexpression reversed the phenotype of genetic BNP deletion. Our results demonstrate the critical role of BNP defect in the development of systemic hypertension and associated end-organ damage in adulthood. © 2015 American Heart Association, Inc.

  12. Pulse wave imaging in normal, hypertensive and aneurysmal human aortas in vivo: a feasibility study

    International Nuclear Information System (INIS)

    Li, Ronny X; Luo, Jianwen; Shahmirzadi, Danial; Konofagou, Elisa E; Balaram, Sandhya K; Chaudhry, Farooq A

    2013-01-01

    Arterial stiffness is a well-established biomarker for cardiovascular risk, especially in the case of hypertension. The progressive stages of an abdominal aortic aneurysm (AAA) have also been associated with varying arterial stiffness. Pulse wave imaging (PWI) is a noninvasive, ultrasound imaging-based technique that uses the pulse wave-induced arterial wall motion to map the propagation of the pulse wave and measure the regional pulse wave velocity (PWV) as an index of arterial stiffness. In this study, the clinical feasibility of PWI was evaluated in normal, hypertensive, and aneurysmal human aortas. Radiofrequency-based speckle tracking was used to estimate the pulse wave-induced displacements in the abdominal aortic walls of normal (N = 15, mean age 32.5 ± 10.2 years), hypertensive (N = 13, mean age 60.8 ± 15.8 years), and aneurysmal (N = 5, mean age 71.6 ± 11.8 years) human subjects. Linear regression of the spatio-temporal variation of the displacement waveform in the anterior aortic wall over a single cardiac cycle yielded the slope as the PWV and the coefficient of determination r 2 as an approximate measure of the pulse wave propagation uniformity. The aortic PWV measurements in all normal, hypertensive, and AAA subjects were 6.03 ± 1.68, 6.69 ± 2.80, and 10.54 ± 6.52 m s −1 , respectively. There was no significant difference (p = 0.15) between the PWVs of the normal and hypertensive subjects while the PWVs of the AAA subjects were significantly higher (p 2 in the AAA subjects was significantly lower (p 2 ) obtained using PWI, in addition to the PWI images and spatio-temporal maps that provide qualitative visualization of the pulse wave, may potentially provide valuable information for the clinical characterization of aneurysms and other vascular pathologies that regionally alter the arterial wall mechanics. (paper)

  13. Novel Rat Model of Repetitive Portal Venous Embolization Mimicking Human Non-Cirrhotic Idiopathic Portal Hypertension

    DEFF Research Database (Denmark)

    Klein, Sabine; Hinüber, Christian; Hittatiya, Kanishka

    2016-01-01

    BACKGROUND: Non-cirrhotic idiopathic portal hypertension (NCIPH) is characterized by splenomegaly, anemia and portal hypertension, while liver function is preserved. However, no animal models have been established yet. This study assessed a rat model of NCIPH and characterized the hemodynamics......, and compared it to human NCIPH. METHODS: Portal pressure (PP) was measured invasively and coloured microspheres were injected in the ileocecal vein in rats. This procedure was performed weekly for 3 weeks (weekly embolization). Rats without and with single embolization served as controls. After four weeks (one...... in the weekly embolization group. Fibrotic markers αSMA and Desmin were upregulated in weekly embolized rats. DISCUSSION: This study establishes a model using repetitive embolization via portal veins, comparable with human NCIPH and may serve to test new therapies....

  14. Effects of corn silk aqueous extract on intraocular pressure of ocular hypertensive human subjects

    Directory of Open Access Journals (Sweden)

    G.O. George

    2013-01-01

    Full Text Available Stigma/style of Zea mays L (Corn silk has been documented to have hypotensive effect on blood pressure and to relieve oedema. However we are not aware of any literature on its hypotensive effect on intraocular pressure (IOP of humans or animals. We studied the effects of water only, masked doses of corn silk aqueous extract (60 mg/kg, 130 mg/kg, 192.5 mg/kg and 260 mg/kg body weight on the IOP and blood pressure (BP of twenty normotensives and twenty ocular hypertensive subjects. Also we compared the effects of the varied doses of corn silk aqueous extract (CSAE with masked doses (5 mg/kg and 10 mg/kg body weight of acetazolamide on IOP of ocular hypertensive subjects only. The results showed that the last three doses of CSAE lowered IOP and BP significantly (p<0.001 within eight hours of administration. The peak effect on IOP was observed after four hours while the peak effect on BP was observed after three hours of administration in the normotensives and ocular hypertensive subjects likewise the hypotensive effect was dose-dependent. The results also showed that 130 mg/kg body weight of CSAE produced the same hypotensive effect on IOP of ocular hypertensive subjects as 5 mg/kg body weight of acetazolamide. Therefore CSAE may have some IOP lowering effects that require further investigation in the management of ocular hypertension. (S Afr Optom 2013 72(3 133-143

  15. Pre-existing hypertension dominates γδT cell reduction in human ischemic stroke.

    Directory of Open Access Journals (Sweden)

    Mateusz G Adamski

    Full Text Available T lymphocytes may play an important role in the evolution of ischemic stroke. Depletion of γδT cells has been found to abrogate ischemia reperfusion injury in murine stroke. However, the role of γδT cells in human ischemic stroke is unknown. We aimed to determine γδT cell counts and γδT cell interleukin 17A (IL-17A production in the clinical setting of ischemic stroke. We also aimed to determine the associations of γδT cell counts with ischemic lesion volume, measures of clinical severity and with major stroke risk factors. Peripheral blood samples from 43 acute ischemic stroke patients and 26 control subjects matched on race and gender were used for flow cytometry and complete blood count analyses. Subsequently, cytokine levels and gene expression were measured in γδT cells. The number of circulating γδT cells was decreased by almost 50% (p = 0.005 in the stroke patients. γδT cell counts did not correlate with lesion volume on magnetic resonance diffusion-weighted imaging or with clinical severity in the stroke patients, but γδT cells showed elevated levels of IL-17A (p = 0.048. Decreased γδT cell counts were also associated with older age (p = 0.004, pre-existing hypertension (p = 0.0005 and prevalent coronary artery disease (p = 0.03, with pre-existing hypertension being the most significant predictor of γδT cell counts in a multivariable analysis. γδT cells in human ischemic stroke are reduced in number and show elevated levels of IL-17A. A major reduction in γδT lymphocytes also occurs in hypertension and may contribute to the development of hypertension-mediated stroke and vascular disease.

  16. Comprehensive genotyping in dyslipidemia: mendelian dyslipidemias caused by rare variants and Mendelian randomization studies using common variants.

    Science.gov (United States)

    Tada, Hayato; Kawashiri, Masa-Aki; Yamagishi, Masakazu

    2017-04-01

    Dyslipidemias, especially hyper-low-density lipoprotein cholesterolemia and hypertriglyceridemia, are important causal risk factors for coronary artery disease. Comprehensive genotyping using the 'next-generation sequencing' technique has facilitated the investigation of Mendelian dyslipidemias, in addition to Mendelian randomization studies using common genetic variants associated with plasma lipids and coronary artery disease. The beneficial effects of low-density lipoprotein cholesterol-lowering therapies on coronary artery disease have been verified by many randomized controlled trials over the years, and subsequent genetic studies have supported these findings. More recently, Mendelian randomization studies have preceded randomized controlled trials. When the on-target/off-target effects of rare variants and common variants exhibit the same direction, novel drugs targeting molecules identified by investigations of rare Mendelian lipid disorders could be promising. Such a strategy could aid in the search for drug discovery seeds other than those for dyslipidemias.

  17. Validation of consistency of Mendelian sampling variance.

    Science.gov (United States)

    Tyrisevä, A-M; Fikse, W F; Mäntysaari, E A; Jakobsen, J; Aamand, G P; Dürr, J; Lidauer, M H

    2018-03-01

    Experiences from international sire evaluation indicate that the multiple-trait across-country evaluation method is sensitive to changes in genetic variance over time. Top bulls from birth year classes with inflated genetic variance will benefit, hampering reliable ranking of bulls. However, none of the methods available today enable countries to validate their national evaluation models for heterogeneity of genetic variance. We describe a new validation method to fill this gap comprising the following steps: estimating within-year genetic variances using Mendelian sampling and its prediction error variance, fitting a weighted linear regression between the estimates and the years under study, identifying possible outliers, and defining a 95% empirical confidence interval for a possible trend in the estimates. We tested the specificity and sensitivity of the proposed validation method with simulated data using a real data structure. Moderate (M) and small (S) size populations were simulated under 3 scenarios: a control with homogeneous variance and 2 scenarios with yearly increases in phenotypic variance of 2 and 10%, respectively. Results showed that the new method was able to estimate genetic variance accurately enough to detect bias in genetic variance. Under the control scenario, the trend in genetic variance was practically zero in setting M. Testing cows with an average birth year class size of more than 43,000 in setting M showed that tolerance values are needed for both the trend and the outlier tests to detect only cases with a practical effect in larger data sets. Regardless of the magnitude (yearly increases in phenotypic variance of 2 or 10%) of the generated trend, it deviated statistically significantly from zero in all data replicates for both cows and bulls in setting M. In setting S with a mean of 27 bulls in a year class, the sampling error and thus the probability of a false-positive result clearly increased. Still, overall estimated genetic

  18. Novel Rat Model of Repetitive Portal Venous Embolization Mimicking Human Non-Cirrhotic Idiopathic Portal Hypertension.

    Science.gov (United States)

    Klein, Sabine; Hinüber, Christian; Hittatiya, Kanishka; Schierwagen, Robert; Uschner, Frank Erhard; Strassburg, Christian P; Fischer, Hans-Peter; Spengler, Ulrich; Trebicka, Jonel

    2016-01-01

    Non-cirrhotic idiopathic portal hypertension (NCIPH) is characterized by splenomegaly, anemia and portal hypertension, while liver function is preserved. However, no animal models have been established yet. This study assessed a rat model of NCIPH and characterized the hemodynamics, and compared it to human NCIPH. Portal pressure (PP) was measured invasively and coloured microspheres were injected in the ileocecal vein in rats. This procedure was performed weekly for 3 weeks (weekly embolization). Rats without and with single embolization served as controls. After four weeks (one week after last embolization), hemodynamics were investigated, hepatic fibrosis and accumulation of myofibroblasts were analysed. General characteristics, laboratory analyses and liver histology were collected in patients with NCIPH. Weekly embolization induced a hyperdynamic circulation, with increased PP. The mesenteric flow and hepatic hydroxyproline content was significantly higher in weekly embolized compared to single embolized rats (mesenteric flow +54.1%, hydroxyproline +41.7%). Mesenteric blood flow and shunt volumes increased, whereas splanchnic vascular resistance was decreased in the weekly embolization group. Fibrotic markers αSMA and Desmin were upregulated in weekly embolized rats. This study establishes a model using repetitive embolization via portal veins, comparable with human NCIPH and may serve to test new therapies.

  19. Renal denervation and hypertension - The need to investigate unintended effects and neural control of the human kidney.

    Science.gov (United States)

    Grisk, Olaf

    2017-05-01

    Increased renal sympathetic nerve activity (RSNA) is present in human and experimental forms of arterial hypertension. Experimental denervation studies showed that renal nerves contribute to the development of hypertension. Clinical trials provided equivocal results on the antihypertensive efficacy of renal denervation in patients spurring discussions on technical aspects of renal denervation and further research on the role of renal nerves for the regulation of kidney function as well as the pathophysiology of hypertension. This review summarizes recent findings on adrenoceptor expression and function in the human kidney, adrenoceptor-dependent regulation of sodium chloride transport in the distal nephron, experimental data on chronic RSNA and the development of high arterial pressure and consequences of renal denervation that may limit its antihypertensive efficacy. Future research needs to reduce the gap between our knowledge on neural control of renal function in animals vs. humans to facilitate translation of experimental animal data to humans. More experimental studies on the temporal relationship between RSNA and arterial pressure in the chronic setting are needed to better define the pathogenetic role of heightened RSNA in different forms of arterial hypertension in order to improve the rational basis for renal denervation in antihypertensive therapy. Finally, research on unintended consequences of renal denervation including but not limited to reinnervation and denervation supersensitivity needs to be intensified to further assess the potential of renal denervation to slow the progression of renal disease and hypertension. Copyright © 2016 Elsevier B.V. All rights reserved.

  20. Animal models for the study of primary and secondary hypertension in humans

    OpenAIRE

    Lin, Hiu Yu; Lee, Yee Ting; Chan, Yin Wah; Tse, Gary

    2016-01-01

    Hypertension is a significant cause of morbidity and mortality worldwide. It is defined as systolic and diastolic blood pressures (SBP/DBP) >140 and 90 mmHg, respectively. Individuals with an SBP between 120 and 139, or DBP between 80 and 89 mmHg, are said to exhibit pre-hypertension. Hypertension can have primary or secondary causes. Primary or essential hypertension is a multifactorial disease caused by interacting environmental and polygenic factors. Secondary causes are renovascular hyper...

  1. Therapeutic vaccines against human and rat renin in spontaneously hypertensive rats.

    Directory of Open Access Journals (Sweden)

    Zhihua Qiu

    Full Text Available Vaccination provides a promising approach for treatment of hypertension and improvement in compliance. As the initiation factor of renin-angiotensin system, renin plays a critical role in hypertension. In this study, we selected six peptides (rR32, rR72, rR215, hR32, hR72, and hR215 belonging to potential epitopes of rat and human renin. The main criteria were as follows: (1 include one of renin catalytic sites or the flap sequence; (2 low/no-similarity when matched with the host proteome; (3 ideal antigenicity and hydrophilicity. The peptides were coupled to keyhole limpet hemocyanin and injected into SpragueDawley (SD rats, spontaneously hypertensive rats (SHRs and Wistar-Kyoto rats. The antisera titers and the binding capacity with renin were detected. The effects of the anti-peptides antibodies on plasma renin activity (PRA and blood pressure were also determined. All peptides elicited strong antibody responses. The antisera titers ranged from 1:32,000 to 1:80,000 in SD rats on day 63. All antisera could bind to renin in vitro. Compared with the control antibody, the antibodies against the rR32, hR32, rR72 and hR72 peptides inhibited PRA level by up to about 50%. Complete cross-reactivity of the anti-rR32 antibody and the anti-hR32 antibody was confirmed. The epitopes rR32 and hR32 vaccines significantly decreased systolic blood pressure (SBP of SHRs up to 15mmHg (175±2 vesus 190±3 mmHg, P = 0.035; 180±2 vesus 195±3 mmHg, P = 0.039, while no obvious effect on SD rats. Additionally, no significant immune-mediated damage was detected in the vaccinated animals. In conclusion, the antigenic peptide hR32 vaccine mimicking the (32Asp catalytic site of human renin may constitute a novel tool for the development of a renin vaccine.

  2. Recurrent recessive mutation in deoxyguanosine kinase causes idiopathic noncirrhotic portal hypertension.

    Science.gov (United States)

    Vilarinho, Sílvia; Sari, Sinan; Yilmaz, Güldal; Stiegler, Amy L; Boggon, Titus J; Jain, Dhanpat; Akyol, Gulen; Dalgic, Buket; Günel, Murat; Lifton, Richard P

    2016-06-01

    Despite advances in the diagnosis and management of idiopathic noncirrhotic portal hypertension, its pathogenesis remains elusive. Insight may be gained from study of early-onset familial idiopathic noncirrhotic portal hypertension, in which Mendelian mutations may account for disease. We performed exome sequencing of eight subjects from six kindreds with onset of portal hypertension of indeterminate etiology during infancy or childhood. Three subjects from two consanguineous families shared the identical rare homozygous p.N46S mutation in DGUOK, a deoxyguanosine kinase required for mitochondrial DNA replication; haplotype sharing demonstrated that the mutation in the two families was inherited from a remote common ancestor. All three affected subjects had stable portal hypertension with noncirrhotic liver disease for 6-16 years of follow-up. This mutation impairs adenosine triphosphate binding and reduces catalytic activity. Loss-of-function mutations in DGUOK have previously been implicated in cirrhosis and liver failure but not in isolated portal hypertension. Interestingly, treatment of patients with human immunodeficiency viral infection with the nucleoside analogue didanosine is known to cause portal hypertension in a subset of patients and lowers deoxyguanosine kinase levels in vitro; the current findings implicate these effects on deoxyguanosine kinase in the causal mechanism. Our findings provide new insight into the mechanisms mediating inherited and acquired noncirrhotic portal hypertension, expand the phenotypic spectrum of DGUOK deficiency, and provide a new genetic test for a specific cause of idiopathic noncirrhotic portal hypertension. (Hepatology 2016;63:1977-1986). © 2016 by the American Association for the Study of Liver Diseases.

  3. A nondegenerate code of deleterious variants in Mendelian loci contributes to complex disease risk.

    Science.gov (United States)

    Blair, David R; Lyttle, Christopher S; Mortensen, Jonathan M; Bearden, Charles F; Jensen, Anders Boeck; Khiabanian, Hossein; Melamed, Rachel; Rabadan, Raul; Bernstam, Elmer V; Brunak, Søren; Jensen, Lars Juhl; Nicolae, Dan; Shah, Nigam H; Grossman, Robert L; Cox, Nancy J; White, Kevin P; Rzhetsky, Andrey

    2013-09-26

    Although countless highly penetrant variants have been associated with Mendelian disorders, the genetic etiologies underlying complex diseases remain largely unresolved. By mining the medical records of over 110 million patients, we examine the extent to which Mendelian variation contributes to complex disease risk. We detect thousands of associations between Mendelian and complex diseases, revealing a nondegenerate, phenotypic code that links each complex disorder to a unique collection of Mendelian loci. Using genome-wide association results, we demonstrate that common variants associated with complex diseases are enriched in the genes indicated by this "Mendelian code." Finally, we detect hundreds of comorbidity associations among Mendelian disorders, and we use probabilistic genetic modeling to demonstrate that Mendelian variants likely contribute nonadditively to the risk for a subset of complex diseases. Overall, this study illustrates a complementary approach for mapping complex disease loci and provides unique predictions concerning the etiologies of specific diseases. Copyright © 2013 Elsevier Inc. All rights reserved.

  4. Bone Morphogenetic Protein (BMP-7 expression is decreased in human hypertensive nephrosclerosis

    Directory of Open Access Journals (Sweden)

    Cohen Clemens D

    2010-11-01

    Full Text Available Abstract Background Bone Morphogenetic Protein (BMP-7 is protective in different animal models of acute and chronic kidney disease. Its role in human kidneys, and in particular hypertensive nephrosclerosis, has thus far not been described. Methods BMP-7 mRNA was quantified using real-time PCR and localised by immunostaining in tissue samples from normal and nephrosclerotic human kidneys. The impact of angiotensin (AT-II and the AT-II receptor antagonist telmisartan on BMP-7 mRNA levels and phosphorylated Smad 1/5/8 (pSmad 1/5/8 expression was quantified in proximal tubular cells (HK-2. Functional characteristics of BMP-7 were evaluated by testing its influence on TGF-β induced epithelial-to-mesenchymal transition (EMT, expression of TGF-β receptor type I (TGF-βRI and phosphorylated Smad 2 (pSmad 2 as well as on TNF-α induced apoptosis of proximal tubular cells. Results BMP-7 was predominantly found in the epithelia of the distal tubule and the collecting duct and was less abundant in proximal tubular cells. In sclerotic kidneys, BMP-7 was significantly decreased as demonstrated by real-time PCR and immunostaining. AT-II stimulation in HK-2 cells led to a significant decrease of BMP-7 and pSmad 1/5/8, which was partially ameliorated upon co-incubation with telmisartan. Only high concentrations of BMP-7 (100 ng/ml were able to reverse TNF-α-induced apoptosis and TGF-β-induced EMT in human proximal tubule cells possibly due to a decreased expression of TGF-βRI. In addition, BMP-7 was able to reverse TGF-β-induced phosphorylation of Smad 2. Conclusions The findings suggest a protective role for BMP-7 by counteracting the TGF-β and TNF-α-induced negative effects. The reduced expression of BMP-7 in patients with hypertensive nephrosclerosis may imply loss of protection and regenerative potential necessary to counter the disease.

  5. Proteomic-Biostatistic Integrated Approach for Finding the Underlying Molecular Determinants of Hypertension in Human Plasma.

    Science.gov (United States)

    Gajjala, Prathibha R; Jankowski, Vera; Heinze, Georg; Bilo, Grzegorz; Zanchetti, Alberto; Noels, Heidi; Liehn, Elisa; Perco, Paul; Schulz, Anna; Delles, Christian; Kork, Felix; Biessen, Erik; Narkiewicz, Krzysztof; Kawecka-Jaszcz, Kalina; Floege, Juergen; Soranna, Davide; Zidek, Walter; Jankowski, Joachim

    2017-08-01

    Despite advancements in lowering blood pressure, the best approach to lower it remains controversial because of the lack of information on the molecular basis of hypertension. We, therefore, performed plasma proteomics of plasma from patients with hypertension to identify molecular determinants detectable in these subjects but not in controls and vice versa. Plasma samples from hypertensive subjects (cases; n=118) and controls (n=85) from the InGenious HyperCare cohort were used for this study and performed mass spectrometric analysis. Using biostatistical methods, plasma peptides specific for hypertension were identified, and a model was developed using least absolute shrinkage and selection operator logistic regression. The underlying peptides were identified and sequenced off-line using matrix-assisted laser desorption ionization orbitrap mass spectrometry. By comparison of the molecular composition of the plasma samples, 27 molecular determinants were identified differently expressed in cases from controls. Seventy percent of the molecular determinants selected were found to occur less likely in hypertensive patients. In cross-validation, the overall R 2 was 0.434, and the area under the curve was 0.891 with 95% confidence interval 0.8482 to 0.9349, P hypertensive patients were found to be -2.007±0.3568 and 3.383±0.2643, respectively, P hypertensives and normotensives. The identified molecular determinants may be the starting point for further studies to clarify the molecular causes of hypertension. © 2017 American Heart Association, Inc.

  6. [Pulmonary arterial hypertension associated with human immunodeficiency virus infection: study of 4 cases].

    Science.gov (United States)

    Pousada, Guillermo; Baloira, Adolfo; Castro-Añón, Olalla; Valverde, Diana

    2016-04-15

    Pulmonary arterial hypertension (PAH) is a rare and progressive disease that can be inherited as autosomal dominant form. The BMPR2, ACVRL1 and ENG genes are main genes involved in the pathology. PAH associated to human immunodeficiency virus (HIV) is another rare disease with a low incidence, prevalence and survival. The main objective of this analysis was to study the clinical and molecular characteristics of PAH associated to HIV patients. We present 4 cases of HIV patients who developed PAH and have been treated with ambrisentan. Pathogenic mutations have been identify in analyzed genes in 3 of the four analyzed patients. In addition, these patients present other changes classified as benign after a thorough in silico analysis. We identified some changes in genetic modifiers that predispose to these patients to more severe phenotype. The clinical analysis can help to define monitoring for these patients and the administration of appropriate treatment. These patients also have shown several pathogenic mutations. Copyright © 2016 Elsevier España, S.L.U. All rights reserved.

  7. [Ultrastructure of the intima of human pial arteries in arterial hypertension].

    Science.gov (United States)

    Chertok, V M; Kotsiuba, A E; Babich, E V

    2009-01-01

    Ultrastructure of the intima of human pial arteries obtained from 5 male cadavers of practically healthy individuals and from 8 cadavers of the patients with the intravitally diagnosed grade I arterial hypertension (AH) was studied by scanning and transmission electron microscopy. AH was found to be associated with the remodeling of the intimal structural elements in the pial arteries. In most arteries, the changes were detected in the microrelief of the luminal surface and in the permeability of the vascular endothelial lining and of the subendothelial layer. During this remodeling, some endothelial cells were found in the state of structural and functional adaptation to the elevated arterial pressure, while the others were undergoing the dystrophic changes. The latter include the cells containing lipid inclusions, as well as the endothelial cells presumably in the state of apoptosis. The destruction of the intercellular junctions, the disturbances in the endothelium permeability contributed to the development of subendothelial layer edema, resulting in its significant thickening. This layer became looser and contained abundant collagen fibrils.

  8. [Efferent innervation of the arteries of human leptomeninx in arterial hypertension].

    Science.gov (United States)

    Chertok, V M; Kotsiuba, A E; Babich, E V

    2009-01-01

    Structure of the efferent nerve plexuses (adrenergic, acetylcholinestherase- and cholinacetyltranspherase-positive, NO-dependent), was studied in the arteries of human leptomeninx with different diameters. Material was obtained from the corpses of the healthy people and of the patients with initial stages of arterial hypertension (AH). It was shown that the concentrations of cholinergic and adrenergic nerve fibers and varicosities in axon terminal part, innervating the arteries with the diameters ranging from 450 till 100 microm, were not significantly different. In these arteries, NO-ergic plexuses were also detected. In patients with AH, regardless the arterial diameters, the significant increase (up to 15-20%) of adrenergic nerve fiber and varicosity concentrations was found. The changes in cholinergic nerve fiber concentration were found to depend on the vessel diameter: the significant decrease of these parameter was observed only in arteries with the diameter of 100-200 microm. No significant changes in nerve plexus concentration was noticed in the arteries with greater or smaller diameter. In NO-ergic neural conductors, the enzyme activity decreased only in the large arteries, and remained almost unchanged in the small vascular branches. The changes in the vasomotor innervation described in AH, are interpreted as a vasomotor innervation dysfunction of the leptomeninx arteries that may result in the hemodynamic disturbances.

  9. Mendelian and non-mendelian mutations affecting surface antigen expression in Paramecium tetraurelia

    International Nuclear Information System (INIS)

    Epstein, L.M.; Forney, J.D.

    1984-01-01

    A screening procedure was devised for the isolation of X-ray-induced mutations affecting the expression of the A immobilization antigen (i-antigen) in Paramecium tetraurelia. Two of the mutations isolated by this procedure proved to be in modifier genes. The two genes are unlinked to each other and unlinked to the structural A i-antigen gene. These are the first modifier genes identified in a Paramecium sp. that affect surface antigen expression. Another mutation was found to be a deletion of sequences just downstream from the A i-antigen gene. In cells carrying this mutation, the A i-antigen gene lies in close proximity to the end of a macronuclear chromosome. The expression of the A i-antigen is not affected in these cells, demonstrating that downstream sequences are not important for the regulation and expression of the A i-antigen gene. A stable cell line was also recovered which shows non-Mendelian inheritance of a macronuclear deletion of the A i-antigen gene. This mutant does not contain the gene in its macronucleus, but contains a complete copy of the gene in its micronucleus. In the cytoplasm of wild-type animals, the micronuclear gene is included in the developing macronucleus; in the cytoplasm of the mutant, the incorporation of the A i-antigen gene into the macronucleus is inhibited. This is the first evidence that a mechanism is available in ciliates to control the expression of a gene by regulating its incorporation into developing macronuclei

  10. Ocular Hypertension

    Science.gov (United States)

    ... Español Eye Health / Eye Health A-Z Ocular Hypertension Sections What Is Ocular Hypertension? Ocular Hypertension Causes ... Hypertension Diagnosis Ocular Hypertension Treatment What Is Ocular Hypertension? Leer en Español: ¿Qué es la hipertensión ocular? ...

  11. Human pentraxin 3 (PTX3 as a novel biomarker for the diagnosis of pulmonary arterial hypertension.

    Directory of Open Access Journals (Sweden)

    Yuichi Tamura

    Full Text Available BACKGROUND: Although inflammation is an important feature of pulmonary arterial hypertension (PAH, the usefulness of local inflammatory markers as biomarkers for PAH is unknown. In this study, we tested whether plasma concentrations of human pentraxin 3 (PTX3, a local inflammatory marker, would be a useful biomarker for detecting PAH. METHODS: Plasma PTX3 concentrations were evaluated in 50 PAH patients (27 with idiopathic PAH, 17 with PAH associated with connective tissue disease (CTD-PAH, and six with congenital heart disease, 100 age and sex-matched healthy controls, and 34 disease-matched CTD patients without PAH. Plasma concentrations of B-type natriuretic peptide (BNP and C-reactive protein (CRP were also determined. RESULTS: Mean PTX3 levels were significantly higher in all PAH patients than in the healthy controls (4.40±0.37 vs. 1.94±0.09 ng/mL, respectively; P<0.001. Using a threshold level of 2.84 ng/mL, PTX3 yielded a sensitivity of 74.0% and a specificity of 84.0% for the detection of PAH. In CTD-PAH patients, mean PTX3 concentrations were significantly higher than in CTD patients without PAH (5.02±0.69 vs. 2.40±0.14 ng/mL, respectively; P<0.001. There was no significant correlation between plasma levels of PTX3 and BNP or CRP. Receiver operating characteristic (ROC curves for screening PAH in patients with CTD revealed that PTX3 (area under the ROC curve 0.866 is superior to BNP. Using a PTX3 threshold of 2.85 ng/mL maximized true-positive and false-negative results (sensitivity 94.1%, specificity 73.5%. CONCLUSION: Plasma concentrations of PTX3 may be a better biomarker of PAH than BNP, especially in patients with CTD.

  12. [Pulmonary hypertension in human immunodeficiency virus-infected patients: the role of antiretroviral therapy].

    Science.gov (United States)

    Olalla, Julián; Urdiales, Daniel; Pombo, Marta; del Arco, Alfonso; de la Torre, Javier; Prada, José Luis

    2014-03-20

    Pulmonary arterial hypertension (PAH) is a serious disorder, more prevalent in patients infected with human immunodeficiency virus (HIV). It is not entirely clear what role is played by highly active antiretroviral therapy (HAART) in PAH development or course. Our aim was to describe PAH prevalence in a series of HIV-infected patients and identify possible links with cumulative and current use of different antiretrovirals. Cross-sectional study of a cohort of HIV-infected patients attending a hospital in southern Spain. Demographic data, data on HIV infection status and on cumulative and recent antiretroviral treatment were recorded. Transthoracic echocardiography was performed in all study participants. PAH was defined as pulmonary artery systolic pressure of 36mmHg or more. A total of 400 patients participated in the study; 178 presented with tricuspid regurgitation and 22 of these presented with PAH (5.5%). No differences were encountered in age, sex, CD4 lymphocytes, proportion of naive patients or patients with AIDS. No differences were encountered in cumulative use of antiretrovirals. However, recent use of lamivudine was associated with a greater presence of PAH, whereas recent use of tenofovir and emtricitabine was associated with a lower presence of PAH. Logistic regression analysis was performed including the use of lamivudine, emtricitabine and tenofovir. Only recent use of tenofovir was associated with a lower presence of PAH (odds ratio 0.31; 95% confidence interval: 0.17-0.84). PAH prevalence in our study was similar to others series. Current use of tenofovir may be associated with lower PAH prevalence. Copyright © 2012 Elsevier España, S.L. All rights reserved.

  13. Angiotensin II Regulates microRNA-132/-212 in Hypertensive Rats and Humans

    DEFF Research Database (Denmark)

    Eskildsen, Tilde V; Jeppesen, Pia L; Schneider, Mikael

    2013-01-01

    MicroRNAs (miRNAs), a group of small non-coding RNAs that fine tune translation of multiple target mRNAs, are emerging as key regulators in cardiovascular development and disease. MiRNAs are involved in cardiac hypertrophy, heart failure and remodeling following cardiac infarction; however, mi...... no effect. Taken together, these data suggest that miR-132 and miR-212 are involved in AngII induced hypertension, providing a new perspective in hypertensive disease mechanisms....

  14. Does higher education protect against obesity? Evidence using Mendelian randomization.

    Science.gov (United States)

    Böckerman, Petri; Viinikainen, Jutta; Pulkki-Råback, Laura; Hakulinen, Christian; Pitkänen, Niina; Lehtimäki, Terho; Pehkonen, Jaakko; Raitakari, Olli T

    2017-08-01

    The aim of this explorative study was to examine the effect of education on obesity using Mendelian randomization. Participants (N=2011) were from the on-going nationally representative Young Finns Study (YFS) that began in 1980 when six cohorts (aged 30, 33, 36, 39, 42 and 45 in 2007) were recruited. The average value of BMI (kg/m 2 ) measurements in 2007 and 2011 and genetic information were linked to comprehensive register-based information on the years of education in 2007. We first used a linear regression (Ordinary Least Squares, OLS) to estimate the relationship between education and BMI. To identify a causal relationship, we exploited Mendelian randomization and used a genetic score as an instrument for education. The genetic score was based on 74 genetic variants that genome-wide association studies (GWASs) have found to be associated with the years of education. Because the genotypes are randomly assigned at conception, the instrument causes exogenous variation in the years of education and thus enables identification of causal effects. The years of education in 2007 were associated with lower BMI in 2007/2011 (regression coefficient (b)=-0.22; 95% Confidence Intervals [CI]=-0.29, -0.14) according to the linear regression results. The results based on Mendelian randomization suggests that there may be a negative causal effect of education on BMI (b=-0.84; 95% CI=-1.77, 0.09). The findings indicate that education could be a protective factor against obesity in advanced countries. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. Janus-kinase-2 relates directly to portal hypertension and to complications in rodent and human cirrhosis.

    Science.gov (United States)

    Klein, Sabine; Rick, Johanna; Lehmann, Jennifer; Schierwagen, Robert; Schierwagen, Irela Gretchen; Verbeke, Len; Hittatiya, Kanishka; Uschner, Frank Erhard; Manekeller, Steffen; Strassburg, Christian P; Wagner, Kay-Uwe; Sayeski, Peter P; Wolf, Dominik; Laleman, Wim; Sauerbruch, Tilman; Trebicka, Jonel

    2017-01-01

    Angiotensin II (AngII) activates via angiotensin-II-type-I receptor (AT1R) Janus-kinase-2 (JAK2)/Arhgef1 pathway and subsequently RHOA/Rho-kinase (ROCK), which induces experimental and probably human liver fibrosis. This study investigated the relationship of JAK2 to experimental and human portal hypertension. The mRNA and protein levels of JAK2/ARHGEF1 signalling components were analysed in 49 human liver samples and correlated with clinical parameters of portal hypertension in these patients. Correspondingly, liver fibrosis (bile duct ligation (BDL), carbon tetrachloride (CCl 4 )) was induced in floxed-Jak2 knock-out mice with SM22-promotor (SM22 Cre+ -Jak2 f/f ). Transcription and contraction of primary myofibroblasts from healthy and fibrotic mice and rats were analysed. In two different cirrhosis models (BDL, CCl 4 ) in rats, the acute haemodynamic effect of the JAK2 inhibitor AG490 was assessed using microsphere technique and isolated liver perfusion experiments. Hepatic transcription of JAK2/ARHGEF1 pathway components was upregulated in liver cirrhosis dependent on aetiology, severity and complications of human liver cirrhosis (Model for End-stage Liver disease (MELD) score, Child score as well as ascites, high-risk varices, spontaneous bacterial peritonitis). SM22 Cre+ - Jak2 f/f mice lacking Jak2 developed less fibrosis and lower portal pressure (PP) than SM22 Cre- -Jak2 f/f upon fibrosis induction. Myofibroblasts from SM22 Cre+ -Jak2 f/f mice expressed less collagen and profibrotic markers upon activation. AG490 relaxed activated hepatic stellate cells in vitro. In cirrhotic rats, AG490 decreased hepatic vascular resistance and consequently the PP in vivo and in situ. Hepatic JAK2/ARHGEF1/ROCK expression is associated with portal hypertension and decompensation in human cirrhosis. The deletion of Jak2 in myofibroblasts attenuated experimental fibrosis and acute inhibition of JAK2 decreased PP. Thus, JAK2 inhibitors, already in clinical use for other

  16. Paraventricular nucleus of the human hypothalamus in primary hypertension: Activation of corticotropin-releasing hormone neurons

    NARCIS (Netherlands)

    Goncharuk, Valeri D.; van Heerikhuize, Joop; Swaab, Dick F.; Buijs, Ruud M.

    2002-01-01

    By using quantitative immunohistochemical and in situ hybridization techniques, we studied corticotropin-releasing hormone (CRH)-producing neurons of the hypothalamic paraventricular nucleus (PVN) in patients who suffered from primary hypertension and died due to acute cardiac failure. The control

  17. Hepatotoxic effects of fenofibrate in spontaneously hypertensive rats expressing human C-reactive protein

    Czech Academy of Sciences Publication Activity Database

    Škop, V.; Trnovská, J.; Oliyarnyk, O.; Marková, I.; Malínská, H.; Kazdová, L.; Zídek, Václav; Landa, Vladimír; Mlejnek, Petr; Šimáková, Miroslava; Kůdela, M.; Pravenec, Michal; Šilhavý, Jan

    2016-01-01

    Roč. 65, č. 6 (2016), s. 891-899 ISSN 0862-8408 R&D Projects: GA MZd(CZ) NT14325 Institutional support: RVO:67985823 Keywords : fenofibrate * rosuvastatin * C-reactive protein * transgenic * spontaneously hypertensive rat * inflammation * hepatotoxic Subject RIV: FB - Endocrinology, Diabetology, Metabolism, Nutrition Impact factor: 1.461, year: 2016

  18. Na(+),K(+)-ATPase of human placenta during gestational hypertension: a biochemical-biophysical study

    Czech Academy of Sciences Publication Activity Database

    Rabini, R. A.; Zolese, G.; Staffolani, R.; Lucarelli, G.; Amler, Evžen; Cester, N.; Mazzanti, L.

    1996-01-01

    Roč. 91, č. 6 (1996), s. 719-723 ISSN 0143-5221 Institutional research plan: CEZ:AV0Z5011922 Keywords : activation energy * fluidity * gestational hypertension Subject RIV: CE - Biochemistry Impact factor: 2.154, year: 1996

  19. Common variants in mendelian kidney disease genes and their association with renal function

    NARCIS (Netherlands)

    A. Parsa (Afshin); C. Fuchsberger (Christian); A. Köttgen (Anna); C.M. O'Seaghdha (Conall); C. Pattaro (Cristian); M. de Andrade (Mariza); D.I. Chasman (Daniel); A. Teumer (Alexander); K. Endlich (Karlhans); M. Olden (Matthias); M-H. Chen (Ming-Huei); A. Tin (Adrienne); Y-J. Kim (Yong-Jin); D. Taliun (Daniel); M. Li (Man); M.F. Feitosa (Mary Furlan); M. Gorski (Mathias); Q. Yang (Qiong); C. Hundertmark (Claudia); M.C. Foster (Michael); N. Glazer (Nicole); A.J. Isaacs (Aaron); M. Rao (Madhumathi); G.D. Smith; J.R. O´Connell; M.V. Struchalin (Maksim); T. Tanaka (Toshiko); G. Li (Guo); S.J. Hwang; E.J. Atkinson (Elizabeth); K. Lohman (Kurt); M. Cornelis (Marilyn); A. Johansson (Åsa); A. Tönjes (Anke); A. Dehghan (Abbas); V. Couraki (Vincent); E.G. Holliday (Elizabeth); R. Sorice; Z. Kutalik (Zoltán); T. Lehtimäki (Terho); T. Esko (Tõnu); H. Deshmukh (Harshal); S. Ulivi (Shelia); A.Y. Chu (Audrey); D. Murgia (Daniela); S. Trompet (Stella); M. Imboden (Medea); B. Kollerits (Barbara); G. Pistis (Giorgio); T.B. Harris (Tamara); L.J. Launer (Lenore); T. Aspelund (Thor); G. Eiriksdottir (Gudny); B.D. Mitchell (Braxton); E.A. Boerwinkle (Eric); H. Schmidt (Helena); E. Hofer (Edith); F.B. Hu (Frank); A. Demirkan (Ayşe); B.A. Oostra (Ben); S.T. Turner (Stephen); J. Ding (Jingzhong); J.S. Andrews (Jeanette); B.I. Freedman (Barry); F. Giulianini (Franco); W. Koenig (Wolfgang); T. Illig (Thomas); A. Döring (Angela); H.E. Wichmann (Heinz Erich); L. Zgaga (Lina); T. Zemunik (Tatijana); M. Boban (Mladen); C. Minelli (Cosetta); H.E. Wheeler (Heather); W. Igl (Wilmar); G. Zaboli (Ghazal); S.H. Wild (Sarah); A.F. Wright (Alan); H. Campbell (Harry); D. Ellinghaus (David); U. Nöthlings (Ute); G. Jacobs (Gunnar); R. Biffar (Reiner); F.D.J. Ernst (Florian); G. Homuth (Georg); H.K. Kroemer (Heyo); M. Nauck (Matthias); S. Stracke (Sylvia); U. Vol̈ker (Uwe); H. Völzke (Henry); P. Kovacs (Peter); M. Stumvoll (Michael); R. Mägi (Reedik); A. Hofman (Albert); A.G. Uitterlinden (André); F. Rivadeneira Ramirez (Fernando); Y.S. Aulchenko (Yurii); O. Polasek (Ozren); N. Hastie (Nick); V. Vitart (Veronique); C. Helmer (Catherine); J.J. Wang (Jie Jin); B. Stengel (Bernd); D. Ruggiero; S.M. Bergmann (Sven); M. Kähönen (Mika); J. Viikari (Jorma); T. Nikopensius (Tiit); M.A. Province (Mike); H.M. Colhoun (H.); A.S.F. Doney (Alex); A. Robino (Antonietta); B.K. Krämer (Bernhard); L. Portas (Laura); I. Ford (Ian); B.M. Buckley (Brendan M.); M. Adam (Martin); G.-A. Thun (Gian-Andri); B. Paulweber (Bernhard); M. Haun (Margot); C. Sala (Cinzia); P. Mitchell (Paul); M. Ciullo; P. Vollenweider (Peter); O. Raitakari (Olli); A. Metspalu (Andres); C.N.A. Palmer (Colin); P. Gasparini (Paolo); M. Pirastu (Mario); J.W. Jukema (Jan Wouter); N.M. Probst-Hensch (Nicole M.); F. Kronenberg (Florian); D. Toniolo (Daniela); V. Gudnason (Vilmundur); A.R. Shuldiner (Alan); J. Coresh (Josef); R. Schmidt (Reinhold); L. Ferrucci (Luigi); C.M. van Duijn (Cornelia); I.B. Borecki (Ingrid); S.L.R. Kardia (Sharon); Y. Liu (YongMei); G.C. Curhan (Gary); I. Rudan (Igor); U. Gyllensten (Ulf); J.F. Wilson (James); A. Franke (Andre); P.P. Pramstaller (Peter Paul); R. Rettig (Rainer); I. Prokopenko (Inga); J.C.M. Witteman (Jacqueline); C. Hayward (Caroline); P.M. Ridker (Paul); M. Bochud (Murielle); I.M. Heid (Iris); D.S. Siscovick (David); C.S. Fox (Caroline); W.H.L. Kao (Wen); C.A. Böger (Carsten)

    2013-01-01

    textabstractMany common genetic variants identified by genome-wide association studies for complex traitsmap to genes previously linked to rare inherited Mendelian disorders. A systematic analysis of common single-nucleotide polymorphisms (SNPs) in genes responsible for Mendelian diseases with

  20. Mitochondria-targeted antioxidant mitoquinone deactivates human and rat hepatic stellate cells and reduces portal hypertension in cirrhotic rats.

    Science.gov (United States)

    Vilaseca, Marina; García-Calderó, Héctor; Lafoz, Erica; Ruart, Maria; López-Sanjurjo, Cristina Isabel; Murphy, Michael P; Deulofeu, Ramon; Bosch, Jaume; Hernández-Gea, Virginia; Gracia-Sancho, Jordi; García-Pagán, Juan Carlos

    2017-07-01

    In cirrhosis, activated hepatic stellate cells (HSC) play a major role in increasing intrahepatic vascular resistance and developing portal hypertension. We have shown that cirrhotic livers have increased reactive oxygen species (ROS), and that antioxidant therapy decreases portal pressure. Considering that mitochondria produce many of these ROS, our aim was to assess the effects of the oral mitochondria-targeted antioxidant mitoquinone on hepatic oxidative stress, HSC phenotype, liver fibrosis and portal hypertension. Ex vivo: Hepatic stellate cells phenotype was analysed in human precision-cut liver slices in response to mitoquinone or vehicle. In vitro: Mitochondrial oxidative stress was analysed in different cell type of livers from control and cirrhotic rats. HSC phenotype, proliferation and viability were assessed in LX2, and in primary human and rat HSC treated with mitoquinone or vehicle. In vivo: CCl 4 - and thioacetamide-cirrhotic rats were treated with mitoquinone (5 mg/kg/day) or the vehicle compound, DecylTPP, for 2 weeks, followed by measurement of oxidative stress, systemic and hepatic haemodynamic, liver fibrosis, HSC phenotype and liver inflammation. Mitoquinone deactivated human and rat HSC, decreased their proliferation but with no effects on viability. In CCl 4 -cirrhotic rats, mitoquinone decreased hepatic oxidative stress, improved HSC phenotype, reduced intrahepatic vascular resistance and diminished liver fibrosis. These effects were associated with a significant reduction in portal pressure without changes in arterial pressure. These results were further confirmed in the thioacetamide-cirrhotic model. We propose mitochondria-targeted antioxidants as a novel treatment approach against portal hypertension and cirrhosis. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  1. The Role of Adiposity in Cardiometabolic Traits: A Mendelian Randomization Analysis

    Science.gov (United States)

    Ploner, Alexander; Fischer, Krista; Horikoshi, Momoko; Sarin, Antti-Pekka; Thorleifsson, Gudmar; Ladenvall, Claes; Kals, Mart; Kuningas, Maris; Draisma, Harmen H. M.; Ried, Janina S.; van Zuydam, Natalie R.; Huikari, Ville; Mangino, Massimo; Sonestedt, Emily; Benyamin, Beben; Nelson, Christopher P.; Rivera, Natalia V.; Kristiansson, Kati; Shen, Huei-yi; Havulinna, Aki S.; Dehghan, Abbas; Donnelly, Louise A.; Kaakinen, Marika; Nuotio, Marja-Liisa; Robertson, Neil; de Bruijn, Renée F. A. G.; Ikram, M. Arfan; Amin, Najaf; Balmforth, Anthony J.; Braund, Peter S.; Doney, Alexander S. F.; Döring, Angela; Elliott, Paul; Esko, Tõnu; Franco, Oscar H.; Gretarsdottir, Solveig; Hartikainen, Anna-Liisa; Heikkilä, Kauko; Herzig, Karl-Heinz; Holm, Hilma; Hottenga, Jouke Jan; Hyppönen, Elina; Illig, Thomas; Isaacs, Aaron; Isomaa, Bo; Karssen, Lennart C.; Kettunen, Johannes; Koenig, Wolfgang; Kuulasmaa, Kari; Laatikainen, Tiina; Laitinen, Jaana; Lindgren, Cecilia; Lyssenko, Valeriya; Läärä, Esa; Rayner, Nigel W.; Männistö, Satu; Pouta, Anneli; Rathmann, Wolfgang; Rivadeneira, Fernando; Ruokonen, Aimo; Savolainen, Markku J.; Sijbrands, Eric J. G.; Small, Kerrin S.; Smit, Jan H.; Steinthorsdottir, Valgerdur; Syvänen, Ann-Christine; Taanila, Anja; Tobin, Martin D.; Uitterlinden, Andre G.; Willems, Sara M.; Willemsen, Gonneke; Witteman, Jacqueline; Perola, Markus; Evans, Alun; Ferrières, Jean; Virtamo, Jarmo; Kee, Frank; Tregouet, David-Alexandre; Arveiler, Dominique; Amouyel, Philippe; Ferrario, Marco M.; Brambilla, Paolo; Hall, Alistair S.; Heath, Andrew C.; Madden, Pamela A. F.; Martin, Nicholas G.; Montgomery, Grant W.; Whitfield, John B.; Jula, Antti; Knekt, Paul; Oostra, Ben; van Duijn, Cornelia M.; Penninx, Brenda W. J. H.; Davey Smith, George; Kaprio, Jaakko; Samani, Nilesh J.; Gieger, Christian; Peters, Annette; Wichmann, H.-Erich; Boomsma, Dorret I.; de Geus, Eco J. C.; Tuomi, TiinaMaija; Power, Chris; Hammond, Christopher J.; Spector, Tim D.; Lind, Lars; Orho-Melander, Marju; Palmer, Colin Neil Alexander; Morris, Andrew D.; Groop, Leif; Järvelin, Marjo-Riitta; Salomaa, Veikko; Vartiainen, Erkki; Hofman, Albert; Ripatti, Samuli; Metspalu, Andres; Thorsteinsdottir, Unnur; Stefansson, Kari; Pedersen, Nancy L.; McCarthy, Mark I.; Ingelsson, Erik; Prokopenko, Inga

    2013-01-01

    Background The association between adiposity and cardiometabolic traits is well known from epidemiological studies. Whilst the causal relationship is clear for some of these traits, for others it is not. We aimed to determine whether adiposity is causally related to various cardiometabolic traits using the Mendelian randomization approach. Methods and Findings We used the adiposity-associated variant rs9939609 at the FTO locus as an instrumental variable (IV) for body mass index (BMI) in a Mendelian randomization design. Thirty-six population-based studies of individuals of European descent contributed to the analyses. Age- and sex-adjusted regression models were fitted to test for association between (i) rs9939609 and BMI (n = 198,502), (ii) rs9939609 and 24 traits, and (iii) BMI and 24 traits. The causal effect of BMI on the outcome measures was quantified by IV estimators. The estimators were compared to the BMI–trait associations derived from the same individuals. In the IV analysis, we demonstrated novel evidence for a causal relationship between adiposity and incident heart failure (hazard ratio, 1.19 per BMI-unit increase; 95% CI, 1.03–1.39) and replicated earlier reports of a causal association with type 2 diabetes, metabolic syndrome, dyslipidemia, and hypertension (odds ratio for IV estimator, 1.1–1.4; all p<0.05). For quantitative traits, our results provide novel evidence for a causal effect of adiposity on the liver enzymes alanine aminotransferase and gamma-glutamyl transferase and confirm previous reports of a causal effect of adiposity on systolic and diastolic blood pressure, fasting insulin, 2-h post-load glucose from the oral glucose tolerance test, C-reactive protein, triglycerides, and high-density lipoprotein cholesterol levels (all p<0.05). The estimated causal effects were in agreement with traditional observational measures in all instances except for type 2 diabetes, where the causal estimate was larger than the observational

  2. The role of adiposity in cardiometabolic traits: a Mendelian randomization analysis.

    Directory of Open Access Journals (Sweden)

    Tove Fall

    Full Text Available The association between adiposity and cardiometabolic traits is well known from epidemiological studies. Whilst the causal relationship is clear for some of these traits, for others it is not. We aimed to determine whether adiposity is causally related to various cardiometabolic traits using the Mendelian randomization approach.We used the adiposity-associated variant rs9939609 at the FTO locus as an instrumental variable (IV for body mass index (BMI in a Mendelian randomization design. Thirty-six population-based studies of individuals of European descent contributed to the analyses. Age- and sex-adjusted regression models were fitted to test for association between (i rs9939609 and BMI (n  =  198,502, (ii rs9939609 and 24 traits, and (iii BMI and 24 traits. The causal effect of BMI on the outcome measures was quantified by IV estimators. The estimators were compared to the BMI-trait associations derived from the same individuals. In the IV analysis, we demonstrated novel evidence for a causal relationship between adiposity and incident heart failure (hazard ratio, 1.19 per BMI-unit increase; 95% CI, 1.03-1.39 and replicated earlier reports of a causal association with type 2 diabetes, metabolic syndrome, dyslipidemia, and hypertension (odds ratio for IV estimator, 1.1-1.4; all p < 0.05. For quantitative traits, our results provide novel evidence for a causal effect of adiposity on the liver enzymes alanine aminotransferase and gamma-glutamyl transferase and confirm previous reports of a causal effect of adiposity on systolic and diastolic blood pressure, fasting insulin, 2-h post-load glucose from the oral glucose tolerance test, C-reactive protein, triglycerides, and high-density lipoprotein cholesterol levels (all p < 0.05. The estimated causal effects were in agreement with traditional observational measures in all instances except for type 2 diabetes, where the causal estimate was larger than the observational estimate (p  =  0

  3. A review of instrumental variable estimators for Mendelian randomization.

    Science.gov (United States)

    Burgess, Stephen; Small, Dylan S; Thompson, Simon G

    2017-10-01

    Instrumental variable analysis is an approach for obtaining causal inferences on the effect of an exposure (risk factor) on an outcome from observational data. It has gained in popularity over the past decade with the use of genetic variants as instrumental variables, known as Mendelian randomization. An instrumental variable is associated with the exposure, but not associated with any confounder of the exposure-outcome association, nor is there any causal pathway from the instrumental variable to the outcome other than via the exposure. Under the assumption that a single instrumental variable or a set of instrumental variables for the exposure is available, the causal effect of the exposure on the outcome can be estimated. There are several methods available for instrumental variable estimation; we consider the ratio method, two-stage methods, likelihood-based methods, and semi-parametric methods. Techniques for obtaining statistical inferences and confidence intervals are presented. The statistical properties of estimates from these methods are compared, and practical advice is given about choosing a suitable analysis method. In particular, bias and coverage properties of estimators are considered, especially with weak instruments. Settings particularly relevant to Mendelian randomization are prioritized in the paper, notably the scenario of a continuous exposure and a continuous or binary outcome.

  4. Bilirubin and Stroke Risk Using a Mendelian Randomization Design.

    Science.gov (United States)

    Lee, Sun Ju; Jee, Yon Ho; Jung, Keum Ji; Hong, Seri; Shin, Eun Soon; Jee, Sun Ha

    2017-05-01

    Circulating bilirubin, a natural antioxidant, is associated with decreased risk of stroke. However, the nature of the relationship between the two remains unknown. We used a Mendelian randomization analysis to assess the causal effect of serum bilirubin on stroke risk in Koreans. The 14 single-nucleotide polymorphisms (SNPs) (bilirubin level in the KCPS-II (Korean Cancer Prevention Study-II) Biobank subcohort consisting of 4793 healthy Korean and 806 stroke cases. Weighted genetic risk score was calculated using 14 SNPs selected from the top SNPs. Both rs6742078 (F statistics=138) and weighted genetic risk score with 14 SNPs (F statistics=187) were strongly associated with bilirubin levels. Simultaneously, serum bilirubin level was associated with decreased risk of stroke in an ordinary least-squares analysis. However, in 2-stage least-squares Mendelian randomization analysis, no causal relationship between serum bilirubin and stroke risk was found. There is no evidence that bilirubin level is causally associated with risk of stroke in Koreans. Therefore, bilirubin level is not a risk determinant of stroke. © 2017 American Heart Association, Inc.

  5. Portal Hypertension

    Science.gov (United States)

    ... Overview of Gallbladder Cancer Additional Content Medical News Portal Hypertension By Steven K. Herrine, MD, Professor of Medicine, ... Liver Hepatic Encephalopathy Jaundice in Adults Liver Failure Portal Hypertension Portal hypertension is abnormally high blood pressure in ...

  6. [Secondary hypertension].

    Science.gov (United States)

    Yoshida, Yuichi; Shibata, Hirotaka

    2015-11-01

    Hypertension is a common disease and a crucial predisposing factor of cardiovascular diseases. Approximately 10% of hypertensive patients are secondary hypertension, a pathogenetic factor of which can be identified. Secondary hypertension consists of endocrine, renal, and other diseases. Primary aldosteronism, Cushing's syndrome, pheochromocytoma, hyperthyroidism, and hypothyroidism result in endocrine hypertension. Renal parenchymal hypertension and renovascular hypertension result in renal hypertension. Other diseases such as obstructive sleep apnea syndrome are also very prevalent in secondary hypertension. It is very crucial to find and treat secondary hypertension at earlier stages since most secondary hypertension is curable or can be dramatically improved by specific treatment. One should keep in mind that screening of secondary hypertension should be done at least once in a daily clinical practice.

  7. Secondary Hypertension

    Science.gov (United States)

    Secondary hypertension Overview Secondary hypertension (secondary high blood pressure) is high blood pressure that's caused by another medical condition. Secondary hypertension can be caused by conditions that affect your kidneys, ...

  8. Parent-offspring conflict and the persistence of pregnancy-induced hypertension in modern humans.

    Directory of Open Access Journals (Sweden)

    Birgitte Hollegaard

    Full Text Available Preeclampsia is a major cause of perinatal mortality and disease affecting 5-10% of all pregnancies worldwide, but its etiology remains poorly understood despite considerable research effort. Parent-offspring conflict theory suggests that such hypertensive disorders of pregnancy may have evolved through the ability of fetal genes to increase maternal blood pressure as this enhances general nutrient supply. However, such mechanisms for inducing hypertension in pregnancy would need to incur sufficient offspring health benefits to compensate for the obvious risks for maternal and fetal health towards the end of pregnancy in order to explain why these disorders have not been removed by natural selection in our hunter-gatherer ancestors. We analyzed >750,000 live births in the Danish National Patient Registry and all registered medical diagnoses for up to 30 years after birth. We show that offspring exposed to pregnancy-induced hypertension (PIH in trimester 1 had significantly reduced overall later-life disease risks, but increased risks when PIH exposure started or developed as preeclampsia in later trimesters. Similar patterns were found for first-year mortality. These results suggest that early PIH leading to improved postpartum survival and health represents a balanced compromise between the reproductive interests of parents and offspring, whereas later onset of PIH may reflect an unbalanced parent-offspring conflict at the detriment of maternal and offspring health.

  9. Education and coronary heart disease: mendelian randomisation study.

    Science.gov (United States)

    Tillmann, Taavi; Vaucher, Julien; Okbay, Aysu; Pikhart, Hynek; Peasey, Anne; Kubinova, Ruzena; Pajak, Andrzej; Tamosiunas, Abdonas; Malyutina, Sofia; Hartwig, Fernando Pires; Fischer, Krista; Veronesi, Giovanni; Palmer, Tom; Bowden, Jack; Davey Smith, George; Bobak, Martin; Holmes, Michael V

    2017-08-30

    Objective  To determine whether educational attainment is a causal risk factor in the development of coronary heart disease. Design  Mendelian randomisation study, using genetic data as proxies for education to minimise confounding. Setting  The main analysis used genetic data from two large consortia (CARDIoGRAMplusC4D and SSGAC), comprising 112 studies from predominantly high income countries. Findings from mendelian randomisation analyses were then compared against results from traditional observational studies (164 170 participants). Finally, genetic data from six additional consortia were analysed to investigate whether longer education can causally alter the common cardiovascular risk factors. Participants  The main analysis was of 543 733 men and women (from CARDIoGRAMplusC4D and SSGAC), predominantly of European origin. Exposure  A one standard deviation increase in the genetic predisposition towards higher education (3.6 years of additional schooling), measured by 162 genetic variants that have been previously associated with education. Main outcome measure  Combined fatal and non-fatal coronary heart disease (63 746 events in CARDIoGRAMplusC4D). Results  Genetic predisposition towards 3.6 years of additional education was associated with a one third lower risk of coronary heart disease (odds ratio 0.67, 95% confidence interval 0.59 to 0.77; P=3×10 -8 ). This was comparable to findings from traditional observational studies (prevalence odds ratio 0.73, 0.68 to 0.78; incidence odds ratio 0.80, 0.76 to 0.83). Sensitivity analyses were consistent with a causal interpretation in which major bias from genetic pleiotropy was unlikely, although this remains an untestable possibility. Genetic predisposition towards longer education was additionally associated with less smoking, lower body mass index, and a favourable blood lipid profile. Conclusions  This mendelian randomisation study found support for the hypothesis that low education is a causal risk

  10. The causal effect of red blood cell folate on genome-wide methylation in cord blood: a Mendelian randomization approach.

    Science.gov (United States)

    Binder, Alexandra M; Michels, Karin B

    2013-12-04

    Investigation of the biological mechanism by which folate acts to affect fetal development can inform appraisal of expected benefits and risk management. This research is ethically imperative given the ubiquity of folic acid fortified products in the US. Considering that folate is an essential component in the one-carbon metabolism pathway that provides methyl groups for DNA methylation, epigenetic modifications provide a putative molecular mechanism mediating the effect of folic acid supplementation on neonatal and pediatric outcomes. In this study we use a Mendelian Randomization Unnecessary approach to assess the effect of red blood cell (RBC) folate on genome-wide DNA methylation in cord blood. Site-specific CpG methylation within the proximal promoter regions of approximately 14,500 genes was analyzed using the Illumina Infinium Human Methylation27 Bead Chip for 50 infants from the Epigenetic Birth Cohort at Brigham and Women's Hospital in Boston. Using methylenetetrahydrofolate reductase genotype as the instrument, the Mendelian Randomization approach identified 7 CpG loci with a significant (mostly positive) association between RBC folate and methylation level. Among the genes in closest proximity to this significant subset of CpG loci, several enriched biologic processes were involved in nucleic acid transport and metabolic processing. Compared to the standard ordinary least squares regression method, our estimates were demonstrated to be more robust to unmeasured confounding. To the authors' knowledge, this is the largest genome-wide analysis of the effects of folate on methylation pattern, and the first to employ Mendelian Randomization to assess the effects of an exposure on epigenetic modifications. These results can help guide future analyses of the causal effects of periconceptional folate levels on candidate pathways.

  11. [Pulmonary hypertension in patients infected with human immunodeficiency virus: current situation].

    Science.gov (United States)

    Soto-Abánades, Clara Itzíar; Alcolea-Batres, Sergio; Ríos-Blanco, Juan José

    2013-01-01

    The increase in survival that has been achieved with the new treatments in the era of highly active antiretroviral therapy, has enabled clinicians and researchers to analyze issues that emerge in the long term in patients with HIV infection. Although the majority of cardiovascular complications have been widely described, the pathogenesis of pulmonary arterial hypertension is still poorly understood, and is one of the more complex and feared complications as it worsens the prognosis and quality of life of these patients This article reviews newer aspects related to the aetiology, symptoms, diagnosis and treatment of this disease. Copyright © 2011 Elsevier España, S.L. All rights reserved.

  12. Dairy consumption, systolic blood pressure, and risk of hypertension

    DEFF Research Database (Denmark)

    Ding, Ming; Huang, Tao; Bergholdt, Helle Km

    2017-01-01

    Objective To examine whether previous observed inverse associations of dairy intake with systolic blood pressure and risk of hypertension were causal.Design Mendelian randomization study using the single nucleotide polymorphism rs4988235 related to lactase persistence as an instrumental variable...... blood pressure but not risk of hypertension (odds ratio 0.98, 0.97 to 1.00; P=0.11).Conclusion The weak inverse association between dairy intake and systolic blood pressure in observational studies was not supported by a comprehensive instrumental variable analysis and systematic review of existing...

  13. Parent-offspring conflict and the persistence of pregnancy-induced hypertension in modern humans

    DEFF Research Database (Denmark)

    Hartsteen, Birgitte Hollegaard; Byars, Sean Geoffrey; Lykke, Jacob

    2013-01-01

    Preeclampsia is a major cause of perinatal mortality and disease affecting 5-10% of all pregnancies worldwide, but its etiology remains poorly understood despite considerable research effort. Parent-offspring conflict theory suggests that such hypertensive disorders of pregnancy may have evolved...... towards the end of pregnancy in order to explain why these disorders have not been removed by natural selection in our hunter-gatherer ancestors. We analyzed >750,000 live births in the Danish National Patient Registry and all registered medical diagnoses for up to 30 years after birth. We show...... that early PIH leading to improved postpartum survival and health represents a balanced compromise between the reproductive interests of parents and offspring, whereas later onset of PIH may reflect an unbalanced parent-offspring conflict at the detriment of maternal and offspring health....

  14. A Nondegenerate Code of Deleterious Variants in Mendelian Loci Contributes to Complex Disease Risk

    DEFF Research Database (Denmark)

    Blair, David R.; Lyttle, Christopher S.; Mortensen, Jonathan M.

    2013-01-01

    Although countless highly penetrant variants have been associated with Mendelian disorders, the genetic etiologies underlying complex diseases remain largely unresolved. By mining the medical records of over 110 million patients, we examine the extent to which Mendelian variation contributes to c...... of complex diseases. Overall, this study illustrates a complementary approach for mapping complex disease loci and provides unique predictions concerning the etiologies of specific diseases....

  15. Hypertensive Crisis

    Science.gov (United States)

    ... Artery Disease Venous Thromboembolism Aortic Aneurysm More Hypertensive Crisis: When You Should Call 9-1-1 for ... Nov 13,2017 A hypertensive ( high blood pressure ) crisis is when blood pressure rises quickly and severely ...

  16. Hypertension, a health economics perspective.

    Science.gov (United States)

    Alcocer, Luis; Cueto, Liliana

    2008-06-01

    The economic aspects of hypertension are critical to modern medicine. The medical, economic, and human costs of untreated and inadequately controlled hypertension are enormous. Hypertension is distributed unequally and with iniquity in different countries and regions of the world. Treatment of hypertension requires an investment over many years to prolong disease-free quality years of life. The high prevalence and high cost of the disease impacts on the microeconomics and macroeconomics of countries and regions. The criteria used for inclusion in clinical guidelines for hypertension impact on the cost and cost/utility of diagnosis or treatment.

  17. Hibiscus sabdariffa L. in the treatment of hypertension and hyperlipidemia: a comprehensive review of animal and human studies

    Science.gov (United States)

    Hopkins, Allison L.; Lamm, Marnie G.; Funk, Janet; Ritenbaugh, Cheryl

    2013-01-01

    calyxes are generally considered the phytochemicals responsible for the antihypertensive and hypocholesterolemic effects, however evidence has also been provided for the role of polyphenols and hibiscus acid. A number of potential mechanisms have been proposed to explain the hypotensive and anticholesterol effects, but the most common explanation is the antioxidant effects of the anthocyanins inhibition of LDL-C oxidation, which impedes atherosclerosis, an important cardiovascular risk factor. This comprehensive body of evidence suggests that extracts of HS are promising as a treatment of hypertension and hyperlipidemia, however more high quality animal and human studies informed by actual therapeutic practices are needed to provide recommendations for use that have the potential for widespread public health benefit. PMID:23333908

  18. Hibiscus sabdariffa L. in the treatment of hypertension and hyperlipidemia: a comprehensive review of animal and human studies.

    Science.gov (United States)

    Hopkins, Allison L; Lamm, Marnie G; Funk, Janet L; Ritenbaugh, Cheryl

    2013-03-01

    calyxes are generally considered the phytochemicals responsible for the antihypertensive and hypocholesterolemic effects, however evidence has also been provided for the role of polyphenols and hibiscus acid. A number of potential mechanisms have been proposed to explain the hypotensive and anticholesterol effects, but the most common explanation is the antioxidant effects of the anthocyanins inhibition of LDL-C oxidation, which impedes atherosclerosis, an important cardiovascular risk factor. This comprehensive body of evidence suggests that extracts of HS are promising as a treatment of hypertension and hyperlipidemia, however more high quality animal and human studies informed by actual therapeutic practices are needed to provide recommendations for use that have the potential for widespread public health benefit. Published by Elsevier B.V.

  19. Analysis of neurodegenerative Mendelian genes in clinically diagnosed Alzheimer Disease.

    Directory of Open Access Journals (Sweden)

    Maria Victoria Fernández

    2017-11-01

    Full Text Available Alzheimer disease (AD, Frontotemporal lobar degeneration (FTD, Amyotrophic lateral sclerosis (ALS and Parkinson disease (PD have a certain degree of clinical, pathological and molecular overlap. Previous studies indicate that causative mutations in AD and FTD/ALS genes can be found in clinical familial AD. We examined the presence of causative and low frequency coding variants in the AD, FTD, ALS and PD Mendelian genes, in over 450 families with clinical history of AD and over 11,710 sporadic cases and cognitive normal participants from North America. Known pathogenic mutations were found in 1.05% of the sporadic cases, in 0.69% of the cognitively normal participants and in 4.22% of the families. A trend towards enrichment, albeit non-significant, was observed for most AD, FTD and PD genes. Only PSEN1 and PINK1 showed consistent association with AD cases when we used ExAC as the control population. These results suggest that current study designs may contain heterogeneity and contamination of the control population, and that current statistical methods for the discovery of novel genes with real pathogenic variants in complex late onset diseases may be inadequate or underpowered to identify genes carrying pathogenic mutations.

  20. Genetic diagnosis of Mendelian disorders via RNA sequencing.

    Science.gov (United States)

    Kremer, Laura S; Bader, Daniel M; Mertes, Christian; Kopajtich, Robert; Pichler, Garwin; Iuso, Arcangela; Haack, Tobias B; Graf, Elisabeth; Schwarzmayr, Thomas; Terrile, Caterina; Koňaříková, Eliška; Repp, Birgit; Kastenmüller, Gabi; Adamski, Jerzy; Lichtner, Peter; Leonhardt, Christoph; Funalot, Benoit; Donati, Alice; Tiranti, Valeria; Lombes, Anne; Jardel, Claude; Gläser, Dieter; Taylor, Robert W; Ghezzi, Daniele; Mayr, Johannes A; Rötig, Agnes; Freisinger, Peter; Distelmaier, Felix; Strom, Tim M; Meitinger, Thomas; Gagneur, Julien; Prokisch, Holger

    2017-06-12

    Across a variety of Mendelian disorders, ∼50-75% of patients do not receive a genetic diagnosis by exome sequencing indicating disease-causing variants in non-coding regions. Although genome sequencing in principle reveals all genetic variants, their sizeable number and poorer annotation make prioritization challenging. Here, we demonstrate the power of transcriptome sequencing to molecularly diagnose 10% (5 of 48) of mitochondriopathy patients and identify candidate genes for the remainder. We find a median of one aberrantly expressed gene, five aberrant splicing events and six mono-allelically expressed rare variants in patient-derived fibroblasts and establish disease-causing roles for each kind. Private exons often arise from cryptic splice sites providing an important clue for variant prioritization. One such event is found in the complex I assembly factor TIMMDC1 establishing a novel disease-associated gene. In conclusion, our study expands the diagnostic tools for detecting non-exonic variants and provides examples of intronic loss-of-function variants with pathological relevance.

  1. Darbishire expands his vision of heredity from Mendelian genetics to inherited memory.

    Science.gov (United States)

    Wood, Roger J

    2015-10-01

    The British biologist A.D. Darbishire (1879-1915) responded to the rediscovery in 1900 of Mendel's theory of heredity by testing it experimentally, first in Oxford, then in Manchester and London. He summarised his conclusions in a textbook 'Breeding and the Mendelian Discovery' (1911), in which he questioned whether Mendelism alone could explain all aspects of practical breeding experience. Already he had begun to think about an alternative theory to give greater emphasis to the widely held conviction among breeders regarding the inheritance of characteristics acquired during an individual's life. Redefining heredity in terms of a germ-plasm based biological memory, he used vocabulary drawn partly from sources outside conventional science, including the metaphysical/vitalistic writings of Samuel Butler and Henri Bergson. An evolving hereditary memory fitted well with the conception of breeding as a creative art aimed at greater economic efficiency. For evolution beyond human control he proposed a self-modifying process, claiming it to surpass in efficiency the chancy mechanism of natural selection proposed by Darwin. From his writings, including early chapters of an unfinished book entitled 'An Introduction to a Biology', we consider how he reached these concepts and how they relate to later advances in understanding the genome and the genetic programme. Copyright © 2015 Elsevier Ltd. All rights reserved.

  2. Resistant Hypertension.

    Science.gov (United States)

    Doroszko, Adrian; Janus, Agnieszka; Szahidewicz-Krupska, Ewa; Mazur, Grzegorz; Derkacz, Arkadiusz

    2016-01-01

    Resistant hypertension is a severe medical condition which is estimated to appear in 9-18% of hypertensive patients. Due to higher cardiovascular risk, this disorder requires special diagnosis and treatment. The heterogeneous etiology, risk factors and comorbidities of resistant hypertension stand in need of sophisticated evaluation to confirm the diagnosis and select the best therapeutic options, which should consider lifestyle modifications as well as pharmacological and interventional treatment. After having excluded pseudohypertension, inappropriate blood pressure measurement and control as well as the white coat effect, suspicion of resistant hypertension requires an analysis of drugs which the hypertensive patient is treated with. According to one definition - ineffective treatment with 3 or more antihypertensive drugs including diuretics makes it possible to diagnose resistant hypertension. A multidrug therapy including angiotensin - converting enzyme inhibitors, angiotensin II receptor blockers, beta blockers, diuretics, long-acting calcium channel blockers and mineralocorticoid receptor antagonists has been demonstrated to be effective in resistant hypertension treatment. Nevertheless, optional, innovative therapies, e.g. a renal denervation or baroreflex activation, may create a novel pathway of blood pressure lowering procedures. The right diagnosis of this disease needs to eliminate the secondary causes of resistant hypertension e.g. obstructive sleep apnea, atherosclerosis and renal or hormonal disorders. This paper briefly summarizes the identification of the causes of resistant hypertension and therapeutic strategies, which may contribute to the proper diagnosis and an improvement of the long term management of resistant hypertension.

  3. Moderate alcohol use and cardiovascular disease from Mendelian randomization.

    Directory of Open Access Journals (Sweden)

    Shiu Lun Au Yeung

    Full Text Available BACKGROUND: Observational studies show moderate alcohol use negatively associated with ischemic heart disease (IHD and cardiovascular disease (CVD. However, healthier attributes among moderate users compared to never users may confound the apparent association. A potentially less biased way to examine the association is Mendelian randomization, using alcohol metabolizing genes which influence alcohol use. METHODS: We used instrumental variable analysis with aldehyde dehydrogenase 2 (ALDH2 genotypes (AA/GA/GG as instrumental variables for alcohol use to examine the association of alcohol use (10 g ethanol/day with CVD risk factors (blood pressure, lipids and glucose and morbidity (self-reported IHD and CVD among men in the Guangzhou Biobank Cohort Study. RESULTS: ALDH2 genotypes were a credible instrument for alcohol use (F-statistic 74.6. Alcohol was positively associated with HDL-cholesterol (0.05 mmol/L per alcohol unit, 95% confidence interval (CI 0.02 to 0.08 and diastolic blood pressure (1.15 mmHg, 95% CI 0.23 to 2.07 but not with systolic blood pressure (1.00 mmHg, 95% CI -0.74 to 2.74, LDL-cholesterol (0.03 mmol/L, 95% CI -0.03 to 0.08, log transformed triglycerides (0.03 mmol/L, 95% CI -0.01 to 0.08 or log transformed fasting glucose (0.01 mmol/L, 95% CI -0.006 to 0.03, self-reported CVD (odds ratio (OR 0.98, 95% CI 0.76 to 1.27 or self-reported IHD (OR 1.10, 95% CI 0.83 to 1.45. CONCLUSION: Low to moderate alcohol use among men had the expected effects on most CVD risk factors but not fasting glucose. Larger studies are needed to confirm the null associations with IHD, CVD and fasting glucose.

  4. Exome Sequencing Identifies Potential Risk Variants for Mendelian Disorders at High Prevalence in Qatar

    Science.gov (United States)

    Rodriguez-Flores, Juan L.; Fakhro, Khalid; Hackett, Neil R.; Salit, Jacqueline; Fuller, Jennifer; Agosto-Perez, Francisco; Gharbiah, Maey; Malek, Joel A.; Zirie, Mahmoud; Jayyousi, Amin; Badii, Ramin; Al-Marri, Ajayeb Al-Nabet; Chouchane, Lotfi; Stadler, Dora J.; Hunter-Zinck, Haley; Mezey, Jason G.; Crystal, Ronald G.

    2013-01-01

    Exome sequencing of families of related individuals has been highly successful in identifying genetic polymorphisms responsible for Mendelian disorders. Here, we demonstrate the value of the reverse approach, where we use exome sequencing of a sample of unrelated individuals to analyze allele frequencies of known causal mutations for Mendelian diseases. We sequenced the exomes of 100 individuals representing the three major genetic subgroups of the Qatari population (Q1 Bedouin, Q2 Persian-South Asian, Q3 African) and identified 37 variants in 33 genes with effects on 36 clinically significant Mendelian diseases. These include variants not present in 1000 Genomes and variants at high frequency when compared to 1000 Genomes populations. Several of these Mendelian variants were only segregating in one Qatari subpopulation, where the observed subpopulation specificity trends were confirmed in an independent population of 386 Qataris. Pre-marital genetic screening in Qatar tests for only 4 out of the 37, such that this study provides a set of Mendelian disease variants with potential impact on the epidemiological profile of the population that could be incorporated into the testing program if further experimental and clinical characterization confirms high penetrance. PMID:24123366

  5. Effects of alpha-2 agonists on renal function in hypertensive humans.

    Science.gov (United States)

    Goldberg, M; Gehr, M

    1985-01-01

    Centrally acting adrenergic agonists, by decreasing peripheral adrenergic activity, are effective antihypertensive agents. The older agents, however, especially methyldopa, have been associated with weight gain, clinical edema, and antihypertensive tolerance when used as monotherapy. While acute studies in humans have demonstrated weight gain and sodium retention with clonidine and guanabenz, chronic administration results in a decrease in weight and plasma volume. The absence of chronic weight gain and of sodium retention could be the result of a counterbalance between hypotension-related antinatriuresis, secondary to a decrease in glomerular filtration rate and renal blood flow, and natriuretic activity, as a result of a decrease in renal sympathetic tone. Whereas natriuresis and water diuresis have been demonstrated in animals with acute clonidine or guanabenz administration, this has not been demonstrated in humans. Recent studies in which saline administration was used to precondition humans to a subsequent natriuretic stimulus (i.e., guanabenz-induced decreased renal adrenergic activity) resulted in stabilization of renal blood flow and natriuresis. Selective reduction renal sympathetic activity affecting salt and water transport may explain why guanabenz and probably also clonidine seem to be devoid of the sodium/fluid-retaining properties that are common with other antihypertensive agents. Because agents of this class have effects other than pure central alpha-2 agonism (such as alpha-1 activity), they might have confounding and counterbalancing side effects leading to sodium and water retention.

  6. Molecular imaging of the human pulmonary vascular endothelium in pulmonary hypertension: a phase II safety and proof of principle trial

    Energy Technology Data Exchange (ETDEWEB)

    Harel, Francois [Montreal Heart Institute, Research Center, Montreal, QC (Canada); Universite de Montreal, Department of Nuclear Medicine, Montreal, Quebec (Canada); Langleben, David; Abikhzer, Gad [McGill University, Lady Davis Institute and Jewish General Hospital, Montreal, Quebec (Canada); Provencher, Steve; Guimond, Jean [Institut Universitaire de Cardiologie et de Pneumologie de Quebec, Quebec (Canada); Fournier, Alain; Letourneau, Myriam [INRS-Institut Armand-Frappier, Laval, Quebec (Canada); Finnerty, Vincent; Nguyen, Quang T.; Levac, Xavier [Montreal Heart Institute, Research Center, Montreal, QC (Canada); Mansour, Asmaa; Guertin, Marie-Claude [Montreal Health Innovation Coordination Center, Montreal, QC (Canada); Dupuis, Jocelyn [Montreal Heart Institute, Research Center, Montreal, QC (Canada); Universite de Montreal, Department of Medicine, Montreal, Quebec (Canada)

    2017-07-15

    The adrenomedullin receptor is densely expressed in the pulmonary vascular endothelium. PulmoBind, an adrenomedullin receptor ligand, was developed for molecular diagnosis of pulmonary vascular disease. We evaluated the safety of PulmoBind SPECT imaging and its capacity to detect pulmonary vascular disease associated with pulmonary hypertension (PH) in a human phase II study. Thirty patients with pulmonary arterial hypertension (PAH, n = 23) or chronic thromboembolic PH (CTEPH, n = 7) in WHO functional class II (n = 26) or III (n = 4) were compared to 15 healthy controls. Lung SPECT was performed after injection of 15 mCi {sup 99m}Tc-PulmoBind in supine position. Qualitative and semi-quantitative analyses of lung uptake were performed. Reproducibility of repeated testing was evaluated in controls after 1 month. PulmoBind injection was well tolerated without any serious adverse event. Imaging was markedly abnormal in PH with ∝50% of subjects showing moderate to severe heterogeneity of moderate to severe extent. The abnormalities were unevenly distributed between the right and left lungs as well as within each lung. Segmental defects compatible with pulmonary embolism were present in 7/7 subjects with CTEPH and in 2/23 subjects with PAH. There were no segmental defects in controls. The PulmoBind activity distribution index, a parameter indicative of heterogeneity, was elevated in PH (65% ± 28%) vs. controls (41% ± 13%, p = 0.0003). In the only subject with vasodilator-responsive idiopathic PAH, PulmoBind lung SPECT was completely normal. Repeated testing 1 month later in healthy controls was well tolerated and showed no significant variability of PulmoBind distribution. In this phase II study, molecular SPECT imaging of the pulmonary vascular endothelium using {sup 99m}Tc-PulmoBind was safe. PulmoBind showed potential to detect both pulmonary embolism and abnormalities indicative of pulmonary vascular disease in PAH. Phase III studies with this novel tracer and

  7. Mineralocorticoid hypertension

    Directory of Open Access Journals (Sweden)

    Vishal Gupta

    2011-01-01

    Full Text Available Hypertension affects about 10 - 25% of the population and is an important risk factor for cardiovascular and renal disease. The renin-angiotensin system is frequently implicated in the pathophysiology of hypertension, be it primary or secondary. The prevalence of primary aldosteronism increases with the severity of hypertension, from 2% in patients with grade 1 hypertension to 20% among resistant hypertensives. Mineralcorticoid hypertension includes a spectrum of disorders ranging from renin-producing pathologies (renin-secreting tumors, malignant hypertension, coarctation of aorta, aldosterone-producing pathologies (primary aldosteronism - Conns syndrome, familial hyperaldosteronism 1, 2, and 3, non-aldosterone mineralocorticoid producing pathologies (apparent mineralocorticoid excess syndrome, Liddle syndrome, deoxycorticosterone-secreting tumors, ectopic adrenocorticotropic hormones (ACTH syndrome, congenitalvadrenal hyperplasia, and drugs with mineraocorticoid activity (locorice, carbenoxole therapy to glucocorticoid receptor resistance syndromes. Clinical presentation includes hypertension with varying severity, hypokalemia, and alkalosis. Ratio of plasma aldosterone concentraion to plasma renin activity remains the best screening tool. Bilateral adrenal venous sampling is the best diagnostic test coupled with a CT scan. Treatment is either surgical (adrenelectomy for unilateral adrenal disease versus medical therapy for idiopathic, ambiguous, or bilateral disease. Medical therapy focuses on blood pressure control and correction of hypokalemia using a combination of anti-hypertensives (calcium channel blockers, angiotensin converting enzyme inhibitors, or angiotensin receptor blockers and potassium-raising therapies (mineralcorticoid receptor antagonist or potassium sparing diuretics. Direct aldosterone synthetase antagonists represent a promising future therapy.

  8. Associations between Potentially Modifiable Risk Factors and Alzheimer Disease: A Mendelian Randomization Study.

    Directory of Open Access Journals (Sweden)

    Søren D Østergaard

    2015-06-01

    Full Text Available Potentially modifiable risk factors including obesity, diabetes, hypertension, and smoking are associated with Alzheimer disease (AD and represent promising targets for intervention. However, the causality of these associations is unclear. We sought to assess the causal nature of these associations using Mendelian randomization (MR.We used SNPs associated with each risk factor as instrumental variables in MR analyses. We considered type 2 diabetes (T2D, NSNPs = 49, fasting glucose (NSNPs = 36, insulin resistance (NSNPs = 10, body mass index (BMI, NSNPs = 32, total cholesterol (NSNPs = 73, HDL-cholesterol (NSNPs = 71, LDL-cholesterol (NSNPs = 57, triglycerides (NSNPs = 39, systolic blood pressure (SBP, NSNPs = 24, smoking initiation (NSNPs = 1, smoking quantity (NSNPs = 3, university completion (NSNPs = 2, and years of education (NSNPs = 1. We calculated MR estimates of associations between each exposure and AD risk using an inverse-variance weighted approach, with summary statistics of SNP-AD associations from the International Genomics of Alzheimer's Project, comprising a total of 17,008 individuals with AD and 37,154 cognitively normal elderly controls. We found that genetically predicted higher SBP was associated with lower AD risk (odds ratio [OR] per standard deviation [15.4 mm Hg] of SBP [95% CI]: 0.75 [0.62-0.91]; p = 3.4 × 10(-3. Genetically predicted higher SBP was also associated with a higher probability of taking antihypertensive medication (p = 6.7 × 10(-8. Genetically predicted smoking quantity was associated with lower AD risk (OR per ten cigarettes per day [95% CI]: 0.67 [0.51-0.89]; p = 6.5 × 10(-3, although we were unable to stratify by smoking history; genetically predicted smoking initiation was not associated with AD risk (OR = 0.70 [0.37, 1.33]; p = 0.28. We saw no evidence of causal associations between glycemic traits, T2D, BMI, or educational attainment and risk of AD (all p > 0.1. Potential limitations of this study

  9. Associations between Potentially Modifiable Risk Factors and Alzheimer Disease: A Mendelian Randomization Study.

    Science.gov (United States)

    Østergaard, Søren D; Mukherjee, Shubhabrata; Sharp, Stephen J; Proitsi, Petroula; Lotta, Luca A; Day, Felix; Perry, John R B; Boehme, Kevin L; Walter, Stefan; Kauwe, John S; Gibbons, Laura E; Larson, Eric B; Powell, John F; Langenberg, Claudia; Crane, Paul K; Wareham, Nicholas J; Scott, Robert A

    2015-06-01

    Potentially modifiable risk factors including obesity, diabetes, hypertension, and smoking are associated with Alzheimer disease (AD) and represent promising targets for intervention. However, the causality of these associations is unclear. We sought to assess the causal nature of these associations using Mendelian randomization (MR). We used SNPs associated with each risk factor as instrumental variables in MR analyses. We considered type 2 diabetes (T2D, NSNPs = 49), fasting glucose (NSNPs = 36), insulin resistance (NSNPs = 10), body mass index (BMI, NSNPs = 32), total cholesterol (NSNPs = 73), HDL-cholesterol (NSNPs = 71), LDL-cholesterol (NSNPs = 57), triglycerides (NSNPs = 39), systolic blood pressure (SBP, NSNPs = 24), smoking initiation (NSNPs = 1), smoking quantity (NSNPs = 3), university completion (NSNPs = 2), and years of education (NSNPs = 1). We calculated MR estimates of associations between each exposure and AD risk using an inverse-variance weighted approach, with summary statistics of SNP-AD associations from the International Genomics of Alzheimer's Project, comprising a total of 17,008 individuals with AD and 37,154 cognitively normal elderly controls. We found that genetically predicted higher SBP was associated with lower AD risk (odds ratio [OR] per standard deviation [15.4 mm Hg] of SBP [95% CI]: 0.75 [0.62-0.91]; p = 3.4 × 10(-3)). Genetically predicted higher SBP was also associated with a higher probability of taking antihypertensive medication (p = 6.7 × 10(-8)). Genetically predicted smoking quantity was associated with lower AD risk (OR per ten cigarettes per day [95% CI]: 0.67 [0.51-0.89]; p = 6.5 × 10(-3)), although we were unable to stratify by smoking history; genetically predicted smoking initiation was not associated with AD risk (OR = 0.70 [0.37, 1.33]; p = 0.28). We saw no evidence of causal associations between glycemic traits, T2D, BMI, or educational attainment and risk of AD (all p > 0.1). Potential limitations of this

  10. Mendelian Randomization Study of Body Mass Index and Colorectal Cancer Risk

    DEFF Research Database (Denmark)

    Thrift, Aaron P.; Gong, Jian; Peters, Ulrike

    2015-01-01

    Background: High body mass index (BMI) is consistently linked to increased risk of colorectal cancer for men, whereas the association is less clear for women. As risk estimates from observational studies may be biased and/or confounded, we conducted a Mendelian randomization study to estimate...... the causal association between BMI and colorectal cancer. Methods: We used data from 10,226 colorectal cancer cases and 10,286 controls of European ancestry. The Mendelian randomization analysis used a weighted genetic risk score, derived from 77 genome-wide association study–identified variants associated......, rather than overall obesity, is a more important risk factor for men requires further investigation. Impact: Overall, conventional epidemiologic and Mendelian randomization studies suggest a strong association between obesity and the risk of colorectal cancer....

  11. Investigating the possible causal association of smoking with depression and anxiety using Mendelian randomisation meta-analysis: The CARTA consortium

    NARCIS (Netherlands)

    A.E. Taylor (Amy E.); M.E. Fluharty (Meg E.); J.H. Bjørngaard (Johan H.); M.E. Gabrielsen (Maiken Elvestad); F. Skorpen (Frank); R.E. Marioni (Riccardo); A. Campbell (Archie); J. Engmann (Jorgen); S.S. Mirza (Saira); A. Loukola (Anu); T. Laatikainen (Tiina); T. Partonen (Timo); M. Kaakinen (Marika); F. Ducci (Francesca); A. Cavadino (Alana); L.L.N. Husemoen (Lise Lotte); T.S. Ahluwalia (Tarunveer Singh); R.K. Jacobsen (Rikke Kart); T. Skaaby (Tea); J.F. Ebstrup (Jeanette Frost); E.L. Mortensen (Erik); C.C. Minica (Camelia C.); J.M. Vink (Jacqueline); G.A.H.M. Willemsen (Gonneke); P. Marques-Vidal (Pedro); C.E. Dale (Caroline E.); A. Amuzu (Antoinette); L.T. Lennon (Lucy T.); J. Lahti (Jari); A. Palotie (Aarno); K. Räikkönen (Katri); A. Wong (Andrew); L. Paternoster (Lavinia); A.P.-Y. Wong (Angelita Pui-Yee); L.J. Horwood (L. John); M. Murphy (Michael); E.C. Johnstone (Elaine C.); M.A. Kennedy (Martin A.); Z. Pausova (Zdenka); T. Paus (Tomáš); Y. Ben-Shlomo; C. Nohr (Christian); D. Kuh (Diana); M. Kivimaki (Mika); J.G. Eriksson (Johan G.); R. Morris (Richard); J.P. Casas (Juan); M. Preisig (Martin); D.I. Boomsma (Dorret); A. Linneberg (Allan); C. Power (Christopher); E. Hypponen (Elina); J. Veijola (Juha); M.-R. Jarvelin (Marjo-Riitta); T. Korhonen (Tellervo); H.W. Tiemeier (Henning); M. Kumari (Meena); D.J. Porteous (David J.); C. Hayward (Caroline); P.R. Romundstad (Pa˚l R.); G.D. Smith; M.R. Munafò (Marcus)

    2014-01-01

    textabstractObjectives: To investigate whether associations of smoking with depression and anxiety are likely to be causal, using a Mendelian randomisation approach. Design: Mendelian randomisation meta-analyses using a genetic variant (rs16969968/rs1051730) as a proxy for smoking heaviness, and

  12. Effects of Metformin on Tissue Oxidative and Dicarbonyl Stress in Transgenic Spontaneously Hypertensive Rats Expressing Human C-Reactive Protein.

    Directory of Open Access Journals (Sweden)

    Hana Malínská

    Full Text Available Inflammation and oxidative and dicarbonyl stress play important roles in the pathogenesis of type 2 diabetes. Metformin is the first-line drug of choice for the treatment of type 2 diabetes because it effectively suppresses gluconeogenesis in the liver. However, its "pleiotropic" effects remain controversial. In the current study, we tested the effects of metformin on inflammation, oxidative and dicarbonyl stress in an animal model of inflammation and metabolic syndrome, using spontaneously hypertensive rats that transgenically express human C-reactive protein (SHR-CRP. We treated 8-month-old male transgenic SHR-CRP rats with metformin (5 mg/kg/day mixed as part of a standard diet for 4 weeks. A corresponding untreated control group of male transgenic SHR-CRP rats were fed a standard diet without metformin. In a similar fashion, we studied a group of nontransgenic SHR treated with metformin and an untreated group of nontransgenic SHR controls. In each group, we studied 6 animals. Parameters of glucose and lipid metabolism and oxidative and dicarbonyl stress were measured using standard methods. Gene expression profiles were determined using Affymetrix GeneChip Arrays. Statistical significance was evaluated by two-way ANOVA. In the SHR-CRP transgenic strain, we found that metformin treatment decreased circulating levels of inflammatory response marker IL-6, TNFα and MCP-1 while levels of human CRP remained unchanged. Metformin significantly reduced oxidative stress (levels of conjugated dienes and TBARS and dicarbonyl stress (levels of methylglyoxal in left ventricles, but not in kidneys. No significant effects of metformin on oxidative and dicarbonyl stress were observed in SHR controls. In addition, metformin treatment reduced adipose tissue lipolysis associated with human CRP. Possible molecular mechanisms of metformin action-studied by gene expression profiling in the liver-revealed deregulated genes from inflammatory and insulin signaling

  13. Association between polymorphism in the human cathepsin L (CTSL 1) promoter with hypertension in the uygur, kazak and han population in china

    International Nuclear Information System (INIS)

    Chen, S.; Wang, Z.; Zhou, C.; Wang, D.W.

    2015-01-01

    To systemically investigate the association between the polymorphism (rs3118869) in cathepsin Lenzyme gene with hypertension in three ethnic groups (Han, Kazak and Uygur) in China. Study Design: Case-control study. Place and Duration of Study: Department of Cardiology, The First Affiliated Hospital, Shihezi Medical College, Shihezi University and Department of Internal Medicine and Genetic Diagnosis Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, from January 2013 to May 2014. Methodology: This case-control study included 1224 patients (422 Uygur, 425 Kazak and 377 Han individuals) with hypertension and 967 healthy unrelated individuals (339 Uygur, 337 Kazak and 291 Han individuals) as controls. The participants came from three ethnic groups (Han, Kazak and Uygur) which were recruited from Xinjiang Province of China. The polymorphism (rs3118869) of the human cathepsin Lgene was genotyped using the TaqMan 5' nuclease assay. Binary logistic regression was built to determine the association of polymorphism with hypertension. Results: The genotype distribution of polymorphism was not significantly different in three ethnic groups. The rs3118869 polymorphism was significantly associated with Essential Hypertension (EH) in co-dominant model (A/C vs. C/C) in total people (OR = 0.697, 95% CI = 0.520 -0.932, p = 0.015), the same result was obtained in recessive model (C/C + A/C vs. A/A) in total people (OR = 0.689, 95% CI = 0.522 -0.910, p = 0.009). Similar finding of rs3118869 in recessive model (C/C + A/C vs. A/A) was also observed after adjusting the variable to the covariates age (OR = 0.629, 95% CI = 0.464 0853, p = 0.003). Conclusion: The study results indicate the A-allele of rs3118869 is a protective factor in hypertension. (author)

  14. The Immune System in Hypertension

    Science.gov (United States)

    Trott, Daniel W.; Harrison, David G.

    2014-01-01

    While hypertension has predominantly been attributed to perturbations of the vasculature, kidney, and central nervous system, research for almost 50 yr has shown that the immune system also contributes to this disease. Inflammatory cells accumulate in the kidneys and vasculature of humans and experimental animals with hypertension and likely…

  15. Hypertension hos gravide

    DEFF Research Database (Denmark)

    Mathiesen, Elisabeth R; Johansen, Marianne; Kamper, Anne Lise

    2009-01-01

    There are four major hypertensive disorders in pregnancy: chronic hypertension, gestational hypertension, preeclampsia and chronic hypertension with superimposed preeclampsia. The indications and efficacy of antihypertensive treatment of the different hypertensive disorders are assessed. Advantages...

  16. A sensitive radioimmunoassay measuring endothelin-like immunoreactivity in human plasma: comparison of levels in patients with essential hypertension and normotensive control subjects

    International Nuclear Information System (INIS)

    Davenport, A.P.; Ashby, M.J.; Easton, Patricia

    1990-01-01

    A radioimmunoassay was developed to measure endothelin-like immunoreactivity in human plasma using antibody raised against endothelin-1 which also cross-reacts with big endothelin-1 and endothelin-2 but not endothelin-3. The sensitivity was 1 fmol/tube with inter- and intra-assay coefficients of variation of 13% and 9%, respectively. Cross-reactivity with endothelin-3 and non-endothelin peptides was less than 1%. Endothelin-like immunoreactivity was present in plasma of hypertensive patients (n = 25) at 5.7±0.5 pmol/1 (mean±SEM), not significantly different from that of age-matched control subjects (5.1±0.5 pmol/1). At these levels, endothelin-1 is unlikely to function as a circulating hormone. In the normotensive group, the concentration of endothelin-like immunoreactivity in plasma was positively correlated with mean arterial blood pressure, but in hypertensive patients it showed significant negative correlation. (author)

  17. Similar Adiponectin Levels in Obese Normotensive and Obese Hypertensive Men and No Vasorelaxant Effect of Adiponectin on Human Arteries

    DEFF Research Database (Denmark)

    Dreier, Rasmus; Asferg, Camilla; Berg, Jais O

    2016-01-01

    Obesity is a strong risk factor for hypertension, but the mechanism linking obesity to hypertension is not fully elucidated. In obesity, circulating concentrations of adiponectin are decreased and hypoadiponectinaemia has in some but not all studies been associated with increased risk of hyperten......Obesity is a strong risk factor for hypertension, but the mechanism linking obesity to hypertension is not fully elucidated. In obesity, circulating concentrations of adiponectin are decreased and hypoadiponectinaemia has in some but not all studies been associated with increased risk...... of hypertension. Due to this inconsistency, we decided to study adiponectin from two aspects in a cross-sectional in vivo study and in an experimental in vitro study. In the cross-sectional study, 103 men with body mass index (BMI) ≥ 30.0 kg/m(2) were studied; 63 had 24-hr ambulatory blood pressure (ABP) ≥ 130....../80 mmHg (ObeseHT) and 40 had 24-hr ABP men with BMI between 20.0 and 24.9 kg/m(2) and 24-hr ABP

  18. Adaptation, allometry, and hypertension.

    Science.gov (United States)

    Weder, A B; Schork, N J

    1994-08-01

    Essential hypertension is a "disease of civilization" but has a clear genetic component. From an evolutionary perspective, persistence in the human genome of elements capable of raising blood pressure presupposes their adaptive significance. Recently, two hypotheses that explicitly appeal to selectionist arguments, the "slavery" and "thrifty gene" theories, have been forwarded. We find neither completely successful, and we advance an alternative explanation of the adaptive importance of genes responsible for hypertension. We propose that blood pressure rises during childhood and adolescence to subserve homeostatic needs of the organism. Specifically, we contend that blood pressure is a flexible element in the repertoire of renal homeostatic mechanisms serving to match renal function to growth. The effect of modern diet and lifestyle on human growth stimulates earlier and more vigorous development, straining biologically necessary relationships between renal and general somatic growth and requiring compensation via homeostatic mechanisms preserved during evolution. Prime among such mechanisms is blood pressure, which rises as a compensation to maintain renal function in the face of greater growth. Since virtually all members of acculturated societies share in the modern lifestyle, the demands imposed by accelerated growth and development result in a populational shift to higher blood pressures, with a consequent increase in the prevalence of hypertension. We propose that hypertension is the product of maladaptation of highly genetically conserved mechanisms subserving important biological homeostatic needs. Elucidation of the mechanisms underlying hypertension will require approaches that examine the developmental processes linking growth to blood pressure.

  19. A Mendelian Randomization Study of Circulating Uric Acid and Type 2 Diabetes

    NARCIS (Netherlands)

    Sluijs, Ivonne; Holmes, Michael V.; van der Schouw, Yvonne T.; Beulens, Joline W J; Asselbergs, Folkert W.; Huerta, José María; Palmer, Tom M.; Arriola, Larraitz; Balkau, Beverley; Barricarte, Aurelio; Boeing, Heiner; Clavel-Chapelon, Françoise; Fagherazzi, Guy; Franks, Paul W.; Gavrila, Diana; Kaaks, Rudolf; Khaw, Kay T ee; Kühn, Tilman; Molina-Montes, Esther; Mortensen, Lotte M axild; Nilsson, Peter M.; Overvad, Kim; Palli, Domenico; Panico, Salvatore; Quirós, J. Ramón; Rolandsson, Olov; Sacerdote, Carlotta; Sala, Núria; Schmidt, Julie A.; Scott, Robert A.; Sieri, Sabina; Slimani, Nadia; Spijkerman, Annemieke M W; Tjonneland, Anne; Travis, Ruth C.; Tumino, Rosario; van der A, Daphne L.; Sharp, Stephen J.; Forouhi, Nita G.; Langenberg, Claudia; Riboli, Elio; Wareham, Nicholas J.

    2015-01-01

    We aimed to investigate the causal effect of circulating uric acid concentrations on type 2 diabetes risk. A Mendelian randomization study was performed using a genetic score with 24 uric acid-associated loci. We used data of the European Prospective Investigation into Cancer and Nutrition

  20. Association between alcohol and cardiovascular disease : Mendelian randomisation analysis based on individual participant data

    NARCIS (Netherlands)

    Holmes, Michael V.; Dale, Caroline E.; Zuccolo, Luisa; Silverwood, Richard J.; Guo, Yiran; Ye, Zheng; Prieto-Merino, David; Dehghan, Abbas; Trompet, Stella; Wong, Andrew; Cavadino, Alana; Drogan, Dagmar; Padmanabhan, Sandosh; Li, Shanshan; Yesupriya, Ajay; Leusink, Maarten|info:eu-repo/dai/nl/357581164; Sundstrom, Johan; Hubacek, Jaroslav A.; Pikhart, Hynek; Swerdlow, Daniel I.; Panayiotou, Andrie G.; Borinskaya, Svetlana A.; Finan, Chris; Shah, Sonia; Kuchenbaecker, Karoline B.; Shah, Tina; Engmann, Jorgen; Folkersen, Lasse; Eriksson, Per; Ricceri, Fulvio; Melander, Olle; Sacerdote, Carlotta; Gamble, Dale M.; Rayaprolu, Sruti; Ross, Owen A.; McLachlan, Stela; Vikhireva, Olga; Sluijs, Ivonne; Scott, Robert A.; Adamkova, Vera; Flicker, Leon; Van Bockxmeer, Frank M.; Power, Christine; Marques-Vidal, Pedro; Meade, Tom; Marmot, Michael G.; Ferro, Jose M.; Paulos-Pinheiro, Sofia; Humphries, Steve E.; Talmud, Philippa J.; Leach, Irene Mateo; Verweij, Niek; Linneberg, Allan; Skaaby, Tea; Doevendans, Pieter A.; Cramer, Maarten J.; Van Der Harst, Pim; Klungel, Olaf H.|info:eu-repo/dai/nl/181447649; Dowling, Nicole F.; Dominiczak, Anna F.; Kumari, Meena; Nicolaides, Andrew N.; Weikert, Cornelia; Boeing, Heiner; Ebrahim, Shah; Gaunt, Tom R.; Price, Jackie F.; Lannfelt, Lars; Peasey, Anne; Kubinova, Ruzena; Pajak, Andrzej; Malyutina, Sofia; Voevoda, Mikhail I.; Tamosiunas, Abdonas; Maitland-van Der Zee, Anke H.|info:eu-repo/dai/nl/255164688; Norman, Paul E.; Hankey, Graeme J.; Bergmann, Manuela M.; Hofman, Albert; Franco, Oscar H.; Cooper, Jackie; Palmen, Jutta; Spiering, Wilko; De Jong, Pim A.; Kuh, Diana; Hardy, Rebecca; Uitterlinden, Andre G.; Ikram, M. Arfan; Ford, Ian; Hyppönen, Elina; Almeida, Osvaldo P.; Wareham, Nicholas J.; Khaw, Kay Tee; Hamsten, Anders; Husemoen, Lise Lotte N; Tjønneland, Anne; Tolstrup, Janne S.; Rimm, Eric; Beulens, Joline W J; Verschuren, W. M Monique; Onland-Moret, N. Charlotte; Hofker, Marten H.; Wannamethee, S. Goya; Whincup, Peter H.; Morris, Richard; Vicente, Astrid M.; Watkins, Hugh; Farrall, Martin; Jukema, J. Wouter; Meschia, James; Cupples, L. Adrienne; Sharp, Stephen J.; Fornage, Myriam; Kooperberg, Charles; LaCroix, Andrea Z.; Dai, James Y.; Lanktree, Matthew B.; Siscovick, David S.; Jorgenson, Eric; Spring, Bonnie; Coresh, Josef; Li, Yun R.; Buxbaum, Sarah G.; Schreiner, Pamela J.; Ellison, R. Curtis; Tsai, Michael Y.; Patel, Sanjay R.; Redline, Susan; Johnson, Andrew D.; Hoogeveen, Ron C.; Hakonarson, Hakon; Rotter, Jerome I.; Boerwinkle, Eric; De Bakker, Paul I W; Kivimaki, Mika; Asselbergs, Folkert W.; Sattar, Naveed; Lawlor, Debbie A.; Whittaker, John; Smith, George Davey; Mukamal, Kenneth; Psaty, Bruce M.; Wilson, James G.; Lange, Leslie A.; Hamidovic, Ajna; Nordestgaard, Børge G.; Bobak, Martin; Leon, David A.; Langenberg, Claudia; Palmer, Tom M.; Reiner, Alex P.; Keating, Brendan J.; Dudbridge, Frank; Casas, Juan P.

    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

  1. Relationship between obesity and the risk of clinically significant depression: Mendelian randomisation study.

    LENUS (Irish Health Repository)

    Hung, Chi-Fa

    2014-07-01

    Obesity has been shown to be associated with depression and it has been suggested that higher body mass index (BMI) increases the risk of depression and other common mental disorders. However, the causal relationship remains unclear and Mendelian randomisation, a form of instrumental variable analysis, has recently been employed to attempt to resolve this issue.

  2. Adult height, coronary heart disease and stroke : A multi-locus Mendelian randomization meta-analysis

    NARCIS (Netherlands)

    Nüesch, Eveline; Dale, Caroline; Palmer, Tom M.; White, Jon; Keating, Brendan J.; van Iperen, Erik P A; Goel, Anuj; Padmanabhan, Sandosh; Asselbergs, F. W.; Verschuren, W. M.; Wijmenga, C.; Van der Schouw, Y. T.; Onland-Moret, N. C.; Lange, Leslie A.; Hovingh, G. K.; Sivapalaratnam, Suthesh; Morris, Richard W.; Whincup, Peter H.; Wannamethe, Goya S.; Gaunt, Tom R.; Ebrahim, Shah; Steel, Laura; Nair, Nikhil; Reiner, Alexander P.; Kooperberg, Charles; Wilson, James F.; Bolton, Jennifer L.; McLachlan, Stela; Price, Jacqueline F.; Strachan, Mark W J; Robertson, Christine M.; Kleber, Marcus E.; Delgado, Graciela; März, Winfried; Melander, Olle; Dominiczak, Anna F.; Farrall, Martin; Watkins, Hugh; Leusink, Maarten; Maitland-van der Zee, Anke H.; de Groot, Mark C H; Dudbridge, Frank; Hingorani, Aroon; Ben-Shlomo, Yoav; Lawlor, Debbie A.; Amuzu, A.; Caufield, M.; Cavadino, A.; Cooper, J.; Davies, T. L.; Day, I. N.; Drenos, F.; Engmann, J.; Finan, C.; Giambartolomei, C.; Hardy, R.; Humphries, S. E.; Hypponen, E.; Kivimaki, M.; Kuh, D.; Kumari, M.; Ong, K.; Plagnol, V.; Power, C.; Richards, M.; Shah, S.; Shah, T.; Sofat, R.; Talmud, P. J.; Wareham, N.; Warren, H.; Whittaker, J. C.; Wong, A.; Zabaneh, D.; Smith, George Davey; Wells, Jonathan C.; Leon, David A.; Holmes, Michael V.; Casas, Juan P.

    2016-01-01

    Background: We investigated causal effect of completed growth, measured by adult height, on coronary heart disease (CHD), stroke and cardiovascular traits, using instrumental variable (IV) Mendelian randomization meta-analysis. Methods: We developed an allele score based on 69 single nucleotide

  3. Common variants in Mendelian kidney disease genes and their association with renal function.

    Science.gov (United States)

    Parsa, Afshin; Fuchsberger, Christian; Köttgen, Anna; O'Seaghdha, Conall M; Pattaro, Cristian; de Andrade, Mariza; Chasman, Daniel I; Teumer, Alexander; Endlich, Karlhans; Olden, Matthias; Chen, Ming-Huei; Tin, Adrienne; Kim, Young J; Taliun, Daniel; Li, Man; Feitosa, Mary; Gorski, Mathias; Yang, Qiong; Hundertmark, Claudia; Foster, Meredith C; Glazer, Nicole; Isaacs, Aaron; Rao, Madhumathi; Smith, Albert V; O'Connell, Jeffrey R; Struchalin, Maksim; Tanaka, Toshiko; Li, Guo; Hwang, Shih-Jen; Atkinson, Elizabeth J; Lohman, Kurt; Cornelis, Marilyn C; Johansson, Asa; Tönjes, Anke; Dehghan, Abbas; Couraki, Vincent; Holliday, Elizabeth G; Sorice, Rossella; Kutalik, Zoltan; Lehtimäki, Terho; Esko, Tõnu; Deshmukh, Harshal; Ulivi, Sheila; Chu, Audrey Y; Murgia, Federico; Trompet, Stella; Imboden, Medea; Kollerits, Barbara; Pistis, Giorgio; Harris, Tamara B; Launer, Lenore J; Aspelund, Thor; Eiriksdottir, Gudny; Mitchell, Braxton D; Boerwinkle, Eric; Schmidt, Helena; Hofer, Edith; Hu, Frank; Demirkan, Ayse; Oostra, Ben A; Turner, Stephen T; Ding, Jingzhong; Andrews, Jeanette S; Freedman, Barry I; Giulianini, Franco; Koenig, Wolfgang; Illig, Thomas; Döring, Angela; Wichmann, H-Erich; Zgaga, Lina; Zemunik, Tatijana; Boban, Mladen; Minelli, Cosetta; Wheeler, Heather E; Igl, Wilmar; Zaboli, Ghazal; Wild, Sarah H; Wright, Alan F; Campbell, Harry; Ellinghaus, David; Nöthlings, Ute; Jacobs, Gunnar; Biffar, Reiner; Ernst, Florian; Homuth, Georg; Kroemer, Heyo K; Nauck, Matthias; Stracke, Sylvia; Völker, Uwe; Völzke, Henry; Kovacs, Peter; Stumvoll, Michael; Mägi, Reedik; Hofman, Albert; Uitterlinden, Andre G; Rivadeneira, Fernando; Aulchenko, Yurii S; Polasek, Ozren; Hastie, Nick; Vitart, Veronique; Helmer, Catherine; Wang, Jie Jin; Stengel, Bénédicte; Ruggiero, Daniela; Bergmann, Sven; Kähönen, Mika; Viikari, Jorma; Nikopensius, Tiit; Province, Michael; Colhoun, Helen; Doney, Alex; Robino, Antonietta; Krämer, Bernhard K; Portas, Laura; Ford, Ian; Buckley, Brendan M; Adam, Martin; Thun, Gian-Andri; Paulweber, Bernhard; Haun, Margot; Sala, Cinzia; Mitchell, Paul; Ciullo, Marina; Vollenweider, Peter; Raitakari, Olli; Metspalu, Andres; Palmer, Colin; Gasparini, Paolo; Pirastu, Mario; Jukema, J Wouter; Probst-Hensch, Nicole M; Kronenberg, Florian; Toniolo, Daniela; Gudnason, Vilmundur; Shuldiner, Alan R; Coresh, Josef; Schmidt, Reinhold; Ferrucci, Luigi; van Duijn, Cornelia M; Borecki, Ingrid; Kardia, Sharon L R; Liu, Yongmei; Curhan, Gary C; Rudan, Igor; Gyllensten, Ulf; Wilson, James F; Franke, Andre; Pramstaller, Peter P; Rettig, Rainer; Prokopenko, Inga; Witteman, Jacqueline; Hayward, Caroline; Ridker, Paul M; Bochud, Murielle; Heid, Iris M; Siscovick, David S; Fox, Caroline S; Kao, W Linda; Böger, Carsten A

    2013-12-01

    Many common genetic variants identified by genome-wide association studies for complex traits map to genes previously linked to rare inherited Mendelian disorders. A systematic analysis of common single-nucleotide polymorphisms (SNPs) in genes responsible for Mendelian diseases with kidney phenotypes has not been performed. We thus developed a comprehensive database of genes for Mendelian kidney conditions and evaluated the association between common genetic variants within these genes and kidney function in the general population. Using the Online Mendelian Inheritance in Man database, we identified 731 unique disease entries related to specific renal search terms and confirmed a kidney phenotype in 218 of these entries, corresponding to mutations in 258 genes. We interrogated common SNPs (minor allele frequency >5%) within these genes for association with the estimated GFR in 74,354 European-ancestry participants from the CKDGen Consortium. However, the top four candidate SNPs (rs6433115 at LRP2, rs1050700 at TSC1, rs249942 at PALB2, and rs9827843 at ROBO2) did not achieve significance in a stage 2 meta-analysis performed in 56,246 additional independent individuals, indicating that these common SNPs are not associated with estimated GFR. The effect of less common or rare variants in these genes on kidney function in the general population and disease-specific cohorts requires further research.

  4. Identification of Mendelian inconsistencies between SNP and pedigree Information of Sibs

    NARCIS (Netherlands)

    Calus, M.P.L.; Mulder, H.A.; Bastiaansen, J.W.M.

    2011-01-01

    Background Using SNP genotypes to apply genomic selection in breeding programs is becoming common practice. Tools to edit and check the quality of genotype data are required. Checking for Mendelian inconsistencies makes it possible to identify animals for which pedigree information and genotype

  5. Identification of Mendelian inconsistencies between SNP and pedigree information of sibs

    Directory of Open Access Journals (Sweden)

    Calus Mario PL

    2011-10-01

    Full Text Available Abstract Background Using SNP genotypes to apply genomic selection in breeding programs is becoming common practice. Tools to edit and check the quality of genotype data are required. Checking for Mendelian inconsistencies makes it possible to identify animals for which pedigree information and genotype information are not in agreement. Methods Straightforward tests to detect Mendelian inconsistencies exist that count the number of opposing homozygous marker (e.g. SNP genotypes between parent and offspring (PAR-OFF. Here, we develop two tests to identify Mendelian inconsistencies between sibs. The first test counts SNP with opposing homozygous genotypes between sib pairs (SIBCOUNT. The second test compares pedigree and SNP-based relationships (SIBREL. All tests iteratively remove animals based on decreasing numbers of inconsistent parents and offspring or sibs. The PAR-OFF test, followed by either SIB test, was applied to a dataset comprising 2,078 genotyped cows and 211 genotyped sires. Theoretical expectations for distributions of test statistics of all three tests were calculated and compared to empirically derived values. Type I and II error rates were calculated after applying the tests to the edited data, while Mendelian inconsistencies were introduced by permuting pedigree against genotype data for various proportions of animals. Results Both SIB tests identified animal pairs for which pedigree and genomic relationships could be considered as inconsistent by visual inspection of a scatter plot of pairwise pedigree and SNP-based relationships. After removal of 235 animals with the PAR-OFF test, SIBCOUNT (SIBREL identified 18 (22 additional inconsistent animals. Seventeen animals were identified by both methods. The numbers of incorrectly deleted animals (Type I error, were equally low for both methods, while the numbers of incorrectly non-deleted animals (Type II error, were considerably higher for SIBREL compared to SIBCOUNT. Conclusions

  6. Plasma urate concentration and risk of coronary heart disease: a Mendelian randomisation analysis

    Science.gov (United States)

    White, Jon; Sofat, Reecha; Hemani, Gibran; Shah, Tina; Engmann, Jorgen; Dale, Caroline; Shah, Sonia; Kruger, Felix A; Giambartolomei, Claudia; Swerdlow, Daniel I; Palmer, Tom; McLachlan, Stela; Langenberg, Claudia; Zabaneh, Delilah; Lovering, Ruth; Cavadino, Alana; Jefferis, Barbara; Finan, Chris; Wong, Andrew; Amuzu, Antoinette; Ong, Ken; Gaunt, Tom R; Warren, Helen; Davies, Teri-Louise; Drenos, Fotios; Cooper, Jackie; Ebrahim, Shah; Lawlor, Debbie A; Talmud, Philippa J; Humphries, Steve E; Power, Christine; Hypponen, Elina; Richards, Marcus; Hardy, Rebecca; Kuh, Diana; Wareham, Nicholas; Ben-Shlomo, Yoav; Day, Ian N; Whincup, Peter; Morris, Richard; Strachan, Mark W J; Price, Jacqueline; Kumari, Meena; Kivimaki, Mika; Plagnol, Vincent; Whittaker, John C; Smith, George Davey; Dudbridge, Frank; Casas, Juan P; Holmes, Michael V; Hingorani, Aroon D

    2016-01-01

    Summary Background Increased circulating plasma urate concentration is associated with an increased risk of coronary heart disease, but the extent of any causative effect of urate on risk of coronary heart disease is still unclear. In this study, we aimed to clarify any causal role of urate on coronary heart disease risk using Mendelian randomisation analysis. Methods We first did a fixed-effects meta-analysis of the observational association of plasma urate and risk of coronary heart disease. We then used a conventional Mendelian randomisation approach to investigate the causal relevance using a genetic instrument based on 31 urate-associated single nucleotide polymorphisms (SNPs). To account for potential pleiotropic associations of certain SNPs with risk factors other than urate, we additionally did both a multivariable Mendelian randomisation analysis, in which the genetic associations of SNPs with systolic and diastolic blood pressure, HDL cholesterol, and triglycerides were included as covariates, and an Egger Mendelian randomisation (MR-Egger) analysis to estimate a causal effect accounting for unmeasured pleiotropy. Findings In the meta-analysis of 17 prospective observational studies (166 486 individuals; 9784 coronary heart disease events) a 1 SD higher urate concentration was associated with an odds ratio (OR) for coronary heart disease of 1·07 (95% CI 1·04–1·10). The corresponding OR estimates from the conventional, multivariable adjusted, and Egger Mendelian randomisation analysis (58 studies; 198 598 individuals; 65 877 events) were 1·18 (95% CI 1·08–1·29), 1·10 (1·00–1·22), and 1·05 (0·92–1·20), respectively, per 1 SD increment in plasma urate. Interpretation Conventional and multivariate Mendelian randomisation analysis implicates a causal role for urate in the development of coronary heart disease, but these estimates might be inflated by hidden pleiotropy. Egger Mendelian randomisation analysis, which accounts for

  7. Hypertension screening

    Science.gov (United States)

    Foulke, J. M.

    1975-01-01

    An attempt was made to measure the response to an announcement of hypertension screening at the Goddard Space Center, to compare the results to those of previous statistics. Education and patient awareness of the problem were stressed.

  8. Endokrin hypertension

    DEFF Research Database (Denmark)

    Poulsen, Per Løgstrup; Ibsen, Hans

    2009-01-01

    Endocrine hypertension is rare, but frequently refractory. Adenomas are common incidental findings. Biochemical tests confirm the diagnosis. Primary aldosteronism is the most common form. Hypokalaemia is an important sign, but 50% of patients may be normokalaemic. The plasma-aldosterone-to-renin ......Endocrine hypertension is rare, but frequently refractory. Adenomas are common incidental findings. Biochemical tests confirm the diagnosis. Primary aldosteronism is the most common form. Hypokalaemia is an important sign, but 50% of patients may be normokalaemic. The plasma...

  9. Catheter-based renal denervation for resistant hypertension: 12-month results of the EnligHTN I first-in-human study using a multielectrode ablation system.

    Science.gov (United States)

    Papademetriou, Vasilios; Tsioufis, Costas P; Sinhal, Ajay; Chew, Derek P; Meredith, Ian T; Malaiapan, Yuvi; Worthley, Matthew I; Worthley, Stephen G

    2014-09-01

    Renal denervation has emerged as a novel approach for the treatment of patients with drug-resistant hypertension. To date, only limited data have been published using multielectrode radiofrequency ablation systems. In this article, we present the 12-month data of EnligHTN I, a first-in-human study using a multielectrode ablation catheter. EnligHTN I enrolled 46 patients (average age, 60±10 years; on average 4.7±1.0 medications) with drug-resistant hypertension. Eligible patients were on ≥3 antihypertensive medications and had a systolic blood pressure (BP) ≥160 mm Hg (≥150 mm Hg for diabetics). Bilateral renal artery ablation was performed using a percutaneous femoral approach and standardized techniques. The average baseline office BP was 176/96 mm Hg, average 24-hour ambulatory BP was 150/83 mm Hg, and average home BP was 158/90 mm Hg. The average reductions (mm Hg) at 1, 3, 6, and 12 months were as follows: office: -28/-10, -27/-10, -26/-10, and -27/-11 mm Hg (Prenal function and no new serious or life-threatening adverse events. One patient with baseline nonocclusive renal artery stenosis progressed to 75% diameter stenosis, requiring renal artery stenting. The 12-month data continue to demonstrate safety and efficacy of the EnligHTN ablation system in patients with drug-resistant hypertension. Home BP measurements parallel measurements obtained with 24-hour ambulatory monitoring. © 2014 American Heart Association, Inc.

  10. Resistant hypertension.

    Science.gov (United States)

    Wei, Fang-Fei; Zhang, Zhen-Yu; Huang, Qi-Fang; Yang, Wen-Yi; Staessen, Jan A

    2018-06-15

    The publication of the first non-randomised proof-of-concept trial of renal denervation as a treatment modality in treatment-resistant hypertension set the stage for a search for novel devices with the expectation that technology would reduce the burden of hypertension by reducing or eliminating the costly and lifelong use of blood pressure lowering medications. As we demonstrate in this review, this idea so attractive to manufacturers and invasive cardiologists and radiologists overlooked decades of careful pathophysiological research in a disease, which still remains enigmatic but remains the major cause of cardiovascular mortality worldwide. To make our point, we first reviewed the prevalence and risks associated with treatment-resistant hypertension. Next, we highlighted the key points required for the diagnosis of treatment-resistant hypertension, including the recording of the ambulatory blood pressure and the assessment of adherence to medication. Finally, we summarised new insights in the management of treatment-resistant hypertension by medication and devices and in the future research. Throughout our review, we focused on new evidence became available since 2013. Our conclusion is that optimising medical treatment based on simple algorithms remains the state of the art in treatment-resistant hypertension.

  11. Key role of the endothelial TGF-β/ALK1/endoglin signaling pathway in humans and rodents pulmonary hypertension.

    Directory of Open Access Journals (Sweden)

    Benoît Gore

    Full Text Available Mutations affecting transforming growth factor-beta (TGF-β superfamily receptors, activin receptor-like kinase (ALK-1, and endoglin (ENG occur in patients with pulmonary arterial hypertension (PAH. To determine whether the TGF-β/ALK1/ENG pathway was involved in PAH, we investigated pulmonary TGF-β, ALK1, ALK5, and ENG expressions in human lung tissue and cultured pulmonary-artery smooth-muscle-cells (PA-SMCs and pulmonary endothelial cells (PECs from 14 patients with idiopathic PAH (iPAH and 15 controls. Seeing that ENG was highly expressed in PEC, we assessed the effects of TGF-β on Smad1/5/8 and Smad2/3 activation and on growth factor production by the cells. Finally, we studied the consequence of ENG deficiency on the chronic hypoxic-PH development by measuring right ventricular (RV systolic pressure (RVSP, RV hypertrophy, and pulmonary arteriolar remodeling in ENG-deficient (Eng+/- and wild-type (Eng+/+ mice. We also evaluated the pulmonary blood vessel density, macrophage infiltration, and cytokine expression in the lungs of the animals. Compared to controls, iPAH patients had higher serum and pulmonary TGF-β levels and increased ALK1 and ENG expressions in lung tissue, predominantly in PECs. Incubation of the cells with TGF-β led to Smad1/5/8 phosphorylation and to a production of FGF2, PDGFb and endothelin-inducing PA-SMC growth. Endoglin deficiency protected mice from hypoxic PH. As compared to wild-type, Eng+/- mice had a lower pulmonary vessel density, and no change in macrophage infiltration after exposure to chronic hypoxia despite the higher pulmonary expressions of interleukin-6 and monocyte chemoattractant protein-1. The TGF-β/ALK1/ENG signaling pathway plays a key role in iPAH and experimental hypoxic PH via a direct effect on PECs leading to production of growth factors and inflammatory cytokines involved in the pathogenesis of PAH.

  12. Dairy consumption and body mass index among adults: Mendelian randomization analysis of 184802 individuals from 25 studies

    Science.gov (United States)

    Associations between dairy intake and body mass index (BMI) have been inconsistently observed in epidemiological studies, and the causal relationship remains ill defined. We performed Mendelian randomization (MR) analysis using an established dairy intake-associated genetic polymorphism located upst...

  13. Renovascular hypertension

    International Nuclear Information System (INIS)

    Thomsen, H.S.; Sos, T.A.; Nielsen, S.L.; Koebenhavns Amts Sygehus, Herlev; Cornell Univ., New York

    1989-01-01

    Hypertension constitutes a major health problem and the challenge is to identify patients having 'surgically' curable renal vascular disease among the majority with so-called essential hypertension. The best of unsatisfactory diagnostic tests are renography and plasma renin activity both before and during angiotensin II blockade. The necessity of better screening tests has increased because of the recent advances in surgical techniques and especially percutaneous transluminal renal angioplasty. The latter has definitely become the method of choice for correction of suspected hemodynamically significant artery stenoses whenever technically feasible. With improved angioplasty techniques the risk of treating renal artery stenosis without hemodynamic and clinical importance (so-called cosmetic repair) has increased. Unfortunately randomized trials including surgery versus angioplasty are not available. It should be kept in mind that only after correction of the stenosis is achieved and the blood pressure has become normal, can the diagnosis of renovascular hypertension be made with certainty. (orig.)

  14. Rosuvastatin ameliorates inflammation, renal fat accumulation, and kidney injury in transgenic spontaneously hypertensive rats expressing human C-reactive protein

    Czech Academy of Sciences Publication Activity Database

    Šilhavý, Jan; Zídek, Václav; Landa, Vladimír; Šimáková, Miroslava; Mlejnek, Petr; Oliyarnyk, O.; Malínská, H.; Kazdová, L.; Mancini, M.; Pravenec, Michal

    2015-01-01

    Roč. 64, č. 3 (2015), s. 295-301 ISSN 0862-8408 R&D Projects: GA MŠk(CZ) LH11049; GA MŠk(CZ) LL1204; GA MZd(CZ) NT14325; GA ČR(CZ) GB14-36804G Institutional support: RVO:67985823 Keywords : rosuvastatin * kidney damage * CRP * transgenic * spontaneously hypertensive rat Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 1.643, year: 2015

  15. Effects of Metformin on Tissue Oxidative and Dicarbonyl Stress in Transgenic Spontaneously Hypertensive Rats Expressing Human C-Reactive Protein

    Czech Academy of Sciences Publication Activity Database

    Malínská, H.; Oliyarnyk, O.; Škop, V.; Šilhavý, Jan; Landa, Vladimír; Zídek, Václav; Mlejnek, Petr; Šimáková, Miroslava; Strnad, Hynek; Kazdová, L.; Pravenec, Michal

    2016-01-01

    Roč. 11, č. 3 (2016), e0150924 E-ISSN 1932-6203 R&D Projects: GA MŠk(CZ) LL1204; GA MZd(CZ) NT14325 Institutional support: RVO:67985823 ; RVO:68378050 Keywords : inflammation * spontaneously hypertensive rat * transgenic * C-reactive protein * dicarbonyl stress * metformin Subject RIV: FB - Endocrinology, Diabetology, Metabolism, Nutrition Impact factor: 2.806, year: 2016

  16. Exercise Hypertension.

    Science.gov (United States)

    Schultz, Martin G; Sharman, James E

    2014-05-01

    Irrespective of apparent 'normal' resting blood pressure (BP), some individuals may experience an excessive elevation in BP with exercise (i.e. systolic BP ≥210 mm Hg in men or ≥190 mm Hg in women or diastolic BP ≥110 mm Hg in men or women), a condition termed exercise hypertension or a 'hypertensive response to exercise' (HRE). An HRE is a relatively common condition that is identified during standard exercise stress testing; however, due to a lack of information with respect to the clinical ramifications of an HRE, little value is usually placed on such a finding. In this review, we discuss both the clinical importance and underlying physiological contributors of exercise hypertension. Indeed, an HRE is associated with an increased propensity for target organ damage and also predicts the future development of hypertension, cardiovascular events and mortality, independent of resting BP. Moreover, recent work has highlighted that some of the elevated cardiovascular risks associated with an HRE may be related to high-normal resting BP (pre-hypertension) or ambulatory 'masked' hypertension and that an HRE may be an early warning signal of abnormal BP control that is otherwise undetected with clinic BP. Whilst an HRE may be amenable to treatment via pharmacological and lifestyle interventions, the exact physiological mechanism of an HRE remains elusive, but it is likely a manifestation of multiple factors including large artery stiffness, increased peripheral resistance, neural circulatory control and metabolic irregularity. Future research focus may be directed towards determining threshold values to denote the increased risk associated with an HRE and further resolution of the underlying physiological factors involved in the pathogenesis of an HRE.

  17. Schistosome-induced cholangiocyte proliferation and osteopontin secretion correlate with fibrosis and portal hypertension in human and murine schistosomiasis mansoni.

    Science.gov (United States)

    Pereira, Thiago A; Syn, Wing-Kin; Machado, Mariana V; Vidigal, Paula V; Resende, Vivian; Voieta, Izabela; Xie, Guanhua; Otoni, Alba; Souza, Márcia M; Santos, Elisângela T; Chan, Isaac S; Trindade, Guilherme V M; Choi, Steve S; Witek, Rafal P; Pereira, Fausto E; Secor, William E; Andrade, Zilton A; Lambertucci, José Roberto; Diehl, Anna Mae

    2015-11-01

    Schistosomiasis is a major cause of portal hypertension worldwide. It associates with portal fibrosis that develops during chronic infection. The mechanisms by which the pathogen evokes these host responses remain unclear. We evaluated the hypothesis that schistosome eggs release factors that directly stimulate liver cells to produce osteopontin (OPN), a pro-fibrogenic protein that stimulates hepatic stellate cells to become myofibroblasts. We also investigated the utility of OPN as a biomarker of fibrosis and/or severity of portal hypertension. Cultured cholangiocytes, Kupffer cells and hepatic stellate cells were treated with soluble egg antigen (SEA); OPN production was quantified by quantitative reverse transcriptase polymerase chain reaction (qRTPCR) and ELISA; cell proliferation was assessed by BrdU (5-bromo-2'-deoxyuridine). Mice were infected with Schistosoma mansoni for 6 or 16 weeks to cause early or advanced fibrosis. Liver OPN was evaluated by qRTPCR and immunohistochemistry (IHC) and correlated with liver fibrosis and serum OPN. Livers from patients with schistosomiasis mansoni (early fibrosis n=15; advanced fibrosis n=72) or healthy adults (n=22) were immunostained for OPN and fibrosis markers. Results were correlated with plasma OPN levels and splenic vein pressures. SEA-induced cholangiocyte proliferation and OPN secretion (Pportal hypertension severity. © 2015 Authors; published by Portland Press Limited.

  18. Essential hypertension vs. secondary hypertension among children.

    Science.gov (United States)

    Gupta-Malhotra, Monesha; Banker, Ashish; Shete, Sanjay; Hashmi, Syed Sharukh; Tyson, John E; Barratt, Michelle S; Hecht, Jacqueline T; Milewicz, Diane M; Boerwinkle, Eric

    2015-01-01

    The aim was to determine the proportions and correlates of essential hypertension among children in a tertiary pediatric hypertension clinic. We evaluated 423 consecutive children and collected demographic and clinical history by retrospective chart review. We identified 275 (65%) hypertensive children (blood pressure >95th percentile per the "Fourth Report on the Diagnosis, Evaluation, and Treatment of High Blood Pressure in Children and Adolescents") from 423 children referred to the clinic for history of elevated blood pressure. The remainder of the patients had normotension (11%), white coat hypertension (11%), prehypertension (10%), and pending diagnosis (3%). Among the 275 hypertensive children, 43% (n = 119; boys = 56%; median age = 12 years; range = 3-17 years) had essential hypertension and 57% (n = 156; boys = 66%; median age = 9 years; range = 0.08-19 years) had secondary hypertension. When compared with those with secondary hypertension, those with essential hypertension had a significantly older age at diagnosis (P = 0.0002), stronger family history of hypertension (94% vs. 68%; P secondary hypertension. The phenotype of essential hypertension can present as early as 3 years of age and is the predominant form of hypertension in children after age of 6 years. Among children with hypertension, those with essential hypertension present at an older age, have a stronger family history of hypertension, and have lower prevalence of preterm birth. © American Journal of Hypertension, Ltd 2014. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  19. The causal effect of vitamin D binding protein (DBP levels on calcemic and cardiometabolic diseases: a Mendelian randomization study.

    Directory of Open Access Journals (Sweden)

    Aaron Leong

    2014-10-01

    Full Text Available Observational studies have shown that vitamin D binding protein (DBP levels, a key determinant of 25-hydroxy-vitamin D (25OHD levels, and 25OHD levels themselves both associate with risk of disease. If 25OHD levels have a causal influence on disease, and DBP lies in this causal pathway, then DBP levels should likewise be causally associated with disease. We undertook a Mendelian randomization study to determine whether DBP levels have causal effects on common calcemic and cardiometabolic disease.We measured DBP and 25OHD levels in 2,254 individuals, followed for up to 10 y, in the Canadian Multicentre Osteoporosis Study (CaMos. Using the single nucleotide polymorphism rs2282679 as an instrumental variable, we applied Mendelian randomization methods to determine the causal effect of DBP on calcemic (osteoporosis and hyperparathyroidism and cardiometabolic diseases (hypertension, type 2 diabetes, coronary artery disease, and stroke and related traits, first in CaMos and then in large-scale genome-wide association study consortia. The effect allele was associated with an age- and sex-adjusted decrease in DBP level of 27.4 mg/l (95% CI 24.7, 30.0; n = 2,254. DBP had a strong observational and causal association with 25OHD levels (p = 3.2 × 10(-19. While DBP levels were observationally associated with calcium and body mass index (BMI, these associations were not supported by causal analyses. Despite well-powered sample sizes from consortia, there were no associations of rs2282679 with any other traits and diseases: fasting glucose (0.00 mmol/l [95% CI -0.01, 0.01]; p = 1.00; n = 46,186; fasting insulin (0.01 pmol/l [95% CI -0.00, 0.01,]; p = 0.22; n = 46,186; BMI (0.00 kg/m(2 [95% CI -0.01, 0.01]; p = 0.80; n = 127,587; bone mineral density (0.01 g/cm(2 [95% CI -0.01, 0.03]; p = 0.36; n = 32,961; mean arterial pressure (-0.06 mm Hg [95% CI -0.19, 0.07]; p = 0.36; n = 28,775; ischemic stroke (odds ratio [OR]  = 1.00 [95% CI 0.97, 1.04]; p = 0.92; n

  20. Hypertension Subtypes among Hypertensive Patients in Ibadan

    OpenAIRE

    Abiodun M. Adeoye; Adewole Adebiyi; Bamidele O. Tayo; Babatunde L. Salako; Adesola Ogunniyi; Richard S. Cooper

    2014-01-01

    Background. Certain hypertension subtypes have been shown to increase the risk for cardiovascular morbidity and mortality and may be related to specific underlying genetic determinants. Inappropriate characterization of subtypes of hypertension makes efforts at elucidating the genetic contributions to the etiology of hypertension largely vapid. We report the hypertension subtypes among patients with hypertension from South-Western Nigeria. Methods. A total of 1858 subjects comprising 76% fema...

  1. Controlling Hypertension

    Centers for Disease Control (CDC) Podcasts

    Hypertension, or high blood pressure, affects one third of U.S. adults and is a leading cause of heart disease and stroke. A recent study found an increase in self-reported high blood pressure among U.S. adults, and an increase in the use of medications to control high blood pressure. In this podcast, Dr. Fleetwood Loustalot discusses the importance of controlling high blood pressure.

  2. Hypertension Subtypes among Hypertensive Patients in Ibadan

    Directory of Open Access Journals (Sweden)

    Abiodun M. Adeoye

    2014-01-01

    Full Text Available Background. Certain hypertension subtypes have been shown to increase the risk for cardiovascular morbidity and mortality and may be related to specific underlying genetic determinants. Inappropriate characterization of subtypes of hypertension makes efforts at elucidating the genetic contributions to the etiology of hypertension largely vapid. We report the hypertension subtypes among patients with hypertension from South-Western Nigeria. Methods. A total of 1858 subjects comprising 76% female, hypertensive, aged 18 and above were recruited into the study from two centers in Ibadan, Nigeria. Hypertension was identified using JNCVII definition and was further grouped into four subtypes: controlled hypertension (CH, isolated systolic hypertension (ISH, isolated diastolic hypertension (IDH, and systolic-diastolic hypertension (SDH. Results. Systolic-diastolic hypertension was the most prevalent. Whereas SDH (77.6% versus 73.5% and IDH (4.9% versus 4.7% were more prevalent among females, ISH (10.1% versus 6.2% was higher among males (P=0.048. Female subjects were more obese (P<0.0001 and SDH was prevalent among the obese group. Conclusion. Gender and obesity significantly influenced the distribution of the hypertension subtypes. Characterization of hypertension by subtypes in genetic association studies could lead to identification of previously unknown genetic variants involved in the etiology of hypertension. Large-scale studies among various ethnic groups may be needed to confirm these observations.

  3. Elevated levels of plasma uric acid and its relation to hypertension in arsenic-endemic human individuals in Bangladesh

    International Nuclear Information System (INIS)

    Huda, Nazmul; Hossain, Shakhawoat; Rahman, Mashiur; Karim, Md. Rezaul; Islam, Khairul; Mamun, Abdullah Al; Hossain, Md. Imam; Mohanto, Nayan Chandra; Alam, Shahnur; Aktar, Sharmin; Arefin, Afroza; Ali, Nurshad; Salam, Kazi Abdus; Aziz, Abdul; Saud, Zahangir Alam; Miyataka, Hideki; Himeno, Seiichiro; Hossain, Khaled

    2014-01-01

    Blood uric acid has been recognized as a putative marker for cardiovascular diseases (CVDs). CVDs are the major causes of arsenic-related morbidity and mortality. However, the association of arsenic exposure with plasma uric acid (PUA) levels in relation to CVDs has not yet been explored. This study for the first time demonstrated the associations of arsenic exposure with PUA levels and its relationship with hypertension. A total of 483 subjects, 322 from arsenic-endemic and 161 from non-endemic areas in Bangladesh were recruited as study subjects. Arsenic concentrations in the drinking water, hair and nails of the study subjects were measured by inductively coupled plasma mass spectroscopy. PUA levels were measured using a colorimetric method. We found that PUA levels were significantly (p < 0.001) higher in males and females living in arsenic-endemic areas than those in non-endemic area. Arsenic exposure (water, hair and nail arsenic) levels showed significant positive correlations with PUA levels. In multiple regression analyses, arsenic exposure levels were found to be the most significant contributors on PUA levels among the other variables that included age, body mass index, blood urea nitrogen, and smoking. There were dose–response relationships between arsenic exposure and PUA levels. Furthermore, diastolic and systolic blood pressure showed significant positive correlations with PUA levels. Finally, the average PUA levels were significantly higher in the hypertensive group than those in the normotensive group in both males and females living in arsenic-endemic areas. These results suggest that arsenic exposure-related elevation of PUA levels may be implicated in arsenic-induced CVDs. - Highlights: • PUA levels were higher in arsenic-endemic subjects than in non-endemic subjects. • Drinking water, hair and nail arsenic showed significant associations with PUA levels. • Drinking water, hair and nail arsenic showed dose–response relationships with

  4. Elevated levels of plasma uric acid and its relation to hypertension in arsenic-endemic human individuals in Bangladesh

    Energy Technology Data Exchange (ETDEWEB)

    Huda, Nazmul [Department of Biochemistry and Molecular Biology, Rajshahi University, Rajshahi 6205 (Bangladesh); Department of Medicine, Rajshahi Medical College, Rajshahi 6000 (Bangladesh); Hossain, Shakhawoat; Rahman, Mashiur [Department of Biochemistry and Molecular Biology, Rajshahi University, Rajshahi 6205 (Bangladesh); Karim, Md. Rezaul [Department of Applied Nutrition and Food Technology, Islamic University, Kushtia 7003 (Bangladesh); Islam, Khairul [Department of Biochemistry and Molecular Biology, Mawlana Bhashani Science and Technology University, Santosh, Tangail 1902 (Bangladesh); Mamun, Abdullah Al; Hossain, Md. Imam; Mohanto, Nayan Chandra; Alam, Shahnur; Aktar, Sharmin; Arefin, Afroza; Ali, Nurshad; Salam, Kazi Abdus; Aziz, Abdul; Saud, Zahangir Alam [Department of Biochemistry and Molecular Biology, Rajshahi University, Rajshahi 6205 (Bangladesh); Miyataka, Hideki; Himeno, Seiichiro [Laboratory of Molecular Nutrition and Toxicology, Faculty of Pharmaceutical Sciences, Tokushima Bunri University, Tokushima 770-8514 (Japan); Hossain, Khaled, E-mail: khossainbio@gmail.com [Department of Biochemistry and Molecular Biology, Rajshahi University, Rajshahi 6205 (Bangladesh)

    2014-11-15

    Blood uric acid has been recognized as a putative marker for cardiovascular diseases (CVDs). CVDs are the major causes of arsenic-related morbidity and mortality. However, the association of arsenic exposure with plasma uric acid (PUA) levels in relation to CVDs has not yet been explored. This study for the first time demonstrated the associations of arsenic exposure with PUA levels and its relationship with hypertension. A total of 483 subjects, 322 from arsenic-endemic and 161 from non-endemic areas in Bangladesh were recruited as study subjects. Arsenic concentrations in the drinking water, hair and nails of the study subjects were measured by inductively coupled plasma mass spectroscopy. PUA levels were measured using a colorimetric method. We found that PUA levels were significantly (p < 0.001) higher in males and females living in arsenic-endemic areas than those in non-endemic area. Arsenic exposure (water, hair and nail arsenic) levels showed significant positive correlations with PUA levels. In multiple regression analyses, arsenic exposure levels were found to be the most significant contributors on PUA levels among the other variables that included age, body mass index, blood urea nitrogen, and smoking. There were dose–response relationships between arsenic exposure and PUA levels. Furthermore, diastolic and systolic blood pressure showed significant positive correlations with PUA levels. Finally, the average PUA levels were significantly higher in the hypertensive group than those in the normotensive group in both males and females living in arsenic-endemic areas. These results suggest that arsenic exposure-related elevation of PUA levels may be implicated in arsenic-induced CVDs. - Highlights: • PUA levels were higher in arsenic-endemic subjects than in non-endemic subjects. • Drinking water, hair and nail arsenic showed significant associations with PUA levels. • Drinking water, hair and nail arsenic showed dose–response relationships with

  5. Pulmonary Hypertension

    Science.gov (United States)

    Kim, John S.; McSweeney, Julia; Lee, Joanne; Ivy, Dunbar

    2015-01-01

    Objective Review the pharmacologic treatment options for pulmonary arterial hypertension (PAH) in the cardiac intensive care setting and summarize the most-recent literature supporting these therapies. Data Sources and Study Selection Literature search for prospective studies, retrospective analyses, and case reports evaluating the safety and efficacy of PAH therapies. Data Extraction Mechanisms of action and pharmacokinetics, treatment recommendations, safety considerations, and outcomes for specific medical therapies. Data Synthesis Specific targeted therapies developed for the treatment of adult patients with PAH have been applied for the benefit of children with PAH. With the exception of inhaled nitric oxide, there are no PAH medications approved for children in the US by the FDA. Unfortunately, data on treatment strategies in children with PAH are limited by the small number of randomized controlled clinical trials evaluating the safety and efficacy of specific treatments. The treatment options for PAH in children focus on endothelial-based pathways. Calcium channel blockers are recommended for use in a very small, select group of children who are responsive to vasoreactivity testing at cardiac catheterization. Phosphodiesterase type 5 inhibitor therapy is the most-commonly recommended oral treatment option in children with PAH. Prostacyclins provide adjunctive therapy for the treatment of PAH as infusions (intravenous and subcutaneous) and inhalation agents. Inhaled nitric oxide is the first line vasodilator therapy in persistent pulmonary hypertension of the newborn, and is commonly used in the treatment of PAH in the Intensive Care Unit (ICU). Endothelin receptor antagonists have been shown to improve exercise tolerance and survival in adult patients with PAH. Soluble Guanylate Cyclase Stimulators are the first drug class to be FDA approved for the treatment of chronic thromboembolic pulmonary hypertension. Conclusions Literature and data supporting the

  6. Managing hypertension by polyphenols.

    Science.gov (United States)

    Fernández-Arroyo, Salvador; Camps, Jordi; Menendez, Javier A; Joven, Jorge

    2015-06-01

    Some polyphenols, obtained from plants of broad use, induce a favorable endothelial response in hypertension and beneficial effects in the management of other metabolic cardiovascular risks. Previous studies in our laboratories using the calyces of Hibiscus sabdariffa as a source of polyphenols show that significant effects on hypertension are noticeable in humans only when provided in high amounts. Available data are suggestive in animal models and ex vivo experiments, but data in humans are difficult to acquire. Additionally, and despite the low bioavailability of polyphenols, intervention studies provide evidence for the protective effects of secondary plant metabolites. Assumptions on public health benefits are limited by the lack of scientific knowledge, robust data derived from large randomized clinical trials, and an accurate assessment of the bioactive components provided by common foodstuff. Because it is likely that clinical effects are the result of multiple interactions among different polyphenols rather than the isolated action of unique compounds, to provide polyphenol-rich botanical extracts as dietary supplements is a suggestive option. Unfortunately, the lack of patent perspectives for the pharmaceutical industries and the high cost of production and release for alimentary industries will hamper the performance of the necessary clinical trials. Here we briefly discuss whether and how such limitations may complicate the extensive use of plant-derived products in the management of hypertension and which steps are the necessary to deal with the predictable complexity in a possible clinical practice. Georg Thieme Verlag KG Stuttgart · New York.

  7. Does greater adiposity increase blood pressure and hypertension risk?: Mendelian randomization using the FTO/MC4R genotype

    DEFF Research Database (Denmark)

    Timpson, Nicholas J; Harbord, Roger; Davey Smith, George

    2009-01-01

    of the causal association between body mass index and blood pressure. This was performed using both rs9939609 (FTO) and rs17782313 (MC4R) genotypes as instruments for body mass index. Avoiding the epidemiological problems of confounding, bias, and reverse causation, we confirmed observational associations...

  8. Hormones and Hypertension

    Science.gov (United States)

    ... role in the start and continuation of primary hypertension. Secondary hypertension is due to other diseases such as kidney ... the body can greatly improve or even cure secondary hypertension. Resources • Find-an-Endocrinologist: www.hormone.org or ...

  9. Pulmonary Hypertension in Scleroderma

    Science.gov (United States)

    PULMONARY HYPERTENSION IN SCLERODERMA PULMONARY HYPERTENSION Pulmonary hypertension (PH) is high blood pressure in the blood vessels of the lungs. If the high ... the right side of the heart. Patients with scleroderma are at increased risk for developing PH from ...

  10. Hypertension and Spina Bifida

    Science.gov (United States)

    SBA National Resource Center: 800-621-3141 Hypertension A disease that often goes undetected. What is hypertension? Hypertension, also called high blood pressure , is a condition in which the arteries of ...

  11. Intracranial Hypertension Research Foundation

    Science.gov (United States)

    ... PARTNERSHIPS Meet our Fundraising Partners Tweet Welcome Intracranial hypertension (IH) is the general term for the neurological ... high. (Old names for IH include Benign Intracranial Hypertension and Pseudotumor Cerebri). The Intracranial Hypertension Research Foundation ...

  12. HIV and Pulmonary Hypertension

    Science.gov (United States)

    ... What do I need to know about pulmonary hypertension in connection with HIV? Although pulmonary hypertension and ... Should an HIV patient be tested for pulmonary hypertension? HIV patients know that medical supervision is critical ...

  13. C reactive protein and chronic obstructive pulmonary disease: a Mendelian randomisation approach

    DEFF Research Database (Denmark)

    Dahl, Morten; Vestbo, Jørgen; Zacho, Jeppe

    2011-01-01

    Background It is unclear whether elevated plasma C reactive protein (CRP) is causally related to chronic obstructive pulmonary disease (COPD). The authors tested the hypothesis that genetically elevated plasma CRP causes COPD using a Mendelian randomisation design. Methods The authors measured high......-sensitivity CRP in plasma, genotyped for four single nucleotide polymorphisms in the CRP gene, and screened for spirometry-defined COPD and hospitalisation due to COPD in 7974 individuals from the Copenhagen City Heart Study and in 32¿652 individuals from the Copenhagen General Population Study. Results Elevated...... plasma CRP >3 mg/l compared with Study and the Copenhagen General Population Study, respectively. Genotype combinations...

  14. Childhood adiposity and risk of type 1 diabetes: A Mendelian randomization study.

    Directory of Open Access Journals (Sweden)

    J C Censin

    2017-08-01

    Full Text Available The incidence of type 1 diabetes (T1D is increasing globally. One hypothesis is that increasing childhood obesity rates may explain part of this increase, but, as T1D is rare, intervention studies are challenging to perform. The aim of this study was to assess this hypothesis with a Mendelian randomization approach that uses genetic variants as instrumental variables to test for causal associations.We created a genetic instrument of 23 single nucleotide polymorphisms (SNPs associated with childhood adiposity in children aged 2-10 years. Summary-level association results for these 23 SNPs with childhood-onset (<17 years T1D were extracted from a meta-analysis of genome-wide association study with 5,913 T1D cases and 8,828 reference samples. Using inverse-variance weighted Mendelian randomization analysis, we found support for an effect of childhood adiposity on T1D risk (odds ratio 1.32, 95% CI 1.06-1.64 per standard deviation score in body mass index [SDS-BMI]. A sensitivity analysis provided evidence of horizontal pleiotropy bias (p = 0.04 diluting the estimates towards the null. We therefore applied Egger regression and multivariable Mendelian randomization methods to control for this type of bias and found evidence in support of a role of childhood adiposity in T1D (odds ratio in Egger regression, 2.76, 95% CI 1.40-5.44. Limitations of our study include that underlying genes and their mechanisms for most of the genetic variants included in the score are not known. Mendelian randomization requires large sample sizes, and power was limited to provide precise estimates. This research has been conducted using data from the Early Growth Genetics (EGG Consortium, the Genetic Investigation of Anthropometric Traits (GIANT Consortium, the Tobacco and Genetics (TAG Consortium, and the Social Science Genetic Association Consortium (SSGAC, as well as meta-analysis results from a T1D genome-wide association study.This study provides genetic support for a

  15. Mendelian randomization study of B-type natriuretic peptide and type 2 diabetes: evidence of causal association from population studies.

    Directory of Open Access Journals (Sweden)

    Roman Pfister

    2011-10-01

    Full Text Available Genetic and epidemiological evidence suggests an inverse association between B-type natriuretic peptide (BNP levels in blood and risk of type 2 diabetes (T2D, but the prospective association of BNP with T2D is uncertain, and it is unclear whether the association is confounded.We analysed the association between levels of the N-terminal fragment of pro-BNP (NT-pro-BNP in blood and risk of incident T2D in a prospective case-cohort study and genotyped the variant rs198389 within the BNP locus in three T2D case-control studies. We combined our results with existing data in a meta-analysis of 11 case-control studies. Using a Mendelian randomization approach, we compared the observed association between rs198389 and T2D to that expected from the NT-pro-BNP level to T2D association and the NT-pro-BNP difference per C allele of rs198389. In participants of our case-cohort study who were free of T2D and cardiovascular disease at baseline, we observed a 21% (95% CI 3%-36% decreased risk of incident T2D per one standard deviation (SD higher log-transformed NT-pro-BNP levels in analysis adjusted for age, sex, body mass index, systolic blood pressure, smoking, family history of T2D, history of hypertension, and levels of triglycerides, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol. The association between rs198389 and T2D observed in case-control studies (odds ratio = 0.94 per C allele, 95% CI 0.91-0.97 was similar to that expected (0.96, 0.93-0.98 based on the pooled estimate for the log-NT-pro-BNP level to T2D association derived from a meta-analysis of our study and published data (hazard ratio = 0.82 per SD, 0.74-0.90 and the difference in NT-pro-BNP levels (0.22 SD, 0.15-0.29 per C allele of rs198389. No significant associations were observed between the rs198389 genotype and potential confounders.Our results provide evidence for a potential causal role of the BNP system in the aetiology of T2D. Further studies

  16. Neonatal hypertension.

    Science.gov (United States)

    Sharma, Deepak; Farahbakhsh, Nazanin; Shastri, Sweta; Sharma, Pradeep

    2017-03-01

    Neonatal hypertension (HT) is a frequently under reported condition and is seen uncommonly in the intensive care unit. Neonatal HT has defined arbitrarily as blood pressure more than 2 standard deviations above the base as per the age or defined as systolic BP more than 95% for infants of similar size, gestational age and postnatal age. It has been diagnosed long back but still is the least studied field in neonatology. There is still lack of universally accepted normotensive data for neonates as per gestational age, weight and post-natal age. Neonatal HT is an important morbidity that needs timely detection and appropriate management, as it can lead to devastating short-term effect on various organs and also poor long-term adverse outcomes. There is no consensus yet about the treatment guidelines and majority of treatment protocols are based on the expert opinion. Neonate with HT should be evaluated in detail starting from antenatal, perinatal, post-natal history, and drug intake by neonate and mother. This review article covers multiple aspects of neonatal hypertension like definition, normotensive data, various etiologies and methods of BP measurement, clinical features, diagnosis and management.

  17. Heavier smoking may lead to a relative increase in waist circumference: evidence for a causal relationship from a Mendelian randomisation meta-analysis. The CARTA consortium

    NARCIS (Netherlands)

    Morris, R.W.; Taylor, A.E.; Fluharty, M.E.; Bjorngaard, J.H.; Asvold, B.O.; Elvestad Gabrielsen, M.; Campbell, A.; Marioni, R.; Kumari, M.; Korhonen, T.; Männistö, S.; Marques-Vidal, P.; Kaakinen, M.; Cavadino, A.; Postmus, I.; Husemoen, L.L.N.; Skaaby, T.; Ahluwalia, T.S.; Treur, J.L.; Willemsen, G.; Dale, C.; Wannamethee, S.G.; Lahti, J.; Palotie, A.; Räikkönen, K.; McConnachie, A.; Padmanabhan, S.; Wong, A.; Dalgard, C.; Paternoster, L.; Ben-Shlomo, Y.; Tyrrell, J.; Horwood, J.; Fergusson, D.M.; Kennedy, M.A.; Nohr, E.A.; Christiansen, L.; Kyvik, K.O.; Kuh, D; Watt, G.; Eriksson, J.G.; Whincup, P.H.; Vink, J.M.; Boomsma, D.I.; Davey Smith, G.; Lawlor, D.; Linneberg, A.; Ford, I.; Jukema, J.W.; Power, C.; Hyppönen, E.; Jarvelin, M.R.; Preisig, M.; Borodulin, K.; Kaprio, J.; Kivimaki, M.; Smith, B.H.; Hayward, C.; Romundstad, P.R.; Sørensen, T.I.A.; Munafò, M.; Sattar, N.

    2015-01-01

    Objectives: To investigate, using a Mendelian randomisation approach, whether heavier smoking is associated with a range of regional adiposity phenotypes, in particular those related to abdominal adiposity. Design: Mendelian randomisation meta-analyses using a genetic variant (rs16969968/rs1051730

  18. Heavier smoking may lead to a relative increase in waist circumference: Evidence for a causal relationship from a Mendelian randomisation meta-analysis. The CARTA consortium

    NARCIS (Netherlands)

    Morris, R.W.; Taylor, A.E.; Fluharty, M.E.; Björngaard, J.H.; Asvold, B.A.; Elvestad Gabrielsen, M.; Campbell, A.; Marioni, R.E.; Kumari, M.; Korhonen, T.; Mannisto, S.; Marques-Vidal, P.; Kaakinen, M.; Cavadino, A.; Postmus, I.; Husemoen, L.L.N.; Skaaby, T.; Ahluwalia, T.V.S.; Treur, J.L.; Willemsen, G.; Dale, C.E.; Wannamethee, S.G.; Lahti, J.; Palotie, A.; Raikkonen, K.; McConnachie, A.; Padmanabhan, S.; Wong, A.; Dalgard, C.; Paternoster, L.; Ben-Shlomo, Y.; Tyrrell, J.; Horwood, J.; Fergusson, D.M.; Kennedy, M.A.; Nohr, E.A.; Christiansen, L.; Kyvik, K.O.; Kuh, D.; Watt, G.; Eriksson, J.G.; Whincup, P.H.; Vink, J.M.; Boomsma, D.I.; Davey Smith, G.; Lawlor, D.A.; Linneberg, A.; Ford, I.; Jukema, J.W.; Power, C.; Hypponen, E.; Jarvelin, M.R.; Preisig, M.; Borodulin, K.; Kaprio, J.; Kivimaki, M.; Smith, B.H.; Hayward, C.; Romundstad, P.R.; Sorensen, T.I.A.; Munafò, M.R.; Sattar, N.

    2015-01-01

    OBJECTIVES: To investigate, using a Mendelian randomisation approach, whether heavier smoking is associated with a range of regional adiposity phenotypes, in particular those related to abdominal adiposity. DESIGN: Mendelian randomisation meta-analyses using a genetic variant (rs16969968/rs1051730

  19. Vitamin D status and hypertension: a review

    Directory of Open Access Journals (Sweden)

    Ke L

    2015-04-01

    relationship. Further studies either combining existing raw data from available cohort studies or conducting further Mendelian analyses are needed to determine whether this represents a causal association. Large randomized controlled trials are also needed to determine whether vitamin supplementation may be beneficial in the prevention or the treatment of hypertension. Keywords: 25OHD, high blood pressure, meta-analysis, prospective, cross-sectional, blood pressure

  20. Association of vitamin D status with arterial blood pressure and hypertension risk

    DEFF Research Database (Denmark)

    Vimaleswaran, Karani S; Cavadino, Alana; Berry, Diane J

    2014-01-01

    BACKGROUND: Low plasma 25-hydroxyvitamin D (25[OH]D) concentration is associated with high arterial blood pressure and hypertension risk, but whether this association is causal is unknown. We used a mendelian randomisation approach to test whether 25(OH)D concentration is causally associated...... with blood pressure and hypertension risk. METHODS: In this mendelian randomisation study, we generated an allele score (25[OH]D synthesis score) based on variants of genes that affect 25(OH)D synthesis or substrate availability (CYP2R1 and DHCR7), which we used as a proxy for 25(OH)D concentration. We meta......, -0·12 mm Hg, 95% CI -0·20 to -0·04; p=0·003) and reduced odds of hypertension (odds ratio [OR] 0·98, 95% CI 0·97-0·99; p=0·0003), but not with decreased diastolic blood pressure (β per 10% increase, -0·02 mm Hg, -0·08 to 0·03; p=0·37). In meta-analyses in which we combined data from D...

  1. Catestatin Gly364Ser Variant Alters Systemic Blood Pressure and the Risk for Hypertension in Human Populations via Endothelial Nitric Oxide Pathway.

    Science.gov (United States)

    Kiranmayi, Malapaka; Chirasani, Venkat R; Allu, Prasanna K R; Subramanian, Lakshmi; Martelli, Elizabeth E; Sahu, Bhavani S; Vishnuprabu, Durairajpandian; Kumaragurubaran, Rathnakumar; Sharma, Saurabh; Bodhini, Dhanasekaran; Dixit, Madhulika; Munirajan, Arasambattu K; Khullar, Madhu; Radha, Venkatesan; Mohan, Viswanathan; Mullasari, Ajit S; Naga Prasad, Sathyamangla V; Senapati, Sanjib; Mahapatra, Nitish R

    2016-08-01

    Catestatin (CST), an endogenous antihypertensive/antiadrenergic peptide, is a novel regulator of cardiovascular physiology. Here, we report case-control studies in 2 geographically/ethnically distinct Indian populations (n≈4000) that showed association of the naturally-occurring human CST-Gly364Ser variant with increased risk for hypertension (age-adjusted odds ratios: 1.483; P=0.009 and 2.951; P=0.005). Consistently, 364Ser allele carriers displayed elevated systolic (up to ≈8 mm Hg; P=0.004) and diastolic (up to ≈6 mm Hg; P=0.001) blood pressure. The variant allele was also found to be in linkage disequilibrium with other functional single-nucleotide polymorphisms in the CHGA promoter and nearby coding region. Functional characterization of the Gly364Ser variant was performed using cellular/molecular biological experiments (viz peptide-receptor binding assays, nitric oxide [NO], phosphorylated extracellular regulated kinase, and phosphorylated endothelial NO synthase estimations) and computational approaches (molecular dynamics simulations for structural analysis of wild-type [CST-WT] and variant [CST-364Ser] peptides and docking of peptide/ligand with β-adrenergic receptors [ADRB1/2]). CST-WT and CST-364Ser peptides differed profoundly in their secondary structures and showed differential interactions with ADRB2; although CST-WT displaced the ligand bound to ADRB2, CST-364Ser failed to do the same. Furthermore, CST-WT significantly inhibited ADRB2-stimulated extracellular regulated kinase activation, suggesting an antagonistic role towards ADRB2 unlike CST-364Ser. Consequently, CST-WT was more potent in NO production in human umbilical vein endothelial cells as compared with CST-364Ser. This NO-producing ability of CST-WT was abrogated by ADRB2 antagonist ICI 118551. In conclusion, CST-364Ser allele enhanced the risk for hypertension in human populations, possibly via diminished endothelial NO production because of altered interactions of CST-364Ser

  2. Bilirubin as a potential causal factor in type 2 diabetes risk: a Mendelian randomization study

    Science.gov (United States)

    Abbasi, Ali; Deetman, Petronella E.; Corpeleijn, Eva; Gansevoort, Ron T.; Gans, Rijk O.B.; Hillege, Hans L.; van der Harst, Pim; Stolk, Ronald P.; Navis, Gerjan; Alizadeh, Behrooz Z.; Bakker, Stephan J.L.

    2014-01-01

    Circulating bilirubin, a natural antioxidant, is associated with decreased risk of type 2 diabetes (T2D), but the nature of the relationship remains unknown. We performed Mendelian randomization in a prospective cohort of 3,381 participants free of diabetes at baseline (aged 28-75 years; women, 52.6%). We used rs6742078 located in UDP-glucuronosyltransferase (UGT1A1) locus as instrumental variable (IV) to study a potential causal effect of serum total bilirubin on T2D risk. T2D developed in a total of 210 (6.2%) participants during a median follow-up of 7.8 years. In adjusted analyses, rs6742078, which explained 19.5% of bilirubin variation, was strongly associated with total bilirubin (a 0.68-SD increase in bilirubin levels per T allele; Pbilirubin levels, we observed a 25% (OR 0.75 [95%CI, 0.62-0.92]; P=0.004) lower risk of T2D. In Mendelian randomization analysis, the causal risk reduction for T2D was estimated to be 42% (causal ORIVestimation per 1-SD increase in log-transformed bilirubin 0.58 [95%CI, 0.39-0.84]; P=0.005), which was comparable to the observational estimate (Durbin-Wu-Hausman chi-square test Pfor difference =0.19). These novel results provide evidence that elevated bilirubin is causally associated with risk of T2D and support its role as a protective determinant. PMID:25368098

  3. Vitamin D and C-Reactive Protein: A Mendelian Randomization Study.

    Directory of Open Access Journals (Sweden)

    Marte C Liefaard

    Full Text Available Vitamin D deficiency is widely prevalent and has been associated with many diseases. It has been suggested that vitamin D has effects on the immune system and inhibits inflammation. The aim of our study was to investigate whether vitamin D has an inhibitory effect on systemic inflammation by assessing the association between serum levels of vitamin D and C-reactive protein. We studied the association between serum 25-hydroxyvitamin D and C-reactive protein through linear regression in 9,649 participants of the Rotterdam Study, an observational, prospective population-based cohort study. We used genetic variants related to vitamin D and CRP to compute a genetic risk score and perform bi-directional Mendelian randomization analysis. In linear regression adjusted for age, sex, cohort and other confounders, natural log-transformed CRP decreased with 0.06 (95% CI: -0.08, -0.03 unit per standard deviation increase in 25-hydroxyvitamin D. Bi-directional Mendelian randomization analyses showed no association between the vitamin D genetic risk score and lnCRP (Beta per SD = -0.018; p = 0.082 or the CRP genetic risk score and 25-hydroxyvitamin D (Beta per SD = 0.001; p = 0.998. In conclusion, higher levels of Vitamin D are associated with lower levels of C-reactive protein. In this study we did not find evidence for this to be the result of a causal relationship.

  4. The Number of Candidate Variants in Exome Sequencing for Mendelian Disease under No Genetic Heterogeneity

    Directory of Open Access Journals (Sweden)

    Jo Nishino

    2013-01-01

    Full Text Available There has been recent success in identifying disease-causing variants in Mendelian disorders by exome sequencing followed by simple filtering techniques. Studies generally assume complete or high penetrance. However, there are likely many failed and unpublished studies due in part to incomplete penetrance or phenocopy. In this study, the expected number of candidate single-nucleotide variants (SNVs in exome data for autosomal dominant or recessive Mendelian disorders was investigated under the assumption of “no genetic heterogeneity.” All variants were assumed to be under the “null model,” and sample allele frequencies were modeled using a standard population genetics theory. To investigate the properties of pedigree data, full-sibs were considered in addition to unrelated individuals. In both cases, particularly regarding full-sibs, the number of SNVs remained very high without controls. The high efficacy of controls was also confirmed. When controls were used with a relatively large total sample size (e.g., N=20, 50, filtering incorporating of incomplete penetrance and phenocopy efficiently reduced the number of candidate SNVs. This suggests that filtering is useful when an assumption of no “genetic heterogeneity” is appropriate and could provide general guidelines for sample size determination.

  5. Metaplasia of the parietal layer of Bowman's capsule in the human kidney. Incidence in alcoholic liver disease and hypertension

    OpenAIRE

    Haensly, William E.

    1988-01-01

    This report is the second of two surveys to determine the incidence of metaplasia of Bowman's parietal epithelium in the human kidney. Human kidney sections obtained at autopsy at the Department of Pathology, University of Texas Medical Branch, Galveston, Texas, were examined with the light microscope. The kidneys were fixed in neutral formalin, sectioned at 6 pm and stained with hematoxylin and eosin. Autopsy records were consulted after kidney section exa...

  6. The Battle Between the Biometricians and the Mendelians: How Sir Francis Galton's Work Caused his Disciples to Reach Conflicting Conclusions About the Hereditary Mechanism

    Science.gov (United States)

    Gillham, Nicholas W.

    2015-01-01

    Francis Galton, Charles Darwin's cousin, had wide and varied interests. They ranged from exploration and travel writing to fingerprinting and the weather. After reading Darwin's On the Origin of Species, Galton reached the conclusion that it should be possible to improve the human stock through selective breeding, as was the case for domestic animals and cultivated plants. Much of the latter half of Galton's career was devoted to trying to devise methods to distinguish men of good stock and then to show that these qualities were inherited. But along the way he invented two important statistical methods: regression and correlation. He also discovered regression to the mean. This led Galton to believe that evolution could not proceed by the small steps envisioned by Darwin, but must proceed by discontinuous changes. Galton's book Natural Inheritance (1889) served as the inspiration for Karl Pearson, W.F.R. Weldon and William Bateson. Pearson and Weldon were interested in continuously varying characters and the application of statistical techniques to their study. Bateson was fascinated by discontinuities and the role they might play in evolution. Galton proposed his Law of Ancestral Heredity in the last decade of the nineteenth century. At first this seemed to work well as an explanation for continuously varying traits of the type that interested Pearson and Weldon. In contrast, Bateson had published a book on discontinuously varying traits so he was in a position to understand and embrace Mendel's principles of inheritance when they were rediscovered in 1900. The subsequent battle between Weldon and Pearson, the biometricians, and Bateson, the Mendelian, went on acrimoniously for several years at the beginning of the twentieth century before Mendelian theory finally won out.

  7. Role of nitric oxide and prostanoids in the regulation of leg blood flow and blood pressure in humans with essential hypertension: effect of high-intensity aerobic training

    DEFF Research Database (Denmark)

    Nyberg, Michael Permin; Jensen, Lasse Gliemann; Thaning, Pia

    2012-01-01

    We examined the role of nitric oxide (NO) and prostanoids in the regulation of leg blood flow and systemic blood pressure before and after 8 weeks of aerobic high-intensity training in individuals with essential hypertension (n=10) and matched healthy control subjects (n=11). Hypertensive subjects...

  8. GALC deletions increase the risk of primary open-angle glaucoma: the role of Mendelian variants in complex disease.

    Directory of Open Access Journals (Sweden)

    Yutao Liu

    Full Text Available DNA copy number variants (CNVs have been reported in many human diseases including autism and schizophrenia. Primary Open Angle Glaucoma (POAG is a complex adult-onset disorder characterized by progressive optic neuropathy and vision loss. Previous studies have identified rare CNVs in POAG; however, their low frequencies prevented formal association testing. We present here the association between POAG risk and a heterozygous deletion in the galactosylceramidase gene (GALC. This CNV was initially identified in a dataset containing 71 Caucasian POAG cases and 478 ethnically matched controls obtained from dbGAP (study accession phs000126.v1.p1. (p = 0.017, fisher's exact test. It was validated with array comparative genomic hybridization (arrayCGH and realtime PCR, and replicated in an independent POAG dataset containing 959 cases and 1852 controls (p = 0.021, OR (odds ratio = 3.5, 95% CI -1.1-12.0. Evidence for association was strengthened when the discovery and replication datasets were combined (p = 0.002; OR = 5.0, 95% CI 1.6-16.4. Several deletions with different endpoints were identified by array CGH of POAG patients. Homozygous deletions that eliminate GALC enzymatic activity cause Krabbe disease, a recessive Mendelian disorder of childhood displaying bilateral optic neuropathy and vision loss. Our findings suggest that heterozygous deletions that reduce GALC activity are a novel mechanism increasing risk of POAG. This is the first report of a statistically-significant association of a CNV with POAG risk, contributing to a growing body of evidence that CNVs play an important role in complex, inherited disorders. Our findings suggest an attractive biomarker and potential therapeutic target for patients with this form of POAG.

  9. Fumaric acid esters can block pro-inflammatory actions of human CRP and ameliorate metabolic disturbances in transgenic spontaneously hypertensive rats.

    Directory of Open Access Journals (Sweden)

    Jan Šilhavý

    Full Text Available Inflammation and oxidative stress have been implicated in the pathogenesis of metabolic disturbances. Esters of fumaric acid, mainly dimethyl fumarate, exhibit immunomodulatory, anti-inflammatory, and anti-oxidative effects. In the current study, we tested the hypothesis that fumaric acid ester (FAE treatment of an animal model of inflammation and metabolic syndrome, the spontaneously hypertensive rat transgenically expressing human C-reactive protein (SHR-CRP, will ameliorate inflammation, oxidative stress, and metabolic disturbances. We studied the effects of FAE treatment by administering Fumaderm, 10 mg/kg body weight for 4 weeks, to male SHR-CRP. Untreated male SHR-CRP rats were used as controls. All rats were fed a high sucrose diet. Compared to untreated controls, rats treated with FAE showed significantly lower levels of endogenous CRP but not transgenic human CRP, and amelioration of inflammation (reduced levels of serum IL6 and TNFα and oxidative stress (reduced levels of lipoperoxidation products in liver, heart, kidney, and plasma. FAE treatment was also associated with lower visceral fat weight and less ectopic fat accumulation in liver and muscle, greater levels of lipolysis, and greater incorporation of glucose into adipose tissue lipids. Analysis of gene expression profiles in the liver with Affymetrix arrays revealed that FAE treatment was associated with differential expression of genes in pathways that involve the regulation of inflammation and oxidative stress. These findings suggest potentially important anti-inflammatory, anti-oxidative, and metabolic effects of FAE in a model of inflammation and metabolic disturbances induced by human CRP.

  10. Hypertension in women

    OpenAIRE

    Hage, Fadi G; Mansur, Sulaf J; Xing, Dongqi; Oparil, Suzanne

    2013-01-01

    Hypertension is the most common modifiable risk factor for cardiovascular disease, the leading cause of death in both men and women. The prevalence and severity of hypertension rise markedly with age, and blood pressure control becomes more difficult with aging in both genders, particularly in women. In addition, there are forms of hypertension that occur exclusively in women, e.g., hypertension related to menopause, oral contraceptive use, or pregnancy (e.g., chronic hypertension, gestationa...

  11. Association Between Telomere Length and Risk of Cancer and Non-Neoplastic Diseases: A Mendelian Randomization Study

    NARCIS (Netherlands)

    Haycock, P.C.; Burgess, S.; Nounu, A.; Zheng, J.; Okoli, G.N.; Bowden, J.; Wade, K.H.; Timpson, N.J.; Evans, D.M.; Willeit, P.; Aviv, A.; Gaunt, T.R.; Hemani, G.; Mangino, M.; Ellis, H.P.; Kurian, K.M.; Pooley, K.A.; Eeles, R.A.; Lee, J.E.; Fang, S.; Chen, W.V.; Law, M.H.; Bowdler, L.M.; Iles, M.M.; Yang, Q.; Worrall, B.B.; Markus, H.S.; Hung, R.J.; Amos, C.I.; Spurdle, A.B.; Thompson, D.J.; O'Mara, T.A.; Wolpin, B.; Amundadottir, L.; Stolzenberg-Solomon, R.; Trichopoulou, A.; Onland-Moret, N.C.; Lund, E.; Duell, E.J.; Canzian, F.; Severi, G.; Overvad, K.; Gunter, M.J.; Tumino, R.; Svenson, U.; Rij, A. van; Baas, A.F.; Bown, M.J.; Samani, N.J.; t'Hof, F.N.G. van; Tromp, G.; Jones, G.T.; Kuivaniemi, H.; Elmore, J.R.; Johansson, M.; McKay, J.; Scelo, G.; Carreras-Torres, R.; Gaborieau, V.; Brennan, P.; Bracci, P.M.; Neale, R.E.; Olson, S.H.; Gallinger, S.; Li, D.; Petersen, G.M.; Risch, H.A.; Klein, A.P.; Han, J.; Abnet, C.C.; Freedman, N.D.; Taylor, P.R.; Maris, J.M.; Aben, K.K.H.; Kiemeney, L.A.; Vermeulen, S.H.; Wiencke, J.K.; Walsh, K.M.; Wrensch, M.; Rice, T.; Turnbull, C.; Litchfield, K.; Paternoster, L.; Standl, M.; Abecasis, G.R.; SanGiovanni, J.P.; Li, Y.; Mijatovic, V.; Sapkota, Y.; Low, S.K.; Zondervan, K.T.; Montgomery, G.W.; Nyholt, D.R.; Heel, D.A. van; Hunt, K.; Arking, D.E.; Ashar, F.N.; Sotoodehnia, N.; Woo, D.; et al.,

    2017-01-01

    Importance: The causal direction and magnitude of the association between telomere length and incidence of cancer and non-neoplastic diseases is uncertain owing to the susceptibility of observational studies to confounding and reverse causation. Objective: To conduct a Mendelian randomization study,

  12. Statistical guidance for experimental design and data analysis of mutation detection in rare monogenic mendelian diseases by exome sequencing.

    Directory of Open Access Journals (Sweden)

    Degui Zhi

    Full Text Available Recently, whole-genome sequencing, especially exome sequencing, has successfully led to the identification of causal mutations for rare monogenic Mendelian diseases. However, it is unclear whether this approach can be generalized and effectively applied to other Mendelian diseases with high locus heterogeneity. Moreover, the current exome sequencing approach has limitations such as false positive and false negative rates of mutation detection due to sequencing errors and other artifacts, but the impact of these limitations on experimental design has not been systematically analyzed. To address these questions, we present a statistical modeling framework to calculate the power, the probability of identifying truly disease-causing genes, under various inheritance models and experimental conditions, providing guidance for both proper experimental design and data analysis. Based on our model, we found that the exome sequencing approach is well-powered for mutation detection in recessive, but not dominant, Mendelian diseases with high locus heterogeneity. A disease gene responsible for as low as 5% of the disease population can be readily identified by sequencing just 200 unrelated patients. Based on these results, for identifying rare Mendelian disease genes, we propose that a viable approach is to combine, sequence, and analyze patients with the same disease together, leveraging the statistical framework presented in this work.

  13. Mendelian Genetics as a Platform for Teaching about Nature of Science and Scientific Inquiry: The Value of Textbooks

    Science.gov (United States)

    Campanile, Megan F.; Lederman, Norman G.; Kampourakis, Kostas

    2015-01-01

    The purpose of this study was to analyze seven widely used high school biology textbooks in order to assess the nature of science knowledge (NOS) and scientific inquiry (SI) aspects they, explicitly or implicitly, conveyed in the Mendelian genetics sections. Textbook excerpts that directly and/or fully matched our statements about NOS and SI were…

  14. Genetic Determinism in the Genetics Curriculum: An Exploratory Study of the Effects of Mendelian and Weldonian Emphases

    Science.gov (United States)

    Jamieson, Annie; Radick, Gregory

    2017-01-01

    Twenty-first-century biology rejects genetic determinism, yet an exaggerated view of the power of genes in the making of bodies and minds remains a problem. What accounts for such tenacity? This article reports an exploratory study suggesting that the common reliance on Mendelian examples and concepts at the start of teaching in basic genetics is…

  15. Mendelian randomisation analysis provides no evidence for a relationship between adult height and testicular cancer risk.

    Science.gov (United States)

    Levy, M; Hall, D; Sud, A; Law, P; Litchfield, K; Dudakia, D; Haugen, T B; Karlsson, R; Reid, A; Huddart, R A; Grotmol, T; Wiklund, F; Houlston, R S; Turnbull, C

    2017-09-01

    Observational studies have suggested anthropometric traits, particularly increased height are associated with an elevated risk of testicular cancer (testicular germ cell tumour). However, there is an inconsistency between study findings, suggesting the possibility of the influence of confounding factors. To examine the association between anthropometric traits and testicular germ cell tumour using an unbiased approach, we performed a Mendelian randomisation study. We used genotype data from genome wide association studies of testicular germ cell tumour totalling 5518 cases and 19,055 controls. Externally weighted polygenic risk scores were created and used to evaluate associations with testicular germ cell tumour risk per one standard deviation (s.d) increase in genetically-defined adult height, adult BMI, adult waist hip ratio adjusted for BMI (WHRadjBMI), adult hip circumference adjusted for BMI (HIPadjBMI), adult waist circumference adjusted for BMI (WCadjBMI), birth weight (BW) and childhood obesity. Mendelian randomisation analysis did not demonstrate an association between any anthropometric trait and testicular germ cell tumour risk. In particular, despite good power, there was no global evidence for association between height and testicular germ cell tumour. However, three SNPs for adult height individually showed association with testicular germ cell tumour (rs4624820: OR = 1.47, 95% CI: 1.41-1.55, p = 2.7 × 10 -57 ; rs12228415: OR = 1.17, 95% CI: 1.11-1.22, p = 3.1 × 10 -10 ; rs7568069: OR = 1.13, 95% CI: 1.07-1.18, p = 1.1 × 10 -6 ). This Mendelian randomisation analysis, based on the largest testicular germ cell tumour genome wide association dataset to date, does not support a causal etiological association between anthropometric traits and testicular germ cell tumour aetiology. Our findings are more compatible with confounding by shared environmental factors, possibly related to prenatal growth with exposure to these risk factors

  16. Alterations of the Gut Microbiome in Hypertension

    Directory of Open Access Journals (Sweden)

    Qiulong Yan

    2017-08-01

    Full Text Available Introduction: Human gut microbiota is believed to be directly or indirectly involved in cardiovascular diseases and hypertension. However, the identification and functional status of the hypertension-related gut microbe(s have not yet been surveyed in a comprehensive manner.Methods: Here we characterized the gut microbiome in hypertension status by comparing fecal samples of 60 patients with primary hypertension and 60 gender-, age-, and body weight-matched healthy controls based on whole-metagenome shotgun sequencing.Results: Hypertension implicated a remarkable gut dysbiosis with significant reduction in within-sample diversity and shift in microbial composition. Metagenome-wide association study (MGWAS revealed 53,953 microbial genes that differ in distribution between the patients and healthy controls (false discovery rate, 0.05 and can be grouped into 68 clusters representing bacterial species. Opportunistic pathogenic taxa, such as, Klebsiella spp., Streptococcus spp., and Parabacteroides merdae were frequently distributed in hypertensive gut microbiome, whereas the short-chain fatty acid producer, such as, Roseburia spp. and Faecalibacterium prausnitzii, were higher in controls. The number of hypertension-associated species also showed stronger correlation to the severity of disease. Functionally, the hypertensive gut microbiome exhibited higher membrane transport, lipopolysaccharide biosynthesis and steroid degradation, while in controls the metabolism of amino acid, cofactors and vitamins was found to be higher. We further provided the microbial markers for disease discrimination and achieved an area under the receiver operator characteristic curve (AUC of 0.78, demonstrating the potential of gut microbiota in prediction of hypertension.Conclusion: These findings represent specific alterations in microbial diversity, genes, species and functions of the hypertensive gut microbiome. Further studies on the causality relationship between

  17. Systolic hypertension in adult nigerians with hypertension

    International Nuclear Information System (INIS)

    Opadijo, O.G.; Salami, T.A.T.; Sanya, E.O.; Omotoso, A.B.O.

    2007-01-01

    To determine the prevalence of both systolic and diastolic hypertensions in relation to age and their impacts on target organ among adult Nigerians with hypertension. Newly diagnosed adult hypertensives, with blood pressure 140/90mm Hg, taken twice with mercury column sphygmomanometer at 3 weeks interval, were studied. The total number of hypertensive patients treated over this period was also taken into consideration. The newly diagnosed hypertensives were classified using JNC VI classification. The frequency of occurrence of target organ damage such as Left Ventricular Hypertrophy (LVH), heart failure, renal impairment etc. was charted according to systolic and or diastolic pressures. The occurrence of systolic or diastolic blood pressure was also related with the age of the patients. Blood metabolic parameters were compared in both systolic and diastolic blood pressures for their possible contributory role. Two thousand seven hundred and ninety-two adult hypertensive patients were managed over the study period. Of them, 218 (7.8%) were newly diagnosed and studied. There were 94 males and 124 females. Seventy-seven (35.3%) were aged 60 years and above with equal frequency in the gender. One hundred and seventy-eight (81.7%) cases had combined systolic and diastolic pressures. Twenty-nine (13.3%) patients had systolic hypertension. Twenty-five (86.2%) of these 29 were aged 50 years and above and 20 (69.0%) were aged 60 years and above. Eleven (5.0%) patients had isolated diastolic hypertension and they were all in the age bracket 40-49 years. Systolic blood pressure was found to be rising with advancing age while diastolic blood pressure peaked at mid 40's and declined. Target organ damage occurred more frequently with systolic hypertension and advancing age than with diastolic hypertension. Systolic hypertension occurred more frequently in this series of adult Nigerians with hypertension. It was higher with advancing age and associated with more target organ

  18. Rules for resolving Mendelian inconsistencies in nuclear pedigrees typed for two-allele markers.

    Directory of Open Access Journals (Sweden)

    Sajjad Ahmad Khan

    Full Text Available Gene-mapping studies, regularly, rely on examination for Mendelian transmission of marker alleles in a pedigree as a way of screening for genotyping errors and mutations. For analysis of family data sets, it is, usually, necessary to resolve or remove the genotyping errors prior to consideration. At the Center of Inherited Disease Research (CIDR, to deal with their large-scale data flow, they formalized their data cleaning approach in a set of rules based on PedCheck output. We scrutinize via carefully designed simulations that how well CIDR's data cleaning rules work in practice. We found that genotype errors in siblings are detected more often than in parents for less polymorphic SNPs and vice versa for more polymorphic SNPs. Through computer simulations, we conclude that some of the CIDR's rules work poorly in some circumstances, and we suggest a set of modified data cleaning rules that may work better than CIDR's rules.

  19. Mendel Lives: The Survival of Mendelian Genetics in the Lysenkoist Classroom, 1937-1964

    Science.gov (United States)

    Peacock, Margaret

    2015-01-01

    The demise of Soviet genetics in the 1930s, 40s, and 50s has stood for many as a prime example of the damage that social and political dogmatism can do when allowed to meddle in the workings of science. In particular, the story of Trofim Lysenko's rise to preeminence and the fall of Mendelian genetics in the Soviet Union has become a lasting testament to the dangers of state power and a seemingly blatant manifestation of totalitarianism in practice. In recent years, historians have begun to complicate this story. The purpose of this article is to examine the extent to which this conventional account of state power in Soviet biology, symbolized by the disappearance of Mendel, still holds true. Using middle school textbooks, encyclopedias, and pedagogical journals that were published between 1934 and 1964 this article argues that despite its efforts, the state apparatus was functionally incapable of eradicating genetics from its schools.

  20. Nuclear IL-33 regulates soluble ST2 receptor and IL-6 expression in primary human arterial endothelial cells and is decreased in idiopathic pulmonary arterial hypertension

    Energy Technology Data Exchange (ETDEWEB)

    Shao, Dongmin [Section of Vascular Biology, National Heart and Lung Institute, Imperial College London, London (United Kingdom); Perros, Frédéric [Faculté de Médecine, Université Paris-Sud, Paris, Clamart (France); Caramori, Gaetano [Dipartimento di Scienze Mediche, Sezione di Medicina Interna e Cardiorespiratoria, Centro Interdipartimentale per lo Studio delle Malattie Infiammatorie delle Vie Aeree e Patologie Fumo-Correlate, University of Ferrara, Ferrara (Italy); Meng, Chao [Section of Vascular Biology, National Heart and Lung Institute, Imperial College London, London (United Kingdom); Department of Geriatrics, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai (China); Dormuller, Peter [Faculté de Médecine, Université Paris-Sud, Paris, Clamart (France); Chou, Pai-Chien [Airways Disease, National Heart and Lung Institute (United Kingdom); Church, Colin [Scottish Pulmonary Vascular Unit, University of Glasgow (United Kingdom); Papi, Alberto; Casolari, Paolo [Dipartimento di Scienze Mediche, Sezione di Medicina Interna e Cardiorespiratoria, Centro Interdipartimentale per lo Studio delle Malattie Infiammatorie delle Vie Aeree e Patologie Fumo-Correlate, University of Ferrara, Ferrara (Italy); Welsh, David; Peacock, Andrew [Scottish Pulmonary Vascular Unit, University of Glasgow (United Kingdom); Humbert, Marc [Faculté de Médecine, Université Paris-Sud, Paris, Clamart (France); Adcock, Ian M. [Airways Disease, National Heart and Lung Institute (United Kingdom); Wort, Stephen J., E-mail: s.wort@imperial.ac.uk [Section of Vascular Biology, National Heart and Lung Institute, Imperial College London, London (United Kingdom)

    2014-08-15

    Highlights: • Nuclear IL-33 expression is reduced in vascular endothelial cells from PAH patients. • Knockdown of IL-33 leads to increased IL-6 and sST2 mRNA expression. • IL-33 binds homeobox motifs in target gene promoters and recruits repressor proteins. - Abstract: Idiopathic pulmonary arterial hypertension (IPAH) is an incurable condition leading to right ventricular failure and death and inflammation is postulated to be associated with vascular remodelling. Interleukin (IL)-33, a member of the “alarmin” family can either act on the membrane ST2 receptor or as a nuclear repressor, to regulate inflammation. We show, using immunohistochemistry, that IL-33 expression is nuclear in the vessels of healthy subjects whereas nuclear IL-33 is markedly diminished in the vessels of IPAH patients. This correlates with reduced IL-33 mRNA expression in their lung. In contrast, serum levels of IL-33 are unchanged in IPAH. However, the expression of the soluble form of ST2, sST2, is enhanced in the serum of IPAH patients. Knock-down of IL-33 in human endothelial cells (ECs) using siRNA is associated with selective modulation of inflammatory genes involved in vascular remodelling including IL-6. Additionally, IL-33 knock-down significantly increased sST2 release from ECs. Chromatin immunoprecipitation demonstrated that IL-33 bound multiple putative homeodomain protein binding motifs in the proximal and distal promoters of ST2 genes. IL-33 formed a complex with the histone methyltransferase SUV39H1, a transcriptional repressor. In conclusion, IL-33 regulates the expression of IL-6 and sST2, an endogenous IL-33 inhibitor, in primary human ECs and may play an important role in the pathogenesis of PAH through recruitment of transcriptional repressor proteins.

  1. Haplotype-based case-control study on human apurinic/apyrimidinic endonuclease 1/redox effector factor-1 gene and essential hypertension.

    Science.gov (United States)

    Naganuma, Takahiro; Nakayama, Tomohiro; Sato, Naoyuki; Fu, Zhenyan; Soma, Masayoshi; Yamaguchi, Mai; Shimodaira, Masanori; Aoi, Noriko; Usami, Ron

    2010-02-01

    Oxidative DNA damage is involved in the pathophysiology of essential hypertension (EH), which is a multifactorial disorder. Apurinic/apyrimidinic endonuclease 1/redox effector factor-1 (APE1/REF-1) is an essential endonuclease in the base excision repair pathway of oxidatively damaged DNA, in addition to having reducing properties that promote the binding of redox-sensitive transcription factors. Blood pressure in APE1/REF-1-knockout mice is reported to be significantly higher than in wild-type mice. The aim of this study was to investigate the relationship between EH and the human APE1/REF-1 gene through a haplotype-based case-control study using single-nucleotide polymorphisms (SNPs). We selected five SNPs in the human APE1/REF-1 gene (rs1760944, rs3136814, rs17111967, rs3136817, and rs1130409), and performed case-control studies in 265 EH patients and 266 age-matched normotensive (NT) subjects. rs17111967 was found to show nonheterogeneity among Japanese subjects. There were no significant differences in the overall distribution of genotypes or alleles for each SNP between EH and NT groups. In the overall distribution of the haplotype-based case-control study constructed based on rs1760944, rs3136817, and rs1130409, the frequency of the G-T-T haplotype was significantly higher in the EH group than in the NT group (2.1% vs. 0.0%, P = 0.001). Multiple logistic regression analysis also revealed significant differences for the G-T-T haplotype, even after adjustment for confounding factors (OR = 8.600, 95% CI: 1.073-68.951, P = 0.043). Based on the present results, the G-T-T haplotype appears to be a genetic marker of EH, and the APE1/REF-1 gene appears to be a susceptibility gene for EH.

  2. Using published data in Mendelian randomization: a blueprint for efficient identification of causal risk factors.

    Science.gov (United States)

    Burgess, Stephen; Scott, Robert A; Timpson, Nicholas J; Davey Smith, George; Thompson, Simon G

    2015-07-01

    Finding individual-level data for adequately-powered Mendelian randomization analyses may be problematic. As publicly-available summarized data on genetic associations with disease outcomes from large consortia are becoming more abundant, use of published data is an attractive analysis strategy for obtaining precise estimates of the causal effects of risk factors on outcomes. We detail the necessary steps for conducting Mendelian randomization investigations using published data, and present novel statistical methods for combining data on the associations of multiple (correlated or uncorrelated) genetic variants with the risk factor and outcome into a single causal effect estimate. A two-sample analysis strategy may be employed, in which evidence on the gene-risk factor and gene-outcome associations are taken from different data sources. These approaches allow the efficient identification of risk factors that are suitable targets for clinical intervention from published data, although the ability to assess the assumptions necessary for causal inference is diminished. Methods and guidance are illustrated using the example of the causal effect of serum calcium levels on fasting glucose concentrations. The estimated causal effect of a 1 standard deviation (0.13 mmol/L) increase in calcium levels on fasting glucose (mM) using a single lead variant from the CASR gene region is 0.044 (95 % credible interval -0.002, 0.100). In contrast, using our method to account for the correlation between variants, the corresponding estimate using 17 genetic variants is 0.022 (95 % credible interval 0.009, 0.035), a more clearly positive causal effect.

  3. Hypertensive retinopathy (image)

    Science.gov (United States)

    ... retina from high blood pressure is called hypertensive retinopathy. It occurs as the existing high blood pressure ... flame hemorrhages and cotton wool spots. As hypertensive retinopathy progresses, hard exudates can appear around the macula ...

  4. Hypertensive heart disease

    Science.gov (United States)

    ... page: //medlineplus.gov/ency/article/000163.htm Hypertensive heart disease To use the sharing features on this page, please enable JavaScript. Hypertensive heart disease refers to heart problems that occur because of ...

  5. Chronic Hypertension in Pregnancy

    Science.gov (United States)

    ... org/ by guest on June 19, 2018 Chronic Hypertension in Pregnancy Ellen W. Seely, MD; Cynthia Maxwell, ... M any women have been diag- nosed with hypertension (blood pressure Ͼ 140/ 90 mm Hg) when ...

  6. Maskeret hypertension i graviditeten

    DEFF Research Database (Denmark)

    Fischer, Margit Bistrup; Thingaard, Ebbe; Andersen, Anita Sylvest

    2018-01-01

    Hypertension during pregnancy is one of the leading causes of maternal and foetal morbidity and mortality. Monitoring of blood pressure is therefore an essential part of prenatal care. Masked hypertension, where blood pressure levels are elevated at home despite normal blood pressure levels...... monitored in a clinical setting, may lead to cardiovascular and obstetric complications equal to those of sustained hypertension. This article discusses masked hypertension and the need for further investigation of blood pressure monitoring during pregnancy....

  7. Maskeret hypertension i graviditeten

    DEFF Research Database (Denmark)

    Fischer, Margit Bistrup; Thingaard, Ebbe; Andersen, Anita Sylvest

    2018-01-01

    Hypertension during pregnancy is one of the leading causes of maternal and foetal morbidity and mortality. Monitoring of blood pressure is therefore an essential part of prenatal care. Masked hypertension, where blood pressure levels are elevated at home despite normal blood pressure levels monit...... monitored in a clinical setting, may lead to cardiovascular and obstetric complications equal to those of sustained hypertension. This article discusses masked hypertension and the need for further investigation of blood pressure monitoring during pregnancy....

  8. Associations of the MCM6-rs3754686 proxy for milk intake in Mediterranean and American populations with cardiovascular biomarkers, disease and mortality: Mendelian randomization

    Science.gov (United States)

    Controversy persists on the association between dairy products, especially milk, and cardiovascular diseases (CVD). Genetic proxies may improve dairy intake estimations, and clarify diet- disease relationships through Mendelian randomization. We meta- analytically (n

  9. Association between Adult Height and Risk of Colorectal, Lung, and Prostate Cancer : Results from Meta-analyses of Prospective Studies and Mendelian Randomization Analyses

    NARCIS (Netherlands)

    Khankari, Nikhil K.; Shu, Xiao Ou; Wen, Wanqing; Kraft, Peter; Lindström, Sara; Peters, Ulrike; Schildkraut, Joellen; Schumacher, Fredrick; Bofetta, Paolo; Risch, Angela; Bickeböller, Heike; Amos, Christopher I.; Easton, Douglas; Eeles, Rosalind A.; Gruber, Stephen B.; Haiman, Christopher A.; Hunter, David J.; Chanock, Stephen J.; Pierce, Brandon L.; Zheng, Wei; Blalock, Kendra; Campbell, Peter T.; Casey, Graham; Conti, David V.; Edlund, Christopher K.; Figueiredo, Jane; James Gauderman, W.; Gong, Jian; Green, Roger C.; Harju, John F.; Harrison, Tabitha A.; Jacobs, Eric J.; Jenkins, Mark A.; Jiao, Shuo; Li, Li; Lin, Yi; Manion, Frank J.; Moreno, Victor; Mukherjee, Bhramar; Raskin, Leon; Schumacher, Fredrick R.; Seminara, Daniela; Severi, Gianluca; Stenzel, Stephanie L.; Thomas, Duncan C.; Hopper, John L.; Southey, Melissa C.; Makalic, Enes; Schmidt, Daniel F.; Fletcher, Olivia; Peto, Julian; Gibson, Lorna; dos Santos Silva, Isabel; Ahsan, Habib; Whittemore, Alice; Waisfisz, Quinten; Meijers-Heijboer, Hanne; Adank, Muriel; van der Luijt, Rob B.; Uitterlinden, Andre G.; Hofman, Albert; Meindl, Alfons; Schmutzler, Rita K.; Müller-Myhsok, Bertram; Lichtner, Peter; Nevanlinna, Heli; Muranen, Taru A.; Aittomäki, Kristiina; Blomqvist, Carl; Chang-Claude, Jenny; Hein, Rebecca; Dahmen, Norbert; Beckman, Lars; Crisponi, Laura; Hall, Per; Czene, Kamila; Irwanto, Astrid; Liu, Jianjun; Easton, Douglas F.; Turnbull, Clare; Rahman, Nazneen; Eeles, Rosalind; Kote-Jarai, Zsofia; Muir, Kenneth; Giles, Graham; Neal, David; Donovan, Jenny L.; Hamdy, Freddie C.; Wiklund, Fredrik; Gronberg, Henrik; Haiman, Christopher; Schumacher, Fred; Travis, Ruth; Riboli, Elio; Hunter, David; Gapstur, Susan; Berndt, Sonja; Chanock, Stephen; Han, Younghun; Su, Li; Wei, Yongyue; Hung, Rayjean J.; Brhane, Yonathan; McLaughlin, John; Brennan, Paul; McKay, James D.; Rosenberger, Albert; Houlston, Richard S.; Caporaso, Neil; Teresa Landi, Maria; Heinrich, Joachim; Wu, Xifeng; Ye, Yuanqing; Christiani, David C.

    2016-01-01

    Background: Observational studies examining associations between adult height and risk of colorectal, prostate, and lung cancers have generated mixed results. We conducted meta-analyses using data from prospective cohort studies and further carried out Mendelian randomization analyses, using

  10. Refeeding hypertension in dietary obesity

    International Nuclear Information System (INIS)

    Ernsberger, P.; Nelson, D.O.

    1988-01-01

    A novel model of nutritionally induced hypertension in the rat is described. Dietary obesity was produced by providing sweet milk in addition to regular chow, which elicited a 52% increase in caloric intake. Despite 54% greater body weight gain and 139% heavier retroperitoneal fat pads, 120 days of overfeeding failed to increase systolic pressure in the conscious state or mean arterial pressure under urethan anesthesia. In contrast, mild hypertension developed in intermittantly fasted obese animals. The first 4-day supplemented fast was initiated 4 wk after the introduction of sweet milk, when the animals were 47 g overweight relative to chow-fed controls. Thereafter, 4 days of starvation were alternated with 2 wk of refeeding for a total of 4 cycles. A rapid fall in systolic blood pressure accompanied the onset of supplemented fasting and was maintained thereafter. With refeeding, blood pressure rose precipitously, despite poststarvation anorexia. Blood pressure tended to rise slightly over the remainder of the realimentation period. After the 4th supplemented fast, hypertension was sustained during 30 days of refeeding. Cumulative caloric intake in starved-refed rats fell within 2% of that in chow-fed controls. Refeeding hypertension appeared to be due to increased sympathetic nervous activity, since (1) cardiac β-adrenergic receptors were downregulated, as indicated by a 40% decrease in the maximum binding of [ 3 H]dihydroalpranolol; and (2) the decrease in heart rate as a result of β-blockade was enhanced. Refeeding hypertension in the dietary obese rat may be a potential animal model for some forms of human obesity-related hypertension

  11. Hypertension after kidney transplantation

    NARCIS (Netherlands)

    Dobrowolski, L.C.

    2016-01-01

    Hypertension increases the cardiovascular risk in kidney transplant recipients (KTRs). In chapter 2 we found that hypertension was highly prevalent in adult (77.2%), paediatric (62.7%) and young adult (86.4%) KTRs. Transition from the paediatric to adult care did not affect hypertension and there

  12. Hypertension in pregnancy

    Directory of Open Access Journals (Sweden)

    Andrea Ungar

    2007-03-01

    Full Text Available Hypertension is the most common medical problem encountered during pregnancy, complicating 2-3% of pregnancies. Hypertensive disorders during pregnancy are classified into 4 categories: chronic hypertension, pre-eclampsia/eclampsia, pre-eclampsia superimposed on chronic hypertension, and gestational hypertension. A relative paucity of investigative data, as well as the frequent difficulty in making an etiological diagnosis, may lead to problems in its management. This case report analyses current concepts regarding the hypertensive disorders of gestation, focusing on chronic hypertension. Chronic hypertension is defined as blood pressure exceeding 140/90 mmHg before pregnancy or before 20 weeks gestation. Hypertensive disorders in pregnancy may cause maternal and fetal morbidity and remain a leading source of maternal mortality. A prompt diagnosis is needed also because hypertension may be an indicator of pre-eclampsia, a condition which can evolve into serious complications. Maintaining blood pressure below 140/90 mmHg is recommended, although treatment should be determined on an individual basis. Many anti-hypertensive agents appear to be safe for use during pregnancy: methildopa has been the most studied of the anti-hypertensive drugs and has the best safety record. Labetalol, idralazine and nifedipine also have been found to be safe; ACE-inhibitors are absolutely contraindicated, because they are associated with intrauterine growth retardation.

  13. Genetik og hypertension

    DEFF Research Database (Denmark)

    Ellervik, Christina; Tarnow, Lisa; Pedersen, Erling Bjerregaard

    2009-01-01

    Monogenic forms of hypertension are very rare, but have a well-characterized heredity. Primary hypertension is very common with a complex and polygenic heredity. Primary hypertension arises due to an interaction between multiple genetic and environmental factors. Its heredity is unknown, although...

  14. Associations between Potentially Modifiable Risk Factors and Alzheimer Disease : A Mendelian Randomization Study

    NARCIS (Netherlands)

    Ostergaard, Soren D.; Mukherjee, Shubhabrata; Sharp, Stephen J.; Proitsi, Petroula; Lotta, Luca A.; Day, Felix; Perry, John R. B.; Boehme, Kevin L.; Walter, Stefan; Kauwe, John S.; Gibbons, Laura E.; Larson, Eric B.; Powell, John F.; Langenberg, Claudia; Crane, Paul K.; Wareham, Nicholas J.; Scott, Robert A.; van der Schouw, YT

    Background Potentially modifiable risk factors including obesity, diabetes, hypertension, and smoking are associated with Alzheimer disease (AD) and represent promising targets for intervention. However, the causality of these associations is unclear. We sought to assess the causal nature of these

  15. Genetic Determinism in the Genetics Curriculum. An Exploratory Study of the Effects of Mendelian and Weldonian Emphases

    Science.gov (United States)

    Jamieson, Annie; Radick, Gregory

    2017-12-01

    Twenty-first-century biology rejects genetic determinism, yet an exaggerated view of the power of genes in the making of bodies and minds remains a problem. What accounts for such tenacity? This article reports an exploratory study suggesting that the common reliance on Mendelian examples and concepts at the start of teaching in basic genetics is an eliminable source of support for determinism. Undergraduate students who attended a standard `Mendelian approach' university course in introductory genetics on average showed no change in their determinist views about genes. By contrast, students who attended an alternative course which, inspired by the work of a critic of early Mendelism, W. F. R. Weldon (1860-1906), replaced an emphasis on Mendel's peas with an emphasis on developmental contexts and their role in bringing about phenotypic variability, were less determinist about genes by the end of teaching. Improvements in both the new Weldonian curriculum and the study design are in view for the future.

  16. The Application of Restriction Landmark Genome Scanning Method for Surveillance of Non-Mendelian Inheritance in F1 Hybrids

    Directory of Open Access Journals (Sweden)

    Tomoko Takamiya

    2009-01-01

    Full Text Available We analyzed inheritance of DNA methylation in reciprocal F1 hybrids (subsp. japonica cv. Nipponbare × subsp. indica cv. Kasalath of rice (Oryza sativa L. using restriction landmark genome scanning (RLGS, and detected differing RLGS spots between the parents and reciprocal F1 hybrids. MspI/HpaII restriction sites in the DNA from these different spots were suspected to be heterozygously methylated in the Nipponbare parent. These spots segregated in F1 plants, but did not segregate in selfed progeny of Nipponbare, showing non-Mendelian inheritance of the methylation status. As a result of RT-PCR and sequencing, a specific allele of the gene nearest to the methylated sites was expressed in reciprocal F1 plants, showing evidence of biased allelic expression. These results show the applicability of RLGS for scanning of non-Mendelian inheritance of DNA methylation and biased allelic expression.

  17. Association of cardiovascular complications with circulating levels of tribbles 3 human homolog and matrix metalloproteinases in Indian type 2 diabetic patients, with or without hypertension

    Directory of Open Access Journals (Sweden)

    Prashant Shirish Ratnaparkhi

    2018-01-01

    Full Text Available Aim and Objective: Matrix metalloproteinases (MMPs and Tribbles 3 (Trb3 human homologue have been reported to induce atherosclerosis. We wanted to evaluate the association of circulating levels of Trb3 human homologue and MMPs (MMP2 and MMP9, with possible cardiovascular complications in Indian type 2 diabetic patients (type 2 diabetes mellitus [T2DM], with or without hypertension (HT. Materials and Methods: Serum from 144 individuals, classified as follows: Group A1= (DM + HT; T2DM> 5 years + HT (n = 55; Group A2 = DM; T2DM <2 years, (n = 28; Group B1 = HT; (n = 31 and Group B2 = HC; (n = 30 age- and sex-matched healthy controls. Anthropometric measurements, biochemical profiles of sugar and lipids were established using auto analyser. MMP2, MMP9, Trb3, oxidised low-density lipoprotein cholesterol, and proinsulin were measured in the serum using ELISA. Results: Using Bonferroni correction, we found that MMP2 levels were increased in (DM + HT, when compared to individuals with DM and HT (P = 0.006 and 0.000. HT group had reduced levels of MMP2, as compared to HC, (P = 0.000. The Mann–Whitney U-test for MMP9 revealed that DM group had elevated levels of MMP9 compared to (DM + HT, HT and HC group, (P = 0.011, 0.000, and 0.001. (DM + HT had elevated levels of MMP9 when compared to HT group, (P = 0.012.. Levels of MMP9 in HT were lower than the HC group, although not significant. Levels of Trb3 were found to be elevated in (DM + HT when compared to DM, (P = 0.032. The levels of Trb3 were higher in the HT, when compared to HC group, although not statistically significant. Multiple linear regression model for Framingham Risk Score, weighted with post prandial blood sugar yielded R2 = 0.338; F = 7.602 (df = 9, P = 0.000. Trb3 (β = −0.179, P = 0.019; MMP2 (β =0.021, P = 0.787 and MMP9 (β = −0.03, P = 0.684. Conclusion: Trb3 is a useful marker for evaluating the association of cardiovascular risk in diabetic patients.

  18. Evaluation of BAG3 levels in healthy subjects, hypertensive patients, and hypertensive diabetic patients.

    Science.gov (United States)

    Derosa, Giuseppe; Maffioli, Pamela; Rosati, Alessandra; M, De Marco; Basile, Anna; D'Angelo, Angela; Romano, Davide; Sahebkar, Amirhossein; Falco, Antonia; Turco, Maria C

    2018-03-01

    BAG3 is a member of human BAG (Bcl-2-associated athanogene) proteins and plays a role in apoptosis, cell adhesion, cytoskeleton remodeling, and autophagy. The aim of this study was to evaluate BAG3 levels in healthy subjects, hypertensive patients, and hypertensive diabetic patients. We enrolled 209 Caucasian adults, of both sex, 18-75 years of age, 77 were healthy controls, 62 were affected by hypertension, and 70 were affected by hypertension and type 2 diabetes. All patients underwent an assessment that included medical history, physical examination, vital signs, a 12-lead electrocardiogram, measurements of systolic (SBP), and diastolic blood pressure (DBP), heart rate (HR), fasting plasma glucose (FPG), glycated hemoglobin (HbA 1c ), triglycerides (TG), transaminases, high sensitivity C-reactive protein (Hs-CRP), and BAG3. We observed higher blood pressure values in hypertensive, and hypertensive diabetic patients compared to controls. As expected, FPG and HbA 1c were higher in diabetic hypertensive patients, compared to the other two groups. No Tg levels differences were recorded among the three groups. Hs-CRP was higher in diabetic hypertensive patients compared to healthy subjects. Finally, BAG3 levels were higher in hypertensives, and hypertensive diabetic patients compared to controls. We observed higher levels of BAG3 in hypertensive patients compared to healthy controls, and even higher levels in hypertensive diabetic patients compared to healthy subjects. This paper could be the first of a long way to identify potential involvement of deregulated BAG3 levels in cardiometabolic diseases. © 2017 Wiley Periodicals, Inc.

  19. Idiopathic portal hypertension

    International Nuclear Information System (INIS)

    Han, Tae Kyun; Ryu, Dae Sik; Kim, Heung Chul; Hur, Hun; Eom, Kyeung Tae; Namkung, Sook; Park, Man Soo; Hwang, Woo Chul; Lee, Kwan Seop

    1996-01-01

    To describe the radiologic findings of idiopathic portal hypertension and to find the points of differentiation between idiopathic portal hypertension and liver cirrhosis. Four portograms in five patients who for four years had suffered from pathologically confirmed idiopathic portal hypertension were retrospectively analyzed and compared with a portogram obtained from a control subject with liver cirrhosis. Portographic finding s of idiopathic portal hypertension were paucity of medium-sized portal branches, irregular and obtuse-angled division of peripheral branches, abrupt interruption and an avascular area beneath the liver margin. A portogram of idiopathic portal hypertension may be useful in differentiation this and liver cirrhosis

  20. SECONDARY (ENDOCRINE HYPERTENSION: LECTURE

    Directory of Open Access Journals (Sweden)

    M. Yu. Yukina

    2016-01-01

    Full Text Available Hypertension is a  very common disease with high morbidity and reduction in quality of life. Endocrine disorders are the most common cause of secondary hypertension affecting ~3% of the population. Primary aldosteronism can be the cause of endocrine hypertension more often than other endocrine disorders. Other less common causes of endocrine hypertension include Cushing syndrome, pheochromocytoma, thyroid disorders, and hyperparathyroidism. Endocrine hypertension is potentially curable if the underlying cause is identified and treated accordingly. Younger age at manifestation of resistance to multiple antihypertensive drugs, together with other clinical signs of an endocrine disorder, should raise the suspicion and prompt the appropriate evaluation.

  1. Liver Enzymes and Risk of Ischemic Heart Disease and Type 2 Diabetes Mellitus: A Mendelian Randomization Study

    OpenAIRE

    Liu, Junxi; Au Yeung, Shiu Lun; Lin, Shi Lin; Leung, Gabriel M.; Schooling, C. Mary

    2016-01-01

    We used Mendelian randomization to estimate the causal effects of the liver enzymes, alanine aminotransferase (ALT), alkaline phosphatase (ALP) and gamma glutamyltransferase (GGT), on diabetes and cardiovascular disease, using genetic variants predicting these liver enzymes at genome wide significance applied to extensively genotyped case-control studies of diabetes (DIAGRAM) and coronary artery disease (CAD)/myocardial infarction (MI) (CARDIoGRAMplusC4D 1000 Genomes). Genetically higher ALT ...

  2. Evaluating the Causal Link Between Malaria Infection and Endemic Burkitt Lymphoma in Northern Uganda: A Mendelian Randomization Study

    OpenAIRE

    Ismail D. Legason; Ruth M. Pfeiffer; Krizia-Ivana Udquim; Andrew W. Bergen; Mateus H. Gouveia; Samuel Kirimunda; Isaac Otim; Eric Karlins; Patrick Kerchan; Hadijah Nabalende; Ariunaa Bayanjargal; Benjamin Emmanuel; Paul Kagwa; Ambrose O. Talisuna; Kishor Bhatia

    2017-01-01

    Background: Plasmodium falciparum (Pf) malaria infection is suspected to cause endemic Burkitt Lymphoma (eBL), but the evidence remains unsettled. An inverse relationship between sickle cell trait (SCT) and eBL, which supports that between malaria and eBL, has been reported before, but in small studies with low power. We investigated this hypothesis in children in a population-based study in northern Uganda using Mendelian Randomization. Methods: Malaria-related polymorphisms (SCT, IL10, I...

  3. Cross-ancestry genome-wide association analysis of corneal thickness strengthens link between complex and Mendelian eye diseases

    OpenAIRE

    Iglesias, Adriana I; Mishra, Aniket; Vitart, Veronique; Bykhovskaya, Yelena; Höhn, René; Springelkamp, Henriët; Cuellar-Partida, Gabriel; Gharahkhani, Puya; Bailey, Jessica N Cooke; Willoughby, Colin E; Li, Xiaohui; Yazar, Seyhan; Nag, Abhishek; Khawaja, Anthony P.; Polasek, Ozren

    2018-01-01

    Central corneal thickness (CCT) is a highly heritable trait associated with complex eye diseases such as keratoconus and glaucoma. We perform a genome-wide association meta-analysis of CCT and identify 19 novel regions. Pathway analyses uncover new, as well as supported the role of connective tissue-related, pathways. Remarkably, >20% of the CCT-loci are near or within Mendelian disorder genes. These included FBN1, ADAMTS2 and TGFB2 which associate with connective tissue disorders (Marfan,...

  4. Effects of BMI, Fat Mass, and Lean Mass on Asthma in Childhood: A Mendelian Randomization Study

    Science.gov (United States)

    Granell, Raquel; Henderson, A. John; Evans, David M.; Smith, George Davey; Ness, Andrew R.; Lewis, Sarah; Palmer, Tom M.; Sterne, Jonathan A. C.

    2014-01-01

    Background Observational studies have reported associations between body mass index (BMI) and asthma, but confounding and reverse causality remain plausible explanations. We aim to investigate evidence for a causal effect of BMI on asthma using a Mendelian randomization approach. Methods and Findings We used Mendelian randomization to investigate causal effects of BMI, fat mass, and lean mass on current asthma at age 7½ y in the Avon Longitudinal Study of Parents and Children (ALSPAC). A weighted allele score based on 32 independent BMI-related single nucleotide polymorphisms (SNPs) was derived from external data, and associations with BMI, fat mass, lean mass, and asthma were estimated. We derived instrumental variable (IV) estimates of causal risk ratios (RRs). 4,835 children had available data on BMI-associated SNPs, asthma, and BMI. The weighted allele score was strongly associated with BMI, fat mass, and lean mass (all p-valuesBMI on asthma was 1.55 (95% CI 1.16–2.07) per kg/m2, p = 0.003. This effect appeared stronger for non-atopic (1.90, 95% CI 1.19–3.03) than for atopic asthma (1.37, 95% CI 0.89–2.11) though there was little evidence of heterogeneity (p = 0.31). The estimated causal RRs for the effects of fat mass and lean mass on asthma were 1.41 (95% CI 1.11–1.79) per 0.5 kg and 2.25 (95% CI 1.23–4.11) per kg, respectively. The possibility of genetic pleiotropy could not be discounted completely; however, additional IV analyses using FTO variant rs1558902 and the other BMI-related SNPs separately provided similar causal effects with wider confidence intervals. Loss of follow-up was unlikely to bias the estimated effects. Conclusions Higher BMI increases the risk of asthma in mid-childhood. Higher BMI may have contributed to the increase in asthma risk toward the end of the 20th century. Please see later in the article for the Editors' Summary PMID:24983943

  5. Height, body mass index, and socioeconomic status: mendelian randomisation study in UK Biobank.

    Science.gov (United States)

    Tyrrell, Jessica; Jones, Samuel E; Beaumont, Robin; Astley, Christina M; Lovell, Rebecca; Yaghootkar, Hanieh; Tuke, Marcus; Ruth, Katherine S; Freathy, Rachel M; Hirschhorn, Joel N; Wood, Andrew R; Murray, Anna; Weedon, Michael N; Frayling, Timothy M

    2016-03-08

    To determine whether height and body mass index (BMI) have a causal role in five measures of socioeconomic status. Mendelian randomisation study to test for causal effects of differences in stature and BMI on five measures of socioeconomic status. Mendelian randomisation exploits the fact that genotypes are randomly assigned at conception and thus not confounded by non-genetic factors. UK Biobank. 119,669 men and women of British ancestry, aged between 37 and 73 years. Age completed full time education, degree level education, job class, annual household income, and Townsend deprivation index. In the UK Biobank study, shorter stature and higher BMI were observationally associated with several measures of lower socioeconomic status. The associations between shorter stature and lower socioeconomic status tended to be stronger in men, and the associations between higher BMI and lower socioeconomic status tended to be stronger in women. For example, a 1 standard deviation (SD) higher BMI was associated with a £210 (€276; $300; 95% confidence interval £84 to £420; P=6 × 10(-3)) lower annual household income in men and a £1890 (£1680 to £2100; P=6 × 10(-15)) lower annual household income in women. Genetic analysis provided evidence that these associations were partly causal. A genetically determined 1 SD (6.3 cm) taller stature caused a 0.06 (0.02 to 0.09) year older age of completing full time education (P=0.01), a 1.12 (1.07 to 1.18) times higher odds of working in a skilled profession (P=6 × 10(-7)), and a £1130 (£680 to £1580) higher annual household income (P=4 × 10(-8)). Associations were stronger in men. A genetically determined 1 SD higher BMI (4.6 kg/m(2)) caused a £2940 (£1680 to £4200; P=1 × 10(-5)) lower annual household income and a 0.10 (0.04 to 0.16) SD (P=0.001) higher level of deprivation in women only. These data support evidence that height and BMI play an important partial role in determining several aspects of a person

  6. Height, body mass index, and socioeconomic status: mendelian randomisation study in UK Biobank

    Science.gov (United States)

    Tyrrell, Jessica; Jones, Samuel E; Beaumont, Robin; Astley, Christina M; Lovell, Rebecca; Yaghootkar, Hanieh; Tuke, Marcus; Ruth, Katherine S; Freathy, Rachel M; Hirschhorn, Joel N; Wood, Andrew R; Murray, Anna; Weedon, Michael N

    2016-01-01

    Objective To determine whether height and body mass index (BMI) have a causal role in five measures of socioeconomic status. Design Mendelian randomisation study to test for causal effects of differences in stature and BMI on five measures of socioeconomic status. Mendelian randomisation exploits the fact that genotypes are randomly assigned at conception and thus not confounded by non-genetic factors. Setting UK Biobank. Participants 119 669 men and women of British ancestry, aged between 37 and 73 years. Main outcome measures Age completed full time education, degree level education, job class, annual household income, and Townsend deprivation index. Results In the UK Biobank study, shorter stature and higher BMI were observationally associated with several measures of lower socioeconomic status. The associations between shorter stature and lower socioeconomic status tended to be stronger in men, and the associations between higher BMI and lower socioeconomic status tended to be stronger in women. For example, a 1 standard deviation (SD) higher BMI was associated with a £210 (€276; $300; 95% confidence interval £84 to £420; P=6×10−3) lower annual household income in men and a £1890 (£1680 to £2100; P=6×10−15) lower annual household income in women. Genetic analysis provided evidence that these associations were partly causal. A genetically determined 1 SD (6.3 cm) taller stature caused a 0.06 (0.02 to 0.09) year older age of completing full time education (P=0.01), a 1.12 (1.07 to 1.18) times higher odds of working in a skilled profession (P=6×10−7), and a £1130 (£680 to £1580) higher annual household income (P=4×10−8). Associations were stronger in men. A genetically determined 1 SD higher BMI (4.6 kg/m2) caused a £2940 (£1680 to £4200; P=1×10−5) lower annual household income and a 0.10 (0.04 to 0.16) SD (P=0.001) higher level of deprivation in women only. Conclusions These data support evidence that height and BMI play an

  7. DETECTION OF MENDELIAN AND GENOTYPE FREQUENCY OF GROWTH HORMONE GENE IN ONGOLE CROSSBRED CATTLE MATED BY THE ARTIFICIAL INSEMINATION TECHNIQUE

    Directory of Open Access Journals (Sweden)

    U. Paputungan

    2012-06-01

    Full Text Available The objectives of this study were to detect the Mendelian mode inheritance of growth hormone (GH and to establish genotype frequency of GH gene in Ongole-crossbred cattle mated by the artificial insemination (AI technique. Total of 76 blood samples were collected from Ongole-crossbred cows and bulls (G0, and their progenies (G1 at the Tumaratas AI service center in North Sulawesi province, Indonesia. All blood samples were screened for the presence of GH locus using a PCR-RFLP method involving restricted enzyme Msp1 on 1.2 % of agarose gel. Data were analyzed using statistical program function in Excel XP. The results showed that GH locus using alleles of Msp1+ and Msp1- enzyme restriction in Ongole-crossbred cows and bulls was inherited to their Ongole-crossbred progenies following the Mendelian mode inheritance. This Mendelian inheritance generated by AI technique was not under genetic equilibrium for the Msp1 genotype frequencies in groups of G0 and G1. The breeding program using genotypes of bulls and cows (G0 for generating the genotype of GH Msp1 enzyme restriction by AI technique should be maintained to increase these various allele dispersion rates for breeding under genetic equilibrium of the Ongole-crossbred cattle population.

  8. Resistance to a bacterial parasite in the crustacean Daphnia magna shows Mendelian segregation with dominance.

    Science.gov (United States)

    Luijckx, P; Fienberg, H; Duneau, D; Ebert, D

    2012-05-01

    The influence of host and parasite genetic background on infection outcome is a topic of great interest because of its pertinence to theoretical issues in evolutionary biology. In the present study, we use a classical genetics approach to examine the mode of inheritance of infection outcome in the crustacean Daphnia magna when exposed to the bacterial parasite Pasteuria ramosa. In contrast to previous studies in this system, we use a clone of P. ramosa, not field isolates, which allows for a more definitive interpretation of results. We test parental, F1, F2, backcross and selfed parental clones (total 284 genotypes) for susceptibility against a clone of P. ramosa using two different methods, infection trials and the recently developed attachment test. We find that D. magna clones reliably exhibit either complete resistance or complete susceptibility to P. ramosa clone C1 and that resistance is dominant, and inherited in a pattern consistent with Mendelian segregation of a single-locus with two alleles. The finding of a single host locus controlling susceptibility to P. ramosa suggests that the previously observed genotype-genotype interactions in this system have a simple genetic basis. This has important implications for the outcome of host-parasite co-evolution. Our results add to the growing body of evidence that resistance to parasites in invertebrates is mostly coded by one or few loci with dominance.

  9. Best (but oft-forgotten) practices: the design, analysis, and interpretation of Mendelian randomization studies1

    Science.gov (United States)

    Bowden, Jack; Relton, Caroline; Davey Smith, George

    2016-01-01

    Mendelian randomization (MR) is an increasingly important tool for appraising causality in observational epidemiology. The technique exploits the principle that genotypes are not generally susceptible to reverse causation bias and confounding, reflecting their fixed nature and Mendel’s first and second laws of inheritance. The approach is, however, subject to important limitations and assumptions that, if unaddressed or compounded by poor study design, can lead to erroneous conclusions. Nevertheless, the advent of 2-sample approaches (in which exposure and outcome are measured in separate samples) and the increasing availability of open-access data from large consortia of genome-wide association studies and population biobanks mean that the approach is likely to become routine practice in evidence synthesis and causal inference research. In this article we provide an overview of the design, analysis, and interpretation of MR studies, with a special emphasis on assumptions and limitations. We also consider different analytic strategies for strengthening causal inference. Although impossible to prove causality with any single approach, MR is a highly cost-effective strategy for prioritizing intervention targets for disease prevention and for strengthening the evidence base for public health policy. PMID:26961927

  10. Testing concordance of instrumental variable effects in generalized linear models with application to Mendelian randomization

    Science.gov (United States)

    Dai, James Y.; Chan, Kwun Chuen Gary; Hsu, Li

    2014-01-01

    Instrumental variable regression is one way to overcome unmeasured confounding and estimate causal effect in observational studies. Built on structural mean models, there has been considerale work recently developed for consistent estimation of causal relative risk and causal odds ratio. Such models can sometimes suffer from identification issues for weak instruments. This hampered the applicability of Mendelian randomization analysis in genetic epidemiology. When there are multiple genetic variants available as instrumental variables, and causal effect is defined in a generalized linear model in the presence of unmeasured confounders, we propose to test concordance between instrumental variable effects on the intermediate exposure and instrumental variable effects on the disease outcome, as a means to test the causal effect. We show that a class of generalized least squares estimators provide valid and consistent tests of causality. For causal effect of a continuous exposure on a dichotomous outcome in logistic models, the proposed estimators are shown to be asymptotically conservative. When the disease outcome is rare, such estimators are consistent due to the log-linear approximation of the logistic function. Optimality of such estimators relative to the well-known two-stage least squares estimator and the double-logistic structural mean model is further discussed. PMID:24863158

  11. Genetic association of telomere length with hepatocellular carcinoma risk: A Mendelian randomization analysis.

    Science.gov (United States)

    Cheng, Yue; Yu, Chengxiao; Huang, Mingtao; Du, Fangzhi; Song, Ci; Ma, Zijian; Zhai, Xiangjun; Yang, Yuan; Liu, Jibin; Bei, Jin-Xin; Jia, Weihua; Jin, Guangfu; Li, Shengping; Zhou, Weiping; Liu, Jianjun; Dai, Juncheng; Hu, Zhibin

    2017-10-01

    Observational studies show an association between telomere length and Hepatocellular carcinoma (HCC) risk, but the relationship is controversial. Particularly, it remains unclear whether the association is due to confounding or biases inherent in conventional epidemiological studies. Here, we applied Mendelian randomization approach to evaluate whether telomere length is causally associated with HCC risk. Individual-level data were from HBV-related HCC Genome-wide association studies (1,538 HBV positive HCC patients and 1,465 HBV positive controls). Genetic risk score, as proxy for actual measured telomere length, derived from nine telomere length-associated genetic variants was used to evaluate the effect of telomere length on HCC risk. We observed a significant risk signal between genetically increased telomere length and HBV-related HCC risk (OR=2.09, 95% CI 1.32-3.31, P=0.002). Furthermore, a U-shaped curve was fitted by the restricted cubic spline curve, which indicated that either short or long telomere length would increase HCC risk (P=0.0022 for non-linearity test). Subgroup analysis did not reveal significant heterogeneity between different age, gender, smoking status and drinking status groups. Our results indicated that a genetic background that favors longer or shorter telomere length may increase HBV-related HCC risk-a U-shaped association. Copyright © 2017 Elsevier Ltd. All rights reserved.

  12. Investigating the causal effect of vitamin D on serum adiponectin using a mendelian randomization approach

    DEFF Research Database (Denmark)

    Husemoen, L. L. N.; Skaaby, T.; Martinussen, Torben

    2014-01-01

    Background/Objectives: The aim was to examine the causal effect of vitamin D on serum adiponectin using a multiple instrument Mendelian randomization approach. Subjects/Methods: Serum 25-hydroxy vitamin D (25(OH)D) and serum total or high molecular weight (HMW) adiponectin were measured in two...... doubling of 25(OH)D was 4.78, 95% CI: 1.96, 7.68, Pvitamin D-binding protein gene and the filaggrin gene as instrumental variables, the causal effect in % was estimated to 61.46, 95% CI: 17.51, 120.28, P=0.003 higher adiponectin per doubling of 25(OH)D. In the MONICA10...... effect estimate in % per doubling of 25(OH)D was 37.13, 95% CI:-3.67, 95.20, P=0.080). Conclusions: The results indicate a possible causal association between serum 25(OH)D and total adiponectin. However, the association was not replicated for HMW adiponectin. Thus, further studies are needed to confirm...

  13. Apolipoprotein e genotype, plasma cholesterol, and cancer: a Mendelian randomization study.

    LENUS (Irish Health Repository)

    Trompet, Stella

    2009-12-01

    Observational studies have shown an association between low plasma cholesterol levels and increased risk of cancer, whereas most randomized clinical trials involving cholesterol-lowering medications have not shown this association. Between 1997 and 2002, the authors assessed the association between plasma cholesterol levels and cancer risk, free from confounding and reverse causality, in a Mendelian randomization study using apolipoprotein E (ApoE) genotype. ApoE genotype, plasma cholesterol levels, and cancer incidence and mortality were measured during a 3-year follow-up period among 2,913 participants in the Prospective Study of Pravastatin in the Elderly at Risk. Subjects within the lowest third of plasma cholesterol level at baseline had increased risks of cancer incidence (hazard ratio (HR) = 1.90, 95% confidence interval (CI): 1.34, 2.70) and cancer mortality (HR = 2.03, 95% CI: 1.23, 3.34) relative to subjects within the highest third of plasma cholesterol. However, carriers of the ApoE2 genotype (n = 332), who had 9% lower plasma cholesterol levels than carriers of the ApoE4 genotype (n = 635), did not have increased risk of cancer incidence (HR = 0.86, 95% CI: 0.50, 1.47) or cancer mortality (HR = 0.70, 95% CI: 0.30, 1.60) compared with ApoE4 carriers. These findings suggest that low cholesterol levels are not causally related to increased cancer risk.

  14. Correcting the Standard Errors of 2-Stage Residual Inclusion Estimators for Mendelian Randomization Studies.

    Science.gov (United States)

    Palmer, Tom M; Holmes, Michael V; Keating, Brendan J; Sheehan, Nuala A

    2017-11-01

    Mendelian randomization studies use genotypes as instrumental variables to test for and estimate the causal effects of modifiable risk factors on outcomes. Two-stage residual inclusion (TSRI) estimators have been used when researchers are willing to make parametric assumptions. However, researchers are currently reporting uncorrected or heteroscedasticity-robust standard errors for these estimates. We compared several different forms of the standard error for linear and logistic TSRI estimates in simulations and in real-data examples. Among others, we consider standard errors modified from the approach of Newey (1987), Terza (2016), and bootstrapping. In our simulations Newey, Terza, bootstrap, and corrected 2-stage least squares (in the linear case) standard errors gave the best results in terms of coverage and type I error. In the real-data examples, the Newey standard errors were 0.5% and 2% larger than the unadjusted standard errors for the linear and logistic TSRI estimators, respectively. We show that TSRI estimators with modified standard errors have correct type I error under the null. Researchers should report TSRI estimates with modified standard errors instead of reporting unadjusted or heteroscedasticity-robust standard errors. © The Author(s) 2017. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health.

  15. Mendelian breeding units versus standard sampling strategies: mitochondrial DNA variation in southwest Sardinia

    Directory of Open Access Journals (Sweden)

    Daria Sanna

    2011-01-01

    Full Text Available We report a sampling strategy based on Mendelian Breeding Units (MBUs, representing an interbreeding group of individuals sharing a common gene pool. The identification of MBUs is crucial for case-control experimental design in association studies. The aim of this work was to evaluate the possible existence of bias in terms of genetic variability and haplogroup frequencies in the MBU sample, due to severe sample selection. In order to reach this goal, the MBU sampling strategy was compared to a standard selection of individuals according to their surname and place of birth. We analysed mitochondrial DNA variation (first hypervariable segment and coding region in unrelated healthy subjects from two different areas of Sardinia: the area around the town of Cabras and the western Campidano area. No statistically significant differences were observed when the two sampling methods were compared, indicating that the stringent sample selection needed to establish a MBU does not alter original genetic variability and haplogroup distribution. Therefore, the MBU sampling strategy can be considered a useful tool in association studies of complex traits.

  16. Age at Menarche and Time Spent in Education: A Mendelian Randomization Study.

    Science.gov (United States)

    Gill, D; Del Greco M, F; Rawson, T M; Sivakumaran, P; Brown, A; Sheehan, N A; Minelli, C

    2017-09-01

    Menarche signifies the primary event in female puberty and is associated with changes in self-identity. It is not clear whether earlier puberty causes girls to spend less time in education. Observational studies on this topic are likely to be affected by confounding environmental factors. The Mendelian randomization (MR) approach addresses these issues by using genetic variants (such as single nucleotide polymorphisms, SNPs) as proxies for the risk factor of interest. We use this technique to explore whether there is a causal effect of age at menarche on time spent in education. Instruments and SNP-age at menarche estimates are identified from a Genome Wide Association Study (GWAS) meta-analysis of 182,416 women of European descent. The effects of instruments on time spent in education are estimated using a GWAS meta-analysis of 118,443 women performed by the Social Science Genetic Association Consortium (SSGAC). In our main analysis, we demonstrate a small but statistically significant causal effect of age at menarche on time spent in education: a 1 year increase in age at menarche is associated with 0.14 years (53 days) increase in time spent in education (95% CI 0.10-0.21 years, p = 3.5 × 10 -8 ). The causal effect is confirmed in sensitivity analyses. In identifying this positive causal effect of age at menarche on time spent in education, we offer further insight into the social effects of puberty in girls.

  17. Noncirrhotic portal hypertension.

    Science.gov (United States)

    Da, Ben L; Koh, Christopher; Heller, Theo

    2018-05-01

    Noncirrhotic portal hypertension represents a heterogeneous group of liver disorders that is characterized by portal hypertension in the absence of cirrhosis. The purpose of this review is to serve as a guide on how to approach a patient with noncirrhotic portal hypertension with a focus on recent developments. Recent studies pertaining to noncirrhotic portal hypertension have investigated aetiological causes, mechanisms of disease, noninvasive diagnostic modalities, clinical characteristics in the paediatric population and novel treatment targets. Noncirrhotic portal hypertension is an underappreciated clinical entity that can be difficult to diagnosis without a healthy suspicion. Diagnosis then relies on a comprehensive understanding of the causes and clinical manifestations of this disease, as well as a careful interpretation of the liver biopsy. Noninvasive approaches to diagnosis may play a significant role moving forward in this disease. Treatment in NCPH remains largely targeted at the individual sequalae of portal hypertension.

  18. Hypertension in Danish seafarers

    DEFF Research Database (Denmark)

    Tu, Mingshan; Jepsen, Jørgen Riis

    2016-01-01

    Background: Due to the high prevalence of arterial hypertension and its role in the development of athe- rosclerosis, myocardial infarction and stroke, hypertension is a major public health challenge worldwide. There is limited knowledge of the prevalence of hypertension among seafarers who......, however, are known to have an excess morbidity and mortality from these disorders. This article addresses the prevalence of hypertension among Danish seafarers and discusses potential risk factors for hypertension in maritime settings. Materials and methods: A representative sample of 629 Danish seafarers...... who had statutory medical examinations was studied from the beginning of October 2011 to the end of June 2012. The medical examination included measurements of blood pressure. The prevalence of hypertension in the study po- pulation was stratified by age, work place on board, smoking status, alcohol...

  19. CGMIM: Automated text-mining of Online Mendelian Inheritance in Man (OMIM to identify genetically-associated cancers and candidate genes

    Directory of Open Access Journals (Sweden)

    Jones Steven

    2005-03-01

    Full Text Available Abstract Background Online Mendelian Inheritance in Man (OMIM is a computerized database of information about genes and heritable traits in human populations, based on information reported in the scientific literature. Our objective was to establish an automated text-mining system for OMIM that will identify genetically-related cancers and cancer-related genes. We developed the computer program CGMIM to search for entries in OMIM that are related to one or more cancer types. We performed manual searches of OMIM to verify the program results. Results In the OMIM database on September 30, 2004, CGMIM identified 1943 genes related to cancer. BRCA2 (OMIM *164757, BRAF (OMIM *164757 and CDKN2A (OMIM *600160 were each related to 14 types of cancer. There were 45 genes related to cancer of the esophagus, 121 genes related to cancer of the stomach, and 21 genes related to both. Analysis of CGMIM results indicate that fewer than three gene entries in OMIM should mention both, and the more than seven-fold discrepancy suggests cancers of the esophagus and stomach are more genetically related than current literature suggests. Conclusion CGMIM identifies genetically-related cancers and cancer-related genes. In several ways, cancers with shared genetic etiology are anticipated to lead to further etiologic hypotheses and advances regarding environmental agents. CGMIM results are posted monthly and the source code can be obtained free of charge from the BC Cancer Research Centre website http://www.bccrc.ca/ccr/CGMIM.

  20. Pediatric portal hypertension

    Science.gov (United States)

    Vogel, Clarissa Barbon

    2017-01-01

    Abstract: Pediatric portal hypertension management is a team approach between the patient, the patient's family, the primary caregiver, and specialty providers. Evidence-based practice guidelines have not been established in pediatrics. This article serves as a review for the primary care NP in the management of pediatric portal hypertension, discussing the etiology, pathophysiology, and clinical presentation of pediatric portal hypertension, diagnostic tests, and treatment and management options. PMID:28406835

  1. Hypertension og hyperlipidaemi

    DEFF Research Database (Denmark)

    Hansen, Henrik Steen; Larsen, Mogens Lytken

    2009-01-01

    Hypertension and hyperlipidemia are well-established and partially overlapping risk factors for cardiovascular disease. Analyses of cardiovascular morbidity in relationship to changes in blood pressure and in serum cholesterol levels have shown that combined reduction of both risk factors...... are important to achieve a reduction in morbidity. Statins have been shown to be effective in preventing both coronary and cerebrovascular events in both hypertensive and normotensive cases. Consequently, most recent guidelines recommend that statin treatment be considered in hypertensive patients aged less...

  2. 42. Hypertension: Morbidity review

    Directory of Open Access Journals (Sweden)

    Hamzullah khan

    2015-10-01

    Conclusions: hypertension is a major modifiable risk factor for coronary artery disease, stroke, eye abnormalities and end stage renal disease, which require proper counseling and management of patients.

  3. The new hypertension guidelines.

    Science.gov (United States)

    Stern, Ralph H

    2013-10-01

    The Canadian Hypertension Education Program (CHEP) has published guidelines annually since 2000. The CHEP guidelines are a model of concise, comprehensive, up-to-date, evidence-rated guidelines for physicians who diagnose and treat hypertension. The guidelines address measurement of blood pressure and the definition of hypertension, secondary hypertension evaluation and treatment, and blood pressure targets and medication choices in patients with and without compelling indications. This review describes CHEP's process for developing guidelines and provides an overview of the 2013 recommendations. ©2013 Wiley Periodicals, Inc.

  4. [Hypertension in women].

    Science.gov (United States)

    Tagle, Rodrigo; Tagle V, Rodrigo; Acevedo, Mónica; Valdés, Gloria

    2013-02-01

    The present review examines the types of hypertension that women may suffer throughout life, their physiopathological characteristics and management. In early life, the currently used low-dose oral contraceptives seldom cause hypertension. Pregnancy provokes preeclampsia, its main medical complication, secondary to inadequate transformation of the spiral arteries and the subsequent multisystem endothelial damage caused by deportation of placental factors and microparticles. Hypertension in preeclampsia is an epiphenomenon which needs to be controlled at levels that reduce maternal risk without impairing placental perfusion. The hemodynamic changes of pregnancy may unmask a hypertensive phenotype, may exacerbate a chronic hypertension, or may complicate hypertension secondary to lupus, renovascular lesions, and pheochromocytoma. On the other hand a primary aldosteronism may benefit from the effect of progesterone and present as a postpartum hypertension. A hypertensive pregnancy, especially preeclampsia, represents a risk for cardiac, vascular and renal disease in later life. Menopause may mimic a pheochromocytoma, and is associated to endothelial dysfunction and salt-sensitivity. Among women, non-pharmacological treatment should be forcefully advocated, except for sodium restriction during pregnancy. The blockade of the renin-angiotensin system should be avoided in women at risk of pregnancy; betablockers could be used with precautions during pregnancy; diuretics, ACE inhibitors and angiotensin receptor antagonists should not be used during breast feeding. Collateral effects of antihypertensives, such as hyponatremia, cough and edema are more common in women. Thus, hypertension in women should be managed according to the different life stages.

  5. [Arterial hypertension due to altitude].

    Science.gov (United States)

    Domej, Wolfgang; Trapp, Michael; Miggitsch, Eva Maria; Krakher, Tiziana; Riedlbauer, Rita; Roher, Peter; Schwaberger, Günther

    2008-01-01

    The behavior of blood pressure under hypoxic conditions depends on individual factors, altitude and duration of stay at altitude. While most humans are normotensive at higher altitudes, a few will react with moderate hypertension or hypotension. Excessive elevation of arterial blood pressure is not even to be expected below 4,000 m. Rather, several weeks' stay at higher altitude will decrease systolic and diastolic blood pressure at rest as well as during physical exertion. A high-altitude treatment for rehabilitation purposes at moderate altitude may be recommended for patients with cardio-circulatory disorders. Improvements can last several months even after returning to accustomed altitudes. Furthermore, endurance-trained hypertensive patients with pharmacologically controlled arterial blood pressure might be able to participate in mountain treks without additional health risk.

  6. Causal Association of Overall Obesity and Abdominal Obesity with Type 2 Diabetes: A Mendelian Randomization Analysis.

    Science.gov (United States)

    Wang, Tao; Zhang, Rong; Ma, Xiaojing; Wang, Shiyun; He, Zhen; Huang, Yeping; Xu, Bo; Li, Yangyang; Zhang, Hong; Jiang, Feng; Bao, Yuqian; Hu, Cheng; Jia, Weiping

    2018-05-01

    This study aimed to compare the causal effect of overall obesity and abdominal obesity on type 2 diabetes among Chinese Han individuals. The causal relationship of BMI and waist-to-hip ratio (WHR) with the risk of glucose deterioration and glycemic traits was compared using two different genetic instruments based on 30 BMI loci and 6 WHR loci with Mendelian randomization (MR) in three prospective cohorts (n = 6,476). Each 1-SD genetically instrumented higher WHR was associated with a 65.7% higher risk of glucose deterioration (95% CI = 1.069-2.569, P = 0.024), whereas no significant association of BMI with glucose deterioration was observed. Furthermore, a causal relationship was found only between BMI and homeostatic model assessment β-cell function (HOMA-B) (β = 0.143, P = 0.001), and there was a nominal association with Stumvoll second-phase insulin secretion traits (β = 0.074, P = 0.022). The significance level did not persist in sensitivity analyses, except in the causal estimate of WHR on the Gutt index in MR-Egger (β = -0.379, P = 0.022) and the causal estimate of BMI on homeostatic model assessment β-cell function in weighted median MR (β = 0.128, P = 0.017). The data from this study support the potential causal relationship between abdominal obesity and hyperglycemia, which may be driven by aggravated insulin resistance, in contrast with the potential causal relationship between overall obesity and insulin secretion. © 2018 The Obesity Society.

  7. Elevated serum urate is a potential factor in reduction of total bilirubin: a Mendelian randomization study

    Science.gov (United States)

    Zhang, Hui; Liu, Jing; Dong, Zheng; Ding, Yue; Qian, Qiaoxia; Zhou, Jingru; Ma, Yanyun; Mei, Zhendong; Chen, Xiangxiang; Li, Yuan; Yuan, Ziyu; Zhang, Juan; Yang, Yajun; Chen, Xingdong; Jin, Li; Zou, Hejian; Wang, Xiaofeng; Wang, Jiucun

    2017-01-01

    Aim A Mendelian randomization study (MRS) can be linked to a “natural” randomized controlled trial in order to avoid potential bias of observational epidemiology. We aimed to study the possible association between serum urate (SU) and total bilirubin (TBIL) using MRS. Materials and Methods An observational epidemiological study using ordinary least squares (OLS) regression and MRS using two-stage least square (TLS) regression was conducted to assess the effect of SU on TBIL. The comparison between the OLS regression and the TLS regression was analyzed by the Durbin-Hausman test. If the p value is significant, it suggests that the OLS regression cannot evaluate the relationship between exposure and outcome, and the TLS regression is precise; while if the p value is not significant, there would be no significant difference between the two regressions. Results A total of 3,753 subjects were analyzed. In OLS regression, there was no significant association between SU and TBIL in all subjects and subgroup analysis (all p > 0.05). However, MRS revealed a negative correlation between SU and TBIL after adjustment for confounders (beta = –0.021, p = 0.010). Further analysis was conducted in different SU subgroups, and results show that elevated SU was associated with a significant reduction in TBIL after adjustment for hyperuricemic subjects (beta = –0.053, p = 0.027). In addition, the results using the Durbin-Hausman test further confirmed a negative effect of SU on TBIL (p = 0.002 and 0.010, respectively). Conclusions This research shows for the first time that elevated SU was a potential causal factor in the reduction of TBIL and it provides strong evidence to resolve the controversial association between SU and TBIL. PMID:29262606

  8. Pro-inflammatory fatty acid profile and colorectal cancer risk: A Mendelian randomisation analysis.

    Science.gov (United States)

    May-Wilson, Sebastian; Sud, Amit; Law, Philip J; Palin, Kimmo; Tuupanen, Sari; Gylfe, Alexandra; Hänninen, Ulrika A; Cajuso, Tatiana; Tanskanen, Tomas; Kondelin, Johanna; Kaasinen, Eevi; Sarin, Antti-Pekka; Eriksson, Johan G; Rissanen, Harri; Knekt, Paul; Pukkala, Eero; Jousilahti, Pekka; Salomaa, Veikko; Ripatti, Samuli; Palotie, Aarno; Renkonen-Sinisalo, Laura; Lepistö, Anna; Böhm, Jan; Mecklin, Jukka-Pekka; Al-Tassan, Nada A; Palles, Claire; Farrington, Susan M; Timofeeva, Maria N; Meyer, Brian F; Wakil, Salma M; Campbell, Harry; Smith, Christopher G; Idziaszczyk, Shelley; Maughan, Timothy S; Fisher, David; Kerr, Rachel; Kerr, David; Passarelli, Michael N; Figueiredo, Jane C; Buchanan, Daniel D; Win, Aung K; Hopper, John L; Jenkins, Mark A; Lindor, Noralane M; Newcomb, Polly A; Gallinger, Steven; Conti, David; Schumacher, Fred; Casey, Graham; Aaltonen, Lauri A; Cheadle, Jeremy P; Tomlinson, Ian P; Dunlop, Malcolm G; Houlston, Richard S

    2017-10-01

    While dietary fat has been established as a risk factor for colorectal cancer (CRC), associations between fatty acids (FAs) and CRC have been inconsistent. Using Mendelian randomisation (MR), we sought to evaluate associations between polyunsaturated (PUFA), monounsaturated (MUFA) and saturated FAs (SFAs) and CRC risk. We analysed genotype data on 9254 CRC cases and 18,386 controls of European ancestry. Externally weighted polygenic risk scores were generated and used to evaluate associations with CRC per one standard deviation increase in genetically defined plasma FA levels. Risk reduction was observed for oleic and palmitoleic MUFAs (OR OA  = 0.77, 95% CI: 0.65-0.92, P = 3.9 × 10 -3 ; OR POA  = 0.36, 95% CI: 0.15-0.84, P = 0.018). PUFAs linoleic and arachidonic acid had negative and positive associations with CRC respectively (OR LA  = 0.95, 95% CI: 0.93-0.98, P = 3.7 × 10 -4 ; OR AA  = 1.05, 95% CI: 1.02-1.07, P = 1.7 × 10 -4 ). The SFA stearic acid was associated with increased CRC risk (OR SA  = 1.17, 95% CI: 1.01-1.35, P = 0.041). Results from our analysis are broadly consistent with a pro-inflammatory FA profile having a detrimental effect in terms of CRC risk. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  9. Low nonfasting triglycerides and reduced all-cause mortality: a mendelian randomization study.

    Science.gov (United States)

    Thomsen, Mette; Varbo, Anette; Tybjærg-Hansen, Anne; Nordestgaard, Børge G

    2014-05-01

    Increased nonfasting plasma triglycerides marking increased amounts of cholesterol in remnant lipoproteins are important risk factors for cardiovascular disease, but whether lifelong reduced concentrations of triglycerides on a genetic basis ultimately lead to reduced all-cause mortality is unknown. We tested this hypothesis. Using individuals from the Copenhagen City Heart Study in a mendelian randomization design, we first tested whether low concentrations of nonfasting triglycerides were associated with reduced all-cause mortality in observational analyses (n = 13 957); second, whether genetic variants in the triglyceride-degrading enzyme lipoprotein lipase, resulting in reduced nonfasting triglycerides and remnant cholesterol, were associated with reduced all-cause mortality (n = 10 208). During a median 24 and 17 years of 100% complete follow-up, 9991 and 4005 individuals died in observational and genetic analyses, respectively. In observational analyses compared to individuals with nonfasting plasma triglycerides of 266-442 mg/dL (3.00-4.99 mmol/L), multivariably adjusted hazard ratios for all-cause mortality were 0.89 (95% CI 0.78-1.02) for 177-265 mg/dL (2.00-2.99 mmol/L), 0.74 (0.65-0.84) for 89-176 mg/dL (1.00-1.99 mmol/L), and 0.59 (0.51-0.68) for individuals with nonfasting triglycerides triglycerides was 0.50 (0.30-0.82), with a corresponding observational hazard ratio of 0.87 (0.85-0.89). Also, the odds ratio for a genetically derived 50% lower concentration in nonfasting triglycerides was 0.43 (0.23-0.80), with a corresponding observational hazard ratio of 0.73 (0.70-0.77). Genetically reduced concentrations of nonfasting plasma triglycerides are associated with reduced all-cause mortality, likely through reduced amounts of cholesterol in remnant lipoproteins.

  10. Decreased serum pyridoxal levels in schizophrenia: meta-analysis and Mendelian randomization analysis

    Science.gov (United States)

    Tomioka, Yukiko; Kinoshita, Makoto; Umehara, Hidehiro; Watanabe, Shin-ya; Nakataki, Masahito; Iwayama, Yoshimi; Toyota, Tomoko; Ikeda, Masashi; Yamamori, Hidenaga; Shimodera, Shinji; Tajima, Atsushi; Hashimoto, Ryota; Iwata, Nakao; Yoshikawa, Takeo; Ohmori, Tetsuro

    2018-01-01

    Background Alterations in one-carbon metabolism have been associated with schizophrenia, and vitamin B6 is one of the key components in this pathway. Methods We first conducted a case–control study of serum pyridoxal levels and schizophrenia in a large Japanese cohort (n = 1276). Subsequently, we conducted a meta-analysis of association studies (n = 2125). Second, we investigated whether rs4654748, which was identified in a genome-wide association study as a vitamin B6-related single nucleotide polymorphism, was genetically implicated in patients with schizophrenia in the Japanese population (n = 10 689). Finally, we assessed the effect of serum pyridoxal levels on schizophrenia risk using a Mendelian randomization (MR) approach. Results Serum pyridoxal levels were significantly lower in patients with schizophrenia than in controls, not only in our cohort, but also in the pooled data set of the meta-analysis of association studies (standardized mean difference −0.48, 95% confidence interval [CI] −0.57 to −0.39, p = 9.8 × 10−24). We failed to find a significant association between rs4654748 and schizophrenia. Furthermore, an MR analysis failed to find a causal relationship between pyridoxal levels and schizophrenia risk (odds ratio 0.99, 95% CI 0.65–1.51, p = 0.96). Limitations Food consumption and medications may have affected serum pyridoxal levels in our cross-sectional study. Sample size, number of instrumental variables and substantial heterogeneity among patients with schizophrenia are limitations of an MR analysis. Conclusion We found decreased serum pyridoxal levels in patients with schizophrenia in this observational study. However, we failed to obtain data supporting a causal relationship between pyridoxal levels and schizophrenia risk using the MR approach. PMID:29688875

  11. Serum iron levels and the risk of Parkinson disease: a Mendelian randomization study.

    Directory of Open Access Journals (Sweden)

    Irene Pichler

    Full Text Available Although levels of iron are known to be increased in the brains of patients with Parkinson disease (PD, epidemiological evidence on a possible effect of iron blood levels on PD risk is inconclusive, with effects reported in opposite directions. Epidemiological studies suffer from problems of confounding and reverse causation, and mendelian randomization (MR represents an alternative approach to provide unconfounded estimates of the effects of biomarkers on disease. We performed a MR study where genes known to modify iron levels were used as instruments to estimate the effect of iron on PD risk, based on estimates of the genetic effects on both iron and PD obtained from the largest sample meta-analyzed to date.We used as instrumental variables three genetic variants influencing iron levels, HFE rs1800562, HFE rs1799945, and TMPRSS6 rs855791. Estimates of their effect on serum iron were based on a recent genome-wide meta-analysis of 21,567 individuals, while estimates of their effect on PD risk were obtained through meta-analysis of genome-wide and candidate gene studies with 20,809 PD cases and 88,892 controls. Separate MR estimates of the effect of iron on PD were obtained for each variant and pooled by meta-analysis. We investigated heterogeneity across the three estimates as an indication of possible pleiotropy and found no evidence of it. The combined MR estimate showed a statistically significant protective effect of iron, with a relative risk reduction for PD of 3% (95% CI 1%-6%; p = 0.001 per 10 µg/dl increase in serum iron.Our study suggests that increased iron levels are causally associated with a decreased risk of developing PD. Further studies are needed to understand the pathophysiological mechanism of action of serum iron on PD risk before recommendations can be made.

  12. Robust inference in summary data Mendelian randomization via the zero modal pleiotropy assumption.

    Science.gov (United States)

    Hartwig, Fernando Pires; Davey Smith, George; Bowden, Jack

    2017-12-01

    Mendelian randomization (MR) is being increasingly used to strengthen causal inference in observational studies. Availability of summary data of genetic associations for a variety of phenotypes from large genome-wide association studies (GWAS) allows straightforward application of MR using summary data methods, typically in a two-sample design. In addition to the conventional inverse variance weighting (IVW) method, recently developed summary data MR methods, such as the MR-Egger and weighted median approaches, allow a relaxation of the instrumental variable assumptions. Here, a new method - the mode-based estimate (MBE) - is proposed to obtain a single causal effect estimate from multiple genetic instruments. The MBE is consistent when the largest number of similar (identical in infinite samples) individual-instrument causal effect estimates comes from valid instruments, even if the majority of instruments are invalid. We evaluate the performance of the method in simulations designed to mimic the two-sample summary data setting, and demonstrate its use by investigating the causal effect of plasma lipid fractions and urate levels on coronary heart disease risk. The MBE presented less bias and lower type-I error rates than other methods under the null in many situations. Its power to detect a causal effect was smaller compared with the IVW and weighted median methods, but was larger than that of MR-Egger regression, with sample size requirements typically smaller than those available from GWAS consortia. The MBE relaxes the instrumental variable assumptions, and should be used in combination with other approaches in sensitivity analyses. © The Author 2017. Published by Oxford University Press on behalf of the International Epidemiological Association

  13. Fumaric Acid Esters Can Block Pro-Inflammatory Actions of Human CRP and Ameliorate Metabolic Disturbances in Transgenic Spontaneously Hypertensive Rats

    Czech Academy of Sciences Publication Activity Database

    Šilhavý, Jan; Zídek, Václav; Mlejnek, Petr; Landa, Vladimír; Šimáková, Miroslava; Strnad, Hynek; Oliyarnyk, O.; Škop, V.; Kazdová, L.; Kurtz, T.; Pravenec, Michal

    2014-01-01

    Roč. 9, č. 7 (2014), e101906 E-ISSN 1932-6203 R&D Projects: GA MZd(CZ) NT14325; GA MŠk(CZ) LH12061; GA MŠk(CZ) LL1204 Institutional support: RVO:67985823 ; RVO:68378050 Keywords : fumaric acid esters * C-reactive protein * transgenic * spontaneously hypertensive rat Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.234, year: 2014

  14. Therapeutic Exercise and Hypertension

    African Journals Online (AJOL)

    Nekky Umera

    patients but may not reduce the BP of normotensive individual. Exercise function ... and mortality in all age groups; it also creates major social, personal and financial ... drug therapy by as symptomatic hypertensive and high cost of drugs particularly in a ..... Events in hypertensive patients randomized to doxagosin versus.

  15. Noncirrotisk intrahepatisk portal hypertension

    DEFF Research Database (Denmark)

    Dam Fialla, Annette; Havelund, Troels

    2007-01-01

    Non-cirrhotic intrahepatic portal hypertension is characterized by portal hypertension in the absence of liver cirrhosis or portal vein thrombosis. The disease is common in the East and rarely seen in the West. Two cases with oesophageal varices are described. The histopathology is heterogeneous...... but includes vascular lesions and portal fibrosis. Patient management follows the current recommendations for variceal bleeding....

  16. Pulmonary Arterial Hypertension

    Science.gov (United States)

    ... heart). This type of pulmonary hypertension was called “secondary pulmonary hypertension” but is now referred to as PH, because the cause is known to be from lung disease, heart disease, or chronic thromboemboli (blood clots). Pulmonary Arterial Hypertension (PAH) used to be ...

  17. Hypertension (High Blood Pressure)

    Science.gov (United States)

    ... Safe Videos for Educators Search English Español Hypertension (High Blood Pressure) KidsHealth / For Teens / Hypertension (High Blood Pressure) What's ... rest temperature diet emotions posture medicines Why Is High Blood Pressure Bad? High blood pressure means a person's heart ...

  18. Cervical Spondylosis and Hypertension

    Science.gov (United States)

    Peng, Baogan; Pang, Xiaodong; Li, Duanming; Yang, Hong

    2015-01-01

    Abstract Cervical spondylosis and hypertension are all common diseases, but the relationship between them has never been studied. Patients with cervical spondylosis are often accompanied with vertigo. Anterior cervical discectomy and fusion is an effective method of treatment for cervical spondylosis with cervical vertigo that is unresponsive to conservative therapy. We report 2 patients of cervical spondylosis with concomitant cervical vertigo and hypertension who were treated successfully with anterior cervical discectomy and fusion. Stimulation of sympathetic nerve fibers in pathologically degenerative disc could produce sympathetic excitation, and induce a sympathetic reflex to cause cervical vertigo and hypertension. In addition, chronic neck pain could contribute to hypertension development through sympathetic arousal and failure of normal homeostatic pain regulatory mechanisms. Cervical spondylosis may be one of the causes of secondary hypertension. Early treatment for resolution of symptoms of cervical spondylosis may have a beneficial impact on cardiovascular disease risk in patients with cervical spondylosis. PMID:25761188

  19. Overweight, adipocytokines and hypertension

    DEFF Research Database (Denmark)

    Seven, Ekim; Husemoen, Lise L N; Wachtell, Kristian

    2014-01-01

    OBJECTIVE:: The adipocytokines, leptin, adiponectin, and interleukin-6, which stimulate liver C-reactive protein (CRP) production, are regarded as potential candidate intermediates between adipose tissue and overweight-induced hypertension. METHODS:: We examined the associations between leptin......, adiponectin, and CRP levels with both prevalent and 5-year incident hypertension (IHT) in a general population of Danish adults (n = 5868, 51.3% women, mean age 45.8 ± 7.9 years). RESULTS:: We recorded 2195 prevalent and 379 incident cases of hypertension. In models including leptin, CRP, adiponectin, sex.......023) in the fully adjusted model. The population attributable risk estimate of IHT owing to overweight was 31%. CONCLUSION:: Leptin, but not adiponectin or CRP, may play a mediating role in overweight-induced hypertension. However, as BMI was a strong independent predictor of hypertension, other factors than leptin...

  20. Hypertension in women.

    Science.gov (United States)

    Pimenta, Eduardo

    2012-02-01

    Hypertension is an important modifiable risk factor for cardiovascular (CV) morbidity and mortality, and a highly prevalent condition in both men and women. However, the prevalence of hypertension is predicted to increase more among women than men. Combined oral contraceptives (COCs) can induce hypertension in a small group of women and, increase CV risk especially among those with hypertension. Both COC-related increased CV risk and blood pressure (BP) returns to pretreatment levels by 3 months of its discontinuation. The effects of menopause and hormone replacement therapy (HRT) on BP are controversial, and COCs and HRT containing the new generation progestin drospirenone are preferred in women with established hypertension. Despite the high incidence of cancer in women, CV disease remains the major cause of death in women and comparable benefit of antihypertensive treatment have been demonstrated in both women and men.

  1. Overweight, adipocytokines and hypertension

    DEFF Research Database (Denmark)

    Seven, Ekim; Husemoen, Lise L N; Wachtell, Kristian

    2014-01-01

    OBJECTIVE: The adipocytokines, leptin, adiponectin, and interleukin-6, which stimulate liver C-reactive protein (CRP) production, are regarded as potential candidate intermediates between adipose tissue and overweight-induced hypertension. METHODS: We examined the associations between leptin......, adiponectin, and CRP levels with both prevalent and 5-year incident hypertension (IHT) in a general population of Danish adults (n = 5,868, 51.3% women, mean age 45.8 ± 7.9 years). RESULTS: We recorded 2195 prevalent and 379 incident cases of hypertension. In models including leptin, CRP, adiponectin, sex.......023) in the fully adjusted model. The population attributable risk estimate of IHT owing to overweight was 31%. CONCLUSION: Leptin, but not adiponectin or CRP, may play a mediating role in overweight-induced hypertension. However, as BMI was a strong independent predictor of hypertension, other factors than leptin...

  2. The Effect of Iron Status on Risk of Coronary Artery Disease: A Mendelian Randomization Study-Brief Report.

    Science.gov (United States)

    Gill, Dipender; Del Greco M, Fabiola; Walker, Ann P; Srai, Surjit K S; Laffan, Michael A; Minelli, Cosetta

    2017-09-01

    Iron status is a modifiable trait that has been implicated in cardiovascular disease. This study uses the Mendelian randomization technique to investigate whether there is any causal effect of iron status on risk of coronary artery disease (CAD). A 2-sample Mendelian randomization approach is used to estimate the effect of iron status on CAD risk. Three loci (rs1800562 and rs1799945 in the HFE gene and rs855791 in TMPRSS6 ) that are each associated with serum iron, transferrin saturation, ferritin, and transferrin in a pattern suggestive of an association with systemic iron status are used as instruments. SNP (single-nucleotide polymorphism)-iron status association estimates are based on a genome-wide association study meta-analysis of 48 972 individuals. SNP-CAD estimates are derived by combining the results of a genome-wide association study meta-analysis of 60 801 CAD cases and 123 504 controls with those of a meta-analysis of 63 746 CAD cases and 130 681 controls obtained from Metabochip and genome-wide association studies. Combined Mendelian randomization estimates are obtained for each marker by pooling results across the 3 instruments. We find evidence of a protective effect of higher iron status on CAD risk (iron odds ratio, 0.94 per SD unit increase; 95% confidence interval, 0.88-1.00; P =0.039; transferrin saturation odds ratio, 0.95 per SD unit increase; 95% confidence interval, 0.91-0.99; P =0.027; log-transformed ferritin odds ratio, 0.85 per SD unit increase; 95% confidence interval, 0.73-0.98; P =0.024; and transferrin odds ratio, 1.08 per SD unit increase; 95% confidence interval, 1.01-1.16; P =0.034). This Mendelian randomization study supports the hypothesis that higher iron status reduces CAD risk. These findings may highlight a therapeutic target. © 2017 American Heart Association, Inc.

  3. Role of the Immune System in Hypertension.

    Science.gov (United States)

    Rodriguez-Iturbe, Bernardo; Pons, Hector; Johnson, Richard J

    2017-07-01

    High blood pressure is present in more than one billion adults worldwide and is the most important modifiable risk factor of death resulting from cardiovascular disease. While many factors contribute to the pathogenesis of hypertension, a role of the immune system has been firmly established by a large number of investigations from many laboratories around the world. Immunosuppressive drugs and inhibition of individual cytokines prevent or ameliorate experimental hypertension, and studies in genetically-modified mouse strains have demonstrated that lymphocytes are necessary participants in the development of hypertension and in hypertensive organ injury. Furthermore, immune reactivity may be the driving force of hypertension in autoimmune diseases. Infiltration of immune cells, oxidative stress, and stimulation of the intrarenal angiotensin system are induced by activation of the innate and adaptive immunity. High blood pressure results from the combined effects of inflammation-induced impairment in the pressure natriuresis relationship, dysfunctional vascular relaxation, and overactivity of the sympathetic nervous system. Imbalances between proinflammatory effector responses and anti-inflammatory responses of regulatory T cells to a large extent determine the severity of inflammation. Experimental and human studies have uncovered autoantigens (isoketal-modified proteins and heat shock protein 70) of potential clinical relevance. Further investigations on the immune reactivity in hypertension may result in the identification of new strategies for the treatment of the disease. Copyright © 2017 the American Physiological Society.

  4. Pulmonary hypertension CT imaging

    International Nuclear Information System (INIS)

    Nedevska, A.

    2013-01-01

    Full text: The right heart catheterization is the gold standard in the diagnosis and determines the severity of pulmonary hypertension. The significant technical progress of noninvasive diagnostic imaging methods significantly improves the pixel density and spatial resolution in the study of cardiovascular structures, thus changes their role and place in the overall diagnostic plan. Learning points: What is the etiology, clinical manifestation and general pathophysiological disorders in pulmonary hypertension. What are the established diagnostic methods in the diagnosis and follow-up of patients with pulmonary hypertension. What is the recommended protocol for CT scanning for patients with clinically suspected or documented pulmonary hypertension. What are the important diagnostic findings in CT scan of a patient with pulmonary hypertension. Discussion: The prospect of instantaneous complex - anatomical and functional cardiopulmonary and vascular diagnostics seems extremely attractive. The contrast enhanced multislice computed (CT ) and magnetic resonance imaging are very suitable methods for imaging the structures of the right heart, with the possibility of obtaining multiple projections and three-dimensional imaging reconstructions . There are specific morphological features that, if carefully analyzed, provide diagnostic information. Thus, it is possible to avoid or at least reduce the frequency of use of invasive diagnostic cardiac catheterization in patients with pulmonary hypertension. Conclusion: This review focuses on the use of contrast-enhanced CT for comprehensive evaluation of patients with pulmonary hypertension and presents the observed characteristic changes in the chest, lung parenchyma , the structures of the right half of the heart and pulmonary vessels

  5. Salsalate ameliorates metabolic disturbances by reducing inflammation in spontaneously hypertensive rats expressing human C-reactive protein and by activating brown adipose tissue in nontransgenic controls

    Czech Academy of Sciences Publication Activity Database

    Trnovská, J.; Šilhavý, Jan; Kuda, Ondřej; Landa, Vladimír; Zídek, Václav; Mlejnek, Petr; Šimáková, Miroslava; Strnad, Hynek; Škop, V.; Oliyarnyk, O.; Kazdová, L.; Haluzík, M.; Pravenec, Michal

    2017-01-01

    Roč. 12, č. 6 (2017), č. článku e0179063. E-ISSN 1932-6203 R&D Projects: GA ČR(CZ) GA13-04420S Institutional support: RVO:67985823 ; RVO:68378050 Keywords : inflammation * insulin resistance * C-reactive protein * spintaneously hypertensive rat * salsalate Subject RIV: EB - Genetics ; Molecular Biology; EB - Genetics ; Molecular Biology (UMG-J) OBOR OECD: Endocrinology and metabolism (including diabetes, hormones); Endocrinology and metabolism (including diabetes, hormones) (UMG-J) Impact factor: 2.806, year: 2016

  6. Dietary omega-3 fatty acids attenuate myocardial arrhythmogenic factors and propensity of the heart to lethal arrhythmias in a rodent model of human essential hypertension

    Czech Academy of Sciences Publication Activity Database

    Radošinská, J.; Bačová, B.; Knezl, V.; Beňová, T.; Žurmanová, J.; Soukup, Tomáš; Arnoštová, P.; Slezák, J.; Goncalvesová, E.; Tribulová, N.

    2013-01-01

    Roč. 31, č. 9 (2013), s. 1876-1885 ISSN 0263-6352 R&D Projects: GA ČR(CZ) GA304/08/0256; GA MŠk(CZ) 7AMB12SK158 Institutional research plan: CEZ:AV0Z50110509 Institutional support: RVO:67985823 Keywords : hypertension * omega-3 polyunsaturated fatty acids * ventricular fibrillation * sinus rhythm restoration * myocardial connexin-43 * protein kinase C * myosin heavy chain Subject RIV: EA - Cell Biology Impact factor: 4.222, year: 2013

  7. Evaluation of genetic markers as instruments for Mendelian randomization studies on vitamin D.

    Directory of Open Access Journals (Sweden)

    Diane J Berry

    Full Text Available Mendelian randomization (MR studies use genetic variants mimicking the influence of a modifiable exposure to assess and quantify a causal association with an outcome, with an aim to avoid problems with confounding and reverse causality affecting other types of observational studies.We evaluated genetic markers that index differences in 25-hydroxyvitamin D (25(OHD as instruments for MR studies on vitamin D.We used data from up-to 6,877 participants in the 1958 British birth cohort with information on genetic markers and 25(OHD. As potential instruments, we selected 20 single nucleotide polymorphisms (SNP which are located in the vitamin D metabolism pathway or affect skin pigmentation/tanning, including 4 SNPs from genome-wide association (GWA meta-analyses on 25(OHD. We analyzed SNP associations with 25(OHD and evaluated the use of allele scores dividing genes to those affecting 25(OHD synthesis (DHCR7, CYP2R1 and metabolism (GC, CYP24A1, CYP27B1. In addition to the GWA SNPs, only two SNPs (CYP27B1, OCA2 showed evidence for association with 25(OHD, with the OCA2 association abolished after lifestyle adjustment. Per allele differences varied between -0.02 and -0.08 nmol/L (P≤0.02 for all, with a 6.1 nmol/L and a 10.2 nmol/L difference in 25(OHD between individuals with highest compared lowest number of risk alleles in synthesis and metabolism allele scores, respectively. Individual SNPs but not allele scores showed associations with lifestyle factors. An exception was geographical region which was associated with synthesis score. Illustrative power calculations (80% power, 5% alpha suggest that approximately 80,000 participants are required to establish a causal effect of vitamin D on blood pressure using the synthesis allele score.Combining SNPs into allele scores provides a more powerful instrument for MR analysis than a single SNP in isolation. Population stratification and the potential for pleiotropic effects need to be considered in MR

  8. Obesity, metabolic factors and risk of different histological types of lung cancer: A Mendelian randomization study.

    Directory of Open Access Journals (Sweden)

    Robert Carreras-Torres

    Full Text Available Assessing the relationship between lung cancer and metabolic conditions is challenging because of the confounding effect of tobacco. Mendelian randomization (MR, or the use of genetic instrumental variables to assess causality, may help to identify the metabolic drivers of lung cancer.We identified genetic instruments for potential metabolic risk factors and evaluated these in relation to risk using 29,266 lung cancer cases (including 11,273 adenocarcinomas, 7,426 squamous cell and 2,664 small cell cases and 56,450 controls. The MR risk analysis suggested a causal effect of body mass index (BMI on lung cancer risk for two of the three major histological subtypes, with evidence of a risk increase for squamous cell carcinoma (odds ratio (OR [95% confidence interval (CI] = 1.20 [1.01-1.43] and for small cell lung cancer (OR [95%CI] = 1.52 [1.15-2.00] for each standard deviation (SD increase in BMI [4.6 kg/m2], but not for adenocarcinoma (OR [95%CI] = 0.93 [0.79-1.08] (Pheterogeneity = 4.3x10-3. Additional analysis using a genetic instrument for BMI showed that each SD increase in BMI increased cigarette consumption by 1.27 cigarettes per day (P = 2.1x10-3, providing novel evidence that a genetic susceptibility to obesity influences smoking patterns. There was also evidence that low-density lipoprotein cholesterol was inversely associated with lung cancer overall risk (OR [95%CI] = 0.90 [0.84-0.97] per SD of 38 mg/dl, while fasting insulin was positively associated (OR [95%CI] = 1.63 [1.25-2.13] per SD of 44.4 pmol/l. Sensitivity analyses including a weighted-median approach and MR-Egger test did not detect other pleiotropic effects biasing the main results.Our results are consistent with a causal role of fasting insulin and low-density lipoprotein cholesterol in lung cancer etiology, as well as for BMI in squamous cell and small cell carcinoma. The latter relation may be mediated by a previously unrecognized effect of obesity on smoking behavior.

  9. Assessing causality in the association between child adiposity and physical activity levels: a Mendelian randomization analysis.

    Directory of Open Access Journals (Sweden)

    Rebecca C Richmond

    2014-03-01

    Full Text Available Cross-sectional studies have shown that objectively measured physical activity is associated with childhood adiposity, and a strong inverse dose-response association with body mass index (BMI has been found. However, few studies have explored the extent to which this association reflects reverse causation. We aimed to determine whether childhood adiposity causally influences levels of physical activity using genetic variants reliably associated with adiposity to estimate causal effects.The Avon Longitudinal Study of Parents and Children collected data on objectively assessed activity levels of 4,296 children at age 11 y with recorded BMI and genotypic data. We used 32 established genetic correlates of BMI combined in a weighted allelic score as an instrumental variable for adiposity to estimate the causal effect of adiposity on activity. In observational analysis, a 3.3 kg/m² (one standard deviation higher BMI was associated with 22.3 (95% CI, 17.0, 27.6 movement counts/min less total physical activity (p = 1.6×10⁻¹⁶, 2.6 (2.1, 3.1 min/d less moderate-to-vigorous-intensity activity (p = 3.7×10⁻²⁹, and 3.5 (1.5, 5.5 min/d more sedentary time (p = 5.0×10⁻⁴. In Mendelian randomization analyses, the same difference in BMI was associated with 32.4 (0.9, 63.9 movement counts/min less total physical activity (p = 0.04 (∼5.3% of the mean counts/minute, 2.8 (0.1, 5.5 min/d less moderate-to-vigorous-intensity activity (p = 0.04, and 13.2 (1.3, 25.2 min/d more sedentary time (p = 0.03. There was no strong evidence for a difference between variable estimates from observational estimates. Similar results were obtained using fat mass index. Low power and poor instrumentation of activity limited causal analysis of the influence of physical activity on BMI.Our results suggest that increased adiposity causes a reduction in physical activity in children and support research into the targeting of BMI in efforts to

  10. Inflammation, insulin resistance, and diabetes--Mendelian randomization using CRP haplotypes points upstream.

    Directory of Open Access Journals (Sweden)

    Eric J Brunner

    2008-08-01

    Full Text Available Raised C-reactive protein (CRP is a risk factor for type 2 diabetes. According to the Mendelian randomization method, the association is likely to be causal if genetic variants that affect CRP level are associated with markers of diabetes development and diabetes. Our objective was to examine the nature of the association between CRP phenotype and diabetes development using CRP haplotypes as instrumental variables.We genotyped three tagging SNPs (CRP + 2302G > A; CRP + 1444T > C; CRP + 4899T > G in the CRP gene and measured serum CRP in 5,274 men and women at mean ages 49 and 61 y (Whitehall II Study. Homeostasis model assessment-insulin resistance (HOMA-IR and hemoglobin A1c (HbA1c were measured at age 61 y. Diabetes was ascertained by glucose tolerance test and self-report. Common major haplotypes were strongly associated with serum CRP levels, but unrelated to obesity, blood pressure, and socioeconomic position, which may confound the association between CRP and diabetes risk. Serum CRP was associated with these potential confounding factors. After adjustment for age and sex, baseline serum CRP was associated with incident diabetes (hazard ratio = 1.39 [95% confidence interval 1.29-1.51], HOMA-IR, and HbA1c, but the associations were considerably attenuated on adjustment for potential confounding factors. In contrast, CRP haplotypes were not associated with HOMA-IR or HbA1c (p = 0.52-0.92. The associations of CRP with HOMA-IR and HbA1c were all null when examined using instrumental variables analysis, with genetic variants as the instrument for serum CRP. Instrumental variables estimates differed from the directly observed associations (p = 0.007-0.11. Pooled analysis of CRP haplotypes and diabetes in Whitehall II and Northwick Park Heart Study II produced null findings (p = 0.25-0.88. Analyses based on the Wellcome Trust Case Control Consortium (1,923 diabetes cases, 2,932 controls using three SNPs in tight linkage disequilibrium with our

  11. Hypertension og nyresygdom

    DEFF Research Database (Denmark)

    Kamper, Anne-Lise; Pedersen, Erling B; Strandgaard, Svend

    2009-01-01

    Renal mechanisms, in particular the renin-angiotensin system and renal salt handling, are of major importance in blood pressure regulation. Co-existence of hypertension and decreased renal function may be due to nephrosclerosis secondary to hypertension, or primary renal disease with secondary...... hypertension. Mild degrees of chronic kidney disease (CKD) can be detected in around 10% of the population, and detection is important as CKD is an important risk factor for atherosclerotic cardiovascular disease. Conversely, heart failure may cause an impairment of renal function. In chronic progressive...

  12. Hypertension og nyresygdom

    DEFF Research Database (Denmark)

    Kamper, Anne-Lise; Pedersen, Erling B; Strandgaard, Svend

    2009-01-01

    Renal mechanisms, in particular the renin-angiotensin system and renal salt handling, are of major importance in blood pressure regulation. Co-existence of hypertension and decreased renal function may be due to nephrosclerosis secondary to hypertension, or primary renal disease with secondary...... hypertension. Mild degrees of chronic kidney disease (CKD) can be detected in around 10% of the population, and detection is important as CKD is an important risk factor for atherosclerotic cardiovascular disease. Conversely, heart failure may cause an impairment of renal function. In chronic progressive...... nephropathy, effective blood pressure lowering is of paramount importance, and angiotensin converting enzyme inhibitors and angiotensin receptor blockers are agents of choice....

  13. Hypertension and Cardiac Arrhythmias

    DEFF Research Database (Denmark)

    Lip, Gregory Y H; Coca, Antonio; Kahan, Thomas

    2017-01-01

    Hypertension (HTN) is a common cardiovascular risk factor leading to heart failure (HF), coronary artery disease (CAD), stroke, peripheral artery disease and chronic renal failure. Hypertensive heart disease can manifest as many types of cardiac arrhythmias, most commonly being atrial fibrillation......) Council on Hypertension convened a Task Force, with representation from the Heart Rhythm Society (HRS), Asia-Pacific Heart Rhythm Society (APHRS), and Sociedad Latinoamericana de Estimulación Cardíaca y Electrofisiología (SOLEACE), with the remit of comprehensively reviewing the available evidence...

  14. The role of red blood cell deformability and Na,K-ATPase function in selected risk factors of cardiovascular diseases in humans: focus on hypertension, diabetes mellitus and hypercholesterolemia.

    Science.gov (United States)

    Radosinska, J; Vrbjar, N

    2016-09-19

    Deformability of red blood cells (RBC) is the ability of RBC to change their shape in order to pass through narrow capillaries in circulation. Deterioration in deformability of RBC contributes to alterations in microcirculatory blood flow and delivery of oxygen to tissues. Several factors are responsible for maintenance of RBC deformability. One of them is the Na,K-ATPase known as crucial enzyme in maintenance of intracellular ionic homeostasis affecting thus regulation of cellular volume and consequently RBC deformability. Decreased deformability of RBC has been found to be the marker of adverse outcomes in cardiovascular diseases (CVD) and the presence of cardiovascular risk factors influences rheological properties of the blood. This review summarizes knowledge concerning the RBC deformability in connection with selected risk factors of CVD, including hypertension, hyperlipidemia, and diabetes mellitus, based exclusively on papers from human studies. We attempted to provide an update on important issues regarding the role of Na,K-ATPase in RBC deformability. In patients suffering from hypertension as well as diabetes mellitus the Na,K-ATPase appears to be responsible for the changes leading to alterations in RBC deformability. The triggering factor for changes of RBC deformability during hypercholesterolemia seems to be the increased content of cholesterol in erythrocyte membranes.

  15. Short Communication Mendelian inheritance, linkage, and genotypic disequilibrium in microsatellite loci of Hymenaea stigonocarpa Mart. ex Hayne (Fabaceae-Caesalpinioideae).

    Science.gov (United States)

    Moraes, M A; Kubota, T Y K; Silva, E C B; Silva, A M; Cambuim, J; Moraes, M L T; Furlani Junior, E; Sebbenn, A M

    2016-07-29

    Hymenaea stigonocarpa is a deciduous and monoecious Neotropical tree species pollinated by bats. Due to overexploitation and habitat destruction, the population size has drastically diminished in nature. No previous study has investigated Mendelian inheritance, linkage, and genotypic disequilibrium in the available microsatellite markers in this species. So, our aim was to estimate these parameters using six microsatellite loci in a sample of 470 adults and 219 juveniles from two populations of H. stigonocarpa. In addition, 30 seeds per tree from 35 seed-trees were collected. Each seed was kept record of the seed-trees and fruit origin. Based on the six microsatellite loci, we found that only 10.6% of the cases showed significant deviations from Mendelian segregation and 15.3% showed linkage. We detected no evidence of genotypic disequilibrium between the loci in the adult trees or juveniles. Thus, our results suggest that these loci can be used with great accuracy in future genetic analyses of H. stigonocarpa populations.

  16. Liver cirrhosis and arterial hypertension

    DEFF Research Database (Denmark)

    Henriksen, Jens Henrik; Møller, Søren

    2006-01-01

    blood pressure. This review considers the alterations in systemic hemodynamics in patients with cirrhosis in relation to essential hypertension and arterial hypertension of the renal origin. Subjects with arterial hypertension (essential, secondary) may become normotensive during the development...... of cirrhosis, and arterial hypertension is rarely manifested in patients with cirrhosis, even in cases with renovascular disease and high circulating renin activity. There is much dispute as to the understanding of homoeostatic regulation in cirrhotic patients with manifest arterial hypertension. This most...

  17. Hypertension and liver disease

    DEFF Research Database (Denmark)

    Henriksen, Jens H; Møller, Søren

    2004-01-01

    to increased arterial blood pressure. Subjects with established arterial hypertension (essential, secondary) may become normotensive during the development of cirrhosis, and arterial hypertension is rarely manifested in patients with cirrhosis, even in cases with renovascular disease and high circulating renin......Arterial hypertension is a common disorder with a frequency of 10% to 15% in subjects in the 40- to 60-year age group. Yet most reports find the prevalence of arterial hypertension in patients with chronic liver disease (cirrhosis) much lower. In this review, we consider the alterations in systemic...... hemodynamics in cirrhosis. The most characteristic findings in cirrhotic patients are vasodilatation with low systemic vascular resistance, increased cardiac output, high arterial compliance, secondary activation of counterregulatory systems (sympathetic nervous system, renin-angiotensin-aldosterone system...

  18. Secondary hypertension in adults.

    Science.gov (United States)

    Puar, Troy Hai Kiat; Mok, Yingjuan; Debajyoti, Roy; Khoo, Joan; How, Choon How; Ng, Alvin Kok Heong

    2016-05-01

    Secondary hypertension occurs in a significant proportion of adult patients (~10%). In young patients, renal causes (glomerulonephritis) and coarctation of the aorta should be considered. In older patients, primary aldosteronism, obstructive sleep apnoea and renal artery stenosis are more prevalent than previously thought. Primary aldosteronism can be screened by taking morning aldosterone and renin levels, and should be considered in patients with severe, resistant or hypokalaemia-associated hypertension. Symptoms of obstructive sleep apnoea should be sought. Worsening of renal function after starting an angiotensin-converting enzyme inhibitor suggests the possibility of renal artery stenosis. Recognition, diagnosis and treatment of secondary causes of hypertension lead to good clinical outcomes and the possible reversal of end-organ damage, in addition to blood pressure control. As most patients with hypertension are managed at the primary care level, it is important for primary care physicians to recognise these conditions and refer patients appropriately. Copyright: © Singapore Medical Association.

  19. Pulmonary Hypertension Overview

    Science.gov (United States)

    ... well as sleep apnea, are common causes of secondary pulmonary hypertension. Other causes include the following: Congestive heart failure Birth defects in the heart Chronic pulmonary thromboembolism (blood clots in the pulmonary arteries) Acquired immunodeficiency syndrome ( ...

  20. Hypertension and Anaesthesia

    African Journals Online (AJOL)

    worldwide, and is a major risk factor for coronary artery disease, myocardial ... pressure falls in different categories of systolic and diastolic pressure the higher ... Without this consensus, the management of the elderly hypertensive patient.

  1. Diabetes + Hypertension (comorbidity)

    Data.gov (United States)

    Allegheny County / City of Pittsburgh / Western PA Regional Data Center — This data set provides de-identified population data for diabetes and hypertension comorbidity prevalence in Allegheny County.

  2. Understanding idiopathic intracranial hypertension

    DEFF Research Database (Denmark)

    Markey, Keira A; Mollan, Susan P; Jensen, Rigmor H

    2016-01-01

    Idiopathic intracranial hypertension is a disorder characterised by raised intracranial pressure that predominantly affects young, obese women. Pathogenesis has not been fully elucidated, but several causal factors have been proposed. Symptoms can include headaches, visual loss, pulsatile tinnitus...

  3. High Blood Pressure (Hypertension)

    Science.gov (United States)

    ... Print Page Text Size: A A A Listen High Blood Pressure (Hypertension) Nearly 1 in 3 American adults has ... weight. How Will I Know if I Have High Blood Pressure? High blood pressure is a silent problem — you ...

  4. Hypertension and cardiac arrhythmias

    DEFF Research Database (Denmark)

    Lip, Gregory Y.H.; Coca, Antonio; Kahan, Thomas

    2017-01-01

    Hypertension is a common cardiovascular risk factor leading to heart failure (HF), coronary artery disease, stroke, peripheral artery disease and chronic renal insufficiency. Hypertensive heart disease can manifest as many cardiac arrhythmias, most commonly being atrial fibrillation (AF). Both...... supraventricular and ventricular arrhythmias may occur in hypertensive patients, especially in those with left ventricular hypertrophy (LVH) or HF. Also, some of the antihypertensive drugs commonly used to reduce blood pressure, such as thiazide diuretics, may result in electrolyte abnormalities (e.g. hypokalaemia......, hypomagnesemia), further contributing to arrhythmias, whereas effective control of blood pressure may prevent the development of the arrhythmias such as AF. In recognizing this close relationship between hypertension and arrhythmias, the European Heart Rhythm Association (EHRA) and the European Society...

  5. Diabetes Mellitus and Hypertension

    OpenAIRE

    Tuğrul, Armağan

    2014-01-01

    Hypertension is a major worldwide health problem. Its prevalence is 1.5-2 times higher in diabetic population than that in non-diabetic individuals. Its pathogenesis depends on diabetic nephropathy in type 1, whereas may be multifactorial in type 2 diabetes mellitus. In diabetics, angiotensin converting enzyme inhibitors are most widely preferred in the treatment of hypertension because of their numerous desirable effects. In this article, the most recent data are presented on the relationshi...

  6. Hypertension og hjernen

    DEFF Research Database (Denmark)

    Christensen, Hanne; Strandgaard, Svend

    2009-01-01

    Hypertension is a major and modifiable risk factor of stroke and dementia. Hypertension causes remodelling of the cerebral resistance vessels, impairing their tolerance to very low blood pressure. In primary prevention of stroke, the effect of beta-blockers is inferior to other classes...... of antihypertensives. In secondary prevention of stroke, ACE-inhibitors and angiotensin blockers may be recommended as first choice drugs. Lowering of the blood pressure is, however, more important than the choice of drug. Udgivelsesdato: 2009-Jun-8...

  7. Cervical Spondylosis and Hypertension

    OpenAIRE

    Peng, Baogan; Pang, Xiaodong; Li, Duanming; Yang, Hong

    2015-01-01

    Abstract Cervical spondylosis and hypertension are all common diseases, but the relationship between them has never been studied. Patients with cervical spondylosis are often accompanied with vertigo. Anterior cervical discectomy and fusion is an effective method of treatment for cervical spondylosis with cervical vertigo that is unresponsive to conservative therapy. We report 2 patients of cervical spondylosis with concomitant cervical vertigo and hypertension who were treated successfully w...

  8. Thromboembolic chronicle pulmonary Hypertension

    International Nuclear Information System (INIS)

    Ovalle, Amador

    2003-01-01

    The thromboembolic chronicle pulmonary Hypertension, also well known as chronic lung thromboembolism not resolved; it is a form not very common of lung thromboembolism. Until very recently was considered a rare curiosity of autopsy, but as the methods of diagnoses have improved and our attitude has changed, the incidence of this nosological entity has experienced a notable increment, but the most excellent in this illness is maybe that it is a form of lung hypertension, potentially recoverable

  9. Renovascular hypertension: bibliographic review

    International Nuclear Information System (INIS)

    Cruz Guzman, Luis Fernando

    2011-01-01

    A review of the literature on the management of the renovascular disease is performed to provide better attention to patients. Renovascular hypertension is defined. The clinical implications and complications of the disease are determined. Pharmacological and surgical management are specified. Endovascular therapy has allowed to determine some indication in the management of hypertension renovascular. Instances where endovascular therapy has been beneficial are detailed. The new interventions for the management of renovascular disease are exposed [es

  10. Definition, classification, and epidemiology of pulmonary arterial hypertension.

    Science.gov (United States)

    Hoeper, Marius M

    2009-08-01

    Pulmonary arterial hypertension (PAH) is a distinct subgroup of pulmonary hypertension that comprises idiopathic PAH, familial/heritable forms, and PAH associated with connective tissue disease, congenital heart disease, portal hypertension, human immunodeficiency virus (HIV) infection, and some other conditions. The hemodynamic definition of PAH was recently revised: PAH is now defined by a mean pulmonary artery pressure at rest > or =25 mm Hg in the presence of a pulmonary capillary wedge pressure or =30 mm Hg during exercise) that was used in the old definition of PAH has been removed because there are no robust data that would allow defining an upper limit of normal for the pulmonary pressure during exercise. The revised classification of pulmonary hypertension still consists of five major groups: (1) PAH, (2) pulmonary hypertension due to left heart disease, (3) pulmonary hypertension due to chronic lung disease and/or hypoxia, (4) chronic thromboembolic pulmonary hypertension, and (5) miscellaneous forms. Modifications have been made in some of these groups, such as the addition of schistosomiasis-related pulmonary hypertension and pulmonary hypertension in patients with chronic hemolytic anemia to group 1.

  11. Biology of portal hypertension.

    Science.gov (United States)

    McConnell, Matthew; Iwakiri, Yasuko

    2018-02-01

    Portal hypertension develops as a result of increased intrahepatic vascular resistance often caused by chronic liver disease that leads to structural distortion by fibrosis, microvascular thrombosis, dysfunction of liver sinusoidal endothelial cells (LSECs), and hepatic stellate cell (HSC) activation. While the basic mechanisms of LSEC and HSC dysregulation have been extensively studied, the role of microvascular thrombosis and platelet function in the pathogenesis of portal hypertension remains to be clearly characterized. As a secondary event, portal hypertension results in splanchnic and systemic arterial vasodilation, leading to the development of a hyperdynamic circulatory syndrome and subsequently to clinically devastating complications including gastroesophageal varices and variceal hemorrhage, hepatic encephalopathy from the formation of portosystemic shunts, ascites, and renal failure due to the hepatorenal syndrome. This review article discusses: (1) mechanisms of sinusoidal portal hypertension, focusing on HSC and LSEC biology, pathological angiogenesis, and the role of microvascular thrombosis and platelets, (2) the mesenteric vasculature in portal hypertension, and (3) future directions for vascular biology research in portal hypertension.

  12. Genetic epidemiology of hypertension: an update on the African diaspora.

    Science.gov (United States)

    Daniel, Harold I; Rotimi, Charles N

    2003-01-01

    Hypertension is a serious global public health problem, affecting approximately 600 million people worldwide. The lifetime risk of developing the condition exceeds 50% in most populations. Despite considerable success in the pharmacological treatment of hypertension in all-human populations, the health-care community still lacks understanding of how and why individuals develop chronically elevated blood pressure. This gap in knowledge, and the high prevalence of hypertension and associated complications in some populations of African descent, have led some to conclude that hypertension is a "different disease" in people of African descent. Despite considerable evidence from epidemiologic studies showing that blood pressure distribution in populations of the African diaspora spans the known spectrum for all human populations, theories in support of unique "defects" among populations of African descent continue to gain wide acceptance. To date, no known environmental factors or genetic variants relevant to the pathophysiology of human hypertension have been found to be unique to Black populations. However, available genetic epidemiologic data demonstrate differential distributions of risk factors that are consistent with current environmental and geographic origins. This review summarizes the available evidence and demonstrates that as the exposure to known risk factors for hypertension (eg, excess consumption of salt and calories, stress, sedentary lifestyle, and degree of urbanization) increases among genetically susceptible individuals, the prevalence of hypertension and associated complications also increases across populations of the African diaspora. This observation is true for all human populations.

  13. Unilateral Carotid Body Resection in Resistant Hypertension

    Directory of Open Access Journals (Sweden)

    Krzysztof Narkiewicz, MD

    2016-08-01

    Full Text Available Animal and human data indicate pathological afferent signaling emanating from the carotid body that drives sympathetically mediated elevations in blood pressure in conditions of hypertension. This first-in-man, proof-of-principle study tested the safety and feasibility of unilateral carotid body resection in 15 patients with drug-resistant hypertension. The procedure proved to be safe and feasible. Overall, no change in blood pressure was found. However, 8 patients showed significant reductions in ambulatory blood pressure coinciding with decreases in sympathetic activity. The carotid body may be a novel target for treating an identifiable subpopulation of humans with hypertension.

  14. Virgin Olive Oil and Hypertension.

    Science.gov (United States)

    Lopez, Sergio; Bermudez, Beatriz; Montserrat-de la Paz, Sergio; Jaramillo, Sara; Abia, Rocio; Muriana, Francisco Jg

    2016-01-01

    The incidence of high blood pressure (BP) along with other cardiovascular (CV) risk factors on human health has been studied for many years. These studies have proven a link between unhealthy dietary habits and sedentary lifestyle with the onset of hypertension, which is a hallmark of CV and cerebrovascular diseases. The Mediterranean diet, declared by the UNESCO as an Intangible Cultural Heritage since 2013, is rich in vegetables, legumes, fruits and virgin olive oil. Thanks to its many beneficial effects, including those with regard to lowering BP, the Mediterranean diet may help people from modern countries to achieve a lower occurrence of CV disease. Data from human and animal studies have shown that the consumption of virgin olive oil shares most of the beneficial effects of the Mediterranean diet. Virgin olive oil is the only edible fat that can be consumed as a natural fruit product with no additives or preservatives, and contains a unique constellation of bioactive entities, namely oleic acid and minor constituents. In this review, we summarize what is known about the effects of virgin olive oil on hypertension.

  15. Mendelian randomization studies do not support a causal role for reduced circulating adiponectin levels in insulin resistance and type 2 diabetes

    NARCIS (Netherlands)

    H. Yaghootkar (Hanieh); C. Lamina (Claudia); R.A. Scott (Robert); Z. Dastani (Zari); M.-F. Hivert (Marie-France); L.L. Warren (Liling); A. Stancáková (Alena); S.G. Buxbaum (Sarah); L.-P. Lyytikäinen (Leo-Pekka); P. Henneman (Peter); Y. Wu (Ying); C.Y.Y. Cheung (Chloe); J.S. Pankow (James); A.U. Jackson (Anne); S. Gustafsson (Stefan); J.H. Zhao (Jing Hua); C. Ballantyne (Christie); W. Xie (Weijia); R.N. Bergman (Richard); M. Boehnke (Michael); F. El Bouazzaoui (Fatiha); F.S. Collins (Francis); S.H. Dunn (Sandra); J. Dupuis (Josée); N.G. Forouhi (Nita); C.J. Gillson (Christopher); A.T. Hattersley (Andrew); J. Hong (Jaeyoung); M. Kähönen (Mika); J. Kuusisto (Johanna); L. Kedenko (Lyudmyla); F. Kronenberg (Florian); A. Doria (Andrea); T.L. Assimes (Themistocles); E. Ferrannini (Ele); T. Hansen (Torben); K. Hao (Ke); H. Häring (Hans); J.W. Knowles (Joshua); C.M. Lindgren (Cecilia); J.J. Nolan (John); J. Paananen (Jussi); O. Pedersen (Oluf); T. Quertermous (Thomas); U. Smith (Ulf); T. Lehtimäki (Terho); C.-T. Liu (Ching-Ti); R.J.F. Loos (Ruth); M.I. McCarthy (Mark); A.D. Morris (Andrew); R.S. Vasan (Ramachandran Srini); T.D. Spector (Timothy); T.M. Teslovich (Tanya); J. Tuomilehto (Jaakko); J.A.P. Willems van Dijk (Ko); J. Viikari (Jorma); N. Zhu (Na); C. Langenberg (Claudia); E. Ingelsson (Erik); R.K. Semple (Robert); A. Sinaiko (Alan); C.N.A. Palmer (Colin); M. Walker (Mark); K.S.L. Lam (Karen); B. Paulweber (Bernhard); K.L. Mohlke (Karen); C.M. van Duijn (Cornelia); O. Raitakari (Olli); A. Bidulescu (Aurelian); N.J. Wareham (Nick); M. Laakso (Markku); D. Waterworth (Dawn); D.A. Lawlor (Debbie); J.B. Meigs (James); J.B. Richards (Brent); T.M. Frayling (Timothy)

    2013-01-01

    textabstractAdiponectin is strongly inversely associated with insulin resistance and type 2 diabetes, but its causal role remains controversial. We used a Mendelian randomization approach to test the hypothesis that adiponectin causally influences insulin resistance and type 2 diabetes. We used

  16. Mendelian Randomisation Studies Do Not Support a Causal Role for Reduced Circulating Adiponectin Levels in Insulin Resistance and Type 2 Diabetes

    DEFF Research Database (Denmark)

    Yaghootkar, Hanieh; Lamina, Claudia; Scott, Robert A

    2013-01-01

    Adiponectin is strongly inversely associated with insulin resistance and type 2 diabetes but its causal role remains controversial. We used a Mendelian randomisation approach to test the hypothesis that adiponectin causally influences insulin resistance and type 2 diabetes. We used genetic varian...

  17. Directional dominance on stature and cognition in diverse human populations

    NARCIS (Netherlands)

    Joshi, Peter K.; Esko, Tonu; Mattsson, Hannele; Eklund, Niina; Gandin, Ilaria; Nutile, Teresa; Jackson, Anne U.; Schurmann, Claudia; Smith, Albert V.; Zhang, Weihua; Okada, Yukinori; Stancakova, Alena; Faul, Jessica D.; Zhao, Wei; Bartz, Traci M.; Concas, Maria Pina; Franceschini, Nora; Enroth, Stefan; Vitart, Veronique; Trompet, Stella; Guo, Xiuqing; Chasman, Daniel I.; O'Connel, Jeffrey R.; Corre, Tanguy; Nongmaithem, Suraj S.; Chen, Yuning; Mangino, Massimo; Ruggiero, Daniela; Traglia, Michela; Farmaki, Aliki-Eleni; Kacprowski, Tim; Bjonnes, Andrew; van der Spek, Ashley; Wu, Ying; Giri, Anil K.; Yanek, Lisa R.; Wang, Lihua; Hofer, Edith; Rietveld, Cornelius A.; McLeod, Olga; Cornelis, Marilyn C.; Pattaro, Cristian; Verweij, Niek; Baumbach, Clemens; Abdellaoui, Abdel; Warren, Helen R.; Vuckovic, Dragana; Mei, Hao; Bouchard, Claude; Perry, John R. B.; Cappellani, Stefania; Mirza, Saira S.; Benton, Miles C.; Broeckel, Ulrich; Medland, Sarah E.; Lind, PenelopeA.; Malerba, Giovanni; Drong, Alexander; Yengo, Loic; Bielak, Lawrence F.; Zhi, Degui; van der Most, Peter J.; Shriner, Daniel; Maegi, Reedik; Hemani, Gibran; Karaderi, Tugce; Wang, Zhaoming; Liu, Tian; Demuth, Ilja; Zhao, Jing Hua; Meng, Weihua; Lataniotis, Lazaros; van der Laan, Sander W.; Bradfield, Jonathan P.; Wood, Andrew R.; Bonnefond, Amelie; Ahluwalia, Tarunveer S.; Hall, LeanneM.; Salvi, Erika; Yazar, Seyhan; Carstensen, Lisbeth; de Haan, Hugoline G.; Abney, Mark; Afzal, Uzma; Allison, Matthew A.; Amin, Najaf; Asselbergs, Folkert W.; Bakker, Stephan J. L.; Barr, R. Graham; Baumeister, Sebastian E.; Benjamin, Daniel J.; Bergmann, Sven; Boerwinkle, Eric; Bottinger, Erwin P.; Campbell, Archie; Chakravarti, Aravinda; Chan, Yingleong; Chanock, Stephen J.; Chen, Constance; Chen, Y. -D. Ida; Collins, Francis S.; Connell, John; Correa, Adolfo; Cupples, L. Adrienne; Smith, George Davey; Davies, Gail; Doerr, Marcus; Ehret, Georg; Ellis, Stephen B.; Feenstra, Bjarke; Feitosa, Mary F.; Ford, Ian; Fox, Caroline S.; Frayling, Timothy M.; Friedrich, Nele; Geller, Frank; Scotland, Generation; Gillham-Nasenya, Irina; Gottesman, Omri; Graff, Misa; Grodstein, Francine; Gu, Charles; Haley, Chris; Hammond, Christopher J.; Harris, Sarah E.; Harris, Tamara B.; Hastie, Nicholas D.; Heard-Costa, Nancy L.; Heikkila, Kauko; Hocking, Lynne J.; Homuth, Georg; Hottenga, Jouke-Jan; Huang, Jinyan; Huffman, Jennifer E.; Hysi, Pirro G.; Ikram, M. Arfan; Ingelsson, Erik; Joensuu, Anni; Johansson, Asa; Jousilahti, Pekka; Jukema, J. Wouter; Kahonen, Mika; Kamatani, Yoichiro; Kanoni, Stavroula; Kerr, Shona M.; Khan, Nazir M.; Koellinger, Philipp; Koistinen, Heikki A.; Kooner, Manraj K.; Kubo, Michiaki; Kuusisto, Johanna; Lahti, Jari; Launer, Lenore J.; Lea, Rodney A.; Lehne, Benjamin; Lehtimaki, Terho; Liewald, David C. M.; Lind, Lars; Loh, Marie; Lokki, Marja-Liisa; London, Stephanie J.; Loomis, Stephanie J.; Loukola, Anu; Lu, Yingchang; Lumley, Thomas; Lundqvist, Annamari; Mannisto, Satu; Marques-Vidal, Pedro; Masciullo, Corrado; Matchan, Angela; Mathias, Rasika A.; Matsuda, Koichi; Meigs, James B.; Meisinger, Christa; Meitinger, Thomas; Menni, Cristina; Mentch, Frank D.; Mihailov, Evelin; Milani, Lili; Montasser, May E.; Montgomery, GrantW.; Morrison, Alanna; Myers, Richard H.; Nadukuru, Rajiv; Navarro, Pau; Nelis, Mari; Nieminen, Markku S.; Nolte, Ilja M.; O'Connor, George T.; Ogunniyi, Adesola; Padmanabhan, Sandosh; Palmas, Walter R.; Pankow, James S.; Patarcic, Inga; Pavani, Francesca; Peyser, Patricia A.; Pietilainen, Kirsi; Poulter, Neil; Prokopenko, Inga; Ralhan, Sarju; Redmond, Paul; Rich, Stephen S.; Rissanen, Harri; Robino, Antonietta; Rose, Lynda M.; Rose, Richard; Sala, Cinzia; Salako, Babatunde; Salomaa, Veikko; Sarin, Antti-Pekka; Saxena, Richa; Schmidt, Helena; Scott, Laura J.; Scott, William R.; Sennblad, Bengt; Seshadri, Sudha; Sever, Peter; Shrestha, Smeeta; Smith, Blair H.; Smith, Jennifer A.; Soranzo, Nicole; Sotoodehnia, Nona; Southam, Lorraine; Stanton, Alice V.; Stathopoulou, Maria G.; Strauch, Konstantin; Strawbridge, Rona J.; Suderman, Matthew J.; Tandon, Nikhil; Tang, Sian-Tsun; Taylor, Kent D.; Tayo, Bamidele O.; Toeglhofer, Anna Maria; Tomaszewski, Maciej; Tsernikova, Natalia; Tuomilehto, Jaakko; Uitterlinden, Andre G.; Vaidya, Dhananjay; Vlieg, Astrid van Hylckama; van Setten, Jessica; Vasankari, Tuula; Vedantam, Sailaja; Vlachopoulou, Efthymia; Vozzi, Diego; Vuoksimaa, Eero; Waldenberger, Melanie; Ware, Erin B.; Wentworth-Shields, William; Whitfield, John B.; Wild, Sarah; Willemsen, Gonneke; Yajnik, Chittaranjan S.; Yao, Jie; Zaza, Gianluigi; Zhu, Xiaofeng; Salem, Rany M.; Melbye, Mads; Bisgaard, Hans; Samani, Nilesh J.; Cusi, Daniele; Mackey, David A.; Cooper, Richard S.; Froguel, Philippe; Pasterkamp, Gerard; Grant, Struan F. A.; Hakonarson, Hakon; Ferrucci, Luigi; Scott, Robert A.; Morris, Andrew D.; Palmer, Colin N. A.; Dedoussis, George; Deloukas, Panos; Bertram, Lars; Lindenberger, Ulman; Berndt, Sonja I.; Lindgren, Cecilia M.; Timpson, Nicholas J.; Toenjes, Anke; Munroe, Patricia B.; Sorensen, Thorkild I. A.; Rotimi, Charles N.; Arnett, Donna K.; Oldehinkel, Albertine J.; Kardia, Sharon L. R.; Balkau, Beverley; Gambaro, Giovanni; Morris, Andrew P.; Eriksson, Johan G.; Wright, Margie J.; Martin, Nicholas G.; Hunt, Steven C.; Starr, John M.; Deary, Ian J.; Griffiths, Lyn R.; Tiemeier, Henning; Pirastu, Nicola; Kaprio, Jaakko; Wareham, Nicholas J.; Perusse, Louis; Wilson, James G.; Girotto, Giorgia; Caulfield, Mark J.; Raitakari, Olli; Boomsma, Dorret I.; Gieger, Christian; van der Harst, Pim; Hicks, Andrew A.; Kraft, Peter; Sinisalo, Juha; Knekt, Paul; Johannesson, Magnus; Magnusson, Patrik K. E.; Hamsten, Anders; Schmidt, Reinhold; Borecki, Ingrid B.; Vartiainen, Erkki; Becker, Diane M.; Bharadwaj, Dwaipayan; Mohlke, Karen L.; Boehnke, Michael; van Duijn, Cornelia M.; Sanghera, Dharambir K.; Teumer, Alexander; Zeggini, Eleftheria; Metspalu, Andres; Gasparini, Paolo; Ulivi, Sheila; Ober, Carole; Toniolo, Daniela; Rudan, Igor; Porteous, David J.; Ciullo, Marina; Spector, Tim D.; Hayward, Caroline; Dupuis, Josee; Loos, Ruth J. F.; Wright, Alan F.; Chandak, Giriraj R.; Vollenweider, Peter; Shuldiner, Alan R.; Ridker, Paul M.; Rotter, Jerome I.; Sattar, Naveed; Gyllensten, Ulf; North, Kari E.; Pirastu, Mario; Psaty, Bruce M.; Weir, David R.; Laakso, Markku; Gudnason, Vilmundur; Takahashi, Atsushi; Chambers, John C.; Kooner, Jaspal S.; Strachan, David P.; Campbell, Harry; Hirschhorn, Joel N.; Perola, Markus; Polasek, Ozren; Wilson, James F.

    2015-01-01

    Homozygosity has long been associated with rare, often devastating, Mendelian disorders(1), and Darwin was one of the first to recognize that inbreeding reduces evolutionary fitness(2). However, the effect of the more distant parental relatedness that is common in modern human populations is less

  18. Directional dominance on stature and cognition in diverse human populations

    NARCIS (Netherlands)

    P.K. Joshi (Peter); T. Esko (Tõnu); H. Mattsson (Hannele); N. Eklund (Niina); I. Gandin (Ilaria); T. Nutile; A.U. Jackson (Anne); C. Schurmann (Claudia); G.D. Smith; W. Zhang (Weihua); Y. Okada (Yukinori); A. Stancáková (Alena); J.D. Faul (Jessica D.); W. Zhao (Wei); T.M. Bartz (Traci M.); M.P. Concas (Maria Pina); N. Franceschini (Nora); S. Enroth (Stefan); V. Vitart (Veronique); S. Trompet (Stella); X. Guo (Xiuqing); D.I. Chasman (Daniel); J.R. O'Connel (Jeffrey R.); T. Corre (Tanguy); S.S. Nongmaithem (Suraj S.); Y. Chen (Yuning); M. Mangino (Massimo); D. Ruggiero; M. Traglia (Michela); A.-E. Farmaki (Aliki-Eleni); T. Kacprowski (Tim); A. Bjonnes (Andrew); A. van der Spek (Ashley); Y. Wu (Ying); A.K. Giri (Anil K.); L.R. Yanek (Lisa); L. Wang (Lihua); E. Hofer (Edith); C.A. Rietveld (Niels); O. McLeod (Olga); M. Cornelis (Marilyn); C. Pattaro (Cristian); N. Verweij (Niek); C. Baumbach (Clemens); A. Abdellaoui (Abdel); H. Warren (Helen); D. Vuckovic (Dragana); H. Mei (Hao); C. Bouchard (Claude); J.R.B. Perry (John); S. Cappellani (Stefania); S.S. Mirza (Saira); M.C. Benton (Miles C.); U. Broeckel (Ulrich); S.E. Medland (Sarah Elizabeth); P.A. Lind (Penelope); G. Malerba (Giovanni); A. Drong (Alexander); L. Yengo (Loic); L.F. Bielak (Lawrence F.); D. Zhi (Degui); P.J. van der Most (Peter); D. Shriner (Daniel); R. Mägi (Reedik); G. Hemani; T. Karaderi (Tugce); Z. Wang (Zhaoming); T. Liu (Tian); I. Demuth (Ilja); J.H. Zhao (Jing Hua); W. Meng (Weihua); L. Lataniotis (Lazaros); S.W. Van Der Laan (Sander W.); J.P. Bradfield (Jonathan); A.R. Wood (Andrew); A. Bonnefond (Amélie); T.S. Ahluwalia (Tarunveer Singh); L.M. Hall (Leanne M.); E. Salvi (Erika); S. Yazar (Seyhan); L. Carstensen (Lisbeth); H.G. De Haan (Hugoline G.); M. Abney (Mark); U. Afzal (Uzma); M.A. Allison (Matthew); N. Amin (Najaf); F.W. Asselbergs (Folkert W.); S.J.L. Bakker (Stephan); R.G. Barr (Graham); S.E. Baumeister (Sebastian); D.J. Benjamin (Daniel J.); S. Bergmann (Sven); E.A. Boerwinkle (Eric); E.P. Bottinger (Erwin P.); A. Campbell (Archie); A. Chakravarti (Aravinda); Y. Chan (Yingleong); S.J. Chanock (Stephen); C. Chen (Constance); Y.-D.I. Chen (Y.-D. Ida); F.S. Collins (Francis); J. Connell (John); A. Correa (Adolfo); L.A. Cupples (Adrienne); G.D. Smith; G. Davies (Gail); M. Dörr (Marcus); G.B. Ehret (Georg); S.B. Ellis (Stephen B.); B. Feenstra (Bjarke); M.F. Feitosa (Mary Furlan); I. Ford; C.S. Fox (Caroline); T.M. Frayling (Timothy); N. Friedrich (Nele); F. Geller (Frank); G. Scotland (Generation); I. Gillham-Nasenya (Irina); R.F. Gottesman (Rebecca); M.J. Graff (Maud J.L.); F. Grodstein (Francine); C. Gu (Charles); C. Haley (Chris); C.J. Hammond (Christopher); S.E. Harris (Sarah); T.B. Harris (Tamara); N. Hastie (Nick); N.L. Heard-Costa (Nancy); K. Heikkilä (Kauko); L.J. Hocking (Lynne); G. Homuth (Georg); J.J. Hottenga (Jouke Jan); J. Huang (Jian); J.E. Huffman (Jennifer); P.G. Hysi (Pirro); M.A. Ikram (Arfan); E. Ingelsson (Erik); A. Joensuu (Anni); A. Johansson (Åsa); P. Jousilahti (Pekka); J.W. Jukema (Jan Wouter); M. Kähönen (Mika); Y. Kamatani (Yoichiro); S. Kanoni (Stavroula); S.M. Kerr (Shona); N.M. Khan (Nazir M.); Ph.D. Koellinger (Philipp); H.A. Koistinen (Heikki A.); M.K. Kooner (Manraj K.); M. Kubo (Michiaki); J. Kuusisto (Johanna); J. Lahti (Jari); L.J. Launer (Lenore); R.A. Lea (Rodney A.); B. Lehne (Benjamin); T. Lehtimäki (Terho); D.C. Liewald (David C.); L. Lind (Lars); M. Loh (Marie); M.L. Lokki; S.J. London (Stephanie J.); S.J. Loomis (Stephanie J.); A. Loukola (Anu); Y. Lu (Yingchang); T. Lumley (Thomas); A. Lundqvist (Annamari); S. Männistö (Satu); P. Marques-Vidal (Pedro); C. Masciullo (Corrado); A. Matchan (Angela); J. Mathias (Jasmine); K. Matsuda (Koichi); J.B. Meigs (James); C. Meisinger (Christa); T. Meitinger (Thomas); C. Menni (Cristina); F.D. Mentch (Frank); E. Mihailov (Evelin); L. Milani (Lili); M.E. Montasser (May E.); G.W. Montgomery (Grant); A.C. Morrison (Alanna); R.H. Myers (Richard); R. Nadukuru (Rajiv); P. Navarro (Pau); M. Nalis (Mari); M.S. Nieminen (Markku S.); I.M. Nolte (Ilja M.); G.T. O'Connor (George); A. Ogunniyi (Adesola); S. Padmanabhan (Sandosh); W. Palmas (Walter); J.S. Pankow (James); I. Patarcic (Inga); F. Pavani (Francesca); P.A. Peyser (Patricia A.); K.H. Pietilainen (Kirsi Hannele); N.R. Poulter (Neil); I. Prokopenko (Inga); S. Ralhan (Sarju); P. Redmond (Paul); S.S. Rich (Stephen S.); H. Rissanen (Harri); A. Robino (Antonietta); L.M. Rose (Lynda M.); R.J. Rose (Richard J.); C. Sala (Cinzia); B. Salako (Babatunde); V. Salomaa (Veikko); A.-P. Sarin; R. Saxena (Richa); R. Schmidt (Reinhold); L.J. Scott (Laura); W.R. Scott (William R.); B. Sennblad (Bengt); S. Seshadri (Sudha); P. Sever (Peter); S. Shrestha (Smeeta); B.H. Smith (Blair); J.A. Smith (Jennifer A); N. Soranzo (Nicole); N. Sotoodehnia (Nona); L. Southam (Lorraine); A. Stanton (Alice); M.G. Stathopoulou (Maria G); K. Strauch (Konstantin); R.J. Strawbridge (Rona); M.J. Suderman (Matthew J.); N. Tandon (Nikhil); S.-T. Tang (Sian-Tsun); K.D. Taylor (Kent D.); B. Tayo (Bamidele); A.M. Töglhofer (Anna Maria); M. Tomaszewski (Maciej); N. Tsernikova (Natalia); J. Tuomilehto (Jaakko); A.G. Uitterlinden (André); D. Vaidya (Dhananjay); A. van Hylckama Vlieg (Astrid); J. van Setten (Jessica); T. Vasankari (Tuula); S. Vedantam (Sailaja); E. Vlachopoulou (Efthymia); D. Vozzi (Diego); E. Vuoksimaa (Eero); M. Waldenberger (Melanie); E.B. Ware (Erin B.); W. Wentworth-Shields (William); J. Whitfield (John); S. Wild (Sarah); G.A.H.M. Willemsen (Gonneke); C.S. Yajnik (Chittaranjan S.); J. Yao (Jie); G. Zaza (Gianluigi); X. Zhu (Xiaofeng); R.M. Salem (Rany); M. Melbye (Mads); H. Bisgaard (Hans); N.J. Samani (Nilesh); D. Cusi (Daniele); D.A. Mackey (David A.); R.S. Cooper (Richard S.); P. Froguel (Philippe); G. Pasterkamp (Gerard); S.F.A. Grant (Struan F.A.); H. Hakonarson (Hakon); L. Ferrucci (Luigi); R.A. Scott (Robert); A.D. Morris (Andrew); C.N.A. Palmer (Colin); G.V. Dedoussis (George V.); P. Deloukas (Panagiotis); L. Bertram (Lars); U. Lindenberger (Ulman); S.I. Berndt (Sonja); C.M. Lindgren (Cecilia); N.J. Timpson (Nicholas); A. Tönjes (Anke); P. Munroe (Patricia); T.I.A. Sørensen (Thorkild I.A.); C. Rotimi (Charles); D.K. Arnett (Donna); A.J. Oldehinkel (Albertine); S.L.R. Kardia (Sharon); B. Balkau (Beverley); G. Gambaro (Giovanni); A.P. Morris (Andrew); J.G. Eriksson (Johan G.); M.J. Wright (Margaret); N.G. Martin (Nicholas); S.C. Hunt (Steven); J.M. Starr (John); I.J. Deary (Ian J.); L.R. Griffiths (Lyn R.); H.W. Tiemeier (Henning); N. Pirastu (Nicola); J. Kaprio (Jaakko); N.J. Wareham (Nick); L. Perusse (Louis); J.G. Wilson (James); S. Girotto; M. Caulfield (Mark); O.T. Raitakari (Olli T.); D.I. Boomsma (Dorret); C. Gieger (Christian); P. van der Harst; A.A. Hicks (Andrew); P. Kraft (Peter); J. Sinisalo (Juha); P. Knekt; M. Johannesson (Magnus); P.K.E. Magnusson (Patrik K. E.); A. Hamsten (Anders); R. Schmidt (Reinhold); I.B. Borecki (Ingrid); E. Vartiainen (Erkki); D.M. Becker (Diane); D. Bharadwaj (Dwaipayan); K.L. Mohlke (Karen); M. Boehnke (Michael); C.M. van Duijn (Cornelia); D.K. Sanghera (Dharambir); A. Teumer (Alexander); E. Zeggini (Eleftheria); A. Metspalu (Andres); P. Gasparini (Paolo); S. Ulivi (Shelia); C. Ober (Carole); D. Toniolo (Daniela); I. Rudan (Igor); D.J. Porteous (David J.); M. Ciullo; T.D. Spector (Timothy); C. Hayward (Caroline); J. Dupuis (Josée); R.J.F. Loos (Ruth); A. Wright (Alan); G.R. Chandak (Giriraj); P. Vollenweider (Peter); A.R. Shuldiner (Alan); P.M. Ridker (Paul); J.I. Rotter (Jerome I.); N. Sattar (Naveed); U. Gyllensten (Ulf); K.E. North (Kari); M. Pirastu (Mario); B.M. Psaty (Bruce); D.R. Weir (David); M. Laakso (Markku); V. Gudnason (Vilmundur); A. Takahashi (Atsushi); J.C. Chambers (John C.); J.S. Kooner (Jaspal S.); D.P. Strachan (David P.); H. Campbell (Harry); J.N. Hirschhorn (Joel N.); M. Perola (Markus); O. Polasek (Ozren); J.F. Wilson (James)

    2015-01-01

    textabstractHomozygosity has long been associated with rare, often devastating, Mendelian disorders, and Darwin was one of the first to recognize that inbreeding reduces evolutionary fitness. However, the effect of the more distant parental relatedness that is common in modern human populations is

  19. Assessing the Causal Relationship of Maternal Height on Birth Size and Gestational Age at Birth: A Mendelian Randomization Analysis

    Science.gov (United States)

    Zhang, Ge; Bacelis, Jonas; Lengyel, Candice; Teramo, Kari; Hallman, Mikko; Helgeland, Øyvind; Johansson, Stefan; Myhre, Ronny; Sengpiel, Verena; Njølstad, Pål Rasmus; Jacobsson, Bo; Muglia, Louis

    2015-01-01

    Background Observational epidemiological studies indicate that maternal height is associated with gestational age at birth and fetal growth measures (i.e., shorter mothers deliver infants at earlier gestational ages with lower birth weight and birth length). Different mechanisms have been postulated to explain these associations. This study aimed to investigate the casual relationships behind the strong association of maternal height with fetal growth measures (i.e., birth length and birth weight) and gestational age by a Mendelian randomization approach. Methods and Findings We conducted a Mendelian randomization analysis using phenotype and genome-wide single nucleotide polymorphism (SNP) data of 3,485 mother/infant pairs from birth cohorts collected from three Nordic countries (Finland, Denmark, and Norway). We constructed a genetic score based on 697 SNPs known to be associated with adult height to index maternal height. To avoid confounding due to genetic sharing between mother and infant, we inferred parental transmission of the height-associated SNPs and utilized the haplotype genetic score derived from nontransmitted alleles as a valid genetic instrument for maternal height. In observational analysis, maternal height was significantly associated with birth length (p = 6.31 × 10−9), birth weight (p = 2.19 × 10−15), and gestational age (p = 1.51 × 10−7). Our parental-specific haplotype score association analysis revealed that birth length and birth weight were significantly associated with the maternal transmitted haplotype score as well as the paternal transmitted haplotype score. Their association with the maternal nontransmitted haplotype score was far less significant, indicating a major fetal genetic influence on these fetal growth measures. In contrast, gestational age was significantly associated with the nontransmitted haplotype score (p = 0.0424) and demonstrated a significant (p = 0.0234) causal effect of every 1 cm increase in maternal

  20. Pregnancy with Portal Hypertension

    Science.gov (United States)

    Aggarwal, Neelam; Negi, Neha; Aggarwal, Aakash; Bodh, Vijay; Dhiman, Radha K.

    2014-01-01

    Even though pregnancy is rare with cirrhosis and advanced liver disease, but it may co-exist in the setting of non-cirrhotic portal hypertension as liver function is preserved but whenever encountered together is a complex clinical dilemma. Pregnancy in a patient with portal hypertension presents a special challenge to the obstetrician as so-called physiological hemodynamic changes associated with pregnancy, needed for meeting demands of the growing fetus, worsen the portal hypertension thereby putting mother at risk of potentially life-threatening complications like variceal hemorrhage. Risks of variceal bleed and hepatic decompensation increase many fold during pregnancy. Optimal management revolves round managing the portal hypertension and its complications. Thus management of such cases requires multi-speciality approach involving obstetricians experienced in dealing with high risk cases, hepatologists, anesthetists and neonatologists. With advancement in medical field, pregnancy is not contra-indicated in these women, as was previously believed. This article focuses on the different aspects of pregnancy with portal hypertension with special emphasis on specific cause wise treatment options to decrease the variceal bleed and hepatic decompensation. Based on extensive review of literature, management from pre-conceptional period to postpartum is outlined in order to have optimal maternal and perinatal outcomes. PMID:25755552

  1. Management of diabetic hypertensives

    Science.gov (United States)

    Ganesh, Jai; Viswanathan, Vijay

    2011-01-01

    Hypertension occurs twice as commonly in diabetics than in comparable nondiabetics. Patients with both disorders have a markedly higher risk for premature microvascular and macrovascular complications. Aggressive control of blood pressure (BP) reduces both micro- and macrovascular complications. In diabetic hypertensives, angiotensin converting enzyme inhibitors (ACEIs) are the first line in management of hypertension, and can be replaced by angiotensin II receptor blockers (ARBs) if patients are intolerant of them. Recent studies suggest ARBs to be on par with ACEI in reducing both macro- and microvascular risks. Adding both these agents may have a beneficial effect on proteinuria, but no extra macrovascular risk reduction. Thiazides can also be used as first line drugs, but are better used along with ACEI/ARBs. Beta-blockers [especially if the patient has coronary artery disease] and calcium channel blockers are used as second line add-on drugs. Multidrug regimens are commonly needed in diabetic hypertensives. Achieving the target BP of <130/80 is the priority rather than the drug combination used in order to arrest and prevent the progression of macro- and microvascular complications in diabetic hypertensives. PMID:22145142

  2. Hypertension in postmenopausal women: how to approach hypertension in menopause.

    Science.gov (United States)

    Modena, Maria Grazia

    2014-09-01

    During fertile life women are usually normo or hypotensive. Hypertension may appear during pregnancy and this represents a peculiar phenomenon increasing nowadays for delay time of pregnancy. Gestational hypertension appears partially similar to hypertension in the context of metabolic syndrome for a similar condition of increased waste circumference. Parity, for the same pathogenesis, has been reported to be associated to peri and postmenopausal hypertension, not confirmed by our study of parous women with transitional non persistent perimenopausal hypertension. Estrogen's deficiency inducing endothelial dysfunction and increased body mass index are the main cause for hypertension in this phase of life. For these reasons lifestyle modification, diet and endothelial active drugs represent the ideal treatment. Antioxidant agents may have a role in prevention and treatment of hypertension. In conclusion, hypertension in women represents a peculiar constellation of different biological and pathogenic factors, which need a specific gender related approach, independent from the male model.

  3. Investigating the possible causal role of coffee consumption with prostate cancer risk and progression using Mendelian randomization analysis

    DEFF Research Database (Denmark)

    Taylor, Amy E; Martin, Richard M; Geybels, Milan S

    2017-01-01

    Coffee consumption has been shown in some studies to be associated with lower risk of prostate cancer. However, it is unclear if this association is causal or due to confounding or reverse causality. We conducted a Mendelian randomisation analysis to investigate the causal effects of coffee...... consumption on prostate cancer risk and progression. We used two genetic variants robustly associated with caffeine intake (rs4410790 and rs2472297) as proxies for coffee consumption in a sample of 46,687 men of European ancestry from 25 studies in the PRACTICAL consortium. Associations between genetic...... variants and prostate cancer case status, stage and grade were assessed by logistic regression and with all-cause and prostate cancer-specific mortality using Cox proportional hazards regression. There was no clear evidence that a genetic risk score combining rs4410790 and rs2472297 was associated...

  4. [The leptin concentration in patients with primary arterial hypertension].

    Science.gov (United States)

    Jołda-Mydłowska, Beata; Przewłocka-Kosmala, Monika; Zyśko, Dorota; Gajek, Jacek; Mazurek, Walentyna

    2006-01-01

    Leptin seems to play a role in the pathogenesis of arterial hypertension by activation of the sympathetic nervous system, influencing water - electrolyte balance and vascular remodeling. It is not known whether leptin is a factor participating in the pathogenesis of primary arterial hypertension or its higher concentration in patients with arterial hypertension reflects only the presence of other factors leading to increased blood pressure. The aim of the study was to try to estimate the leptin participation in the development of the arterial hypertension, to evaluate the concentration of leptin in blood serum of patients with mild, moderate and severe arterial hypertension and to determine the relationships between the observed leptin concentration, arterial hypertension degree according to WHO criteria and body mass. The investigations were performed on 74 untreated patients aged 19-74 years (mean 47 +/- 12 years ). In this group there were 33 women aged 35-74 years (mean 51 +/- 10 years) and 41 men aged 19-73 years (mean 45 +/- 14 years). The mild arterial hypertension was observed in 24 patients, moderate hypertension in 34 patients and severe hypertension in 16. The obesity, identified when BMI was equal or higher than 30 kg/m2, was observed in 4 patients with mild hypertension, in 9 with moderate hypertension and in 6 with severe hypertension. All patients had normal renal function. The leptin concentration was determined by the radioimmunological method using the Human Leptin RIA Kit by LINCO Research, Inc. (Cat# HL-81 K). The analysis of the obtained results was performed using Statistica for Windows PL.V5.0. The concentration of leptin in patients with mild hypertension was 3.61 +/- 2.22 ng/ml, in patients with moderate hypertension was 12.65 +/- 8.48 and in patients with severe hypertension 33.51 +/- 28.45 ng/ml. The concentration of leptin in obese patients was 24.83 +/- 26.60 and in patients without obesity was 10.57 +/- 11.99 ng/ml. 1. In patients with

  5. Knowledge and awareness of hypertension among patients with systemic hypertension.

    Science.gov (United States)

    Familoni, B. Oluranti; Ogun, S. Abayomi; Aina, A. Olutoyin

    2004-01-01

    BACKGROUND: In Nigeria, systemic hypertension is the commonest noncommunicable disease, and public awareness about hypertension and its determinants is poor. This study aims to assess the knowledge and level of awareness of the disease among hypertensive patients attending the medical outpatient clinic of Olabisi Onabanjo University Teaching Hospital (OOUTH). METHODOLOGY: Hypertensive patients who attended the medical outpatient clinic during the one-year study period and gave their consent were recruited into the study. Response to a questionnaire on various aspects of hypertension was analyzed using the STATA for Windows software. RESULTS: There were 254 hypertensive patients, of which 111 were males and 143 were females, giving a male: female ratio of 1:1.3. The mean age (SD) of the patients was 51 years +/- 12.2; 52.4% of the participants were aware that hypertension was the commonest noncommunicable disease in Nigeria. About one in 10 patients (11.4%) was aware that "nil symptom" is the commonest symptom of hypertension, while 37% were not aware that hypertension could cause renal failure. Only about one-third (35.4%) of the patients knew that hypertension should ideally be treated for life, while 58.3% believed that antihypertensive drugs should be used only when there are symptoms. The remaining 6.3% believed that the treatment of hypertension should be for periods ranging from two weeks to five years but not for life. CONCLUSION: This study has demonstrated inadequate knowledge of hypertension in patients with hypertension in our study population. Conscious efforts should be made and time set aside to health educate hypertensive patients. Organization of "hypertensive club or society" could be encouraged. These will reduce dissemination of false or inaccurate information by hypertensive patients to the public and its attendant dangers. PMID:15160976

  6. Investigating causal associations between use of nicotine, alcohol, caffeine and cannabis: a two-sample bidirectional Mendelian randomization study.

    Science.gov (United States)

    Verweij, Karin J H; Treur, Jorien L; Vink, Jacqueline M

    2018-07-01

    Epidemiological studies consistently show co-occurrence of use of different addictive substances. Whether these associations are causal or due to overlapping underlying influences remains an important question in addiction research. Methodological advances have made it possible to use published genetic associations to infer causal relationships between phenotypes. In this exploratory study, we used Mendelian randomization (MR) to examine the causality of well-established associations between nicotine, alcohol, caffeine and cannabis use. Two-sample MR was employed to estimate bidirectional causal effects between four addictive substances: nicotine (smoking initiation and cigarettes smoked per day), caffeine (cups of coffee per day), alcohol (units per week) and cannabis (initiation). Based on existing genome-wide association results we selected genetic variants associated with the exposure measure as an instrument to estimate causal effects. Where possible we applied sensitivity analyses (MR-Egger and weighted median) more robust to horizontal pleiotropy. Most MR tests did not reveal causal associations. There was some weak evidence for a causal positive effect of genetically instrumented alcohol use on smoking initiation and of cigarettes per day on caffeine use, but these were not supported by the sensitivity analyses. There was also some suggestive evidence for a positive effect of alcohol use on caffeine use (only with MR-Egger) and smoking initiation on cannabis initiation (only with weighted median). None of the suggestive causal associations survived corrections for multiple testing. Two-sample Mendelian randomization analyses found little evidence for causal relationships between nicotine, alcohol, caffeine and cannabis use. © 2018 Society for the Study of Addiction.

  7. Arsenic metabolism efficiency has a causal role in arsenic toxicity: Mendelian randomization and gene-environment interaction.

    Science.gov (United States)

    Pierce, Brandon L; Tong, Lin; Argos, Maria; Gao, Jianjun; Farzana, Jasmine; Roy, Shantanu; Paul-Brutus, Rachelle; Rahaman, Ronald; Rakibuz-Zaman, Muhammad; Parvez, Faruque; Ahmed, Alauddin; Quasem, Iftekhar; Hore, Samar K; Alam, Shafiul; Islam, Tariqul; Harjes, Judith; Sarwar, Golam; Slavkovich, Vesna; Gamble, Mary V; Chen, Yu; Yunus, Mohammad; Rahman, Mahfuzar; Baron, John A; Graziano, Joseph H; Ahsan, Habibul

    2013-12-01

    Arsenic exposure through drinking water is a serious global health issue. Observational studies suggest that individuals who metabolize arsenic efficiently are at lower risk for toxicities such as arsenical skin lesions. Using two single nucleotide polymorphisms(SNPs) in the 10q24.32 region (near AS3MT) that show independent associations with metabolism efficiency, Mendelian randomization can be used to assess whether the association between metabolism efficiency and skin lesions is likely to be causal. Using data on 2060 arsenic-exposed Bangladeshi individuals, we estimated associations for two 10q24.32 SNPs with relative concentrations of three urinary arsenic species (representing metabolism efficiency): inorganic arsenic (iAs), monomethylarsonic acid(MMA) and dimethylarsinic acid (DMA). SNP-based predictions of iAs%, MMA% and DMA% were tested for association with skin lesion status among 2483 cases and 2857 controls. Causal odds ratios for skin lesions were 0.90 (95% confidence interval[CI]: 0.87, 0.95), 1.19 (CI: 1.10, 1.28) and 1.23 (CI: 1.12, 1.36)for a one standard deviation increase in DMA%, MMA% and iAs%,respectively. We demonstrated genotype-arsenic interaction, with metabolism-related variants showing stronger associations with skin lesion risk among individuals with high arsenic exposure (synergy index: 1.37; CI: 1.11, 1.62). We provide strong evidence for a causal relationship between arsenic metabolism efficiency and skin lesion risk. Mendelian randomization can be used to assess the causal role of arsenic exposure and metabolism in a wide array of health conditions.exposure and metabolism in a wide array of health conditions.Developing interventions that increase arsenic metabolism efficiency are likely to reduce the impact of arsenic exposure on health.

  8. Health system strengthening and hypertension management in China.

    Science.gov (United States)

    Huang, Kehui; Song, Yu Ting; He, Yong Huan; Feng, Xing Lin

    2016-01-01

    Non-communicable diseases are the leading causes of global burden of diseases, and hypertension is one of the most important risk factors. Hypertension prevalence doubled in China in the past decade and affects more than 300 million Chinese people. In the review we systematically searched peer-reviewed publications that link health system level factors with hypertension management in China and provide the current knowledge on how to improve a country's health system to manage the hypertension epidemic. A framework was developed to guide the review. The database of PubMed, CNKI were systematically searched from inception to April 13, 2016. Two authors independently screened the searched results for inclusion, conducted data extraction and appraised the quality of studies. Key findings were described according to the framework. Five hundred seventy-two publications were identified, where 11 articles were left according to the inclusion and exclusion criteria. The study periods range from 2010 to 2015. All about 11 researches linked health system factors to the outcome of hypertension management. And the outcomes were just focused on the awareness, treatment and control of hypertension but not hypertension incidence. One study is about the role of health system governance, investigating the performance of different organized community health care centers; three studies were about health financing comparing differences in insurance coverage; three studies were about health information practicing the hypertension guidelines of China or the WHO, and the rest three about mechanisms of health service delivery. No researches were identified about physical resources for health and human resources for health. Hypertension prevalence has been rising rapidly in China and the management of hypertension in China is a detection problem rather than treatment problem. Limited evidence shows the positive effect of health system factors on hypertension management and joint efforts

  9. Hypertension og nyresygdom

    DEFF Research Database (Denmark)

    Kamper, Anne-Lise; Pedersen, Erling B; Strandgaard, Svend

    2009-01-01

    Renal mechanisms, in particular the renin-angiotensin system and renal salt handling, are of major importance in blood pressure regulation. Co-existence of hypertension and decreased renal function may be due to nephrosclerosis secondary to hypertension, or primary renal disease with secondary...... hypertension. Mild degrees of chronic kidney disease (CKD) can be detected in around 10% of the population, and detection is important as CKD is an important risk factor for atherosclerotic cardiovascular disease. Conversely, heart failure may cause an impairment of renal function. In chronic progressive...... nephropathy, effective blood pressure lowering is of paramount importance, and angiotensin converting enzyme inhibitors and angiotensin receptor blockers are agents of choice. Udgivelsesdato: 2009-Jun-15...

  10. [Hypertension and renal disease

    DEFF Research Database (Denmark)

    Kamper, A.L.; Pedersen, E.B.; Strandgaard, S.

    2009-01-01

    Renal mechanisms, in particular the renin-angiotensin system and renal salt handling, are of major importance in blood pressure regulation. Co-existence of hypertension and decreased renal function may be due to nephrosclerosis secondary to hypertension, or primary renal disease with secondary...... hypertension. Mild degrees of chronic kidney disease (CKD) can be detected in around 10% of the population, and detection is important as CKD is an important risk factor for atherosclerotic cardiovascular disease. Conversely, heart failure may cause an impairment of renal function. In chronic progressive...... nephropathy, effective blood pressure lowering is of paramount importance, and angiotensin converting enzyme inhibitors and angiotensin receptor blockers are agents of choice Udgivelsesdato: 2009/6/15...

  11. Echocardiography in Arterial Hypertension.

    Science.gov (United States)

    de Simone, Giovanni; Mancusi, Costantino; Esposito, Roberta; De Luca, Nicola; Galderisi, Maurizio

    2018-05-02

    Hypertension is a condition characterized by pressure and/or volume overloads and echocardiography is helpful and feasible to understand hemodynamic mechanisms. Echocardiographic information is sometimes critical and susceptible of modifying decision making. In this review, we provide detailed descriptions of the parameters that can be derived from a standard transthoracic echocardiogram, including some more recent techniques. We will also explain how each parameter might have impact in the evaluation of the hypertensive patient and give indications on when to refer patients to echo-labs, which parameters are critical and which ones might be redundant, and how to use the information obtained in the report. Cardiac geometry, LV systolic and diastolic function, LV pump performance, output impedance and left atrial function are parameters that might be altered in arterial hypertension, but not necessarily doctors need the whole information for decision making. The critical measures are provided.

  12. [Hypertension in females].

    Science.gov (United States)

    Cífková, Renata

    2015-05-01

    Hypertension is the most common cardiovascular disorder affecting more males in younger age groups; in the age group of 45-64, it is equally frequent in both genders, it is more common in elderly females. Blood pressure increases more in females around the menopause. Use of hormonal replacement therapy is not associated with an BP increase but, because of increased risk of coronary events, stroke, and thromboembolic events, HRT is not re-commended in CVD prevention. There is a similar decrease in BP by antihypertensive drugs in both genders as well as benefit from antihypertensive treatment. Women report about a double rate of adverse events of antihypertensive drugs. Oral contraception use is associated with a mild BP increase in most women and development of overt hypertension in about 5 %. Pre-eclampsia is associated with increased risk of developing CVD later in life (more frequent development of hypertension, myocardial infarction, and stroke).

  13. Peripheral adrenergic receptors in hypertension

    NARCIS (Netherlands)

    Michel, M. C.; Brodde, O. E.; Insel, P. A.

    1990-01-01

    Increased sympathoadrenal activity appears to play an important role in the development or maintenance of elevated blood pressure in hypertensive patients and various animal models of hypertension. Alterations of adrenergic receptor number or responsiveness might contribute to this increased

  14. Radiation-induced renovascular hypertension

    International Nuclear Information System (INIS)

    Staab, G.E.; Tegtmeyer, C.J.; Constable, W.C.

    1976-01-01

    Radiation is known to produce changes in the small vessels and interstitium of the kidneys resulting in hypertension. Two cases of renal artery stenosis and resultant hypertension secondary to abdominal irradiation are reported and the literature is reviewed

  15. Pulmonary arterial hypertension : an update

    NARCIS (Netherlands)

    Hoendermis, E. S.

    2011-01-01

    Pulmonary arterial hypertension (PAH), defined as group 1 of the World Heart Organisation (WHO) classification of pulmonary hypertension, is an uncommon disorder of the pulmonary vascular system. It is characterised by an increased pulmonary artery pressure, increased pulmonary vascular resistance

  16. Knowing hypertension and diabetes

    DEFF Research Database (Denmark)

    Whyte, Susan Reynolds

    2015-01-01

    In Uganda, hypertension and diabetes have only recently been included in the health policy agenda. As they become treatable disorders, they take on more distinct contours in people's minds. This article relates knowledge about these two conditions to health institutions and technology...... for diagnosing and treating them. The response to the AIDS epidemic in Uganda provides an important context for, and contrast with, the emergence of hypertension and diabetes as social phenomena. Ethnographic fieldwork shows the interplay between experience of these conditions and the political economy...

  17. Idiopathic intracranial hypertension

    DEFF Research Database (Denmark)

    Yri, Hanne M; Jensen, Rigmor H

    2015-01-01

    AIMS: The aims of this article are to characterize the headache in idiopathic intracranial hypertension (IIH) and to field-test the ICHD diagnostic criteria for headache attributed to IIH. MATERIALS AND METHODS: We included 44 patients with new-onset IIH. Thirty-four patients with suspected but u...... tinnitus may suggest intracranial hypertension. Based on data from a well-defined IIH cohort, we propose a revision of the ICDH-3 beta diagnostic criteria with improved clinical applicability and increased sensitivity and specificity....

  18. Hypertension and renovascular disease

    DEFF Research Database (Denmark)

    Hasbak, P; Ibsen, H; Jensen, Lars Thorbjørn

    2002-01-01

    The clinical value of renal vein renin sampling (RVRS) as a prognostic tool in the treatment of renovascular hypertension was evaluated. One hundred consecutive patients were included over a 4-year period of time. About half of the patients (49%) were treated interventionally by PTRA (21%), nephr......The clinical value of renal vein renin sampling (RVRS) as a prognostic tool in the treatment of renovascular hypertension was evaluated. One hundred consecutive patients were included over a 4-year period of time. About half of the patients (49%) were treated interventionally by PTRA (21...

  19. Hyperuricemia in Childhood Primary Hypertension

    OpenAIRE

    Feig, Daniel I.; Johnson, Richard J.

    2003-01-01

    Experimental animal models suggest that uric acid might have a pathogenic role in the early development of primary hypertension. We hypothesized that serum uric acid is correlated with blood pressure in children with new-onset, untreated, primary hypertension. We evaluated 125 consecutive children referred to the Baylor Pediatric Renal Program for evaluation of hypertension. None of the subjects had previously been evaluated or treated for hypertension. The children ranged in age from 6 to 18...

  20. Hypertension and experimental stroke therapies

    OpenAIRE

    O'Collins, Victoria E; Donnan, Geoffrey A; Macleod, Malcolm R; Howells, David W

    2013-01-01

    Hypertension is an established target for long-term stroke prevention but procedures for management of hypertension in acute stroke are less certain. Here, we analyze basic science data to examine the impact of hypertension on candidate stroke therapies and of anti-hypertensive treatments on stroke outcome. Methods: Data were pooled from 3,288 acute ischemic stroke experiments (47,899 animals) testing the effect of therapies on infarct size (published 1978–2010). Data were combined using meta...

  1. EMERGENCY STATES IN ARTERIAL HYPERTENSION

    Directory of Open Access Journals (Sweden)

    M. A. Gurevich

    2014-01-01

    Full Text Available The article describes in detail potential emergency states in patients with different stages of arterial hypertension with special attention to diagnosis and rational management of hypertensive crisis. Differentiated approach to management of different forms of hypertensive crisis is specified.

  2. Primary lung hypertension in-patient with hypertension portal

    International Nuclear Information System (INIS)

    Restrepo Uribe; Villa Restrepo, Alfredo

    1990-01-01

    Thorax x-rays were reviewed in 18 patients with portal hypertension. In 28% of these we found radiologic signs of pulmonary hypertension of the precapillary type. The existing relation between primary pulmonary hypertension and portal hypertension has been established in different scientific papers. In the published series the incidence of primary pulmonary hypertension is less than the one of found in these patients the physiopathology of this association is reviewed, and as a hypothetic manner it is postulated the possible roll of the hypoxaemia of the residents, at the altitude of the Bogota city. (2.640 mts) as a helping factor in this phenomenon

  3. Decoding white coat hypertension

    Science.gov (United States)

    Bloomfield, Dennis A; Park, Alex

    2017-01-01

    There is arguably no less understood or more intriguing problem in hypertension that the “white coat” condition, the standard concept of which is significantly blood pressure reading obtained by medical personnel of authoritative standing than that obtained by more junior and less authoritative personnel and by the patients themselves. Using hospital-initiated ambulatory blood pressure monitoring, the while effect manifests as initial and ending pressure elevations, and, in treated patients, a low daytime profile. The effect is essentially systolic. Pure diastolic white coat hypertension appears to be exceedingly rare. On the basis of the studies, we believe that the white coat phenomenon is a common, periodic, neuro-endocrine reflex conditioned by anticipation of having the blood pressure taken and the fear of what this measurement may indicate concerning future illness. It does not change with time, or with prolonged association with the physician, particularly with advancing years, it may be superimposed upon essential hypertension, and in patients receiving hypertensive medication, blunting of the nighttime dip, which occurs in about half the patients, may be a compensatory mechanisms, rather than an indication of cardiovascular risk. Rather than the blunted dip, the morning surge or the widened pulse pressure, cardiovascular risk appears to be related to elevation of the average night time pressure. PMID:28352632

  4. Angiography for renal hypertension

    International Nuclear Information System (INIS)

    Chuang, V.P.; Ernst, C.B.

    1985-01-01

    As angioplasty and operative techniques have become more precise and successful, so have evaluation techniques. Preoperative arteriography is indispensible for deciding on the appropriate treatment modality and the specifics of the procedure. Arteriography, therefore, remains the cornerstone in managing renovascular hypertension and renal arterial disease

  5. Children and Hypertension.

    Science.gov (United States)

    Carter, Denise

    1983-01-01

    Since children as young as seven years old can suffer from hypertension, all children should have blood pressure checked during physical examinations. Guidelines for testing children's blood pressure are presented along with suggestions about what schools and parents can do to help deal with the problem. (PP)

  6. Project "Hypertension Alert."

    Science.gov (United States)

    Sailors, Emma Lou

    1983-01-01

    "Hypertension Alert," a 1979-80 blood pressure screening-awareness project of the Yonkers, New York Public Schools, is described. Data is analyzed in tables for ethnic composition, and range of blood pressure readings for the high school, junior high school, and elementary school students tested. (Author/JMK)

  7. Hypertensive Heart Disease

    DEFF Research Database (Denmark)

    Wachtell, Kristian

    2011-01-01

    Abstract Hypertensive heart disease is prevalent and during the last decade it has been determined that patients with left ventricular (LV) hypertrophy have increased cardiovascular morbidity and mortality. However, many have doubted the effectiveness of LV mass assessment because it is difficult...

  8. What Is Pulmonary Hypertension?

    Science.gov (United States)

    ... Artery Disease Venous Thromboembolism Aortic Aneurysm More Pulmonary Hypertension - High Blood Pressure in the Heart-to-Lung System Updated:Jan ... Pressure" This content was last reviewed October 2016. High Blood Pressure • Home • Get the Facts About HBP Introduction What ...

  9. Hypertension og hjertet

    DEFF Research Database (Denmark)

    Wachtell, Kristian; Andersen, Niels Holmark; Svendsen, Tage Lysbo

    2009-01-01

    of left ventricular mass is associated with substantial and significant reduction of cardiovascular morbidity and mortality. Hypertension is strongly associated with increased risk of subsequent heart failure. Meta analysis data suggests that reduction in blood pressure is also associated with very...

  10. Fermented milk for hypertension

    DEFF Research Database (Denmark)

    Usinger, Lotte; Reimer, Christina; Ibsen, Hans

    2012-01-01

    Fermented milk has been suggested to have a blood pressure lowering effect through increased content of proteins and peptides produced during the bacterial fermentation. Hypertension is one of the major risk factors for cardiovascular disease world wide and new blood pressure reducing lifestyle...

  11. Nitroglycerin kan give hypertension

    DEFF Research Database (Denmark)

    Mørup, Peter; Levinsen, Tine Holbæk; Hovind, Peter

    2011-01-01

    Hg. The conclusion was that her response was a paradoxical response to glycerylnitrate, orthostatism and a pathological response to massage of the carotid artery. This is the third reported case on paradoxical hypertension induced by glyceryl nitrates. It is speculated that dysfunction of the cerebral bloodflow...

  12. Alterações histopatológicas em placentas humanas relacionadas às síndromes hipertensivas Histopathological changes in human placentas related to hypertensive disorders

    Directory of Open Access Journals (Sweden)

    Luciano Guimarães Artico

    2009-01-01

    Full Text Available OBJETIVO: determinar a prevalência de alterações histopatológicas em placentas humanas, relacionadas às síndromes hipertensivas. MÉTODOS: estudo de corte transversal, que comparou as alterações histopatológicas identificadas em 43 placentas oriundas de gestantes do grupo de hipertensas (GrHip com as de 33 placentas de gestantes do grupo de normotensas (GrNor. Foram analisados o peso, volume e ocorrência macro e microscópica de infartos, coágulos, hematomas, aterose (obliteração parcial, espessamento de camadas e presença de vasos hialinizados e alterações de Tenney-Parker (ausentes, discretas e proeminentes, bem como a localização de infartos e coágulos (central, periférico ou associação de ambos. Para a análise estatística foram usados os testes do χ2 e t de Student, bem como médias, desvios padrões e percentuais. Considerou-se como significante um pPURPOSE: to determine the prevalence of histopathological changes, in human placentas, related to hypertensive syndromes. METHODS: a transversal study that compares histopathological changes identified in 43 placentae from hypertensive pregnant women (HypPr, with the ones from 33 placentae from normotensive pregnant women (NorPr. The weight, volume and macroscopic and microscopic occurrence of infarctions, clots, hematomas, atherosis (partial obliteration, thickness of layers and presence of blood vessels hyalinization and Tenney-Parker changes (absent, discreet and prominent, as well as the locating of infarctions and clots (central, peripheral or the association of both have been analyzed. The χ2 and t Student tests have been used for the statistical analysis, as well as medians, standard deviations and ratios. It has been considered as significant, p<0.05. RESULTS: the macroscopic study of HypPr placentae have presented lower weight (461.1 versus 572.1 g and volume (437.4 versus 542.0 cm³, higher infarction (51.2 versus 45.5%; p<0.05: OR=1.15 and clots (51.2 versus

  13. Implementation of MP3 player for music therapy on hypertension.

    Science.gov (United States)

    Yu, J Y; Huang, D F; Li, Y; Zhang, Y T

    2009-01-01

    Hypertension is a common clinical disease and a major risk to human health. Many clinical findings indicate that certain types of music can reduce blood pressure (BP), and music therapy is considered as an important part of anti-hypertension treatment. We integrate our former related research achievement into the new MP3 player, which can also detect the current BP value with a cuffless measurement method. According to the current BP value, the MP3 player selects certain types of music for playing in order to alleviate the hypertension of patients.

  14. Pulmonary Hypertension and Pulmonary Vasodilators.

    Science.gov (United States)

    Keller, Roberta L

    2016-03-01

    Pulmonary hypertension in the perinatal period can present acutely (persistent pulmonary hypertension of the newborn) or chronically. Clinical and echocardiographic diagnosis of acute pulmonary hypertension is well accepted but there are no broadly validated criteria for echocardiographic diagnosis of pulmonary hypertension later in the clinical course, although there are significant populations of infants with lung disease at risk for this diagnosis. Contributing cardiovascular comorbidities are common in infants with pulmonary hypertension and lung disease. It is not clear who should be treated without confirmation of pulmonary vascular disease by cardiac catheterization, with concurrent evaluation of any contributing cardiovascular comorbidities. Copyright © 2016 Elsevier Inc. All rights reserved.

  15. Epidemic of hypertension in Ghana: a systematic review

    Directory of Open Access Journals (Sweden)

    Bosu William K

    2010-07-01

    Full Text Available Abstract Background Hypertension is a major risk factor for many cardiovascular diseases in developing countries. A comprehensive review of the prevalence of hypertension provides crucial information for the evaluation and implementation of appropriate programmes. Methods The PubMed and Google Scholar databases were searched for published articles on the population-based prevalence of adult hypertension in Ghana between 1970 and August 2009, supplemented by a manual search of retrieved references. Fifteen unique population-based articles in non-pregnant humans were obtained. In addition, two relevant unpublished graduate student theses from one university department were identified after a search of its 1996-2008 theses. Results The age and sex composition of study populations, sampling strategy, measurement of blood pressure, definition of hypertension varied between studies. The prevalence of hypertension (BP ≥ 140/90 mmHg ± antihypertensive treatment ranged from 19% to 48% between studies. Sex differences were generally minimal whereas urban populations tended to have higher prevalence than rural population in studies with mixed population types. Factors independently associated with hypertension included older age group, over-nutrition and alcohol consumption. Whereas there was a trend towards improved awareness, treatment and control between 1972 and 2005, less than one-third of hypertensive subjects were aware they had hypertension and less than one-tenth had their blood pressures controlled in most studies. Conclusion Hypertension is clearly an important public health problem in Ghana, even in the poorest rural communities. Emerging opportunities such as the national health insurance scheme, a new health policy emphasising health promotion and healthier lifestyles and effective treatment should help prevent and control hypertension.

  16. Genetic Risk Score for Essential Hypertension and Risk of Preeclampsia.

    Science.gov (United States)

    Smith, Caitlin J; Saftlas, Audrey F; Spracklen, Cassandra N; Triche, Elizabeth W; Bjonnes, Andrew; Keating, Brendan; Saxena, Richa; Breheny, Patrick J; Dewan, Andrew T; Robinson, Jennifer G; Hoh, Josephine; Ryckman, Kelli K

    2016-01-01

    Preeclampsia is a hypertensive complication of pregnancy characterized by novel onset of hypertension after 20 weeks gestation, accompanied by proteinuria. Epidemiological evidence suggests that genetic susceptibility exists for preeclampsia; however, whether preeclampsia is the result of underlying genetic risk for essential hypertension has yet to be investigated. Based on the hypertensive state that is characteristic of preeclampsia, we aimed to determine if established genetic risk scores (GRSs) for hypertension and blood pressure are associated with preeclampsia. Subjects consisted of 162 preeclamptic cases and 108 normotensive pregnant controls, all of Iowa residence. Subjects' DNA was extracted from buccal swab samples and genotyped on the Affymetrix Genome-wide Human SNP Array 6.0 (Affymetrix, Santa Clara, CA). Missing genotypes were imputed using MaCH and Minimac software. GRSs were calculated for hypertension, systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean arterial pressure (MAP) using established genetic risk loci for each outcome. Regression analyses were performed to determine the association between GRS and risk of preeclampsia. These analyses were replicated in an independent US population of 516 cases and 1,097 controls of European ancestry. GRSs for hypertension, SBP, DBP, and MAP were not significantly associated with risk for preeclampsia (P > 0.189). The results of the replication analysis also yielded nonsignificant associations. GRSs for hypertension and blood pressure are not associated with preeclampsia, suggesting that an underlying predisposition to essential hypertension is not on the causal pathway of preeclampsia. © American Journal of Hypertension, Ltd 2015. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  17. [Hypertension in polycystic ovary syndrome].

    Science.gov (United States)

    Ben Salem Hachmi, L; Ben Salem Hachmi, S; Bouzid, C; Younsi, N; Smida, H; Bouguerra, R; Ben Slama, C

    2006-01-01

    Polycystic ovary syndrome (PCOS) is associated with multiple cardiovascular risk factors. The aims of this study are to investigate the prevalence of hypertension in a female population with PCOS and to correlate hypertension with her clinical and hormonal profile. it is a transversal study of 79 PCOS patients with mean age of 25 +/- 7 years (range 13-44). PCOS diagnosis is made by Rotterdam consensus criteria's (2003). WHO definition of hypertension is used (BP 140/90 mmHg). Blood pressure is measured three times in each patient. Ovarian echography and biochemical assays (GnRH test, androgens, cholesterol, triglycerides, and oral glucose tolerance test) are made before the 5th day of the menstrual cycle. 12% of PCOS women have hypertension. Family history of hypertension is not a predictive factor of hypertension in our study. PCOS patients with hypertension are not significantly older than those without hypertension (28.4 +/- 6.5 vs. 25.2 +/- 7; p = 0.12). If compared to PCOS women without hypertension, those with hypertension have a significantly higher BMI (39.2 +/- 7 vs. 29.6; p = 0.0004). PCOS patients with and without hypertension do not differ significantly in their level of androgens and total cholesterol. Triglycerides level is higher in PCOS patients with hypertension (p = 0.06). In oral glucose tolerance test, areas under the curve of insulin and glucose are significantly higher in PCOS patients with hypertension (respectively p = 0.06 and 0.02). The area under the curve of LH during GnRH test is lower in PCOS patients with hypertension (p = 0.04).

  18. Developmental Origins and Nephron Endowment in Hypertension

    Directory of Open Access Journals (Sweden)

    Shari Gurusinghe

    2017-06-01

    Full Text Available Primary hypertension continues to be one of the main risk factors for cardiovascular disease worldwide. A stable intrauterine environment is critical for the future development and health of the fetus. The developing kidney has been found to be especially vulnerable during this time period, and epidemiological studies have demonstrated that an adverse in utero environment is associated with an increased risk of hypertension and chronic kidney disease. Macro- and micronutrient deficiencies as well as exposure to tobacco, alcohol, and certain medications during gestation have been shown to negatively impact nephrogenesis and reduce one’s nephron number. In 1988, Brenner et al. put forth the controversial hypothesis that a reduced nephron complement is a risk factor for hypertension and chronic kidney disease in adulthood. Since then numerous animal and human studies have confirmed this relationship demonstrating that there is an inverse association between blood pressure and nephron number. As our understanding of the developmental programming of hypertension and other non-communicable diseases improves, more effective preventive health measures can be developed in the future.

  19. Sex differences in angiotensin II- induced hypertension

    Directory of Open Access Journals (Sweden)

    B. Xue

    2007-05-01

    Full Text Available Sex differences in the development of hypertension and cardiovascular disease have been described in humans and in animal models. In this paper we will review some of our studies which have as their emphasis the examination of the role of sex differences and sex steroids in modulating the central actions of angiotensin II (ANG II via interactions with free radicals and nitric oxide, generating pathways within brain circumventricular organs and in central sympathomodulatory systems. Our studies indicate that low-dose infusions of ANG II result in hypertension in wild-type male mice but not in intact wild-type females. Furthermore, we have demonstrated that ANG II-induced hypertension in males is blocked by central infusions of the androgen receptor antagonist, flutamide, and by central infusions of the superoxide dismutase mimetic, tempol. We have also found that, in comparison to females, males show greater levels of intracellular reactive oxygen species in circumventricular organ neurons following long-term ANG II infusions. In female mice, ovariectomy, central blockade of estrogen receptors or total knockout of estrogen a receptors augments the pressor effects of ANG II. Finally, in females but not in males, central blockade of nitric oxide synthase increases the pressor effects of ANG II. Taken together, these results suggest that sex differences and estrogen and testosterone play important roles in the development of ANG II-induced hypertension.

  20. The evolving definition of systemic arterial hypertension.

    Science.gov (United States)

    Ram, C Venkata S; Giles, Thomas D

    2010-05-01

    Systemic hypertension is an important risk factor for premature cardiovascular disease. Hypertension also contributes to excessive morbidity and mortality. Whereas excellent therapeutic options are available to treat hypertension, there is an unsettled issue about the very definition of hypertension. At what level of blood pressure should we treat hypertension? Does the definition of hypertension change in the presence of co-morbid conditions? This article covers in detail the evolving concepts in the diagnosis and management of hypertension.

  1. Low LDL cholesterol, PCSK9 and HMGCR genetic variation, and risk of Alzheimer's disease and Parkinson's disease: Mendelian randomisation study.

    Science.gov (United States)

    Benn, Marianne; Nordestgaard, Børge G; Frikke-Schmidt, Ruth; Tybjærg-Hansen, Anne

    2017-04-24

    Objective  To test the hypothesis that low density lipoprotein (LDL) cholesterol due to genetic variation in the genes responsible for LDL cholesterol metabolism and biosynthesis( PCSK9 and 3-hydroxy-3-methylglutaryl-CoA reductase ( HMGCR ), respectively) is associated with a high risk of Alzheimer's disease, vascular dementia, any dementia, and Parkinson's disease in the general population. Design  Mendelian randomisation study. Setting  Copenhagen General Population Study and Copenhagen City Heart Study. Participants  111 194 individuals from the Danish general population. Main outcome measures  Risk of Alzheimer's disease, vascular dementia, all dementia, and Parkinson's disease. Results  In observational analyses, the multifactorially adjusted hazard ratio for Parkinson's disease in participants with an LDL cholesterol level LDL cholesterol level. In genetic, causal analyses adjusted for age, sex, and year of birth, the risk ratios for a lifelong 1 mmol/L lower LDL cholesterol level were 0.57 (0.27 to 1.17) for Alzheimer's disease, 0.81 (0.34 to 1.89) for vascular dementia, 0.66 (0.34 to 1.26) for any dementia, and 1.02 (0.26 to 4.00) for Parkinson's disease. Summary level data from the International Genomics of Alzheimer's Project using Egger Mendelian randomisation analysis gave a risk ratio for Alzheimer's disease of 0.24 (0.02 to 2.79) for 26 PCSK9 and HMGCR variants, and of 0.64 (0.52 to 0.79) for 380 variants of LDL cholesterol level lowering. Conclusion  Low LDL cholesterol levels due to PCSK9 and HMGCR variants had no causal effect on high risk of Alzheimer's disease, vascular dementia, any dementia, or Parkinson's disease; however, low LDL cholesterol levels may have a causal effect in reducing the risk of Alzheimer's disease. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  2. Hepatic angiography: Portal hypertension

    International Nuclear Information System (INIS)

    Oliver, T.W. Jr.; Sones, P.J. Jr.

    1985-01-01

    Portal hypertension is usually a manifestation of underlying hepatic parenchymal disease, although it may be secondary to portal or hepatic venous thrombosis and rarely to hyperdynamic portal states. Portal hypertension may present as encephalopathy, ascites, jaundice, hepatic failure, or catastrophic upper gastrointestinal hemorrhage. Radiologic investigation should include indirect or direct measurements of portal pressure, assessment of portal venous perfusion, visualization of collaterals, and demonstration of arterial and venous anatomy for potential shunt procedure. Following survival of initial variceal bleeding, the most effective procedure to prevent recurrent hemorrhage is a shunt to decompress the varices. The decision whether to intervene medically or surgically during the acute hemorrhagic episode as well as the type of shunt used to prevent future hemorrhage is the subject of continuing controversy

  3. [Exercise in arterial hypertension].

    Science.gov (United States)

    Predel, Hans-Georg; Schramm, Thomas

    2006-09-01

    Regular endurance training has established itself as a major therapeutic principle in the specter of nonpharmacological measures in arterial hypertension. An initial medical check as well as an adequate technique, dosage and intensity of the prescribed exercise training are mandatory. With respect to the concomitant pharmacological treatment, it should be considered that the beneficial effects of lifestyle modification will not be counteracted by the chosen antihypertensive drug but, ideally, synergistically supported. Based on the individual clinical situation, principally all antihypertensive drugs recommended by the current European guidelines, may be prescribed as mono- or combination therapy.beta-receptor blockers are especially capable of controlling excessive exercise-induced blood pressure increase; however, they have metabolic and exercise physiological limitations. The neutrality concerning metabolic and exercise physiological parameters as well as the positive profile of side effects favor ACE inhibitors, long-acting calcium channel blockers and especially AT(1) antagonists in physically active hypertensive patients with concomitant metabolic syndrome.

  4. [Chronic hypertension and pregnancy].

    Science.gov (United States)

    Lecarpentier, Edouard; Tsatsaris, Vassili

    2012-09-01

    Hypertensive disorders in pregnancy are a leading cause of maternal and perinatal mortality and morbidity. The management of patients with chronic hypertension requires a multidisciplinary approach prior to conception, during pregnancy and post-partum. In the preconception period, fetotoxic agents should be discontinued. It is also essential to undertake a full cardiovascular examination which may, in some cases, question the possibility of pregnancy. During pregnancy, blood pressure should be monitored and controlled, but not necessarily returned to a normal value. Low blood pressure levels could indeed lead to placental hypoperfusion and fetal growth restriction. Close clinical, biological and ultrasound monitoring is recommended, even postpartum, since those patients are at higher risk for preeclampsia.

  5. Adrenal Mass Causing Secondary Hypertension.

    Science.gov (United States)

    Robinson, Darlene Y

    2015-11-01

    Most hypertensive patients have essential (primary) hypertension; only 5% to 10% have a secondary cause. Two clinical characteristics suggestive of secondary hypertension are early onset (hypertension (>180/110 mm Hg). When faced with these findings, clinicians should consider a secondary cause of hypertension. A 22-year-old woman being evaluated for asthma exacerbation in the emergency department was noted to have severe persistent hypertension. Additional evaluation revealed severe hypokalemia, metabolic alkalosis, and hypernatremia. The patient was admitted to the hospital for blood pressure management, electrolyte replacement, and further evaluation of presumed hyperaldosteronism. Diagnostic imaging revealed a large adrenal mass. Surgical resection was performed, leading to a diagnosis of hyperaldosteronism caused by adrenal carcinoma. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Secondary hypertension is far less common than essential hypertension; however, considering the large volume of patients seen in emergency departments, it is likely that some will have secondary hypertension. Emergency physicians should be aware of the clinical characteristics that suggest secondary hypertension so that the appropriate diagnostic and treatment pathways can be pursued. Copyright © 2015 Elsevier Inc. All rights reserved.

  6. Neurological disorders in hypertensive patients

    Directory of Open Access Journals (Sweden)

    N. V. Vakhnina

    2015-01-01

    Full Text Available Hypertension is one of the most common vascular diseases. The brain as target organs in hypertension is damaged more often and earlier. Neurological complications due to hypertension are frequently hyperdiagnosed in Russian neurological practice. Thus, headache, dizziness, impaired recall of recent events, nocturnal sleep disorders, and many other complaints in a hypertensive patient are usually regarded as a manifestation of dyscirculatory encephalopathy. At the same time headaches (tension headache and migraine in hypertensive patients are predominantly primary; headache associated with dramatic marked elevations in blood pressure is encountered in only a small number of patients. The role of cerebrovascular diseases in the development of dizziness in hypertensive patients is also overestimated. The vast majority of cases, patients with this complaint are in fact identified to have benign paroxysmal postural vertigo, Mеniеre’s disease, vestibular neuronitis, or vestibular migraine. Psychogenic disorders or multisensory insufficiency are generally responsible for non-systemic vertigo in hypertensive patients. Chronic cerebral circulatory insufficiency may cause non-systemic vertigo as a subjective equivalent of postural instability.Cognitive impairments (CIs are the most common and earliest manifestation of cerebrovascular lesion in hypertension. In most cases, CIs in hypertension were vascular and associated with cerebrovascular lesion due to lacunar infarcts and leukoaraiosis. However, mixed CIs frequently occur when hypertensive patients are also found to have signs of a degenerative disease, most commonly in Alzheimer’s disease.

  7. Epidemiology of hypertensive kidney disease.

    Science.gov (United States)

    Udani, Suneel; Lazich, Ivana; Bakris, George L

    2011-01-01

    The prevalence of hypertension, chronic kidney disease (CKD) and end-stage renal disease (ESRD) attributable to hypertension continues to rise worldwide. Identifying the precise prevalence of CKD attributable to hypertension is difficult owing to the absence of uniform criteria to establish a diagnosis of hypertensive nephropathy. Despite the increasing prevalence of CKD-associated hypertension, awareness of hypertension among individuals with CKD remains suboptimal and rates of blood-pressure control remain poor. Targeted subgroups involved in studies of CKD seem to reach better rates of blood-pressure control, suggesting that this therapeutic goal can be achieved in patients with CKD. Elevated blood-pressure levels are associated with CKD progression. However, the optimal blood-pressure level and pharmacological agent remains unclear. Physicians treating patients with CKD must recognize the importance of maintaining optimal salt and volume balance to achieve blood-pressure goals. Furthermore, agents that modify the renin-angiotensin-aldosterone axis can be an important adjunct to therapy and physicians must monitor expected changes in serum creatinine and electrolyte levels after their administration. Hypertension remains a common factor complicating CKD. Future investigations identifying early signs of hypertension-related CKD, increasing awareness of the effects of hypertension in CKD and determining optimal therapeutic interventions might help reduce the incidence of hypertensive nephropathy.

  8. Angiography in portal hypertension

    Energy Technology Data Exchange (ETDEWEB)

    Zeitler, E

    1982-04-05

    We report on the cooperative possibilities the radiologist has as to diagnosis and therapy of portal hypertension. The catheter angiography allows to make a differentiation between pre- and intrahepatic bloc and the localization of bleeding esophagus varices. Only after all endoscopic measures with sclerotherapy and Laser coagulation have failed, catheter angiography will be carried out as a therapeutic measure. The future development, however, will give the opportunity to a series of therapeutic attempts on the field of interventional radiology.

  9. Renal denervation and hypertension.

    Science.gov (United States)

    Schlaich, Markus P; Krum, Henry; Sobotka, Paul A; Esler, Murray D

    2011-06-01

    Essential hypertension remains one of the biggest challenges in medicine with an enormous impact on both individual and society levels. With the exception of relatively rare monogenetic forms of hypertension, there is now general agreement that the condition is multifactorial in nature and hence requires therapeutic approaches targeting several aspects of the underlying pathophysiology. Accordingly, all major guidelines promote a combination of lifestyle interventions and combination pharmacotherapy to reach target blood pressure (BP) levels in order to reduce overall cardiovascular risk in affected patients. Although this approach works for many, it fails in a considerable number of patients for various reasons including drug-intolerance, noncompliance, physician inertia, and others, leaving them at unacceptably high cardiovascular risk. The quest for additional therapeutic approaches to safely and effectively manage hypertension continues and expands to the reappraisal of older concepts such as renal denervation. Based on the robust preclinical and clinical data surrounding the role of renal sympathetic nerves in various aspects of BP control very recent efforts have led to the development of a novel catheter-based approach using radiofrequency (RF) energy to selectively target and disrupt the renal nerves. The available evidence from the limited number of uncontrolled hypertensive patients in whom renal denervation has been performed are auspicious and indicate that the procedure has a favorable safety profile and is associated with a substantial and presumably sustained BP reduction. Although promising, a myriad of questions are far from being conclusively answered and require our concerted research efforts to explore the full potential and possible risks of this approach. Here we briefly review the science surrounding renal denervation, summarize the current data on safety and efficacy of renal nerve ablation, and discuss some of the open questions that need

  10. Angiography in portal hypertension

    International Nuclear Information System (INIS)

    Zeitler, E.

    1982-01-01

    We report on the cooperative possibilities the radiologist has as to diagnosis and therapy of portal hypertension. The catheter angiography allows to make a differentiation between pre- and intrahepatic bloc and the localization of bleeding esophagus varices. Only after all endoscopic measures with sclerotherapy and Laser coagulation have failed, catheter angiography will be carried out as a therapeutic measure. The future development, however, will give the opportunity to a series of therapeutic attempts on the field of interventional radiology. (orig.) [de

  11. Cerebrovascular mental stress reactivity is impaired in hypertension

    Directory of Open Access Journals (Sweden)

    Naqvi Tasneem Z

    2009-07-01

    Full Text Available Abstract Background Brachial artery reactivity in response to shear stress is altered in subjects with hypertension. Since endothelial dysfunction is generalized, we hypothesized that carotid artery (CA reactivity would also be altered in hypertension. Purpose To compare (CA endothelium-dependent vasodilation in response to mental stress in normal and hypertensive subjects. Methods We evaluated CA reactivity to mental stress in 10 young healthy human volunteers (aged 23 ± 4 years, 20 older healthy volunteers (aged 49 ± 11 years and in 28 patients with essential hypertension (aged 51 ± 13 years. In 10 healthy volunteers and 12 hypertensive subjects, middle cerebral artery (MCA PW transcranial Doppler was performed before and 3 minutes after mental stress. Results Mental stress by Stroop color word conflict, math or anger recall tests caused CA vasodilation in young healthy subjects (0.61 ± 0.06 to 0.65 ± 0.07 cm, p Conclusion Mental stress produces CA vasodilation and is accompanied by an increase in CA and MCA blood flow in healthy subjects. This mental stress induced CA vasodilation and flow reserve is attenuated in subjects with hypertension and may reflect cerebral vascular endothelial dysfunction. Assessment of mental stress induced CA reactivity by ultrasound is a novel method for assessing the impact of hypertension on cerebrovascular endothelial function and blood flow reserve.

  12. [Resistant hypertension: An update].

    Science.gov (United States)

    Renna, N F

    2018-02-04

    An estimated 10% to 20% of hypertensive patients could be considered resistant to treatment (RH). These are patients who are not controlled using three drugs, at the maximum tolerated doses, including a diuretic, as well as those with high blood pressure controlled using four or more drugs. The term is used to identify patients that might benefit from special diagnostic and/or therapeutic consideration. The term 'refractory hypertension' has recently been proposed as a novel phenotype of antihypertensive failure. It refers to patients whose blood pressure cannot be controlled with maximum treatment. The first studies of this phenotype indicate that it is rare and affects less than 5% of patients with RH. Adherence to or compliance with medical treatment is key to defining resistant hypertension. Closer attention has been paid to clinical and experimental research since the first scientific statement for the diagnosis, assessment and treatment of RH from the American Heart Association, and in the European guidelines, was published in 2008. This review will set out the concepts relating to prevalence, prognosis and compliance and cover the latest developments on this subject. Copyright © 2018 SEH-LELHA. Publicado por Elsevier España, S.L.U. All rights reserved.

  13. Hypertensive target organ damage in Ghanaian civil servants with hypertension.

    Directory of Open Access Journals (Sweden)

    Juliet Addo

    2009-08-01

    Full Text Available Low levels of detection, treatment and control of hypertension have repeatedly been reported from sub Saharan Africa, potentially increasing the likelihood of target organ damage.A cross-sectional study was conducted on 1015 urban civil servants aged > or = 25 years from seven central government ministries in Accra, Ghana. Participants diagnosed to have hypertension were examined for target organ involvement. Hypertensive target organ damage was defined as the detection of any of the following: left ventricular hypertrophy diagnosed by electrocardiogram, reduction in glomerular filtration rate, the presence of hypertensive retinopathy or a history of a stroke.Of the 219 hypertensive participants examined, 104 (47.5% had evidence of target organ damage. The presence of target organ damage was associated with higher systolic and diastolic blood pressure levels. The odds of developing hypertensive target organ damage was five to six times higher in participants with blood pressure (BP > or = 180/110 mmHg compared to those with BP < 140/90 mmHg, and there was a trend to higher odds of target organ damage with increasing BP (p = 0.001. Women had about lower odds of developing target organ damage compared to men.The high prevalence of target organ damage in this working population associated with increasing blood pressure, emphasises the need for hypertension control programs aimed at improving the detection of hypertension, and importantly addressing the issues inhibiting the effective treatment and control of people with hypertension in the population.

  14. [Control of hypertension in nursing homes].

    Science.gov (United States)

    Thomas, J M; Alvarez, W; Mulaj, M; De Breucker, S; Leeman, M; Pepersack, T

    2006-09-01

    In a cross sectional study we determined prevalence of hypertension among institutionalized old subjects. Prevalence of hypertension was 69%. Among detected hypertensive patients, 76% received an antihypertensive drug treatment. 61% of the declared hypertensive patients and 80% of the treated hypertensive patients had their blood pressure controlled. The general practitioners should better detect and treat this common geriatric problem associated with a high comorbidity.

  15. Semiparametric methods for estimation of a nonlinear exposure‐outcome relationship using instrumental variables with application to Mendelian randomization

    Science.gov (United States)

    Staley, James R.

    2017-01-01

    ABSTRACT Mendelian randomization, the use of genetic variants as instrumental variables (IV), can test for and estimate the causal effect of an exposure on an outcome. Most IV methods assume that the function relating the exposure to the expected value of the outcome (the exposure‐outcome relationship) is linear. However, in practice, this assumption may not hold. Indeed, often the primary question of interest is to assess the shape of this relationship. We present two novel IV methods for investigating the shape of the exposure‐outcome relationship: a fractional polynomial method and a piecewise linear method. We divide the population into strata using the exposure distribution, and estimate a causal effect, referred to as a localized average causal effect (LACE), in each stratum of population. The fractional polynomial method performs metaregression on these LACE estimates. The piecewise linear method estimates a continuous piecewise linear function, the gradient of which is the LACE estimate in each stratum. Both methods were demonstrated in a simulation study to estimate the true exposure‐outcome relationship well, particularly when the relationship was a fractional polynomial (for the fractional polynomial method) or was piecewise linear (for the piecewise linear method). The methods were used to investigate the shape of relationship of body mass index with systolic blood pressure and diastolic blood pressure. PMID:28317167

  16. Habitual coffee consumption and risk of type 2 diabetes, ischemic heart disease, depression and Alzheimer's disease: a Mendelian randomization study.

    Science.gov (United States)

    Kwok, Man Ki; Leung, Gabriel M; Schooling, C Mary

    2016-11-15

    Observationally, coffee is inversely associated with type 2 diabetes mellitus (T2DM), depression and Alzheimer's disease, but not ischemic heart disease (IHD). Coffee features as possibly protective in the 2015 Dietary Guidelines for Americans. Short-term trials suggest coffee has neutral effect on most glycemic traits, but raises lipids and adiponectin. To clarify we compared T2DM, depression, Alzheimer's disease, and IHD and its risk factors by genetically predicted coffee consumption using two-sample Mendelian randomization applied to large extensively genotyped case-control and cross-sectional studies. Childhood cognition was used as a negative control outcome. Genetically predicted coffee consumption was not associated with T2DM (odds ratio (OR) 1.02, 95% confidence interval (CI) 0.76 to 1.36), depression (0.89, 95% CI 0.66 to 1.21), Alzheimer's disease (1.17, 95% CI 0.96 to 1.43), IHD (0.96, 95% CI 0.80 to 1.14), lipids, glycemic traits, adiposity or adiponectin. Coffee was unrelated to childhood cognition. Consistent with observational studies, coffee was unrelated to IHD, and, as expected, childhood cognition. However, contrary to observational findings, coffee may not have beneficial effects on T2DM, depression or Alzheimer's disease. These findings clarify the role of coffee with relevance to dietary guidelines and suggest interventions to prevent these complex chronic diseases should be sought elsewhere.

  17. Mendelian susceptibility to mycobacterial disease: genetic, immunological, and clinical features of inborn errors of IFN-γ immunity

    Science.gov (United States)

    Bustamante, Jacinta; Boisson-Dupuis, Stéphanie; Abel, Laurent; Casanova, Jean-Laurent

    2014-01-01

    Mendelian susceptibility to mycobacterial disease (MSMD) is a rare condition characterized by predisposition to clinical disease caused by weakly virulent mycobacteria, such as BCG vaccines and environmental mycobacteria, in otherwise healthy individuals with no overt abnormalities in routine hematological and immunological tests. MSMD designation does not recapitulate all the clinical features, as patients are also prone to salmonellosis, candidiasis and tuberculosis, and more rarely to infections with other intramacrophagic bacteria, fungi, or parasites, and even, perhaps, a few viruses. Since 1996, nine MSMD-causing genes, including seven autosomal (IFNGR1, IFNGR2, STAT1, IL12B, IL12RB1, ISG15, and IRF8) and two X-linked (NEMO, CYBB) genes have been discovered. The high level of allelic heterogeneity has already led to the definition of 18 different disorders. The nine gene products are physiologically related, as all are involved in IFN-γ-dependent immunity. These disorders impair the production of (IL12B, IL12RB1, IRF8, ISG15, NEMO) or the response to (IFNGR1, IFNGR2, STAT1, IRF8, CYBB) IFN-γ. These defects account for only about half the known MSMD cases. Patients with MSMD-causing genetic defects may display other infectious diseases, or even remain asymptomatic. Most of these inborn errors do not show complete clinical penetrance for the case-definition phenotype of MSMD. We review here the genetic, immunological, and clinical features of patients with inborn errors of IFN-γ-dependent immunity. PMID:25453225

  18. Combating Combination of Hypertension and Diabetes in Different Rat Models

    Directory of Open Access Journals (Sweden)

    Talma Rosenthal

    2010-03-01

    Full Text Available Rat experimental models are used extensively for studying physiological mechanisms and treatments of hypertension and diabetes co-existence. Each one of these conditions is a major risk factor for cardiovascular disease (CVD, and the combination of the two conditions is a potent enhancer of CVD. Five major animal models that advanced our understanding of the mechanisms and therapeutic approaches in humans are discussed in this review: Zucker, Goto-Kakizaki, SHROB, SHR/NDmcr-cp and Cohen Rosenthal diabetic hypertensive (CRDH rats. The use of various drugs, such as angiotensin-converting enzyme (ACE inhibitors (ACEIs, various angiotensin receptor blockers (ARBs, and calcium channel blockers (CCBs, to combat the effects of concomitant pathologies on the combination of diabetes and hypertension, as well as the non-pharmacological approach are reviewed in detail for each rat model. Results from experiments on these models indicate that classical factors contributing to the pathology of hypertension and diabetes combination—Including hypertension, hyperglycemia, hyperinsulinemia and hyperlipidemia—can now be treated, although these treatments do not completely prevent renal complications. Animal studies have focused on several mechanisms involved in hypertension/diabetes that remain to be translated into clinical medicine, including hypoxia, oxidative stress, and advanced glycation. Several target molecules have been identified that need to be incorporated into a treatment modality. The challenge continues to be the identification and interpretation of the clinical evidence from the animal models and their application to human treatment.

  19. Hypertension--forekomst og behandling

    DEFF Research Database (Denmark)

    Ibsen, Hans; Jørgensen, Torben; Jensen, Gorm B

    2009-01-01

    Hypertension is the most important modifiable risk factor for cardiovascular disease. However, less than half of all hypertensives have their blood pressure reduced to relevant goals. The prevalence of hypertension in Denmark was found to be between 26% and 40% of the adult population. Just over ...... half were aware of the diagnosis, but less than half were in treatment. Blood pressure control in patients who are undergoing treatment has improved during recent years, but there is still a gap to achievable control rates....

  20. Hypertension--forekomst og behandling

    DEFF Research Database (Denmark)

    Ibsen, Hans; Jørgensen, Torben; Jensen, Gorm B

    2009-01-01

    Hypertension is the most important modifiable risk factor for cardiovascular disease. However, less than half of all hypertensives have their blood pressure reduced to relevant goals. The prevalence of hypertension in Denmark was found to be between 26% and 40% of the adult population. Just over...... half were aware of the diagnosis, but less than half were in treatment. Blood pressure control in patients who are undergoing treatment has improved during recent years, but there is still a gap to achievable control rates....

  1. Hypertension og det metaboliske syndrom

    DEFF Research Database (Denmark)

    Olsen, Michael Hecht; Jeppesen, Jørgen; Larsen, Mogens Lytken

    2009-01-01

    The metabolic syndrome is a relatively prevalent condition characterized by co-existence of several metabolic and cardiovascular risk factors including hypertension. Patients with hypertension have an increased risk of developing the metabolic syndrome which, in turn, increases the cardiovascular...... syndrome is of clinical importance as it makes the treating physician test for other elements of the syndrome in patients with one of the elements, e.g. hypertension. Udgivelsesdato: 2009-Jun...

  2. Hypertension og det metaboliske syndrom

    DEFF Research Database (Denmark)

    Olsen, Michael; Jeppesen, Jørgen; Larsen, Mogens

    2009-01-01

    The metabolic syndrome is a relatively prevalent condition characterized by co-existence of several metabolic and cardiovascular risk factors including hypertension. Patients with hypertension have an increased risk of developing the metabolic syndrome which, in turn, increases the cardiovascular...... syndrome is of clinical importance as it makes the treating physician test for other elements of the syndrome in patients with one of the elements, e.g. hypertension. Udgivelsesdato: 2009-Jun-15...

  3. Intelligence : shared genetic basis between Mendelian disorders and a polygenic trait

    NARCIS (Netherlands)

    Franić, Sanja; Groen-Blokhuis, Maria M; Dolan, Conor V; Kattenberg, Mathijs V; Pool, René; Xiao, Xiangjun; Scheet, Paul A; Ehli, Erik A; Davies, Gareth E; van der Sluis, Sophie; Abdellaoui, Abdel; Hansell, Narelle K; Martin, Nicholas G; Hudziak, James J; van Beijsterveldt, Catherina E M; Swagerman, Suzanne C; Hulshoff Pol, Hilleke E; de Geus, Eco J C; Bartels, Meike; Ropers, H Hilger; Hottenga, Jouke-Jan; Boomsma, Dorret I

    2015-01-01

    Multiple inquiries into the genetic etiology of human traits indicated an overlap between genes underlying monogenic disorders (eg, skeletal growth defects) and those affecting continuous variability of related quantitative traits (eg, height). Extending the idea of a shared genetic basis between a

  4. [Hepatopulmonary syndrome and portopulmonary hypertension].

    Science.gov (United States)

    Marcu, Cristina; Schiffer, Eduardo; Aubert, John-David; Vionnet, Julien; Yerly, Patrick; Deltenre, Pierre; Marot, Astrid

    2017-08-30

    Hepatopulmonary syndrome (HPS) and portopulmonary hypertension (POPH) are two frequent pulmonary complications of liver disease. Portal hypertension is a key element in the pathogenesis of both disorders, which are however distinct in terms of pathogenesis, diagnosis and treatment. HPS corresponds to an abnormal arterial oxygenation in relation with the development of intrapulmonary vascular dilatations. POPH is a pulmonary arterial hypertension in the setting of portal hypertension and elevated pulmonary vascular resistance. As both diseases are associated with an increased risk of morbidity and mortality, it is important to screen and evaluate the severity of these two disorders particularly in liver transplant candidates.

  5. Vascular inflammatory cells in hypertension

    Directory of Open Access Journals (Sweden)

    David G. Harrison

    2012-05-01

    Full Text Available Hypertension is a common disorder with uncertain etiology. In the last several years, it has become evident that components of both the innate and adaptive immune system play an essential role in hypertension. Macrophages and T cells accumulate in the perivascular fat, the heart and the kidney of hypertensive patients and in animals with experimental hypertension. Various immunosuppressive agents lower blood pressure and prevent end-organ damage. Mice lacking lymphocytes are protected against hypertension, and adoptive transfer of T cells, but not B cells in the animals restores their blood pressure response to stimuli such as angiotensin II or high salt. Recent studies have shown that mice lacking macrophages have blunted hypertension in response to angiotensin II and that genetic deletion of macrophages markedly reduces experimental hypertension. Dendritic cells have also been implicated in this disease. Many hypertensive stimuli have triggering effects on the central nervous system and signals arising from the circumventricular organ seem to promote inflammation. Studies have suggested that central signals activate macrophages and T cells, which home to the kidney and vasculature and release cytokines, including IL-6 and IL-17, which in turn cause renal and vascular dysfunction and lead to blood pressure elevation. These recent discoveries provide a new understanding of hypertension and provide novel therapeutic opportunities for treatment of this serious disease.

  6. Pulmonary hypertension in older adults.

    Science.gov (United States)

    McArdle, John R; Trow, Terence K; Lerz, Kathryn

    2007-12-01

    Pulmonary hypertension is a frequently encountered problem in older patients. True idiopathic pulmonary arterial hypertension can also be seen and requires careful exclusion in older patients. Institution of therapies must be tempered with an appreciation of individual comorbidities and functional limitations that may affect patients' ability to comply and benefit from the complex treatments available for pulmonary arterial hypertension. This article reviews the existing data on the various forms of pulmonary hypertension presenting in older patients and on appropriate therapy in this challenging population.

  7. Milan hypertensive rat as a model for studying cation transport abnormality in genetic hypertension

    International Nuclear Information System (INIS)

    Ferrari, P.; Barber, B.R.; Torielli, L.; Ferrandi, M.; Salardi, S.; Bianchi, G.

    1987-01-01

    Environmental factors, genetic polymorphisms, and different experimental designs have been the main impediments to evaluating a genetic association between cell membrane cation transport abnormalities and human essential or genetic hypertension. We review the results obtained in the Milan hypertensive strain of rats (MHS) and in its appropriate control normotensive strain (MNS) to illustrate our approach to defining the role of cation transport abnormality in a type of genetic hypertension. Before the development of a difference in blood pressure between the two strains, the comparison of kidney and erythrocyte functions showed that MHS had an increased glomerular filtration rate and urinary output, and lower plasma renin and urine osmolality. Kidney cross-transplantation between the strains showed that hypertension is transplanted with the kidney. Proximal tubular cell volume and sodium content were lower in MHS while sodium transport across the brush border membrane vesicles of MHS was faster. Erythrocytes in MHS were smaller and had lower sodium concentration, and Na+-K+ cotransport and passive permeability were faster. The differences in volume, sodium content, and Na+-K+ cotransport between erythrocytes of the two strains persisted after transplantation of bone marrow to irradiated F1 (MHS X MNS) hybrids. Moreover, in normal segregating F2 hybrid populations there was a positive correlation between blood pressure and Na+-K+ cotransport. These results suggest a genetic and functional link in MHS between cell membrane cation transport abnormalities and hypertension. Thus, erythrocyte cell membrane may be used for approaching the problem of defining the genetically determined molecular mechanism underlying the development of a type of essential hypertension. 35 references

  8. ESSENTIAL ARTERIAL HYPERTENSION AND RISK FACTORS ASSOCIATED WITH HYPERTENSIVE NEPHROPATHY

    Directory of Open Access Journals (Sweden)

    Boban Milojković

    2014-12-01

    Full Text Available Arterial hypertension is a major risk factor that predisposes to cardiovascular disorders and is responsible for most of the morbidity and mortality in patients. Hypertension is closely associated with the kidney, because kidney disease can be both the cause and consequence of increased blood pressure. Elevation of blood pressure is a strong independent risk factor for hypertensive nephropathy and development of ESRD. The pathogenesis of ischemic hypertensive nephropathy (IHN is multifactoral, and in addition to blood pressure other factors contribute to the development of this renal pathology and its progression to end-stage renal disease. These include obesity, smoking, male gender and other still unknown risk factors. The aim of this paper was to analyse the association between essential arterial hypertension and renal hypertensive disease and prevalence of other atherosclerotic risk factors in patients with developed hypertensive renal disease. In this prospective cross sectional study 283 patients of both genders with diagnosed essential hypertension and hypertensive renal disease were analysed. The anamnestic data related to age, duration of hypertension, history of smoking, presence of hypertensive retinopathy, hypertrophy of the left chamber and data about previous renal diseases were collected through conversation and medical documentation. The clinical examination comprise determination of blood pressure, body mass index (BMI, lipid parameters (total cholesterol, LDL cholesterol, HDL cholesterol and triglycerides, serum urea and creatinine, urine, albumin and protein concentration. The total number of 283 patients (185 males and 98 females with HN was analyzed. The analysis revealed significantly higher proportion of males aged over 60 years with IHN. The mean age of examined hypertensive patients with IHN is 62.6±8.8 years with duration of hypertension 19.8±5.9 years. All examined patients had hypertensive retinopathy and

  9. Evaluation and management of pediatric hypertensive crises: hypertensive urgency and hypertensive emergencies

    Directory of Open Access Journals (Sweden)

    Patel NH

    2012-11-01

    Full Text Available Nirali H Patel,1 Sarah K Romero,2 David C Kaelber31Division of Emergency Medicine, Akron Children's Hospital, Akron, OH, USA; 2Division of Emergency Medicine, Rainbow Babies and Children's Hospital, Cleveland, OH, USA; 3Departments of Information Services, Internal Medicine, Pediatrics, and Epidemiology and Biostatistics, The Center for Clinical Informatics Research and Education, The MetroHealth System and School of Medicine, Case Western Reserve University, Cleveland OH, USAAbstract: Hypertension (HTN in the pediatric population is estimated to have a world-wide prevalence of 2%-5%. As with adults, pediatric patients with HTN can present with hypertensive crises include hypertensive urgency and hypertensive emergencies. However, pediatric blood pressure problems have a greater chance of being from secondary causes of HTN, as opposed to primary HTN, than in adults. Thorough evaluation of a child with a hypertensive emergency includes accurate blood pressure readings, complete and focused symptom history, and appropriate past medical, surgical, and family history. Physical exam should include height, weight, four-limb blood pressures, a general overall examination and especially detailed cardiovascular and neurological examinations, including fundoscopic examination. Initial work-up should typically include electrocardiography, chest X-ray, serum chemistries, complete blood count, and urinalysis. Initial management of hypertensive emergencies generally includes the use of intravenous or oral antihypertensive medications, as well as appropriate, typically outpatient, follow-up. Emergency department goals for hypertensive crises are to (1 safely lower blood pressure, and (2 treat/minimize acute end organ damage, while (3 identifying underlying etiology. Intravenous antihypertensive medications are the treatment modality of choice for hypertensive emergencies with the goal of reducing systolic blood pressure by 25% of the original value over an 8

  10. Prevalence and persistence of masked hypertension in treated hypertensive patients

    NARCIS (Netherlands)

    Verberk, Willem J.; Thien, Theo; Kroon, Abraham A.; Lenders, Jacques W. M.; van Montfrans, Gert A.; Smit, Andries J.; de Leeuw, Peter W.

    2007-01-01

    Background: Masked hypertension (MH) is defined as a normal blood pressure in the physician's office and an elevated blood pressure when measured out-of-office. The cause of MH may be termed the masked hypertension effect (MHE), and is not restricted to blood-pressure (BP) values around the

  11. Prevalence and persistence of masked hypertension in treated hypertensive patients.

    NARCIS (Netherlands)

    Verberk, W.J.; Thien, Th.; Kroon, A.A.; Lenders, J.W.M.; Montfrans, G.A. van; Smit, A.J.; Leeuw, P.W. de

    2007-01-01

    BACKGROUND: Masked hypertension (MH) is defined as a normal blood pressure in the physician's office and an elevated blood pressure when measured out-of-office. The cause of MH may be termed the masked hypertension effect (MHE), and is not restricted to blood-pressure (BP) values around the

  12. Prevalence and persistence of masked hypertension in treated hypertensive patients

    NARCIS (Netherlands)

    Verberk, Willem J.; Thien, Theo; Kroon, Abraham A.; Lenders, Jacques W. M.; van Montfrans, Gert A.; Smit, Andries J.; de Leeuw, Peter W.

    2007-01-01

    BACKGROUND: Masked hypertension (MH) is defined as a normal blood pressure in the physician's office and an elevated blood pressure when measured out-of-office. The cause of MH may be termed the masked hypertension effect (MHE), and is not restricted to blood-pressure (BP) values around the

  13. Dietary habits of hypertensive patients in a tertiary hypertension ...

    African Journals Online (AJOL)

    Introduction: The prescriptions regarding non-pharmacological care in the management of hypertension has been carefully defined by the various practice guidelines. However, there is paucity of data on dietary practices in our environment, therefore this study set out to determine the dietary practices of hypertensive ...

  14. Drug induced hypertension--An unappreciated cause of secondary hypertension.

    Science.gov (United States)

    Grossman, Alon; Messerli, Franz H; Grossman, Ehud

    2015-09-15

    Most patients with hypertension have essential hypertension or well-known forms of secondary hypertension, such as renal disease, renal artery stenosis, or common endocrine diseases (hyperaldosteronism or pheochromocytoma). Physicians are less aware of drug induced hypertension. A variety of therapeutic agents or chemical substances may increase blood pressure. When a patient with well controlled hypertension is presented with acute blood pressure elevation, use of drug or chemical substance which increases blood pressure should be suspected. Drug-induced blood pressure increases are usually minor and short-lived, although rare hypertensive emergencies associated with use of certain drugs have been reported. Careful evaluation of prescription and non-prescription medications is crucial in the evaluation of the hypertensive individual and may obviate the need for expensive and unnecessary evaluations. Discontinuation of the offending agent will usually achieve adequate blood pressure control. When use of a chemical agent which increases blood pressure is mandatory, anti-hypertensive therapy may facilitate continued use of this agent. We summarize the therapeutic agents or chemical substances that elevate blood pressure and their mechanisms of action. Copyright © 2015 Elsevier B.V. All rights reserved.

  15. Pre-Hypertension and Hypertension in Adolescence: How much ...

    African Journals Online (AJOL)

    Background: Hypertension is an important worldwide public-health challenge because of its high frequency and concomitant risks of cardiovascular and kidney disease. Previous studies have documented that hypertension may begin in adolescence, perhaps even in childhood. Objectives: This study set out to determine ...

  16. Liquorice: a root cause of secondary hypertension

    OpenAIRE

    Varma, Ravi; Ross, Calum N.

    2017-01-01

    We describe a patient presenting with hypertension and hypokalaemia who was ultimately diagnosed with liquorice- induced pseudohyperaldosteronism. This rare cause of secondary hypertension illustrates the importance of a methodical approach to the assessment of hypertension.

  17. ORIGINAL ARTICLES Hypertension Guideline 2003 Update

    African Journals Online (AJOL)

    reduction of BP in the elderly and in those with severe hypertension should .... management of hypertension in adults by health care .... They may demonstrate postural and post- ..... Persons with severe hypertension fall into three categories.

  18. Genetics Home Reference: pulmonary arterial hypertension

    Science.gov (United States)

    ... Home Health Conditions Pulmonary arterial hypertension Pulmonary arterial hypertension Printable PDF Open All Close All Enable Javascript ... view the expand/collapse boxes. Description Pulmonary arterial hypertension is a progressive disorder characterized by abnormally high ...

  19. Isolated Systolic Hypertension: A Health Concern?

    Science.gov (United States)

    Isolated systolic hypertension: A health concern? Is having a high top number (systolic) blood pressure, but a normal bottom number (diastolic) ... mm Hg, you have a common type of high blood pressure called isolated systolic hypertension. Isolated systolic hypertension can ...

  20. Prevalence, Treatment, and Control Rates of Conventional and Ambulatory Hypertension Across 10 Populations in 3 Continents.

    Science.gov (United States)

    Melgarejo, Jesus D; Maestre, Gladys E; Thijs, Lutgarde; Asayama, Kei; Boggia, José; Casiglia, Edoardo; Hansen, Tine W; Imai, Yutaka; Jacobs, Lotte; Jeppesen, Jørgen; Kawecka-Jaszcz, Kalina; Kuznetsova, Tatiana; Li, Yan; Malyutina, Sofia; Nikitin, Yuri; Ohkubo, Takayoshi; Stolarz-Skrzypek, Katarzyna; Wang, Ji-Guang; Staessen, Jan A

    2017-07-01

    Hypertension is a major global health problem, but prevalence rates vary widely among regions. To determine prevalence, treatment, and control rates of hypertension, we measured conventional blood pressure (BP) and 24-hour ambulatory BP in 6546 subjects, aged 40 to 79 years, recruited from 10 community-dwelling cohorts on 3 continents. We determined how between-cohort differences in risk factors and socioeconomic factors influence hypertension rates. The overall prevalence was 49.3% (range between cohorts, 40.0%-86.8%) for conventional hypertension (conventional BP ≥140/90 mm Hg) and 48.7% (35.2%-66.5%) for ambulatory hypertension (ambulatory BP ≥130/80 mm Hg). Treatment and control rates for conventional hypertension were 48.0% (33.5%-74.1%) and 38.6% (10.1%-55.3%) respectively. The corresponding rates for ambulatory hypertension were 48.6% (30.5%-71.9%) and 45.6% (18.6%-64.2%). Among 1677 untreated subjects with conventional hypertension, 35.7% had white coat hypertension (23.5%-56.2%). Masked hypertension (conventional BP hypertension rates. Higher social and economic development, measured by the Human Development Index, was associated with lower rates of conventional and ambulatory hypertension. In conclusion, high rates of hypertension in all cohorts examined demonstrate the need for improvements in prevention, treatment, and control. Strategies for the management of hypertension should continue to not only focus on preventable and modifiable risk factors but also consider societal issues. © 2017 American Heart Association, Inc.

  1. Pharmacotherapy for mild hypertension

    Directory of Open Access Journals (Sweden)

    Diana Diao

    2012-01-01

    Full Text Available BACKGROUND: People with no previous cardiovascular events or cardiovascular disease represent a primary prevention population. The benefits and harms of treating mild hypertension in primary prevention patients are not known at present. This review examines the existing randomized controlled trial (RCT evidence. OBJECTIVE: Primary objective: To quantify the effects of antihypertensive drug therapy on mortality and morbidity in adults with mild hypertension (systolic blood pressure (BP 140-159 mmHg and/or diastolic BP 90-99 mmHg and without cardiovascular disease. METHODS: Search: We searched CENTRAL (2011, Issue 1, MEDLINE (1948 to May 2011, EMBASE (1980 to May 2011 and reference lists of articles. The Cochrane Database of Systematic Reviews and the Database of Abstracts of Reviews of Effectiveness (DARE were searched for previous reviews and meta-analyses of anti-hypertensive drug treatment compared to placebo or no treatment trials up until the end of 2011. Selection criteria: RCTs of at least 1 year duration. Data collection and analysis: The outcomes assessed were mortality, stroke, coronary heart disease (CHD, total cardiovascular events (CVS, and withdrawals due to adverse effects. MAIN RESULTS: Of 11 RCTs identified 4 were included in this review, with 8,912 participants. Treatment for 4 to 5 years with antihypertensive drugs as compared to placebo did not reduce total mortality (RR 0.85, 95% CI 0.63, 1.15. In 7,080 participants treatment with antihypertensive drugs as compared to placebo did not reduce coronary heart disease (RR 1.12, 95% CI 0.80, 1.57, stroke (RR 0.51, 95% CI 0.24, 1.08, or total cardiovascular events (RR 0.97, 95% CI 0.72, 1.32. Withdrawals due to adverse effects were increased by drug therapy (RR 4.80, 95% CI 4.14, 5.57, ARR 9%. AUTHORS' CONCLUSIONS: Antihypertensive drugs used in the treatment of adults (primary prevention with mild hypertension (systolic BP 140-159 mmHg and/or diastolic BP 90-99 mmHg have not been

  2. Nocturnal Hypertension: Neglected Issue in Comprehensive Hypertension Management

    Directory of Open Access Journals (Sweden)

    Andi Kristanto

    2016-09-01

    Full Text Available The body circardian rhythm affects blood pressure variability at day and night, therefore blood pressure at day and night might be different. Nocturnal hypertension is defined as increase of blood pressure >120/70mmHg at night, which is caused by disturbed circadian rhythm, and associated with higher cardiovascular and cerebrovascular events also mortality in hypertensive patients. Nocturnal hypertension and declining blood pressure pattern, can only be detected by continuous examination for 24 hours, also known as ambulatory blood pressure measurement (ABPM. Chronotherapy, has become a strategy for managing the hypertensive nocturnal patients, by taking hypertensive medication at night to obtain normal blood pressure decrease in accordance with the normal circadian rhythm and, improving blood pressure control.

  3. THE MITOCHONDRIAL PARADIGM FOR CARDIOVASCULAR DISEASE SUSCEPTIBILITY AND CELLULAR FUNCTION: A COMPLEMENTARY CONCEPT TO MENDELIAN GENETICS

    Science.gov (United States)

    Kryzwanski, David M.; Moellering, Douglas; Fetterman, Jessica L.; Dunham-Snary, Kimberly J.; Sammy, Melissa J.; Ballinger, Scott W.

    2013-01-01

    While there is general agreement that cardiovascular disease (CVD) development is influenced by a combination of genetic, environmental, and behavioral contributors, the actual mechanistic basis of how these factors initiate or promote CVD development in some individuals while others with identical risk profiles do not, is not clearly understood. This review considers the potential role for mitochondrial genetics and function in determining CVD susceptibility from the standpoint that the original features that molded cellular function were based upon mitochondrial-nuclear relationships established millions of years ago and were likely refined during prehistoric environmental selection events that today, are largely absent. Consequently, contemporary risk factors that influence our susceptibility to a variety of age-related diseases, including CVD were probably not part of the dynamics that defined the processes of mitochondrial – nuclear interaction, and thus, cell function. In this regard, the selective conditions that contributed to cellular functionality and evolution should be given more consideration when interpreting and designing experimental data and strategies. Finally, future studies that probe beyond epidemiologic associations are required. These studies will serve as the initial steps for addressing the provocative concept that contemporary human disease susceptibility is the result of selection events for mitochondrial function that increased chances for prehistoric human survival and reproductive success. PMID:21647091

  4. Assessment of knowledge about hypertension

    Directory of Open Access Journals (Sweden)

    Paweł Węgorowski

    2017-07-01

    Patient knowledge about hypertension and its effects can affect the effectiveness of treatment. Medical education should be of paramount importance for medical staff, with particular attention to the self-control of blood pressure by patients. In summary, it is important to note that due to the high risk of complications, both treatment and prevention of hypertension are important.

  5. Resistant Hypertension and Cardiorenovascular Risk

    Directory of Open Access Journals (Sweden)

    Prkacin Ingrid

    2017-06-01

    Full Text Available Studies have documented independent contribution of sympathetic activation to the cardiovascular disease continuum. Hypertension is one of the leading modifiable factors. Most if not all the benefit of antihypertensive treatment depends on blood pressure lowering, regardless how it is obtained. Resistant hypertension is defined as blood pressure that remains uncontrolled in spite of the concurrent use of three antihypertensive drugs of different classes. Ideally, one of the three drugs should be a diuretic, and all drugs should be prescribed at optimal dose amounts. Poor adherence to antihypertensive therapy, undiscovered secondary causes (e.g. obstructive sleep apnea, primary aldosteronism, renal artery stenosis, and lifestyle factors (e.g. obesity, excessive sodium intake, heavy alcohol intake, various drug interactions are the most common causes of resistant hypertension. Cardio(renovascular morbidity and mortality are significantly higher in resistant hypertensive than in general hypertensive population, as such patients are typically presented with a long-standing history of poorly controlled hypertension. Early diagnosis and treatment is needed to avoid further end-organ damage to prevent cardiorenovascular remodeling. Treatment strategy includes lifestyle changes, adding a mineralocorticoid receptor antagonist, treatment adherence in cardiovascular prevention and, in case of failure to control blood pressure, renal sympathetic denervation or baroreceptor activation therapy. The comparative outcomes in resistant hypertension deserve better understanding. In this review, the most current approaches to resistant hypertension and cardiovascular risk based on the available literature evidence will be discussed.

  6. Endocrine hypertension – Cushing's syndrome

    Science.gov (United States)

    Singh, Yashpal; Kotwal, Narendra; Menon, A. S.

    2011-01-01

    Hypertension is a major and frequent comorbid finding of Cushing's syndrome. This review discusses the etiology and pathophysiology of hypertension in Cushing's syndrome, while suggesting methods of management of this condition. It also provides an overview of diagnosis and management strategies in this disease. PMID:22145133

  7. Genetic predisposition to increased blood cholesterol and triglyceride lipid levels and risk of Alzheimer disease: a Mendelian randomization analysis.

    Directory of Open Access Journals (Sweden)

    Petroula Proitsi

    2014-09-01

    Full Text Available Although altered lipid metabolism has been extensively implicated in the pathogenesis of Alzheimer disease (AD through cell biological, epidemiological, and genetic studies, the molecular mechanisms linking cholesterol and AD pathology are still not well understood and contradictory results have been reported. We have used a Mendelian randomization approach to dissect the causal nature of the association between circulating lipid levels and late onset AD (LOAD and test the hypothesis that genetically raised lipid levels increase the risk of LOAD.We included 3,914 patients with LOAD, 1,675 older individuals without LOAD, and 4,989 individuals from the general population from six genome wide studies drawn from a white population (total n=10,578. We constructed weighted genotype risk scores (GRSs for four blood lipid phenotypes (high-density lipoprotein cholesterol [HDL-c], low-density lipoprotein cholesterol [LDL-c], triglycerides, and total cholesterol using well-established SNPs in 157 loci for blood lipids reported by Willer and colleagues (2013. Both full GRSs using all SNPs associated with each trait at p<5×10-8 and trait specific scores using SNPs associated exclusively with each trait at p<5 × 10-8 were developed. We used logistic regression to investigate whether the GRSs were associated with LOAD in each study and results were combined together by meta-analysis. We found no association between any of the full GRSs and LOAD (meta-analysis results: odds ratio [OR]=1.005, 95% CI 0.82-1.24, p = 0.962 per 1 unit increase in HDL-c; OR=0.901, 95% CI 0.65-1.25, p=0.530 per 1 unit increase in LDL-c; OR=1.104, 95% CI 0.89-1.37, p=0.362 per 1 unit increase in triglycerides; and OR=0.954, 95% CI 0.76-1.21, p=0.688 per 1 unit increase in total cholesterol. Results for the trait specific scores were similar; however, the trait specific scores explained much smaller phenotypic variance.Genetic predisposition to increased blood cholesterol and

  8. Liver cirrhosis and arterial hypertension

    DEFF Research Database (Denmark)

    Henriksen, Jens Henrik; Møller, Søren

    2006-01-01

    blood pressure. This review considers the alterations in systemic hemodynamics in patients with cirrhosis in relation to essential hypertension and arterial hypertension of the renal origin. Subjects with arterial hypertension (essential, secondary) may become normotensive during the development......Characteristic findings in patients with cirrhosis are vasodilatation with low overall systemic vascular resistance, high arterial compliance, increased cardiac output, secondary activation of counter-regulatory systems (renin-angiotensin-aldosterone system, sympathetic nervous system, release...... of cirrhosis, and arterial hypertension is rarely manifested in patients with cirrhosis, even in cases with renovascular disease and high circulating renin activity. There is much dispute as to the understanding of homoeostatic regulation in cirrhotic patients with manifest arterial hypertension. This most...

  9. Childhood BMI and Adult Type 2 Diabetes, Coronary Artery Diseases, Chronic Kidney Disease, and Cardiometabolic Traits: A Mendelian Randomization Analysis.

    Science.gov (United States)

    Geng, Tingting; Smith, Caren E; Li, Changwei; Huang, Tao

    2018-05-01

    To test the causal effect of childhood BMI on adult cardiometabolic diseases using a Mendelian randomization analysis. We used 15 single nucleotide polymorphisms as instrumental variables for childhood BMI to test the causal effect of childhood BMI on cardiometabolic diseases using summary-level data from consortia. We found that a 1-SD increase in childhood BMI (kg/m 2 ) was associated with an 83% increase in risk of type 2 diabetes (odds ratio [OR] 1.83 [95% CI 1.46, 2.30]; P = 2.5 × 10 -7 ) and a 28% increase in risk of coronary artery disease (CAD) (OR 1.28 [95% CI 1.17, 1.39]; P = 2.1 × 10 -8 ) at the Bonferroni-adjusted level of significance ( P BMI was associated with a 0.587-SD increase in adulthood BMI (kg/m 2 ), a 0.062-SD increase in hip circumference (cm), a 0.602-SD increase in waist circumference (cm), a 0.111 pmol/L increase in log fasting insulin, a 0.068 increase in log-transformed HOMA of ß-cell function (%), a 0.126 increase in log-transformed HOMA of insulin resistance (%), and a 0.109-SD increase in triglyceride (mg/dL) but a 0.138-SD decrease in HDL (mg/dL) in adults at the Bonferroni-adjusted level of significance ( P BMI was associated with increased risk of type 2 diabetes and CAD in adult life. These results provide evidence supportive of a causal association between childhood BMI and these outcomes. © 2018 by the American Diabetes Association.

  10. Increased alcohol consumption as a cause of alcoholism, without similar evidence for depression: a Mendelian randomization study.

    Science.gov (United States)

    Wium-Andersen, Marie Kim; Ørsted, David Dynnes; Tolstrup, Janne Schurmann; Nordestgaard, Børge Grønne

    2015-04-01

    Increased alcohol consumption has been associated with depression and alcoholism, but whether these associations are causal remains unclear. We tested whether alcohol consumption is causally associated with depression and alcoholism. We included 78,154 men and women aged 20-100 years randomly selected in 1991-2010 from the general population of Copenhagen, Denmark, and genotyped 68,486 participants for two genetic variants in two alcohol dehydrogenase (ADH) genes, ADH-1B (rs1229984) and ADH-1C (rs698). We performed observational and causal analyses using a Mendelian randomization design with antidepressant medication use and hospitalization/death, with depression and alcoholism as outcomes. In prospective analyses, the multifactorially adjusted hazard ratio for participants reporting >6 drinks/day vs participants reporting 0.1-1 drinks/day was 1.28 (95% confidence interval, 1.00-1.65) for prescription antidepressant use, with a corresponding hazard ratio of 0.80 (0.45-1.45) for hospitalization/death with depression and of 11.7 (8.77-15.6) for hospitalization/death with alcoholism. For hospitalization/death with alcoholism, instrumental variable analysis yielded a causal odds ratio of 28.6 (95 % confidence interval 6.47-126) for an increase of 1 drink/day estimated from the combined genotype combination, whereas the corresponding multifactorially adjusted observational odds ratio was 1.28 (1.25-1.31). Corresponding odds ratios were 1.11 (0.67-1.83) causal and 1.04 (1.03-1.06) observational for prescription antidepressant use, and 4.52 (0.99-20.5) causal and 0.98 (0.94-1.03) observational for hospitalization/death with depression. These data indicate that the association between increased alcohol consumption and alcoholism is causal, without similar strong evidence for depression. © The Author 2014; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association.

  11. The Mendelian inheritance of rare flesh and shell colour variants in the black-lipped pearl oyster (Pinctada margaritifera).

    Science.gov (United States)

    Ky, Chin-Long; Nakasai, Seiji; Pommier, Steve; Sham Koua, Manaarii; Devaux, Dominique

    2016-10-01

    Pinctada margaritifera is French Polynesia's most economically important aquaculture species. This pearl oyster has the specific ability to produce cultured pearls with a very wide range of colours, depending on the colour phenotypes of donor oysters used. Its aquaculture is still based on natural spat collection from wild stocks. We investigated three rare colour variants of P. margaritifera - orange flesh, and red and white shell colour phenotypes - in comparison with the wild-type black flesh and shell commonly found in this species. The study aimed to assess the geographic distribution and genetic basis of these colour variants. Colour frequencies were evaluated during transfer and graft processes of pearl oyster seed captured at collector stations. Among the collection locations studied, Mangareva Island showed the highest rate of the orange flesh phenotype, whereas Takaroa and Takume atolls had relatively high rates of red and white shell phenotypes respectively. Broodstocks were made of these rare colour variants, and crosses were performed to produce first- and second-generation progenies to investigate segregation. The results were consistent with Mendelian ratios and suggest a distinct model with no co-dominance: (i) a two-allele model for flesh trait, whereby the orange allele is recessive to the black fleshed type, and (ii) a three-allele model for shell trait, whereby the black wild-type allele is dominant to the red coloration, which is dominant to the white shell. Furthermore, the proposed model provides the basis for producing selected donor pearl oyster lines through hatchery propagation. © 2016 Stichting International Foundation for Animal Genetics.

  12. Smoking is associated with, but does not cause, depressed mood in pregnancy--a mendelian randomization study.

    Directory of Open Access Journals (Sweden)

    Sarah J Lewis

    Full Text Available Smokers have a higher prevalence of major depressive episodes and depressive symptoms than the general population, but whether this association is causal, or is due to confounding or reverse causation is uncertain because of the problems inherent in some epidemiological studies. Mendelian randomization, in which a genetic variant is used as a surrogate for measuring exposure, is an approach which may be used to better understand this association. We investigated the rs1051730 single nucleotide polymorphism in the nicotine acetylcholine receptor gene cluster (CHRNA5-CHRNA3-CHRNB4, associated with smoking phenotypes, to determine whether women who continued to smoke were also more likely to report a low mood during pregnancy. We found among women who smoked pre-pregnancy, those with the 1051730 T allele smoked more and were less likely to quit smoking during pregnancy, but were also less likely to report high levels of depressed mood at 18 weeks of pregnancy (per allele OR = 0.84, 95%CI 0.72 to 0.99, p = 0.034. The association between genotype and depressed mood was limited to women who were smokers prior to pregnancy, with weak evidence of an interaction between smoking status and genotype (p = 0.07. Our results do not support a causal role of smoking on depressed mood, but are consistent with a self-medication hypothesis, whereby smoking is used to alleviate symptoms of depression. A replication study using multiple genetic variants which influence smoking via different pathways is required to confirm these findings and provide evidence that the genetic variant is reflecting the effect of quitting smoking on depressed mood, and is not directly affecting mood.

  13. Mendelian randomization analysis of a time-varying exposure for binary disease outcomes using functional data analysis methods.

    Science.gov (United States)

    Cao, Ying; Rajan, Suja S; Wei, Peng

    2016-12-01

    A Mendelian randomization (MR) analysis is performed to analyze the causal effect of an exposure variable on a disease outcome in observational studies, by using genetic variants that affect the disease outcome only through the exposure variable. This method has recently gained popularity among epidemiologists given the success of genetic association studies. Many exposure variables of interest in epidemiological studies are time varying, for example, body mass index (BMI). Although longitudinal data have been collected in many cohort studies, current MR studies only use one measurement of a time-varying exposure variable, which cannot adequately capture the long-term time-varying information. We propose using the functional principal component analysis method to recover the underlying individual trajectory of the time-varying exposure from the sparsely and irregularly observed longitudinal data, and then conduct MR analysis using the recovered curves. We further propose two MR analysis methods. The first assumes a cumulative effect of the time-varying exposure variable on the disease risk, while the second assumes a time-varying genetic effect and employs functional regression models. We focus on statistical testing for a causal effect. Our simulation studies mimicking the real data show that the proposed functional data analysis based methods incorporating longitudinal data have substantial power gains compared to standard MR analysis using only one measurement. We used the Framingham Heart Study data to demonstrate the promising performance of the new methods as well as inconsistent results produced by the standard MR analysis that relies on a single measurement of the exposure at some arbitrary time point. © 2016 WILEY PERIODICALS, INC.

  14. Evaluating the Causal Link Between Malaria Infection and Endemic Burkitt Lymphoma in Northern Uganda: A Mendelian Randomization Study.

    Science.gov (United States)

    Legason, Ismail D; Pfeiffer, Ruth M; Udquim, Krizia-Ivana; Bergen, Andrew W; Gouveia, Mateus H; Kirimunda, Samuel; Otim, Isaac; Karlins, Eric; Kerchan, Patrick; Nabalende, Hadijah; Bayanjargal, Ariunaa; Emmanuel, Benjamin; Kagwa, Paul; Talisuna, Ambrose O; Bhatia, Kishor; Yeager, Meredith; Biggar, Robert J; Ayers, Leona W; Reynolds, Steven J; Goedert, James J; Ogwang, Martin D; Fraumeni, Joseph F; Prokunina-Olsson, Ludmila; Mbulaiteye, Sam M

    2017-11-01

    Plasmodium falciparum (Pf) malaria infection is suspected to cause endemic Burkitt Lymphoma (eBL), but the evidence remains unsettled. An inverse relationship between sickle cell trait (SCT) and eBL, which supports that between malaria and eBL, has been reported before, but in small studies with low power. We investigated this hypothesis in children in a population-based study in northern Uganda using Mendelian Randomization. Malaria-related polymorphisms (SCT, IL10, IL1A, CD36, SEMA3C, and IFNAR1) were genotyped in 202 eBL cases and 624 controls enrolled during 2010-2015. We modeled associations between genotypes and eBL or malaria using logistic regression. SCT was associated with decreased risk of eBL (adjusted odds ratio [OR] 0·37, 95% CI 0·21-0·66; p=0·0003). Decreased risk of eBL was associated with IL10 rs1800896-CT (OR 0·73, 95% CI 0·50-1·07) and -CC genotypes (OR 0·53, 95% CI 0·29-0·95, p trend =0·019); IL1A rs2856838-AG (OR 0·56, 95% CI 0·39-0·81) and -AA genotype (OR 0·50, 95% CI 0·28-1·01, p trend =0·0016); and SEMA3C rs4461841-CT or -CC genotypes (OR 0·57, 95% CI 0·35-0·93, p=0·0193). SCT and IL10 rs1800896, IL1A rs2856838, but not SEMA3C rs4461841, polymorphisms were associated with decreased risk of malaria in the controls. Our results support a causal effect of malaria infection on eBL. Published by Elsevier B.V.

  15. Three genome-wide association studies and a linkage analysis identify HERC2 as a human iris color gene

    NARCIS (Netherlands)

    Kayser, Manfred; Liu, Fan; Janssens, A. Cecile J. W.; Rivadeneira, Fernando; Lao, Oscar; van Duijn, Kate; Vermeulen, Mark; Arp, Pascal; Jhamai, Mila M.; van Ijcken, Wilfred F. J.; den Dunnen, Johan T.; Heath, Simon; Zelenika, Diana; Despriet, Dominiek D. G.; Klaver, Caroline C. W.; Vingerling, Johannes R.; de Jong, Paulus T. V. M.; Hofman, Albert; Aulchenko, Yurii S.; Uitterlinden, Andre G.; Oostra, Ben A.; van Duijn, Cornelia M.

    2008-01-01

    Human iris color was one of the first traits for which Mendelian segregation was established. To date, the genetics of iris color is still not fully understood and is of interest, particularly in view of forensic applications. In three independent genome-wide association (GWA) studies of a total of

  16. Dutch guideline for the management of hypertensive crisis -- 2010 revision

    NARCIS (Netherlands)

    van den Born, B. J. H.; Beutler, J. J.; Gaillard, C. A. J. M.; de Gooijer, A.; van den Meiracker, A. H.; Kroon, A. A.

    2011-01-01

    Hypertensive crises are divided into hypertensive urgencies and emergencies. Together they form a heterogeneous group of acute hypertensive disorders depending on the presence or type of target organs involved. Despite better treatment options for hypertension, hypertensive crisis and its associated

  17. Management of hypertension in pregnancy.

    Science.gov (United States)

    Chung, N A; Beevers, D G; Lip, G Y

    2001-01-01

    Hypertension is an important cause of both maternal and fetal morbidity and mortality in pregnant women. There are still no definitive guidelines as to when and how patients should be treated, but it is important that appropriate treatment is initiated early in patients at highest risk and they are closely monitored. Hypertension in pregnancy can be a difficult condition to diagnose and treat because of the numerous and differing classification systems that have been used in the past. One classification system, which accounts for the multisystem involvement which can occur in pre-eclampsia and eclampsia, divides hypertension in pregnancy into 3 main groups: pre-eclampsia, gestational hypertension and chronic hypertension. Little benefit to the fetus has been shown from treating gestational and chronic hypertension, but studies in this area have been small and would not have had the power to show a difference in outcome between treated and untreated groups. However, the reduction in morbidity and mortality in the treatment of pre-eclampsia is significant. Therefore, all pregnancies complicated by hypertension require monitoring to detect the possible onset of superimposed pre-eclampsia/eclampsia. Institutions should have a management strategy for those mothers with severe hypertension including a multidisciplinary approach, where the patient is to be monitored and which antihypertensive agents are to be used. It should not be forgotten that the definitive treatment for severe hypertension is delivery of the fetus despite risks to fetal morbidity and mortality. This will reduce blood pressure, but hypertension per se may still persist post partum requiring short term therapy.

  18. OBESITY-INDUCED HYPERTENSION: INTERACTION OF NEUROHUMORAL AND RENAL MECHANISMS

    Science.gov (United States)

    Hall, John E.; do Carmo, Jussara M.; da Silva, Alexandre A.; Wang, Zhen; Hall, Michael E.

    2015-01-01

    Excess weight gain, especially when associated with increased visceral adiposity, is a major cause of hypertension, accounting for 65–75% of the risk for human primary (essential) hypertension. Increased renal tubular sodium reabsorption impairs pressure natriuresis and plays an important role in initiating obesity hypertension. The mediators of abnormal kidney function and increased blood pressure during development of obesity hypertension include 1) physical compression of the kidneys by fat in and around the kidneys, 2) activation of the renin-angiotensin-aldosterone system (RAAS), and 3) increased sympathetic nervous system (SNS) activity. Activation of the RAAS system is likely due, in part, to renal compression as well as SNS activation. However, obesity also causes mineralocorticoid receptor activation independent of aldosterone or angiotensin II. The mechanisms for SNS activation in obesity have not been fully elucidated but appear to require leptin and activation of the brain melanocortin system. With prolonged obesity and development of target organ injury, especially renal injury, obesity-associated hypertension becomes more difficult to control, often requiring multiple antihypertensive drugs and treatment of other risk factors, including dyslipidemia, insulin resistance and diabetes, and inflammation. Unless effective anti-obesity drugs are developed, the impact of obesity on hypertension and related cardiovascular, renal and metabolic disorders is likely to become even more important in the future as the prevalence of obesity continues to increase. PMID:25767285

  19. Definition and management of hypertension among Haitian immigrants: a qualitative study.

    Science.gov (United States)

    Sanon, Marie-Anne; Mohammed, Selina A; McCullagh, Marjorie C

    2014-08-01

    Hypertension is a major health concern among Haitian immigrants, one of the largest Caribbean immigrant groups in the United States. Yet, little is known about how Hatian immigrants define and manage hypertension. For this qualitative study, face-to-face semi-structured interviews were conducted with 31 Haitian immigrants in Miami Dade County, Florida. Results indicated that most Haitian immigrants used the Haitian Creole word tansyon to represent hypertension. Tansyon was considered as either a normal condition of the human body or a maladi (illness). Both traditional biomedical and alternative approaches were used to manage hypertension. The findings show that how Haitian immigrants defined hypertension shaped their beliefs about its occurrence and the resulting management strategies used. Those who believed tansyon was a normal body condition did not take any management measures. Awareness and understanding of Haitian immigrants' beliefs about and approaches to hypertension management can enhance culturally sensitive care and improve health outcomes.

  20. Seclusion, decision-making power, and gender disparities in adult health: Examining hypertension in India.

    Science.gov (United States)

    Stroope, Samuel

    2015-09-01

    Research on the social determinants of health in developing countries is increasingly focusing on the importance of gender. Cardiovascular conditions such as hypertension are a growing concern in developing countries, where they are now the leading cause of death. Researchers have documented differences in hypertension between men and women, but the importance of gendered practices in shaping these differences has been left unexamined. Using national data from the India Human Development Survey 2005 (N=101,593), this study assesses the moderating role of two salient and widespread gendered practices-women's seclusion and decision-making power-on hypertension disparities between women and men. Both seclusion and low decision-making power are associated with increased odds of hypertension for women, but in the case of seclusion reduced hypertension for men. Results also show the gender gap in hypertension is exacerbated with women's seclusion and low decision-making power. Copyright © 2015 Elsevier Inc. All rights reserved.

  1. Assessing the associations of blood metabolites with osteoporosis: a Mendelian randomization study.

    Science.gov (United States)

    Liu, Li; Wen, Yan; Zhang, Lei; Xu, Peng; Liang, Xiao; Du, Yanan; Li, Ping; He, Awen; Fan, QianRui; Hao, Jingcan; Wang, Wenyu; Guo, Xiong; Shen, Hui; Tian, Qing; Zhang, Feng; Deng, Hong-Wen

    2018-03-01

    Osteoporosis is a metabolic bone disease. The impact of blood metabolites on the development of osteoporosis remains elusive now. To explore the relationship between blood metabolites and osteoporosis. We used 2,286 unrelated Caucasian subjects as discovery samples and 3,143 unrelated Caucasian subjects from the Framingham heart study (FHS) as replication samples. Bone mineral density (BMD) were measured using dual-energy X-ray absorptiometry. Genome-wide SNP genotyping was performed using Affymetrix Human SNP Array 6.0 (for discovery samples) and Affymetrix SNP 500K and 50K array (for FHS replication samples). The SNP sets significantly associated with blood metabolites were obtained from a published whole-genome sequencing study. For each subject, the genetic risk score (GRS) of metabolite was calculated from the genotype data of metabolite associated SNP sets. Pearson correlation analysis was conducted to evaluate the potential impact of blood metabolites on the variations bone phenotypes. 10,000 permutations were conducted to calculate the empirical P value and false discovery rate (FDR). 481 blood metabolites were analyzed in this study. We identified multiple blood metabolites associated with hip BMD, such as 1,5-anhydroglucitol(1,5-AG) (Pdiscovery metabolites on the variations of BMD, and identified several candidate blood metabolites for osteoporosis.

  2. Pulmonary arterial hypertension

    Science.gov (United States)

    2013-01-01

    Pulmonary arterial hypertension (PAH) is a chronic and progressive disease leading to right heart failure and ultimately death if untreated. The first classification of PH was proposed in 1973. In 2008, the fourth World Symposium on PH held in Dana Point (California, USA) revised previous classifications. Currently, PH is devided into five subgroups. Group 1 includes patients suffering from idiopathic or familial PAH with or without germline mutations. Patients with a diagnosis of PAH should systematically been screened regarding to underlying mutations of BMPR2 gene (bone morphogenetic protein receptor type 2) or more rarely of ACVRL1 (activine receptor-like kinase type 1), ENG (endogline) or Smad8 genes. Pulmonary veno occusive disease and pulmonary capillary hemagiomatosis are individualized and designated as clinical group 1'. Group 2 'Pulmonary hypertension due to left heart diseases' is divided into three sub-groups: systolic dysfonction, diastolic dysfonction and valvular dysfonction. Group 3 'Pulmonary hypertension due to respiratory diseases' includes a heterogenous subgroup of respiratory diseases like PH due to pulmonary fibrosis, COPD, lung emphysema or interstitial lung disease for exemple. Group 4 includes chronic thromboembolic pulmonary hypertension without any distinction of proximal or distal forms. Group 5 regroup PH patients with unclear multifactorial mechanisms. Invasive hemodynamic assessment with right heart catheterization is requested to confirm the definite diagnosis of PH showing a resting mean pulmonary artery pressure (mPAP) of ≥ 25 mmHg and a normal pulmonary capillary wedge pressure (PCWP) of ≤ 15 mmHg. The assessment of PCWP may allow the distinction between pre-capillary and post-capillary PH (PCWP > 15 mmHg). Echocardiography is an important tool in the management of patients with underlying suspicion of PH. The European Society of Cardiology and the European Respiratory Society (ESC-ERS) guidelines specify its role

  3. Association between Adult Height and Risk of Colorectal, Lung, and Prostate Cancer: Results from Meta-analyses of Prospective Studies and Mendelian Randomization Analyses

    Science.gov (United States)

    Khankari, Nikhil K.; Shu, Xiao-Ou; Wen, Wanqing; Kraft, Peter; Lindström, Sara; Peters, Ulrike; Schildkraut, Joellen; Schumacher, Fredrick; Bofetta, Paolo; Risch, Angela; Bickeböller, Heike; Amos, Christopher I.; Easton, Douglas; Gruber, Stephen B.; Haiman, Christopher A.; Hunter, David J.; Chanock, Stephen J.; Pierce, Brandon L.; Zheng, Wei

    2016-01-01

    Background Observational studies examining associations between adult height and risk of colorectal, prostate, and lung cancers have generated mixed results. We conducted meta-analyses using data from prospective cohort studies and further carried out Mendelian randomization analyses, using height-associated genetic variants identified in a genome-wide association study (GWAS), to evaluate the association of adult height with these cancers. Methods and Findings A systematic review of prospective studies was conducted using the PubMed, Embase, and Web of Science databases. Using meta-analyses, results obtained from 62 studies were summarized for the association of a 10-cm increase in height with cancer risk. Mendelian randomization analyses were conducted using summary statistics obtained for 423 genetic variants identified from a recent GWAS of adult height and from a cancer genetics consortium study of multiple cancers that included 47,800 cases and 81,353 controls. For a 10-cm increase in height, the summary relative risks derived from the meta-analyses of prospective studies were 1.12 (95% CI 1.10, 1.15), 1.07 (95% CI 1.05, 1.10), and 1.06 (95% CI 1.02, 1.11) for colorectal, prostate, and lung cancers, respectively. Mendelian randomization analyses showed increased risks of colorectal (odds ratio [OR] = 1.58, 95% CI 1.14, 2.18) and lung cancer (OR = 1.10, 95% CI 1.00, 1.22) associated with each 10-cm increase in genetically predicted height. No association was observed for prostate cancer (OR = 1.03, 95% CI 0.92, 1.15). Our meta-analysis was limited to published studies. The sample size for the Mendelian randomization analysis of colorectal cancer was relatively small, thus affecting the precision of the point estimate. Conclusions Our study provides evidence for a potential causal association of adult height with the risk of colorectal and lung cancers and suggests that certain genetic factors and biological pathways affecting adult height may also affect the

  4. Mental stress and hypertension, an evolutionary framework: some historical perspectives of the 1960 World Health Organization Prague Hypertension Meeting.

    Science.gov (United States)

    Kuchel, Otto

    2003-03-01

    Emotional stress acutely and repetitively causing blood pressure increase or aggravating existing hypertension is usually not reflected by norepinephrine and epinephrine increase but by a sudden rise of dopamine, the third "defensive" catecholamine coping with the damaging neuropsychological and cardiovascular actions of the first two. This double-edged sympathetic response to emotional stress evolves during human lifespan and long-term evolution of hypertension. In the course of philogenesis it carries a potential mismatch between the normal physiology of the human dopaminergic system and current environmental (emotional particularly) conditions in industrialized countries. This offers a rational support to a mental stress-cardiovascular diseases relationship proposed 40 years ago in a WHO report which followed a memorable 1960 Prague Hypertension Meeting.

  5. Hypertension in Patients with Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Souza, Vinicius Barbosa de; Silva, Eduardo Nani; Ribeiro, Mario Luiz; Martins, Wolney de Andrade, E-mail: wolney@cardiol.br [Curso de Pós-Graduação em Ciências Cardiovasculares da Universidade Federal Fluminense, Niterói, RJ (Brazil)

    2015-03-15

    There is a known association between chemotherapy and radiotherapy for treatment of cancer patients and development or worsening of hypertension. The aim of this article is to review this association. A literature search was conducted for articles reporting this association on the databases PubMed, SciELO and LILACS between 1993 and 2013. There was a high coprevalence of hypertension and cancer, since both diseases share the same risk factors, such as sedentary lifestyle, obesity, smoking, unhealthy diet and alcohol abuse. The use of chemotherapy and adjuvant drugs effective in the treatment of cancer increased the survival rate of these patients and, consequently, increased the incidence of hypertension. We described the association between the use of angiogenesis inhibitors (bevacizumab, sorafenib and sunitinib), corticosteroids, erythropoietin and non-steroidal anti-inflammatory drugs with the development of hypertension. We also described the relationship between hypertension and carotid baroreceptor injury secondary to cervical radiotherapy. Morbidity and mortality increased in patients with cancer and hypertension without proper antihypertensive treatment. We concluded that there is need for early diagnosis, effective monitoring and treatment strategies for hypertension in cancer patients in order to reduce cardiovascular morbidity and mortality.

  6. Hypertension in Patients with Cancer

    International Nuclear Information System (INIS)

    Souza, Vinicius Barbosa de; Silva, Eduardo Nani; Ribeiro, Mario Luiz; Martins, Wolney de Andrade

    2015-01-01

    There is a known association between chemotherapy and radiotherapy for treatment of cancer patients and development or worsening of hypertension. The aim of this article is to review this association. A literature search was conducted for articles reporting this association on the databases PubMed, SciELO and LILACS between 1993 and 2013. There was a high coprevalence of hypertension and cancer, since both diseases share the same risk factors, such as sedentary lifestyle, obesity, smoking, unhealthy diet and alcohol abuse. The use of chemotherapy and adjuvant drugs effective in the treatment of cancer increased the survival rate of these patients and, consequently, increased the incidence of hypertension. We described the association between the use of angiogenesis inhibitors (bevacizumab, sorafenib and sunitinib), corticosteroids, erythropoietin and non-steroidal anti-inflammatory drugs with the development of hypertension. We also described the relationship between hypertension and carotid baroreceptor injury secondary to cervical radiotherapy. Morbidity and mortality increased in patients with cancer and hypertension without proper antihypertensive treatment. We concluded that there is need for early diagnosis, effective monitoring and treatment strategies for hypertension in cancer patients in order to reduce cardiovascular morbidity and mortality

  7. Vascular Remodeling in Experimental Hypertension

    Directory of Open Access Journals (Sweden)

    Norma R. Risler

    2005-01-01

    Full Text Available The basic hemodynamic abnormality in hypertension is an increased peripheral resistance that is due mainly to a decreased vascular lumen derived from structural changes in the small arteries wall, named (as a whole vascular remodeling. The vascular wall is an active, flexible, and integrated organ made up of cellular (endothelial cells, smooth muscle cells, adventitia cells, and fibroblasts and noncellular (extracellular matrix components, which in a dynamic way change shape or number, or reorganize in response to physiological and pathological stimuli, maintaining the integrity of the vessel wall in physiological conditions or participating in the vascular changes in cardiovascular diseases such as hypertension. Research focused on new signaling pathways and molecules that can participate in the mechanisms of vascular remodeling has provided evidence showing that vascular structure is not only affected by blood pressure, but also by mechanisms that are independent of the increased pressure. This review will provide an overview of the evidence, explaining some of the pathophysiologic mechanisms participating in the development of the vascular remodeling, in experimental models of hypertension, with special reference to the findings in spontaneously hypertensive rats as a model of essential hypertension, and in fructose-fed rats as a model of secondary hypertension, in the context of the metabolic syndrome. The understanding of the mechanisms producing the vascular alterations will allow the development of novel pharmacological tools for vascular protection in hypertensive disease.

  8. Does exercise pulmonary hypertension exist?

    Science.gov (United States)

    Lau, Edmund M; Chemla, Denis; Whyte, Kenneth; Kovacs, Gabor; Olschewski, Horst; Herve, Philippe

    2016-09-01

    The exercise definition of pulmonary hypertension using a mean pulmonary artery pressure threshold of greater than 30 mmHg was abandoned following the 4th World Pulmonary Hypertension Symposium in 2008, as this definition was not supported by evidence and healthy individuals frequently exceed this threshold. Meanwhile, the clinical value of exercise pulmonary hemodynamic testing has also been questioned. Recent data support the notion that an abnormal pulmonary hemodynamic response during exercise (or exercise pulmonary hypertension) is associated with symptoms and exercise limitation. Pathophysiologic mechanisms accounting for the development of exercise pulmonary hypertension include increased vascular resistance, excessive elevation in left atrial pressure and/or increased volume of trapped air during exercise, resulting in a steep rise in pulmonary artery pressure relative to cardiac output. Recent evidence suggests that exercise pulmonary hypertension may be defined by a mean pulmonary artery pressure surpassing 30 mmHg together with a simultaneous total pulmonary resistance exceeding 3 WU. Exercise pulmonary hypertension is a clinically relevant entity and an improved definition has been suggested based on new evidence. Exercise pulmonary hemodynamics may help unmask early or latent disease, particularly in populations that are at high risk for the development of pulmonary hypertension.

  9. A Standardized DNA Variant Scoring System for Pathogenicity Assessments in Mendelian Disorders.

    Science.gov (United States)

    Karbassi, Izabela; Maston, Glenn A; Love, Angela; DiVincenzo, Christina; Braastad, Corey D; Elzinga, Christopher D; Bright, Alison R; Previte, Domenic; Zhang, Ke; Rowland, Charles M; McCarthy, Michele; Lapierre, Jennifer L; Dubois, Felicita; Medeiros, Katelyn A; Batish, Sat Dev; Jones, Jeffrey; Liaquat, Khalida; Hoffman, Carol A; Jaremko, Malgorzata; Wang, Zhenyuan; Sun, Weimin; Buller-Burckle, Arlene; Strom, Charles M; Keiles, Steven B; Higgins, Joseph J

    2016-01-01

    We developed a rules-based scoring system to classify DNA variants into five categories including pathogenic, likely pathogenic, variant of uncertain significance (VUS), likely benign, and benign. Over 16,500 pathogenicity assessments on 11,894 variants from 338 genes were analyzed for pathogenicity based on prediction tools, population frequency, co-occurrence, segregation, and functional studies collected from internal and external sources. Scores were calculated by trained scientists using a quantitative framework that assigned differential weighting to these five types of data. We performed descriptive and comparative statistics on the dataset and tested interobserver concordance among the trained scientists. Private variants defined as variants found within single families (n = 5,182), were either VUS (80.5%; n = 4,169) or likely pathogenic (19.5%; n = 1,013). The remaining variants (n = 6,712) were VUS (38.4%; n = 2,577) or likely benign/benign (34.7%; n = 2,327) or likely pathogenic/pathogenic (26.9%, n = 1,808). Exact agreement between the trained scientists on the final variant score was 98.5% [95% confidence interval (CI) (98.0, 98.9)] with an interobserver consistency of 97% [95% CI (91.5, 99.4)]. Variant scores were stable and showed increasing odds of being in agreement with new data when re-evaluated periodically. This carefully curated, standardized variant pathogenicity scoring system provides reliable pathogenicity scores for DNA variants encountered in a clinical laboratory setting. © 2015 The Authors. **Human Mutation published by Wiley Periodicals, Inc.

  10. Clinical Whole-Exome Sequencing for the Diagnosis of Mendelian Disorders

    Science.gov (United States)

    Yang, Yaping; Muzny, Donna M.; Reid, Jeffrey G.; Bainbridge, Matthew N.; Willis, Alecia; Ward, Patricia A.; Braxton, Alicia; Beuten, Joke; Xia, Fan; Niu, Zhiyv; Hardison, Matthew; Person, Richard; Bekheirnia, Mir Reza; Leduc, Magalie S.; Kirby, Amelia; Pham, Peter; Scull, Jennifer; Wang, Min; Ding, Yan; Plon, Sharon E.; Lupski, James R.; Beaudet, Arthur L.; Gibbs, Richard A.; Eng, Christine M.

    2014-01-01

    BACKGROUND Whole-exome sequencing is a diagnostic approach for the identification of molecular defects in patients with suspected genetic disorders. METHODS We developed technical, bioinformatic, interpretive, and validation pipelines for whole-exome sequencing in a certified clinical laboratory to identify sequence variants underlying disease phenotypes in patients. RESULTS We present data on the first 250 probands for whom referring physicians ordered whole-exome sequencing. Patients presented with a range of phenotypes suggesting potential genetic causes. Approximately 80% were children with neurologic pheno-types. Insurance coverage was similar to that for established genetic tests. We identified 86 mutated alleles that were highly likely to be causative in 62 of the 250 patients, achieving a 25% molecular diagnostic rate (95% confidence interval, 20 to 31). Among the 62 patients, 33 had autosomal dominant disease, 16 had auto-somal recessive disease, and 9 had X-linked disease. A total of 4 probands received two nonoverlapping molecular diagnoses, which potentially challenged the clinical diagnosis that had been made on the basis of history and physical examination. A total of 83% of the autosomal dominant mutant alleles and 40% of the X-linked mutant alleles occurred de novo. Recurrent clinical phenotypes occurred in patients with mutations that were highly likely to be causative in the same genes and in different genes responsible for genetically heterogeneous disorders. CONCLUSIONS Whole-exome sequencing identified the underlying genetic defect in 25% of consecutive patients referred for evaluation of a possible genetic condition. (Funded by the National Human Genome Research Institute.) PMID:24088041

  11. Masked Uncontrolled Hypertension in CKD.

    Science.gov (United States)

    Agarwal, Rajiv; Pappas, Maria K; Sinha, Arjun D

    2016-03-01

    Masked uncontrolled hypertension (MUCH) is diagnosed in patients treated for hypertension who are normotensive in the clinic but hypertensive outside. In this study of 333 veterans with CKD, we prospectively evaluated the prevalence of MUCH as determined by ambulatory BP monitoring using three definitions of hypertension (daytime hypertension ≥135/85 mmHg; either nighttime hypertension ≥120/70 mmHg or daytime hypertension; and 24-hour hypertension ≥130/80 mmHg) or by home BP monitoring (hypertension ≥135/85 mmHg). The prevalence of MUCH was 26.7% by daytime ambulatory BP, 32.8% by 24-hour ambulatory BP, 56.1% by daytime or night-time ambulatory BP, and 50.8% by home BP. To assess the reproducibility of the diagnosis, we repeated these measurements after 4 weeks. Agreement in MUCH diagnosis by ambulatory BP was 75-78% (κ coefficient for agreement, 0.44-0.51), depending on the definition used. In contrast, home BP showed an agreement of only 63% and a κ coefficient of 0.25. Prevalence of MUCH increased with increasing clinic systolic BP: 2% in the 90-110 mmHg group, 17% in the 110-119 mmHg group, 34% in the 120-129 mmHg group, and 66% in the 130-139 mmHg group. Clinic BP was a good determinant of MUCH (receiver operating characteristic area under the curve 0.82; 95% confidence interval 0.76-0.87). In diagnosing MUCH, home BP was not different from clinic BP. In conclusion, among people with CKD, MUCH is common and reproducible, and should be suspected when clinic BP is in the prehypertensive range. Confirmation of MUCH diagnosis should rely on ambulatory BP monitoring. Copyright © 2016 by the American Society of Nephrology.

  12. pre-hypertension and hypertension in apparently healthy ...

    African Journals Online (AJOL)

    user

    hypertension among urban adolescents in Calabar, south eastern Nigeria. This was a ... disease later in life but also to significantly increase .... beam balance is not available (Paynter and ..... keeping with work done among Nigerian School.

  13. Ethical Dilemmas when Diagnosing Hypertension

    Directory of Open Access Journals (Sweden)

    Sandra Santana López

    2012-12-01

    Full Text Available A review on the ethical dilemmas in the diagnosis of hypertension and some elements in the emergence of the bioethics concept was performed. Ethical conflicts that appear at each stage of diagnosis of hypertension: at the time of providing the information, at the point of indication and performance of diagnostic tests, when communicating the diagnosis and during subsequent decision making were identified. We conclude that technological development will introduce new ethical decisions in the diagnosis of hypertension that will increasingly involve the interests of society and create, in one way or another, ethical and moral conflict in the decision making process.

  14. [Hypertension in women after menopause].

    Science.gov (United States)

    Beaufils, Michel

    2006-06-01

    Menopause coincides with an increase in the incidence of hypertension in women. A direct role of estrogen deprivation in this increased blood pressure remains a topic of debate. Menopause probably accelerates the arterial changes related to aging. Hormone replacement therapy does not influence blood pressure significantly and is not contraindicated in hypertensive women. The effect of hormone replacement treatment on cardiovascular risk was recently the object of controversy. It does not increase risk except in cases of late treatment in older women who already have atherosclerosis. Hypertension management in women is otherwise similar to management in men.

  15. Hypertension--forekomst og behandling

    DEFF Research Database (Denmark)

    Ibsen, Hans; Jørgensen, Torben; Jensen, Gorm B

    2009-01-01

    Hypertension is the most important modifiable risk factor for cardiovascular disease. However, less than half of all hypertensives have their blood pressure reduced to relevant goals. The prevalence of hypertension in Denmark was found to be between 26% and 40% of the adult population. Just over...... half were aware of the diagnosis, but less than half were in treatment. Blood pressure control in patients who are undergoing treatment has improved during recent years, but there is still a gap to achievable control rates. Udgivelsesdato: 2009-Jun-8...

  16. [The magnetotherapy of hypertension patients].

    Science.gov (United States)

    Ivanov, S G; Smirnov, V V; Solov'eva, F V; Liashevskaia, S P; Selezneva, L Iu

    1990-01-01

    A study was made of the influence of the constant MKM2-1 magnets on patients suffering from essential hypertension. Continuous action of the magnetic field, created by such magnets, on the patients with stage II essential hypertension was noted to result in a decrease of arterial pressure without the occurrence of any side effects and in a simultaneous reduction of the scope of drug administration. Apart from that fact, magnetotherapy was discovered to produce a beneficial effect on the central hemodynamics and microcirculation. The use of the MKM2-1 magnets may be regarded as a feasible method of the treatment of essential hypertension patients at any medical institution.

  17. Definition and classification of pulmonary hypertension.

    Science.gov (United States)

    Humbert, Marc; Montani, David; Evgenov, Oleg V; Simonneau, Gérald

    2013-01-01

    Pulmonary hypertension is defined as an increase of mean pulmonary arterial pressure ≥25 mmHg at rest as assessed by right heart catheterization. According to different combinations of values of pulmonary wedge pressure, pulmonary vascular resistance and cardiac output, a hemodynamic classification of pulmonary hypertension has been proposed. Of major importance is the pulmonary wedge pressure which allows to distinguish pre-capillary (pulmonary wedge pressure ≤15 mmHg) and post-capillary (pulmonary wedge pressure >15 mmHg) pulmonary hypertension. Pre-capillary pulmonary hypertension includes the clinical groups 1 (pulmonary arterial hypertension), 3 (pulmonary hypertension due to lung diseases and/or hypoxia), 4 (chronic thrombo-embolic pulmonary hypertension) and 5 (pulmonary hypertension with unclear and/or multifactorial mechanisms). Post-capillary pulmonary hypertension corresponds to the clinical group 2 (pulmonary hypertension due to left heart diseases).

  18. [Diagnostic of secondary hypertension in clinical practice].

    Science.gov (United States)

    Somlóová, Z; Rosa, J; Petrák, O; Strauch, B; Zelinka, T; Holaj, R; Widimský, J

    2011-09-01

    Arterial hypertension is a common worldwide disease with a prevalence of approximately 26%. Secondary cause is known in 5-10% of patients with hypertension. We should think of secondary hypertension in all patients with resistant hypertension, in patients with sudden deterioration in the control of hypertension and in patients with laboratory and clinical signs of diseases associated with secondary hypertension. It is important to distinguish between secondary hypertension and pseudo-resistance (noncompliance to treatment, white coat syndrome). Secondary causes of hypertension can be divided into endocrine (primary aldosteronism, pheochromocytoma, hypercortisolism, hyperparathyreoidism), renal - renovascular and renal parenchymal hypertension, and other causes as sleep apnoe syndrome, hypertension in pregnancy, coarctation of the aorta and intracranial tumors.

  19. Definition and classification of hypertension: an update.

    Science.gov (United States)

    Giles, Thomas D; Materson, Barry J; Cohn, Jay N; Kostis, John B

    2009-11-01

    Since the publication of a paper by the American Society of Hypertension, Inc. Writing Group in 2003, some refinements have occurred in the definition of hypertension. Blood pressure is now recognized as a biomarker for hypertension, and a distinction is made between the various stages of hypertension and global cardiovascular risk. This paper discusses the logic underlying the refinements in the definition of hypertension. 2009 Wiley Periodical, Inc.

  20. Biomarkers in white-coat hypertension

    OpenAIRE

    Martin, Catherine Ann

    2017-01-01

    The introduction of ambulatory blood pressure monitoring in the 1960s provided new insights into the nature of high blood pressure disorders. Blood pressure is now categorised into four quadrants:normotension, masked hypertension, hypertension and white-coat hypertension. In white-coat hypertension blood pressure is elevated when taken at the doctor’s office but normal if taken outside the doctor’s office. Several controversies are associated with white-coat hypertension, which are discuss...

  1. Causal relationship between obesity and vitamin D status: bi-directional Mendelian randomization analysis of multiple cohorts.

    Directory of Open Access Journals (Sweden)

    Karani S Vimaleswaran

    Full Text Available Obesity is associated with vitamin D deficiency, and both are areas of active public health concern. We explored the causality and direction of the relationship between body mass index (BMI and 25-hydroxyvitamin D [25(OHD] using genetic markers as instrumental variables (IVs in bi-directional Mendelian randomization (MR analysis.We used information from 21 adult cohorts (up to 42,024 participants with 12 BMI-related SNPs (combined in an allelic score to produce an instrument for BMI and four SNPs associated with 25(OHD (combined in two allelic scores, separately for genes encoding its synthesis or metabolism as an instrument for vitamin D. Regression estimates for the IVs (allele scores were generated within-study and pooled by meta-analysis to generate summary effects. Associations between vitamin D scores and BMI were confirmed in the Genetic Investigation of Anthropometric Traits (GIANT consortium (n = 123,864. Each 1 kg/m(2 higher BMI was associated with 1.15% lower 25(OHD (p = 6.52×10⁻²⁷. The BMI allele score was associated both with BMI (p = 6.30×10⁻⁶² and 25(OHD (-0.06% [95% CI -0.10 to -0.02], p = 0.004 in the cohorts that underwent meta-analysis. The two vitamin D allele scores were strongly associated with 25(OHD (p≤8.07×10⁻⁵⁷ for both scores but not with BMI (synthesis score, p = 0.88; metabolism score, p = 0.08 in the meta-analysis. A 10% higher genetically instrumented BMI was associated with 4.2% lower 25(OHD concentrations (IV ratio: -4.2 [95% CI -7.1 to -1.3], p = 0.005. No association was seen for genetically instrumented 25(OHD with BMI, a finding that was confirmed using data from the GIANT consortium (p≥0.57 for both vitamin D scores.On the basis of a bi-directional genetic approach that limits confounding, our study suggests that a higher BMI leads to lower 25(OHD, while any effects of lower 25(OHD increasing BMI are likely to be small. Population level interventions to

  2. Estimating the causal influence of body mass index on risk of Parkinson disease: A Mendelian randomisation study.

    Directory of Open Access Journals (Sweden)

    Alastair J Noyce

    2017-06-01

    Full Text Available Both positive and negative associations between higher body mass index (BMI and Parkinson disease (PD have been reported in observational studies, but it has been difficult to establish causality because of the possibility of residual confounding or reverse causation. To our knowledge, Mendelian randomisation (MR-the use of genetic instrumental variables (IVs to explore causal effects-has not previously been used to test the effect of BMI on PD.Two-sample MR was undertaken using genome-wide association (GWA study data. The associations between the genetic instruments and BMI were obtained from the GIANT consortium and consisted of the per-allele difference in mean BMI for 77 independent variants that reached genome-wide significance. The per-allele difference in log-odds of PD for each of these variants was estimated from a recent meta-analysis, which included 13,708 cases of PD and 95,282 controls. The inverse-variance weighted method was used to estimate a pooled odds ratio (OR for the effect of a 5-kg/m2 higher BMI on PD. Evidence of directional pleiotropy averaged across all variants was sought using MR-Egger regression. Frailty simulations were used to assess whether causal associations were affected by mortality selection. A combined genetic IV expected to confer a lifetime exposure of 5-kg/m2 higher BMI was associated with a lower risk of PD (OR 0.82, 95% CI 0.69-0.98. MR-Egger regression gave similar results, suggesting that directional pleiotropy was unlikely to be biasing the result (intercept 0.002; p = 0.654. However, the apparent protective influence of higher BMI could be at least partially induced by survival bias in the PD GWA study, as demonstrated by frailty simulations. Other important limitations of this application of MR include the inability to analyse non-linear associations, to undertake subgroup analyses, and to gain mechanistic insights.In this large study using two-sample MR, we found that variants known to influence

  3. Sex differences in primary hypertension

    Science.gov (United States)

    2012-01-01

    Men have higher blood pressure than women through much of life regardless of race and ethnicity. This is a robust and highly conserved sex difference that it is also observed across species including dogs, rats, mice and chickens and it is found in induced, genetic and transgenic animal models of hypertension. Not only do the differences between the ovarian and testicular hormonal milieu contribute to this sexual dimorphism in blood pressure, the sex chromosomes also play a role in and of themselves. This review primarily focuses on epidemiological studies of blood pressure in men and women and experimental models of hypertension in both sexes. Gaps in current knowledge regarding what underlie male-female differences in blood pressure control are discussed. Elucidating the mechanisms underlying sex differences in hypertension may lead to the development of anti-hypertensives tailored to one's sex and ultimately to improved therapeutic strategies for treating this disease and preventing its devastating consequences. PMID:22417477

  4. Intracranial Hypertension: Medication and Surgery

    Science.gov (United States)

    ... fallen out of favor, unless there is a secondary inflammatory process caused by an underlying disease like ... have little effect on headaches caused by intracranial hypertension, they may temporarily affect the intensity of a ...

  5. Hypertension presenting early in pregnancy

    OpenAIRE

    Melvin, Audrey; Kinsley, Brendan

    2015-01-01

    Key Clinical Message Paraganglioma in pregnancy is an exceedingly rare and potentially life?threatening diagnosis. It is important that the clinicians consider secondary causes when women present with hypertension in early pregnancy.

  6. Liver Disease and Pulmonary Hypertension

    Science.gov (United States)

    Facebook Twitter Instagram YouTube About PHA Contact Join Careers Store My Account Donate Patients About PH Diagnosis Treatments Newly ... areas © 2017 Pulmonary Hypertension Association. All Rights Reserved. Facebook Twitter Instagram YouTube

  7. Liver Hypertension: Treatment in Infancy !

    Indian Academy of Sciences (India)

    First page Back Continue Last page Overview Graphics. Liver Hypertension: Treatment in Infancy ! Liver Disease > Heart. No good non-invasive method. Repeated measurements problematic. Drug efficacy 50% at best. No predictors of response. We Need YOU !!

  8. [Menopause: Hypertension and vascular disease].

    Science.gov (United States)

    Zilberman, J M

    Hypertension is the main cardiovascular risk factor affecting 25% of women. Hormone changes and hypertension after menopause may lead to higher target organ damage and cardiovascular disease such as increased arterial stiffness, coronary diseases, chronic heart failure and stroke. The physiopathological mechanisms involved in the development of hypertension and cardiovascular diseases in menopausal women are controversial. There are pharmacokinetic and pharmacodynamic differences in both sexes, the women have more coughing when using the converting-enzyme inhibitors, more cramps when using thiazide diuretics and more oedema in the inferior limbs when using calcium antagonists. The aim of this review is to analyse possible physiopathological mechanisms involved in hypertension after menopause and to gain a better understanding of the biological effects mediated by vascular ageing in women when the level of oestrogen protective effect decreases over the vascular system. Copyright © 2017 SEH-LELHA. Publicado por Elsevier España, S.L.U. All rights reserved.

  9. RFLP's for the human pepsinogen A haplotypes (PGA)

    Energy Technology Data Exchange (ETDEWEB)

    Taggart, R T; Boudi, F B; Bell, G I

    1988-10-11

    PGA 101 is a 1340 bp cDNA clone containing exons 1-9 of the predicted human pepsinogen A coding sequence. Two distinct polymorphisms are detected with EcoRI and Bg1 II. Analysis with these enzymes provides for discrimination of the PGA haplotypes A, B, and C containing three, two and one PGA genes respectively. The PGA complex is located at 11q13. Mendelian inheritance was demonstrated in 20 families.

  10. What is hypertension in diabetes?

    DEFF Research Database (Denmark)

    Hansen, K W; Poulsen, P L; Ebbehøj, E

    2001-01-01

    AIMS: To establish reference data for ambulatory blood pressure (AMBP) in normotensive, normoalbuminuric Type 1 diabetic patients and characterize the relation to clinic blood pressure (BP). To evaluate the statement of the third working party of the British Hypertension Society (BHS) that a target...... clinic BP in diabetes diabetic patients, who had never received anti-hypertensive drugs. Clinic BP was determined as the mean of at least three auscultatory...

  11. Radiological imaging in endocrine hypertension

    Directory of Open Access Journals (Sweden)

    Chandan J Das

    2011-01-01

    Full Text Available While different generations of assays have played important role in elucidating causes of different endocrine disorders, radiological techniques are instrumental in localizing the pathology. This statement cannot be truer in any disease entity other than endocrine hypertension. This review makes an effort to highlight the role of different radiological modalities, especially ultrasonography, computed tomography and magnetic resonance imaging, in the evaluation of different causes of endocrine hypertension.

  12. A focus on paediatric hypertension

    Directory of Open Access Journals (Sweden)

    Pier Paolo Bassareo

    2015-04-01

    Full Text Available Hypertension can begin early in childhood, as occasional increases in blood pressure or abnormal blood pressure responses to physical or emotional stress. High blood pressure in juvenile age is defined as a blood pressure repeatedly above the 95th percentile of specific nomograms. Its worldwide prevalence ranges from 1% to about 10%. The purpose of this paper is to perform an overview about characteristics, diagnosis, risk factors, therapy, and prognosis of paediatric hypertension.

  13. [Hypertension during pregnancy: Epidemiology, definition].

    Science.gov (United States)

    Fauvel, Jean-Pierre

    2016-01-01

    Hypertension in pregnancy has several forms that differ by their mechanisms and their consequences for mothers and fetus. Chronic hypertension is defined by SBP≥140mm Hg or DBP≥90mm Hg before pregnancy or before the 20th week of amenorrhea. Gestational hypertension is defined by SBP≥140mm Hg or DBP≥90mm Hg during or after the 20th week of amenorrhea. Preeclampsia is the occurrence of hypertension and proteinuria after 20weeks of amenorrhea. Severe preeclampsia is accompanied by clinical signs and symptoms indicating visceral pain. The HELLP syndrome is a severe preeclampsia accompanied by intravascular hemolysis and hepatic cytolysis. Eclampsia is characterized by seizures of the tonic-clonic type. A chronic hypertension is observed in 1-5% of pregnancies. Gestational hypertension without proteinuria appears in 5-6% of pregnancies. A preeclampsia develops in 1-2% of pregnancies, but much more frequently (up 34%) in the presence of risk factors. High blood pressure during pregnancy remains, by its complications, the leading cause of maternal morbidity and mortality. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  14. Renal sympathetic denervation in hypertension.

    Science.gov (United States)

    Doumas, Michael; Faselis, Charles; Papademetriou, Vasilios

    2011-11-01

    Despite the abundance of antihypertensive drugs, resistant hypertension remains a major clinical problem. Recent technological advances render interventional management of resistant hypertension one of the hottest topics in the hypertension field. The aim of this review is to present the pathophysiologic background and the mechanisms mediating blood pressure reduction after renal sympathetic denervation, to analyze recent findings with this fascinating approach and to critically suggest future research directions. Catheter-based, ablation-induced renal sympathetic denervation was initially studied in 45 patients with resistant hypertension in a proof-of-concept study. Impressive blood pressure reductions of about 30/15  mmHg were achieved at 6 months, without serious complications. A second, controlled, randomized (but not blinded) study confirmed the results, verifying the efficacy and safety of the procedure. A recent report revealed the 2-year durability of blood pressure reduction. Data published so far indicate that ablation-induced renal denervation is a feasible, effective, and well tolerated interventional approach for the management of resistant hypertension. The groundbreaking studies of renal denervation in drug-resistant hypertension pave the way for further research in other disease conditions in which sympathetic overactivity seems to play a critical role. This initial wave of enthusiasm needs to be followed by rigorous investigation, for the proper identification of the potential and the limitations, indications, and contraindications of this approach.

  15. Hypertension and obstructive sleep apnea

    Directory of Open Access Journals (Sweden)

    Phillips CL

    2013-05-01

    Full Text Available Craig L Phillips,1–3 Denise M O'Driscoll4,51Department of Respiratory and Sleep Medicine, Royal North Shore Hospital, Sydney, Australia; 2National Health and Medical Research Council Center for Integrated Research and Understanding of Sleep, Woolcock Institute of Medical Research, University of Sydney, Sydney, Australia; 3Discipline of Sleep Medicine, Sydney Medical School, University of Sydney, Sydney, Australia; 4Monash Lung and Sleep, Monash Medical Centre, Monash University, Melbourne, Australia; 5Department of Medicine, Southern Clinical School, Monash University, Melbourne, AustraliaAbstract: Obstructive sleep apnea (OSA is increasingly being recognized as a major health burden with strong focus on the associated cardiovascular risk. Studies from the last two decades have provided strong evidence for a causal role of OSA in the development of systemic hypertension. The acute physiological changes that occur during apnea promote nocturnal hypertension and may lead to the development of sustained daytime hypertension via the pathways of sympathetic activation, inflammation, oxidative stress, and endothelial dysfunction. This review will focus on the acute hemodynamic disturbances and associated intermittent hypoxia that characterize OSA and the potential pathophysiological mechanisms responsible for the development of hypertension in OSA. In addition the epidemiology of OSA and hypertension, as well as the role of treatment of OSA, in improving blood pressure control will be examined.Keywords: obstructive sleep apnea, hypertension, intermittent hypoxia, ambulatory blood pressure, sympathetic activation

  16. Hypertensive thalamic hemorrhage

    International Nuclear Information System (INIS)

    Munaka, Masahiro; Nishikawa, Michio; Hirai, Osamu; Kaneko, Takaaki; Watanabe, Syu; Fukuma, Jun; Handa, Hajime

    1988-01-01

    In the past six years, we have had experience with 40 patients with hypertensive thalamic hemorrhages, as verified by CT scan at our hospital within 24 hours. These patients were classified into the following three groups according to the location of the bleeding point and the size of the hematoma: (1) anteromedial (4 cases), (2) posterolateral (16 cases), and (3) massive (20 cases). The (1) and (2) hematomas were small (less than 3 cm in diameter), while those in (3) were large (more than 3 cm in diameter). Twenty cases (50% of all the thalamic hematomas) were small hematomas. The characteristic clinical symptoms of the anteromedial type were a mild disturbance of consciousness and thalamic dementia, while those of the posterolateral type were motor and sensory disturbance, and thalamic aphasia, respectively. Twenty cases (50%) were large hematomas. The clinical symptoms of these cases were mainly consciousness disturbance; 7 of them expired. Based on this experience, it may be considered that the patients whose hematoma size was larger than 3 cm had a poor prognosis and that the patients with the posterolateral type had a poor functional diagnosis. (author)

  17. Paranormal healing and hypertension

    Science.gov (United States)

    Beutler, Jaap J; Attevelt, Johannes T M; Schouten, Sybo A; Faber, Joop A J; Mees, Evert J Dorhout; Geijskes, Gijsbert G

    1988-01-01

    A prospective randomised trial was carried out to see whether paranormal healing by laying on of hands might reduce blood pressure in essential hypertension and whether such an effect might be due to a paranormal, psychological, or placebo factor. Patients were randomised to three treatment groups: paranormal healing by laying on of hands (n=40), paranormal healing at a distance (n=37), and no paranormal healing (controls; n=38). Healing at a distance and no paranormal healing were investigated double blind. Systolic and diastolic blood pressures were significantly reduced in all three groups at week 15 (mean reduction (95% confidence interval) 17·1 (14·0 to 20·2)/8·3 (6·6 to 10·0) mm Hg). Only the successive reductions in diastolic blood pressures among the groups from week to week were significantly different. Each week diastolic pressure was consistently lower (average 1·9 mm Hg) after healing at a distance compared with control, but on paired comparison these differences were not significant. Probably week to week variations among the groups accounted for any differences noted. In this study no treatment was consistently better than another and the data cannot therefore be taken as evidence of a paranormal effect on blood pressure. Probably the fall in blood pressure in all three groups either was caused by the psychosocial approach or was a placebo effect of the trial itself. PMID:3134082

  18. Melatonin, mitochondria and hypertension.

    Science.gov (United States)

    Baltatu, Ovidiu C; Amaral, Fernanda G; Campos, Luciana A; Cipolla-Neto, Jose

    2017-11-01

    Melatonin, due to its multiple means and mechanisms of action, plays a fundamental role in the regulation of the organismal physiology by fine tunning several functions. The cardiovascular system is an important site of action as melatonin regulates blood pressure both by central and peripheral interventions, in addition to its relation with the renin-angiotensin system. Besides, the systemic management of several processes, melatonin acts on mitochondria regulation to maintain a healthy cardiovascular system. Hypertension affects target organs in different ways and cellular energy metabolism is frequently involved due to mitochondrial alterations that include a rise in reactive oxygen species production and an ATP synthesis decrease. The discussion that follows shows the role played by melatonin in the regulation of mitochondrial physiology in several levels of the cardiovascular system, including brain, heart, kidney, blood vessels and, particularly, regulating the renin-angiotensin system. This discussion shows the putative importance of using melatonin as a therapeutic tool involving its antioxidant potential and its action on mitochondrial physiology in the cardiovascular system.

  19. Splanchnic-aortic inflammatory axis in experimental portal hypertension

    Science.gov (United States)

    Aller, Maria-Angeles; de las Heras, Natalia; Nava, Maria-Paz; Regadera, Javier; Arias, Jaime; Lahera, Vicente

    2013-01-01

    Splanchnic and systemic low-grade inflammation has been proposed to be a consequence of long-term prehepatic portal hypertension. This experimental model causes minimal alternations in the liver, thus making a more selective study possible for the pathological changes characteristic of prehepatic portal hypertension. Low-grade splanchnic inflammation after long-term triple partial portal vein ligation could be associated with liver steatosis and portal hypertensive intestinal vasculopathy. In fact, we have previously shown that prehepatic portal hypertension in the rat induces liver steatosis and changes in lipid and carbohydrate metabolism similar to those produced in chronic inflammatory conditions described in metabolic syndrome in humans. Dysbiosis and bacterial translocation in this experimental model suggest the existence of a portal hypertensive intestinal microbiome implicated in both the splanchnic and systemic alterations related to prehepatic portal hypertension. Among the systemic impairments, aortopathy characterized by oxidative stress, increased levels of proinflammatory cytokines and profibrogenic mediators stand out. In this experimental model of long-term triple portal vein ligated-rats, the abdominal aortic proinflammatory response could be attributed to oxidative stress. Thus, the increased aortic reduced-nicotinamide-adenine dinucleotide phosphate [NAD(P)H] oxidase activity could be associated with reactive oxygen species production and promote aortic inflammation. Also, oxidative stress mediated by NAD(P)H oxidase has been associated with risk factors for inflammation and atherosclerosis. The splanchnic and systemic pathology that is produced in the long term after triple partial portal vein ligation in the rat reinforces the validity of this experimental model to study the chronic low-grade inflammatory response induced by prehepatic portal hypertension. PMID:24307792

  20. Hypertension in dogs and cats: Causes and effects

    Directory of Open Access Journals (Sweden)

    Stepanović Predrag

    2005-01-01

    Full Text Available During the nineties of the past century, several authors underscored the necessity of measuring blood pressure during a regular clinical examination of veterinary patients, because hypertension occurs as an accessory symptom in the course of diseased conditions. In addition to blood pressure measurements, most authors believe that it is necessary also to examine intraocular pressure, like in human medicine. Hypertension can be defined as a chronic increase of the systolic and diastolic blood pressure. Systemic blood pressure is proportionate to the heart rate and total peripheral resistance, while physiological control depends on the reninangiotensin system, aldosterone, prostaglandin, adrenergic and neurogenic factors. Some other factors can also have an influence on the measured values of blood pressure (such as age, sex, race, temperament, environment, and, in part, also how and where the pressure measurement was taken. It has been generally accepted in veterinary medicine than an animal can be considered hypertensive if the measured systolic/diastolic pressures are higher than 180/100 mm Hg. Hypertension can be primary (sometimes also defined as essential or idiopathic when it is a consequence of several factors which include heart, neurological, kidney, endocrine, and metabolic aspects. Hypertension is defined as secondary when it occurs as a consequence of certain chronic disorders (such as hyperthyroidism, hypothyroidism, hyperadrenocorticism, pheochromocytoma, and diabetes mellitus. Blood pressure can be measured in animals using direct or indirect methods. The oscilometric and the ultrasonographic methods are equally used in the world today. Following detailed studies by large numbers of authors, the physiological frameworks of blood pressure in animals have been precisely determined. Different treatments are applied in the therapy of hypertension in animals, such as: restrictive diets, diuretics, a, and (3 blockers, blockers of calcium

  1. Renal Tissue Oxygenation in Essential Hypertension and Chronic Kidney Disease

    Directory of Open Access Journals (Sweden)

    Menno Pruijm

    2013-01-01

    Full Text Available Animal studies suggest that renal tissue hypoxia plays an important role in the development of renal damage in hypertension and renal diseases, yet human data were scarce due to the lack of noninvasive methods. Over the last decade, blood oxygenation level-dependent magnetic resonance imaging (BOLD-MRI, detecting deoxyhemoglobin in hypoxic renal tissue, has become a powerful tool to assess kidney oxygenation noninvasively in humans. This paper provides an overview of BOLD-MRI studies performed in patients suffering from essential hypertension or chronic kidney disease (CKD. In line with animal studies, acute changes in cortical and medullary oxygenation have been observed after the administration of medication (furosemide, blockers of the renin-angiotensin system or alterations in sodium intake in these patient groups, underlining the important role of renal sodium handling in kidney oxygenation. In contrast, no BOLD-MRI studies have convincingly demonstrated that renal oxygenation is chronically reduced in essential hypertension or in CKD or chronically altered after long-term medication intake. More studies are required to clarify this discrepancy and to further unravel the role of renal oxygenation in the development and progression of essential hypertension and CKD in humans.

  2. Macrophages under pressure: the role of macrophage polarization in hypertension.

    Science.gov (United States)

    Harwani, Sailesh C

    2018-01-01

    Hypertension is a multifactorial disease involving the nervous, renal, and cardiovascular systems. Macrophages are the most abundant and ubiquitous immune cells, placing them in a unique position to serve as key mediators between these components. The polarization of macrophages confers vast phenotypic and functional plasticity, allowing them to act as proinflammatory, homeostatic, and anti-inflammatory agents. Key differences between the M1 and M2 phenotypes, the 2 subsets at the extremes of this polarization spectrum, place macrophages at a juncture to mediate many mechanisms involved in the pathogenesis of hypertension. Neuronal and non-neuronal regulation of the immune system, that is, the "neuroimmuno" axis, plays an integral role in the polarization of macrophages. In hypertension, the neuroimmuno axis results in synchronization of macrophage mobilization from immune cell reservoirs and their chemotaxis, via increased expression of chemoattractants, to end organs critical in the development of hypertension. This complicated system is largely coordinated by the dichotomous actions of the autonomic neuronal and non-neuronal activation of cholinergic, adrenergic, and neurohormonal receptors on macrophages, leading to their ability to "switch" between phenotypes at sites of active inflammation. Data from experimental models and human studies are in concordance with each other and support a central role for macrophage polarization in the pathogenesis of hypertension. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. [Pulmonary hypertension associated with congenital heart disease and Eisenmenger syndrome].

    Science.gov (United States)

    Calderón-Colmenero, Juan; Sandoval Zárate, Julio; Beltrán Gámez, Miguel

    2015-01-01

    Pulmonary arterial hypertension is a common complication of congenital heart disease (CHD). Congenital cardiopathies are the most frequent congenital malformations. The prevalence in our country remains unknown, based on birthrate, it is calculated that 12,000 to 16,000 infants in our country have some cardiac malformation. In patients with an uncorrected left-to-right shunt, increased pulmonary pressure leads to vascular remodeling and endothelial dysfunction secondary to an imbalance in vasoactive mediators which promotes vasoconstriction, inflammation, thrombosis, cell proliferation, impaired apotosis and fibrosis. The progressive rise in pulmonary vascular resistance and increased pressures in the right heart provocated reversal of the shunt may arise with the development of Eisenmenger' syndrome the most advanced form de Pulmonary arterial hypertension associated with congenital heart disease. The prevalence of Pulmonary arterial hypertension associated with CHD has fallen in developed countries in recent years that is not yet achieved in developing countries therefore diagnosed late as lack of hospital infrastructure and human resources for the care of patients with CHD. With the development of targeted medical treatments for pulmonary arterial hypertension, the concept of a combined medical and interventional/surgical approach for patients with Pulmonary arterial hypertension associated with CHD is a reality. We need to know the pathophysiological factors involved as well as a careful evaluation to determine the best therapeutic strategy. Copyright © 2014 Instituto Nacional de Cardiología Ignacio Chávez. Published by Masson Doyma México S.A. All rights reserved.

  4. New therapies for arterial hypertension.

    Science.gov (United States)

    Pagliaro, Beniamino; Santolamazza, Caterina; Rubattu, Speranza; Volpe, Massimo

    2016-03-01

    Arterial hypertension is the most common chronic disease in developed countries and it is the leading risk factor for stroke, ischemic heart disease, congestive heart failure, chronic renal failure and peripheral artery disease. Its prevalence appears to be about 30-45% of the general population. Recent European guidelines estimate that up to 15-20% of the hypertensive patients are not controlled on a dual antihypertensive combination and they require three or more different antihypertensive drug classes to achieve adequate blood pressure control. The guidelines confirmed that diuretics, beta-blockers, calcium-channel blockers, angiotensin-converting enzyme inhibitors and angiotensin receptor blockers are suitable for the initiation and maintenance of antihypertensive treatment, either as monotherapy or in combination therapy. Very few antihypertensive agents have reached the market over the last few years, but no new therapeutic class has really emerged. The long-term adherence to cardiovascular drugs is still low in both primary and secondary prevention of cardiovascular diseases. In particular, the issue of compliance is persistently high in hypertension, despite the fixed-dose combination therapy. As a consequence, a cohort of high-risk hypertensive population, represented by patients affected by refractory and resistant hypertension, can be identified. Therefore, the need of controlling BP in high-risk patients may be addressed, in part, by the development of new drugs, devices and procedures that are designed to treat hypertension and comorbidities. In this review we will comprehensively discuss the current literature on recent therapeutic advances in hypertension, including both medical therapy and interventional procedures.

  5. Has Human Evolution Stopped?

    Directory of Open Access Journals (Sweden)

    Alan R. Templeton

    2010-07-01

    Full Text Available It has been argued that human evolution has stopped because humans now adapt to their environment via cultural evolution and not biological evolution. However, all organisms adapt to their environment, and humans are no exception. Culture defines much of the human environment, so cultural evolution has actually led to adaptive evolution in humans. Examples are given to illustrate the rapid pace of adaptive evolution in response to cultural innovations. These adaptive responses have important implications for infectious diseases, Mendelian genetic diseases, and systemic diseases in current human populations. Moreover, evolution proceeds by mechanisms other than natural selection. The recent growth in human population size has greatly increased the reservoir of mutational variants in the human gene pool, thereby enhancing the potential for human evolution. The increase in human population size coupled with our increased capacity to move across the globe has induced a rapid and ongoing evolutionary shift in how genetic variation is distributed within and among local human populations. In particular, genetic differences between human populations are rapidly diminishing and individual heterozygosity is increasing, with beneficial health effects. Finally, even when cultural evolution eliminates selection on a trait, the trait can still evolve due to natural selection on other traits. Our traits are not isolated, independent units, but rather are integrated into a functional whole, so selection on one trait can cause evolution to occur on another trait, sometimes with mildly maladaptive consequences.

  6. Hypertension – a public health problem

    Directory of Open Access Journals (Sweden)

    Zélia Maria de Sousa Araújo Santos

    2011-12-01

    ,collaboration among various sectors, and sustainabledevelopment. If one brings the perspective relating healthto life conditions, multiple elements, such as physical,psychological and social will emerge as linked to ahealthy life. Nevertheless, an importance should be givento the development of community participation regardingpopulational abilities.Finally, the problems related to hypertension needsolutions through prevention and/or control of risk factorssince childhood, as well as adhesion to therapeuticalconducts aiming control, in the diagnosed cases, on allfields of human activity – home, work and other socialenvironments.REFERENCES1. Andrade JP, Vilas-Boas F, Chagas HA. Aspectosepidemiológicos da aderência ao tratamento dahipertensão arterial sistêmica. Arqui Bras Cardiol.2009; 79(2:375-89.2. Santos ZMSA, Frota MA, Cruz DM, Holanda SDO.Adesão do cliente hipertenso ao tratamento: análisecom abordagem interdisciplinar. Texto Contex Enferm.2005; 14(3:87-99.

  7. Accelerated Hypertension after Venlafaxine Usage

    Directory of Open Access Journals (Sweden)

    Yüksel Kıvrak

    2014-01-01

    Full Text Available Venlafaxine is the first antidepressant that acts via inhibiting serotonin and noradrenaline reuptake. Hypertension is observed in doses exceeding 300 mg/day and is the most feared complication. We report a patient with accelerated hypertension after venlafaxine use observed at a dose of 150 mg/day. A 23-year-old patient with symptoms of insomnia, depression, anhedonia, fatigue admitted our clinic. Venlafaxine at a dose of 75 mg/day was initiated after he was diagnosed with major depressive disorder. After 5 months, venlafaxine dose was uptitrated to 150 mg/day due to inadequate response to drug. After using venlafaxine for ten months at the dose of 150 mg/day, he admitted our clinic with headache and epistaxis. He was hospitalized after his blood pressure was measured as 210/170 mmHg. No secondary causes for hypertension were found, and venlafaxine treatment was considered possible etiologic factor. After stopping venlafaxine treatment, his blood pressure was reverted back to normal limits. While mild elevation of blood pressure could be observed after venlafaxine treatment, this case shows that accelerated hypertension with a diastolic blood pressure rise above 120 mmHg could be observed at relatively low doses of venlafaxine. Close monitoring of blood pressure is necessary after initiation of treatment, as accelerated hypertension could cause endorgan damage with potentially catastrophic results.

  8. Heat stress proteins in hypertension

    International Nuclear Information System (INIS)

    Malo, D.; Tremblay, J.; Pang, S.C.; Schlager, G.; Hamet, P.

    1986-01-01

    It has been described that spontaneously hypertensive rats (SHR) are more sensitive to an acute environmental heat stress and that cultured cardiomyocytes from neonatal SHR are demonstrated to be more thermosensitive. In addition, chronically heat exposed spontaneously hypertensive mice leads to a decrease of blood pressure in these animals. Heat shock is known to induce the synthesis of a new set of proteins (HSP) in every cell tested. This ubiquitous response seems to be involved in the induction of a thermotolerant state. The synthesis of 70K HSP was observed in lymphocytes isolated from the spleen of chronically heated mice. They used lymphocytes, previously isolated on a ficoll gradient, to evaluate the HSP induction in normotensive (WKY) and hypertensive (SHR) rats. The heat shock was induced by exposing the lymphocytes at 46 0 C during 5 min in a hot water bath. The cells were then labeled with ( 75 Se)-methionine, washed, homogenized and separated on 5-30% SDS-polyacrylamide gel. Preliminary results suggest an abnormal pattern of induction of 70K and 90K HSP in hypertension. Heat sensitivity, thermotolerance and expression of HSP may, thus, be related to hypertension

  9. Hypertension in master endurance athletes.

    Science.gov (United States)

    Hernelahti, M; Kujala, U M; Kaprio, J; Karjalainen, J; Sarna, S

    1998-11-01

    To determine whether long-term very vigorous endurance training prevents hypertension. Cohort study of master orienteering runners and controls. Finland. In 1995, a health questionnaire was completed by 264 male orienteering runners (response rate 90.4%) who had been top-ranked in competitions among men aged 35-59 years in 1984, and by 388 similarly aged male controls (response rate 87.1%) who were healthy at the age of 20 years and free of overt ischemic heart disease in 1985. Self-report of medication for hypertension. In the endurance athlete group, the crude prevalence (8.7%) of subjects who had used medication for hypertension was less than a third of that in the control group (27.8%). Even after adjusting for age and body mass index, the difference between the groups was still significant (odds ratio for athletes 0.43, 95% confidence interval 0.25-0.76). Long-term vigorous endurance training is associated with a low prevalence of hypertension. Some of the effect can be explained by a lower body mass, but exercise seems to induce a lower rate of hypertension by other mechanisms than by decreasing body weight

  10. Renal Dysfunction Induced by Kidney-Specific Gene Deletion of Hsd11b2 as a Primary Cause of Salt-Dependent Hypertension.

    Science.gov (United States)

    Ueda, Kohei; Nishimoto, Mitsuhiro; Hirohama, Daigoro; Ayuzawa, Nobuhiro; Kawarazaki, Wakako; Watanabe, Atsushi; Shimosawa, Tatsuo; Loffing, Johannes; Zhang, Ming-Zhi; Marumo, Takeshi; Fujita, Toshiro

    2017-07-01

    Genome-wide analysis of renal sodium-transporting system has identified specific variations of Mendelian hypertensive disorders, including HSD11B2 gene variants in apparent mineralocorticoid excess. However, these genetic variations in extrarenal tissue can be involved in developing hypertension, as demonstrated in former studies using global and brain-specific Hsd11b2 knockout rodents. To re-examine the importance of renal dysfunction on developing hypertension, we generated kidney-specific Hsd11b2 knockout mice. The knockout mice exhibited systemic hypertension, which was abolished by reducing salt intake, suggesting its salt-dependency. In addition, we detected an increase in renal membrane expressions of cleaved epithelial sodium channel-α and T53-phosphorylated Na + -Cl - cotransporter in the knockout mice. Acute intraperitoneal administration of amiloride-induced natriuresis and increased urinary sodium/potassium ratio more in the knockout mice compared with those in the wild-type control mice. Chronic administration of amiloride and high-KCl diet significantly decreased mean blood pressure in the knockout mice, which was accompanied with the correction of hypokalemia and the resultant decrease in Na + -Cl - cotransporter phosphorylation. Accordingly, a Na + -Cl - cotransporter blocker hydrochlorothiazide significantly decreased mean blood pressure in the knockout mice. Chronic administration of mineralocorticoid receptor antagonist spironolactone significantly decreased mean blood pressure of the knockout mice along with downregulation of cleaved epithelial sodium channel-α and phosphorylated Na + -Cl - cotransporter expression in the knockout kidney. Our data suggest that kidney-specific deficiency of 11β-HSD2 leads to salt-dependent hypertension, which is attributed to mineralocorticoid receptor-epithelial sodium channel-Na + -Cl - cotransporter activation in the kidney, and provides evidence that renal dysfunction is essential for developing the

  11. Renovascular hypertension - imaging and treatment

    International Nuclear Information System (INIS)

    Brkljačić, B.

    2015-01-01

    Full text: Imaging is very important in diagnosing renovascular hypertension (RVHT). The role of color duplex Doppler, CT angiography, MR angiography and DS angiography will be presented, advantages and disadvantages discussed. The treatment of RVHT can be medical, surgical or endovascular. Endovascular treatment is a domain of vascular interventional radiology; endovascular treatment of renovascular hypertension consists of PTA alone or PTA and stenting of renal arteries in patients who have haemodynamically significant stenosis of renal artery due to fibromuscular dysplasia or atherosclerosis. Atherosclerotic renal artery stenosis results in increased production of renin, angiotensin II, aldosterone; plasma rennin activity of is increased in renal vein of ischemic kidney that retains sodium and water. Atherosclerotic lesions are typically ostial. Long-standing hypertension damages intrarenal vessels of unprotected kidney. Hypertension and renal failure may persist after removal of stenotic kidney. It usually affects older people. Fibromuscular dysplasia is non-atherosclerotic, is more common in women, occurs at younger age (average 35 yrs). Treatment of choice is PTA alone. Results are much better than in atherosclerotic RAS, where PTA + stenting are indicated. Endovascular treatment may result in complications, minor local or major complications, mostly related to the interventional technique. While PTA for the treatment of FMD is clearly indicated, the conflicting data exist over years regarding indications, benefits, complications and advantages of PTA / stent over medical therapy for treatment of atherosclerotic renovascular hypertension. Although 25-30% of patients with impaired renal function can recover glomerular filtration after revascularization, many have no apparent change in kidney function and 19-25% experience a significant loss of kidney function, some as a result of atheroemboli. The results of ASTRAL, STAR and CORAL studies will be presented

  12. Infantile Renovascular Hypertension with Failure to Thrive.

    Science.gov (United States)

    Phillips, Amanda R; Eliason, Jonathan L; Stanley, James C; Coleman, Dawn M

    2016-05-01

    Severe hypertension in infancy is a rare cause of failure to thrive. The successful surgical management of this disease in an infant having refractory renovascular hypertension and growth failure is reported. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. Hypercortisolism in obesity-associated hypertension.

    Science.gov (United States)

    Varughese, Amy G; Nimkevych, Oksana; Uwaifo, Gabriel I

    2014-07-01

    Obesity is prevalent worldwide and associated with co-morbidities that result in increased cardiovascular risk. Hypertension is the most prevalent obesity comorbidity associated with increased cardiovascular risk. Obesity hypertension is a distinct subtype of essential hypertension. While endogenous Cushing's syndrome is an uncommon cause of both obesity and hypertension, the recent recognition of other hypercortisolemic states has raised the profile of hypercortisolism as an important contributor in obesity hypertension. The high prevalence of exogenous, iatrogenic, pseudo, and subclinical Cushing's syndromes makes hypercortisolism an important diagnostic consideration in the evaluation and management of patients with obesity hypertension who are resistant to conventional management. Available data suggest that the renin-angiotensin-aldosterone system modulating antihypertensives have the best efficacy in hypercortisolism-mediated obesity hypertension. Strategies aimed at reducing cortisol production and action also have utility. This review provides a comprehensive overview of the epidemiology, etiopathogenesis and management options available for glucocorticoid-mediated obesity hypertension.

  14. Prevalence and Predictors of Hypertension History among ...

    African Journals Online (AJOL)

    Prof Yaro

    hypertension history was thus observed among respondents in older age ... more than 40 percent of adults are hypertensive (Bygbjerg, 2012). ... they face, which is a recognized major impediment to the control of the condition (Joshi et al.,.

  15. Missed medical appointment among hypertensive and diabetic ...

    African Journals Online (AJOL)

    Keywords: Missed medical appointments, Hypertensive, Diabetic outpatients, Medication adherence, ... 12 weeks, at 95 % confidence level and 5 % error margin, 300 hypertensive ... monthly income and health insurance status of respondents ...

  16. Pressure Points: Preventing and Controlling Hypertension

    Science.gov (United States)

    ... Issue Past Issues Pressure Points: Preventing and Controlling Hypertension Past Issues / Summer 2006 Table of Contents For ... diagnosed with high blood pressure." Aditional Information On Hypertension MedlinePlus: High blood pressure: http://www.nlm.nih. ...

  17. Sickle Cell Disease and Pulmonary Hypertension

    Science.gov (United States)

    ... My doctor wants to screen me for pulmonary hypertension. Why is this? Sickle cell disease (SCD), a ... What are some of the symptoms of pulmonary hypertension? Because they are somewhat general symptoms, the characteristics ...

  18. Hereditary Hemorrhagic Telangiectasia (HHT) and Pulmonary Hypertension

    Science.gov (United States)

    ... has said these might be symptoms of pulmonary hypertension. How does this relate to my HHT? About ... differences are significant. In HHT-associated pulmonary arterial hypertension, abnormal blood flow through the blood vessels in ...

  19. Lung Transplantation in Patients with Pulmonary Hypertension

    Science.gov (United States)

    ... 00:00 Lung Transplantation in Patients with Pulmonary Hypertension Consensus Statements Issued by the Scientific Leadership Council ... a treatment option for selected patients with pulmonary hypertension (PH) when medical therapy is no longer effective. ...

  20. Recurrence of hypertensive disorders of pregnancy

    DEFF Research Database (Denmark)

    van Oostwaard, Miriam F; Langenveld, Josje; Schuit, Ewoud

    2015-01-01

    OBJECTIVE: We performed an individual participant data (IPD) metaanalysis to calculate the recurrence risk of hypertensive disorders of pregnancy (HDP) and recurrence of individual hypertensive syndromes. STUDY DESIGN: We performed an electronic literature search for cohort studies that reported ...

  1. Syphilis mimicking idiopathic intracranial hypertension

    DEFF Research Database (Denmark)

    Yri, Hanne; Wegener, Marianne; Jensen, Rigmor

    2011-01-01

    Idiopathic intracranial hypertension (IIH) is a condition of yet unknown aetiology affecting predominantly obese females of childbearing age. IIH is a diagnosis of exclusion as raised cerebrospinal fluid pressure may occur secondary to numerous other medical conditions. An atypical phenotype...... or an atypical disease course should alert the physician to reevaluate a presumed IIH-diagnosis. The authors report a case of a 32-year-old non-obese male with intracranial hypertension, secondary to a syphilitic central nervous system infection, initially misdiagnosed as being idiopathic. Upon relevant...

  2. Extrahepatic portal hypertension in childhood

    International Nuclear Information System (INIS)

    Takehara, Hiroo; Komi, Nobuhiko; Goh, Masahiro; Yoshida, Sadahiro; Kameoka, Kazuhiro; Hino, Masao; Sui, Osamu

    1986-01-01

    Four pediatric patients with extrahepatic portal hypertension had undergone portography and computerized radionuclide angiography in order to examine shape of portal system and to evaluate hepatic blood flow before and aftersurgical treatment. In all patients, cavernous transformation of portal system was demonstrated by portography, and in one of them spontaneous splenorenal shunt occurred. In 3 of them, who underwent esophageal transsection combined with paraesophagogastric devascularization and splenectomy, so-called direct operation, increase of portal blood flow was revealed by computerized radionuclide angiography. It is suggested that direct operation increasing portal blood flow after surgery is effective in treating extrahepatic portal hypertension in childhood. (author)

  3. Radiological diagnosis of pulmonary hypertension

    International Nuclear Information System (INIS)

    Huebsch, P.; Jenny, C.; Schwaighofer, B.; Seidl, G.; Burghuber, O.C.

    1987-01-01

    In 43 patients with obstructive and restrictive lung disease a catheterisation of the right heart with measurement of pulmonary artery pressure was performed. In a retrospective study several radiological parameters of pulmonary hypertension were evaluated on the chest radiographs of these patients. Considering those parameters on the p.a. and lateral chest radiograph, the diagnosis of pulmonary hypertension in patients with elevated pulmonary artery pressure at rest can be made with great accuracy. When pulmonary artery pressure is elevated only during exercise, the accuracy of radiological diagnosis is much lower. (orig.) [de

  4. PPARs Link Early Life Nutritional Insults to Later Programmed Hypertension and Metabolic Syndrome

    Directory of Open Access Journals (Sweden)

    You-Lin Tain

    2015-12-01

    Full Text Available Hypertension is an important component of metabolic syndrome. Adulthood hypertension and metabolic syndrome can be programmed in response to nutritional insults in early life. Peroxisome proliferator-activated receptors (PPARs serve as a nutrient-sensing signaling linking nutritional programming to hypertension and metabolic syndrome. All three members of PPARs, PPARα, PPARβ/δ, and PPARγ, are expressed in the kidney and involved in blood pressure control. This review provides an overview of potential clinical applications of targeting on the PPARs in the kidney to prevent programmed hypertension and metabolic syndrome, with an emphasis on the following areas: mechanistic insights to interpret programmed hypertension; the link between the PPARs, nutritional insults, and programmed hypertension and metabolic syndrome; the impact of PPAR signaling pathway in a maternal high-fructose model; and current experimental studies on early intervention by PPAR modulators to prevent programmed hypertension and metabolic syndrome. Animal studies employing a reprogramming strategy via targeting PPARs to prevent hypertension have demonstrated interesting results. It is critical that the observed effects on developmental reprogramming in animal models are replicated in human studies, to halt the globally-growing epidemic of metabolic syndrome-related diseases.

  5. Magnetic resonance imaging in pulmonary hypertension. Magnetresonanztomographie bei pulmonaler Hypertension

    Energy Technology Data Exchange (ETDEWEB)

    Neuhold, A.; Stiskal, M.; Czerny, C. (Institut fuer Bildgebende Diagnostik, Rudolfinerhaus, Vienna (Austria)); Frank, H.; Globits, S.; Glogar, D.; Mlczoch, J. (Universitaetsklinik fuer Kardiologie, Vienna (Austria))

    1992-09-01

    We examined 23 patients with pulmonary hypertension of varying aetiology by MRI and compared the results with those of right heart catheterisation. The best correlation was obtained between right ventricular mural thickness and mean pulmonary pressure (R = 0.91, p = 0.001). There was significant correlation (R = 0.85, p = 0.001) for the diameter of the inferior vena cava, which was dilated in all patients with pulmonary hypertension. There was no significant correlation between mean pulmonary pressure and the diameters of the superior vena cava or the main pulmonary artery branches (R = 0.55 and 0.75 respectively, p < 0.05). Amongst functional measurements there was a correlation between right ventricular ejection fraction and mean pulmonary artery pressure (R = 0.71, p = 0.001). There was no correlation between right ventricular end-systolic and end-diastolic volume. In all patients with pulmonary hypertension, dynamic flow sensitive gradient echo sequences showed the presence of tricuspid insufficiency. A further semiquantitative criterion for the presence of pulmonary hypertension in 4 patients (17%) was an abnormal signal from the main pulmonary artery in early to mid-systole shown on T[sub 1]-weighted transverse sections. (orig./GDG).

  6. Oestrogen receptor alpha in pulmonary hypertension.

    Science.gov (United States)

    Wright, Audrey F; Ewart, Marie-Ann; Mair, Kirsty; Nilsen, Margaret; Dempsie, Yvonne; Loughlin, Lynn; Maclean, Margaret R

    2015-05-01

    Pulmonary arterial hypertension (PAH) occurs more frequently in women with mutations in bone morphogenetic protein receptor type 2 (BMPR2) and dysfunctional BMPR2 signalling underpinning heritable PAH. We have previously shown that serotonin can uncover a pulmonary hypertensive phenotype in BMPR2(+/-) mice and that oestrogen can increase serotinergic signalling in human pulmonary arterial smooth muscle cells (hPASMCs). Hence, here we wished to characterize the expression of oestrogen receptors (ERs) in male and female human pulmonary arteries and have examined the influence of oestrogen and serotonin on BMPR2 and ERα expression. By immunohistochemistry, we showed that ERα, ERβ, and G-protein-coupled receptors are expressed in human pulmonary arteries localizing mainly to the smooth muscle layer which also expresses the serotonin transporter (SERT). Protein expression of ERα protein was higher in female PAH patient hPASMCs compared with male and serotonin also increased the expression of ERα. 17β-estradiol induced proliferation of hPASMCs via ERα activation and this engaged mitogen-activated protein kinase and Akt signalling. Female mice over-expressing SERT (SERT(+) mice) develop PH and the ERα antagonist MPP attenuated the development of PH in normoxic and hypoxic female SERT(+) mice. The therapeutic effects of MPP were accompanied by increased expression of BMPR2 in mouse lung. ERα is highly expressed in female hPASMCs from PAH patients and mediates oestrogen-induced proliferation of hPASMCs via mitogen-activated protein kinase and Akt signalling. Serotonin can increase ERα expression in hPASMCs and antagonism of ERα reverses serotonin-dependent PH in the mouse and increases BMPR2 expression. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.

  7. Arterial hypertension in women at different ages

    OpenAIRE

    Pacheco-Romero, José

    2011-01-01

    Hypertension is associated to co-morbidities such as diabetes mellitus, coronary artery disease, stroke, peripheral vascular disease, chronic renal failure, entities that decrease life span. Peruvians suffer from arterial hypertension with characteristics similar to those of the general population. Early detection and treatment of hypertension should benefit them with years of quality of life. The occurrence of arterial hypertension in women from childhood through menopause, including reprodu...

  8. CAROTID BODY POTENTIATION DURING CHRONIC INTERMITTENT HYPOXIA: IMPLICATION FOR HYPERTENSION

    Directory of Open Access Journals (Sweden)

    Rodrigo eDel Rio

    2014-11-01

    Full Text Available Autonomic dysfunction is involved in the development of hypertension in humans with obstructive sleep apnea, and animals exposed to chronic intermittent hypoxia (CIH. It has been proposed that a crucial step in the development of the hypertension is the potentiation of the carotid body (CB chemosensory responses to hypoxia, but the temporal progression of the CB chemosensory, autonomic and hypertensive changes induced by CIH are not known. We tested the hypothesis that CB potentiation precedes the autonomic imbalance and the hypertension in rats exposed to CIH. Thus, we studied the changes in CB chemosensory and ventilatory responsiveness to hypoxia, the spontaneous baroreflex sensitivity (BRS, heart rate variability (HRV and arterial blood pressure in pentobarbital anesthetized rats exposed to CIH for 7, 14 and 21 days. After 7 days of CIH, CB chemosensory and ventilatory responses to hypoxia were enhanced, while BRS was significantly reduced by 2-fold in CIH-rats compared to sham-rats. These alterations persisted until 21 days of CIH. After 14 days, CIH shifted the HRV power spectra suggesting a predominance of sympathetic over parasympathetic tone. In contrast, hypertension was found after 21 days of CIH. Concomitant changes between the gain of spectral HRV, BRS and ventilatory hypoxic chemoreflex showed that the CIH-induced BRS attenuation preceded the HRV changes. CIH induced a simultaneous decrease of the BRS gain along with an increase of the hypoxic ventilatory gain. Present results show that CIH-induced persistent hypertension was preceded by early changes in CB chemosensory control of cardiorespiratory and autonomic function.

  9. Potential renovascular hypertension, space missions, and the role of magnesium

    Directory of Open Access Journals (Sweden)

    William J Rowe

    2009-11-01

    Full Text Available William J RoweFormer Assistant Clinical Professor of Medicine, Medical University of Ohio at Toledo, Keswick, VA, USAAbstract: Space flight (SF and dust inhalation in habitats cause hypertension whereas in SF (alone there is no consistent hypertension but reduced diurnal blood pressure (BP variation instead. Current pharmaceutical subcutaneous delivery systems are inadequate and there is impairment in the absorption, metabolism, excretion, and deterioration of some pharmaceuticals. Data obtained from the National Aeronautics and Space Administration through the Freedom of Information Act shows that Irwin returned from his 12-day Apollo 15 mission in 1971 and was administered a bicycle stress test. With just three minutes of exercise, his BP was >275/125 mm Hg (heart rate of only 130 beats per minute. There was no acute renal insult. Irwin’s apparent spontaneous remission is suggested to be related to the increase of a protective vasodilator, and his atrial natriuretic peptide (ANP reduced with SF because of reduced plasma volume. With invariable malabsorption and loss of bone/muscle storage sites, there are significant (P < 0.0001 reductions of magnesium (Mg required for ANP synthesis and release. Reductions of Mg and ANP can trigger pronounced angiotensin (200%, endothelin, and catecholamine elevations (clearly shown in recent years and vicious cycles between the latter and Mg deficits. There is proteinuria, elevated creatinine, and reduced renal concentrating ability with the potential for progressive inflammatory and oxidative stress-induced renal disease and hypertension with vicious cycles. After SF, animals show myocardial endothelial injuries and increased vascular resistance of extremities in humans. Even without dust, hypertension might eventually develop from renovascular hypertension during very long missions. Without sufficient endothelial protection from pharmaceuticals, a comprehensive gene research program should begin now

  10. Childhood hypertension: what does the radiologist contribute?

    Energy Technology Data Exchange (ETDEWEB)

    Roebuck, Derek [Great Ormond Street Hospital for Children NHS Trust, Radiology Department, London (United Kingdom)

    2008-06-15

    Hypertension may be essential (primary) or secondary to a variety of causes. The most important risk factors for essential hypertension are obesity and a family history of high BP, but there are also associations with sleep apnoea, low birth weight and prematurity. The most important cause of secondary hypertension in childhood is chronic renal disease. (orig.)

  11. Childhood hypertension: what does the radiologist contribute?

    International Nuclear Information System (INIS)

    Roebuck, Derek

    Hypertension may be essential (primary) or secondary to a variety of causes. The most important risk factors for essential hypertension are obesity and a family history of high BP, but there are also associations with sleep apnoea, low birth weight and prematurity. The most important cause of secondary hypertension in childhood is chronic renal disease. (orig.)

  12. The renal transcriptome in experimental hypertension

    NARCIS (Netherlands)

    Wesseling, S.

    2007-01-01

    The renal transcriptome in experimental hypertension The kidneys importantly determine blood pressure. Kidney dysfunction can result in hypertension, which in turn leads to renal damage. In primary hypertension the cause is unknown. The condition is polygenic, however, which genetic defects cause

  13. Ruling out secondary causes of hypertension.

    Science.gov (United States)

    Ott, Christian; Schneider, Markus P; Schmieder, Roland E

    2013-05-01

    In the majority of hypertensive patients, no particular cause for abnormal blood pressure is evident (primary or essential hypertension). In contrast, in the minority of patients with secondary hypertension a specific underlying cause is responsible for the elevated blood pressure. The prevalence of secondary hypertension is higher in patients with resistant hypertension than in the general hypertensive population and increases with age. The list of secondary forms of hypertension is long and prevalence of the individual causes of secondary hypertension varies. Hence, this review divides them into two categories: common causes and rare causes. If appropriately diagnosed and treated, patients with a secondary form of hypertension might be cured, or at least show an improvement in their blood pressure control. Consequently, screening for secondary causes of hypertension plays an essential part in the care of patients with arterial hypertension. If the basal work-up raises the suspicion of a secondary cause of hypertension, specific diagnostic procedures become necessary, some of which can be performed by primary care physicians, while others require specialist input.

  14. Orthostatic hypertension: profile of a Nigerian population ...

    African Journals Online (AJOL)

    Background: The aim of this study was to determine the prevalence, age, sex distribution and blood pressure (BP) pattern of patients with orthostatic hypertension in a cohort of hypertensives. Method: A total of 179 patients on follow-up treatment in a hypertension clinic were assessed for age, sex and BP in the seated ...

  15. Treatment Algorithm of a Hypertension Specialist

    Czech Academy of Sciences Publication Activity Database

    Peleška, Jan; Anger, Z.; Buchtela, David; Tomečková, Marie; Veselý, Arnošt; Zvárová, Jana

    2007-01-01

    Roč. 25, Suppl. 2 (2007), S 383-S 383 ISSN 0952-1178. [European Meeting on Hypertension /17./. 15.06.2007-19.06.2007, Milan] R&D Projects: GA AV ČR 1ET200300413 Institutional research plan: CEZ:AV0Z10300504 Keywords : treatment algorithm for hypertension * hypertension specialist Subject RIV: FA - Cardiovascular Diseases incl. Cardiotharic Surgery

  16. High Blood Pressure (Hypertension) (For Parents)

    Science.gov (United States)

    ... Safe Videos for Educators Search English Español Hypertension (High Blood Pressure) KidsHealth / For Parents / Hypertension (High Blood Pressure) What's ... High Blood Pressure) Treated? Print What Is Hypertension (High Blood Pressure)? Blood pressure is the pressure of blood against ...

  17. [Knowledge level of hypertensive patients about hypertension. Relationship between knowledge level and hypertension control].

    Science.gov (United States)

    Benítez Camps, M; Egocheaga Cabello, M Isabel; Dalfó Baqué, A; Bajo García, J; Vara González, L; Sanchis Doménech, C; Martín Rioboo, E; Ureña Fernández, T; Domínguez Sardiña, M; Bonet Pla, A

    2015-01-01

    To assess the knowledge of the hypertensive patients about their hypertension and their relation to its control. Cross-sectional study among 400 hypertensive patients, all over 18 years, selected from 50 primary-care centres, who responded to an hypertension-related survey. Included variables were survey items, age, gender, educational level, professional occupation, blood pressure data and antihypertensive treatment. The obtained differences were analyzed using the chi-square test, Kruskal-Wallis, Wilcoxon, Anova and Bonferroni methods. There were 323 valid surveys. 52.9% of respondents were women, the average age: 65.4 years (SD: 11.2), 54.8% of them had primary education. 39.6% were aware of the objectives of systolic BP control. Only 19.6% having knowledge of those for diastolic BP control, with no differences between controlled and uncontrolled (systolic BP: 39% vs 38.1%, P=.887; diastolic BP: 19.2% vs 21%, P=.721). Over 70% knew about lifestyle changes, without significant differences between controlled and uncontrolled respondents. 82% of controlled respondents, and 79% of those uncontrolled, recognized the chronical nature of the treatment (P=.548), but 15.1% of the controlled respondents and 12.4% of uncontrolled respondents did not see the relation between the treatment and hypertension control (P=.525). 31.1% believed to be well-controlled, but in fact was not. Our patients doesn't know blood pressure targets of control. There isn't relationship between this knowledge and control of hypertension. Copyright © 2014 SEHLELHA. Published by Elsevier Espana. All rights reserved.

  18. Pulmonary hypertension associated with non-cirrhotic portal hypertension in systemic lupus erythematosus.

    OpenAIRE

    Woolf, D.; Voigt, M. D.; Jaskiewicz, K.; Kalla, A. A.

    1994-01-01

    A case of non-cirrhotic portal hypertension in a patient with systemic lupus erythematosus, the first of our knowledge, is described. Severe pulmonary hypertension was associated with the portal hypertension and with markers of active auto-immunity. Pulmonary hypertension has not previously been associated with non-cirrhotic portal hypertension. The coexistence of vasculopathy of the portal and pulmonary vascular beds in this patient with active autoimmunity supports the postulate that portal...

  19. Idiopathic Intracranial Hypertension (Pseudotumor Cerebri)

    Science.gov (United States)

    ... cause is determined and is referred to as “secondary” intracranial hypertension. What are the risk factors for idiopathic intracranial ... clotting disorders, anemia and malnutrition. Can idiopathic intracranial ... to be “secondary” which affects males and females equally. The second ...

  20. Masked hypertension in diabetes mellitus

    DEFF Research Database (Denmark)

    Franklin, Stanley S; Thijs, Lutgarde; Li, Yan

    2013-01-01

    Although distinguishing features of masked hypertension in diabetics are well known, the significance of antihypertensive treatment on clinical practice decisions has not been fully explored. We analyzed 9691 subjects from the population-based 11-country International Database on Ambulatory Blood...

  1. [Hypertension: once primary, always primary?

    NARCIS (Netherlands)

    Braam, R.L.; Pieters, G.F.F.M.; Thien, Th.

    2002-01-01

    Three patients diagnosed with primary hypertension suddenly developed hard-to-treat blood pressure after several years of stable blood pressure. One patient, a man aged 48 years, had developed a renal artery stenosis, which had not been present five years earlier. The other two patients, a man aged

  2. Hypertension control in brazilian publications

    Energy Technology Data Exchange (ETDEWEB)

    Pinho, Natália de Alencar; Pierin, Angela Maria Geraldo, E-mail: pierin@usp.br [Universidade de São Paulo, Escola de Enfermagem, São Paulo, SP (Brazil)

    2013-09-15

    Hypertension is a major public health problem due to its high prevalence and cardiovascular complications. Its treatment is aimed at reducing cardiovascular morbidity and mortality, its goal being to maintain blood pressure levels below 140/90 mm Hg. Hypertension control in Brazil is low, and nationwide rates are unknown. The objective of this review was to provide an overview on hypertension control in Brazil from publications in a database. We identified 45 publications. In population-based studies, the highest control rate (57.6%) was reported in a multicenter study in 100 municipalities and the city of São José do Rio Preto, São Paulo state (52.4%), while the lowest rates (around 10%) were identified in microregions of the Rio Grande do Sul state and in the city of Tubarão, Santa Catarina state. In conclusion, the studies assessed showed a wide variation in hypertension control rates. It is worth noting that the comparison between studies was a major limiting factor, because of the different methods used.

  3. Hypertensive disorders in twin pregnancy

    NARCIS (Netherlands)

    J.G. Santema (Job); E. Koppelaar (Elin); H.C.S. Wallenburg (Henk)

    1995-01-01

    textabstractObjective: To compare the incidence and severity of pregnancy-induced hypertensive disorders in twin pregnancy and in singleton gestation. Study design: Case-control study in the setting of a University Hospital. Each pregnancy of a consecutive series of 187 twin pregnancies attending

  4. Management of pulmonary arterial hypertension.

    LENUS (Irish Health Repository)

    Judge, Eoin P

    2013-02-01

    Pulmonary arterial hypertension (PAH) is a complex disease with a high mortality. Management of this disease is underpinned by supportive and general therapies delivered by multidisciplinary teams in specialist centres. In recent years, a number of PAH-specific therapies have improved patient outcomes. This article will discuss the management of PAH in the context of relevant recently published studies in this area.

  5. Hypertension control in brazilian publications

    International Nuclear Information System (INIS)

    Pinho, Natália de Alencar; Pierin, Angela Maria Geraldo

    2013-01-01

    Hypertension is a major public health problem due to its high prevalence and cardiovascular complications. Its treatment is aimed at reducing cardiovascular morbidity and mortality, its goal being to maintain blood pressure levels below 140/90 mm Hg. Hypertension control in Brazil is low, and nationwide rates are unknown. The objective of this review was to provide an overview on hypertension control in Brazil from publications in a database. We identified 45 publications. In population-based studies, the highest control rate (57.6%) was reported in a multicenter study in 100 municipalities and the city of São José do Rio Preto, São Paulo state (52.4%), while the lowest rates (around 10%) were identified in microregions of the Rio Grande do Sul state and in the city of Tubarão, Santa Catarina state. In conclusion, the studies assessed showed a wide variation in hypertension control rates. It is worth noting that the comparison between studies was a major limiting factor, because of the different methods used

  6. Intraabdominal hypertension og abdominalt kompartmentsyndrom

    DEFF Research Database (Denmark)

    Sonne, Morten; Hillingsø, Jens

    2008-01-01

    Intraabdominal hypertension (IAH) and abdominal compartment syndrome (ACS) are rare conditions with high mortality. IAH is an intraabdominal pressure (IAP) above 12 mmHg and ACS an IAP above 20 mmHg with evidence of organ dysfunction. IAP is measured indirectly via the bladder or stomach. Various...

  7. What Is IH (Intracranial Hypertension)?

    Science.gov (United States)

    ... Store What is IH? What is IH? Intracranial hypertension literally means that the pressure of cerebrospinal fluid ( ... is too high. “Intracranial” means “within the skull.” “Hypertension” means “high fluid pressure.” To understand how this ...

  8. Link between insulin resistance and hypertension: What is the evidence from evolutionary biology?

    Science.gov (United States)

    Zhou, Ming-Sheng; Wang, Aimei; Yu, Hong

    2014-01-31

    Insulin resistance and hypertension are considered as prototypical "diseases of civilization" that are manifested in the modern environment as plentiful food and sedentary life. The human propensity for insulin resistance and hypertension is a product, at least in part, of our evolutionary history. Adaptation to ancient lifestyle characterized by a low sodium, low-calorie food supply and physical stress to injury response has driven our evolution to shape and preserve a thrifty genotype, which is favorite with energy-saving and sodium conservation. As our civilization evolved, a sedentary lifestyle and sodium- and energy-rich diet, the thrifty genotype is no longer advantageous, and may be maladaptive to disease phenotype, such as hypertension, obesity and insulin resistance syndrome. This article reviews human evolution and the impact of the modern environment on hypertension and insulin resistance.

  9. Role of sympathetic nervous system and neuropeptides in obesity hypertension

    Directory of Open Access Journals (Sweden)

    J.E. Hall

    2000-06-01

    Full Text Available Obesity is the most common cause of human essential hypertension in most industrialized countries. Although the precise mechanisms of obesity hypertension are not fully understood, considerable evidence suggests that excess renal sodium reabsorption and a hypertensive shift of pressure natriuresis play a major role. Sympathetic activation appears to mediate at least part of the obesity-induced sodium retention and hypertension since adrenergic blockade or renal denervation markedly attenuates these changes. Recent observations suggest that leptin and its multiple interactions with neuropeptides in the hypothalamus may link excess weight gain with increased sympathetic activity. Leptin is produced mainly in adipocytes and is believed to regulate energy balance by acting on the hypothalamus to reduce food intake and to increase energy expenditure via sympathetic activation. Short-term administration of leptin into the cerebral ventricles increases renal sympathetic activity, and long-term leptin infusion at rates that mimic plasma concentrations found in obesity raises arterial pressure and heart rate via adrenergic activation in non-obese rodents. Transgenic mice overexpressing leptin also develop hypertension. Acute studies suggest that the renal sympathetic effects of leptin may depend on interactions with other neurochemical pathways in the hypothalamus, including the melanocortin-4 receptor (MC4-R. However, the role of this pathway in mediating the long-term effects of leptin on blood pressure is unclear. Also, it is uncertain whether there is resistance to the chronic renal sympathetic and blood pressure effects of leptin in obese subjects. In addition, leptin also has other cardiovascular and renal actions, such as stimulation of nitric oxide formation and improvement of insulin sensitivity, which may tend to reduce blood pressure in some conditions. Although the role of these mechanisms in human obesity has not been elucidated, this

  10. Device-based approaches for renal nerve ablation for hypertension and beyond

    OpenAIRE

    Alicia Ann Thorp; Markus Peter Schlaich; Markus Peter Schlaich

    2015-01-01

    Animal and human studies have demonstrated that chronic activation of renal sympathetic nerves is critical in the pathogenesis and perpetuation of treatment-resistant hypertension. Bilateral renal denervation has emerged as a safe and effective, non-pharmacological treatment for resistant hypertension that involves the selective ablation of efferent and afferent renal nerves to lower blood pressure. However, the most recent and largest randomized controlled trial failed to confirm the primacy...

  11. Cerebrovascular gene expression in spontaneously hypertensive rats

    DEFF Research Database (Denmark)

    Grell, Anne-Sofie; Frederiksen, Simona Denise; Edvinsson, Lars

    2017-01-01

    Hypertension is a hemodynamic disorder and one of the most important and well-established risk factors for vascular diseases such as stroke. Blood vessels exposed to chronic shear stress develop structural changes and remodeling of the vascular wall through many complex mechanisms. However......, the molecular mechanisms involved are not fully understood. Hypertension-susceptible genes may provide a novel insight into potential molecular mechanisms of hypertension and secondary complications associated with hypertension. The aim of this exploratory study was to identify gene expression differences......, the identified genes in the middle cerebral arteries from spontaneously hypertensive rats could be possible mediators of the vascular changes and secondary complications associated with hypertension. This study supports the selection of key genes to investigate in the future research of hypertension-induced end...

  12. Diuretics in the treatment of hypertension.

    Science.gov (United States)

    Blowey, Douglas L

    2016-12-01

    Diuretics have long been used for the treatment of hypertension. Thiazide diuretics are the most commonly prescribed diuretics for hypertension, but other classes of diuretics may be useful in alternative circumstances. Although diuretics are no longer considered the preferred agent for treatment of hypertension in adults and children, they remain acceptable first-line options. Diuretics effectively decrease blood pressure in hypertensive patients, and in adults with hypertension reduce the risk of adverse cardiovascular outcomes. Because of varied pharmacokinetic and pharmacodynamic differences, chlorthalidone may be the preferred thiazide diuretic in the treatment of primary hypertension. Other types of diuretics (e.g., loop, potassium sparing) may be useful for the treatment of hypertension related to chronic kidney disease (CKD) and other varied conditions. Common side effects of thiazides are mostly dose-related and involve electrolyte and metabolic abnormalities.

  13. [Hypertension in women (contraception and menopause].

    Science.gov (United States)

    Beaufils, M

    2000-11-01

    There are three circumstances where hypertension develops specifically in women: oral contraception, pregnancy, and menopause. Oral contraception usually shifts the blood pressure moderately upwards, but hypertension appears in less than 5% of women. Still it may (rarely) be very severe. Hypertension is poorly related to the dosage of the estrogenic compound, but rather to the nature and dosage of the progestive part. This hypertension does not significantly increase the cardiovascular risk of these women. The role of menopause itself in the trigging of hypertension remains uncertain. It seems however that confounding factors such as age, body weight, sodium balance and so on explain the increased incidence of hypertension after menopause. The latter is also associated with an increase of cardiovascular risk, which requires adequate treatment. Hormone replacement therapy is not contra-indicated, even in hypertensive patients.

  14. Catheter-based renal denervation for resistant hypertension: Twenty-four month results of the EnligHTN I first-in-human study using a multi-electrode ablation system.

    Science.gov (United States)

    Tsioufis, Costas P; Papademetriou, Vasilios; Dimitriadis, Kyriakos S; Kasiakogias, Alexandros; Tsiachris, Dimitrios; Worthley, Matthew I; Sinhal, Ajay R; Chew, Derek P; Meredith, Ian T; Malaiapan, Yuvi; Thomopoulos, Costas; Kallikazaros, Ioannis; Tousoulis, Dimitrios; Worthley, Stephen G

    2015-12-15

    Long term safety and efficacy data of multi-electrode ablation system for renal denervation (RDN) in patients with drug resistant hypertension (dRHT) are limited. We studied 46 patients (age: 60 ± 10 years, 4.7 ± 1.0 antihypertensive drugs) with drug resistant hypertension (dRHT). Reduction in office BP at 24 months from baseline was -29/-13 mmHg, while the reduction in 24-hour ambulatory BP and in home BP at 24 months were -13/-7 mmHg and -11/-6 mmHg respectively (p<0.05 for all). A correlation analysis revealed that baseline office and ambulatory BP were related to the extent of office and ambulatory BP drop. Apart from higher body mass index (33.3 ± 4.7 vs 29.5 ± 6.2 kg/m(2), p<0.05), there were no differences in patients that were RDN responders defined as ≥10 mmHg decrease (74%, n=34) compared to non-responders. Stepwise logistic regression analysis revealed no prognosticators of RDN response (p=NS for all). At 24 months there were no new serious device or procedure related adverse events. The EnligHTN I study shows that the multi-electrode ablation system provides a safe method of RDN in dRHT accompanied by a clinically relevant and sustained BP reduction. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  15. Masked Hypertension and Incident Clinic Hypertension among African Americans in the Jackson Heart Study

    Science.gov (United States)

    Abdalla, Marwah; Booth, John N.; Seals, Samantha R.; Spruill, Tanya M.; Viera, Anthony J.; Diaz, Keith M.; Sims, Mario; Muntner, Paul; Shimbo, Daichi

    2016-01-01

    Masked hypertension, defined as non-elevated clinic blood pressure and elevated out-of-clinic blood pressure may be an intermediary stage in the progression from normotension to hypertension. We examined the associations of out-of-clinic blood pressure and masked hypertension using ambulatory blood pressure monitoring with incident clinic hypertension in the Jackson Heart Study, a prospective cohort of African Americans. Analyses included 317 participants with clinic blood pressure hypertension was defined as mean daytime blood pressure ≥135/85mmHg; masked nighttime hypertension as mean nighttime blood pressure ≥120/70mmHg; and masked 24-hour hypertension as mean 24-hour blood pressure ≥130/80mmHg. Incident clinic hypertension, assessed at study visits in 2005–2008 and 2009–2012, was defined as the first visit with clinic systolic/diastolic blood pressure ≥140/90mmHg or antihypertensive medication use. During a median follow-up of 8.1 years, there were 187 (59.0%) incident cases of clinic hypertension. Clinic hypertension developed in 79.2% and 42.2% of participants with and without any masked hypertension, 85.7% and 50.4% with and without masked daytime hypertension, 79.9% and 43.7% with and without masked nighttime hypertension and 85.7% and 48.2% with and without masked 24-hour hypertension, respectively. Multivariable-adjusted hazard ratios (95% CI) of incident clinic hypertension for any masked hypertension and masked daytime, nighttime, and 24-hour hypertension were 2.13 (1.51–3.02), 1.79 (1.24–2.60), 2.22 (1.58–3.12), and 1.91 (1.32–2.75), respectively. These findings suggest that ambulatory blood pressure monitoring can identify African Americans at increased risk for developing clinic hypertension. PMID:27185746

  16. Recent advances in the management of resistant hypertension

    OpenAIRE

    Manolis, Athanasios J.; Kallistratos, Manolis S.; Doumas, Michalis; Pagoni, Stamatina; Poulimenos, Leonidas

    2015-01-01

    And suddenly, following the preliminary results of renal denervation and carotid baroreceptor stimulation, a big interest in resistant hypertension rose, and all interventionists, many of them with no previous experience with hypertension, fell in love with hypertension and especially resistant hypertension. In the European Society of Hypertension/International Society of Hypertension (ESH/ISH) 2014 Joint Hypertension meeting in Athens, there were no more than four to five sessions related to...

  17. Malignant hypertension and hypertensive encephalopathy in primary aldosteronism caused by adrenal adenoma

    Directory of Open Access Journals (Sweden)

    Bortolotto Luiz Aparecido

    2003-01-01

    Full Text Available Two cases are reported as follows: 1 1 female patient with accelerated-malignant hypertension secondary to an aldosterone-producing adrenal adenoma; and 2 1 female patient with adrenal adenoma, severe hypertension, and hypertensive encephalopathy. This association is a rare clinical finding, and malignant hypertension may modify the hormonal characteristic of primary aldosteronism, making its diagnosis more difficult. The diagnosis of primary aldosteronism should be considered in patients with malignant hypertension or hypertensive encephalopathy if persistent hypokalemia occurs. Identification of primary aldosteronism is of paramount importance for the patient's evolution, because the surgical treatment makes the prognosis more favorable.

  18. [Psychological approaches in hypertension management].

    Science.gov (United States)

    Abgrall-Barbry, Gaëlle; Consoli, Silla M

    2006-06-01

    Stress factors, especially high levels of occupational stress, are associated with hypertension. Several so-called psychological techniques have been applied to hypertension: biofeedback, relaxation techniques (Schultz' autogenic training, Jacobson's progressive relaxation), transcendental meditation, and cognitive behavioral techniques for stress management. Randomized studies show that the best results come from cognitive behavioral methods, whether or not they include relaxation techniques. Other forms of psychotherapy (such as psychoanalysis) may be useful, although their benefits for blood pressure have not been tested in controlled trials. Patients should be informed about the personal benefits they may obtain from psychological treatment. Indications are hyperreactivity to stress, high levels of occupational stress, and difficulty in tolerating or complying with antihypertensive drugs.

  19. Pregnancy in pulmonary arterial hypertension

    Directory of Open Access Journals (Sweden)

    Karen M. Olsson

    2016-12-01

    Full Text Available Despite advanced therapies, maternal mortality in women with pulmonary arterial hypertension (PAH remains high in pregnancy and is especially high during the post-partum period. However, recent data indicates that morbidity and mortality during pregnancy and after birth have improved for PAH patients. The current European Society of Cardiology/European Respiratory Society guidelines recommend that women with PAH should not become pregnant. Therefore, the risks associated with pregnancy must be emphasised and counselling offered to women at the time of PAH diagnosis and to women with PAH who become pregnant. Early termination should be discussed. Women who choose to continue with their pregnancy should be treated at specialised pulmonary hypertension centres with experience in managing PAH during and after pregnancy.

  20. Pregnancy in pulmonary arterial hypertension.

    Science.gov (United States)

    Olsson, Karen M; Channick, Richard

    2016-12-01

    Despite advanced therapies, maternal mortality in women with pulmonary arterial hypertension (PAH) remains high in pregnancy and is especially high during the post-partum period. However, recent data indicates that morbidity and mortality during pregnancy and after birth have improved for PAH patients. The current European Society of Cardiology/European Respiratory Society guidelines recommend that women with PAH should not become pregnant. Therefore, the risks associated with pregnancy must be emphasised and counselling offered to women at the time of PAH diagnosis and to women with PAH who become pregnant. Early termination should be discussed. Women who choose to continue with their pregnancy should be treated at specialised pulmonary hypertension centres with experience in managing PAH during and after pregnancy. Copyright ©ERS 2016.

  1. Echocardiographic abnormalities in hypertensive patients

    International Nuclear Information System (INIS)

    Rodulfo Garcia, Maikel; Tornes Perez, Victor Manuel; Castellanos Tardo, Juan Ramon

    2012-01-01

    A descriptive cross-sectional study was carried out in 120 hypertensive patients with a course of 5 or more years, who went to the emergency room of 'Saturnino Lora' Provincial Teaching Hospital from November 2010 to November 2011 in order to determine the presence or absence of echocardiographic abnormalities typical of hypertension. Of these, 78,3 % was affected, most of whom reported not to continue with regular previous medical treatment, and 21,7 % had not these abnormalities. Age group of 50-60 years, males and blacks prevailed in the case material. The most significant echocardiographic findings were left ventricular hypertrophy and heart failure with ejection fraction of left ventricle preserved

  2. Emergency Management of Hypertension in Children

    Directory of Open Access Journals (Sweden)

    Dinesh Singh

    2012-01-01

    Full Text Available Systemic arterial hypertension in children has traditionally been thought to be secondary in origin. Increased incidence of risk factors like obesity, sedentary life-styles, and faulty dietary habits has led to increased prevalence of the primary arterial hypertension (PAH, particularly in adolescent age children. PAH has become a global epidemic worldwide imposing huge economic constraint on health care. Sudden acute increase in systolic and diastolic blood pressure can lead to hypertensive crisis. While it generally pertains to secondary hypertension, occurrence of hypertensive crisis in PAH is however rare in children. Hypertensive crisis has been further subclassified depending on presence or absence of end-organ damage into hypertensive emergency or urgency. Both hypertensive emergencies and urgencies are known to cause significant morbidity and mortality. Increasing awareness among the physicians, targeted at investigation of the pathophysiology of hypertension and its complications, better screening methods, generation, and implementation of novel treatment modalities will impact overall outcomes. In this paper, we discuss the etiology, pathogenesis, and management of hypertensive crisis in children. An extensive database search using keywords was done to obtain the information.

  3. Secondary Hypertension: Discovering the Underlying Cause.

    Science.gov (United States)

    Charles, Lesley; Triscott, Jean; Dobbs, Bonnie

    2017-10-01

    Most patients with hypertension have no clear etiology and are classified as having primary hypertension. However, 5% to 10% of these patients may have secondary hypertension, which indicates an underlying and potentially reversible cause. The prevalence and potential etiologies of secondary hypertension vary by age. The most common causes in children are renal parenchymal disease and coarctation of the aorta. In adults 65 years and older, atherosclerotic renal artery stenosis, renal failure, and hypothyroidism are common causes. Secondary hypertension should be considered in the presence of suggestive symptoms and signs, such as severe or resistant hypertension, age of onset younger than 30 years (especially before puberty), malignant or accelerated hypertension, and an acute rise in blood pressure from previously stable readings. Additionally, renovascular hypertension should be considered in patients with an increase in serum creatinine of at least 50% occurring within one week of initiating angiotensin-converting enzyme inhibitor or angiotensin receptor blocker therapy; severe hypertension and a unilateral smaller kidney or difference in kidney size greater than 1.5 cm; or recurrent flash pulmonary edema. Other underlying causes of secondary hypertension include hyperaldosteronism, obstructive sleep apnea, pheochromocytoma, Cushing syndrome, thyroid disease, coarctation of the aorta, and use of certain medications.

  4. Food Patterns, Lifestyle, and Hypertension

    Directory of Open Access Journals (Sweden)

    Golnaz Arjmand

    2016-06-01

    Full Text Available High blood pressure (BP is considered as a strong predisposing factor for cardiovascular diseases (CVD Environmental and genetic factors may have a role in high blood pressures. Nutrition has a potential role in the prevention of hypertension and its sequelae. Effect of lowering blood pressure by modification of complex dietary patterns may be the result of synergism between the various components of certain foods or food combinations rather than of the specific effect of a particular nutrient. Vegetarian Diet, Mediterranean Diet, and Dash Diet are three food patterns which have been associated with lowering BP. Vegetarian Diet are characterized by high intake of legumes, nuts, vegetables, and fruits. A relatively high polyunsaturated to saturated fat ratio will make by this kind of diet. Low fat content and high potassium, magnesium, and fiber content of this diet, all factors possibly cooperating to the reduction of blood pressure. Mediterranean Diet has low animal and dairy products as well as saturated fatty acids and cholesterol; it is rich in plant food, legumes, fiber, and antioxidant vitamins with olive oil as the main source of fat. The dietary approaches to stop hypertension (DASH is a success process in control of hypertension, which emphasizes vegetables and fruits and dairy foods with low-fat, it also includes more nuts, poultry, fish, and, whole grains and lower amounts of red meat, fats, sweets, and sugar-containing beverages. DASH diet is poorer in total and saturated fat and cholesterol and richer in potassium, magnesium, calcium, and fiber in comparison to the habitual Western diet. In conclusion, although multiple dietary factors can influence on BP and each factor has a modest effect; the combined effects of those factors can be substantial. In the current study, we review food patterns, lifestyle, and their relationship with hypertension and the possible mechanisms involved.

  5. Syphilis mimicking idiopathic intracranial hypertension

    DEFF Research Database (Denmark)

    Yri, Hanne; Wegener, Marianne; Jensen, Rigmor

    2011-01-01

    Idiopathic intracranial hypertension (IIH) is a condition of yet unknown aetiology affecting predominantly obese females of childbearing age. IIH is a diagnosis of exclusion as raised cerebrospinal fluid pressure may occur secondary to numerous other medical conditions. An atypical phenotype or a...... antibiotic treatment, signs and symptoms of elevated intracranial pressure resolved completely. Syphilis is a rare, but very important, differential diagnosis that in this case was clinically indistinguishable from IIH....

  6. Polycystic ovary disease and the risk of pregnancy-induced hypertension.

    Science.gov (United States)

    Kashyap, S; Claman, P

    2000-12-01

    To compare the incidence of pregnancy-induced hypertension in patients with and without polycystic ovary disease (PCOD). We conducted a retrospective, case-control analysis of patients who achieved singleton pregnancies with human menopausal gonadotropin (hMG) therapy. Twenty-two PCOD patients were compared to 27 infertility patients without PCOD who were pregnant after hMG therapy. Non-PCOD patients received hMG for superovulation as part of superovulation/intrauterine insemination or in vitro fertilization/embryo transfer. PCOD patients were receiving hMG for simple ovulation induction. Pregnancy-induced hypertension was defined as late pregnancy blood pressure > 140/90 mm Hg on two readings six hours apart and return to normal blood pressure by four to six weeks postpartum. There were no differences between PCOD and non-PCOD patients with reference to age, body mass index, parity or other pregnancy-induced hypertension risk factors (i.e., chronic hypertension, diabetes or chronic renal disease). Pregnant PCOD patients had a much higher incidence of pregnancy-induced hypertension, 31.8% (7/22), versus non-PCOD patients, who only had a pregnancy-induced hypertension incidence of 3.7% (1/27) (P = .016, OR = 12.1, 95% CI = 1.3-566.8). PCOD patients are at very high risk of pregnancy-induced hypertension when pregnant after ovulation induction.

  7. Role of aliskiren in cardio-renal protection and use in hypertensives with multiple risk factors

    Directory of Open Access Journals (Sweden)

    Eduardo Pimenta

    2009-06-01

    Full Text Available Eduardo Pimenta1, Suzanne Oparil21Endocrine Hypertension Research Centre and Clinical Centre of Research Excellence in Cardiovascular Disease and Metabolic Disorders, University of Queensland School of Medicine, Greenslopes Princess Alexandra Hospitals, Brisbane, QLD, Australia; 2Vascular Biology and Hypertension Program, University of Alabama at Birmingham, Birmingham, AL, USAAbstract: The renin–angiotensin–aldosterone system (RAAS is a key mediator of blood pressure (BP and volume regulation in both normotensive and hypertensive persons. Stimulation of RAAS also contributes to hypertension-related target organ damage. The renin–angiotensinogen reaction is the first and rate-limiting step in the generation of angiotensin II (Ang II and has been a target of antihypertensive drug development for decades. Aliskiren is the first in a new class of orally effective direct renin inhibitors (DRIs and is approved for the treatment of hypertension in humans. It effectively reduces BP in the general population of hypertensive patients and has a tolerability and safety profile similar to placebo. Aliskiren has favorable effects on vascular inflammation and remodeling, on neurohumoral mediators of various forms of cardiovascular disease, including heart failure, and on proteinuria in diabetic patients. Additional outcome trials are needed to establish the role of this novel class of antihypertensive medication in preventing cardiovascular disease morbidity and mortality.Keywords: hypertension, renin inhibitors, renin-angiotensin-aldosterone system

  8. White coat hypertension in pediatrics.

    Science.gov (United States)

    Jurko, Alexander; Minarik, Milan; Jurko, Tomas; Tonhajzerova, Ingrid

    2016-01-15

    The article summarizes current information on blood pressure changes in children during clinic visit. White coat as a general dressing of physicians and health care personnel has been widely accepted at the end of the 19th century. Two problems can be associated with the use of white coat: white coat phenomenon and white coat hypertension. Children often attribute pain and other unpleasant experience to the white coat and refuse afterwards cooperation with examinations. Definition of white coat hypertension in the literature is not uniform. It has been defined as elevated blood pressure in the hospital or clinic with normal blood pressure at home measured during the day by ambulatory blood pressure monitoring system. White coat effect is defined as temporary increase in blood pressure before and during visit in the clinic, regardless what the average daily ambulatory blood pressure values are. Clinical importance of white coat hypertension is mainly because of higher risk for cardiovascular accidents that are dependent on end organ damage (heart, vessels, kidney). Current data do not allow any clear recommendations for the treatment. Pharmacological therapy is usually started in the presence of hypertrophic left ventricle, changes in intimal/medial wall thickness of carotic arteries, microalbuminuria and other cardiovascular risk factors. Nonpharmacological therapy is less controversial and certainly more appropriate. Patients have to change their life style, need to eliminate as much cardiovascular risk factors as possible and sustain a regular blood pressure monitoring.

  9. Decoding resistant hypertension signalling pathways.

    Science.gov (United States)

    Parreira, Ricardo Cambraia; Lacerda, Leandro Heleno Guimarães; Vasconcellos, Rebecca; Lima, Swiany Silveira; Santos, Anderson Kenedy; Fontana, Vanessa; Sandrim, Valéria Cristina; Resende, Rodrigo Ribeiro

    2017-12-01

    Resistant hypertension (RH) is a clinical condition in which the hypertensive patient has become resistant to drug therapy and is often associated with increased cardiovascular morbidity and mortality. Several signalling pathways have been studied and related to the development and progression of RH: modulation of sympathetic activity by leptin and aldosterone, primary aldosteronism, arterial stiffness, endothelial dysfunction and variations in the renin-angiotensin-aldosterone system (RAAS). miRNAs comprise a family of small non-coding RNAs that participate in the regulation of gene expression at post-transcriptional level. miRNAs are involved in the development of both cardiovascular damage and hypertension. Little is known of the molecular mechanisms that lead to development and progression of this condition. This review aims to cover the potential roles of miRNAs in the mechanisms associated with the development and consequences of RH, and explore the current state of the art of diagnostic and therapeutic tools based on miRNA approaches. © 2017 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

  10. Cadmium in blood and hypertension

    International Nuclear Information System (INIS)

    Eum, Ki-Do; Lee, Mi-Sun; Paek, Domyung

    2008-01-01

    Objectives:: This study is to examine the effect of cadmium exposure on blood pressure in Korean general population. Methods:: The study population consisted of 958 men and 944 women who participated in the 2005 Korean National Health and Nutrition Examination Survey (KNHANES), in which blood pressure and blood cadmium were measured from each participant. Results:: The mean blood cadmium level was 1.67 μg/L (median level 1.55). The prevalence of hypertension was 26.2%. The blood cadmium level was significantly higher among those subjects with hypertension than those without (mean level 1.77 versus 1.64 μg/dL). After adjusting for covariates, the odds ratio of hypertension comparing the highest to the lowest tertile of cadmium in blood was 1.51 (95% confidence interval 1.13 to 2.05), and a dose-response relationship was observed. Systolic, diastolic, and mean arterial blood pressure were all positively associated with blood cadmium level, and this effect of cadmium on blood pressure was markedly stronger when the kidney function was reduced. Conclusions:: Cadmium exposures at the current level may have increased the blood pressure of Korean general population

  11. Treatment of pediatric pulmonary hypertension

    Directory of Open Access Journals (Sweden)

    Amy Hawkins

    2009-06-01

    Full Text Available Amy Hawkins, Robert TullohDepartment of Congenital Heart Disease, Bristol Royal Hospital for Children, Bristol UKAbstract: Pulmonary hypertension was once thought to be a rare condition and only managed in specialized centers. Now however, with the advent of echocardiography, it is found in many clinical scenarios, in the neonate with chronic lung disease, in the acute setting in the intensive care unit, in connective tissue disease and in cardiology pre- and postoperatively. We have a better understanding of the pathological process and have a range of medication which is starting to be able to palliate this previously fatal condition. This review describes the areas that are known in this condition and those that are less familiar. The basic physiology behind pulmonary hypertension and pulmonary vascular disease is explained. The histopathologic process and the various diagnostic tools are described and are followed by the current and future therapy at our disposal.Keywords: pulmonary hypertension, congenital heart disease, pulmonary vascular resistance, pulmonary vasodilators

  12. Spaceflight-Induced Intracranial Hypertension.

    Science.gov (United States)

    Michael, Alex P; Marshall-Bowman, Karina

    2015-06-01

    Although once a widely speculated about and largely theoretical topic, spaceflight-induced intracranial hypertension has gained acceptance as a distinct clinical phenomenon, yet the underlying physiological mechanisms are still poorly understood. In the past, many terms were used to describe the symptoms of malaise, nausea, vomiting, and vertigo, though longer duration spaceflights have increased the prevalence of overlapping symptoms of headache and visual disturbance. Spaceflight-induced visual pathology is thought to be a manifestation of increased intracranial pressure (ICP) because of its similar presentation to cases of known intracranial hypertension on Earth as well as the documentation of increased ICP by lumbar puncture in symptomatic astronauts upon return to gravity. The most likely mechanisms of spaceflight-induced increased ICP include a cephalad shift of body fluids, venous outflow obstruction, blood-brain barrier breakdown, and disruption to CSF flow. The relative contribution of increased ICP to the symptoms experienced during spaceflight is currently unknown, though other factors recently posited to contribute include local effects on ocular structures, individual differences in metabolism, and the vasodilator effects of carbon dioxide. This review article attempts to consolidate the literature regarding spaceflight-induced intracranial hypertension and distinguish it from other pathologies with similar symptomatology. It discusses the proposed physiological causes and the pathological manifestations of increased ICP in the spaceflight environment and provides considerations for future long-term space travel. In the future, it will be critical to develop countermeasures so that astronauts can participate at their peak potential and return safely to Earth.

  13. Cadmium in blood and hypertension

    Energy Technology Data Exchange (ETDEWEB)

    Eum, Ki-Do; Lee, Mi-Sun [Department of Environmental Health, Graduate School of Public Health and Institute of Health and Environment, Seoul National University, Seoul (Korea, Republic of); Paek, Domyung [Department of Environmental Health, Graduate School of Public Health and Institute of Health and Environment, Seoul National University, Seoul (Korea, Republic of)], E-mail: paekdm@snu.ac.kr

    2008-12-15

    Objectives:: This study is to examine the effect of cadmium exposure on blood pressure in Korean general population. Methods:: The study population consisted of 958 men and 944 women who participated in the 2005 Korean National Health and Nutrition Examination Survey (KNHANES), in which blood pressure and blood cadmium were measured from each participant. Results:: The mean blood cadmium level was 1.67 {mu}g/L (median level 1.55). The prevalence of hypertension was 26.2%. The blood cadmium level was significantly higher among those subjects with hypertension than those without (mean level 1.77 versus 1.64 {mu}g/dL). After adjusting for covariates, the odds ratio of hypertension comparing the highest to the lowest tertile of cadmium in blood was 1.51 (95% confidence interval 1.13 to 2.05), and a dose-response relationship was observed. Systolic, diastolic, and mean arterial blood pressure were all positively associated with blood cadmium level, and this effect of cadmium on blood pressure was markedly stronger when the kidney function was reduced. Conclusions:: Cadmium exposures at the current level may have increased the blood pressure of Korean general population.

  14. High-altitude pulmonary hypertension

    Directory of Open Access Journals (Sweden)

    X-Q. Xu

    2009-03-01

    Full Text Available High-altitude pulmonary hypertension (HAPH is a specific disease affecting populations that live at high elevations. The prevalence of HAPH among those residing at high altitudes needs to be further defined. Whereas reduction in nitric oxide production may be one mechanism for the development of HAPH, the roles of endothelin-1 and prostaglandin I2 pathways in the pathogenesis of HAPH deserve further study. Although some studies have suggested that genetic factors contribute to the pathogenesis of HAPH, data published to date are insufficient for the identification of a significant number of gene polymorphims in HAPH. The clinical presentation of HAPH is nonspecific. Exertional dyspnoea is the most common symptom and signs related to right heart failure are common in late stages of HAPH. Echocardiography is the most useful screening tool and right heart catheterisation is the gold standard for the diagnosis of HAPH. The ideal management for HAPH is migration to lower altitudes. Phosphodiesterase 5 is an attractive drug target for the treatment of HAPH. In addition, acetazolamide is a promising therapeutic agent for high-altitude pulmonary hypertension. To date, no evidence has confirmed whether endothelin-receptor antagonists have efficacy in the treatment of high-altitude pulmonary hypertension.

  15. Pulmonary hypertension of the newborn.

    Science.gov (United States)

    Stayer, Stephen A; Liu, Yang

    2010-09-01

    Pulmonary hypertension presenting in the neonatal period can be due to congenital heart malformations (most commonly associated with obstruction to pulmonary venous drainage), high output cardiac failure from large arteriovenous malformations and persistent pulmonary hypertension of the newborn (PPHN). Of these, the most common cause is PPHN. PPHN develops when pulmonary vascular resistance (PVR) remains elevated after birth, resulting in right-to-left shunting of blood through foetal circulatory pathways. The PVR may remain elevated due to pulmonary hypoplasia, like that seen with congenital diaphragmatic hernia; maldevelopment of the pulmonary arteries, seen in meconium aspiration syndrome; and maladaption of the pulmonary vascular bed as occurs with perinatal asphyxia. These newborn patients typically require mechanical ventilatory support and those with underlying lung disease may benefit from high-frequency oscillatory ventilation or extra-corporeal membrane oxygenation (ECMO). Direct pulmonary vasodilators, such as inhaled nitric oxide, have been shown to improve the outcome and reduce the need for ECMO. However, there is very limited experience with other pulmonary vasodilators. The goals for anaesthetic management are (1) to provide an adequate depth of anaesthesia to ablate the rise in PVR associated with surgical stimuli; (2) to maintain adequate ventilation and oxygenation; and (3) to be prepared to treat a pulmonary hypertensive crisis--an acute rise in PVR with associated cardiovascular collapse.

  16. Anaphylactic reactions presenting with hypertension.

    Science.gov (United States)

    Solmazgul, Emrullah; Kutlu, Ali; Dogru, Salim; Ozalper, Veysel; Cetindagli, Ibrahim; Sezer, Ogun; Salmanoglu, Musa; Kilic, Erol; Karabacak, Ercan; Ozturk, Sami

    2016-01-01

    Although a few case reports about hypertensive anaphylaxis (HA) are available in the present literature, there is no study about the prevalence of HA. In this study, we review our cases with anaphylaxis presenting with hypertension and ascertain its prevalence. The documents of the patients who had anaphylactic reactions after the procedures performed for the diagnosis and treatment of allergic diseases in GATA Haydarpasa Clinic of Allergy and Immunology between January 2010 and December 2014 were retrospectively reviewed. Within the study period, 324 patients had undergone 4332 procedures in which 62 of them had developed anaphylaxis. During the procedures, the rate of anaphylaxis was found to be 1.43 %. The rate of HA among the anaphylaxis patients was 12.9 % (8 of 62 patients). During treatments, 2 patients received adrenaline injections without any adverse reaction. HA may be seen at a considerable rate during an anaphylactic reaction. Anaphylaxis and hypertension can be recovered by adrenaline injection when required. According to the best of our knowledge, this study is the first original study about the prevalence of HA in English-language medical literature.

  17. Determination of serum cadmium and lead in patients of ischemic hear disease associated with or without hypertension and diabetes mellitus

    International Nuclear Information System (INIS)

    Nagra, S.A.; Zikrya, B.; Maqbool, T.

    1999-01-01

    Human health and trace minerals are closely associated with each other. The vital role of trace elements has become clear in the recent years. The relation of trace elements in serum varies with the state of human health, ecology and under different pathological conditions. Determination of cadmium, and lead in the blood serum of normal, hypertensive patients, Ischemic heart patients, diabetic patients, hypertensive patients having diabetes, ischemic heart patients with diabetes, and hypertensive patients having ischemic heart disease, was carried out by using atomic absorption spectroscopic techniques. The results indicated that the concentration of cadmium and lead was elevated as compared with the normal and discussed in this paper. (author)

  18. Mechanisms and mediators of hypertension induced by erythropoietin and related molecules.

    Science.gov (United States)

    Agarwal, Rajiv

    2017-12-08

    Hypertension is a common but frequently overlooked adverse effect of erythropoietin (EPO) therapy. Underreporting of hypertension with EPO is likely due to either more aggressively managing hypertension through the prescription of antihypertensive drugs or closer attention to dry weight. The purpose and focus of this review is to critically evaluate the mechanisms of EPO-induced hypertension. Preclinical data are considered first, followed by clinical data where available. Mediated by a variety of molecules, there is an imbalance in the vascular tone favoring net vasoconstriction that mediates EPO-induced hypertension. Animal studies show the primary importance of chronic kidney disease in the genesis of EPO-induced hypertension. Preclinical studies show deranged regulation of the nitric oxide, endothelins and porstanoids and the sympathoadrenal and renin-angiotensin pathways as causes of EPO-induced hypertension. Human studies suggest that EPO administration is also associated with increased responsiveness to catecholamines and angiotensin II on vascular tissue; in addition, hypoxia-induced vasodilation may be impaired in those with EPO-induced hypertension. There is little evidence for EPO as a direct vasoconstrictor or its effect on blood viscosity as a mechanism of EPO-induced hypertension. EPO-induced hypertension, at least in part, appears to be independent of an increase in hemoglobin, because experiments show that hemoglobin may be increased by EPO without an increase in blood pressure (BP) by simply treating the animals with EPO-binding protein and that treatment with EPO in the setting of iron deficiency may not increase hemoglobin but may still increase BP. However, experimental data are not consistent across studies and better mechanistic designs are needed, especially in patients with chronic kidney disease, to dissect the precise mechanism of EPO-induced hypertension. Animal studies suggest that hypoxia-inducible factor stablizers may induce

  19. Plasma ET-1 Concentrations Are Elevated in Pregnant Women with Hypertension -Meta-Analysis of Clinical Studies

    Directory of Open Access Journals (Sweden)

    Yong-Ping Lu

    2017-11-01

    Full Text Available Background/Aims: The ET system might be involved in the pathogenesis of hypertensive disorders during pregnancy. The objective is to analyse the impact of ET-1 in hypertensive pregnant women by a strict meta-analysis of published human clinical studies. Methods: Based on the principle of Cochrane systematic reviews, Cohort studies in PubMed (Medline, Google Scholar and China Biological Medicine Database (CBM-disc designed to identify the role of endothelin-1 (ET-1 in the pathophysiology of gestational hypertension and preeclampsia were screened. Review Manager Version 5.0 (Rev-Man 5.0 was applied for statistical analysis. Mean difference and 95% confidence interval (CI were shown in inverse variance (IV fixed-effects model or IV random-effects model. Results: Sixteen published cohort studies including 1739 hypertensive cases and 409 controls were used in the meta-analysis. ET-1 plasma concentrations were higher in hypertensive pregnant women as compared to the controls (mean difference between groups: 19.02 [15.60~22.44], P < 0.00001,. These finding were driven by severity of hypertension and/or degree of proteinuria. Conclusion: Plasma ET-1 concentrations are elevated in hypertensive disorders during human pregnancy. In particular women with preeclampsia (hypertensive pregnant women with proteinuria have substantially elevated plasma ET-1 concentration as compared to pregnant women with normal blood pressure.

  20. Knowledge of Hypertensive Patients With or Without HIV on ...

    African Journals Online (AJOL)

    Erah

    hypertensive medicines than in those who were on anti-hypertensive medicines alone prior to being placed on ARVs. Pharmacists' knowledge of hypertension and anti-hypertensive agents. Table 4 presents data on pharnacists' knowledge of hypentension. Only 15 % of pharmacists could clearly define hypertension.

  1. Dutch guideline for the management of hypertensive crisis -- 2010 revision.

    Science.gov (United States)

    van den Born, B J H; Beutler, J J; Gaillard, C A J M; de Gooijer, A; van den Meiracker, A H; Kroon, A A

    2011-05-01

    Hypertensive crises are divided into hypertensive urgencies and emergencies. Together they form a heterogeneous group of acute hypertensive disorders depending on the presence or type of target organs involved. Despite better treatment options for hypertension, hypertensive crisis and its associated complications remain relatively common. In the Netherlands the number of patients starting renal replacement therapy because of 'malignant hypertension' has increased in the past two decades. In 2003, the first Dutch guideline on hypertensive crisis was released to allow a standardised evidence-based approach for patients presenting with a hypertensive crisis. In this paper we give an overview of the current management of hypertensive crisis and discuss several important changes incorporated in the 2010 revision. These changes include a modification in terminology replacing 'malignant hypertension' with 'hypertensive crisis with retinopathy and reclassification of hypertensive crisis with retinopathy under hypertensive emergencies instead of urgencies. With regard to the treatment of hypertensive emergencies, nicardipine instead of nitroprusside or labetalol is favoured for the management of perioperative hypertension, whereas labetalol has become the drug of choice for the treatment of hypertension associated with pre-eclampsia. For the treatment of hypertensive urgencies, oral administration of nifedipine retard instead of captopril is recommended as first-line therapy. In addition, a section on the management of hypertensive emergencies according to the type of target organ involved has been added. Efforts to increase the awareness and treatment of hypertension in the population at large may lower the incidence of hypertensive crisis and its complications.

  2. Managing hypertension in the newborn infants

    Directory of Open Access Journals (Sweden)

    Azar Nickavar

    2014-01-01

    Full Text Available Hypertension in newborn infants, particularly those requiring intensive care, is becoming increasingly recognized, with prevalence of 0.2-3%. Recent studies have established normative tables for blood pressure (BP in both term and pre-term infants based on the gestational age, postnatal age, gender, weight and height, identifying the neonates at increased risk for early-onset cardiovascular disease. Common causes of neonatal hypertension include thromboembolic complications secondary to umbilical artery catheterization, congenital renal structural malformation, renovascular disease, aortic coarctation, as well as acute kidney injury and certain medications. A careful diagnostic evaluation should lead to identification of the underlying cause of hypertension in most infants. Treatment options should be tailored to the severity; and underlying cause of hypertension, including intravenous and/or oral therapy. This review summarizes recent work in these areas, focusing on optimal BP measurement, definition, evaluation and management of hypertension as well as advances in drug therapy of neonatal hypertension.

  3. [Secondary Arterial Hypertension: Uncertainties in Diagnosis].

    Science.gov (United States)

    Dinis, Paulo Gomes; Cachulo, Maria Carmo; Fernandes, Andreia; Paiva, Luis; Gonçalves, Lino

    2017-06-30

    Arterial hypertension is regarded today as a global public health problem, and the prevalence rate in Portugal is 26.9%. According to the etiology, is classified into primary or secondary arterial hypertension. In about 90% of cases it is not possible to establish a cause, so is called primary arterial hypertension. In the remaining 5 to 10%, it can be identified secondary causes, which are potentially treatable. For secondary arterial hypertension study to be cost-effective, it is essential to understand which patients investigate, and evaluate the best strategy to adopt. The main causes identified as responsible for secondary arterial hypertension are: kidney disease; endocrine and vascular diseases and obstructive sleep apnea. Among these some are consensual, and others more controversial in the literature. In this regard we present two cases of arterial hypertension, which are potentially secondary in etiology, but still focus of debate.

  4. Systemic hypertension and non-cardiac surgery.

    Science.gov (United States)

    Misra, Satyajeet

    2017-09-01

    Primary systemic hypertension affects 10%-25% of individuals presenting for surgery and anaesthesia and constitutes an important cause of cancellation of elective surgeries. Much of the fear stems from the fact that hypertension may lead to adverse perioperative outcomes. Although long-standing hypertension increases the risk of stroke, renal dysfunction or major adverse cardiovascular events, the same is usually not seen in the perioperative period if blood pressure is <180/110 mmHg and this has been the overriding theme in the recent guidelines on perioperative blood pressure management. Newer concepts include isolated systolic hypertension and pulse pressure hypertension that are increasingly used to stratify risk. The aim of this review is to focus on the adult patient with chronic primary systemic hypertension posted for elective non-cardiac surgery and outline the perioperative concerns.

  5. Secondary hypertension, issues in diagnosis and treatment.

    Science.gov (United States)

    Pullalarevu, Raghavesh; Akbar, Ghulam; Teehan, Geoffrey

    2014-12-01

    Secondary hypertension (SH) often implies a correctable form of nonessential hypertension. Often certain clinical clues prompt a more extensive evaluation of the causes of the hypertension. Renovascular disease, intrinsic renal disease, primary hyperaldosteronism, and obstructive sleep apnea represent the most common causes of SH. This article defines the disorder and details its epidemiology, prevalence, pathophysiology, physical findings, and treatment strategies. Copyright © 2014 Elsevier Inc. All rights reserved.

  6. Drug Resistant Hypertension - No SIMPLE Way Out

    OpenAIRE

    Janusz Skrzypecki; Marcin Ufnal

    2015-01-01

    Hypertension poses growing challenge for health policy-makers and doctors worldwide. Recently published results of Symplicity-III trial (HTN-3), the first blinded, randomized, multicenter study on the efficacy of renal denervation for the treatment of resistant hypertension did not show a significant reduction of BP in patients with resistant hypertension 6 months after renal-artery denervation, as compared with controls. In this paper we review clinical and experimental studies on renal dene...

  7. Hypertension Vaccine may be a boon to millions in developing world.

    Science.gov (United States)

    Bairwa, Mohan; Pilania, Manju; Gupta, Vivek; Yadav, Kapil

    2014-01-01

    Hypertension affects around 40% adults aged 25 years and more worldwide, and accounts for 7% of total disability-adjusted life-years. A simple algorithmic program is required to manage hypertension consisting of screening, life style measures, treatment and follow-up, a reliable drug supply and distribution system, and a credible health information system. Despite availability of effective antihypertensive drugs, long term treatment is still costly, tedious, and at the population level rather unsuccessful. Hypertension leaves patients and families with an avoidable heavy economic burden due to failure to control blood pressure. Health policy needs to address gross imbalance between prevention and management by increasing contribution to the preventive programs. During 21st century, the risk factors for morbidity and mortality have been changed, and researchers have started to work upon vaccines against lifestyle diseases like hypertension, diabetes etc. Researchers began experimenting with vaccines against the renin-angiotensin system to control hypertension around six decades ago. The vaccine candidates against hypertension namely ATR12181, pHAV-4Ang IIs, CYT006-AngQb, AngI-R, ATRQβ-001 have shown promising results. A candidate vaccine, CYT006-AngQb, has crossed initial phase and moved into phase 2 trials. However, more human studies in subsequent phases of trials are required to establish the safety and efficacy of anti-hypertensive vaccine. If proved safe and cost effective, a vaccine even with 50% efficacy against hypertension may protect about 90 million people from hypertension and its heavy economic burden. It can be an appropriate solution for low compliance to antihypertensive drug therapy as well as an avalanche to induce efforts on various chronic disease vaccine development programs.

  8. Resistance Training in Spontaneously Hypertensive Rats with Severe Hypertension

    Directory of Open Access Journals (Sweden)

    Rodrigo Vanerson Passos Neves

    2016-01-01

    Full Text Available Abstract Background: Resistance training (RT has been recommended as a non-pharmacological treatment for moderate hypertension. In spite of the important role of exercise intensity on training prescription, there is still no data regarding the effects of RT intensity on severe hypertension (SH. Objective: This study examined the effects of two RT protocols (vertical ladder climbing, performed at different overloads of maximal weight carried (MWC, on blood pressure (BP and muscle strength of spontaneously hypertensive rats (SHR with SH. Methods: Fifteen male SHR ENT#091;206 ± 10 mmHg of systolic BP (SBPENT#093; and five Wistar Kyoto rats (WKY; 119 ± 10 mmHg of SBP were divided into 4 groups: sedentary (SED-WKY and SHR (SED-SHR; RT1-SHR training relative to body weight (~40% of MWC; and RT2-SHR training relative to MWC test (~70% of MWC. Systolic BP and heart rate (HR were measured weekly using the tail-cuff method. The progression of muscle strength was determined once every fifteen days. The RT consisted of 3 weekly sessions on non-consecutive days for 12-weeks. Results: Both RT protocols prevented the increase in SBP (delta - 5 and -7 mmHg, respectively; p > 0.05, whereas SBP of the SED-SHR group increased by 19 mmHg (p 0.05. Conclusions: Our data indicated that both RT protocols were effective in preventing chronic elevation of SBP in SH. Additionally, a higher RT overload induced a greater increase in muscle strength.

  9. Renal denervation therapy for hypertension: pathways for moving development forward.

    Science.gov (United States)

    White, William B; Galis, Zorina S; Henegar, Jeffrey; Kandzari, David E; Victor, Ronald; Sica, Domenic; Townsend, Raymond R; Turner, J Rick; Virmani, Renu; Mauri, Laura

    2015-05-01

    This scientific statement provides a summary of presentations and discussions at a cardiovascular Think Tank co-sponsored by the American Society of Hypertension (ASH), the United States Food and Drug Administration (FDA), and the National Heart, Lung, and Blood Institute (NHLBI) held in North Bethesda, Maryland, on June 26, 2014. Studies of device therapies for the treatment of hypertension are requested by regulators to evaluate their safety and efficacy during their development programs. Think Tank participants thought that important considerations in undertaking such studies were: (1) Preclinical assessment: how likely it is that both efficacy and safety data indicating benefit in humans will be obtained, and/or whether a plausible mechanism of action for efficacy can be identified; (2) Early human trial(s): the ability to determine that the device has an acceptable benefit-to-risk balance for its use in the intended patient population and without the influence of drug therapy during a short-term follow-up period; and (3) Pivotal Phase III trial(s): the ability to prove the effectiveness of the device in a broad population in which the trial can be made as non-confounded as possible while still allowing for the determination for benefits when added to antihypertensive therapies. Copyright © 2015 American Society of Hypertension. All rights reserved.

  10. Are human endogenous retroviruses triggers of autoimmune diseases?

    DEFF Research Database (Denmark)

    Nexø, Bjørn A; Villesen, Palle; Nissen, Kari K

    2016-01-01

    factors. Viruses including human endogenous retroviruses have long been linked to the occurrence of autoimmunity, but never proven to be causative factors. Endogenous viruses are retroviral sequences embedded in the host germline DNA and transmitted vertically through successive generations in a Mendelian...... manner. In this study by means of genetic epidemiology, we have searched for the involvement of endogenous retroviruses in three selected autoimmune diseases: multiple sclerosis, type 1 diabetes mellitus, and rheumatoid arthritis. We found that at least one human endogenous retroviral locus...

  11. Functional impact of the human mobilome.

    Science.gov (United States)

    Babatz, Timothy D; Burns, Kathleen H

    2013-06-01

    The human genome is replete with interspersed repetitive sequences derived from the propagation of mobile DNA elements. Three families of human retrotransposons remain active today: LINE1, Alu, and SVA elements. Since 1988, de novo insertions at previously recognized disease loci have been shown to generate highly penetrant alleles in Mendelian disorders. Only recently has the extent of germline-transmitted retrotransposon insertion polymorphism (RIP) in human populations been fully realized. Also exciting are recent studies of somatic retrotransposition in human tissues and reports of tumor-specific insertions, suggesting roles in tissue heterogeneity and tumorigenesis. Here we discuss mobile elements in human disease with an emphasis on exciting developments from the last several years. Copyright © 2013 Elsevier Ltd. All rights reserved.

  12. Clinical Observation on Hypertension in Diabetes Mellitus(Hypertension : Pathophysiology and Treatment)

    OpenAIRE

    奈良, 芳則; 尾崎, 信紘; 山田, 彬; 浜, 斉; 谷, 長行; Nara, Yoshinori; Ozaki, Nobuhiro; Yamada, Akira; Hama, Hitoshi; Tani, Nagayuki

    1989-01-01

    The incidence of hypertension is approximately twice as common in patients with diabetes mellitus as it is in those without. Both hypertension and diabetes mellitus are major risk factors for arteriosclerotic diseases (cerebral infarction, cardiovascular disease etw). A positive correlation exists between the presence of hypertension and retinopathy or nephropathy in patients with diabetes mellitus. This article provides practical approach in the management of hypertension with diabetes melli...

  13. Alpha- and beta-adrenoceptors in hypertension. II. Platelet alpha 2- and lymphocyte beta 2-adrenoceptors in children of parents with essential hypertension. A model for the pathogenesis of the genetically determined hypertension

    NARCIS (Netherlands)

    Michel, M. C.; Galal, O.; Stoermer, J.; Bock, K. D.; Brodde, O. E.

    1989-01-01

    To study whether changes in alpha- and beta-adrenoceptors in human essential hypertension (EHT) might be genetically determined, we assessed platelet alpha 2- and lymphocyte beta 2-adrenoceptor density in 48 normotensive children of normotensive parents (NT) and in 41 normotensive children with one

  14. Prevalence and persistence of masked hypertension in treated hypertensive patients.

    Science.gov (United States)

    Verberk, Willem J; Thien, Theo; Kroon, Abraham A; Lenders, Jacques W M; van Montfrans, Gert A; Smit, Andries J; de Leeuw, Peter W

    2007-12-01

    Masked hypertension (MH) is defined as a normal blood pressure in the physician's office and an elevated blood pressure when measured out-of-office. The cause of MH may be termed the masked hypertension effect (MHE), and is not restricted to blood-pressure (BP) values around the thresholds for normal BP. We investigated the prevalence and persistence of MH and MHE in patients who were being treated for high BP and who had been followed for a period of 1 year. One hundred and sixty-one treated hypertensive patients underwent office blood-pressure measurements (OBPMs) at seven visits and self-performed blood-pressure measurements (SBPMs) for 1 week before each visit over a period of 1 year. All measurements were performed with the same type of automatic device. At each visit, MH was determined according to the European Society of Hypertension definition (OBPM, /=135 mm Hg or 85 mm Hg). In addition, we determined prevalences of MHE at 5/3 mm Hg (SBPM exceeds OBPM by 5 mm Hg systolic and 3 mm Hg diastolic), and MHE at 10/6 mm Hg (SBPM exceeds OBPM by 10 mm Hg systolic and 6 mm Hg diastolic), respectively. During the entire study, 50% of the patients had MH, and 40% had MHE at 5/3 mm Hg at least once. At four sequential OBPM visits, 2% consistently had MH, and 3% had MHE at 5/3 mm Hg or MHE at 10/6 mm Hg. The prevalence of MH increased with lower OBPM levels but remained rather constant for MHE at 5/3 mm Hg and MHE at 10/6 mm Hg. The persistence of MH and the MHE over time in individual patients was low. We conclude that MH and MHE at 5/3 mm Hg and MHE at 10/6 mm Hg commonly occur in treated patients, but are not persistent phenomena and probably result from an accidentally low OBPM value on one particular occasion.

  15. [Definition and clinical characteristics of mild hypertension].

    Science.gov (United States)

    Saruta, Takao

    2008-08-01

    Mild hypertension is defined as blood pressure level of 140-159 mmHg systolic and/or 90-99 mmHg diastolic. The patients with blood pressure level of mild hypertension occupy about 60% of total hypertensive patients in Japan, and most of them are free of subjective symptoms except elevated blood pressure. However, some of the patients with mild hypertension develop cardiovascular events, since thay have occasionally cardiovascular damages on this level of blood pressure and several risk factors of cardiovascular diseases such as diabetes mellitus and hyperlipidemia.

  16. Radiologic evaluation of neonatal and childhood hypertension

    International Nuclear Information System (INIS)

    Amour, T.S.; Siegel, M.J.

    1986-01-01

    The authors reviewed the radiographic findings in 40 neonates and 90 children and adolescents with hypertension. In neonates the common causes of secondary hypertension were renal vascular thrombosis (33%), polycystic kidney disease (25%), and obstructive uropathy (17%). US and renal scans were the most useful studies and yielded diagnostic information in approximately 70% of cases. Surgically correctable hypertension was found in almost half the patients. In patients over 1 year of age, the common causes of hypertension were medical renal disease (50%) and renovascular hypetension (15%). Urography, scintigraphy, and arteriography played a crucial role in their evaluation

  17. [Primary and secondary arterial hypertension - update 2016].

    Science.gov (United States)

    Sanner, Bernd; Hausberg, Martin

    2016-06-01

    In patients with hypertension without diabetes and with an increased risk of cardiovascular complications a blood pressure of below 130 mmHg should be targeted. Hypertensive patients with an age above 80 years should be treated in the same way as younger hypertensive patients if they are otherwise healthy and functionally independent. On the other hand frail elderly patients could have an increased morbidity and mortality with intensive blood pressure control. In patients with resistant hypertension spironolactone was the most effective drug when given in addition to their baseline drugs (ACE-inhibitor/angiotensin receptor antagonist, calcium channel blocker and thiazide diuretic). © Georg Thieme Verlag KG Stuttgart · New York.

  18. Symptomatic subsyndromal depression in hospitalized hypertensive patients.

    Science.gov (United States)

    Chiaie, Roberto Delle; Iannucci, Gino; Paroli, Marino; Salviati, Massimo; Caredda, Maria; Pasquini, Massimo; Biondi, Massimo

    2011-12-01

    Clinicians generally agree on the association between depression and hypertension. Less clear is if the nature of the link is direct or indirect and if this should be considered confined only to syndromal forms or if it concerns also subsyndromal affective presentations. This study investigated the nature of the association between hypertension and subsyndromal depression in hospitalized hypertensive patients. 196 hypertensive and 96 non hypertensive inpatients underwent a SCID interview, to exclude patients positive for any Axis I or Axis II diagnosis. Symptomatic Subsyndromal Depression (SSD) was identified according to criteria proposed by Judd. Psychopathological assessment was performed with Anxiety Sensitivity Index (ASI) and Hopkins Symptom Checklist-90 (SCL-90). Clinical assessments included blood pressure measurement, evaluation of general health conditions and screening cardiovascular risk factors (smoke, alcohol, body weight, sedentary life style). Hypertensives met more frequently criteria for SSD. They also scored higher on ASI and SCL-90. However, those with more severe physical conditions, if compared with more healthy patients, did not show increased psychopathological severity. Similarly, psychopathological symptom severity did not differ among hypertensives positive for other cardiovascular risk factors, commonly more frequent among depressed subjects. Further analyses are needed to explore the potential advantage obtained on blood pressure control by treating SSD. Hospitalized hypertensives, more frequently satisfied criteria for Symptomatic Subsyndromal Depression. These milder affective forms are probably directly linked to the presence of hypertension, rather than being indirectly associated to physical impairment or to higher prevalence of other cardiovascular risk factors. Copyright © 2011. Published by Elsevier B.V.

  19. Physical Activity and the Prevention of Hypertension

    Science.gov (United States)

    Diaz, Keith M.; Shimbo, Daichi

    2013-01-01

    As the worldwide prevalence of hypertension continues to increase, the primary prevention of hypertension has become an important global public health initiative. Physical activity is commonly recommended as an important lifestyle modification that may aid in the prevention of hypertension. Recent epidemiologic evidence has demonstrated a consistent, temporal, and dose-dependent relationship between physical activity and the development of hypertension. Experimental evidence from interventional studies have further confirmed a relationship between physical activity and hypertension as the favorable effects of exercise on blood pressure reduction have been well characterized in recent years. Despite the available evidence strongly supporting a role for physical activity in the prevention of hypertension, many unanswered questions regarding the protective benefits of physical activity in high-risk individuals, the factors that may moderate the relationship between physical activity and hypertension, and the optimal prescription for hypertension prevention remain. We review the most recent evidence for the role of physical activity in the prevention of hypertension and discuss recent studies that have sought to address these unanswered questions. PMID:24052212

  20. E1. Risk of chronic hypertension in women with a history of hypertensive disorders of pregnancy

    DEFF Research Database (Denmark)

    Behrens, I; Basit, S; Melbye, M

    2016-01-01

    BACKGROUND: Women with a history of hypertensive disorders of pregnancy (HDP) are known to have an increased risk of hypertension years after their pregnancy. However, how soon after an affected pregnancy the risk of hypertension increases and how/whether this risk evolves over time, is unclear. ...