Genetic determinants of inherited susceptibility to hypercholesterolemia - a comprehensive literature review.

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Paththinige, C S; Sirisena, N D; Dissanayake, Vhw

2017-06-02

Hypercholesterolemia is a strong determinant of mortality and morbidity associated with cardiovascular diseases and a major contributor to the global disease burden. Mutations in four genes (LDLR, APOB, PCSK9 and LDLRAP1) account for the majority of cases with familial hypercholesterolemia. However, a substantial proportion of adults with hypercholesterolemia do not have a mutation in any of these four genes. This indicates the probability of having other genes with a causative or contributory role in the pathogenesis of hypercholesterolemia and suggests a polygenic inheritance of this condition. Here in, we review the recent evidence of association of the genetic variants with hypercholesterolemia and the three lipid traits; total cholesterol (TC), HDL-cholesterol (HDL-C) and LDL-cholesterol (LDL-C), their biological pathways and the associated pathogenetic mechanisms. Nearly 80 genes involved in lipid metabolism (encoding structural components of lipoproteins, lipoprotein receptors and related proteins, enzymes, lipid transporters, lipid transfer proteins, and activators or inhibitors of protein function and gene transcription) with single nucleotide variants (SNVs) that are recognized to be associated with hypercholesterolemia and serum lipid traits in genome-wide association studies and candidate gene studies were identified. In addition, genome-wide association studies in different populations have identified SNVs associated with TC, HDL-C and LDL-C in nearly 120 genes within or in the vicinity of the genes that are not known to be involved in lipid metabolism. Over 90% of the SNVs in both these groups are located outside the coding regions of the genes. These findings indicates that there might be a considerable number of unrecognized processes and mechanisms of lipid homeostasis, which when disrupted, would lead to hypercholesterolemia. Knowledge of these molecular pathways will enable the discovery of novel treatment and preventive methods as well as

Hypercholesterolemia Tunes Hematopoietic Stem/Progenitor Cells for Inflammation and Atherosclerosis.

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Ma, Xiaojuan; Feng, Yingmei

2016-07-19

As the pathological basis of cardiovascular disease (CVD), atherosclerosis is featured as a chronic inflammation. Hypercholesterolemia is an independent risk factor for CVD. Accumulated studies have shown that hypercholesterolemia is associated with myeloid cell expansion, which stimulates innate and adaptive immune responses, strengthens inflammation, and accelerates atherosclerosis progression. Hematopoietic stem/progenitor cells (HSPC) in bone marrow (BM) expresses a panel of lipoprotein receptors to control cholesterol homeostasis. Deficiency of these receptors abrogates cellular cholesterol efflux, resulting in HSPC proliferation and differentiation in hypercholesterolemic mice. Reduction of the cholesterol level in the lipid rafts by infusion of reconstituted high-density lipoprotein (HDL) or its major apolipoprotein, apoA-I, reverses hypercholesterolemia-induced HSPC expansion. Apart from impaired cholesterol metabolism, inhibition of reactive oxygen species production suppresses HSPC activation and leukocytosis. These data indicate that the mechanisms underlying the effects of hypercholesterolemia on HSPC proliferation and differentiation could be multifaceted. Furthermore, dyslipidemia also regulates HSPC-neighboring cells, resulting in HSPC mobilization. In the article, we review how hypercholesterolemia evokes HSPC activation and mobilization directly or via its modification of BM microenvironment. We hope this review will bring light to finding key molecules to control HSPC expansion, inflammation, and atherosclerosis for the treatment of CVD.

Scientific Disagreement and Evidential Pluralism: Lessons from the Studies on Hypercholesterolemia

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Veli-Pekka Parkkinen

2018-05-01

Full Text Available Inconsistencies between scientific theories have been studied, by and large, from the perspective of paraconsistent logic. This approach considered the formal properties of theories and the structure of inferences one can legitimately draw from theories. However, inconsistencies can be also analysed from the perspective of modelling practices, in particular how modelling practices may lead scientists to form opinions and attitudes that are different, but not necessarily inconsistent (from a logical point of view. In such cases, it is preferable to talk about disagreement, rather than inconsistency. Disagreement may originate in, or concern, a number of epistemic, socio-political or psychological factors. In this paper, we offer an account of the ‘loci and reasons’ for disagreement at different stages of the scientific process. We then present a controversial episode in the health sciences: the studies on hypercholesterolemia. The causes and effects of high levels of cholesterol in blood have been long and hotly debated, to the point of deserving the name of ‘cholesterol wars’; the debate, to be sure, isn’t settled yet. In this contribution, we focus on some selected loci and reasons for disagreement that occurred between 1920 and 1994 in the studies on hypercholesterolemia. We hope that our analysis of ‘loci and reasons’ for disagreement may shed light on the cholesterol wars, and possibly on other episodes of scientific disagreement.

THE REDUCTION OF CHOLESTEROL WITH CUPPING THERAPY ON CHOLESTEROL REDUCTION IN PATIENTS WITH HYPERCHOLESTEROLEMIA

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Zahid Fikri

2017-04-01

Full Text Available Introduction: Hypercholesterolemia is a risk factor causes of death at younger ages. Hypercholesterolemia may increase the risk of atherosclerosis, coronary heart disease, pancreatitis (pancreas inflammation in organs, diabetes mellitus, thyroid disorders, liver disease and kidney disease. Many patients with hypercholesterolemia using cupping therapy. Cupping therapy is alternative treatment process of throwing dirty blood from the body through the skin surface. The objective of this study was to determine the effect of cupping therapy to decrease cholesterol levels in patients with hypercholesterolemia. Method: Design used in this study was quasy experimental design. The population is all patients with hypercholesterolemia in the health center plaza Gresik. The total sample is 18 respondents, taken according to inclusion criteria. Independent variable is the cupping therapy. The dependent variable was the decrease in cholesterol levels. Data were collected using a questionnaire and observation of cholesterol. Data were analyzed using independent t-test and paired t tests with signi fi cance level α < 0.05. Result: The results show that cholesterol levels in patients with hypercholesterolemia treated groups decreased majority. Independent statistical analysis using t-test showed p = 0.001 and with the Paired t-test p value = 0.003. Discussion: This result means that there are significant effects of cupping therapy on cholesterol reduction in patients with hypercholesterolemia aged 45 years and over. Further research needs to be done in control diet, lifestyle and daily activities for the success of cupping therapy.

Genetics Home Reference: hypercholesterolemia

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... Encyclopedia: Familial hypercholesterolemia Encyclopedia: High blood cholesterol and triglycerides Encyclopedia: Xanthoma Health Topic: Cholesterol Health Topic: High Cholesterol in Children and Teens Health Topic: Lipid Metabolism Disorders Genetic and Rare Diseases Information Center (1 ...

Hypercholesterolemia downregulates autophagy in the rat heart.

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Giricz, Zoltán; Koncsos, Gábor; Rajtík, Tomáš; Varga, Zoltán V; Baranyai, Tamás; Csonka, Csaba; Szobi, Adrián; Adameová, Adriana; Gottlieb, Roberta A; Ferdinandy, Péter

2017-03-23

We have previously shown that efficiency of ischemic conditioning is diminished in hypercholesterolemia and that autophagy is necessary for cardioprotection. However, it is unknown whether isolated hypercholesterolemia disturbs autophagy or the mammalian target of rapamycin (mTOR) pathways. Therefore, we investigated whether isolated hypercholesterolemia modulates cardiac autophagy-related pathways or programmed cell death mechanisms such as apoptosis and necroptosis in rat heart. Male Wistar rats were fed either normal chow (NORM; n = 9) or with 2% cholesterol and 0.25% cholic acid-enriched diet (CHOL; n = 9) for 12 weeks. CHOL rats exhibited a 41% increase in plasma total cholesterol level over that of NORM rats (4.09 mmol/L vs. 2.89 mmol/L) at the end of diet period. Animals were sacrificed, hearts were excised and briefly washed out. Left ventricles were snap-frozen for determination of markers of autophagy, mTOR pathway, apoptosis, and necroptosis by Western blot. Isolated hypercholesterolemia was associated with a significant reduction in expression of cardiac autophagy markers such as LC3-II, Beclin-1, Rubicon and RAB7 as compared to controls. Phosphorylation of ribosomal S6, a surrogate marker for mTOR activity, was increased in CHOL samples. Cleaved caspase-3, a marker of apoptosis, increased in CHOL hearts, while no difference in the expression of necroptotic marker RIP1, RIP3 and MLKL was detected between treatments. This is the first comprehensive analysis of autophagy and programmed cell death pathways of apoptosis and necroptosis in hearts of hypercholesterolemic rats. Our data show that isolated hypercholesterolemia suppresses basal cardiac autophagy and that the decrease in autophagy may be a result of an activated mTOR pathway. Reduced autophagy was accompanied by increased apoptosis, while cardiac necroptosis was not modulated by isolated hypercholesterolemia. Decreased basal autophagy and elevated apoptosis may be responsible for the

Trends in Determinants of Hypercholesterolemia among Chinese Adults between 2002 and 2012: Results from theNational Nutrition Survey.

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Song, Peng-Kun; Li, Hong; Man, Qing-Qing; Jia, Shan-Shan; Li, Li-Xiang; Zhang, Jian

2017-03-15

Hypercholesterolemia is a known risk factor for cardiovascular diseases and affects a high proportion of the population. This study aimed to assess and compare the determinants of hypercholesterolemia among Chinese adults aged 18 years and above, from 2002 to 2012. The study used a stratified multistage cluster sampling method to select participants. Sociodemographic and lifestyle information was collected during face-to-face interviews. Dietary intake was calculated by 3-day, 24-h dietary records in combination with weighted edible oil and condiments. Hypercholesterolemia was defined as total cholesterol above 6.22 mmol/L (240 mg/dL) from fasting blood samples. The study included 47,701 (mean age 43.0 years) and 39,870 (mean age 51.0 years) participants in 2002 and 2010-2012 surveys respectively. The weighted prevalence of hypercholesterolemia increased from 1.6% (2.1% urban, 1.0% rural) in 2002 to 6.0% (6.4% urban, 5.1% rural) in 2012. The intake of plant-based food decreased but the intake of pork increased over the 10 years. A high intake of protein and pork, alcohol drinking and overweight/obesity were positively associated with hypercholesterolemia. Neither education nor fruit and vegetable intake were associated with hypercholesterolemia. In conclusion, the burden of hypercholesterolemia increased substantially between 2002 and 2012 in China. Unhealthy lifestyle factors and change in traditional dietary pattern were positively associated with hypercholesterolemia. Further research on the role of diet in the development and prevention of hypercholesterolemia is needed.

Polygenic Versus Monogenic Causes of Hypercholesterolemia Ascertained Clinically.

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Wang, Jian; Dron, Jacqueline S; Ban, Matthew R; Robinson, John F; McIntyre, Adam D; Alazzam, Maher; Zhao, Pei Jun; Dilliott, Allison A; Cao, Henian; Huff, Murray W; Rhainds, David; Low-Kam, Cécile; Dubé, Marie-Pierre; Lettre, Guillaume; Tardif, Jean-Claude; Hegele, Robert A

2016-12-01

Next-generation sequencing technology is transforming our understanding of heterozygous familial hypercholesterolemia, including revision of prevalence estimates and attribution of polygenic effects. Here, we examined the contributions of monogenic and polygenic factors in patients with severe hypercholesterolemia referred to a specialty clinic. We applied targeted next-generation sequencing with custom annotation, coupled with evaluation of large-scale copy number variation and polygenic scores for raised low-density lipoprotein cholesterol in a cohort of 313 individuals with severe hypercholesterolemia, defined as low-density lipoprotein cholesterol >5.0 mmol/L (>194 mg/dL). We found that (1) monogenic familial hypercholesterolemia-causing mutations detected by targeted next-generation sequencing were present in 47.3% of individuals; (2) the percentage of individuals with monogenic mutations increased to 53.7% when copy number variations were included; (3) the percentage further increased to 67.1% when individuals with extreme polygenic scores were included; and (4) the percentage of individuals with an identified genetic component increased from 57.0% to 92.0% as low-density lipoprotein cholesterol level increased from 5.0 to >8.0 mmol/L (194 to >310 mg/dL). In a clinically ascertained sample with severe hypercholesterolemia, we found that most patients had a discrete genetic basis detected using a comprehensive screening approach that includes targeted next-generation sequencing, an assay for copy number variations, and polygenic trait scores. © 2016 American Heart Association, Inc.

Children with hypercholesterolemia of unknown cause: Value of genetic risk scores.

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Sjouke, Barbara; Tanck, Michael W T; Fouchier, Sigrid W; Defesche, Joep C; Hutten, Barbara A; Wiegman, Albert; Kastelein, John J P; Hovingh, G Kees

2016-01-01

Familial hypercholesterolemia (FH) is caused by mutations in LDLR, APOB, or PCSK9, and in a previous study, we identified a causative mutation in these FH genes in 95% (255 of 269) of children with the FH phenotype. It has been hypothesized that a polygenic form of hypercholesterolemia is present in FH patients in whom no mutation is identified in the 3 FH genes. To address whether a polygenic form of hypercholesterolemia, defined as high-weighted effect of low-density lipoprotein cholesterol (LDL-C) raising SNPs expressed as the genetic risk score (GRS), is present in the remaining 14 children. On reassessment of the molecular diagnosis and clinical phenotype, 8 FH kindreds met the criteria for hypercholesterolemia of unknown cause and were included in this study. We calculated a weighted GRS comprising 10 established LDL-C-associated SNPs and the APOE genotype in these index cases and evaluated whether the index cases were characterized by an increased GRS compared to 26 first-degree relatives. Phenotypically affected and unaffected individuals could not be distinguished based on any of the risk scores. In this and our previous study, we show that a causal mutation in LDLR, APOB, and PCSK9 can be identified in almost all children with a definite clinical diagnosis of FH. In the small group of patients without a mutation, we did not observe a higher GRS compared with unaffected relatives, which suggests that the FH phenotype is not caused by the aggregate of LDL-C increasing SNPs. Our data imply that application of the GRS is not instrumental as a diagnostic tool to individually define clinically diagnosed FH patients with polygenic hypercholesterolemia in our study population. Copyright © 2016 National Lipid Association. Published by Elsevier Inc. All rights reserved.

Hypercholesterolemia Induces Differentiation of Regulatory T Cells in the Liver.

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Mailer, Reiner K W; Gisterå, Anton; Polyzos, Konstantinos A; Ketelhuth, Daniel F J; Hansson, Göran K

2017-05-26

The liver is the central organ that responds to dietary cholesterol intake and facilitates the release and clearance of lipoprotein particles. Persistent hypercholesterolemia leads to immune responses against lipoprotein particles that drive atherosclerosis. However, the effect of hypercholesterolemia on hepatic T-cell differentiation remains unknown. To investigate hepatic T-cell subsets upon hypercholesterolemia. We observed that hypercholesterolemia elevated the intrahepatic regulatory T (Treg) cell population and increased the expression of transforming growth factor-β1 in the liver. Adoptive transfer experiments revealed that intrahepatically differentiated Treg cells relocated to the inflamed aorta in atherosclerosis-prone low-density lipoprotein receptor deficient ( Ldlr -/- ) mice. Moreover, hypercholesterolemia induced the differentiation of intrahepatic, but not intrasplenic, Th17 cells in wild-type mice, whereas the disrupted liver homeostasis in hypercholesterolemic Ldlr -/- mice led to intrahepatic Th1 cell differentiation and CD11b + CD11c + leukocyte accumulation. Our results elucidate a new mechanism that controls intrahepatic T-cell differentiation during atherosclerosis development and indicates that intrahepatically differentiated T cells contribute to the CD4 + T-cell pool in the atherosclerotic aorta. © 2017 American Heart Association, Inc.

Hypercholesterolemia in Renal Transplant Recipients; contributing Factors, Effect of Dietary Modification and Fluvastatin Therapy

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Rahed Awad

1999-01-01

Full Text Available Hypercholesterolemia which frequently follows renal transplantation, places kidney graft recipients at an increased risk for atherosclerosis and cardiovascular diseases. We attempt in this study to determine the prevalence, and evaluate severity and treatment of hypercholesterolemia in kidney transplant recipients. We studied 78 renal transplant patients with a mean age of 42.1 years and mean transplant duration of 6.2 years (range from six months to 8.5 years. They were on triple immunosuppressive therapy and had serum creatinine level of less than 160µmol/L. Thirty-one patients (39.8% were found to have blood cholesterol levels > 6.4 mmol/L. Significant positive correlation was found between hypercholesterolemia and cyclosporine blood levels above 200 ng/ml (p< 0.0009. Furthermore, proteinuria positively correlated with hypercholesterolemia (p< 0.0006. There was no significant correlation between cholesterol blood level and the patient age, sex, presence of diabetes, prednisolone, dose, or treatment with C.-blockers and diuretics. Dietary modification was not effective in reducing the blood cholesterol level in our patients, so we used fluvastatin in a dose of 20 to 40 mg daily for a period of three months. This drug was effective in lowering the mean cholesterol blood levels from 7.1 to 5.2 mmol/L (p< 0.005. One out of 19-electromyogram studies showed abnormal pattern. We did not notice change in the levels of creatinine phosphokinase, serum creatinine or lover enzymes. In conclusion, hyper-cholesterolemia is common in stable renal transplant patients. The presence of proteinuria and the high level of blood cyclosporine are significantly associated with hypercholesterolemia. Low-dose fluvastatin was well-tolerated and effective cholesterol lowering treatment.

Familial hypercholesterolemia in the danish general population

DEFF Research Database (Denmark)

Benn, Marianne; Watts, Gerald F; Tybjaerg-Hansen, Anne

2012-01-01

.0-17.4) in definite/probable FH compared with non-FH subjects, after adjusting for age, gender, body mass index, hypertension, metabolic syndrome and diabetes, and smoking. The corresponding adjusted odds ratio for coronary artery disease in FH subjects on cholesterol-lowering medication was 10.3 (7......Context: The diagnosis of familial hypercholesterolemia (FH) can be made using the Dutch Lipid Clinic Network criteria. This employs the personal and family history of premature coronary artery disease and hypercholesterolemia and the presence of a pathogenic mutation in the low-density lipoprotein...

Correlates of Untreated Hypercholesterolemia in Older Adults: A Community-Based Household Survey in China

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Hu, Zhi; Zaman, M. Justin; Wang, Jingjing; Peacock, Janet L.; Chen, Ruoling

2015-01-01

Hypercholesterolemia is common in older adults and less treated, but little is known about correlates of untreated hypercholesterolemia. Using a standard interview method we examined a random sample of 7,572 participants aged ≥60 years in a community-based household survey across 7 provinces of China during 2007–2012, and documented 328 cases of hypercholesterolemia from self-reported doctor diagnosis. Compared to participants with normal cholesterol, older adults with hypercholesterolemia had higher socioeconomic position and larger body mass index. In patients with hypercholesterolemia, 209 were not treated using lipid-lowering medications (63.7%, 95% confidence interval (CI) 58.5%–68.9%). Untreated hypercholesterolemia was significantly associated with female sex (adjusted odds ratio 2.13, 95%CI 1.17–3.89), current smoking (3.48, 1.44–8.44), heavy alcohol drinking (3.13,1.11–8.84), chronic bronchitis (2.37,1.14–4.90) and high level of meat consumptions (2.85,1.22–6.65). Although having coronary heart disease exposed participants for treatment, half of participants with coronary heart disease did not receive lipid-lowering medications. Among hypercholesterolemia participants with stroke, hypertension or diabetes, more than half of them did not receive lipid-lowering medications. The high proportion of untreated hypercholesterolemia in older, high-risk Chinese adults needs to be mitigated through multi-faceted primary and secondary prevention strategies to increase population opportunities of treating hypercholesterolemia. PMID:26161751

Nonpharmacological lipoprotein apheresis reduces arterial inflammation in familial hypercholesterolemia

NARCIS (Netherlands)

van Wijk, Diederik F.; Sjouke, Barbara; Figueroa, Amparo; Emami, Hamed; van der Valk, Fleur M.; MacNabb, Megan H.; Hemphill, Linda C.; Schulte, Dominik M.; Koopman, Marion G.; Lobatto, Mark E.; Verberne, Hein J.; Fayad, Zahi A.; Kastelein, John J. P.; Mulder, Willem J. M.; Hovingh, G. Kees; Tawakol, Ahmed; Stroes, Erik S. G.

2014-01-01

Patients with familial hypercholesterolemia (FH) are characterized by elevated atherogenic lipoprotein particles, predominantly low-density lipoprotein cholesterol (LDL-C), which is associated with accelerated atherogenesis and increased cardiovascular risk. This study used (18)F-fluorodeoxyglucose

Awareness of diabetes, hypertension, and hypercholesterolemia in Malaysia.

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Yen, Steven T; Tan, Andrew K G; Mustapha, Feisul I

2017-09-01

Policy interventions for cardiovascular diseases require individual awareness of ailments. Such awareness is also key to individuals making changes to their lifestyle and dietary habits. The present study investigated the association of sociodemographic, health, and lifestyle factors with the awareness and prevalence of three ailments: diabetes, hypertension, and hypercholesterolemia. Data were obtained from the Malaysia Non-Communicable Disease Surveillance-1. Logistic regressions were estimated and odds ratios of exposure variables calculated. Diabetes awareness was associated with work hours, age, family history of illnesses, and ethnicity. Individuals with diminished hypertension awareness included those who were younger, without family history of illnesses, not obese, working more hours, and not adhering to a healthy diet. Low awareness of hypercholesterolemia was associated with younger age, lower education level, living in rural areas, female gender, no family history of illnesses, non-obesity, and minority ethnic background. Prevalence generally had the same pattern of association with the exposure variables. Various sociodemographic and health and lifestyle characteristics were associated with diabetes, hypertension, and hypercholesterolemia awareness in Malaysia, albeit with varying outcomes. Therefore, programs focusing on lifestyle improvements should be targeted at high-risk subgroups, such as individuals working longer hours and young adults, who are less likely to be aware of their health risk factors. © 2016 Ruijin Hospital, Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.

Efficacy and safety of rosuvastatin therapy in children and adolescents with familial hypercholesterolemia: Results from the CHARON study

NARCIS (Netherlands)

Braamskamp, Marjet J. A. M.; Langslet, Gisle; McCrindle, Brian W.; Cassiman, David; Francis, Gordon A.; Gagné, Claude; Gaudet, Daniel; Morrison, Katherine M.; Wiegman, Albert; Turner, Traci; Kusters, D. Meeike; Miller, Elinor; Raichlen, Joel S.; Wissmar, Jenny; Martin, Paul D.; Stein, Evan A.; Kastelein, John J. P.

2015-01-01

Heterozygous familial hypercholesterolemia (HeFH) is an autosomal dominant disorder leading to premature atherosclerosis. Guidelines recommend initiating statins early to reduce low-density lipoprotein cholesterol (LDL-C). Studies have evaluated rosuvastatin in children aged ≥10 years, but its

Clinical characteristics and evaluation of LDL-cholesterol treatment of the Spanish Familial Hypercholesterolemia Longitudinal Cohort Study (SAFEHEART)

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Familial hypercholesterolemia (FH) patients are at high risk for premature coronary heart disease (CHD). Despite the use of statins, most patients do not achieve an optimal LDL-cholesterol goal. The aims of this study are to describe baseline characteristics and to evaluate Lipid Lowering Therapy (L...

Pregnancy in women suffering from familial hypercholesterolemia: a harmful period for both mother and newborn?

NARCIS (Netherlands)

Avis, Hans J.; Hutten, Barbara A.; Twickler, Marcel Th B.; Kastelein, John J. P.; van der Post, Joris A. M.; Stalenhoef, Anton F.; Vissers, Maud N.

2009-01-01

Purpose of review The present review aims to highlight the consequences for mother and child of profound hypercholesterolemia during pregnancy of women with familial hypercholesterolemia. Recent findings Familial hypercholesterolemia is increasingly diagnosed in younger patients due to the existence

Screening College Students for Hypercholesterolemia.

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Faigel, Harris C.

1992-01-01

Describes one college's mandatory mass cholesterol screening for new students. Each year, over 30 beginning students with unknown hypercholesterolemia were detected. The program suggests that mass screening efficiently and economically identifies students who would benefit from cholesterol reduction, a modifiable risk in coronary artery disease.…

Early Onset Intrauterine Growth Restriction in a Mouse Model of Gestational Hypercholesterolemia and Atherosclerosis

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Busso, Dolores; Mascareño, Lilian; Salas, Francisca; Berkowitz, Loni; Santander, Nicolás; Quiroz, Alonso; Amigo, Ludwig; Valdés, Gloria; Rigotti, Attilio

2014-01-01

The susceptibility to develop atherosclerosis is increased by intrauterine growth restriction and prenatal exposure to maternal hypercholesterolemia. Here, we studied whether mouse gestational hypercholesterolemia and atherosclerosis affected fetal development and growth at different stages of gestation. Female LDLR KO mice fed a proatherogenic, high cholesterol (HC) diet for 3 weeks before conception and during pregnancy exhibited a significant increase in non-HDL cholesterol and developed atherosclerosis. At embryonic days 12.5 (E12.5), E15.5, and E18.5, maternal gestational hypercholesterolemia and atherosclerosis were associated to a 22–24% reduction in male and female fetal weight without alterations in fetal number/litter or morphology nor placental weight or structure. Feeding the HC diet exclusively at the periconceptional period did not alter fetal growth, suggesting that maternal hypercholesterolemia affected fetal weight only after implantation. Vitamin E supplementation (1,000 UI of α-tocopherol/kg) of HC-fed females did not change the mean weight of E18.5 fetuses but reduced the percentage of fetuses exhibiting body weights below the 10th percentile of weight (HC: 90% vs. HC/VitE: 68%). In conclusion, our results showed that maternal gestational hypercholesterolemia and atherosclerosis in mice were associated to early onset fetal growth restriction and that dietary vitamin E supplementation had a beneficial impact on this condition. PMID:25295255

Two-year efficacy and safety of Simvastatin 80 mg in familial hypercholesterolemia (The examination of probands and relatives in statin studies with familial hypercholesterolemia [ExPRESS FH])

NARCIS (Netherlands)

de Sauvage Nolting, Pernette R. W.; Buirma, Rudolf J. A.; Hutten, Barbara A.; Kastelein, John J. P.

2002-01-01

High-dose (80 mg) simvastatin is efficacious in both reducing low-density lipoprotein cholesterol (-48%) and triglyceride (-26%) levels and in elevating high-density lipoprotein cholesterol (+ 13%) levels in a large cohort of patients with familial hypercholesterolemia. No tachyphylaxis was seen

PCSK9 Inhibition With Monoclonal Antibodies: Modern Management of Hypercholesterolemia

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Santos, Raul D.

2016-01-01

Abstract Current guidelines for hypercholesterolemia treatment emphasize lifestyle modification and lipid‐modifying therapy to reduce the risk for cardiovascular disease. Statins are the primary class of agents used for the treatment of hypercholesterolemia. Although statins are effective for many patients, they fail to achieve optimal reduction in lipids for some patients, including those who have or are at high risk for cardiovascular disease. The PCSK9 gene was identified in the past decade as a potential therapeutic target for the management of patients with hypercholesterolemia. Pharmacologic interventions to decrease PCSK9 levels are in development, with the most promising approach using monoclonal antibodies that bind to PCSK9 in the plasma. Two monoclonal antibodies, alirocumab and evolocumab, have recently been approved for the treatment of hypercholesterolemia, and a third one, bococizumab, is in phase 3 clinical development. All 3 agents achieve significant reductions in levels of low‐density lipoprotein cholesterol, as well as reductions in non‐high‐density lipoprotein cholesterol, apolipoprotein B, and lipoprotein(a). Long‐term outcome trials are under way to determine the sustained efficacy, safety, and tolerability of PCSK9 inhibitors and whether this novel class of agents decreases the risk for major cardiovascular events in patients on lipid‐modifying therapy. Available data suggest that PCSK9 inhibitors provide a robust reduction in atherogenic cholesterol levels with a good safety profile, especially for patients who fail to obtain an optimal clinical response to statin therapy, those who are statin intolerant or have contraindications to statin therapy, and those with familial hypercholesterolemia. PMID:27195910

Carotid intima-media thickness correlation with lipid profile in patients with familial hypercholesterolemia versus controls

International Nuclear Information System (INIS)

Khan, S.P.; Ahmed, K.Z.; Ghani, R.

2010-01-01

To determine the variations in carotid intima-media thickness (CIMT) in familial hypercholesterolemia (FH) patients and its use as predictive marker for premature cardiovascular diseases. Familial hypercholesterolemia was clinically diagnosed by premature coronary diseases, xanthomas, arcus cornealis and family history of premature coronary heart diseases. Controls were age matched normal individuals without hypercholesterolemia. Their lipid profile was tested after overnight fasting. CIMT was measured in mm using B-mode ultrasonography using linear probe. Student t-test was applied to compare mean CIMT of cases and the control. The mean CIMT values of the FH cases were correlated with LDL using Pearson's correlation test. Forty cases with hypercholesterolemia gave consent to participate in the study. These patients had total cholesterol 200 mg/dL and LDL 160 mg/dL as compared to twenty controls of similar age with total cholesterol ? 200 mg/dL and LDL 130 mg/dL. Mean CIMT for the cases was 0.77 + 0.18 mm while mean CIMT for control was 0.59 + 0.08 mm. The mean CIMT for the cases ranged from 0.7-1.83 mm and 0.48-0.73 mm for controls. Among the FH cases, 25% (n=11) had arterial plaques. Mean CIMT was significantly correlated to LDL-cholesterol (r 0.725**, p < 0.001). In this study, CIMT was found to be significantly increased in familial hypercholesterolemia and it correlated with raised LDL-cholesterol. Both are predictive of premature cardiovascular diseases. (author)

The examination of cardiac metabolism of patients with hypercholesterolemia by phosphorus-31 magnetic resonance spectroscopy

International Nuclear Information System (INIS)

Martinek, M.

2001-07-01

Objectives: we decided to investigate weather alterations in high energy phosphates occur in the myocardium of persons with hypercholesterolemia. Background: myocardial high energy phosphates have been shown to be reduced in various diseases of the heart such as coronary artery disease, heart failure and dilated cardiomyopathy. The latest studies on hypercholesterolemia show direct effects of high serum cholesterol on heart muscle cells, so do studies on statins. Methods: in the present study 32 male patients (mean age 48) with hypercholesterolemia and 27 male healthy volunteers (mean age 44,5) as age matched controls were included. The patients were divided into a statin-treated (n = 17) and an untreated subgroup (n = 15). Using a 1,5 Tesla whole-body magnetic resonance scanner (Siemens, Germany) phosphor-31 magnetic resonance spectroscopic imaging (31P MRSI) of the heart was performed in all subjects. The 31P MRSI slab (slab thickness = 40 mm, field of view = 320 mm, matrix 32 x 32, TR = 323 ms, TE 3 ms) contained the left anterior ventricular wall (region of interest = 32 ml). The measurement was triggered on electrocardiography. The ratios of phosphocreatinine (PCr) to β-adenosine-triphosphate (β-ATP) were calculated. Results: the myocardium of untreated patients with hypercholesterolemia shows significantly decreased ratios of PCr/β-ATP compared with patients treated with statins (2,09 vs. 2,45). When comparing the untreated group with healthy persons there was a trend to significance for a difference of the groups (2,09 vs. 2,34). Conclusion: with this study we demonstrate the first time alterations of high energy phosphates in the myocardium of persons with hypercholesterolemia and the beneficial effects of statins on these parameters. (author)

Various tomato extract dose effect on lipid profile of hypercholesterolemia Rats

Science.gov (United States)

Purwantoyo, E.; Marwoto, P.; Iswari, R. S.

2018-03-01

The influence of tomato lycopene on hypercholesterolemia has been studied many times. Post Test Randomized Control Group Design is used as the research design. A total of 24 white rats were made hypercholesterolemia before treatment, then they were divided into 4 groups randomly, i.e. K1 (control group), K2, K3, and K4 (Treatment groups 1, 2 and 3). Treatment groups were administered with tomato extract. K2 (given 6 mg / head / day), K3 (12 mg / head / day), K4 (24mg / head / day). The result of ANOVA test showed significant difference (p lipid profile in terms of triglycerides, total cholesterol and LDL-cholesterol.

Polymorphism at the TRIB1 gene modulates plasma lipid levels: insight from the Spanish familial hypercholesterolemia cohort study

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rs17321515 SNP has been associated with variation in LDL-C, high density lipoprotein cholesterol and triglycerides concentrations. This effect has never been studied in patients with severe hypercholesterolemia. Therefore, our aims were to assess the association of the rs17321515 (TRIB1) SNP with pl...

Relationship between XspI Site Polymorphisms of LDL-R Gene and Serum IL-2 and IL-10 in Patients with Hypercholesterolemia.

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Zhang, Mingming; Lu, Yamin; Liu, Xin; Zhang, Xiaobin; Zhang, Cuigai; Gao, Wei; Tie, Yanqing

2016-11-01

Relationship has been identified in sporadic reports between polymorphisms and hypercholesterolemia. However, the relationship between inflammatory cytokines and polymorphism of low-density lipoprotein receptor (LDL-R) gene in hypercholesterolemia is unclear. This study aimed to explore the relationship and significance between polymorphisms of LDL-R gene and serum Interleukin-2 (IL-2), IL-10 in patients with hypercholesterolemia. PCR-RFLP and direct DNA sequencing assay were employed to determine polymorphism of LDL-R gene in 900 patients with hypercholesterolemia and 400 healthy cases. ELISA was applied to assay serum concentration of IL-2 and IL-10. Blood lipid indexes were tested in all cases. Compared with the healthy controls, level of IL-2 increased significantly, while IL-10 decreased significantly (P hypercholesterolemia. © 2016 Wiley Periodicals, Inc.

Diet, hypertension, hypercholesterolemia and diabetes in ischemic heart diseases

International Nuclear Information System (INIS)

Hamideh, S.; Behzad, M.; Hassan, E.; Mojtaba, S.

2007-01-01

Ischemic Heart Diseases (IHD) have the highest cause of mortality in the Islamic Republic of Iran. Unhealthy dietary habits as a major threat make our country prone to an epidemic of non-communicable diseases in the next two decades. The aim of this study was to determine the association of diet, hypertension, hypercholesterolemia and diabetes with risk of developing IHD in Tehran. This case - control study was conducted during 2003 and 2004 in Tehran Heart Center and Tehran Shahid Rajaii Hospital. A sample of 100 IHD patients (cases) and 100 individuals free of cardiovascular symptoms (controls) were entered into the study; the Controls were matched to the IHD patients by age (+- years) and sex. Information was recorded by Food Frequency Questionnaire (FFQ). All data were analyzed with the SPSS for windows, version11. Multivariate analysis showed a significant and positive association between Hypertension, Hypercholesterolemia and Diabetes and risk of developing IHD. Odds ratios for these three risk factors with 95% confidence interval (CI) were: 3.9, 12 and 8.6 respectively. In he cases consumption of high dairy fat and fried foods were significantly high, that increased the risk of IHD 9.8 and 54.6 times, respectively. Also low intake of fish was directly associated with increase of the IHD risk (95% CI, OR: 13.9). Moreover low consumption of vegetables and fruits independently increased the risk of IHD 19.8 times in cases group. Hypertension, hypercholesterolemia and diabetes have a significant association with development of IHD. High consumption of fatty food and low consumption of fish, vegetables and fruits also contribute to development of IHD. (author)

Portuguese Familial Hypercholesterolemia Study: presentation of the study and preliminary results.

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Bourbon, Mafalda; Rato, Quitéria

2006-11-01

Familial hypercholesterolemia (FH) is an autosomal dominant genetic disorder caused, in the majority of cases, by a partial or total lack of functional low density lipoprotein receptors (LDLR). Mutations in the LDLR gene lead to increased plasma cholesterol levels, resulting in cholesterol deposition in the arteries, thereby increasing the risk of premature coronary heart disease. The homozygous form of FH is rare but heterozygous FH is common, although underdiagnosed in many populations, including the Portuguese. In 1999 the Portuguese Familial Hypercholesterolemia Study was begun at the National Institute of Health. The aim of the Portuguese Familial H ypercholesterolemia Study is to perform an epidemiological study to determine the prevalence and distribution of FH in Portugal and to better understand the pathophysiology of coronary heart disease in these patients. The aim of the present work is to present the study's criteria and organization as well as its preliminary results. The study population consists of individuals of both sexes and all ages with a clinical diagnosis of FH, with biochemical and molecular characterization being performed. The clinical criteria used for the diagnosis of FH were adapted from those of the Simon Broome Heart Research Trust. The study is organized in five stages: 1. selection of individuals with a clinical diagnosis of FH; 2. completion of a clinical questionnaire and declaration of informed consent; 3. collection of blood samples; 4. biochemical characterization; 5. molecular study of three genes associated with the FH phenotype: LDLR, apolipoprotein B (APOB) and proprotein convertase subtilisin/kexin type 9 (PCSK9). Between 1999 and June 2006 the LDLR gene and the APOB gene of 141 index cases (38 children and 103 adults) were studied. In 78 of these index cases (76 heterozygotes and two homozygotes) 50 different mutations in the LDLR gene were identified, and two unrelated individuals were found to have the ApoB3500 mutation

Medication adherence, cascade screening, and lifestyle patterns among women with hypercholesterolemia: Results from the WomenHeart survey.

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Benson, Gretchen; Witt, Dawn R; VanWormer, Jeffrey J; Campbell, Susan M; Sillah, Arthur; Hayes, Sharonne N; Lui, Matt; Gulati, Martha

2016-01-01

Hypercholesterolemia is a major risk factor for cardiovascular disease. Women with hypercholesterolemia and familial hypercholesterolemia (FH) are a high-risk group often underdiagnosed, undertreated, and unaware of the need for cascade screening. The objectives were to identify the prevalence of hypercholesterolemia and FH in 2 national databases, explore lifestyle/medication adherence, and examine rates of cascade screening (lipid testing in all first-degree relatives) among those with FH. This was a cross-sectional study of women who completed an online survey in 2014. Outcomes were examined for 3 groups: diagnosed, probable, and no FH. For FH, multivariable logistic regression was used to examine the association between family member screening for FH and sociodemographic and/or clinical characteristics. There were 761 respondents with a mean (±standard deviation) age of 59 ± 10.1 years; 26% reported FH, 22% probable FH, and 51% no FH. Eighty-three percent of the total sample and 95% with FH take a statin. In those with hypercholesterolemia and FH, 65% and 58% reported high medication adherence, respectively. Women with probable FH consumed significantly fewer fruits/vegetables and were less active. FH cascade screening was: siblings 54%, parents 37%, and children 34%. Marital status, annual household income, and diabetes were significantly associated with cascade screening. In a survey of informed women with hypercholesterolemia and FH, cascade screening is underused. Our findings warrant increased efforts to identify cascade screening barriers. Early detection and treatment of hypercholesterolemia/FH is a priority for women, and their first-degree relatives, as this may dramatically reduce cardiovascular disease impact. Copyright © 2016 National Lipid Association. Published by Elsevier Inc. All rights reserved.

Incidence and prevalence of hypercholesterolemia in Portugal: a systemic review. Part II.

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Costa, João; Borges, Margarida; Oliveira, Eduardo; Gouveia, Miguel; Carneiro, António Vaz

2003-05-01

Over 50% of the mortality and disability caused by ischemic heart disease and stroke could be avoided by controlling individual risk factors (hypertension, hypercholesterolemia, smoking and obesity). The ignorance of the extent and impact of hypercholesterolemia (HC) in Portugal prompted us to undertake this systematic review of the prevalence and incidence of hyperlipidemia in Portugal, based exclusively on work published nationally. We included every study published in the country that could provide data on the prevalence or incidence of hypercholesterolemia. The search strategy included an electronic search of national and international biomedical databases (Medline, Index Revistas Médicas Portuguesas, the Portuguese Directorate-General for Health and the Portuguese National School of Public Health), screening of reference lists from the individual studies, and personal contacts with institutions, groups and authors (such as the Portuguese Foundation of Cardiology). The data--recorded in electronic format--was collected independently by two of the authors (JC and MB), with consensus achieved with a third (AVC) when there were differences in the study coding. We could only identify one paper on the incidence of HC in Portugal, which gave an incidence of 559 new cases per 100,000 inhabitants, increasing with age up to 54 years for men and 64 years for women. There was a higher incidence in men than in women up to the age of 54, but at more advanced ages this relationship was reversed. Prevalence studies on HC included 53,445 individuals overall, with sample size lower than 1000 in most of the individual studies. The most frequently used criterion for HC was > 200 mg/dL, with the mean level being higher in most studies. We calculated the mean prevalence for several cut-off points (190 mg/dL: 63.8%; 200 mg/dL: 56.7%; 240 mg/dL: 31.7%; 250 mg/dL: 21%). Due to the heterogeneity of the data, these results are to be interpreted with caution, even though they are

Incidence and prevalence of hypercholesterolemia in Portugal: a systematic review. Part I.

Science.gov (United States)

Costa, João; Borges, Margarida; Oliveira, Eduardo; Gouveia, Miguel; Carneiro, António Vaz

2003-04-01

Over 50% of the mortality and disability caused by ischemic heart disease and stroke could be avoided by controlling individual risk factors (hypertension, hypercholesterolemia, smoking and obesity). The ignorance of the extent and impact of hypercholesterolemia (HC) in Portugal prompted us to undertake this systematic review of the prevalence and incidence of hyperlipidemia in Portugal, based exclusively on work published nationally. We included every study published in the country that could provide data on the prevalence or incidence of hypercholesterolemia. The search strategy included an electronic search of national and international biomedical databases (Medline, Index Revistas Médicas Portuguesas, the Portuguese Directorate-General for Health and the Portuguese National School of Public Health), screening of reference lists from the individual studies, and personal contacts with institutions, groups and authors (such as the Portuguese Foundation of Cardiology). The data--recorded in electronic format--was collected independently by two of the authors (JC and MB), with consensus achieved with a third (AVC) when there were differences in the study coding. We could only identify one paper on the incidence of HC in Portugal, which gave an incidence of 559 new cases per 100,000 inhabitants, increasing with age up to 54 years for men and 64 years for women. There was a higher incidence in men than in women up to the age of 54, but at more advanced ages this relationship was reversed. Prevalence studies on HC included 53,445 individuals overall, with sample size lower than 1000 in most of the individual studies. The most frequently used criterion for HC was > 200 mg/dL, with the mean level being higher in most studies. We calculated the mean prevalence for several cut-off points (190 mg/dL: 63.8%; 200 mg/dL: 56.7%; 240 mg/dL: 31.7%; 250 mg/dL: 21%). Due to the heterogeneity of the data, these results are to be interpreted with caution, even though they are

Genetics of familial hypercholesterolemia: a tool for development of novel lipid lowering pharmaceuticals?

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Volta, Andrea; Hovingh, G. Kees; Grefhorst, Aldo

2018-01-01

Familial hypercholesterolemia is characterized by high LDL cholesterol and an elevated risk to develop coronary heart disease. Mutations in LDL receptor-mediated cholesterol uptake are the main cause of familial hypercholesterolemia. However, multiple mutations in various other genes are also

Black ginseng extract ameliorates hypercholesterolemia in rats

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Evelyn Saba

2016-04-01

Conclusion: Administration of BG extracts to Sprague Dawley rats fed with high-cholesterol diet ameliorated hypercholesterolemia, which was mediated via modulation of cholesterol-metabolizing marker genes. This data throw a light on BG's cardioprotective effects.

Hypercholesterolemia and Myocardial function evaluated via Tissue Doppler Imaging

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Kotaru Pavan

2009-11-01

Full Text Available Abstract Objective To establish a link between hypercholesterolemia and myocardial dysfunction. Background Heart failure is a complex disease involving changes in systolic and diastolic function. Newer echocardiographic imaging modalities may be able to detect discreet changes in myocardial function associated with hypercholesterolemia. Therefore we sought to establish a link between hypercholesterolemia and myocardial dysfunction with tissue Doppler imaging (TDI. Methods Twenty-seven rabbits were studied: 7 were fed normal chow (group 1 and 20 a high cholesterol diet (10 with ezetimibe, 1 mg/kg/day; group 2 and 10 without, group 3. Echocardiographic images were obtained under general anesthesia. Serum cholesterol levels were obtained at baseline, 3 and 6 months and myocardial cholesterol levels measured following euthanasia. Results Doppler measurements, including E/A, E'/A' and S' were significantly lower in group 3 compared to both groups 1 and 2 but no significant differences were noted in chamber sizes or ejection fraction among the groups. Average serum cholesterol was higher in group 3 compared to groups 1 and 2 respectively (495 ± 305 mg/dl vs. 114 ± 95 mg/dl and 87 ± 37 mg/dl; p 2 = 0.17 p = 0.04, r2 = 0.37 p = 0.001 and r2 = 0.24 p = 0.01. Conclusion Cholesterol load in the serum and myocardium was significantly associated with decreased systolic and diastolic function by TDI. Moreover, lipid lowering was protective.

Timely diagnosis of sitosterolemia by next generation sequencing in two children with severe hypercholesterolemia.

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Buonuomo, Paola Sabrina; Iughetti, Lorenzo; Pisciotta, Livia; Rabacchi, Claudio; Papadia, Francesco; Bruzzi, Patrizia; Tummolo, Albina; Bartuli, Andrea; Cortese, Claudio; Bertolini, Stefano; Calandra, Sebastiano

2017-07-01

Severe hypercholesterolemia associated or not with xanthomas in a child may suggest the diagnosis of homozygous autosomal dominant hypercholesterolemia (ADH), autosomal recessive hypercholesterolemia (ARH) or sitosterolemia, depending on the transmission of hypercholesterolemia in the patient's family. Sitosterolemia is a recessive disorder characterized by high plasma levels of cholesterol and plant sterols due to mutations in the ABCG5 or the ABCG8 gene, leading to a loss of function of the ATP-binding cassette (ABC) heterodimer transporter G5-G8. We aimed to perform the molecular characterization of two children with severe primary hypercholesterolemia. Case #1 was a 2 year-old girl with high LDL-cholesterol (690 mg/dl) and tuberous and intertriginous xanthomas. Case #2 was a 7 year-old boy with elevated LDL-C (432 mg/dl) but no xanthomas. In both cases, at least one parent had elevated LDL-cholesterol levels. For the molecular diagnosis, we applied targeted next generation sequencing (NGS), which unexpectedly revealed that both patients were compound heterozygous for nonsense mutations: Case #1 in ABCG5 gene [p.(Gln251*)/p.(Arg446*)] and Case #2 in ABCG8 gene [p.(Ser107*)/p.(Trp361*)]. Both children had extremely high serum sitosterol and campesterol levels, thus confirming the diagnosis of sisterolemia. A low-fat/low-sterol diet was promptly adopted with and without the addition of ezetimibe for Case #1 and Case #2, respectively. In both patients, serum total and LDL-cholesterol decreased dramatically in two months and progressively normalized. Targeted NGS allows the rapid diagnosis of sitosterolemia in children with severe hypercholesterolemia, even though their family history does not unequivocally suggest a recessive transmission of hypercholesterolemia. A timely diagnosis is crucial to avoid delays in treatment. Copyright © 2017 Elsevier B.V. All rights reserved.

Intrauterine programming mechanism for hypercholesterolemia in prenatal caffeine-exposed female adult rat offspring.

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Xu, Dan; Luo, Hanwen W; Hu, Wen; Hu, Shuwei W; Yuan, Chao; Wang, Guihua H; Zhang, Li; Yu, Hong; Magdalou, Jacques; Chen, Liaobin B; Wang, Hui

2018-05-02

Clinical and animal studies have indicated that hypercholesterolemia and its associated diseases have intrauterine developmental origins. Our previous studies showed that prenatal caffeine exposure (PCE) led to fetal overexposure to maternal glucocorticoids (GCs) and increased serum total cholesterol levels in adult rat offspring. This study further confirms the intrauterine programming of PCE-induced hypercholesterolemia in female adult rat offspring. Pregnant Wistar rats were intragastrically administered caffeine (30, 60, and 120 mg/kg/d) from gestational day (GD)9 to 20. Female rat offspring were euthanized at GD20 and postnatal wk 12; several adult rat offspring were additionally subjected to ice-water swimming stimulation to induce chronic stress prior to death. The effects of GCs on cholesterol metabolism and epigenetic regulation were verified using the L02 cell line. The results showed that PCE induced hypercholesterolemia in adult offspring, which manifested as significantly higher levels of serum total cholesterol and LDL cholesterol (LDL-C) as well as higher ratios of LDL-C/HDL cholesterol. We further found that the cholesterol levels were increased in fetal livers but were decreased in fetal blood, accompanied by increased maternal blood cholesterol levels and reduced placental cholesterol transport. Furthermore, analysis of PCE offspring in the uterus and in a postnatal basal/chronic stress state and the results of in vitro experiments showed that hepatic cholesterol metabolism underwent GC-dependent changes and was associated with cholesterol synthase via abnormalities in 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) histone acetylation. We concluded that, to compensate for intrauterine placentally derived decreases in fetal blood cholesterol levels, high intrauterine GC levels activated fetal hepatic CCAAT enhancer binding protein α signaling and down-regulated Sirtuin1 expression, which mediated the high levels of histone acetylation ( via H3K9

A Snack Dietary Pattern Increases the Risk of Hypercholesterolemia in Northern Chinese Adults: A Prospective Cohort Study.

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Na, Lixin; Han, Tianshu; Zhang, Wei; Wu, Xiaoyan; Na, Guanqiong; Du, Shanshan; Li, Ying; Sun, Changhao

2015-01-01

The evidence about the effect of dietary patterns on blood cholesterol from cohort studies was very scarce. The study was to identify the association of dietary patterns with lipid profile, especially cholesterol, in a cohort in north China. Using a 1-year food frequency questionnaire, we assessed the dietary intake of 4515 adults from the Harbin People's Health Study in 2008, aged 20-74 years. Principle component analysis was used to identify dietary patterns. The follow-up was completed in 2012. Fasting blood samples were collected for the determination of blood lipid concentrations. Logistic regression models were used to evaluate the association of dietary patterns with the incidence of hypercholesterolemia, hypertriglyceridemia, and low-HDL cholesterolemia. Five dietary patterns were identified ("staple food", "vegetable, fruit and milk", "potato, soybean and egg", "snack", and "meat"). The relative risk (RR) between the extreme tertiles of the snack dietary pattern scores was 1.72 (95% CI = 1.14, 2.59, P = 0.004) for hypercholesterolemia, 1.39 (1.13, 1.75, P = 0.036) for hypertriglyceridemia, after adjustment for age, sex, education, body mass index, smoking, alcohol consumption, energy intake, exercise and baseline lipid concentrations. There was a significant positive association between the snack dietary pattern scores and fasting serum total cholesterol (SRC (standardized regression coefficient) = 0.262, P = 0.025), LDL-c (SRC = 0.324, P = 0.002) and triglycerides (SRC = 0.253, P = 0.035), after adjustment for the multiple variables above. Moreover, the adjusted RR of hypertriglyceridemia between the extreme tertiles was 0.73 (0.56, 0.94, P = 0.025) for the vegetable, fruit and milk dietary pattern, and 1.86 (1.33, 2.41, P = 0.005) for the meat dietary pattern. The snack dietary pattern was a newly emerged dietary pattern in northern Chinese adults. It appears conceivable that the risk of hypercholesterolemia can be reduced by changing the snack dietary

A Snack Dietary Pattern Increases the Risk of Hypercholesterolemia in Northern Chinese Adults: A Prospective Cohort Study.

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Lixin Na

Full Text Available The evidence about the effect of dietary patterns on blood cholesterol from cohort studies was very scarce. The study was to identify the association of dietary patterns with lipid profile, especially cholesterol, in a cohort in north China. Using a 1-year food frequency questionnaire, we assessed the dietary intake of 4515 adults from the Harbin People's Health Study in 2008, aged 20-74 years. Principle component analysis was used to identify dietary patterns. The follow-up was completed in 2012. Fasting blood samples were collected for the determination of blood lipid concentrations. Logistic regression models were used to evaluate the association of dietary patterns with the incidence of hypercholesterolemia, hypertriglyceridemia, and low-HDL cholesterolemia. Five dietary patterns were identified ("staple food", "vegetable, fruit and milk", "potato, soybean and egg", "snack", and "meat". The relative risk (RR between the extreme tertiles of the snack dietary pattern scores was 1.72 (95% CI = 1.14, 2.59, P = 0.004 for hypercholesterolemia, 1.39 (1.13, 1.75, P = 0.036 for hypertriglyceridemia, after adjustment for age, sex, education, body mass index, smoking, alcohol consumption, energy intake, exercise and baseline lipid concentrations. There was a significant positive association between the snack dietary pattern scores and fasting serum total cholesterol (SRC (standardized regression coefficient = 0.262, P = 0.025, LDL-c (SRC = 0.324, P = 0.002 and triglycerides (SRC = 0.253, P = 0.035, after adjustment for the multiple variables above. Moreover, the adjusted RR of hypertriglyceridemia between the extreme tertiles was 0.73 (0.56, 0.94, P = 0.025 for the vegetable, fruit and milk dietary pattern, and 1.86 (1.33, 2.41, P = 0.005 for the meat dietary pattern. The snack dietary pattern was a newly emerged dietary pattern in northern Chinese adults. It appears conceivable that the risk of hypercholesterolemia can be reduced by changing the snack

Incidence and prevalence of hypercholesterolemia in Portugal: a systematic review. Part III.

Science.gov (United States)

Costa, João; Borges, Margarida; Oliveira, Eduardo; Gouveia, Miguel; Carneiro, António Vaz

2003-06-01

Over 50% of the mortality and disability caused by ischemic heart disease and stroke could be avoided by controlling individual risk factors (hypertension, hypercholesterolemia, smoking and obesity). The ignorance of the extent and impact of hypercholesterolemia (HC) in Portugal prompted us to undertake this systematic review of the prevalence and incidence of hyperlipidemia in Portugal, based exclusively on work published nationally. We included every study published in the country that could provide data on the prevalence or incidence of hypercholesterolemia. The search strategy included an electronic search of national and international biomedical databases (Medline, Index Revistas Médicas Portuguesas, the Portuguese Directorate-General for Health and the Portuguese National School of Public Health), screening of reference lists from the individual studies, and personal contacts with institutions, groups and authors (such as the Portuguese Foundation of Cardiology). The data--recorded in electronic format--was collected independently by two of the authors (JC and MB), with consensus achieved with a third (AVC) when there were differences in the study coding. We could only identify one paper on the incidence of HC in Portugal, which gave an incidence of 559 new cases per 100,000 inhabitants, increasing with age up to 54 years for men and 64 years for women. There was a higher incidence in men than in women up to the age of 54, but at more advanced ages this relationship was reversed. Prevalence studies on HC included 53,445 individuals overall, with sample size lower than 1000 in most of the individual studies. The most frequently used criterion for HC was > 200 mg/dL, with the mean level being higher in most studies. We calculated the mean prevalence for several cut-off points (> or = 190 mg/dL: 63.8%; > or = 200 mg/dL: 56.7%; > or = 240 mg/dL; 31.7%; > or 250 mg/d; 21%). Due to the heterogeneity of the data, these results are to be interpreted with caution

Genetic diagnosis of familial hypercholesterolemia using a DNA-array based platform

NARCIS (Netherlands)

Alonso, Rodrigo; Defesche, Joep C.; Tejedor, Diego; Castillo, Sergio; Stef, Marianne; Mata, Nelva; Gomez-Enterria, Pilar; Martinez-Faedo, Ceferino; Forga, Lluis; Mata, Pedro

2009-01-01

The aim of this study was to validate the Lipochip genetic diagnostic platform by assessing effectiveness, sensitivity, specificity and costs for the identification of patients with familial hypercholesterolemia (FH) in Spain. This platform includes the use of a DNA micro array, the detection of

DIAGNOSIS AND TREATMENT OF PATIENTS WITH SEVERE HYPERCHOLESTEROLEMIA IN REAL OUTPATIENT PRACTICE (ACCORDING TO THE RECVASA REGISTRY

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A. I. Ershova

2014-01-01

Full Text Available Hypercholesterolemia is a proven risk factor for atherosclerotic cardiovascular diseases and for their complications.Aim. To assess the quality of diagnosis and treatment of patients with severe hypercholesterolemia (total cholesterol >6.2 mmol/L in the real outpatient practice.Material and methods. All patients with a diagnosis of arterial hypertension, ischemic heart disease, chronic heart failure, atrial fibrillation applied to primary care physicians or cardiologists in one of the randomly selected out-patient clinic of Ryazan in March-May 2012 and included into the RECVASA registry were enrolled into the study group (n=1642.Results. The group of patients with severe hypercholesterolemia consisted of 561 (44% patients at the age of 67 (59-75 years [Me (25% -75%]. At that, diagnosis of hyperlipidemia was indicated only in 9% of outpatient cards. Data of one or more blood chemistries including low density cholesterol (LDC levels were presented only in 7% of outpatient cards. 83.7% of patients with severe hypercholesterolemia were classified as patients at high or very high cardiovascular risk, but statins were recommended only to 17.8% of them. Statins were mainly recommended in moderate doses; only one patient took atorvastatin 40 mg per day. Blood LDC levels were examined only in 5% of patients during statins therapy; nobody of them reached target LDC levels.Conclusion. The study data revealed the presence of a high prevalence of severe hypercholesterolemia in patients with cardiovascular diseases and poor quality of diagnosis and treatment in these patients in the real outpatient practice.

Polysaccharide from fuzi (FPS) prevents hypercholesterolemia in rats.

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Huang, Xiongqing; Tang, Juan; Zhou, Qin; Lu, Hanping; Wu, Yiling; Wu, Weikang

2010-01-28

Polysaccharide from fuzi (FPS), a Chinese herbal medicine extract, has been demonstrated to exert lipid lowering affects. In this study we examined potential mechanisms underlying this affect, specifically alterations in expression of the LDL-receptor (LDL-R), 3-hydroxy-3-methyl glutaryl (HMG)-CoA reductase and cytochrome P450 7alpha-1 (CYP7alpha-1), using a rat model of hypercholesterolemia. Male rats were fed either a normal or high cholesterol (HC) diet for two-weeks. Half of the rats on the HC diet were orally gavaged with FPS (224 mg/kg, 448 mg/kg or 896 mg/kg diet) daily. Serum lipid levels were quantified at end of the study period as were liver levels of LDL-R protein and mRNA expression of CYP7alpha-1 and HMG-CoA. Serum cholesterol and LDL-C concentrations were significantly elevated from control in HC rats, but not in those treated with FPS (P FPS group (P FPS group compared to both other groups (P FPS in hypercholesteremic rats is caused at least in part by increased hepatic LDL-R and CYP7alpha-1 expression and decreased HMG-CoA expression. Further study is needed to determine precisely where and how FPS exerts these effects. FPS offers potential as a therapeutic agent for the treatment of hypercholesterolemia.

Hypercholesterolemia Impaired Sperm Functionality in Rabbits

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Monclus, Maria A.; Cabrillana, Maria E.; Clementi, Marisa A.; Espínola, Leandro S.; Cid Barría, Jose L.; Vincenti, Amanda E.; Santi, Analia G.; Fornés, Miguel W.

2010-01-01

Hypercholesterolemia represents a high risk factor for frequent diseases and it has also been associated with poor semen quality that may lead to male infertility. The aim of this study was to analyze semen and sperm function in diet-induced hypercholesterolemic rabbits. Twelve adult White New Zealand male rabbits were fed ad libitum a control diet or a diet supplemented with 0.05% cholesterol. Rabbits under cholesterol-enriched diet significantly increased total cholesterol level in the serum. Semen examination revealed a significant reduction in semen volume and sperm motility in hypercholesterolemic rabbits (HCR). Sperm cell morphology was seriously affected, displaying primarily a “folded head”-head fold along the major axe-, and the presence of cytoplasmic droplet on sperm flagellum. Cholesterol was particularly increased in acrosomal region when detected by filipin probe. The rise in cholesterol concentration in sperm cells was determined quantitatively by Gas chromatographic-mass spectrometric analyses. We also found a reduction of protein tyrosine phosphorylation in sperm incubated under capacitating conditions from HCR. Interestingly, the addition of Protein Kinase A pathway activators -dibutyryl-cyclic AMP and iso-butylmethylxanthine- to the medium restored sperm capacitation. Finally, it was also reported a significant decrease in the percentage of reacted sperm in the presence of progesterone. In conclusion, our data showed that diet-induced hypercholesterolemia adversely affects semen quality and sperm motility, capacitation and acrosomal reaction in rabbits; probably due to an increase in cellular cholesterol content that alters membrane related events. PMID:20976152

Cardiovascular Risk Factors (Diabetes, Hypertension, Hypercholesterolemia and Metabolic Syndrome) in Older People with Intellectual Disability: Results of the HA-ID Study

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de Winter, C. F.; Bastiaanse, L. P.; Hilgenkamp, T. I. M.; Evenhuis, H. M.; Echteld, M. A.

2012-01-01

Hypertension, diabetes, hypercholesterolemia and the metabolic syndrome are important risk factors for cardiovascular disease (CVD). In older people with intellectual disability (ID), CVD is a substantial morbidity risk. The aims of the present study, which was part of the Healthy Ageing in Intellectual Disability (HA-ID) study, were (1) to…

Hypocholesterolemic and Antiatherosclerotic Potential of Basella alba Leaf Extract in Hypercholesterolemia-Induced Rabbits

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Gunasekaran Baskaran

2015-01-01

Full Text Available Hypercholesterolemia is the major risk factor that leads to atherosclerosis. Nowadays, alternative treatment using medicinal plants gained much attention since the usage of statins leads to adverse health effects, especially liver and muscle toxicity. This study was designed to investigate the hypocholesterolemic and antiatherosclerotic effects of Basella alba (B. alba using hypercholesterolemia-induced rabbits. Twenty New Zealand white rabbits were divided into 5 groups and fed with varying diets: normal diet, 2% high cholesterol diet (HCD, 2% HCD + 10 mg/kg simvastatin, 2% HCD + 100 mg/kg B. alba extract, and 2% HCD + 200 mg/kg B. alba extract, respectively. The treatment with B. alba extract significantly lowered the levels of total cholesterol, LDL, and triglycerides and increased HDL and antioxidant enzymes (SOD and GPx levels. The elevated levels of liver enzymes (AST and ALT and creatine kinase were noted in hypercholesterolemic and statin treated groups indicating liver and muscle injuries. Treatment with B. alba extract also significantly suppressed the aortic plaque formation and reduced the intima: media ratio as observed in simvastatin-treated group. This is the first in vivo study on B. alba that suggests its potential as an alternative therapeutic agent for hypercholesterolemia and atherosclerosis.

Evidence of Lifestyle Modification in the Management of Hypercholesterolemia

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Mannu, GS; Zaman, MJS; Gupta, A; HU, Rehman; Myint, PK

2013-01-01

Background: Coronary heart disease (CHD) is the leading cause of morbidity and mortality worldwide. The growth of ageing populations in developing countries with progressively urbanized lifestyles are major contributors. The key risk factors for CHD such as hypercholesterolemia, diabetes mellitus, and obesity are likely to increase in the future. These risk factors are modifiable through lifestyle. Objectives: To review current literature on the potential benefit of cholesterol lowering in CHD risk reduction with a particular focus on the evidence of non-pharmacological/lifestyle management of hypercholesterolemia. Methods: Medline/PubMed systematic search was conducted using a two-tier approach limited to all recent English language papers. Primary search was conducted using key words and phrases and all abstracts were subsequently screened and relevant papers were selected. The next tier of searching was conducted by (1) reviewing the citation lists of the selected papers and (2) by using PubMed weblink for related papers. Over 3600 reports were reviewed. Results: Target cholesterol levels set out in various guidelines could be achieved by lifestyle changes, including diet, weight reduction, and increased physical activity with the goal of reducing total cholesterol to hypercholesterolemia is an important cause of CHD. Non-pharmacological methods provide initial as well as long-term measures to address this issue. PMID:22998604

Two novel mutations in exon 3 and 4 of low density lipoprotein (LDL) receptor gene in patients with heterozygous familial hypercholesterolemia

International Nuclear Information System (INIS)

Khan, S.P.

2011-01-01

Objective: To determine the common mutation of low density lipoprotein receptor in hypercholesterolemia patients requiring screening for heterozygous familial hypercholesterolemia (HeFH) in Karachi. Study Design: Case-series. Place and Duration of Study: Dr. Ziauddin Hospital Laboratory and Dr. Rubina Ghani's Pathological and Molecular Laboratories, Karachi, for the PCR bench work from June 2008 to October 2009. Methodology: All the patients selected for this study were from Dr. Ziauddin Hospital and National Institute of Cardiovascular Diseases. All the patients having high total cholesterol and LDL-cholesterol were included in this study with premature coronary artery diseases or a family history of hypercholesterolemia. Exclusion criteria included Diabetes mellitus, hypertension, renal disease, hypothyroidism and steroid therapy. After lipid profile with overnight fasting, DNA was extracted from whole blood collected in EDTA (ethylenediamine tetra acetic acid) tube and multiplex PCR (polymerase chain reaction) using forward and reverse primers of exons 3, 4, 9 and 14 of base pairs 162, 431, 550 and 496 respectively. Results: Out of total of 120 hypercholesterolemia cases, 42 patients were classical cases of HeFH (heterozygous familial hypercholesterolemia) with xanthomas, xanthelasmas and LDL-C > 160 mg/dl. The total cholesterol (260 +- 57 mg/dL) and LDL-C (192 +- 39 mg/dL ) of cases was significantly high as compared to, controls having total cholesterol (184 9 +- 27 mg/dL) and LDL-C (105 +- 22 mg/dL), p > 0.001. Two novel point mutations were noted in exon 3 and exon 4. The other 78 cases were probable with raised LDL-C (low density lipoprotein cholesterol) and family history of premature coronary heart diseases. Conclusion: The frequency of HeFH was 35% classical and 65% probable cases out of total 120 hypercholesterolemia patients from two tertiary care hospitals in Karachi. The point mutation on exon 3 and exon 4 of LDLR gene was the most common. PCR is

Familial hypercholesterolemia: Screening, treatment and follow-up from pregnancy into young adulthood

NARCIS (Netherlands)

Kusters, D.M.

2016-01-01

In part 1, the consequences of familial hypercholesterolemia (FH) during pregnancy for the unborn child are explored. Part II comprises several studies on the screening, diagnosis and follow-up of children with FH. The treatment of children with FH is studied in part III, with the most important

Comparison of ezetimibe plus simvastatin versus simvastatin monotherapy on atherosclerosis progression in familial hypercholesterolemia: Design and rationale of the Ezetimibe and Simvastatin in Hypercholesterolemia Enhances Atherosclerosis Regression (ENHANCE) trial

NARCIS (Netherlands)

Kastelein, John J. P.; Sager, Philip T.; de Groot, Eric; Veltri, Enrico

2005-01-01

Background Lipid lowering through statin therapy significantly reduces the risk of cardiovascular events. The ENHANCE study is an international 2-year, randomized, double-blind, controlled trial designed to test the hypothesis that treatment of hypercholesterolemia by use of 2 complementary agents,

Trends in self-reported prevalence and management of hypertension, hypercholesterolemia and diabetes in Swiss adults, 1997-2007

Science.gov (United States)

2011-01-01

Background Switzerland has a low mortality rate from cardiovascular diseases, but little is known regarding prevalence and management of cardiovascular risk factors (CV RFs: hypertension, hypercholesterolemia and diabetes) in the general population. In this study, we assessed 10-year trends in self-reported prevalence and management of cardiovascular risk factors in Switzerland. Methods data from three national health interview surveys conducted between 1997 and 2007 in representative samples of the Swiss adult population (49,261 subjects overall). Self-reported CV RFs prevalence, treatment and control levels were computed. The sample was weighted to match the sex - and age distribution, geographical location and nationality of the entire adult population of Switzerland. Results self-reported prevalence of hypertension, hypercholesterolemia and diabetes increased from 22.1%, 11.9% and 3.3% in 1997 to 24.1%, 17.4% and 4.8% in 2007, respectively. Prevalence of self-reported treatment among subjects with CV RFs also increased from 52.1%, 18.5% and 50.0% in 1997 to 60.4%, 38.8% and 53.3% in 2007 for hypertension, hypercholesterolemia and diabetes, respectively. Self-reported control levels increased from 56.4%, 52.9% and 50.0% in 1997 to 80.6%, 75.1% and 53.3% in 2007 for hypertension, hypercholesterolemia and diabetes, respectively. Finally, screening during the last 12 months increased from 84.5%, 86.5% and 87.4% in 1997 to 94.0%, 94.6% and 94.1% in 2007 for hypertension, hypercholesterolemia and diabetes, respectively. Conclusion in Switzerland, the prevalences of self-reported hypertension, hypercholesterolemia and diabetes have increased between 1997 and 2007. Management and screening have improved, but further improvements can still be achieved as over one third of subjects with reported CV RFs are not treated. PMID:21332996

Nutraceuticals for the treatment of hypercholesterolemia.

Science.gov (United States)

Mannarino, Massimo R; Ministrini, Stefano; Pirro, Matteo

2014-09-01

Hypercholesterolemia is a well-established modifiable cardiovascular risk factor and its treatment is an essential aim in preventing cardiovascular disease. Current guidelines highlight lifestyle intervention as a primary issue in the treatment of the patient with hypercholesterolemia. Therapeutic lifestyle changes are often insufficient to achieve desirable cholesterol levels. This is particularly true for high risk patients; however, also low risk patients, whose cholesterol levels are not necessarily far from recommended targets, have either sub-optimal or even significantly increased lipid levels. Nutraceuticals are borderline devices between nutrients and drugs providing a supplementation of particular nutrients with beneficial effects on health. Several nutraceuticals have been suggested to improve plasma lipid profile. The literature counted over 40 nutraceutical substances with a supposed beneficial effect on lipid metabolism; for some of them a number of clinical trials highlighted a cholesterol lowering effect and a possible positive influence on cardiovascular prognosis. The aim of this article is to review the main evidences supporting or denying the efficacy and safety of some of the most commonly used nutraceuticals with supposed cholesterol lowering activity. Copyright © 2014 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.

Posttesticular sperm maturation, infertility, and hypercholesterolemia

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Marjorie Whitfield

2015-01-01

Full Text Available Cholesterol is a key molecule in the mammalian physiology of especial particular importance for the reproductive system as it is the common precursor for steroid hormone synthesis. Cholesterol is also a recognized modulator of sperm functions, not only at the level of gametogenesis. Cholesterol homeostasis regulation is crucial for posttesticular sperm maturation, and imbalanced cholesterol levels may particularly affect these posttesticular events. Metabolic lipid disorders (dyslipidemia affect male fertility but are most of the time studied from the angle of endocrine/testicular consequences. This review will focus on the deleterious effects of a particular dyslipidemia, i.e., hypercholesterolemia, on posttesticular maturation of mammalian spermatozoa.

No certain predictors for mutation status in a Danish cohort with familial hypercholesterolemia: a descriptive study

DEFF Research Database (Denmark)

Nybo, Mads; Brusgaard, Klaus; Hansen, Annebirthe Bo

2007-01-01

OBJECTIVE: In order to enable clinicians to refer the right persons suspected of familial hypercholesterolemia (FH) for mutation screening, a retrospective study was conducted in a Danish FH cohort. DESIGN AND METHODS: The study comprised 643 probands and 395 relatives, of which 421 individuals had...... a pathogenic mutation, and 211 had cardiovascular disease (CVD). Logistic regression, Cox regression, and receiver operating characteristics (ROC) curves were used to find optimal predictive variables for mutation status and evaluate risk factors for CVD. RESULTS: Age alone had significant predictive power...... criteria should therefore be referred in order to facilitate family tracing and genetic counseling...

Extreme phenotypes in hypercholesterolemia : From genotype to therapy

NARCIS (Netherlands)

Sjouke, B.

2017-01-01

Familial hypercholesterolemia (FH) is an inherited disorder of cholesterol metabolism, resulting in increased LDL-cholesterol levels and, as a consequence, an increased risk for coronary heart disease. Recently, many causal FH mutations in different genes have been identified and advances in genetic

Hypercholesterolemia Causes Circadian Dysfunction: A Potential Risk Factor for Cardiovascular Disease

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Makoto Akashi

2017-06-01

Full Text Available Hypercholesterolemia is a well-known risk factor for a wide range of diseases in developed countries. Here, we report that mice lacking functional LDLR (low density lipoprotein receptor, an animal model of human familial hypercholesterolemia, show circadian abnormalities. In free running behavioral experiments in constant darkness, these mice showed a prolonged active phase and distinctly bimodal rhythms. Even when the circadian rhythms were entrained by light and dark cycles, these mice showed a significant attenuation of behavioral onset intensity at the start of the dark period. Further, we hypothesized that the combination of hypercholesterolemia and circadian abnormalities may affect cardiovascular disease progression. To examine this possibility, we generated LDLR-deficient mice with impaired circadian rhythms by simultaneously introducing a mutation into Period2, a core clock gene, and found that these mice showed a significant enlargement of artery plaque area with an increase in inflammatory cytokine IL-6 levels. These results suggest that circadian dysfunction may be associated with the development or progression of cardiovascular diseases.

Hypercholesterolemia with consumption of PFOA-laced Western diets is dependent on strain and sex of mice

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Sandra L. Rebholz

Full Text Available Perfluorooctanoic acid (PFOA is a man-made surfactant with a number of industrial applications. It has a long half-life environmentally and biologically. Past studies suggest a direct relationship between plasma cholesterol and PFOA serum concentrations in humans and an inverse one in rodents fed standard rodent chow, making it difficult to examine mechanisms responsible for the potential PFOA-induced hypercholesterolemia and altered sterol metabolism. To examine dietary modification of PFOA-induced effects, C57BL/6 and BALB/c mice were fed PFOA in a fat- and cholesterol-containing diet. When fed these high fat diets, PFOA ingestion resulted in marked hypercholesterolemia in male and female C57BL/6 mice and less robust hypercholesterolemia in male BALB/c mice. The PFOA-induced hypercholesterolemia appeared to be the result of increased liver masses and altered expression of genes associated with hepatic sterol output, specifically bile acid production. mRNA levels of genes associated with sterol input were reduced only in C57BL/6 females, the mice with the greatest increase in plasma cholesterol levels. Strain-specific PFOA-induced changes in cholesterol concentrations in mammary tissues and ovaries paralleled changes in plasma cholesterol levels. mRNA levels of sterol-related genes were reduced in ovaries of C57BL/6 but not in BALB/c mice and not in mammary tissues. Our data suggest that PFOA ingestion leads to hypercholesterolemia in mice fed fat and cholesterol and effects are dependent upon the genetic background and gender of the mice with C57BL/6 female mice being most responsive to PFOA. Keywords: Perfluorooctanoic acid, C8, PFC, PFAS, Cholesterol, Dietary fat

Exome Sequencing and Directed Clinical Phenotyping Diagnose Cholesterol Ester Storage Disease Presenting as Autosomal Recessive Hypercholesterolemia

NARCIS (Netherlands)

Stitziel, Nathan O.; Fouchier, Sigrid W.; Sjouke, Barbara; Peloso, Gina M.; Moscoso, Alessa M.; Auer, Paul L.; Goel, Anuj; Gigante, Bruna; Barnes, Timothy A.; Melander, Olle; Orho-Melander, Marju; Duga, Stefano; Sivapalaratnam, Suthesh; Nikpay, Majid; Martinelli, Nicola; Girelli, Domenico; Jackson, Rebecca D.; Kooperberg, Charles; Lange, Leslie A.; Ardissino, Diego; McPherson, Ruth; Farrall, Martin; Watkins, Hugh; Reilly, Muredach P.; Rader, Daniel J.; de Faire, Ulf; Schunkert, Heribert; Erdmann, Jeanette; Samani, Nilesh J.; Charnas, Lawrence; Altshuler, David; Gabriel, Stacey; Kastelein, John J. P.; Defesche, Joep C.; Nederveen, Aart J.; Kathiresan, Sekar; Hovingh, G. Kees

2013-01-01

Objective Autosomal recessive hypercholesterolemia is a rare inherited disorder, characterized by extremely high total and low-density lipoprotein cholesterol levels, that has been previously linked to mutations in LDLRAP1. We identified a family with autosomal recessive hypercholesterolemia not

Efficacy and safety of alirocumab in patients with hypercholesterolemia not adequately controlled with non-statin lipid-lowering therapy or the lowest strength of statin: ODYSSEY NIPPON study design and rationale.

Science.gov (United States)

Teramoto, Tamio; Kondo, Akira; Kiyosue, Arihiro; Harada-Shiba, Mariko; Ishigaki, Yasushi; Tobita, Kimimasa; Kawabata, Yumiko; Ozaki, Asuka; Baccara-Dinet, Marie T; Sata, Masataka

2017-06-17

Statins are generally well-tolerated and serious side effects are infrequent, but some patients experience adverse events and reduce their statin dose or discontinue treatment altogether. Alirocumab is a highly specific, fully human monoclonal antibody to proprotein convertase subtilisin/kexin type 9 (PCSK9), which can produce substantial and sustained reductions of low-density lipoprotein cholesterol (LDL-C). The randomized, double-blind, placebo-controlled, parallel-group, phase 3 ODYSSEY NIPPON study will explore alirocumab 150 mg every 4 weeks (Q4W) in 163 Japanese patients with hypercholesterolemia who are on the lowest-strength dose of atorvastatin (5 mg/day) or are receiving a non-statin lipid-lowering therapy (LLT) (fenofibrate, bezafibrate, ezetimibe, or diet therapy alone). Hypercholesterolemia is defined as LDL-C ≥ 100 mg/dL (2.6 mmol/L) in patients with heterozygous familial hypercholesterolemia or non-familial hypercholesterolemia with a history of documented coronary heart disease, or ≥120 mg/dL (3.1 mmol/L) in patients with non-familial hypercholesterolemia classified as primary prevention category III (i.e. high-risk patients). During the 12-week double-blind treatment period, patients will be randomized (1:1:1) to receive alirocumab subcutaneously (SC) 150 mg Q4W alternating with placebo for alirocumab Q4W, or alirocumab 150 mg SC every 2 weeks (Q2W), or SC placebo Q2W. The primary efficacy endpoint is the percentage change in calculated LDL-C from baseline to week 12. The long-term safety and tolerability of alirocumab will also be investigated. The ODYSSEY NIPPON study will provide insights into the efficacy and safety of alirocumab 150 mg Q4W or 150 mg Q2W among Japanese patients with hypercholesterolemia who are on the lowest-strength dose of atorvastatin, or are receiving a non-statin LLT (including diet therapy alone). ClinicalTrials.gov number: NCT02584504.

MicroRNA-30c Mimic Mitigates Hypercholesterolemia and Atherosclerosis in Mice*

Science.gov (United States)

Irani, Sara; Pan, Xiaoyue; Peck, Bailey C. E.; Iqbal, Jahangir; Sethupathy, Praveen; Hussain, M. Mahmood

2016-01-01

High plasma cholesterol levels are a major risk factor for atherosclerosis. Plasma cholesterol can be reduced by inhibiting lipoprotein production; however, this is associated with steatosis. Previously we showed that lentivirally mediated hepatic expression of microRNA-30c (miR-30c) reduced hyperlipidemia and atherosclerosis in mice without causing hepatosteatosis. Because viral therapy would be formidable, we examined whether a miR-30c mimic can be used to mitigate hyperlipidemia and atherosclerosis without inducing steatosis. Delivery of a miR-30c mimic to the liver diminished diet-induced hypercholesterolemia in C57BL/6J mice. Reductions in plasma cholesterol levels were significantly correlated with increases in hepatic miR-30c levels. Long term dose escalation studies showed that miR-30c mimic caused sustained reductions in plasma cholesterol with no obvious side effects. Furthermore, miR-30c mimic significantly reduced hypercholesterolemia and atherosclerosis in Apoe−/− mice. Mechanistic studies showed that miR-30c mimic had no effect on LDL clearance but reduced lipoprotein production by down-regulating microsomal triglyceride transfer protein expression. MiR-30c had no effect on fatty acid oxidation but reduced lipid synthesis. Additionally, whole transcriptome analysis revealed that miR-30c mimic significantly down-regulated hepatic lipid synthesis pathways. Therefore, miR-30c lowers plasma cholesterol and mitigates atherosclerosis by reducing microsomal triglyceride transfer protein expression and lipoprotein production and avoids steatosis by diminishing lipid syntheses. It mitigates atherosclerosis most likely by reducing lipoprotein production and plasma cholesterol. These findings establish that increasing hepatic miR-30c levels is a viable treatment option for reducing hypercholesterolemia and atherosclerosis. PMID:27365390

Automated in vivo platform for the discovery of functional food treatments of hypercholesterolemia.

Directory of Open Access Journals (Sweden)

Robert M Littleton

Full Text Available The zebrafish is becoming an increasingly popular model system for both automated drug discovery and investigating hypercholesterolemia. Here we combine these aspects and for the first time develop an automated high-content confocal assay for treatments of hypercholesterolemia. We also create two algorithms for automated analysis of cardiodynamic data acquired by high-speed confocal microscopy. The first algorithm computes cardiac parameters solely from the frequency-domain representation of cardiodynamic data while the second uses both frequency- and time-domain data. The combined approach resulted in smaller differences relative to manual measurements. The methods are implemented to test the ability of a methanolic extract of the hawthorn plant (Crataegus laevigata to treat hypercholesterolemia and its peripheral cardiovascular effects. Results demonstrate the utility of these methods and suggest the extract has both antihypercholesterolemic and postitively inotropic properties.

Hypercholesterolemia and apolipoprotein B expression: Regulation by selenium status

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Bansal Mohinder P

2005-11-01

Full Text Available Abstract Background Apolipoprotein B (apoB contains ligand-binding domain for the binding of LDL to LDL-R site, which enables the removal of LDL from circulation. Our recent data showed that selenium (Se is involved in the lipid metabolism. The present study was aimed to understand the effect of Se deficiency (0.02 ppm and selenium supplementation (1 ppm on apoB expression in liver during hypercholesterolemia in male Sprague Dawley rats. Animals were fed with control and high cholesterol diet (2% for 1 and 2 months. ApoB levels by ELISA and protein expression by western blot was done. Hepatic LDL receptor (LDL-R activity (in vivo and mRNA expression by RT-PCR was monitored. Results In selenium deficiency and on high cholesterol diet (HCD feeding apoB levels increased and LDL-R expression decreased significantly after 2 months. On 1 ppm selenium supplementation apoB expression significantly decreased and LDL-R expression increased after 2 months. But after one month of treatment there was no significant change observed in apoB and LDL-R expression. Conclusion So the present study demonstrates that Se deficiency leads to up regulation of apoB expression during experimental hypercholesterolemia. Selenium supplementation upto 1 ppm leads to downregulation of apoB expression. Further, this study will highlight the nutritional value of Se supplementation in lipid metabolism.

Association of job sectors with type 2 diabetes mellitus, hypercholesterolemia and obesity: a cross-sectional study from the Malaysian Cohort (TMC) project.

Science.gov (United States)

Borhanuddin, Boekhtiar; Ahmad, Norfazilah; Shah, Shamsul Azhar; Murad, Nor Azian Abdul; Zakaria, Syed Zulkifli Syed; Kamaruddin, Mohd Arman; Jalal, Nazihah Abd; Yusuf, Nurul Ain Mhd; Patah, Afzan Effiza Abdul; Dauni, Andri; Sallam, Wan Ahmad Faisal Wan; Jamal, Rahman

2018-02-15

The investigation of risk factors of cardiovascular disease (e.g., major endocrine, nutritional and metabolic diseases) across job sectors is useful for targeted public health intervention. This study examined the occurrence of type 2 diabetes mellitus (T2DM), hypercholesterolemia and obesity in 21 job sectors in the general population. A baseline cross-sectional analysis of the Malaysian Cohort was conducted, which included 105 391 adults. Multiple logistic regression analyses were conducted for these three diseases across 20 job sectors compared with the unemployed/homemaker sector. The prevalence of T2DM, hypercholesterolemia and obesity was 16.7%, 38.8% and 33.3%, respectively. The Accommodation & Food Service Activities and Transportation & Storage sectors had significantly higher odds for T2DM (adjusted [adj.] prevalence odds ratio [POR] 1.18, p=0.007 and adj. POR 1.15, p=0.008, respectively). No job sector had significantly higher odds for hypercholesterolemia compared with the unemployed/homemaker sector. Only the Accommodation & Food Service Activities sector had significantly higher odds for obesity (adj. POR 1.17, p≤0.001). Many job sectors were significantly associated with lower odds of having these three diseases when compared with the unemployed/homemaker sector. These differing associations between diverse job sectors and these diseases are important for public health intervention initiatives and prioritization.

Effect of ascorbic acid on prevention of hypercholesterolemia induced atherosclerosis.

Science.gov (United States)

Das, S; Ray, R; Snehlata; Das, N; Srivastava, L M

2006-04-01

The notion that oxidation of lipids and propagation of free radicals may contribute to the pathogenesis of atherosclerosis is supported by a large body of evidence. To circumvent the damage caused by oxygen free radicals, antioxidants are needed which provide the much needed neutralization of free radical by allowing the pairing of electrons. In this study we have investigated the effect of ascorbic acid, a water soluble antioxidant on the development of hypercholesterolemia induced atherosclerosis in rabbits. Rabbits were made hypercholesterolemic and atherosclerotic by feeding 100 mg cholesterol/day. Different doses of ascorbic acid were administered to these rabbits. Low dose of ascorbic acid (0.5 mg/100 g body weight/day) did not have any significant effect on the percent of total area covered by atherosclerotic plaque. However, ascorbic acid when fed at a higher dose (15 mg/100 g body weight/day) was highly effective in reducing the atherogenecity. With this dose the percent of total surface area covered by atherosclerotic plaque was significantly less (p ascorbic acid may have great promise in the prevention of hypercholesterolemia induced atherosclerosis.

Coronary and peripheral endothelial function in HIV patients studied with positron emission tomography and flow-mediated dilation: relation to hypercholesterolemia

DEFF Research Database (Denmark)

Lebech, Anne-Mette; Kristoffersen, Ulrik Sloth; Wiinberg, Niels

2008-01-01

BACKGROUND: The mechanisms underlying increased cardiovascular risk in HIV patients in antiretroviral therapy (ART) are not known. Our aim was to study the endothelial function of the coronary arteries by cardiac perfusion positron emission tomography (PET), in HIV patients with normal or high...... in hypercholesterolemic patients. Also, the increased level of plasma endothelial markers found in HIV patients was not related to hypercholesterolemia....

Impact of LDL apheresis on atheroprotective reverse cholesterol transport pathway in familial hypercholesterolemia

NARCIS (Netherlands)

Orsoni, Alexina; Villard, Elise F.; Bruckert, Eric; Robillard, Paul; Carrie, Alain; Bonnefont-Rousselot, Dominique; Chapman, M. John; Dallinga-Thie, Geesje M.; Le Goff, Wilfried; Guerin, Maryse

2012-01-01

In familial hypercholesterolemia (FH), low HDL cholesterol (HDL-C) levels are associated with functional alterations of HDL particles that reduce their capacity to mediate the reverse cholesterol transport (RCT) pathway. The objective of this study was to evaluate the consequences of LDL apheresis

Effects of Karela (Bitter Melon; Momordica charantia) on genes of lipids and carbohydrates metabolism in experimental hypercholesterolemia: biochemical, molecular and histopathological study.

Science.gov (United States)

Saad, Dalia Yossri; Soliman, Mohamed Mohamed; Baiomy, Ahmed A; Yassin, Magdy Hassan; El-Sawy, Hanan Basiouni

2017-06-17

Hypercholesterolemia is a serious diseases associated with type-2 diabetes, atherosclerosis, cardiovascular disorders and liver diseases. Humans seek for safe herbal medication such as karela (Momordica charantia/bitter melon) to treat such disorders to avoid side effect of pharmacotherapies widely used. Forty male Wistar rats were divided into four equal groups; control group with free access to food and water, cholesterol administered group (40 mg/kg BW orally); karela administered group (5 g /kg BW orally) and mixture of cholesterol and karela. The treatments continued for 10 weeks. Karela was given for hypercholesterolemic rats after 6 weeks of cholesterol administration. Serum, liver and epididymal adipose tissues were taken for biochemical, histopathological and genetic assessments. Hypercholesterolemia induced a decrease in serum superoxide dismutase (SOD), catalase, reduced glutathione (GSH) and an increase in malondialdehyde (MDA) levels that were ameliorated by karela administration. Hypercholesterolemia up regulated antioxidants mRNA expression and altered the expression of carbohydrate metabolism genes. In parallel, hypercholesterolemic groups showed significant changes in the expression of PPAR-alpha and gamma, lipolysis, lipogenesis and cholesterol metabolism such as carnitine palmitoyltransferase-1 (CPT-1). Acyl CoA oxidase (ACO), fatty acids synthase (FAS), sterol responsible element binding protein-1c (SREBP1c), 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG-CoAR) and cholesterol 7α-hydroxylase (CYP7A1) at hepatic and adipose tissue levels. Interestingly, Karela ameliorated all altered genes confirming its hypocholesterolemic effect. Histopathological and immunohistochemical findings revealed that hypercholesterolemia induced hepatic tissue changes compared with control. These changes include cholesterol clefts, necrosis, karyolysis and sever congestion of portal blood vessel. Caspase-3 immunoreactivity showed positive expression in

Premature Coronary Artery Disease due to Homozygous Familial Hypercholesterolemia in a 12-Year-Old Girl

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Filiz Ekici

2018-03-01

Full Text Available Background: Homozygous familial hypercholesterolemia is a rare inherited metabolic disease caused by low-density lipoprotein receptor abnormality. Patients with homozygous familial hypercholesterolemia have an increased risk of cardiovascular complication that usually occurs in the first decade of life. Here, we report a 12-year-old girl with an unpredicted presentation for coronary artery disease and found to have homozygous familial hypercholesterolemia. Case Report: A 12-year-old girl was admitted to our unit with syncope. Chest X-ray showed bilateral diffuse pneumonic consolidation and mild cardiomegaly. We detected stable ST depression by electrocardiography. Echocardiography showed normal systolic functions. Troponin-1 levels were high (66 mcg/dL, upper limit: 0.04 mcg/dL. Influenza A virus DNA was detected by the respiratory viral panel. After her successful treatment for acute pneumonia and myocarditis due to Influenza A virus, her syncope attacks persisted. Marked ST elevation was observed during exercise electrocardiography. Coronary angiography showed severe occlusions in the coronary arteries. High serum levels of total cholesterol (756 mg/dL and low-density lipoprotein-C (556 mg/dL were noticed. She had no tendon xanthomas. Medical histories revealed that her family members were diagnosed with heterozygous familial hypercholesterolemia. A coronary bypass surgery was performed. Statin and ezetimibe treatments were started. We also planned lipid apheresis. Conclusion: Children with homozygous familial hypercholesterolemia may present with symptoms of premature coronary heart disease requiring a routine lipid test and careful anamnesis.

Black ginseng extract ameliorates hypercholesterolemia in rats.

Science.gov (United States)

Saba, Evelyn; Jeon, Bo Ra; Jeong, Da-Hye; Lee, Kija; Goo, Youn-Kyoung; Kim, Seung-Hyung; Sung, Chang-Keun; Roh, Seong-Soo; Kim, Sung Dae; Kim, Hyun-Kyoung; Rhee, Man-Hee

2016-04-01

Ginseng (Panax ginseng Meyer) is a well-characterized medicinal herb listed in the classic oriental herbal dictionary as "Shin-nong-bon-cho-kyung." Ginseng has diverse pharmacologic and therapeutic properties. Black ginseng (BG, Ginseng Radix nigra) is produced by repeatedly steaming fresh ginseng nine times. Studies of BG have shown that prolonged heat treatment enhances the antioxidant activity with increased radical scavenging activity. Several recent studies have showed the effects of BG on increased lipid profiles in mice. In this study report the effects of water and ethanol extracts of BG on hypercholesterolemia in rats. To our knowledge, this is the first time such an effect has been reported. Experiments were conducted on male Sprague Dawley rats fed with a high-cholesterol diet supplemented with the water and ethanol extracts of BG (200 mg/kg). Their blood cholesterol levels, serum white blood cell levels, and cholesterol-metabolizing marker genes messenger RNA (mRNA) expression were determined. Liver and adipose tissues were histologically analyzed. We found that BG extracts efficiently reduced the total serum cholesterol levels, low-density lipoprotein (LDL) levels with increased food efficiency ratio and increased number of neutrophil cells. It also attenuated the key genes responsible for lipogenesis, that is, acetyl-coenzyme A (CoA) acetyltransferase 2, 3-hydroxy-3-methyl-glutaryl-CoA reductase, and sterol regulatory element-binding protein 2, at the mRNA level inside liver cells. Furthermore, the BG extract also reduced the accumulation of fat in adipose tissues, and inhibited the neutral fat content in liver cells stained with hematoxylin and eosin and oil red O. Administration of BG extracts to Sprague Dawley rats fed with high-cholesterol diet ameliorated hypercholesterolemia, which was mediated via modulation of cholesterol-metabolizing marker genes. This data throw a light on BG's cardioprotective effects.

MicroRNA-30c Mimic Mitigates Hypercholesterolemia and Atherosclerosis in Mice.

Science.gov (United States)

Irani, Sara; Pan, Xiaoyue; Peck, Bailey C E; Iqbal, Jahangir; Sethupathy, Praveen; Hussain, M Mahmood

2016-08-26

High plasma cholesterol levels are a major risk factor for atherosclerosis. Plasma cholesterol can be reduced by inhibiting lipoprotein production; however, this is associated with steatosis. Previously we showed that lentivirally mediated hepatic expression of microRNA-30c (miR-30c) reduced hyperlipidemia and atherosclerosis in mice without causing hepatosteatosis. Because viral therapy would be formidable, we examined whether a miR-30c mimic can be used to mitigate hyperlipidemia and atherosclerosis without inducing steatosis. Delivery of a miR-30c mimic to the liver diminished diet-induced hypercholesterolemia in C57BL/6J mice. Reductions in plasma cholesterol levels were significantly correlated with increases in hepatic miR-30c levels. Long term dose escalation studies showed that miR-30c mimic caused sustained reductions in plasma cholesterol with no obvious side effects. Furthermore, miR-30c mimic significantly reduced hypercholesterolemia and atherosclerosis in Apoe(-/-) mice. Mechanistic studies showed that miR-30c mimic had no effect on LDL clearance but reduced lipoprotein production by down-regulating microsomal triglyceride transfer protein expression. MiR-30c had no effect on fatty acid oxidation but reduced lipid synthesis. Additionally, whole transcriptome analysis revealed that miR-30c mimic significantly down-regulated hepatic lipid synthesis pathways. Therefore, miR-30c lowers plasma cholesterol and mitigates atherosclerosis by reducing microsomal triglyceride transfer protein expression and lipoprotein production and avoids steatosis by diminishing lipid syntheses. It mitigates atherosclerosis most likely by reducing lipoprotein production and plasma cholesterol. These findings establish that increasing hepatic miR-30c levels is a viable treatment option for reducing hypercholesterolemia and atherosclerosis. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Outcomes in Patients With Metastatic Renal Cell Carcinoma Who Develop Everolimus-Related Hyperglycemia and Hypercholesterolemia: Combined Subgroup Analyses of the RECORD-1 and REACT Trials.

Science.gov (United States)

Bono, Petri; Oudard, Stephane; Bodrogi, Istvan; Hutson, Thomas E; Escudier, Bernard; Machiels, Jean-Pascal; Thompson, John A; Figlin, Robert A; Ravaud, Alain; Basaran, Mert; Porta, Camillo; Bracarda, Sergio; Brechenmacher, Thomas; Lin, Chinjune; Voi, Maurizio; Grunwald, Viktor; Motzer, Robert J

2016-10-01

Hyperglycemia and hypercholesterolemia are class effects of mammalian target of rapamycin inhibitors. The purpose of this study was to characterize safety and efficacy of patients with metastatic renal cell carcinoma (mRCC) treated with everolimus in RECORD-1 (REnal Cell cancer treatment with Oral RAD001 given Daily) and REACT (RAD001 Expanded Access Clinical Trial in RCC) who developed these events. Adults with vascular endothelial growth factor-refractory mRCC received everolimus 10 mg/d in the randomized RECORD-1 (n = 277) and open-label REACT (n = 1367) studies. Outcomes included safety, treatment duration, overall response, and progression-free survival for patients who developed hypercholesterolemia or hyperglycemia. In RECORD-1, 12% (33 of 277) and 20% (55 of 277) of patients developed any grade hyperglycemia or hypercholesterolemia, respectively, with only 6% (78 of 1367) and 1% (14 of 1367) of the same events, respectively, in REACT. Median everolimus treatment duration was similar for patients with hyperglycemia or hypercholesterolemia (RECORD-1, 6.2 and 6.2 months, respectively; REACT, 4.4 and 4.5 months, respectively), but longer than the overall populations (RECORD-1, 4.6 months; REACT, 3.2 months). In RECORD-1/REACT, 82%/68% of patients with hyperglycemia and 75%/71% of patients with hypercholesterolemia achieved partial response or stable disease. The incidence of clinically notable Grade 3 or 4 adverse events, other than anemia and lymphopenia, appeared to be similar across trials and subgroups. Although there was a trend for improved progression-free survival with development of hyperglycemia or hypercholesterolemia, the association was not statistically significant. Hyperglycemia and hypercholesterolemia were observed in low numbers of patients, and although these events might be associated with improved response to everolimus, the differences were not significant. These findings should be validated with prospective biomarker studies. Copyright

The prevalence and prognostic importance of possible familial hypercholesterolemia in patients with myocardial infarction

DEFF Research Database (Denmark)

Rerup, Sofie Aagaard; Bang, Lia E; Mogensen, Ulrik M

2016-01-01

AIMS: Familial hypercholesterolemia (FH) is a common genetic disorder causing accelerated atherosclerosis and premature cardiovascular disease. The aim of this study was to examine the prevalence and prognostic significance of possible FH in patients with myocardial infarction (MI). METHODS...

Induced-hypercholesterolemia as a probable cause of alterations in ...

African Journals Online (AJOL)

Methods: The telemetry technique was used to investigate the cardiovascular dysfunctions in induced hypercholesterolemia in Wistar Kyoto (WKY) rats. Methods for this investigation include: inducing hypercholesterolemic condition in Wistar Kyoto rats through diet; measuring the blood cholesterol levels of the experimental ...

Homozygous familial hypercholesterolemia (HoFH in Germany: an epidemiological survey

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Walzer S

2013-05-01

Full Text Available S Walzer,1 K Travers,2 S Rieder,3 E Erazo-Fischer,3 D Matusiewicz41MArS Market Access and Pricing Strategy UG (hb, Weil am Rhein, Germany; 2United Biosource Corporation, Lexington, USA; 3Alcimed GmbH, Cologne, Germany; 4Institute for Health Care Management and Research, Faculty of Economics and Business Administration, University of Duisburg-Essen, Essen, GermanyIntroduction: In Europe a disease is recognized as rare if less than 1 in 2000 people suffer from the specific disease. In patients with familial homozygous hypercholesterolemia (HoFH the accumulation of low-density lipoprotein cholesterol (LDL-C leads to generalized atherosclerosis due to an insufficient functioning of the LDL-C receptors. Patients die early sometimes even in the mid-30s, from myocardial infarction or stroke. For the German population, insufficient epidemiological evidence exists.Methods: A systematic literature search in EMBASE and Medline was performed in conjunction with a targeted manual search for epidemiological HoFH studies. Additionally a nationwide survey was conducted in Germany in all identified apheresis- and lipid centers. The purpose of the survey was the validation of the systematic literature search results based on empirical (practice data.Results: In total 961 publications were found, 874 were excluded based on pre-defined exclusion criteria leaving only 87 for further review. After review of the identified abstracts (n = 87 23 publications were identified as epidemiological studies. Only one publication was found which reported a prevalence of 1:1,000,000. The qualitative survey among 187 physicians in Germany also revealed a low prevalence: 95 HoFH patients were identified in 35 centers.Conclusion: The estimated frequency of homozygous familial hypercholesterolemia patients in Germany is around 95 (1:860,000 and the disease should be recognized as rare according to the definition of the European Medical Agency.Keywords: epidemiology, homozygous

Magnetic resonance imaging of Achilles tendon xanthomas in familial hypercholesterolemia

International Nuclear Information System (INIS)

Liem, M.S.L.; Bloem, J.L.; Schipper, J.

1992-01-01

The demonstration of tendon xanthomas is helpful in diagnosing heterozygous familial hypercholesterolemia. We investigated the possibility the lipid element with magnetic resonance (MR) imaging in seven patients with familial hypercholesterolemia and six controls. Although the mean relative signal intensities measured on long TR/TE spin echo sequences of the tendon were significantly higher in patients than in controls, the lack of such elevation does not rule out the presence of such lesions. MR imaging and US provide equal information on the anatomy of the Achilles tendon; as an abnormally increased signal intensity within the xanthoma on MRI was found in only a minority of our patients, the value of MRI in the demonstration of Achilles tendon xanthomas is limited when using conventional T1 and T2 spin echo sequences. (orig./DG)

Endogenous glucocorticoids exacerbate cholestasis-associated liver injury and hypercholesterolemia in mice.

Science.gov (United States)

van der Geest, Rick; Ouweneel, Amber B; van der Sluis, Ronald J; Groen, Albert K; Van Eck, Miranda; Hoekstra, Menno

2016-09-01

Cholestatic liver disease is characterized by a disruption of bile flow, bile acid toxicity, liver injury, and hypercholesterolemia. Relatively high secretion of glucocorticoids by the adrenals has been observed under cholestatic conditions. Here we investigated a contribution of the rise in endogenous glucocorticoids to initial stage cholestasis pathology. Adrenalectomized or sham-operated control C57BL/6 mice were given an oral dose of alpha-naphthylisothiocyanate to induce cholestasis. Adrenalectomy effectively lowered plasma corticosterone levels (18±5ng/ml vs 472±58ng/ml; Phypercholesterolemia. In conclusion, we have shown that endogenous glucocorticoids exacerbate the liver injury and hypercholesterolemia associated with acute cholestasis in mice. Copyright © 2016 Elsevier Inc. All rights reserved.

Premature cardiovascular disease in young women with heterozygous familial hypercholesterolemia

NARCIS (Netherlands)

van der Graaf, Anouk; Hutten, Barbara A.; Kastelein, John J. P.; Vissers, Maud N.

2006-01-01

Heterozygous familial hypercholesterolemia is associated with elevated low-density lipoprotein cholesterol levels and the development of premature cardiovascular disease. Despite this general statement, data regarding the incidence of cardiovascular disease in young women with familial

Retrospective analysis of cohort database: Phenotypic variability in a large dataset of patients confirmed to have homozygous familial hypercholesterolemia

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Frederick J. Raal

2016-06-01

Full Text Available These data describe the phenotypic variability in a large cohort of patients confirmed to have homozygous familial hypercholesterolemia. Herein, we describe the observed relationship of treated low-density lipoprotein cholesterol with age. We also overlay the low-density lipoprotein receptor gene (LDLR functional status with these phenotypic data. A full description of these data is available in our recent study published in Atherosclerosis, “Phenotype Diversity Among Patients With Homozygous Familial Hypercholesterolemia: A Cohort Study” (Raal et al., 2016 [1].

Carotid atherosclerosis progression in familial hypercholesterolemia patients: A pooled analysis of the ASAP, ENHANCE, RADIANCE 1, and CAPTIVATE studies

NARCIS (Netherlands)

M. Vergeer (Menno); R. Zhou (Rong); M.L. Bots (Michiel); R. Duivenvoorden (Raphaël); J. Koglin (Jörg); F. Akdim (Fatima); Y.B. Mitchel (Yale); R. Huijgen (Roeland); A. Sapre (Aditi); E. de Groot (Eric); E.J.G. Sijbrands (Eric); R.C. Pasternak (Richard); C. Gagné (Claude); A.D. Marais (David); C. Ballantyne (Christie); J.L. Isaacsohn (Jonathan); A.F. Stalenhoef (Anton); J.J.P. Kastelein (John)

2010-01-01

textabstractBackground-Until recently, patients with heterozygous familial hypercholesterolemia (HeFH) were considered the best subjects for the assessment of changes in carotid intima-media thickness (cIMT) in randomized intervention trials. Our aims were to investigate whether contemporary

Evidence for a partial deficiency of the LDL (apo B,E) receptor within a family of rhesus monkeys with a spontaneous hypercholesterolemia

International Nuclear Information System (INIS)

Scanu, A.M.; Khalil, A.; Tidore, M.; Kaiser, M.; Pfaffinger, D.; Carey, D.; Dawson, G.

1987-01-01

Spontaneous hypercholesterolemia is rare among non-human primates. Through screening of a rhesus monkey colony they have identified a family in which 3 out of its 6 members have a persistent hypercholesterolemia on a cholesterol-free Purina Chow diet and are high responders to a dietary fat challenge. On a basal diet the 3 affected animals also exhibited high plasma levels of LDL and apoB. To shed light on the mechanism of the hypercholesterolemia they have grown in culture fibroblasts from skin biopsies obtained from all members of the rhesus monkey family and 12 control. Binding studies at 4 0 C and ligand blotting experiments using 125 I-LDL of either normolipidemic rhesus monkeys or human subjects have shown that the fibroblasts from the 3 monkeys with a spontaneous hypercholesterolemia have a significant reduction of the number of LDL receptor and to the same extent as fibroblasts derived from subjects with heterozygous FH studied at the same time. The data suggest that the spontaneous elevation of plasma cholesterol observed in the 3 family members is related, at least in part, to a defective uptake of LDL by the LDL receptor pathway

Whole plant based treatment of hypercholesterolemia with Crataegus laevigata in a zebrafish model

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Littleton Robert M

2012-07-01

Full Text Available Abstract Background Consumers are increasingly turning to plant-based complementary and alternative medicines to treat hypercholesterolemia. Many of these treatments are untested and their efficacy is unknown. This multitude of potential remedies necessitates a model system amenable to testing large numbers of organisms that maintains similarity to humans in both mode of drug administration and overall physiology. Here we develop the larval zebrafish (4–30 days post fertilization as a vertebrate model of dietary plant-based treatment of hypercholesterolemia and test the effects of Crataegus laevigata in this model. Methods Larval zebrafish were fed high cholesterol diets infused with fluorescent sterols and phytomedicines. Plants were ground with mortar and pestle into a fine powder before addition to food. Fluorescent sterols were utilized to optically quantify relative difference in intravascular cholesterol levels between groups of fish. We utilized the Zeiss 7-Live Duo high-speed confocal platform in order to both quantify intravascular sterol fluorescence and to capture video of the heart beat for determination of cardiac output. Results In this investigation we developed and utilized a larval zebrafish model to investigate dietary plant-based intervention of the pathophysiology of hypercholesterolemia. We found BODIPY-cholesterol effectively labels diet-introduced intravascular cholesterol levels (P t-test. We also established that zebrafish cardiac output declines as cholesterol dose increases (difference between 0.1% and 8% (w/w high cholesterol diet-treated cardiac output significant at P  Conclusions The results of this study demonstrate that the larval zebrafish has the potential to become a powerful model to test plant based dietary intervention of hypercholesterolemia. Using this model we have shown that hawthorn leaves and flowers have the potential to affect cardiac output as well as intravascular cholesterol levels

Carotid atherosclerosis progression in familial hypercholesterolemia patients: a pooled analysis of the ASAP, ENHANCE, RADIANCE 1, and CAPTIVATE studies.

NARCIS (Netherlands)

Vergeer, M.; Zhou, R.; Bots, M.L.; Duivenvoorden, R.; Koglin, J.; Akdim, F.; Mitchel, Y.B.; Huijgen, R.; Sapre, A.; Groot, E. de; Sijbrands, E.J.; Pasternak, R.C.; Gagne, C.; Marais, A.D.; Ballantyne, C.M.; Isaacsohn, J.L.; Stalenhoef, A.F.H.; Kastelein, J.J.

2010-01-01

BACKGROUND: Until recently, patients with heterozygous familial hypercholesterolemia (HeFH) were considered the best subjects for the assessment of changes in carotid intima-media thickness (cIMT) in randomized intervention trials. Our aims were to investigate whether contemporary statin-treated

Effect Of GAMMA Irradiated Thyme As Natural Antioxidant On Hypercholesterolemia Senile Rats

International Nuclear Information System (INIS)

El-Shahat, A.N.; Hamza, R.G.

2011-01-01

Hypercholesterolemia, high cholesterol diet and oxidative stress increase serum total cholesterol and LDL-cholesterol levels resulting in increased risk for development of atherosclerosis. Thyme (as antioxidant) has been commonly used in foods mainly for the flavour and preservation and also as herbal medicinal products. Antioxidants play an important role in inhibiting and scavenging free radicals, thus, providing protection to humans against infectious and degenerative diseases. This study was carried out to determine the effect of using thyme as supplement on serum levels of lipids, glucose and lipid peroxidation in hypercholesterolemia senile rats. GC-MS analysis of essential oil showed that the number of identified compounds was 12, especially thymol and carvacrol (natural antioxidants). Senile male rats were fed on hypercholesterolemia diet (HCD) containing cholesterol (1% w/w) and sodium cholate (0.2% w/w). Twenty eight male rats were equally and randomly categorized into four groups. Rats of group (1) fed on balanced commercial diet, group (2) fed on high cholesterol diet for 8 weeks, groups (3) and (4) fed on high cholesterol diet supplemented with either raw or irradiated thyme (1% w/w) for 8 weeks. The results obtained revealed that rats fed on high cholesterol diet significantly showed increase in serum total lipids, TG, TC, LDL-C, VLDL-C as well as ratio risk, associated with remarkable decrease in HDL-C. A significant increase was observed in the level of lipid peroxidation (TBARS) associated with significant decrease in hepatic antioxidant enzymes (glutathion reductase; GSH and catalase; CAT) and total antioxidant capacity. Also, high cholesterol diet induced significant elevation in the level of glucose and liver enzymes (AST, ALT, ALP). The results obtained revealed that feeding rats on HCD containing either raw or irradiated thyme (1% w/w) induced significant improvement in the mentioned parameters. Also, the thyme suppressed lipid peroxidation

Experiences of guilt and shame in patients with familial hypercholesterolemia: a qualitative interview study

DEFF Research Database (Denmark)

Frich, J.C.; Malterud, K.; Fugelli, P.

2007-01-01

professionals who they felt had a moralizing attitude when counseling on lifestyle and diets. One group took this as a sign of care. Another group conveyed experiences of being humiliated in consultations. CONCLUSION: Patients with familial hypercholesterolemia may experience guilt and shame related to how...... they manage their condition. Health professionals' counseling about lifestyle and diet may induce guilt and shame in patients. PRACTICE IMPLICATIONS: Health professionals should be sensitive to a patient's readiness for counseling in order to diminish the risk of unintentionally inducing guilt and shame...

Elevated Atherosclerosis-Related Gene Expression, Monocyte Activation and Microparticle-Release Are Related to Increased Lipoprotein-Associated Oxidative Stress in Familial Hypercholesterolemia

DEFF Research Database (Denmark)

Hjuler Nielsen, Morten; Irvine, Helle; Vedel, Simon

2015-01-01

OBJECTIVE: Animal and in vitro studies have suggested that hypercholesterolemia and increased oxidative stress predisposes to monocyte activation and enhanced accumulation of oxidized LDL cholesterol (oxLDL-C) through a CD36-dependent mechanism. The aim of this study was to investigate the hypoth......OBJECTIVE: Animal and in vitro studies have suggested that hypercholesterolemia and increased oxidative stress predisposes to monocyte activation and enhanced accumulation of oxidized LDL cholesterol (oxLDL-C) through a CD36-dependent mechanism. The aim of this study was to investigate...... in subjects with heterozygous familial hypercholesterolemia (FH), in particular in the presence of Achilles tendon xanthomas (ATX). APPROACH AND RESULTS: We studied thirty FH subjects with and without ATX and twenty-three healthy control subjects. Intima-media thickness (IMT) and Achilles tendon (AT......LDL-C-CD36 interaction was increased in FH, especially in ATX+ subjects. Monocyte chemokine receptor CX3CR1 was identified as an independent contributor to IMT. CONCLUSIONS: Our data support that lipoprotein-associated oxidative stress is involved in accelerated atherosclerosis in FH, particularly...

Carotid Atherosclerosis Progression in Familial Hypercholesterolemia Patients A Pooled Analysis of the ASAP, ENHANCE, RADIANCE 1, and CAPTIVATE Studies

NARCIS (Netherlands)

Vergeer, Menno; Zhou, Rong; Bots, Michiel L.; Duivenvoorden, Raphaël; Koglin, Joerg; Akdim, Fatima; Mitchel, Yale B.; Huijgen, Roeland; Sapre, Aditi; de Groot, Eric; Sijbrands, Eric J. G.; Pasternak, Richard C.; Gagné, Claude; Marais, A. David; Ballantyne, Christie M.; Isaacsohn, Jonathan L.; Stalenhoef, Anton F. H.; Kastelein, John J. P.

2010-01-01

Background-Until recently, patients with heterozygous familial hypercholesterolemia (HeFH) were considered the best subjects for the assessment of changes in carotid intima-media thickness (cIMT) in randomized intervention trials. Our aims were to investigate whether contemporary statin-treated HeFH

Endogenous glucocorticoids exacerbate cholestasis-associated liver injury and hypercholesterolemia in mice

International Nuclear Information System (INIS)

Geest, Rick van der; Ouweneel, Amber B.; Sluis, Ronald J. van der; Groen, Albert K.; Van Eck, Miranda; Hoekstra, Menno

2016-01-01

Cholestatic liver disease is characterized by a disruption of bile flow, bile acid toxicity, liver injury, and hypercholesterolemia. Relatively high secretion of glucocorticoids by the adrenals has been observed under cholestatic conditions. Here we investigated a contribution of the rise in endogenous glucocorticoids to initial stage cholestasis pathology. Adrenalectomized or sham-operated control C57BL/6 mice were given an oral dose of alpha-naphthylisothiocyanate to induce cholestasis. Adrenalectomy effectively lowered plasma corticosterone levels (18 ± 5 ng/ml vs 472 ± 58 ng/ml; P < 0.001) and disrupted the metabolic and anti-inflammatory glucocorticoid function. Adrenal removal did not exacerbate the cholestasis extent. In contrast, the cholestasis-associated liver injury was markedly lower in adrenalectomized mice as compared to controls as evidenced by a 84%–93% decrease in liver necrosis and plasma alanine aminotransferase and bile acid levels (P < 0.001 for all). Gene expression analysis on livers from adrenalectomized mice suggested the absence of bile acid toxicity-associated farnesoid X receptor signaling in the context of a 44% (P < 0.01) and 82% (P < 0.001) reduction in sodium/bile acid cotransporter member 1 transcript level as compared to respectively control and non-diseased mice. Adrenalectomy reduced the expression of the cholesterol synthesis gene HMG-CoA reductase by 70% (P < 0.05), which translated into a 73% lower plasma total cholesterol level (P < 0.05). Treatment of C57BL/6 mice with the glucocorticoid receptor antagonist RU-486 recapitulated the protective effect of adrenalectomy on indices of liver injury and hypercholesterolemia. In conclusion, we have shown that endogenous glucocorticoids exacerbate the liver injury and hypercholesterolemia associated with acute cholestasis in mice. - Highlights: • Cholestasis is associated with increased plasma glucocorticoid levels in mice. • Adrenalectomy lowers cholestasis-associated liver

Endogenous glucocorticoids exacerbate cholestasis-associated liver injury and hypercholesterolemia in mice

Energy Technology Data Exchange (ETDEWEB)

Geest, Rick van der, E-mail: r.van.der.geest@lacdr.leidenuniv.nl [Leiden Academic Centre for Drug Research (Netherlands); Ouweneel, Amber B., E-mail: a.b.ouweneel@lacdr.leidenuniv.nl [Leiden Academic Centre for Drug Research (Netherlands); Sluis, Ronald J. van der, E-mail: r.vandersluis@lacdr.leidenuniv.nl [Leiden Academic Centre for Drug Research (Netherlands); Groen, Albert K., E-mail: a.k.groen@umcg.nl [University Medical Center Groningen (Netherlands); Van Eck, Miranda, E-mail: m.eck@lacdr.leidenuniv.nl [Leiden Academic Centre for Drug Research (Netherlands); Hoekstra, Menno, E-mail: hoekstra@lacdr.leidenuniv.nl [Leiden Academic Centre for Drug Research (Netherlands)

2016-09-01

Cholestatic liver disease is characterized by a disruption of bile flow, bile acid toxicity, liver injury, and hypercholesterolemia. Relatively high secretion of glucocorticoids by the adrenals has been observed under cholestatic conditions. Here we investigated a contribution of the rise in endogenous glucocorticoids to initial stage cholestasis pathology. Adrenalectomized or sham-operated control C57BL/6 mice were given an oral dose of alpha-naphthylisothiocyanate to induce cholestasis. Adrenalectomy effectively lowered plasma corticosterone levels (18 ± 5 ng/ml vs 472 ± 58 ng/ml; P < 0.001) and disrupted the metabolic and anti-inflammatory glucocorticoid function. Adrenal removal did not exacerbate the cholestasis extent. In contrast, the cholestasis-associated liver injury was markedly lower in adrenalectomized mice as compared to controls as evidenced by a 84%–93% decrease in liver necrosis and plasma alanine aminotransferase and bile acid levels (P < 0.001 for all). Gene expression analysis on livers from adrenalectomized mice suggested the absence of bile acid toxicity-associated farnesoid X receptor signaling in the context of a 44% (P < 0.01) and 82% (P < 0.001) reduction in sodium/bile acid cotransporter member 1 transcript level as compared to respectively control and non-diseased mice. Adrenalectomy reduced the expression of the cholesterol synthesis gene HMG-CoA reductase by 70% (P < 0.05), which translated into a 73% lower plasma total cholesterol level (P < 0.05). Treatment of C57BL/6 mice with the glucocorticoid receptor antagonist RU-486 recapitulated the protective effect of adrenalectomy on indices of liver injury and hypercholesterolemia. In conclusion, we have shown that endogenous glucocorticoids exacerbate the liver injury and hypercholesterolemia associated with acute cholestasis in mice. - Highlights: • Cholestasis is associated with increased plasma glucocorticoid levels in mice. • Adrenalectomy lowers cholestasis-associated liver

Six years of treatment with the HELP system of a patient with familial hypercholesterolemia

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Nascimento M.M.

2002-01-01

Full Text Available The purpose of the present report is to demonstrate the long-term efficacy and safety of heparin-induced extracorporeal lipoprotein precipitation (HELP of LDL-c and fibrinogen in the management of familial hypercholesterolemia. From June 1992 to June 1998 a 22-year-old young male patient with familial hypercholesterolemia (double heterozygote for C660X and S305C resistant to medication and diet and with symptomatic coronary artery disease (angina was treated weekly with 90-min sessions of the HELP system. The patient had also been previously submitted to right coronary artery angioplasty. The efficacy of the method was evaluated by comparing the reduction of total cholesterol, LDL-c and fibrinogen before and after the sessions and before and after initiation of the study (data are reported as averages for each year. During the study, angina episodes disappeared and there were no detectable adverse effects of the treatment. Total cholesterol (TC, fibrinogen, and LDL-c decreased significantly after each session by 59.6, 66.1 and 64%, respectively. HDL-c showed a nonsignificant reduction of 20.4%. Comparative mean values pre- and post-treatment values in the study showed significant differences: TC (488 vs 188 mg/dl, LDL-c (416.4 vs 145 mg/dl, and fibrinogen (144.2 vs 57.4 mg/dl. There was no significant change in HDL-c level: 29.4 vs 23 mg/dl. These data show that the HELP system, even for a long period of time, is a safe and efficient mode of treatment of familial hypercholesterolemia and is associated with disappearance of angina symptoms.

Use of targeted exome sequencing in genetic diagnosis of Chinese familial hypercholesterolemia.

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Wen-Feng Wu

Full Text Available Familial hypercholesterolemia is an autosomal dominant inherited disease characterized by elevated plasma low-density lipoprotein cholesterol (LDL-C. It is mainly caused by mutations of the low-density lipoprotein receptor (LDLR gene. Currently, the methods of whole genome sequencing or whole exome sequencing for screening mutations in familial hypercholesterolemia are not applicable in China due to high cost. We performed targeted exome sequencing of 167 genes implicated in the homozygous phenotype of a proband pedigree to identify candidate mutations, validated them in the family of the proband, studied the functions of the mutant protein, and followed up serum lipid levels after treatment. We discovered that exon 9 c.1268 T>C and exon 8 c.1129 T>G compound heterozygous mutations in the LDLR gene in the proband derived from the mother and father, respectively, in which the mutation of c.1129 T>G has not been reported previously. The mutant LDL-R protein had 57% and 52% binding and internalization functions, respectively, compared with that of the wild type. After 6 months of therapy, the LDL-C level of the proband decreased by more than 50% and the LDL-C of the other family members with heterozygous mutation also reduced to normal. Targeted exome sequencing is an effective method for screening mutation genes in familial hypercholesterolemia. The exon 8 and 9 mutations of the LDLR gene were pedigree mutations. The functions of the mutant LDL-R protein were decreased significantly compared with that of the wild type. Simvastatin plus ezetimibe was proven safe and effective in this preschool-age child.

Effects of hypercholesterolemia of renal hemodynamics: study in patients with nephrotic syndrome.

Science.gov (United States)

Fuiano, G; Esposito, C; Sepe, V; Colucci, G; Bovino, M; Rosa, M; Balletta, M; Bellinghieri, G; Conte, G; Cianciaruso, B; Dal Canton, A

1996-01-01

Experimental and clinical studies have demonstrated a positive relationship between hyperlipidemia and rate of progression of renal disease, suggesting that lipids can induce or aggravate glomerular injury mainly by interacting with mesangial cells. Nevertheless, recently has been demonstrated that increased cholesterol levels can also induce endothelial cell dysfunction. Thus, since endothelium is known to play a major role in modulating the vascular tone, we have tested the possibility that hypercholesterolemia impairs the renal hemodynamics in patients with active nephrotic syndrome and elevated serum cholesterol levels. In this single-blind, nonrandom study, 12 patients were treated with pravastatin (group T, treated, n = 12) and 8 with placebo (group C, controls, n = 8). The controls were studied after the pravastatin group had been completed. Before starting the treatment the patients underwent basal determinations including routine laboratory investigations and PAH and inulin clearances. The same determinations were repeated after 48 h, and 6 and 12 weeks from the beginning of the treatment. The study at 48 h was performed to see if pravastatin had a direct, cholesterol-independent effect on renal function. The following basal results were reported (mean +/- SEM; group T vs. group C): serum cholesterol (mmol/l) 9.7 +/- 0.4 vs. 9.1 +/- 0.3 (NS); proteinuria (g/24 h): 6.2 +/- 0.2 vs. 7.0 +/- 0.7 (NS); PAH clearance (ml/min): 353 +/- 21 vs. 385 +/- 31 (NS); inulin clearance (ml/min): 62.5 +/- 7.7 vs. 67 +/- 9.3 (NS). After 48 h, no changes were observed in both groups. Subsequently, in group T, the following percentage changes of basal levels were observed: serum cholesterol -21.4 +/- 3.2% at 6 weeks (p < 0.05) and -34.9 +/- 3.2% at 12 weeks (p < 0.01); inulin clearance +3 +/- 3.7% at 6 weeks (NS) and +9.3 +/- 2.9% at 12 weeks (p < 0.05); PAH clearance +7 +/- 3.1% at 6 weeks (p < 0.05) and +21.2 +/- 5.5% at 12 weeks (p < 0.01). By contrast, no significant

Atherogenic lipoprotein particle size and concentrations and the effect of pravastatin in children with familial hypercholesterolemia

NARCIS (Netherlands)

van der Graaf, Anouk; Rodenburg, Jessica; Vissers, Maud N.; Hutten, Barbara A.; Wiegman, Albert; Trip, Mieke D.; Stroes, Erik S. G.; Wijburg, Frits A.; Otvos, James D.; Kastelein, John J. P.

2008-01-01

OBJECTIVE: To determine lipoprotein particle concentrations and size in children with familial hypercholesterolemia (FH) and investigate the effect of pravastatin therapy on these measures. STUDY DESIGN: Lipoprotein particle concentrations and sizes were examined by nuclear magnetic resonance (NMR)

Hypercholesterolemia Increases the Production of Leukotriene B4 in Neutrophils by Enhancing the Nuclear Localization of 5-Lipoxygenase

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Xiao-Feng Lai

2014-11-01

Full Text Available Aims: Neutrophils can synthesize leukotriene B4 (LTB4 by activating the 5-lipoxygenase (5-LOsignaling pathway. LTB4 is a pro-inflammatory mediator associated with the etiology and progression of atherosclerosis. It can increase function and number of neutrophils in an autocrine manner. Since hypercholesterolemia is associated with an increase in the number and function of neutrophils, we hypothesized that this effect could be mediated through increased production of LTB4 in neutrophils. Methods/Results: Hypercholesterolemia was modeled in Wistar rats by feeding them with a high cholesterol diet. The induction of hypercholesterolemia caused an increase in the plasma levels of LTB4, following lipopolysaccharide stimulation. This effect was recapitulated in vitro, both in the presence and absence of stimulation with the activator of 5-LO, A23187. Neutrophils in hypercholesterolemia rats expressed similar total levels of 5-LO as control rats, but displayed increased nuclear localization of 5-LO, as well as elevated levels of phosphorylated 5-LO and ERK1/2. In vitro, MβCD/cholesterol complexes enriched cholesterol in neutrophils, resulted in similar changes in 5-LO/LTB4. In addition, these alterations could be inhibited with the ERK inhibitor PD98059. Conclusion: Hypercholesterolemia increases LTB4 production in neutrophils by increasing the nuclear localization of 5-LO, which is the result of its phosphorylation by activated ERK1/2.

Complement regulation in murine and human hypercholesterolemia and role in the control of macrophage and smooth muscle cell proliferation.

Science.gov (United States)

Verdeguer, Francisco; Castro, Claudia; Kubicek, Markus; Pla, Davinia; Vila-Caballer, Marian; Vinué, Angela; Civeira, Fernando; Pocoví, Miguel; Calvete, Juan José; Andrés, Vicente

2007-11-01

Mounting evidence suggests that activation of complement, an important constituent of innate immunity, contributes to atherosclerosis. Here we investigated the expression of complement components (CCs) in the setting of experimental and clinical hypercholesterolemia, a major risk factor for atherosclerosis, their effects on vascular smooth muscle cell (VSMC) and macrophage proliferation, and the underlying molecular mechanisms. For this study we analyzed the mRNA and protein expression of several CCs in plasma and aorta of hypercholesterolemic atherosclerosis-prone apolipoprotein E-null mice (apoE-KO) and in plasma of normocholesterolemic subjects and familial hypercholesterolemia (FH) patients. We also carried out in vitro molecular studies to assess the role of CCs on the control of macrophage and VSMC proliferation. Fat-fed apoE-KO mice experiencing severe hypercholesterolemia (approximately 400 mg/dL), but not fat-fed wild-type controls with plasma cholesterol levelfeeding when hypercholesterolemia was manifested yet atherosclerotic lesions were absent or incipient. Rapid C3 and C4 protein upregulation was also observed in the plasma of fat-fed apoE-KO mice, and FH patients exhibited higher plasmatic C3a, C4 gamma chain, C1s and C3c alpha chain protein levels than normocholesterolemic subjects. In vitro, C3 and C3a, but not C3a-desArg, C4 and C1q, promoted macrophage and VSMC proliferation through Gi protein-dependent activation of extracellular signal-regulated kinase 1/2 (ERK1/2). We also found that C3-enriched FH plasma evoked a stronger mitogenic response in macrophages than normocholesterolemic plasma, and treatment with anti-C3 antibodies eliminated this difference. Both experimental and clinical hypercholesterolemia coincides with a concerted activation of several CCs. However, only C3 and C3a elicited a mitogenic response in cultured VSMCs and macrophages through Gi protein-dependent ERK1/2 activation. Thus, excess of C3/C3a in hypercholesterolemic apo

Familial hypercholesterolemia with multiple cutaneous xanthomas

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Reddy BSN

2006-01-01

Full Text Available An interesting episode of homozygous familial hypercholesterolemia affecting four children born to a consanguinous parents belonging to two different families is reported for its rarity. The patients had multiple cutaneous xanthomas including the characteristic xanthoma tendinosum, xanthoma interosseum, xanthoma tuberosum, and xanthelasma palpebrarum. Prominent corneal arcus juvenalis has been noted in three children. Gross elevation of serum levels of low density lipoprotein cholesterol (LDLc with normal values of triglycerides have been found in all patients. They have been prescribed medication with oral tablets of simvastatin and advised fat restricted diet and regular follow up in the clinic at periodic intervals.

Involvement of interleukin-1 in lead nitrate-induced hypercholesterolemia in mice.

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Kojima, Misaki; Ashino, Takashi; Yoshida, Takemi; Iwakura, Yoichiro; Degawa, Masakuni

2012-01-01

Hepatic 3-hydroxy-3-methylglutaryl-CoA reductase (HMGR) and cholesterol 7α-hydroxylase (Cyp7a1) are rate-limiting enzymes for cholesterol biosynthesis and catabolism, respectively. Involvement of inflammatory cytokines, particularly interleukin-1 (IL-1), in alterations of HMGR and Cyp7a1 gene expression during development of lead nitrate (LN)-induced hypercholesterolemia was examined in IL-1α/β-knockout (IL-1-KO) and wild-type (WT) mice. Lead nitrate treatment of WT mice led to not only a marked downregulation of the Cyp7a1 gene at 6-12 h, but also a significant upregulation of the HMGR gene at 12 h. However, such changes were not observed at significant levels in IL-1-KO mice, although a slight, transient downregulation of the Cyp7a1 gene and a minimal upregulation of the HMGR gene occurred at 6 h and 24 h, respectively. Consequently, LN treatment led to development of hypercholesterolemia at 24 h in WT mice, but not in IL-1-KO mice. Furthermore, in WT mice, significant LN-mediated increases were observed at 3-6 h in hepatic IL-1 levels, which can modulate gene expression of Cyp7a1 and HMGR. These findings indicate that, in mice, LN-mediated increases in hepatic IL-1 levels contribute, at least in part, to altered expressions of Cyp7a1 and HMGR genes, and eventually to hypercholesterolemia development.

Plasma lipoprotein(a) levels in patients with homozygous autosomal dominant hypercholesterolemia

NARCIS (Netherlands)

Sjouke, B.; Yahya, R.; Tanck, M.W.T.; Defesche, J.C.; Graaf, J. de; Wiegman, A.; Kastelein, J.J.; Mulder, M.T.; Hovingh, G.K.; Roeters van Lennep, J.E.

2017-01-01

BACKGROUND: Patients with autosomal dominant hypercholesterolemia (ADH), caused by mutations in either low-density lipoprotein receptor (LDLR), apolipoprotein B (APOB), or proprotein convertase subtilisin-kexin type 9 (PCSK9) are characterized by high low-density lipoprotein cholesterol levels and

Comparison of the efficacy and safety of rosuvastatin 10 mg and atorvastatin 20 mg in high-risk patients with hypercholesterolemia – Prospective study to evaluate the Use of Low doses of the Statins Atorvastatin and Rosuvastatin (PULSAR

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García Hugo

2006-12-01

Full Text Available Abstract Background Many patients at high risk of cardiovascular disease do not achieve recommended low-density lipoprotein cholesterol (LDL-C goals. This study compared the efficacy and safety of low doses of rosuvastatin (10 mg and atorvastatin (20 mg in high-risk patients with hypercholesterolemia. Methods A total of 996 patients with hypercholesterolemia (LDL-C ≥ 3.4 and Results Rosuvastatin 10 mg reduced LDL-C levels significantly more than atorvastatin 20 mg at week 6 (44.6% vs. 42.7%, p Conclusion In high-risk patients with hypercholesterolemia, rosuvastatin 10 mg was more efficacious than atorvastatin 20 mg at reducing LDL-C, enabling LDL-C goal achievement and improving other lipid parameters. Both treatments were well tolerated.

Association Between Familial Hypercholesterolemia and Prevalence of Type 2 Diabetes Mellitus

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Besseling, Joost; Kastelein, John J. P.; Defesche, Joep C.; Hutten, Barbara A.; Hovingh, G. Kees

2015-01-01

IMPORTANCE Familial hypercholesterolemia is characterized by impaired uptake of cholesterol in peripheral tissues, including the liver and the pancreas. In contrast, statins increase the cellular cholesterol uptake and are associated with increased risk for type 2 diabetes mellitus. We hypothesize

Plasma lipoprotein(a) levels in patients with homozygous autosomal dominant hypercholesterolemia

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Sjouke, Barbara; Yahya, Reyhana; Tanck, Michael W. T.; Defesche, Joep C.; de Graaf, Jacqueline; Wiegman, Albert; Kastelein, John J. P.; Mulder, Monique T.; Hovingh, G. Kees; Roeters van Lennep, Jeanine E.

2017-01-01

Patients with autosomal dominant hypercholesterolemia (ADH), caused by mutations in either low-density lipoprotein receptor (LDLR), apolipoprotein B (APOB), or proprotein convertase subtilisin-kexin type 9 (PCSK9) are characterized by high low-density lipoprotein cholesterol levels and in some

The prevalence of familial hypercholesterolemia in teenagers from Timișoara

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Andreea Dumitrescu¹,²,

2016-12-01

Full Text Available INTRODUCTION FH is one of the most frequent monogenic cholesterol disorders but its prevalence is not very well documented. Variations between 1/200-1/137 individuals have been reported in adult patients. Due to persistent hypercholesterolemia, these patients are exposed to a high risk of developing early cardiovascular disease. Although cardiovascular events usualy occur in early adulthood, the atherosclerotic prosess asymtomaticlaly commences in childhood. OBJECTIVES study aims to uncover the prevalence of dyslipidemia in teenagers from Timișoara MATERIALS AND METHODS We have conducted an epidemiological study between March and June 2016 on 318 children aged between 10-11 years old (4-th grade.We have tested the lipid profile ( total cholesterol, LDL cholesterol, HDL cholesterol, triglycerides from capillary blood using a point of care LipidoCare Analyzer. RESULTS Out of 318 children included in our study 242 (76,1% had a normal lipid profile, 56 (17,1% had mild hypercholesterolemia( LDL cholesterol values ranging between 130-160 mg/dl, 12 (3,77% had severe hypercholesterolemia (LDL cholesterol values were over 160 mg/dl and 8 (2,51% children had hypertriglyceridemia. Out of this group, 2 children (0,62%-1/159 had LDL cholesterol values over 190 mg/dl, which indicates a high probability of FH. CONCLUSIONS The prevalence of dyslipidemia in the studied group was similar to the scientific data reported in literature. Although this screeening is the first of it’s kind in Romania and was conducted on a large group of subjects, the results cannot be generalized. Further studies are needed in order to establish the etiology of dyslipidemia and it’s prevalence in romanian teenagers. REFERENCES 1.Wiegman A, ,Gidding SS, Watts GF et al. European Atherosclerosis Society Consensus Panel. Familial hypercholesterolaemia in children and adolescents: gaining decades of life by optimizing detection and treatment. Eur Heart J. 2015;36:2425-37. 2.Børge G

Linseed oil increases HDL3 cholesterol and decreases blood pressure in patients diagnosed with mild hypercholesterolemia.

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Skoczyńska, Anna H; Gluza, Ewa; Wojakowska, Anna; Turczyn, Barbara; Skoczyńska, Marta

2018-04-24

Linseed oil has cardio-protective effects. However, its antihypertensive action has not yet been well characterized. The primary purpose of the study was to evaluate the effect of short-term dietary supplementation with linseed oil on blood pressure (BP) and lipid metabolism in patients with mild hypercholesterolemia. The secondary aim was to evaluate the effect of linseed oil on nitric oxide pathway and selected serum trace metals. 150 volunteers: 43 men (49.9±11.5 years) and 107 women (53.2±10.3 years), diagnosed with mild hypercholesterolemia, were assessed prospectively for BP and lipids' levels, before and after lipid-lowering diet plus linseed oil supplementation at a dose of 15 ml daily for 4 weeks (study groups) or 4-weekly lipid-lowering diet (control group). The multivariate logistic regression analysis model was used to determine the effect of linseed oil on BP after adjustment for age, gender, height, body weight, BMI, smoking and alcohol consumption. The supplementation with linseed oil significantly decreased LDL- and non-HDL cholesterol, and increased HDL- and HDL₃- cholesterol levels. Additionally, linseed oil decreased diastolic BP in men (CI:-6.0;-1.1, poil reduced (poil consumption was associated with a decrease in mean BP (aOR 3.85, 95%CI 1.32-11.33). Our findings confirm the benefit of short-term linseed oil use in mild hypercholesterolemia, in particular in patients with increased blood pressure.

Statin treatment in children with familial hypercholesterolemia - The younger, the better

NARCIS (Netherlands)

Rodenburg, Jessica; Vissers, Maud N.; Wiegman, Albert; van Trotsenburg, A. S. Paul; van der Graaf, Anouk; de Groot, Eric; Wijburg, Frits A.; Kastelein, John J. P.; Hutten, Barbara A.

2007-01-01

Background - We previously demonstrated in a randomized placebo- controlled trial that 2-year pravastatin treatment induced a significant regression of carotid intima-media thickness (IMT) in 8- to 18-year-old children with familial hypercholesterolemia. Subsequently, we continued to follow up these

Marketed drugs used for the management of hypercholesterolemia as anticancer armament

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Papanagnou P

2017-09-01

Full Text Available Panagiota Papanagnou,1 Theodora Stivarou,2 Ioannis Papageorgiou,1 Georgios E Papadopoulos,3 Anastasios Pappas1 1Department of Urology, Agios Savvas Cancer Hospital, Athens, Greece; 2Immunology Laboratory, Immunology Department, Hellenic Pasteur Institute, Athens, Greece; 3Department of Biochemistry and Biotechnology, University of Thessaly, Larissa, Greece Abstract: The design of novel pharmacologic agents as well as their approval for sale in markets all over the world is a tedious and pricey process. Inevitably, oncologic patients commonly experience unwanted effects of new anticancer drugs, while the acquisition of clinical experience for these drugs is largely based on doctor–patient partnership which is not always effective. The repositioning of marketed non-antineoplastic drugs that hopefully exhibit anticancer properties into the field of oncology is a challenging option that gains ground and attracts preclinical and clinical research in an effort to override all these hindrances and minimize the risk for reduced efficacy and/or personalized toxicity. This review aims to present the anticancer properties of drugs used for the management of hypercholesterolemia. A global view of the antitumorigenicity of all marketed antihypercholesterolemic drugs is of major importance, given that atherosclerosis, which is etiologically linked to hypercholesterolemia, is a leading worldwide cause of morbidity and mortality, while hypercholesterolemia and tumorigenesis are known to be interrelated. In vitro, in vivo and clinical literature data accumulated so far outline the mechanistic basis of the antitumor function of these agents and how they could find application at the clinical setting. Keywords: antihypercholesterolemic agents, cancer, synergism, repurposing

Unusual xanthomas in a young patient with heterozygous familial hypercholesterolemia and type III hyperlipoproteinemia

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Feussner, G.; Dobmeyer, J. [Univ. of Heidelberg (Germany); Nissen, H.; Hansen, T.S. [Odense Univ. Hospital (Denmark)

1996-10-16

We report on a 20-year-old man with the combination of two independent familial lipoprotein disorders: heterozygous familial hypercholesterolemia (FH) and type III hyperlipoproteinemia (HLP). Familial hypercholesterolemia was diagnosed by elevated total and low density lipoprotein cholesterol levels and family history. By denaturing gradient gel electrophoresis, DNA sequencing and restriction fragment length polymorphism analysis, a G{r_arrow}A splice donor mutation in intron 3 of the proband`s low density lipoprotein receptor gene was identified as the underlying molecular defect. This mutation was described previously as a receptor-negative founder mutation in Norway (FH-Elverum) and subsequently in 6 unrelated heterozygous English patients, creating a severe phenotype of familial hypercholesterolemia. Type III HLP was confirmed by homozygosity for apolipoprotein (apo) E2 and an elevated ratio of very low density lipoprotein cholesterol to serum triglycerides (0.40; normal ratio about 0.20). The patient has unusual flat xanthomas in the interdigital webs of the hands which are normally not found in either disease. These dermatological findings might therefore be indicative of the rare combination of both disorders of lipoprotein metabolism in one individual. 29 refs., 5 figs., 1 tab.

Hypercholesterolemia causes psychomotor abnormalities in mice and alterations in cortico-striatal biogenic amine neurotransmitters: Relevance to Parkinson's disease.

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Paul, Rajib; Choudhury, Amarendranath; Chandra Boruah, Dulal; Devi, Rajlakshmi; Bhattacharya, Pallab; Choudhury, Manabendra Dutta; Borah, Anupom

2017-09-01

The symptoms of Parkinson's disease (PD) include motor behavioral abnormalities, which appear as a result of the extensive loss of the striatal biogenic amine, dopamine. Various endogenous molecules, including cholesterol, have been put forward as putative contributors in the pathogenesis of PD. Earlier reports have provided a strong link between the elevated level of plasma cholesterol (hypercholesterolemia) and onset of PD. However, the role of hypercholesterolemia on brain functions in terms of neurotransmitter metabolism and associated behavioral manifestations remain elusive. We tested in Swiss albino mice whether hypercholesterolemia induced by high-cholesterol diet would affect dopamine and serotonin metabolism in discrete brain regions that would precipitate in psychomotor behavioral manifestations. High-cholesterol diet for 12 weeks caused a significant increase in blood total cholesterol level, which validated the model as hypercholesterolemic. Tests for akinesia, catalepsy, swimming ability and gait pattern (increased stride length) have revealed that hypercholesterolemic mice develop motor behavioral abnormalities, which are similar to the behavioral phenotypes of PD. Moreover, hypercholesterolemia caused depressive-like behavior in mice, as indicated by the increased immobility time in the forced swim test. We found a significant depletion of dopamine in striatum and serotonin in cortex of hypercholesterolemic mice. The significant decrease in tyrosine hydroxylase immunoreactivity in striatum supports the observed depleted level dopamine in striatum, which is relevant to the pathophysiology of PD. In conclusion, hypercholesterolemia-induced depleted levels of cortical and striatal biogenic amines reported hereby are similar to the PD pathology, which might be associated with the observed psychomotor behavioral abnormalities. Copyright © 2017 Elsevier Ltd. All rights reserved.

rs11613352 polymorphism (TT genotype) associates with a decrease of triglycerides and an increase of HDL in familial hypercholesterolemia patients.

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Aledo, Rosa; Padró, Teresa; Mata, Pedro; Alonso, Rodrigo; Badimon, Lina

2015-04-01

Recent genome-wide association studies have identified a locus on chromosome 12q13.3 associated with plasma levels of triglyceride and high-density lipoprotein cholesterol, with rs11613352 being the lead single nucleotide polymorphism in this genome-wide association study locus. The aim of the study is to investigate the involvement of rs11613352 in a population with high cardiovascular risk due to familial hypercholesterolemia. The single nucleotide polymorphism was genotyped by Taqman(®) assay in a cohort of 601 unrelated familial hypercholesterolemia patients and its association with plasma triglyceride and high-density lipoprotein cholesterol levels was analyzed by multivariate methods based on linear regression. Minimal allele frequency was 0.17 and genotype frequencies were 0.69, 0.27, and 0.04 for CC, CT, and TT genotypes, respectively. The polymorphism is associated in a recessive manner (TT genotype) with a decrease in triglyceride levels (P=.002) and with an increase in high-density lipoprotein cholesterol levels (P=.021) after adjusting by age and sex. The polymorphism rs11613352 may contribute to modulate the cardiovascular risk by modifying plasma lipid levels in familial hypercholesterolemia patients. Copyright © 2014 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.

Drinking of chokeberry juice from the ecological farm Dzieciolowo and distensibility of brachial artery in men with mild hypercholesterolemia.

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Poreba, Rafal; Skoczynska, Anna; Gac, Pawel; Poreba, Malgorzata; Jedrychowska, Iwona; Affelska-Jercha, Anna; Turczyn, Barbara; Wojakowska, Anna; Oszmianski, Jan; Andrzejak, Ryszard

2009-01-01

The aim of the study was to estimate the influence of drinking chokeberry juice on the endothelial function in men with mild hypercholesterolemia. It was shown that chronic treatment with flavonoids improves vascular function and reduces cardiovascular remodelling by increasing NO release from endothelial cells. A group of 35 men diagnosed with mild hypercholesterolemia (mean age: 53.9 +-5.8 years), with no earlier pharmacological treatment, were enrolled to the study. In all men, assessment of endothelial function, and serum lipids level were carried out at four time points: at the beginning of the studies, after 6 weeks of regular drinking of chokeberry juice, after 6 weeks without drinking the juice, then after repeated 6 weeks of drinking chokeberry juice. During the study, significant decreases in serum total cholesterol, LDL cholesterol and triglycerides levels were observed. A statistically significant increase in serum nitric oxide (NO) concentration and in the flow mediated dilatation (FMD) were observed. At the beginning, FMD > or = 7 % was present in 13 of 35 subjects (37.1 %). After 6 weeks of regular chokeberry juice drinking, FMD > or = 7 % was present in 29 of 35 subjects (82.9 %). However, after 6 weeks abstaining from drinking the juice and repeated exposure to 6 weeks drinking of chokeberry juice, FMD > or = 7 % was present in all studied subjects. Regular drinking of chokeberry juice has a beneficial effect on endothelial function and lipid metabolism in men with mild hypercholesterolemia.

Effects of Atorvastatin on Ventricular Late Potentials and Repolarization Dispersion in Patients with Hypercholesterolemia

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Chih-Sheng Chu

2007-05-01

Full Text Available Emerging evidence suggests that statins have a favorable impact on the reduction of arrhythmia events and sudden cardiac death in patients with structural heart disease. We aimed to investigate the possibly and directly favorable effects of statins on ventricular late potentials, QT dispersion, and transmural dispersion of repolarization attained by analyzing clinical electrocardiography (ECG risk stratification parameters in patients with hypercholesterolemia without structural heart disease. In total, 82 patients (45 females; mean age, 62 ± 10 years with hypercholesterolemia were enrolled in this prospective study to examine the effects of statin therapy (atorvastatin 10mg/day for 3 months on ECG risk stratification parameters. Surface 12-lead ECG and signal-average ECG (SAECG were recorded before and after statin treatment. The SAECG parameters, QT dispersion, Bazett-corrected QT (QTc dispersion, T wave peak-to-end interval (Tpe, and percentage of Tpe/QT interval were calculated and compared before and after statin therapy. Twelve-lead ambulatory 24-hour ECGs were recorded in 12 patients. The results demonstrated that after statin therapy for 3 months, serum levels of total cholesterol and low-density lipoprotein cholesterol were significantly reduced (both p values < 0.001. However, neither significant changes of each SAECG parameter nor the frequency of late potentials were demonstrated after atorvastatin therapy. In addition, no significant changes in QT dispersion, QTc dispersion, Tpe, or Tpe/QT were found. However, 24-hour ambulatory ECG revealed a flattening effect of circadian variation of QTc dispersion after atorvastatin therapy. In conclusion, the favorable antiarrhythmia effect of atorvastatin (10 mg/day therapy cannot be directly reflected by analyzing these noninvasive ECG risk stratification parameters in low-risk patients with hypercholesterolemia.

ABCB4 mediates diet-induced hypercholesterolemia in laboratory opossums.

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Chan, Jeannie; Mahaney, Michael C; Kushwaha, Rampratap S; VandeBerg, Jane F; VandeBerg, John L

2010-10-01

High-responding opossums are susceptible to developing hypercholesterolemia on a high-cholesterol diet, but low-responding opossums are resistant. The observation of low biliary cholesterol and low biliary phospholipids in high responders suggested that the ABCB4 gene affects response to dietary cholesterol. Two missense mutations (Arg29Gly and Ile235Leu) were found in the ABCB4 gene of high responders. High responders (ATHH strain) were bred with low responders (ATHE or ATHL strain) to produce F1 and F2 progeny in two different genetic crosses (KUSH6 and JCX) to determine the effect of ABCB4 allelic variants on plasma cholesterol concentrations after a dietary challenge. Pedigree-based genetic association analyses consistently implicated a variant in ABCB4 or a closely linked locus as a major, but not the sole, genetic contributor to variation in the plasma cholesterol response to dietary cholesterol. High responders, but not low responders, developed liver injury as indicated by elevated plasma biomarkers of liver function, probably reflecting damage to the canalicular membrane by bile salts because of impaired phospholipid secretion. Our results implicate ABCB4 as a major determinant of diet-induced hypercholesterolemia in high-responding opossums and suggest that other genes interact with ABCB4 to regulate lipemic response to dietary cholesterol.

Normal cholesterol levels with lovastatin (Mevinolin) therapy in a child with homozygous familial hypercholesterolemia following liver transplantation

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East, C.; Grundy, S.M.; Bilheimer, D.W.

1986-01-01

Patients with homozygous familial hypercholesterolemia produce no normal low-density lipoprotein (LDL) receptors, and as a result, LDL accumulates in plasma, causing severe premature atherosclerosis. Two years ago, liver transplantation was performed in a child with homozygous familial hypercholesterolemia, restoring LDL receptor activity to about 60% of normal and reducing the LDL cholesterol level by 81%. However, the patient's lipoprotein levels remained significantly elevated for her age and sex. Treatment with lovastatin (mevinolin) one year after transplantation produced a marked improvement in the patient's lipoprotein profile. The total and LDL cholesterol levels fell 40% and 49%, respectively, to values within the normal range. The level of very low-density lipoprotein cholesterol fell 41%, and the level of total triglycerides declined 28%. While lovastatin therapy decreased the production rate of LDL by 35%, it did not affect the LDL fractional clearance rate. Thus, the combination of liver transplantation and lovastatin restored total and LDL cholesterol levels to normal in this patient with homozygous familial hypercholesterolemia

Modulation of cholesterol transport by maternal hypercholesterolemia in human full-term placenta.

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Ran Zhang

Full Text Available The significance of maternal cholesterol transporting to the fetus under normal as well as pathological circumstances is less understood. The objective of this study was to observe the effects of maternal hypercholesterolemia on placental cholesterol transportation. Human full-time placenta, maternal and venous cord blood were sampled at delivery from the pregnant women with serum total cholesterol (TC concentrations at third trimester higher than 7.25 mM (n = 19 and the pregnant women with normal TC concentrations (n = 19. Serum lipids and expression of genes related to cholesterol transportation were measured by western blot or real-time PCR. The results indicated that serum TC, high density lipoprotein cholesterol (HDL-C, and low density lipoprotein cholesterol (LDL-C levels were significantly increased, in pregnancies, but decreased in cord blood in hypercholesterolemic group compared to the matched control group. All the subjects were no-drinking, non-smoker, and gestational disease free. The mRNA expression of lipoprotein receptors, including LDLR and VLDLR were significantly increased, while the protein expression of PCSK9 was significantly increased in hypercholesterolemic placenta. In conclusion, maternal hypercholesterolemia might decrease the transportation of cholesterol from mother to fetus because of the high levels of PCSK9 protein expression.

Hypercholesterolemia Up-Regulates the Expression of Intermedin and Its Receptor Components in the Aorta of Rats via Inducing the Oxidative Stress.

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Meng, Qingtao; Shi, Di; Feng, Jiayue; Su, Yanling; Long, Yang; He, Sen; Wang, Si; Wang, Yong; Zhang, Xiangxun; Chen, Xiaoping

2016-01-01

Hypercholesterolemia can cause damage to the artery. Intermedin (IMD) is a novel member of the calcitonin gene-related peptide family. This study aims to investigate the aortic expression of IMD and its receptors in hypercholesterolemia without atherosclerosis. Male Wistar rats were fed with high cholesterol diet, with or without simvastatin and vitamin C. Both the malondialdehyde (MDA) and superoxide dismutase (SOD) in plasma and aorta were determined as the oxidative stress biomarkers. The plasma IMD was assessed by radioimmunoassay. Within the aorta, the mRNA expression of IMD along with its receptor components was determined, and the corresponding protein level of the CRLR/RAMPs was also assessed. The hypercholesterolemia rats without atherosclerotic lesion manifested a higher level of MDA and SOD and the plasma IMD elevated. Increased expression of IMD and all its receptor components (CRLR, RAMP1, RAMP2, and RAMP3) were displayed within the aorta. The simvastatin indirectly attenuated oxidative stress by improving lipid profiles, while the vitamin C directly reduced oxidative stress without interfering with the serum lipids. Both simvastatin and vitamin C ameliorated the aortic injury, decreased the plasma IMD level, and recovered the expression of IMD and its receptors within the aorta. The up-regulated expression of IMD is observed within the aorta of the hypercholesterolemia rats. In addition, the oxidative stress participates in the up-regulation. © 2016 by the Association of Clinical Scientists, Inc.

EFFECTS OF EXERCISE ON THE PLASMA LIPID PROFILE IN HISPANIOLAN AMAZON PARROTS (AMAZONA VENTRALIS) WITH NATURALLY OCCURRING HYPERCHOLESTEROLEMIA.

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Gustavsen, Kate A; Stanhope, Kimber L; Lin, Amy S; Graham, James L; Havel, Peter J; Paul-Murphy, Joanne R

2016-09-01

Hypercholesterolemia is common in psittacines, and Amazon parrots ( Amazona spp.) are particularly susceptible. Associations have been demonstrated between naturally occurring and experimentally induced hypercholesterolemia and atherosclerosis in psittacines. Daily exercise improves lipid metabolism in humans and other mammals, as well as pigeons and chickens, under varying experimental conditions. Hispaniolan Amazon parrots ( Amazona ventralis ) with naturally occurring hypercholesterolemia (343-576 mg/dl) were divided into two groups. An exercised group (n = 8) was housed as a flock and exercised daily with 30 min of aviary flight and 30 min walking on a rotating perch. A sedentary control group (n = 4) was housed in individual cages with no exercise regime. A plasma lipid panel, including total cholesterol, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol, and triglycerides, was validated for this species. Body weight, chest girth, and the lipid panel were measured at 0, 61, and 105 days. Hematology and plasma biochemistry were measured at 0 and 105 days. Weight and girth were significantly lower in exercised than sedentary parrots at 61 and 105 days. HDL-C concentrations were significantly higher in exercised parrots at 61 days but returned to near baseline by 105 days. There were no significant changes in hematology, biochemistry, or other lipid panel parameters. Results were similar to studies in humans and animal models, in which increased HDL-C was the most consistent effect of exercise on circulating lipid and lipoprotein parameters. The return toward baseline HDL-C may have resulted from decreased participation in aviary flight. Additional investigation will be required to determine the amount of exercise and change in circulating lipid-related parameters necessary to improve long-term wellness in psittacine species predisposed to hypercholesterolemia.

Effect of fixed-dose combinations of ezetimibe plus rosuvastatin in patients with primary hypercholesterolemia: MRS-ROZE (Multicenter Randomized Study of ROsuvastatin and eZEtimibe).

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Kim, Kyung-Jin; Kim, Sang-Hyun; Yoon, Young Won; Rha, Seung-Woon; Hong, Soon-Jun; Kwak, Choong-Hwan; Kim, Weon; Nam, Chang-Wook; Rhee, Moo-Yong; Park, Tae-Ho; Hong, Taek-Jong; Park, Sungha; Ahn, Youngkeun; Lee, Namho; Jeon, Hui-Kyung; Jeon, Dong-Woon; Han, Kyoo-Rok; Moon, Keon-Woong; Chae, In-Ho; Kim, Hyo-Soo

2016-10-01

We aimed to compare the effects of fixed-dose combinations of ezetimibe plus rosuvastatin to rosuvastatin alone in patients with primary hypercholesterolemia, including a subgroup analysis of patients with diabetes mellitus (DM) or metabolic syndrome (MetS). This multicenter eight-week randomized double-blind phase III study evaluated the safety and efficacy of fixed-dose combinations of ezetimibe 10 mg plus rosuvastatin, compared with rosuvastatin alone in patients with primary hypercholesterolemia. Four hundred and seven patients with primary hypercholesterolemia who required lipid-lowering treatment according to the ATP III guideline were randomized to one of the following six treatments for 8 weeks: fixed-dose combinations with ezetimibe 10 mg daily plus rosuvastatin (5, 10, or 20 mg daily) or rosuvastatin alone (5, 10, or 20 mg daily). Fixed-dose combination of ezetimibe plus rosuvastatin significantly reduced LDL cholesterol, total cholesterol, and triglyceride levels compared with rosuvastatin alone. Depending on the rosuvastatin dose, these fixed-dose combinations of ezetimibe plus rosuvastatin provided LDL cholesterol, total cholesterol, and triglyceride reductions of 56%-63%, 37%-43%, and 19%-24%, respectively. Moreover, the effect of combination treatment on cholesterol levels was more pronounced in patients with DM or MetS than in non-DM or non-MetS patients, respectively, whereas the effect of rosuvastatin alone did not differ between DM vs non-DM or MetS vs non-MetS patients. Fixed-dose combinations of ezetimibe and rosuvastatin provided significantly superior efficacy to rosuvastatin alone in lowering LDL cholesterol, total cholesterol, and triglyceride levels. Moreover, the reduction rate was greater in patients with DM or MetS. © 2016 The Authors Cardiovascular Therapeutics Published by John Wiley & Sons Ltd.

Proprotein Convertase Subtilisin Kexin Type 9 Inhibition for Autosomal Recessive Hypercholesterolemia-Brief Report.

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Thedrez, Aurélie; Sjouke, Barbara; Passard, Maxime; Prampart-Fauvet, Simon; Guédon, Alexis; Croyal, Mikael; Dallinga-Thie, Geesje; Peter, Jorge; Blom, Dirk; Ciccarese, Milco; Cefalù, Angelo B; Pisciotta, Livia; Santos, Raul D; Averna, Maurizio; Raal, Frederick; Pintus, Paolo; Cossu, Maria; Hovingh, Kees; Lambert, Gilles

2016-08-01

Proprotein convertase subtilisin kexin type 9 (PCSK9) inhibitors lower low-density lipoprotein (LDL) cholesterol in the vast majority of patients with autosomal dominant familial hypercholesterolemia. Will PCSK9 inhibition with monoclonal antibodies, in particular alirocumab, be of therapeutic value for patients with autosomal recessive hypercholesterolemia (ARH)? Primary lymphocytes were obtained from 28 genetically characterized ARH patients and 11 controls. ARH lymphocytes treated with mevastatin were incubated with increasing doses of recombinant PCSK9 with or without saturating concentrations of alirocumab. Cell surface LDL receptor expression measured by flow cytometry and confocal microscopy was higher in ARH than in control lymphocytes. PCSK9 significantly reduced LDL receptor expression in ARH lymphocytes albeit to a lower extent than in control lymphocytes (25% versus 76%, respectively), an effect reversed by alirocumab. Fluorescent LDL cellular uptake, also measured by flow cytometry, was reduced in ARH lymphocytes compared with control lymphocytes. PCSK9 significantly lowered LDL cellular uptake in ARH lymphocytes, on average by 18%, compared with a 46% reduction observed in control lymphocytes, an effect also reversed by alirocumab. Overall, the effects of recombinant PCSK9, and hence of alirocumab, on LDL receptor expression and function were significantly less pronounced in ARH than in control cells. PCSK9 inhibition with alirocumab on top of statin treatment has the potential to lower LDL cholesterol in some autosomal recessive hypercholesterolemia patients. © 2016 American Heart Association, Inc.

Family history of cardiovascular events and endothelial dysfunction in children with familial hypercholesterolemia

NARCIS (Netherlands)

de Jongh, Saskia; Lilien, Marc R.; Bakker, Henk D.; Hutten, Barbara A.; Kastelein, John J. P.; Stroes, Erik S. G.

2002-01-01

Objectives: in patients with familial hypercholesterolemia (FH), the propensity towards atherosclerosis may vary considerably. In the general population, a positive family history is associated with an increased risk for cardiovascular events. Since endothelial dysfunction is predictive for future

Familial hypercholesterolemia: A review

International Nuclear Information System (INIS)

Varghese, Mithun J

2014-01-01

Familial hypercholesterolemia (FH) is a genetic disorder of lipoprotein metabolism resulting in elevated serum low-density lipoprotein (LDL) cholesterol levels leading to increased risk for premature cardiovascular diseases (CVDs). The diagnosis of this condition is based on clinical features, family history, and elevated LDL-cholesterol levels aided more recently by genetic testing. As the atherosclerotic burden is dependent on the degree and duration of exposure to raised LDL-cholesterol levels, early diagnosis and initiation of treatment is paramount. Statins are presently the mainstay in the management of these patients, although newer drugs, LDL apheresis, and other investigational therapies may play a role in certain subsets of FH, which are challenging to treat. Together these novel treatments have notably improved the prognosis of FH, especially that of the heterozygous patients. Despite these achievements, a majority of children fail to attain targeted lipid goals owing to persistent shortcomings in diagnosis, monitoring, and treatment. This review aims to highlight the screening, diagnosis, goals of therapy, and management options in patients with FH

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

NARCIS (Netherlands)

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

2016-01-01

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

R353Q polymorphism in the factor VII gene and cardiovascular risk in Heterozygous Familial Hypercholesterolemia: a case-control study.

Science.gov (United States)

Criado-García, Juan; Fuentes, Francisco; Cruz-Teno, Cristina; García-Rios, Antonio; Jiménez-Morales, Anabel; Delgado-Lista, Javier; Mata, Pedro; Alonso, Rodrigo; López-Miranda, José; Pérez-Jiménez, Francisco

2011-04-09

Heterozygous Familial Hypercholesterolemia (FH) is a genetic disorder characterized by a high risk of cardiovascular disease. Certain polymorphisms of the factor VII gene have been associated with the development of coronary artery disease and there is a known association between factor VII levels and polymorphic variants in this gene. To date, no study has evaluated the association between factor VII and coronary artery disease in patients with FH. This case-control study comprised 720 patients (546 with FH and 174 controls). We determined the prevalence and allele frequencies of the R353Q polymorphism of factor VII, the plasma levels of factor VII antigen (FVII Ag) and whether they could be predictive factors for cardiovascular risk. 75% (410) of the patients with FH were RR, 23% (127) RQ and 1.6% (9) QQ; in the control group 75.3% (131) were RR, 21.3% (37) RQ and 3.4% (6) QQ (p = 0.32). No statistically significant associations were observed in the distribution of genotypes and allele frequencies between case (FH) and control groups. Nor did we find differences when we evaluated the relationship between the R353Q polymorphism and cardiovascular risk (including coronary disease, ischemic stroke and peripheral arterial disease), either in the univariate analysis or after adjustment for sex, age, arterial hypertension, body mass index, xanthomas, diabetes, smoking, HDLc and LDLc and lipid-lowering treatment. The FVII Ag concentrations behaved in a similar fashion, with no differences for the interaction between controls and those with FH (RR vs. RQ/QQ; p = 0.96). In the subgroup of patients with FH no association was found among cardiovascular disease, genotype and FVII Ag levels (RR vs. RQ/QQ; p = 0.97). Our study did not find a direct relationship between cardiovascular risk in patients with Heterozygous Familial Hypercholesterolemia, the R353Q polymorphism of factor VII and FVII Ag levels.

Animal model of atherosclerosis using rabbit experimentally induced by combination of X-ray and hypercholesterolemia

International Nuclear Information System (INIS)

Ishiyama, Tomotoshi; Sawai, Takashi; Okuma, Tsuneo; Mori, Shozo

1995-01-01

An attempt was made to prepare an animal model of atherosclerosis similar to human lesions. The experimental animals were male Japanese white rabbits weighting about 2 kg. Hypercholesterolemia was experimentally induced by giving a 1% cholesterol diet. Four weeks later, a single dose of 45 Gy was delivered to the femur to produce vascular changes. Soon after irradiation, immunohistochemical examination revealed the adhesion and invasion of macrophages to endothelial cells, followed by accumulation of foam cells and thickness of the intimal plaques. Three months after irradiation, these thickened plaques became fibrotic, calcified, and necrotic. The tunica media was thinned and the internal elastic lamella was destroyed. Irradiated arteries exhibited not only severe narrowing of the lumen but also aneurysmal dilation and the lesions of the irradiated arteries resembled human atherosclerosis. In conclusion, the atherosclerotic model produced by combining experimental hypercholesterolemia and X-ray irradiaiton may serve as a useful model for studies on atherosclerosis because it can be prepared with no need of complicated or time-consuming procedures. (N.K.)

The Antithrombotic and Fibrinolytic Effect of Natto in Hypercholesterolemia Rats

OpenAIRE

Park, Kum-Ju; Kang, Jung Il; Kim, Tae-Seok; Yeo, Ik-Hyun

2012-01-01

Antithrombotic and fibrinolytic activity of natto was evaluated on platelet aggregation in vitro and in vivo. Natto showed inhibitory effects on platelet aggregation induced by adenosine 5′diphosphate (ADP) and collagen. Orally administered natto also showed fibrinolytic activity in hypercholesterolemia rats. Normal levels of natto, when administered for four weeks, shortened euglobulin clot lysis time (ECLT) and prolonged partial thromboplastin time (PATT) significantly compared to non-treat...

Functional role of CD11c+ monocytes in atherogenesis associated with hypercholesterolemia

Science.gov (United States)

Monocyte activation and migration into the arterial wall are key events in atherogenesis associated with hypercholesterolemia. CD11c/CD18, a beta2 integrin expressed on human monocytes and a subset of mouse monocytes, has been shown to play a distinct role in human monocyte adhesion on endothelial c...

Efficacy and safety of rosuvastatin every other day compared with once daily in patients with hypercholesterolemia.

Science.gov (United States)

Wongwiwatthananukit, Supakit; Sansanayudh, Nakarin; Dhummauppakorn, Rawadee; Kitiyadisai, Chutiporn

2006-11-01

Although most patients with hypercholesterolemia require life-long therapy with statins, these drugs are underused due to high costs. Every-other-day therapy could be one strategy to resolve this problem. To compare the efficacy and safety of rosuvastatin 10 mg administered every other day versus once daily. An 8 week, randomized, open-label, parallel trial was conducted at the outpatient department of Phramongkutklao Hospital in Bangkok, Thailand. Eighty patients with primary hypercholesterolemia were equally randomized to receive rosuvastatin 10 mg once daily or every other day; 76 patients completed the study. Laboratory data were assessed at baseline and at the end of the study. Low-density lipoprotein cholesterol (LDL-C) levels were reduced by 48% and 39% in the once-daily and every-other-day groups, respectively (p = 0.011). The percentage of patients who achieved LDL-C goals according to National Cholesterol Education Program-Adult Treatment Panel III guidelines was not significantly different between the once-daily (85%) and every-other-day (70%) groups (p = 0.180). In addition, both regimens were well tolerated, with no patient developing an elevation of more than 3 times baseline levels of aspartate aminotransferase or alanine aminotransferase or 10 times that of creatine kinase. As expected, the monthly cost per percent LDL-C reduction of the once-daily (0.72 dollars) regimen was about 38% higher than that of the every-other-day (0.44 dollars) regimen. Every-other-day dosing of rosuvastatin may be an alternative regimen for cost savings, without a major decrease in therapeutic benefit or increase in adverse events, in patients with hypercholesterolemia. The number of patients achieving their LDL-C goal using the every-other-day regimen is comparable with the number using the once-daily regimen, especially in the low-risk patient category.

ABCB4 mediates diet-induced hypercholesterolemia in laboratory opossums[S

Science.gov (United States)

Chan, Jeannie; Mahaney, Michael C.; Kushwaha, Rampratap S.; VandeBerg, Jane F.; VandeBerg, John L.

2010-01-01

High-responding opossums are susceptible to developing hypercholesterolemia on a high-cholesterol diet, but low-responding opossums are resistant. The observation of low biliary cholesterol and low biliary phospholipids in high responders suggested that the ABCB4 gene affects response to dietary cholesterol. Two missense mutations (Arg29Gly and Ile235Leu) were found in the ABCB4 gene of high responders. High responders (ATHH strain) were bred with low responders (ATHE or ATHL strain) to produce F1 and F2 progeny in two different genetic crosses (KUSH6 and JCX) to determine the effect of ABCB4 allelic variants on plasma cholesterol concentrations after a dietary challenge. Pedigree-based genetic association analyses consistently implicated a variant in ABCB4 or a closely linked locus as a major, but not the sole, genetic contributor to variation in the plasma cholesterol response to dietary cholesterol. High responders, but not low responders, developed liver injury as indicated by elevated plasma biomarkers of liver function, probably reflecting damage to the canalicular membrane by bile salts because of impaired phospholipid secretion. Our results implicate ABCB4 as a major determinant of diet-induced hypercholesterolemia in high-responding opossums and suggest that other genes interact with ABCB4 to regulate lipemic response to dietary cholesterol. PMID:20488799

Hypercholesterolemia reduces collateral artery growth more dominantly than hyperglycemia or insulin resistance in mice

NARCIS (Netherlands)

Weel, V. van; Vries, M. de; Voshol, P.J.; Verloop, R.E.; Eilers, P.H.C.; Hinsbergh, V.W.M. van; Bockel, J.H. van; Quax, P.H.A.

2006-01-01

OBJECTIVE - Collateral artery development (arteriogenesis), a vital compensatory mechanism in patients with arterial obstructive disease, may be deregulated by vascular risk factors, eg, diabetes or hypercholesterolemia. Here, we compared the effects of either disturbed glucose metabolism or

Effect Of Using Ginger And / Or Cinnamon, As An Irradiated Supplement, On Lipid Profiles And Antioxidant Activities Of Dietary-Induced Hypercholesterolemia In Rats

International Nuclear Information System (INIS)

Farag, M.F.S.; Osman, N.N.; Yonies, B.M.

2007-01-01

Combating hypercholesterolemia is one of the modern nutrition directions. Towards this goal, hypercholesterolemia diet (HCD) containing cholesterol (1% w/w) and sodium cholate (0.2% w/w) was investigated on male Wister rats. Ginger and/or cinnamon (1% w/w) irradiated with 10 KGy were added to the HCD as a decontaminated supplement to evaluate the efficacy of these spices in reducing hypercholesterolemia. Their effects on serum and hepatic lipid, atherogenic index, blood and liver lipid peroxidation and antioxidant properties were determined. It was found that, the use of either ginger or cinnamon or both reduced TG, TC and LDL-C and increased HDL-C. Also, these spices suppressed lipid peroxidation via enhancement of antioxidant activities. The mixture of the two spices was more effective on the studied parameters in HCD fed rats. Thus, it could be concluded that intake of ginger and cinnamon may minimize the risk of atherosclerosis associated with a high cholesterol diet. These overall results support the future use of these spices and that continuous spices intake may be recommended in human

Corneal arcus and xanthomas in homozygous familial hypercholesterolemia: First report from China

Directory of Open Access Journals (Sweden)

Xin Meng

2013-01-01

Full Text Available We report the case of a 12-year-old male who developed corneal arcus and multiple skin lesions with a 10-year history of xanthomas. The lesions appeared over his fingers, hands, elbows, knees, buttocks and feet. Laboratory studies showed a total serum cholesterol level of 752.1 mg/dL; a triglyceride level of 96.6 mg/dL; a low-density lipoprotein cholesterol level of 661.3 mg/dL. Findings were consistent with homozygous familial hypercholesterolemia. To our knowledge, this is the first such case to be reported from China.

Relationship between vascular dysfunction in peripheral arteries and ischemic episodes during daily life in patients with ischemic heart disease and hypercholesterolemia

DEFF Research Database (Denmark)

Søndergaard, Eva; Møller, Jacob E; Egstrup, Kenneth

2002-01-01

cardiovascular risk factors. CONCLUSIONS: These results indicate a significant relationship between ischemic episodes and vascular dysfunction in patients with ischemic heart disease and hypercholesterolemia and may justify an aggressive preventive therapy targeted directly at the endothelium.......BACKGROUND: It is well established that endothelial dysfunction is present in patients with ischemic heart disease and hypercholesterolemia. Some of these patients will have signs of transient myocardial ischemia during Holter monitoring. We sought to describe the correlation between daily life...... ischemia and signs of endothelial dysfunction as assessed by means of brachial vasoreactivity. METHODS: We included in the study 131 patients with documented ischemic heart disease and a serum cholesterol level of > or =5 mmol/L before the institution of lipid-lowering treatment and dietary intervention...

ABCB4 mediates diet-induced hypercholesterolemia in laboratory opossums[S

OpenAIRE

Chan, Jeannie; Mahaney, Michael C.; Kushwaha, Rampratap S.; VandeBerg, Jane F.; VandeBerg, John L.

2010-01-01

High-responding opossums are susceptible to developing hypercholesterolemia on a high-cholesterol diet, but low-responding opossums are resistant. The observation of low biliary cholesterol and low biliary phospholipids in high responders suggested that the ABCB4 gene affects response to dietary cholesterol. Two missense mutations (Arg29Gly and Ile235Leu) were found in the ABCB4 gene of high responders. High responders (ATHH strain) were bred with low responders (ATHE or ATHL strain) to produ...

[Hypercholesterolemia reduction in children and adolescents after two years of intervention].

Science.gov (United States)

Robledo, Jorge A; Siccardi, Leonardo J; Cosio, Francisco; Rodríguez, María I; Robledo, Pamela; Rojas, Natalia; Lubetkin, Alberto

2009-12-01

Hypercholesterolemia, one of the main risk factors for cardiovascular diseases, can be detected since childhood. The early detection and a suitable educational process would allow to generate changes of habits and to decrease its prevalence. In 2003, total cholesterol (TC) > 170 mg/dl was found in 39.2% school children and adolescents, aged 5-17 years, of Jovita, Córdoba. To assess cholesterol levels decrease after an educational process and to analyze the relation between hypercholesterolemia and family history for cardiovascular diseases. Formal and no formal educational intervention was developed for two years, through curricular adaptations, talks, campaigns in radio and TV, graphic press, drama, workshops and leaflets. In 2005, cholesterol level was assessed, along with a survey on changes of nutritional habits and physical activity, and family history. A group of 161 students was assesses in both opportunities. There was a significant reduction in total cholesterol (average 13 mg/dl; p 199 mg/dl, the variations of the averages were: TC= -21 mg/dl, LDL-C= -16 mg/dl. The survey revealed improvements in the habits; family history was positive in 59%, unknown in 14%, and negative in 27%, the last ones had the best response to the intervention. A significant reduction of TC was obtained in the studied population; this may be due to the educational intervention. More than a quarter of the individuals presented negative family history for cardiovascular risk factors. Decrease in TC was proportionally better in this group than in those with positive family history.

Atorvastatin treatment does not affect gonadal and adrenal hormones in type 2 diabetes patients with mild to moderate hypercholesterolemia.

Science.gov (United States)

Santini, Stefano A; Carrozza, Cinzia; Lulli, Paola; Zuppi, Cecilia; CarloTonolo, Gian; Musumeci, Salvatore

2003-01-01

Atorvastatin, a second generation synthetic 3-hydroxy 3-methylglutaryl-coenzyme-A (HMG-CoA) reductase inhibitor used in the treatment of hypercholesterolemia, reduces both intracellular cholesterol synthesis and serum cholesterol levels, and this could have a potential negative impact on gonadal and adrenal steroidogenesis. Hypercholesterolemia in type 2 diabetes, even when mild, must be treated in an aggressive way, due to the more strict therapeutic goals than in the non diabetic population. Since the wide use of 3-hydroxy 3-methylglutaryl-coenzyme-A (HMG-CoA) reductase inhibitor (statins) in type 2 diabetes, the main aim of our study was to evaluate the effects of "therapeutic" doses of atorvastatin on gonadal and adrenal hormones in 24 type 2 diabetic patients (16 males and 8 postmenopausal females), with mild to moderate hypercholesterolemia (LDL-cholesterol = 150.1 +/- 32.0 and 189.9 +/- 32.9 mg/dl, respectively) studied before and after a 3 months treatment with atorvastatin (20 mg/day). In all patients, lipids and serum cortisol, dehydroepiandrosterone sulphate (DHEA-S), androstendione and sex hormone binding globulin (SHBG) were measured, with the addition, only in males, of testosterone and free testosterone index. After atorvastatin treatment a significant decrease in total and LDL cholesterol was observed (p < 0.05), while HDL-cholesterol did not significantly change ( p = N.S.), as no significant difference was found between steroid hormones measured before and after atorvastatin either in male and females. In conclusion, our data suggest that, in type 2 diabetic patients, the use of atorvastatin has no clinically important effects on either gonadal or adrenal steroid hormones.

Perinatal Hypercholesterolemia Exacerbates Atherosclerosis Lesions in Offspring by Altering Metabolism of Trimethylamine-N-Oxide and Bile Acids.

Science.gov (United States)

Trenteseaux, Charlotte; Gaston, Anh-Thu; Aguesse, Audrey; Poupeau, Guillaume; de Coppet, Pierre; Andriantsitohaina, Ramaroson; Laschet, Jamila; Amarger, Valérie; Krempf, Michel; Nobecourt-Dupuy, Estelle; Ouguerram, Khadija

2017-11-01

Experimental studies suggest that maternal hypercholesterolemia may be relevant for the early onset of cardiovascular disease in offspring. We investigated the effect of perinatal hypercholesterolemia on the atherosclerosis development in the offspring of apolipoprotein E-deficient mice and the underlying mechanism. Atherosclerosis and related parameters were studied in adult male or female apolipoprotein E-deficient mice offspring from either normocholesterolemic or hypercholesterolemic mothers and normocholesterolemic fathers. Female born to hypercholesterolemic mothers had more aortic root lesions than female born to normocholesterolemic mothers. Lesions in whole aorta did not differ between groups. Higher trimethylamine-N-oxide levels and Fmo3 hepatic gene expression were higher in female born to hypercholesterolemic mothers offspring compared with female born to normocholesterolemic mothers and male. Trimethylamine-N-oxide levels were correlated with the size of atherosclerotic root lesions. Levels of hepatic cholesterol and gallbladder bile acid were greater in male born to hypercholesterolemic mothers compared with male born to normocholesterolemic mothers. At 18 weeks of age, female born to hypercholesterolemic mothers showed lower hepatic Scarb1 and Cyp7a1 but higher Nr1h4 gene expression compared with female born to normocholesterolemic mothers. Male born to hypercholesterolemic mothers showed an increase in Scarb1 and Ldlr gene expression compared with male born to normocholesterolemic mothers. At 25 weeks of age, female born to hypercholesterolemic mothers had lower Cyp7a1 gene expression compared with female born to normocholesterolemic mothers. DNA methylation of Fmo3, Scarb1 , and Ldlr promoter regions was slightly modified and may explain the mRNA expression modulation. Our findings suggest that maternal hypercholesterolemia may exacerbate the development of atherosclerosis in female offspring by affecting metabolism of trimethylamine-N-oxide and

Sweet Preference Associated with the Risk of Hypercholesterolemia Among Middle-Aged Women in Korea.

Science.gov (United States)

Shin, Yoonjin; Lee, Soojin; Kim, Yangha

2018-04-05

Sweet preference has been reported to be associated with various health problems. This study examined the influence of sweet taste preference on the risk of dyslipidemia in Korean middle-aged women. The study selected 3,609 middle-aged women from the Korean Genome and Epidemiology Study (KoGES) and classified them into two groups on the basis of whether or not they preferred sweet taste. Dietary intake was analyzed using a semiquantitative food frequency questionnaire. Serum lipid profiles and anthropometric variables were measured. Subjects who preferred the sweet taste had significantly higher intakes of sugar products and sweet drink than those who did not prefer the sweet taste. Subjects who preferred the sweet taste showed higher carbohydrate and fat intake and less fiber intake than those who did not prefer the sweet taste. The serum concentrations of total cholesterol and low-density lipoprotein (LDL) cholesterol were significantly higher in subjects who preferred the sweet taste than those who did not prefer. Furthermore, subjects who preferred the sweet taste showed a significantly higher odds ratio (OR) for hypercholesterolemia (OR 1.22; 95% CI (1.01-1.45)) and hyper-LDL cholesterolemia (OR 1.33; 95% CI (1.11-1.60)) than those who did not prefer the sweet taste. Our results suggested that preference for sweet taste may increase the consumption of sugar products and sweet drinks, which is partially linked to the risk of hypercholesterolemia and hyper-LDL cholesterolemia in Korean middle-aged women.

Water-Soluble Chitosan Nanoparticles Inhibit Hypercholesterolemia Induced by Feeding a High-Fat Diet in Male Sprague-Dawley Rats

International Nuclear Information System (INIS)

Tao, Y.; Zhang, H.; Gao, B.; Guo, J.; Hu, Y.; Su, Z.

2011-01-01

Chitosan, a deacetylated product of chitin, has been demonstrated to lower cholesterol in humans and animals. However, chitosan is not fully soluble in water which would influence absorption in the human intestine. In addition, water-soluble chitosan (WSC) has higher reactivity compared to chitosan. The present study was designed to clarify the effects of WSC and water-soluble chitosan nanoparticles (WSC-NPs) on hypercholesterolemia induced by feeding a high-fat diet in male Sprague-Dawley rats. WSC-NPs were prepared by the ionic gelation method and the spray-drying technique. The nanoparticles were spherical in shape and had a smooth surface. The mean size of WSC-NPs was 650 nm variing from 500 to 800?nm. Results showed that WSC-NPs reduced the blood lipids and plasma viscosity significantly and increased the serum superoxide dismutase (SOD) activities significantly. This paper is the first report of the lipid-lowering effects of WSC-NPs suggesting that the WSC-NPs could be used for the treatment of hypercholesterolemia

Intestinal CREBH overexpression prevents high-cholesterol diet-induced hypercholesterolemia by reducing Npc1l1 expression

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Takuya Kikuchi

2016-11-01

Conclusion: Intestinal CREBH regulates dietary cholesterol flow from the small intestine by controlling the expression of multiple intestinal transporters. We propose that intestinal CREBH could be a therapeutic target for hypercholesterolemia.

Efficacy of Rosuvastatin in Children With Homozygous Familial Hypercholesterolemia and Association With Underlying Genetic Mutations

NARCIS (Netherlands)

Stein, Evan A.; Dann, Eldad J.; Wiegman, Albert; Skovby, Flemming; Gaudet, Daniel; Sokal, Etienne; Charng, Min-Ji; Mohamed, Mafauzy; Luirink, Ilse; Raichlen, Joel S.; Sundén, Mattias; Carlsson, Stefan C.; Raal, Frederick J.; Kastelein, John J. P.

2017-01-01

BACKGROUND Homozygous familial hypercholesterolemia (HoFH), a rare genetic disorder, is characterized by extremely elevated levels of low-density lipoprotein cholesterol (LDL-C) and accelerated atherosclerotic cardiovascular disease. Statin treatment starts at diagnosis, but no statin has been

R353Q polymorphism in the factor VII gene and cardiovascular risk in Heterozygous Familial Hypercholesterolemia: a case-control study

Directory of Open Access Journals (Sweden)

Pérez-Jiménez Francisco

2011-04-01

Full Text Available Abstract Background Heterozygous Familial Hypercholesterolemia (FH is a genetic disorder characterized by a high risk of cardiovascular disease. Certain polymorphisms of the factor VII gene have been associated with the development of coronary artery disease and there is a known association between factor VII levels and polymorphic variants in this gene. To date, no study has evaluated the association between factor VII and coronary artery disease in patients with FH. Results This case-control study comprised 720 patients (546 with FH and 174 controls. We determined the prevalence and allele frequencies of the R353Q polymorphism of factor VII, the plasma levels of factor VII antigen (FVII Ag and whether they could be predictive factors for cardiovascular risk. 75% (410 of the patients with FH were RR, 23% (127 RQ and 1.6% (9 QQ; in the control group 75.3% (131 were RR, 21.3% (37 RQ and 3.4% (6 QQ (p = 0.32. No statistically significant associations were observed in the distribution of genotypes and allele frequencies between case (FH and control groups. Nor did we find differences when we evaluated the relationship between the R353Q polymorphism and cardiovascular risk (including coronary disease, ischemic stroke and peripheral arterial disease, either in the univariate analysis or after adjustment for sex, age, arterial hypertension, body mass index, xanthomas, diabetes, smoking, HDLc and LDLc and lipid-lowering treatment. The FVII Ag concentrations behaved in a similar fashion, with no differences for the interaction between controls and those with FH (RR vs. RQ/QQ; p = 0.96. In the subgroup of patients with FH no association was found among cardiovascular disease, genotype and FVII Ag levels (RR vs. RQ/QQ; p = 0.97. Conclusions Our study did not find a direct relationship between cardiovascular risk in patients with Heterozygous Familial Hypercholesterolemia, the R353Q polymorphism of factor VII and FVII Ag levels.

Efficacy and Safety of Alirocumab 150 mg Every 4 Weeks in Patients With Hypercholesterolemia Not on Statin Therapy

DEFF Research Database (Denmark)

Stroes, Erik; Guyton, John R; Lepor, Norman

2016-01-01

controlled hypercholesterolemia and not on statin (majority with statin-associated muscle symptoms), receiving treatment with fenofibrate, ezetimibe, or diet alone. METHODS AND RESULTS: Patients were randomly assigned to placebo, alirocumab 150 mg Q4W or 75 mg Q2W (calibrator arm), with dose adjustment......: Alirocumab 150 mg Q4W can be considered in patients not on statin with inadequately controlled hypercholesterolemia as a convenient option for lowering LDL-C. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT02023879....

HMG-CoA reductase inhibitory activity and phytocomponent investigation of Basella alba leaf extract as a treatment for hypercholesterolemia

Directory of Open Access Journals (Sweden)

Baskaran G

2015-01-01

Full Text Available Gunasekaran Baskaran,1 Shamala Salvamani,1 Siti Aqlima Ahmad,1 Noor Azmi Shaharuddin,1 Parveen Devi Pattiram,2 Mohd Yunus Shukor1 1Department of Biochemistry, Faculty of Biotechnology and Biomolecular Sciences, 2Department of Food Technology, Faculty of Food Science and Technology, Universiti Putra Malaysia, Selangor, Malaysia Abstract: The enzyme 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA reductase is the key enzyme of the mevalonate pathway that produces cholesterol. Inhibition of HMG-CoA reductase reduces cholesterol biosynthesis in the liver. Synthetic drugs, statins, are commonly used for the treatment of hypercholesterolemia. Due to the side effects of statins, natural HMG-CoA reductase inhibitors of plant origin are needed. In this study, 25 medicinal plant methanol extracts were screened for anti-HMG-CoA reductase activity. Basella alba leaf extract showed the highest inhibitory effect at about 74%. Thus, B. alba was examined in order to investigate its phytochemical components. Gas chromatography with tandem mass spectrometry and reversed phase high-performance liquid chromatography analysis revealed the presence of phenol 2,6-bis(1,1-dimethylethyl, 1-heptatriacotanol, oleic acid, eicosyl ester, naringin, apigenin, luteolin, ascorbic acid, and a-tocopherol, which have been reported to possess antihypercholesterolemic effects. Further investigation of in vivo models should be performed in order to confirm its potential as an alternative treatment for hypercholesterolemia and related cardiovascular diseases. Keywords: HMG-CoA reductase, Basella alba, phytochemical, GC-MS/MS, RP-HPLC, hypercholesterolemia

Lipid phenotype and heritage pattern in families with genetic hypercholesterolemia not related to LDLR, APOB, PCSK9, or APOE.

Science.gov (United States)

Jarauta, Estíbaliz; Pérez-Ruiz, María Rosario; Pérez-Calahorra, Sofia; Mateo-Gallego, Rocio; Cenarro, Ana; Cofán, Montserrat; Ros, Emilio; Civeira, Fernando; Tejedor, Maria Teresa

A substantial proportion of individuals clinically diagnosed as familial hypercholesterolemia (FH) do not carry pathogenic mutations in candidate genes. Whether in them the high cholesterol trait is transmitted monogenically has not been studied. We assessed the inheritance pattern, penetrance, and expression of high low-density lipoprotein (LDL)-cholesterol (LDLc) in families with genetic hypercholesterolemia (GH) without known causative mutations (non-FH-GH). The study included probands with a clinical diagnosis of FH and their families attending 2 lipid clinics in Spain. Inclusion criteria for probands were LDLc >95th percentile, triglycerides 90th percentile, >5 points in the Dutch Lipid Clinic Network criteria score, and absence of mutations in LDLR, APOB, PCSK9 or APOE. Eleven FH families with a LDLR mutation were also examined for comparison. We analyzed 49 non-FH-GH probands and 277 first-and second-degree relatives. LDLc was >90th percentile in 37.8% of blood relatives, at concentrations similar to those of probands. LDLc had a normal distribution in non-FH-GH families, in contrast with a bimodal distribution in FH families. When a dominant model was tested, family-based association tests gave much lower heritability values for total cholesterol and LDLc in non-FH-GH (0.39 and 0.32, respectively) than in FH (0.78 and 0.61, respectively). Non-FH-GH families have a milder lipid phenotype than genetically defined FH. The heritage pattern of LDLc in non-FH-GH does not fit with a monogenic disorder. Our findings support the concept that most non-FH-GHs are polygenic hypercholesterolemias. Copyright © 2016 National Lipid Association. Published by Elsevier Inc. All rights reserved.

Non-invasive detection of aortic and coronary atherosclerosis in homozygous familial hypercholesterolemia by 64 slice multi-detector row computed tomography angiography

Science.gov (United States)

Homozygous familial hypercholesterolemia (HoFH) is a rare disorder characterized by the early onset of atherosclerosis, often at the ostia of coronary arteries. In this study we document for the first time that aortic and coronary atherosclerosis can be detected using 64 slice multiple detector row ...

Effects of antioxidant vitamins along with atorvastatin and atorvastatin–niacin combination on diet-induced hypercholesterolemia in rats

OpenAIRE

Solanki, Yogendrasinh B; Bhatt, Rajendra V

2010-01-01

The present study investigated the effects of antioxidant vitamins along with atorvastatin and atorvastatinniacin combination on diet-induced hypercholesterolemia in rats. High cholesterol diet produced a significant increase in the serum total cholesterol, LDL-C, VLDL-C, TG, atherogenic index and decrease in HDL-C and HDL/LDL ratio. The lipid peroxidation and oxidative stress were significantly high in the hyperlipidemic control group. Atorvastatin improved atherogenic index but not the HDL/...

Simvastatin and asymmetric dimethylarginine-homocysteine metabolic pathways in patients with newly detected severe hypercholesterolemia.

Science.gov (United States)

Vladimirova-Kitova, Ludmila G; Deneva, Tania I

2010-01-01

The idea that statin therapy decreases asymmetric dimethylarginine through lowering low-density lipoprotein cholesterol levels seems logic. However, controversy exists in the literature concerning this issue. This study compares the effect of moderate (40 mg) to high (80 mg) simvastatin doses on asymmetric dimethylarginine levels in patients with newly detected severe hypercholesterolemia (after targeted LDL levels of or = 7.5 mmol/L and low-density lipoprotein cholesterol > or = 4.9 mmol/L). Asymmetric dimethylarginine levels were determined by enzyme-linked immunosorbent assay, total homocystein by the high performance liquid chromatography method. A statistically significant decrease exists in total cholesterol, triglycerides, low-density lipoprotein cholesterol and apolipoprotein-B levels as well as apolipoprotein-B/apolipoprotein-A1 index following one month of 40 mg simvastatin therapy (P homocystein levels were also decreased but the difference was not significant (p = 0.571; p = 0.569). A dose-dependent effect was established comparing the influence of moderate (40 mg) to high (80 mg) simvastatin doses on the tested atherogenic biomarkers (lipid profile, apolipoprotein-A1, apolipoprotein-B). Asymmetric dimethylarginine and total homocystein levels showed a statistically significant decrease with 80 mg simvastatin (p homocysteine in contrast to high dose (80 mg) after targeted LDL of < or = 2.6 mmol/L levels are reached in patients with newly detected severe hypercholesterolemia.

Premature Valvular Heart Disease in Homozygous Familial Hypercholesterolemia.

Science.gov (United States)

Fahed, Akl C; Shibbani, Kamel; Andary, Rabih R; Arabi, Mariam T; Habib, Robert H; Nguyen, Denis D; Haddad, Fady F; Moubarak, Elie; Nemer, Georges; Azar, Sami T; Bitar, Fadi F

2017-01-01

Valvular heart disease frequently occurs as a consequence of premature atherosclerosis in individuals with familial hypercholesterolemia (FH). Studies have primarily focused on aortic valve calcification in heterozygous FH, but there is paucity of data on the incidence of valvular disease in homozygous FH. We performed echocardiographic studies in 33 relatively young patients (mean age: 26 years) with homozygous FH (mean LDL of 447 mg/dL, 73% on LDL apheresis) to look for subclinical valvulopathy. Twenty-one patients had evidence of valvulopathy of the aortic or mitral valves, while seven subjects showed notable mitral regurgitation. Older patients were more likely to have aortic valve calcification (>21 versus ≤21 years: 59% versus 12.5%; p = 0.01) despite lower LDL levels at the time of the study (385 versus 513 mg/dL; p = 0.016). Patients with valvulopathy were older and had comparable LDL levels and a lower carotid intima-media thickness. Our data suggests that, in homozygous FH patients, valvulopathy (1) is present across a wide age spectrum and LDL levels and (2) is less likely to be influenced by lipid-lowering treatment. Echocardiographic studies that focused on aortic root thickening and stenosis and regurgitation are thus likely an effective modality for serial follow-up of subclinical valvular heart disease.

Oxidized low-density lipoprotein in children with familial hypercholesterolemia and unaffected siblings: effect of pravastatin

NARCIS (Netherlands)

Rodenburg, Jessica; Vissers, Maud N.; Wiegman, Albert; Miller, Elizabeth R.; Ridker, Paul M.; Witztum, Joseph L.; Kastelein, John J. P.; Tsimikas, Sotirios

2006-01-01

OBJECTIVES: To assess the role of oxidized phospholipids (OxPLs) in children with familial hypercholesterolemia (FH) and the effect of pravastatin. BACKGROUND: Oxidized phospholipids are a major component of oxidized low-density lipoprotein (OxLDL) and are bound to lipoprotein (a) [Lp(a)]. The

Water-Soluble Chitosan Nanoparticles Inhibit Hypercholesterolemia Induced by Feeding a High-Fat Diet in Male Sprague-Dawley Rats

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Yi Tao

2011-01-01

Full Text Available Chitosan, a deacetylated product of chitin, has been demonstrated to lower cholesterol in humans and animals. However, chitosan is not fully soluble in water which would influence absorption in the human intestine. In addition, water-soluble chitosan (WSC has higher reactivity compared to chitosan. The present study was designed to clarify the effects of WSC and water-soluble chitosan nanoparticles (WSC-NPs on hypercholesterolemia induced by feeding a high-fat diet in male Sprague-Dawley rats. WSC-NPs were prepared by the ionic gelation method and the spray-drying technique. The nanoparticles were spherical in shape and had a smooth surface. The mean size of WSC-NPs was 650 nm variing from 500 to 800 nm. Results showed that WSC-NPs reduced the blood lipids and plasma viscosity significantly and increased the serum superoxide dismutase (SOD activities significantly. This paper is the first report of the lipid-lowering effects of WSC-NPs suggesting that the WSC-NPs could be used for the treatment of hypercholesterolemia.

HYPOCHOLESTEROLEMIC AND ANTI-OXIDATIVE PROPERTIES OF GERMINATED BROWN RICE (GBR IN HYPERCHOLESTEROLEMIA-INDUCED RATS

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Froilan Bernard Matias

2014-02-01

Full Text Available Hypercholesterolemia, as one of the causes of obesity, affects vital organs in the body, such as the liver and kidney, resulting to oxidative stress. Germinated Brown Rice (GBR as a food-based solution in dealing with this condition is highly recommended. In this study, the effects of GBR on hypercholesterolemia-induced rats were evaluated by measuring and analyzing the changes on body weight, serum lipid profiles (TC, TG, LDL and HDL, liver function (ALT and AST, kidney function (Crea and Urea and its antioxidant capacity (MDA, SOD, GSH-PX and TAOC. Thirty (30 SD male rats were divided into 5 groups (6 rats per group; Group A was given normal basal diet, Group B (hypercholesterolemic group was given a high fat diet, while Groups C, D, and E were given 12.5%, 25% and 50% GBR, respectively. Groups C, D and E were fed with high fat diet for 4 weeks, then fed with the GBR feeds, accordingly, for another 5 weeks. Sera and liver samples were collected for testing and evaluation. Hypercholesterolemia was successfully induced in Groups B, C, D, and E after 4 weeks. Noticeable responses were observed in groups fed with GBR after 5 weeks. Group E fed with 50% GBR showed the satisfactory results (significant at p<0.05 in weight gain, serum lipid profiles, liver function enzymes, creatinine, urea and oxidative stress markers compared to the hypercholesterolemic group. The hypocholesterolemic and antioxidant properties of GBR were found to have a dose-response effect where higher percentage of GBR showed acceptable results as compared to the normal and hypercholesterolemic groups. GBR showed to effectively lessen TC, TG and LDL while increases HDL. It effectively protects the liver while its kidney protective ability was associated to its hypocholesterolemic properties. Oxidative stress was reduced as shown by a decline in lipid peroxidation and improved antioxidant production. In addition, the abovementioned GBR‘s properties are combined effects of its

Impact of Statin Therapy on the Blood Pressure-Lowering Efficacy of a Single-Pill Perindopril/Amlodipine Combination in Hypertensive Patients with Hypercholesterolemia.

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Sirenko, Yuriy; Radchenko, Ganna

2017-03-01

Several lines of research indicate that statins can lower blood pressure (BP) independently of their lipid-lowering effects when used as monotherapy and in combination with antihypertensive agents. This short-term, open-label study examined whether statin therapy had a synergistic effect on the BP-lowering efficacy of perindopril/amlodipine in a subgroup of patients in the PERSPECTIVA study with concomitant hypertension and hypercholesterolemia, with or without statin at baseline. The PERSPECTIVA study recruited 732 adults with untreated or uncontrolled hypertension. This subgroup analysis of PERSPECTIVA included 587 patients with concomitant hypertension and hypercholesterolemia (mean age 56.7 years) of whom 226 were receiving a statin at baseline (statin [+] group) and 361 were not (statin [-] group). All patients received treatment with single-pill combination perindopril/amlodipine at a dose of 5/5, 10/5 or 10/10 mg/day. The study duration was 60 days with follow-up visits for BP monitoring at 7, 15, 30 and 60 days. At day 60, BP control (statin [+] vs statin [-] group: 73 vs 64% respectively (+14%, P statin [+] group, the single-pill perindopril/amlodipine combination significantly reduced BP in patients previously untreated (n = 18), or treated with monotherapy (n = 97), dual therapy (n = 93), or triple therapy (n = 18): -38.8/-20.0, -39.1/-20.1, -38.0/-19.4, -39.9/-18.3 mmHg respectively (P statin [+] group (0.9%) vs the statin [-] group (2.5%). BP control rates in patients with uncontrolled hypertension and concomitant hypercholesterolemia are significantly improved with a treatment regimen that combines perindopril/amlodipine with statin therapy, regardless of previous antihypertensive therapy. This subanalysis of the PERSPECTIVA study supports the synergistic BP-lowering effect of statins and perindopril/amlodipine.

Characterization of Autosomal Dominant Hypercholesterolemia Caused by PCSK9 Gain of Function Mutations and Its Specific Treatment With Alirocumab, a PCSK9 Monoclonal Antibody

NARCIS (Netherlands)

Hopkins, Paul N.; Defesche, Joep; Fouchier, Sigrid W.; Bruckert, Eric; Luc, Gérald; Cariou, Bertrand; Sjouke, Barbara; Leren, Trond P.; Harada-Shiba, Mariko; Mabuchi, Hiroshi; Rabès, Jean-Pierre; Carrié, Alain; van Heyningen, Charles; Carreau, Valérie; Farnier, Michel; Teoh, Yee P.; Bourbon, Mafalda; Kawashiri, Masa-Aki; Nohara, Atsushi; Soran, Handrean; Marais, A. David; Tada, Hayato; Abifadel, Marianne; Boileau, Catherine; Chanu, Bernard; Katsuda, Shoji; Kishimoto, Ichiro; Lambert, Gilles; Makino, Hisashi; Miyamoto, Yoshihiro; Pichelin, Matthieu; Yagi, Kunimasa; Yamagishi, Masakazu; Zair, Yassine; Mellis, Scott; Yancopoulos, George D.; Stahl, Neil; Mendoza, Johanna; Du, Yunling; Hamon, Sara; Krempf, Michel; Swergold, Gary D.

2015-01-01

Background Patients with PCSK9 gene gain of function (GOF) mutations have a rare form of autosomal dominant hypercholesterolemia. However, data examining their clinical characteristics and geographic distribution are lacking. Furthermore, no randomized treatment study in this population has been

Cholesterol concentrations in lipoprotein fractions separated by anion-exchange-high-performance liquid chromatography in healthy dogs and dogs with hypercholesterolemia.

Science.gov (United States)

Oda, Hitomi; Mori, Akihiro; Hirowatari, Yuji; Takoura, Toshie; Manita, Daisuke; Takahashi, Tomoya; Shono, Saori; Onozawa, Eri; Mizutani, Hisashi; Miki, Yohei; Itabashi, Yukiko; Sako, Toshinori

2017-10-01

Anion-exchange (AEX)-high-performance liquid chromatography (HPLC) for measurement of cholesterol can be used to separate serum lipoproteins (high-density lipoprotein (HDL); low-density lipoprotein (LDL); intermediate-density lipoprotein (IDL); very-low-density lipoprotein (VLDL)) in humans. However, AEX-HPLC has not been applied in veterinary practice. We had three objectives: (i) the validation of AEX-HPLC methods including the correlation of serum cholesterol concentration in lipoprotein fraction measured by AEX-HPLC and gel permeation-HPLC (GP-HPLC) in healthy dogs and those with hypercholesterolemia was investigated; (ii) the reference intervals of lipoprotein fractions measured by AEX-HPLC from healthy dogs (n=40) was established; (iii) lipoprotein fractions from the serum of healthy dogs (n=12) and dogs with hypercholesterolemia (n=23) were compared. Analytic reproducibility and precision of AEX-HPLC were acceptable. Positive correlation between serum concentrations of total cholesterol (Total-Chol), HDL cholesterol (HDL-Chol), LDL cholesterol (LDL-Chol)+IDL cholesterol (IDL-Chol), and VLDL cholesterol (VLDL-Chol) was noted for AEX-HPLC and GP-HPLC in healthy dogs and dogs with hypercholesterolemia. Reference intervals measured by AEX-HPLC for serum concentrations of Total-Chol, HDL-Chol, and LDL-Chol were determined to be 2.97-9.32, 2.79-6.57, 0.16-3.28mmol/L (2.5-97.5% interval), respectively. Furthermore, there was significant difference in lipoprotein profiles between healthy and dogs with hypercholesterolemia. These results suggest that AEX-HPLC can be used to evaluate lipoprotein profiles in dogs and could be a new useful indicator of hyperlipidemia in dogs. Copyright © 2017 Elsevier Ltd. All rights reserved.

LDL-apheresis depletes apoE-HDL and pre-β1-HDL in familial hypercholesterolemia: relevance to atheroprotection

NARCIS (Netherlands)

Orsoni, Alexina; Saheb, Samir; Levels, Johannes H. M.; Dallinga-Thie, Geesje; Atassi, Marielle; Bittar, Randa; Robillard, Paul; Bruckert, Eric; Kontush, Anatol; Carrié, Alain; Chapman, M. John

2011-01-01

Subnormal HDL-cholesterol (HDL-C) and apolipoprotein (apo)AI levels are characteristic of familial hypercholesterolemia (FH), reflecting perturbed intravascular metabolism with compositional anomalies in HDL particles, including apoE enrichment. Does LDL-apheresis, which reduces HDL-cholesterol,

New Approaches in Detection and Treatment of Familial Hypercholesterolemia.

Science.gov (United States)

Hartgers, Merel L; Ray, Kausik K; Hovingh, G Kees

2015-12-01

Familial hypercholesterolemia (FH) is an autosomal dominant genetic disorder that clinically leads to increased low density lipoprotein-cholesterol (LDL-C) levels. As a consequence, FH patients are at high risk for cardiovascular disease (CVD). Mutations are found in genes coding for the LDLR, apoB, and PCSK9, although FH cannot be ruled out in the absence of a mutation in one of these genes. It is pivotal to diagnose FH at an early age, since lipid lowering results in a decreased risk of cardiovascular complications especially if initiated early, but unfortunately FH is largely underdiagnosed. While a number of clinical criteria are available, identification of a pathogenic mutation in any of the three aforementioned genes is seen by many as a way to establish a definitive diagnosis of FH. It should be remembered that clinical treatment is based on LDL-C levels and not solely on presence or absence of genetic mutations as LDL-C is what drives risk. Traditionally, mutation detection has been done by means of dideoxy sequencing. However, novel molecular testing methods are gradually being introduced. These next generation sequencing-based methods are likely to be applied on broader scale once their efficacy and effect on cost are being established. Statins are the first-line therapy of choice for FH patients as they have been proven to reduce CVD risk across a range of conditions including hypercholesterolemia (though not specifically tested in FH). However, in a significant proportion of FH patients LDL-C goals are not met, despite the use of maximal statin doses and additional lipid-lowering therapies. This underlines the need for additional therapies, and inhibition of PCSK9 and CETP is among the most promising new therapeutic options. In this review, we aim to provide an overview of the latest information about the definition, diagnosis, screening, and current and novel therapies for FH.

The Impact of Lipoprotein-Associated Oxidative Stress on Cell-Specific Microvesicle Release in Patients with Familial Hypercholesterolemia

DEFF Research Database (Denmark)

Nielsen, M H; Irvine, H; Vedel, S

2016-01-01

Objective. Microvesicles (MVs) are small cell-derived particles shed upon activation. Familial hypercholesterolemia (FH) particularly when associated with Achilles tendon xanthomas (ATX) predisposes to atherosclerosis, possibly through oxLDL-C interaction with the CD36 receptor. To investigate...

Premature Valvular Heart Disease in Homozygous Familial Hypercholesterolemia

Directory of Open Access Journals (Sweden)

Akl C. Fahed

2017-01-01

Full Text Available Valvular heart disease frequently occurs as a consequence of premature atherosclerosis in individuals with familial hypercholesterolemia (FH. Studies have primarily focused on aortic valve calcification in heterozygous FH, but there is paucity of data on the incidence of valvular disease in homozygous FH. We performed echocardiographic studies in 33 relatively young patients (mean age: 26 years with homozygous FH (mean LDL of 447 mg/dL, 73% on LDL apheresis to look for subclinical valvulopathy. Twenty-one patients had evidence of valvulopathy of the aortic or mitral valves, while seven subjects showed notable mitral regurgitation. Older patients were more likely to have aortic valve calcification (>21 versus ≤21 years: 59% versus 12.5%; p = 0.01 despite lower LDL levels at the time of the study (385 versus 513 mg/dL; p = 0.016. Patients with valvulopathy were older and had comparable LDL levels and a lower carotid intima-media thickness. Our data suggests that, in homozygous FH patients, valvulopathy (1 is present across a wide age spectrum and LDL levels and (2 is less likely to be influenced by lipid-lowering treatment. Echocardiographic studies that focused on aortic root thickening and stenosis and regurgitation are thus likely an effective modality for serial follow-up of subclinical valvular heart disease.

The Impact of Lipoprotein-Associated Oxidative Stress on Cell-Specific Microvesicle Release in Patients with Familial Hypercholesterolemia

DEFF Research Database (Denmark)

Nielsen, Morten Hjuler; Irvine, H; Vedel, S

2016-01-01

Objective. Microvesicles (MVs) are small cell-derived particles shed upon activation. Familial hypercholesterolemia (FH) particularly when associated with Achilles tendon xanthomas (ATX) predisposes to atherosclerosis, possibly through oxLDL-C interaction with the CD36 receptor. To investigate th...

Ezetimibe--a new approach in hypercholesterolemia management.

Science.gov (United States)

Suchy, Dariusz; Łabuzek, Krzysztof; Stadnicki, Antoni; Okopień, Bogusław

2011-01-01

Ezetimibe is the first agent used in hypercholesterolemia treatment known to lower intestinal cholesterol uptake that is able to inhibit NPC1L1 transport proteins in the brush boarder of enterocytes and macrophages. Furthermore, it demonstrates anti-inflammatory and immunomodulatory properties and influences the expression of certain antigens. The drug is rapidly absorbed from the gastrointestinal tract and is then glucuronidated to form the active metabolite. It also undergoes extensive enterohepatic circulation. Various genetic polymorphisms seem to influence the pharmacokinetics of ezetimibe with different effects. The drug also presents a complex impact on cytochrome P450 enzymes, as it is a metabolism-dependent inhibitor of CYP3A4. Ezetimibe does not demonstrate any clinically significant interactions with statins, fibrates, mipomersen sodium, levothyroxine or lopinavir. However, its effect in conjunction with cyclosporine is not neutral. The use of this cholesterol absorption inhibitor has been shown to be safe and effective among patients after cardiac, renal and liver transplants, as well as in HIV patients.

Management of Hypercholesterolemia, Appropriateness of Therapeutic Approaches and New Drugs in Patients with High Cardiovascular Risk.

Science.gov (United States)

Agabiti Rosei, Enrico; Salvetti, Massimo

2016-09-01

Control of lipid levels is one of the most effective strategies for cardiovascular (CV) event prevention. In fact, many clinical trials have clearly demonstrated that low-density lipoprotein cholesterol (LDL-C) lowering, primarily with statins, reduces major CV events and mortality. The evidence from these trials has been useful in designing the cholesterol treatment guidelines, which are mainly aimed at preventing and managing cardiovascular disease (CVD). However, available data indicate that a large proportion of patients fail to achieve lipid goals, and this is particularly frequent in patients at high or very high CV risk. Furthermore, owing to side effects, a significant percentage of patients cannot tolerate statin treatment. Hence, researchers have focused their attention on novel LDL-C-lowering agents that act via mechanisms distinct from that of statins. Among the new compounds under investigation, the monoclonal antibodies to proprotein convertase subtilisin/kexin type 9 (PCSK9) seem particularly promising, having recently been shown to be well tolerated and highly effective at lowering LDL-C, with a possible effect on the occurrence of CV events. Currently, alirocumab is approved by the US Food and Drug Administration (FDA) as an adjunct to diet and maximally tolerated statin therapy for use in adults with heterozygous familial hypercholesterolemia (FH) or those with atherosclerotic CV disease who require additional LDL-C lowering; it has also been recently approved by the European Medicines Agency (EMA) for use in patients with heterozygous FH, non-familial hypercholesterolemia or mixed dyslipidemia in whom statins are ineffective or not tolerated. Evolocumab is approved by the FDA as an adjunct to diet and maximally tolerated statins for adults with hetero- and homozygous FH and those with atherosclerotic CV disease who require additional lowering of LDL-C, and by the EMA in adults with primary hypercholesterolemia or mixed dyslipidemia, as an adjunct

Rho kinase inhibitor fasudil mitigates high-cholesterol diet-induced hypercholesterolemia and vascular damage.

Science.gov (United States)

Abdali, Nibrass Taher; Yaseen, Awny H; Said, Eman; Ibrahim, Tarek M

2017-04-01

The current study was designed to investigate the potential beneficial therapeutic outcome of Rho kinase inhibitor (fasudil) against hypercholesterolemia-induced myocardial and vascular injury in rabbits together with diet modification. Sixteen male rabbits were randomly divided into four groups: normal control group which received standard rabbit chow, hypercholesterolemic control group, and treated groups which received cholesterol-rich rabbit chow (1.5% cholesterol) for 8 weeks. Treated groups received either fasudil (100 mg/kg/day) or rosuvastatin (2.5 mg/kg/day) starting from the ninth week for further 4 weeks with interruption of the cholesterol-rich chow. Biochemical assessment of serum cholesterol, triglyceride, high-density lipoprotein (HDL), low-density lipoprotein (LDL), and myocardial oxidative/antioxidant biomarkers malondialdehyde (MDA), superoxide dismutase (SOD), and reduced glutathione (GSH), besides biochemical assessment of serum nitric oxide (NO), creatine kinase (CK), and lactate dehydrogenase (LDH) activities and serum total antioxidant capacity (TAC), was conducted. Serum vascular cell adhesion molecule 1 (VCAM-1) and serum Rho-associated protein kinase 1 (ROCK-1) were also evaluated along with histopathological examination of aorta specimens. Fasudil administration significantly decreased serum cholesterol, triglyceride (TG), and LDL and significantly increased serum HDL, with concomitant decrease in serum CK and LDH activities, NO, and restoration of serum TAC. Myocardial MDA significantly declined; SOD activity and GSH contents were restored. Serum ROCK-1 and VCAM-1 levels significantly declined as well. Vascular improvement was confirmed with histopathological examination, which revealed normal aortic intema with the absence of atheromas. Fasudil has promising anti-atherogenic activity mediated primarily via alleviation of hypercholesterolemia-induced oxidative stress and modulation of inflammatory response.

Rosuvastatin lowers coenzyme Q10 levels, but not mitochondrial adenosine triphosphate synthesis, in children with familial hypercholesterolemia

NARCIS (Netherlands)

Avis, Hans J.; Hargreaves, Ian P.; Ruiter, Jos P. N.; Land, John M.; Wanders, Ronald J.; Wijburg, Frits A.

2011-01-01

To investigate whether statin therapy affects coenzyme Q10 (CoQ10) status in children with heterozygous familial hypercholesterolemia (FH). Samples were obtained at baseline (treatment naïve) and after dose titration with rosuvastatin, aiming for a low-density lipoprotein cholesterol level of 110

Intensive Treat-to-Target Statin Therapy in High-Risk Japanese Patients With Hypercholesterolemia and Diabetic Retinopathy: Report of a Randomized Study.

Science.gov (United States)

Itoh, Hiroshi; Komuro, Issei; Takeuchi, Masahiro; Akasaka, Takashi; Daida, Hiroyuki; Egashira, Yoshiki; Fujita, Hideo; Higaki, Jitsuo; Hirata, Ken-Ichi; Ishibashi, Shun; Isshiki, Takaaki; Ito, Sadayoshi; Kashiwagi, Atsunori; Kato, Satoshi; Kitagawa, Kazuo; Kitakaze, Masafumi; Kitazono, Takanari; Kurabayashi, Masahiko; Miyauchi, Katsumi; Murakami, Tomoaki; Murohara, Toyoaki; Node, Koichi; Ogawa, Susumu; Saito, Yoshihiko; Seino, Yoshihiko; Shigeeda, Takashi; Shindo, Shunya; Sugawara, Masahiro; Sugiyama, Seigo; Terauchi, Yasuo; Tsutsui, Hiroyuki; Ueshima, Kenji; Utsunomiya, Kazunori; Yamagishi, Masakazu; Yamazaki, Tsutomu; Yo, Shoei; Yokote, Koutaro; Yoshida, Kiyoshi; Yoshimura, Michihiro; Yoshimura, Nagahisa; Nakao, Kazuwa; Nagai, Ryozo

2018-06-01

Diabetes is associated with high risk of cardiovascular (CV) events, particularly in patients with dyslipidemia and diabetic complications. We investigated the incidence of CV events with intensive or standard lipid-lowering therapy in patients with hypercholesterolemia, diabetic retinopathy, and no history of coronary artery disease (treat-to-target approach). In this multicenter, prospective, randomized, open-label, blinded end point study, eligible patients were randomly assigned (1:1) to intensive statin therapy targeting LDL cholesterol (LDL-C) targeting LDL-C 100-120 mg/dL ( n = 2,524). Mean follow-up was 37 ± 13 months. LDL-C at 36 months was 76.5 ± 21.6 mg/dL in the intensive group and 104.1 ± 22.1 mg/dL in the standard group ( P target strategy in high-risk patients deserves further investigation. © 2018 by the American Diabetes Association.

Gonadal steroids, gonadotropins and DHEAS in young adults with familial hypercholesterolemia who had initiated statin therapy in childhood

NARCIS (Netherlands)

Braamskamp, Marjet J. A. M.; Kusters, D. Meeike; Wiegman, Albert; Avis, Hans J.; Wijburg, Frits A.; Kastelein, John J. P.; van Trotsenburg, A. S. Paul; Hutten, Barbara A.

2015-01-01

Statins are currently the preferred pharmacological therapy in children with familial hypercholesterolemia (FH) with the aim to prevent premature cardiovascular disease (CVD). However, concerns have been raised that lowering cholesterol levels with statins could interfere with hormone production. In

Lipid-altering efficacy and safety of ezetimibe/simvastatin versus atorvastatin in patients with hypercholesterolemia and the metabolic syndrome (from the VYMET study)

DEFF Research Database (Denmark)

Robinson, Jennifer G; Ballantyne, Christie M; Grundy, Scott M

2009-01-01

the lipid-lowering efficacy of ezetimibe/simvastatin 10/20 mg versus atorvastatin 10 or 20 mg, and ezetimibe/simvastatin 10/40 mg versus atorvastatin 40 mg in 1,128 patients with hypercholesterolemia and the metabolic syndrome. The primary end point was the percentage of change from baseline in low......, apolipoprotein B, and lipid/lipoprotein ratios resulted with ezetimibe/simvastatin compared with atorvastatin at all specified dose comparisons (p .../simvastatin than with atorvastatin at all dose comparisons (p atorvastatin 10 mg (p atorvastatin 40 mg (p

Five Vessel Coronary Arter Bypass Graft Surgery in a Case with Familial Hypercholesterolemia

Directory of Open Access Journals (Sweden)

Sureyya Talay

2014-08-01

Full Text Available We report a case of a rare and sypmtomatic familyal hypercholesterolemia case with an end-point of coronary artery bypass surgery at the age of 16. Patient was evaluated at the emergency department with chest pain and discomfort. Physical examination were within normal limits. The electrocardiogram showed a normal sinus rhythm for 108/ min. Arterial blood pressure was 90/60 mmHg. Lungs and heart were clear to auscultation. Patient was under treatment with a prior diagnosis of familial hypercholesterolemia (FH for one year by daily 40 mgs rosuvastatine. A coronary artery angiography was performed for chest pain. Multivessel coronary artery disease was diagnosed with a total occlusion of left anterior descending artery. Transthoracic echocardiography presented a left ventricular (LV ejection fraction 50%, LV diameters 44/26 mm, aneurysm formation at interatrial septum and mild dyskinesia of anterior wall. Thus, a five vessel emergent coronary artery graft bypass surgery was performed at this early age. FH is with a severe elevation in total cholesterol (TC and low density lipoprotein cholesterol (LDL in an autosomal dominant characteristic disorder that approximately occurs in 1 per 500 persons by its heterozygous form. FH is most certainly associated with premature coronary artery disease (CAD with catasthrophic early age results. [Cukurova Med J 2014; 39(4.000: 872-875

Clinical outcome of patients with familial hypercholesterolemia and coronary artery disease undergoing partial ileal bypass surgery

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Jaqueline Scholz Issa

2000-07-01

Full Text Available Familial hypercholesterolemia is characterized by high serum levels of total cholesterol and LDL-cholesterol. It may be homozygous or heterozygous. In homozygous patients, LDL-cholesterol levels range from 500 to 1000mg/dL and coronary artery disease is precocious, usually manifesting itself between the 2nd and 3rd decades of life. The diagnosis is often made by the presence of xanthoma tuberosum and tendinous xanthomas that appear between the 1st and 2nd decades of life. The use of high doses of statins or even unusual procedures (apheresis, partial ileal bypass surgery, liver transplantation, gene therapy, or both, is necessary for increasing survival and improving quality of life, because a reduction in cholesterol levels is essential for stabilizing the coronary artery disease and reducing xanthomas. We report our experience with 3 patients with xanthomatous familial hypercholesterolemia and coronary artery disease, who underwent partial ileal bypass surgery. Their follow-up over the years (approximately 8 years showed a mean 30% reduction in total cholesterol, with a significant reduction in the xanthomas and stabilization of the coronary artery disease.

Family-specific aggregation of lipid GWAS variants confers the susceptibility to familial hypercholesterolemia in a large Austrian family

NARCIS (Netherlands)

Nikkola, Elina; Ko, Arthur; Alvarez, Marcus; Cantor, Rita M.; Garske, Kristina; Kim, Elliot; Gee, Stephanie; Rodriguez, Alejandra; Muxel, Reinhard; Matikainen, Niina; Söderlund, Sanni; Motazacker, Mahdi M.; Borén, Jan; Lamina, Claudia; Kronenberg, Florian; Schneider, Wolfgang J.; Palotie, Aarno; Laakso, Markku; Taskinen, Marja-Riitta; Pajukanta, Päivi

2017-01-01

Background and aims: Hypercholesterolemia confers susceptibility to cardiovascular disease (CVD). Both serum total cholesterol (TC) and LDL-cholesterol (LDL-C) exhibit a strong genetic component (heritability estimates 0.41-0.50). However, a large part of this heritability cannot be explained by the

Use of next-generation sequencing to detect LDLR gene copy number variation in familial hypercholesterolemia[S

Science.gov (United States)

Iacocca, Michael A.; Wang, Jian; Dron, Jacqueline S.; Robinson, John F.; McIntyre, Adam D.; Cao, Henian

2017-01-01

Familial hypercholesterolemia (FH) is a heritable condition of severely elevated LDL cholesterol, caused predominantly by autosomal codominant mutations in the LDL receptor gene (LDLR). In providing a molecular diagnosis for FH, the current procedure often includes targeted next-generation sequencing (NGS) panels for the detection of small-scale DNA variants, followed by multiplex ligation-dependent probe amplification (MLPA) in LDLR for the detection of whole-exon copy number variants (CNVs). The latter is essential because ∼10% of FH cases are attributed to CNVs in LDLR; accounting for them decreases false negative findings. Here, we determined the potential of replacing MLPA with bioinformatic analysis applied to NGS data, which uses depth-of-coverage analysis as its principal method to identify whole-exon CNV events. In analysis of 388 FH patient samples, there was 100% concordance in LDLR CNV detection between these two methods: 38 reported CNVs identified by MLPA were also successfully detected by our NGS method, while 350 samples negative for CNVs by MLPA were also negative by NGS. This result suggests that MLPA can be removed from the routine diagnostic screening for FH, significantly reducing associated costs, resources, and analysis time, while promoting more widespread assessment of this important class of mutations across diagnostic laboratories. PMID:28874442

Efficacy and safety of ETC-1002, a novel investigational low-density lipoprotein-cholesterol-lowering therapy for the treatment of patients with hypercholesterolemia and type 2 diabetes mellitus.

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Gutierrez, Maria J; Rosenberg, Noah L; Macdougall, Diane E; Hanselman, Jeffrey C; Margulies, Janice R; Strange, Poul; Milad, Mark A; McBride, Scott J; Newton, Roger S

2014-03-01

8-Hydroxy-2,2,14,14-tetramethylpentadecanedioic acid (ETC-1002) is a small molecule with a unique mechanism of action shown in nonclinical studies to modulate pathways of cholesterol, fatty acid, and carbohydrate metabolism. In previous phase 2 clinical trials, once daily oral treatment with ETC-1002 significantly reduced low-density lipoprotein-cholesterol in patients with hypercholesterolemia. In this trial, the lipid-lowering efficacy of ETC-1002 was evaluated in patients with type 2 diabetes mellitus and hypercholesterolemia. Additional cardiometabolic biomarkers, including glycemic measures, were also assessed. A single-center, double-blind, placebo-controlled trial evaluated 60 patients with type 2 diabetes mellitus and elevated low-density lipoprotein-cholesterol. Patients discontinued all diabetes mellitus and lipid-regulating drugs and were randomized to receive ETC-1002 80 mg QD for 2 weeks followed by 120 mg QD for 2 weeks or placebo for 4 weeks. ETC-1002 lowered low-density lipoprotein-cholesterol levels by 43±2.6% (least squares mean±SE), compared with a reduction of 4±2.5% by placebo at day 29 (Pdiabetes mellitus and hypercholesterolemia without worsening glycemic control. ETC-1002 was well tolerated in this population. http://www.clinicaltrials.gov. Unique identifier: NCT# 01607294.

The impact of mild hypercholesterolemia on glycemic and hormonal profiles, menstrual characteristics and the ovarian morphology of women with polycystic ovarian syndrome.

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Pergialiotis, Vasilios; Trakakis, Eftihios; Chrelias, Charalampos; Papantoniou, Nikolaos; Hatziagelaki, Erifili

2018-03-29

Background The severity of polycystic ovarian syndrome (PCOS) has been clearly associated with insulin resistance, obesity and metabolic syndrome. The purpose of the present cross-sectional study is to investigate whether mild hypercholesterolemia alters the biochemical and clinical profile of PCOS patients. Methods Our study is based on a prospectively collected population of women of reproductive age who were diagnosed with PCOS according to the definition of the Rotterdam European Society of Human Reproduction and Embryology/American Society for Reproductive Medicine (ASRM/ESHRE) criteria. For the correlation analysis we used the non-parametric Spearman's rank correlation coefficient. Partial correlation was also performed to control for potential confounders observed in the univariate analysis. Results Overall, 235 patients were included. Their mean age ranged between 14 and 45 years old and the body mass index (BMI) between 17 and 54. Women with mild hypercholesterolemia had a higher BMI and their fasting insulin was increased as well as indices of insulin resistance [Homeostatic model assessment (HOMA), quantitative insulin sensitivity check index (QUICKI), Matsuda index] compared to women with PCOS with normal cholesterol levels. Correlation statistics suggested that the effect of serum lipids on the hormonal profile of patients was weak. Both low-density lipoprotein (LDL) and high-density lipoprotein (HDL) exerted a significant mild negative correlation to glucose and insulin. However, after controlling the results for BMI and age (the two variables that were found significantly different in the univariate analysis) we observed that this effect was non-significant. Conclusion Mild hypercholesterolemia does not affect the hormonal profile of patients with PCOS; hence, to date, there is no evidence to suggest its treatment for the correction of menstrual and hormonal abnormalities in PCOS women.

Efficacy of functional foods mixture in improving hypercholesterolemia, inflammatory and endothelial dysfunction biomarkers-induced by high cholesterol diet.

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Al-Muzafar, Hessah Mohammed; Amin, Kamal Adel

2017-10-06

Hypercholesterolemia associated with cardiovascular diseases is a global health issue that could be alleviated by functional foods. This study aimed to explore the effects of a high-cholesterol diet on lipid profile, cardiac, inflammatory, and endothelial dysfunction biomarkers, and the possible improvement by functional foods mixture. Male albino rats weighing 100-150 g were randomly divided into four equal groups: 1st control, giving a normal diet; the 2nd received high-cholesterol diet for 8 weeks, the 3rd received the high-cholesterol diet + functional foods mixture, and the 4th administered high-cholesterol diet +atorvastatin (20 mg) orally. The results showed a significant increase in lipid profile and cardiac biomarkers levels (lactate dehydrogenase, creatine kinase and homocystein), also inflammatory markers, as, tumor necrotic factor alpha and chronic reactive proteins were elevated, moreover, vascular adhesion molecule-1 and nitric oxide synthase were disturbed in high-cholesterol diet compared with normal group. While administration of atorvastatin and functional foods mixture ameliorated these alterations. Administration of functional foods mixture and atorvastatin were effective in treating hypercholesterolemia, reduce the risk of inflammation and cardiovascular biomarkers with a high safety margin. These efficiencies may be due to its active ingredient that improve the imbalance in the measured biomarkers.

Effects and Interactions of Prenatal Ethanol Exposure, a Post-Weaning High-Fat Diet and Gender on Adult Hypercholesterolemia Occurrence in Offspring Rats.

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Qi, Yongjian; Luo, Hanwen; Hu, Shuwei; Wu, Yimeng; Magdalou, Jacques; Chen, Liaobin; Wang, Hui

2017-01-01

Prenatal ethanol exposure (PEE) could induce intrauterine programming of hypothalamic-pituitary-adrenal axis-associated neuroendocrine metabolism, resulting in intrauterine growth retardation and susceptibility to adult hypercholesterolemia in offspring. This study aimed to analyse the effects and interactions of PEE, a post-weaning high-fat diet (HFD) and gender on the occurrence of adult hypercholesterolemia in offspring rats. Wistar female rats were treated with ethanol (4 g/kg.d) at gestational days 11-20. The offspring were given a normal diet or HFD after weaning, and the blood cholesterol metabolism phenotype and expression of hepatic cholesterol metabolism related genes were detected in 24-week-old offspring. Furthermore, the interactions among PEE, HFD, and gender on hypercholesterolemia occurrence were analysed. PEE increased the serum total cholesterol (TCH) and low-density lipoprotein-cholesterol (LDL-C) levels and decreased the serum high-density lipoprotein-cholesterol (HDL-C) level in adult offspring rats; the changes in female offspring were greater than those in males. At the same time, the mRNA expression levels of hepatic cholesterol metabolic enzymes (apolipoprotein B (ApoB) and 7α-hydroxylase (CYP7A1))-were increased, while the mRNA expression levels of the scavenger receptor B1 (SR-B1) and LDL receptor (LDLR) were decreased. Furthermore, a three-way ANOVA showed there were interactions among PEE, post-weaning HFD and gender. For PEE offspring, a post-weaning HFD aggravated the elevated hepatic ApoB and CYP7A1 expression and reduced SR-B1 and LDLR expression; the changes in hepatic SR-B1 and CYP7A1 expression were greater in female HFD rats than in males. Our findings suggest that a post-weaning HFD could aggravate offspring hypercholesterolemia caused by PEE and that this mechanism might be associated with hepatic cholesterol metabolic disorders that are aggravated by a post-weaning HFD; hepatic cholesterol metabolism was more sensitive to

Comprehensive gene expression profiling reveals synergistic functional networks in cerebral vessels after hypertension or hypercholesterolemia.

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Wei-Yi Ong

Full Text Available Atherosclerotic stenosis of cerebral arteries or intracranial large artery disease (ICLAD is a major cause of stroke especially in Asians, Hispanics and Africans, but relatively little is known about gene expression changes in vessels at risk. This study compares comprehensive gene expression profiles in the middle cerebral artery (MCA of New Zealand White rabbits exposed to two stroke risk factors i.e. hypertension and/or hypercholesterolemia, by the 2-Kidney-1-Clip method, or dietary supplementation with cholesterol. Microarray and Ingenuity Pathway Analyses of the MCA of the hypertensive rabbits showed up-regulated genes in networks containing the node molecules: UBC (ubiquitin, P38 MAPK, ERK, NFkB, SERPINB2, MMP1 and APP (amyloid precursor protein; and down-regulated genes related to MAPK, ERK 1/2, Akt, 26 s proteasome, histone H3 and UBC. The MCA of hypercholesterolemic rabbits showed differentially expressed genes that are surprisingly, linked to almost the same node molecules as the hypertensive rabbits, despite a relatively low percentage of 'common genes' (21 and 7% between the two conditions. Up-regulated common genes were related to: UBC, SERPINB2, TNF, HNF4A (hepatocyte nuclear factor 4A and APP, and down-regulated genes, related to UBC. Increased HNF4A message and protein were verified in the aorta. Together, these findings reveal similar nodal molecules and gene pathways in cerebral vessels affected by hypertension or hypercholesterolemia, which could be a basis for synergistic action of risk factors in the pathogenesis of ICLAD.

Comprehensive Gene Expression Profiling Reveals Synergistic Functional Networks in Cerebral Vessels after Hypertension or Hypercholesterolemia

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Ong, Wei-Yi; Ng, Mary Pei-Ern; Loke, Sau-Yeen; Jin, Shalai; Wu, Ya-Jun; Tanaka, Kazuhiro; Wong, Peter Tsun-Hon

2013-01-01

Atherosclerotic stenosis of cerebral arteries or intracranial large artery disease (ICLAD) is a major cause of stroke especially in Asians, Hispanics and Africans, but relatively little is known about gene expression changes in vessels at risk. This study compares comprehensive gene expression profiles in the middle cerebral artery (MCA) of New Zealand White rabbits exposed to two stroke risk factors i.e. hypertension and/or hypercholesterolemia, by the 2-Kidney-1-Clip method, or dietary supplementation with cholesterol. Microarray and Ingenuity Pathway Analyses of the MCA of the hypertensive rabbits showed up-regulated genes in networks containing the node molecules: UBC (ubiquitin), P38 MAPK, ERK, NFkB, SERPINB2, MMP1 and APP (amyloid precursor protein); and down-regulated genes related to MAPK, ERK 1/2, Akt, 26 s proteasome, histone H3 and UBC. The MCA of hypercholesterolemic rabbits showed differentially expressed genes that are surprisingly, linked to almost the same node molecules as the hypertensive rabbits, despite a relatively low percentage of ‘common genes’ (21 and 7%) between the two conditions. Up-regulated common genes were related to: UBC, SERPINB2, TNF, HNF4A (hepatocyte nuclear factor 4A) and APP, and down-regulated genes, related to UBC. Increased HNF4A message and protein were verified in the aorta. Together, these findings reveal similar nodal molecules and gene pathways in cerebral vessels affected by hypertension or hypercholesterolemia, which could be a basis for synergistic action of risk factors in the pathogenesis of ICLAD. PMID:23874591

Retrospective analysis of cohort database: Phenotypic variability in a large dataset of patients confirmed to have homozygous familial hypercholesterolemia

NARCIS (Netherlands)

Raal, Frederick J.; Sjouke, Barbara; Hovingh, G. Kees; Isaac, Barton F.

2016-01-01

These data describe the phenotypic variability in a large cohort of patients confirmed to have homozygous familial hypercholesterolemia. Herein, we describe the observed relationship of treated low-density lipoprotein cholesterol with age. We also overlay the low-density lipoprotein receptor gene

Antihypercholesterolemic and Antioxidative Potential of an Extract of the Plant, Piper betle, and Its Active Constituent, Eugenol, in Triton WR-1339-Induced Hypercholesterolemia in Experimental Rats

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Karuppasamy Venkadeswaran

2014-01-01

Full Text Available Hypercholesterolemia is a dominant risk factor for atherosclerosis and cardiovascular diseases. In the present study, the putative antihypercholesterolemic and antioxidative properties of an ethanolic extract of Piper betle and of its active constituent, eugenol, were evaluated in experimental hypercholesterolemia induced by a single intraperitoneal injection of Triton WR-1339 (300 mg/kg b.wt in Wistar rats. Saline-treated hypercholesterolemic rats revealed significantly higher mean blood/serum levels of glucose, total cholesterol, triglycerides, low density and very low density lipoprotein cholesterol, and of serum hepatic marker enzymes; in addition, significantly lower mean serum levels of high density lipoprotein cholesterol and significantly lower mean activities of enzymatic antioxidants and nonenzymatic antioxidants were noted in hepatic tissue samples from saline-treated hypercholesterolemic rats, compared to controls. However, in hypercholesterolemic rats receiving the Piper betle extract (500 mg/kg b.wt or eugenol (5 mg/kg b.wt for seven days orally, all these parameters were significantly better than those in saline-treated hypercholesterolemic rats. The hypercholesterolemia-ameliorating effect was better defined in eugenol-treated than in Piper betle extract-treated rats, being as effective as that of the standard lipid-lowering drug, lovastatin (10 mg/kg b.wt. These results suggest that eugenol, an active constituent of the Piper betle extract, possesses antihypercholesterolemic and other activities in experimental hypercholesterolemic Wistar rats.

Antihypercholesterolemic and Antioxidative Potential of an Extract of the Plant, Piper betle, and Its Active Constituent, Eugenol, in Triton WR-1339-Induced Hypercholesterolemia in Experimental Rats.

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Venkadeswaran, Karuppasamy; Muralidharan, Arumugam Ramachandran; Annadurai, Thangaraj; Ruban, Vasanthakumar Vasantha; Sundararajan, Mahalingam; Anandhi, Ramalingam; Thomas, Philip A; Geraldine, Pitchairaj

2014-01-01

Hypercholesterolemia is a dominant risk factor for atherosclerosis and cardiovascular diseases. In the present study, the putative antihypercholesterolemic and antioxidative properties of an ethanolic extract of Piper betle and of its active constituent, eugenol, were evaluated in experimental hypercholesterolemia induced by a single intraperitoneal injection of Triton WR-1339 (300 mg/kg b.wt) in Wistar rats. Saline-treated hypercholesterolemic rats revealed significantly higher mean blood/serum levels of glucose, total cholesterol, triglycerides, low density and very low density lipoprotein cholesterol, and of serum hepatic marker enzymes; in addition, significantly lower mean serum levels of high density lipoprotein cholesterol and significantly lower mean activities of enzymatic antioxidants and nonenzymatic antioxidants were noted in hepatic tissue samples from saline-treated hypercholesterolemic rats, compared to controls. However, in hypercholesterolemic rats receiving the Piper betle extract (500 mg/kg b.wt) or eugenol (5 mg/kg b.wt) for seven days orally, all these parameters were significantly better than those in saline-treated hypercholesterolemic rats. The hypercholesterolemia-ameliorating effect was better defined in eugenol-treated than in Piper betle extract-treated rats, being as effective as that of the standard lipid-lowering drug, lovastatin (10 mg/kg b.wt). These results suggest that eugenol, an active constituent of the Piper betle extract, possesses antihypercholesterolemic and other activities in experimental hypercholesterolemic Wistar rats.

Hypercholesterolemia and hepatic steatosis in mice fed on low-cost high-fat diet - doi: 10.4025/actascihealthsci.v35i1.10871

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Lívia Bracht

2013-03-01

Full Text Available To verify whether high-fat diet prepared from commercial diet plus chocolate, roasted peanuts and corn cookies induces hypercholesterolemia in mice and whether there is any hepatic involvement in this type of animal testing. Swiss mice received a high-fat diet for 15 and 30 days; plasma cholesterol, triglycerides and glucose rates were determined. Hepatic impairment was evaluated by histopathological analysis. Cholesterol levels increased 43% in animals treated with high-fat diet for 30 days. Further, histopathological analysis revealed that treatment of animals for 15 and 30 days produced hepatic steatosis and steatohepatitis, respectively. Experimental model is suitable for assessing the action of anti-hypercholesterolemia and the treatment of steatohepatitis.  

Successful treatment of homozygous familial hypercholesterolemia using cascade filtration plasmapheresis.

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Kardaş, Fatih; Cetin, Aysun; Solmaz, Musa; Büyükoğlan, Rüksan; Kaynar, Leylagül; Kendirci, Mustafa; Eser, Bülent; Unal, Ali

2012-12-01

The aim of this study was to report the efficacy of low-density lipoprotein cholesterol (LDL-C) apheresisusing a cascade filtration system in pediatric patients with homozygous familial hypercholesterolemia (FH), and toclarify the associated adverse effects and difficulties. LDL-C apheresis using a cascade filtration system was performed in 3 pediatric patientswith homozygous FH; in total, 120 apheresis sessions were performed. Cascade filtration therapy significantly reduced the mean LDL-C values from 418 ± 62 mg/dL to 145 ± 43 mg/dL (p= 0.011). We observed an acute mean reduction in the plasma level of total cholesterol (57.9%), LDL-C (70.8%),and high-density lipoprotein cholesterol (HDL-C) (40.7%). Treatments were well tolerated. The most frequent clinicaladverse effects were hypotension in 3 sessions (2.5%), chills (1.7%) in 2 sessions, and nausea/vomiting in 3 sessions(2.5%). Our experience using the cascade filtration system with 3 patients included good clinical outcomes andlaboratory findings, safe usage, and minor adverse effects and technical problems. None declared.

Randomized, placebo-controlled trial of mipomersen in patients with severe hypercholesterolemia receiving maximally tolerated lipid-lowering therapy.

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Mary P McGowan

potential pharmacologic option for lowering LDL-C in patients with severe hypercholesterolemia not adequately controlled using existing therapies. Future studies will explore alternative dosing schedules aimed at minimizing side effects.ClinicalTrials.gov NCT00794664.

Usefulness of Genetic Polymorphisms and Conventional Risk Factors to Predict Coronary Heart Disease in Patients With Familial Hypercholesterolemia

NARCIS (Netherlands)

van der Net, Jeroen B.; Janssens, A. Cecile J. W.; Defesche, Joep C.; Kastelein, John J. P.; Sijbrands, Eric J. G.; Steyerberg, Ewout W.

2009-01-01

Familial hypercholesterolemia (FH) is an autosomal dominant disorder with an associated high risk of coronary heart disease (CHD). The considerable variation in age of onset of CHD in patients with FH is believed to arise from conventional risk factors, as well as genetic variation other than in the

A 3-year study of atorvastatin in children and adolescents with heterozygous familial hypercholesterolemia.

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Langslet, Gisle; Breazna, Andrei; Drogari, Euridiki

2016-01-01

The efficacy and safety of atorvastatin in children/adolescents aged 10-17 years with heterozygous familial hypercholesterolemia (HeFH) have been demonstrated in trials of up to 1 year in duration. However, the efficacy/safety of >1 year use of atorvastatin in children/adolescents with HeFH, including children from 6 years of age, has not been assessed. To characterize the efficacy and safety of atorvastatin over 3 years and to assess the impact on growth and development in children aged 6-15 years with HeFH. A total of 272 subjects aged 6-15 years with HeFH and low-density lipoprotein cholesterol (LDL-C) ≥4.0 mmol/L (154 mg/dL) were enrolled in a 3-year study (NCT00827606). Subjects were initiated on atorvastatin (5 mg or 10 mg) with doses increased to up to 80 mg based on LDL-C levels. Mean percentage reductions from baseline in LDL-C at 36 months/early termination were 43.8% for subjects at Tanner stage (TS) 1 and 39.9% for TS ≥2. There was no evidence of variations in the lipid-lowering efficacy of atorvastatin between the TS groups analyzed (1 vs ≥2) or in subjects aged Atorvastatin had a favorable safety and tolerability profile, and only 6 (2.2%) subjects discontinued because of adverse events. Atorvastatin over 3 years was efficacious, had no impact on growth/maturation, and was well tolerated in children and adolescents with HeFH aged 6-15 years. Copyright © 2016 National Lipid Association. Published by Elsevier Inc. All rights reserved.

Increased Hepatic Expression of Endothelial Lipase Inhibits Cholesterol Diet-Induced Hypercholesterolemia and Atherosclerosis in Transgenic Rabbits.

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Wang, Chuan; Nishijima, Kazutoshi; Kitajima, Shuji; Niimi, Manabu; Yan, Haizhao; Chen, Yajie; Ning, Bo; Matsuhisa, Fumikazu; Liu, Enqi; Zhang, Jifeng; Chen, Y Eugene; Fan, Jianglin

2017-07-01

Endothelial lipase (EL) is a key determinant in plasma high-density lipoprotein-cholesterol. However, functional roles of EL on the development of atherosclerosis have not been clarified. We investigated whether hepatic expression of EL affects plasma lipoprotein metabolism and cholesterol diet-induced atherosclerosis. We generated transgenic (Tg) rabbits expressing the human EL gene in the liver and then examined the effects of EL expression on plasma lipids and lipoproteins and compared the susceptibility of Tg rabbits with cholesterol diet-induced atherosclerosis with non-Tg littermates. On a chow diet, hepatic expression of human EL in Tg rabbits led to remarkable reductions in plasma levels of total cholesterol, phospholipids, and high-density lipoprotein-cholesterol compared with non-Tg controls. On a cholesterol-rich diet for 16 weeks, Tg rabbits exhibited significantly lower hypercholesterolemia and less atherosclerosis than non-Tg littermates. In Tg rabbits, gross lesion area of aortic atherosclerosis was reduced by 52%, and the lesions were characterized by fewer macrophages and smooth muscle cells compared with non-Tg littermates. Increased hepatic expression of EL attenuates cholesterol diet-induced hypercholesterolemia and protects against atherosclerosis. © 2017 American Heart Association, Inc.

Mutations in the gene for lipoprotein lipase. A cause for low HDL cholesterol levels in individuals heterozygous for familial hypercholesterolemia

NARCIS (Netherlands)

Pimstone, S. N.; Gagné, S. E.; Gagné, C.; Lupien, P. J.; Gaudet, D.; Williams, R. R.; Kotze, M.; Reymer, P. W.; Defesche, J. C.; Kastelein, J. J.

1995-01-01

Familial hypercholesterolemia (FH) is characterized by elevated plasma concentrations of LDL cholesterol resulting from mutations in the gene for the LDL receptor. Low HDL cholesterol levels are seen frequently in patients both heterozygous and homozygous for mutations in this gene. Suggested

High doses of garlic extract significantly attenuated the ratio of serum LDL to HDL level in rat-fed with hypercholesterolemia diet.

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Ebrahimi, Tahereh; Behdad, Behnoosh; Abbasi, Maryam Agha; Rabati, Rahman Ghaffarzadegan; Fayyaz, Amir Farshid; Behnod, Vahid; Asgari, Ali

2015-06-20

Hypercholesterolemia is associated with an increased risk of heart disease. In this study, we investigated the antihyperlipidemic effects of garlic (Allium sativum L.) in rat models of hypercholesterolemic. Wistar male rats were randomly divided into 4 diet groups with garlic supplementation. Male Wistar rats were fed by standard pellet diet (group I), standard diet supplemented with 4% garlic (group II), lipogenic diet (containing sunflower oil, cholesterol and ethanol) equivalent to 200 mg raw garlic/kg body weight (raw) (group III) and lipogenic diet equivalent to 400 mg raw garlic/kg body weight (raw) (group IV). Rats fed 400 g/kg garlic extract(GE), had a significantly lower concentration of serum low-density lipoprotein cholesterol (LDL-C) cholesterol and elevated HDL -C cholesterol at day 28 (P garlic supplementation (P garlic in reducing lateral side effects of hyperlipidemia. Our data demonstrate that GE has protective effects on HDL in rats with high LDL intake. Therefore, it could be used to remedy hypercholesterolemia with help reduce risk of coronary heart disease The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1834155749171141.

Ten years of lipoprotein apheresis for familial hypercholesterolemia in Malaysia: A creative approach by a cardiologist in a developing country

NARCIS (Netherlands)

Khoo, Kah Lin; Page, Michael M.; Liew, Yin Mei; Defesche, Joep C.; Watts, Gerald F.

2016-01-01

Familial hypercholesterolemia (FH) leads to premature coronary artery disease and aortic stenosis, with undertreated severe forms causing death at a young age. Lipoprotein apheresis (LA) is often required for lowering low-density lipoprotein cholesterol levels in severe FH. The objective of this

Familial hypercholesterolemia and atherosclerosis in cloned minipigs created by DNA transposition of a human PCSK9 gain-of-function mutant

DEFF Research Database (Denmark)

Al-Mashhadi, Rozh Husain; Sørensen, Charlotte Brandt; Kragh, Peter M.

2013-01-01

dominant hypercholesterolemia and accelerates atherosclerosis in humans. Using Sleeping Beauty DNA transposition and cloning by somatic cell nuclear transfer, we created Yucatan minipigs with liver-specific expression of human D374Y-PCSK9. D374Y-PCSK9 transgenic pigs displayed reduced hepatic low...

Successful Treatment Of Homozygous Familial Hypercholesterolemia Using Cascade Filtration Plasmapheresis

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Fatih Kardas

2012-12-01

Full Text Available OBJECTIVE: The aim of our study is to discuss the efficacy of low-density lipoprotein-cholesterol (LDL-C apheresis procedure using the cascade filtration system for pediatric patients with homozygous familial hypercholesterolemia (FH, and to clarify the adverse effects and difficulties. METHODS: LDL apheresis using the cascade filtration system was performed in 3 pediatric patients with homozygous FH. In total, 120 apheresis sessions were performed for all patients. RESULTS: Cascade filtration therapy significantly reduced the mean LDL-C values from 418 ± 62 mg/dl to 145 ± 43 mg/dl (p<0.05. We determined an acute mean reduction in the plasma levels of total cholesterol (57.9%, LDL cholesterol (70.8%, and high-density lipoprotein (HDL cholesterol (40.7%. Treatments were well tolerated. The most frequent clinical adverse effects were hypotension in 3 sessions (2.5%, chills/feeling cold (1.7% in 2 sessions, and nausea and vomiting in 3 sessions (2.5%. CONCLUSION: Our experience with three patients using the cascade filtration system were, good clinical outcomes, laboratory findings, safety of usage, minor adverse effects and technical problems.

Optimal Use of Plant Stanol Ester in the Management of Hypercholesterolemia

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Susanna Rosin

2015-01-01

Full Text Available Plant stanol ester is a natural compound which is used as a cholesterol-lowering ingredient in functional foods and food supplements. The safety and efficacy of plant stanol ester have been confirmed in more than 70 published clinical studies and the ingredient is a well-established and widely recommended dietary measure to reduce serum cholesterol. Daily intake of 2 g plant stanols as plant stanol ester lowers LDL-cholesterol by 10%, on average. In Europe, foods with added plant stanol ester have been on the market for 20 years, and today such products are also available in many Asian and American countries. Despite the well-documented efficacy, the full potential in cholesterol reduction may not be reached if plant stanol ester is not used according to recommendations. This review therefore concentrates on the optimal use of plant stanol ester as part of dietary management of hypercholesterolemia. For optimal cholesterol lowering aiming at a lower risk of cardiovascular disease, plant stanol ester should be used daily, in sufficient amounts, with a meal and in combination with other recommended dietary changes.

PCSK9 Antibodies for the Treatment of Hypercholesterolemia

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Ioanna Gouni-Berthold

2014-12-01

Full Text Available The serine protease proprotein convertase subtilisin/kexin type 9 (PCSK9 binds to the low-density lipoprotein (LDL receptor (LDLR and directs it to lysosomes for intracellular degradation. This results in decreased numbers of LDLR available on the hepatic cell surface to bind LDL particles and remove them from the circulation and therefore to a subsequent increase in circulating LDL-cholesterol (LDL-C plasma levels. Since 2003, when the role of PCSK9 in LDL-C metabolism was discovered, there have been major efforts to develop efficient and safe methods to inhibit it. Amongst those, monoclonal antibodies against PCSK9 are the furthest in development, with multiple phase 3 trials already published and with cardiovascular endpoint trials currently underway. Two fully human monoclonal antibodies, evolocumab (AMG 145 and alirocumab (REGN727/SAR236553, have been extensively studied in a wide range of subjects, such as those with statin intolerance, as an add-on to statin therapy, as a monotherapy and in patients with familial hypercholesterolemia. PCSK9 antibodies result in a consistent and robust decrease in LDL-C plasma levels ranging from 40% to 70%, either on top of statins or as a monotherapy. If the safety data from the on-going phase 3 trials remain as reassuring as the data available till now, PCSK9 antibodies will offer a novel, powerful therapeutic option to decrease LDL-C plasma levels and, hopefully, cardiovascular risk.

Randomized controlled trial of oatmeal consumption versus noodle consumption on blood lipids of urban Chinese adults with hypercholesterolemia.

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Zhang, Jian; Li, Lixiang; Song, Pengkun; Wang, Chunrong; Man, Qingqing; Meng, Liping; Cai, Jenny; Kurilich, Anne

2012-08-06

Cardiovascular disease (CVD) is the leading cause of death in China and worldwide. Whole grain oats can reduce risk of CVD by reducing total and LDL-cholesterol, major risk factors for CVD. While this association has been established in many populations, data from Asian populations is limited. Thus, this study investigated the impact of oat consumption on cholesterol levels in Chinese adults. Male and female data from this work were previously published separately in mandarin in two Chinese journals. The combined male and female data were reanalyzed and are presented here. A randomized, controlled, parallel-arm study was conducted at Beijing Hospital, Beijing china. Subjects were adults (men and women) with mild to moderate hypercholesterolemia. The oat group (n=85) consumed 100 grams of instant oat cereal versus the control group (n=81) who consumed 100 grams of wheat flour-based noodles daily for 6 weeks. Laboratory and anthropometric measurements were conducted at baseline and at the end of the 6-week intervention. Dietary fiber intake increased significantly in the oat group compared to the control group at the end of the 6-week intervention. Total-, LDL-cholesterol and waist circumference decreased significantly in the oat group compared to the control. HDL-cholesterol decreased significantly in the control group versus the oat group. There were no significant changes in blood pressure, other anthropometric or laboratory measures between the two groups at the end of the intervention. Instant oatmeal consumed daily for 6 weeks significantly increased fiber intake and decreased major risk factors for CVD in Chinese adults with hypercholesterolemia. Increased consumption of whole grains, including oats, should continue to be encouraged.

Randomized controlled trial of oatmeal consumption versus noodle consumption on blood lipids of urban Chinese adults with hypercholesterolemia

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Zhang Jian

2012-08-01

Full Text Available Abstract Background Cardiovascular disease (CVD is the leading cause of death in China and worldwide. Whole grain oats can reduce risk of CVD by reducing total and LDL-cholesterol, major risk factors for CVD. While this association has been established in many populations, data from Asian populations is limited. Thus, this study investigated the impact of oat consumption on cholesterol levels in Chinese adults. Male and female data from this work were previously published separately in mandarin in two Chinese journals. The combined male and female data were reanalyzed and are presented here. Methods A randomized, controlled, parallel-arm study was conducted at Beijing Hospital, Beijing china. Subjects were adults (men and women with mild to moderate hypercholesterolemia. The oat group (n=85 consumed 100grams of instant oat cereal versus the control group (n=81 who consumed 100grams of wheat flour-based noodles daily for 6weeks. Laboratory and anthropometric measurements were conducted at baseline and at the end of the 6-week intervention. Results Dietary fiber intake increased significantly in the oat group compared to the control group at the end of the 6-week intervention. Total-, LDL-cholesterol and waist circumference decreased significantly in the oat group compared to the control. HDL-cholesterol decreased significantly in the control group versus the oat group. There were no significant changes in blood pressure, other anthropometric or laboratory measures between the two groups at the end of the intervention. Conclusions Instant oatmeal consumed daily for 6 weeks significantly increased fiber intake and decreased major risk factors for CVD in Chinese adults with hypercholesterolemia. Increased consumption of whole grains, including oats, should continue to be encouraged.

Clinical Features and Gaps in the Management of Probable Familial Hypercholesterolemia and Cardiovascular Disease.

Science.gov (United States)

Zafrir, Barak; Jubran, Ayman; Lavie, Gil; Halon, David A; Flugelman, Moshe Y; Shapira, Chen

2017-12-25

Familial hypercholesterolemia (FH) is associated with premature atherosclerotic cardiovascular disease (ASCVD). The introduction of potent therapeutic agents underlies the importance of improving clinical diagnosis and treatment gaps in FH.Methods and Results:A regional database of 1,690 adult patients with high-probability FH based on age-dependent peak-low-density lipoprotein cholesterol (LDL-C) cut-offs and exclusion of secondary causes of severe hypercholesterolemia, was examined to explore the clinical manifestations and current needs in the management of ASCVD, which was present in 248 patients (15%), of whom 83% had coronary artery disease (CAD); 19%, stroke; and 13%, peripheral artery disease. ASCVD was associated with male gender, higher peak LDL-C, lower high-density lipoprotein cholesterol (HDL-C), and traditional risk factor burden. Despite high-intensity statin (prescribed in 83% and combined with ezetimibe in 42%), attainment of LDL-C treatment goals was low, and associated with treatment intensity and drug adherence. Multivessel CAD (adjusted hazard ratios (HR), 3.05; 95% CI: 1.65-5.64), myocardial infarction, and the presence of ≥1 traditional risk factor (HR, 2.59; 95% CI: 1.42-4.71), were associated with repeat coronary revascularizations, in contrast with peak LDL-C >300 mg/dL (HR, 1.13; 95% CI: 0.66-1.91). Main manifestations of ASCVD in FH patients were premature, multivessel CAD with need for recurrent revascularization, associated with classical cardiovascular risk factors but not with peak LDL-C. In spite of intensive therapy with lipid-lowering agents, treatment gaps were significant, with low attainment of LDL-C treatment goals.

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

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

2017-07-01

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

Association of Peripheral Arterial and Cardiovascular Diseases in Familial Hypercholesterolemia

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Pereira, Carolina; Miname, Marcio; Makdisse, Marcia; Kalil, Roberto Filho; Santos, Raul D.

2014-01-01

Familial hypercholesterolemia (FH) is an autosomal dominant genetic disease characterized by an elevation in the serum levels of total cholesterol and of low-density lipoproteins (LDL- c). Known to be closely related to the atherosclerotic process, FH can determine the development of early obstructive lesions in different arterial beds. In this context, FH has also been proposed to be a risk factor for peripheral arterial disease (PAD). This observational cross-sectional study assessed the association of PAD with other manifestations of cardiovascular disease (CVD), such as coronary artery and cerebrovascular disease, in patients with heterozygous FH. The diagnosis of PAD was established by ankle-brachial index (ABI) values ≤ 0.90. This study assessed 202 patients (35% of men) with heterozygous FH (90.6% with LDL receptor mutations), mean age of 51 ± 14 years and total cholesterol levels of 342 ± 86 mg /dL. The prevalences of PAD and previous CVD were 17% and 28.2 %, respectively. On multivariate analysis, an independent association between CVD and the diagnosis of PAD was observed (OR = 2.50; 95% CI: 1.004 - 6.230; p = 0.049). Systematic screening for PAD by use of ABI is feasible to assess patients with FH, and it might indicate an increased risk for CVD. However, further studies are required to determine the role of ABI as a tool to assess the cardiovascular risk of those patients

Association of Peripheral Arterial and Cardiovascular Diseases in Familial Hypercholesterolemia

Directory of Open Access Journals (Sweden)

Carolina Pereira

2014-08-01

Full Text Available Background: Familial hypercholesterolemia (FH is an autosomal dominant genetic disease characterized by an elevation in the serum levels of total cholesterol and of low-density lipoproteins (LDL- c. Known to be closely related to the atherosclerotic process, FH can determine the development of early obstructive lesions in different arterial beds. In this context, FH has also been proposed to be a risk factor for peripheral arterial disease (PAD. Objective: This observational cross-sectional study assessed the association of PAD with other manifestations of cardiovascular disease (CVD, such as coronary artery and cerebrovascular disease, in patients with heterozygous FH. Methods: The diagnosis of PAD was established by ankle-brachial index (ABI values ≤ 0.90. This study assessed 202 patients (35% of men with heterozygous FH (90.6% with LDL receptor mutations, mean age of 51 ± 14 years and total cholesterol levels of 342 ± 86 mg /dL. Results: The prevalences of PAD and previous CVD were 17% and 28.2 %, respectively. On multivariate analysis, an independent association between CVD and the diagnosis of PAD was observed (OR = 2.50; 95% CI: 1.004 - 6.230; p = 0.049. Conclusion: Systematic screening for PAD by use of ABI is feasible to assess patients with FH, and it might indicate an increased risk for CVD. However, further studies are required to determine the role of ABI as a tool to assess the cardiovascular risk of those patients.

Association of Peripheral Arterial and Cardiovascular Diseases in Familial Hypercholesterolemia

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Pereira, Carolina [Instituto do Coração HCFMUSP, São Paulo, SP (Brazil); Hospital Israelita Albert Einstein, São Paulo, SP (Brazil); Miname, Marcio [Instituto do Coração HCFMUSP, São Paulo, SP (Brazil); Makdisse, Marcia [Hospital Israelita Albert Einstein, São Paulo, SP (Brazil); Kalil, Roberto Filho [Instituto do Coração HCFMUSP, São Paulo, SP (Brazil); Santos, Raul D., E-mail: rdsf@cardiol.br [Instituto do Coração HCFMUSP, São Paulo, SP (Brazil); Hospital Israelita Albert Einstein, São Paulo, SP (Brazil)

2014-08-15

Familial hypercholesterolemia (FH) is an autosomal dominant genetic disease characterized by an elevation in the serum levels of total cholesterol and of low-density lipoproteins (LDL- c). Known to be closely related to the atherosclerotic process, FH can determine the development of early obstructive lesions in different arterial beds. In this context, FH has also been proposed to be a risk factor for peripheral arterial disease (PAD). This observational cross-sectional study assessed the association of PAD with other manifestations of cardiovascular disease (CVD), such as coronary artery and cerebrovascular disease, in patients with heterozygous FH. The diagnosis of PAD was established by ankle-brachial index (ABI) values ≤ 0.90. This study assessed 202 patients (35% of men) with heterozygous FH (90.6% with LDL receptor mutations), mean age of 51 ± 14 years and total cholesterol levels of 342 ± 86 mg /dL. The prevalences of PAD and previous CVD were 17% and 28.2 %, respectively. On multivariate analysis, an independent association between CVD and the diagnosis of PAD was observed (OR = 2.50; 95% CI: 1.004 - 6.230; p = 0.049). Systematic screening for PAD by use of ABI is feasible to assess patients with FH, and it might indicate an increased risk for CVD. However, further studies are required to determine the role of ABI as a tool to assess the cardiovascular risk of those patients.

Recent origin and spread of a common Lithuanian mutation, G197del LDLR, causing familial hypercholesterolemia: positive selection is not always necessary to account for disease incidence among Ashkenazi Jews

NARCIS (Netherlands)

Durst, R.; Colombo, R.; Shpitzen, S.; Avi, L. B.; Friedlander, Y.; Wexler, R.; Raal, F. J.; Marais, D. A.; Defesche, J. C.; Mandelshtam, M. Y.; Kotze, M. J.; Leitersdorf, E.; Meiner, V.

2001-01-01

G197del is the most prevalent LDL receptor (LDLR) mutation causing familial hypercholesterolemia (FH) in Ashkenazi Jew (AJ) individuals. The purpose of this study was to determine the origin, age, and population distribution of G197del, as well as to explore environmental and genetic effects on

Is Time an Important Problem in Management of Hypertension and Hypercholesterolemia by Using an Amlodipine-Atorvastatin Single Pill Combination?

Science.gov (United States)

Zeng, Rui; Wang, Mian; Zhang, Li

2016-07-26

BACKGROUND Is the timing of dosing for amlodipine and atorvastatin important with regard to therapeutic efficacy? To answer this question, we designed an outpatient, practice-based, case-control study lasting 8 weeks. MATERIAL AND METHODS Two hundred patients were divided into 2 groups: in Group I, patients were provided with a single pill containing amlodipine/atorvastatin (5/20 mg) to be taken each night at 10 pm, and in Group II, patients were taking amlodipine (5 mg) and atorvastatin (20 mg) each morning at 7 am. RESULTS Our results indicated no obvious difference in blood pressure control between the 2 groups. Taking amlodipine at night not only lowered blood pressure, but it also provided better control during the peak blood pressure in the morning. Hypercholesterolemia control in the 2 groups was also not significantly different, taking atorvastatin in the morning was as effective as dosing at night in patients with hypercholesterolemia. While the carotid IMT, hs-CRP, and LVMI were significantly lower after treatment, no differences were found between the 2 groups. Although no obvious difference was found in adverse drug reactions between the 2 groups, compliance was much better in the single-pill group than in patients taking the 2 medications separately. CONCLUSIONS In conclusion, single-pill amlodipine-atorvastatin taken at night can lower blood pressure and reduce the morning peak blood pressure levels the next day. Additionally, this dosing method could improve patient adherence to the therapy.

ACAT inhibition and progression of carotid atherosclerosis in patients with familial hypercholesterolemia: the CAPTIVATE randomized trial.

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Meuwese, Marijn C; de Groot, Eric; Duivenvoorden, Raphaël; Trip, Mieke D; Ose, Leiv; Maritz, Frans J; Basart, Dick C G; Kastelein, John J P; Habib, Rafik; Davidson, Michael H; Zwinderman, Aeilko H; Schwocho, Lee R; Stein, Evan A

2009-03-18

Inhibition of acyl coenzyme A:cholesterol acyltransferase (ACAT), an intracellular enzyme involved in cholesterol accumulation, with pactimibe was developed to assist in the prevention of cardiovascular disease. To evaluate the efficacy and safety of pactimibe in inhibition of atherosclerosis. A prospective, randomized, stratified, double-blind, placebo-controlled study (Carotid Atherosclerosis Progression Trial Investigating Vascular ACAT Inhibition Treatment Effects [CAPTIVATE]) of 892 patients heterozygous for familial hypercholesterolemia conducted at 40 lipid clinics in the United States, Canada, Europe, South Africa, and Israel between February 1, 2004, and December 31, 2005. Study was terminated on October 26, 2005. Participants received either 100 mg/d of pactimibe (n = 443) or matching placebo (n = 438), in addition to standard lipid-lowering therapy. Carotid atherosclerosis, assessed by ultrasound carotid intima-media thickness (CIMT), at baseline, 12, 18, and 24 months. Maximum CIMT was the primary end point and mean CIMT the secondary end point. Because pactimibe failed to show efficacy in the intravascular coronary ultrasound ACTIVATE study, the CAPTIVATE study was terminated prematurely after a follow-up of 15 months. After 6 months of treatment with pactimibe, low-density lipoprotein cholesterol increased by 7.3% (SD, 23%) compared with 1.4% (SD, 28%) in the placebo group (P = .001). The carotid ultrasonographic scans of the 716 patients with at least 2 scans and obtained at least 40 weeks apart were analyzed. Maximum CIMT measurements did not show a pactimibe treatment effect (difference, 0.004 mm; 95% confidence interval [CI], -0.023 to 0.015 mm; P = .64); however, the less variable mean CIMT measurement revealed an increase of 0.014 mm (95% CI, -0.027 to 0.000 mm; P = .04) in patients administered pactimibe vs placebo. Major cardiovascular events (cardiovascular death, myocardial infarction, and stroke) occurred more often in patients administered

[Comparison of pravastatin and diet in the treatment of hypercholesterolemia].

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Palazzuoli, V; Mondillo, S; Faglia, S; D'Aprile, N; Mangiacotti, L

1995-10-01

Aim of this study is to point out a correct therapy for the treatment of poligenic hypercholesterolemia resistant to dietetic treatment. There have been studied 40 patients which, after repeated haematochemical controls, resulted affected by dyslipidaemia with prevalent increase of the cholesterol levels. After 30 days of standard hypo-caloric dietetic treatment were enrolled 23 patients, 13 males and 10 females, who presented a plasmatic cholesterol level superior to 250 mg% and LDL superior to 160 mg%. All the patients continued the dietetic treatment; 10 patients began pravastatin therapy at a dose of 20 mg/die while to the rest of them was given placebo. The 30th, 60th, 120th day were controlled the following haematochemical parameters: lipidic frame haematology, hepatic and renal function, glycemia and CPK. After 4 months of treatment the average plasmatic levels of cholesterol resulted different in the two groups: mg% (p < 0.001) in the pravastatin group and 262 mg% (P = ns) in the control group. Then, the pravastatin therapy was suspended and all 23 patients continued for 30 days, dietetic treatment and placebo. After 6 months a new control of the lipidic frame was performed. Our results showed that the hypocholesterolic therapy must be continued for ever. In fact, the suspension of the treatment is followed by an immediate rebound of the dislipidaemia which plasmatic cholesterol levels even superior to the basic levels with probable negative repercussion on the cardiovascular system.

Carotid atherosclerosis progression in familial hypercholesterolemia patients: a pooled analysis of the ASAP, ENHANCE, RADIANCE 1, and CAPTIVATE studies.

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Vergeer, Menno; Zhou, Rong; Bots, Michiel L; Duivenvoorden, Raphaël; Koglin, Joerg; Akdim, Fatima; Mitchel, Yale B; Huijgen, Roeland; Sapre, Aditi; de Groot, Eric; Sijbrands, Eric J G; Pasternak, Richard C; Gagné, Claude; Marais, A David; Ballantyne, Christie M; Isaacsohn, Jonathan L; Stalenhoef, Anton F; Kastelein, John J P

2010-07-01

Until recently, patients with heterozygous familial hypercholesterolemia (HeFH) were considered the best subjects for the assessment of changes in carotid intima-media thickness (cIMT) in randomized intervention trials. Our aims were to investigate whether contemporary statin-treated HeFH patients still show accelerated cIMT increase and to assess the impact of statin treatment, before and after random assignment, on atherosclerosis progression. We retrospectively evaluated cIMT change, and prior statin treatment and postbaseline LDL-C change as predictors of cIMT change, in 1513 HeFH patients who were randomly assigned to the statin arms of the early ASAP and more recent RADIANCE 1, CAPTIVATE, and ENHANCE studies. In the 3 recent studies combined, mean cIMT increased at only 33%of the rate of the simvastatin-treated patients in the ASAP study (0.014 mm/2 years [95% confidence interval, -0.0003-0.028] versus 0.041 mm/2 years [95% confidence interval, 0.020-0.061]; P<0.05). Patients whose statin therapy could be intensified, as evidenced by an LDL-C decrease after the initiation of on-trial statin therapy, showed cIMT decrease in the first 6 to 12 months and a much lower cIMT increase measured over the full 2 years. In line with this, previously statin-naive HeFH patients showed a lower overall cIMT increase. Over the years, intensification of statin therapy in HeFH patients has resulted in an impressive decrease in carotid atherosclerosis progression. In studies that assess other antiatherosclerotic modalities, statin therapy may still induce rapid changes in cIMT. For future cIMT studies, our analyses suggest that patient populations other than intensively pretreated HeFH patients should be selected and that the statin regimen should not be changed on study initiation.

[The role of structural heterogeneity of circulating lipids in the regulation of lipoprotein metabolism in the plasma and lymph in hypercholesterolemia in dogs].

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Kosukhin, A B; Akhmetova, B S

1986-01-01

Fatty acid spectrum of lipoproteins was studied in intestinal steam lymph and blood plasma of dogs with alimentary hypercholesterolemia. Mechanism of cholesterol accumulation in blood plasma appears to relate to increase in content of cholesterol palmitate which is secreted from intestine into lymph and hydrolyzed slowly in liver tissue. Alterations in composition of fatty acid acyls of cholesterol esters, of phosphatidyl cholines and triacyl glycerides as well as effect of these alterations on the lecithin-cholesterol acyl-transferase reaction and lipoprotein lipolysis are discussed.

Contemporary Trends in the Management and Outcomes of Patients With Familial Hypercholesterolemia in Canada: A Prospective Observational Study.

Science.gov (United States)

Brunham, Liam R; Cermakova, Lubomira; Lee, Terry; Priecelova, Ida; Alloul, Karine; de Chantal, Marilyn; Francis, Gordon A; Frohlich, Jiri

2017-03-01

Heterozygous familial hypercholesterolemia (HeFH) is one of the most common genetic diseases in the world and an important cause of premature cardiovascular (CV) disease. The purpose of this study was to characterize the clinical features, current treatment patterns, and CV outcomes of patients with HeFH in British Columbia, Canada. We conducted a longitudinal observational study of patients with HeFH attending a specialized lipid clinic. We collected data on lipid levels, medication use, and CV events at baseline and last follow-up. We recruited 339 patients with clinically diagnosed HeFH, with a total of 3700 person-years of follow-up. The mean low-density lipoprotein cholesterol (LDL-C) level was 5.9 mmol/L at baseline and 3.7 mmol/L at last follow-up. Use of lipid-lowering therapy (LLT) increased from 35.7% at baseline to 84.7% at last follow-up. A ≥ 50% reduction in LDL-C level was achieved in 34.5% of patients, and an LDL-C level ≤ 2 mmol/L was seen in 8.3%. The overall CV event rate in this cohort was 33.5/1000 person-years. Among patients who had a CV event during follow-up, 59% experienced a recurrent event within 5 years. These data contribute to our understanding of contemporary trends in the management of patients with HeFH in Canada. Despite a majority of patients receiving LLT, few patients reached high-risk lipid targets. These data highlight important opportunities to improve the care of patients with HeFH. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Lysosomal acid lipase deficiency: A hidden disease among cohorts of familial hypercholesterolemia?

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Chora, Joana Rita; Alves, Ana Catarina; Medeiros, Ana Margarida; Mariano, Cibelle; Lobarinhas, Goreti; Guerra, António; Mansilha, Helena; Cortez-Pinto, Helena; Bourbon, Mafalda

Lysosomal acid lipase deficiency (LALD) is an autosomal recessive disorder and an unrecognized cause of dyslipidemia. Patients usually present with dyslipidemia and altered liver function and mutations in LIPA gene are the underlying cause of LALD. The aim of this study was to investigate LALD in individuals with severe dyslipidemia and/or liver steatosis. Coding, splice regions, and promoter region of LIPA were sequenced by Sanger sequencing in a cohort of mutation-negative familial hypercholesterolemia (FH) patients (n = 492) and in a population sample comprising individuals with several types of dyslipidemia and/or liver steatosis (n = 258). This study led to the identification of LALD in 4 children referred to the Portuguese FH Study, all with a clinical diagnosis of FH. Mild liver dysfunction was present at the age of FH diagnosis; however, a diagnosis of LALD was not considered. No adults at the time of referral have been identified with LALD. LALD is a life-threatening disorder, and early identification is crucial for the implementation of specific treatment to avoid premature mortality. FH cohorts should be investigated to identify possible LALD patients, who will need appropriate treatment. These results highlight the importance of correctly identifying the etiology of the dyslipidemia. Copyright © 2017 National Lipid Association. Published by Elsevier Inc. All rights reserved.

Prickly pear induces upregulation of liver LDL binding in familial heterozygous hypercholesterolemia

International Nuclear Information System (INIS)

Palumbo, B.; Palumbo, R.; Efthimiou, Y.; Stamatopoulos, J.; Sinzinger, H.; Oguogho, A.; Budinsky, A.; Sinzinger, H.

2003-01-01

The hypoglycemic effect of prickly pear is well known by native local Indian population since a long time. Beside the beneficial effects on lipid metabolism, oxidation injury and platelet function has been claimed in experimental animals. We recently found an upregulation of apo-B/E receptor. We therefore examined 10 patients with isolated heterozygous familial hypercholesterolemia (FH) being enrolled in a dietary run-in phase of 6 weeks after dietary counselling and a further 6 weeks of prickly pear addition. Uptake of autologous 123 I-radiolabeled LDL was determined at entry as well as after 6 weeks of daily prickly pear ingestion. We found a significant (p 176.4 mg/dl; p 123 I-LDL binding by prickly pear in FH-patients in vivo and indicate that prickly pear exerts a significant hypolipidemic action via receptor upregulation. (author)

Pregnancy in a Woman with Homozygous Familial Hypercholesterolemia Not on Low-Density Lipoprotein Apheresis

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Akl C. Fahed

2012-11-01

Full Text Available Pregnancy in women with homozygous familial hypercholesterolemia (FH has been rarely reported and might pose risks on the mother and her fetus. Although most reported cases remained on low-density lipoprotein (LDL apheresis, there are no clear guidelines regarding the management of this entity. We report the first case of an uncomplicated pregnancy in a 24-year-old homozygous FH woman who was not maintained on LDL apheresis. FH expresses a wide variability in the phenotype, and management of homozygous FH cases who desire to become pregnant should be individualized based on preconceptional assessment with frequent antenatal follow-up. Decisions on management should be made after weighing the risks versus benefits of LDL apheresis.

[Recomendations for clinical use of food enriched phytosterols/phytostanols handling hypercholesterolemia].

Science.gov (United States)

Merino, Jordi; Masana, Luis; Guijarro, Carlos; Ascaso, Juan; Lagares, Manuel; Civeira, Fernando

2014-01-01

Raised low-density lipoprotein cholesterol (LDLc) plasma concentration is a major risk factor for atherosclerotic cardiovascular disease. Despite international recommendations on hypercholesterolemia management the percentage of individuals with LDLc plasma concentration above goals according to their global cardiovascular risk remains high, and additional therapeutic strategies should be evaluated. Consumption of functional foods enriched with phytosterols (PSRs) and phytostanols (PSNs) reduces LDLc concentrations by 10% as average. Although recommended as part of any lipid-lowering diet in the first intervention step, PSRs/PSNs maintain their LDL reduction capacity when administered with lipid-lowering drugs; therefore, they can be also considered in some cases as an adjuvant to drug therapy. In this document we summarise the latest evidence regarding the LDL reducing effects of PSR/PSN supplementation, alone or as an add-on to hipolipemic drugs and the international recommendations of its clinical use. Copyright © 2014 Sociedad Española de Arteriosclerosis. Published by Elsevier España. All rights reserved.

Lipoprotein metabolism in familial hypercholesterolemia: Serial assessment using a one-step ultracentrifugation method

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Hayato Tada

2015-04-01

Full Text Available Objectives: It is well known that familial hypercholesterolemia (FH is a common inherited disorder that can markedly elevate the level of plasma LDL cholesterol. However, little data exists regarding the clinical impact of the plasma triglyceride (TG-rich lipoprotein fraction, including VLDL and IDL, in FH. Thus, we assessed the hypothesis that the mutations in the LDL receptor modulate lipoprotein metabolism other than the LDL fraction. Design and methods: We investigated plasma lipoprotein with a one-step ultracentrifugation method for 146 controls (mean age=61.4±17.1 yr, mean LDL cholesterol=92.7±61.2 mg/dl, 213 heterozygous mutation-determined FH subjects (mean age=46.0±18.0 yr, mean LDL cholesterol=225.1±61.2 mg/dl, and 16 homozygous/compound heterozygous mutation-determined FH subjects (mean age=26.9±17.1 yr, mean LDL cholesterol=428.6±86.1 mg/dl. In addition, we evaluated cholesterol/TG ratio in each lipoprotein fraction separated by ultracentrifugation. Results: In addition to total cholesterol and LDL cholesterol levels, VLDL cholesterol (19.5±10.4, 25.2±19.3, 29.5±21.4 mg/dl, respectively and IDL cholesterol (8.3±3.7, 16.8±11.5, 40.0±37.3 mg/dl, respectively exhibited a tri-model distribution according to their status in LDL receptor mutation(s. Moreover, the ratios of cholesterol/TG of each lipoprotein fraction increased significantly in heterozygous FH and homozygous/compound heterozygous FH groups, compared with that of controls, suggesting that the abnormality in LDL receptor modulates the quality as well as the quantity of each lipoprotein fraction. Conclusions: Our results indicate that cholesterol in TG-rich lipoproteins, including VLDL and IDL, are significantly higher in FH subjects, revealing a tri-modal distribution according to the number of LDL receptor mutations. Keywords: LDL cholesterol, Familial hypercholesterolemia, Ultracentrifugation, Lipoprotein

Dietary supplementation of defatted kenaf (Hibiscus cannabinus L.) seed meal and its phenolics-saponins rich extract effectively attenuates diet-induced hypercholesterolemia in rats.

Science.gov (United States)

Chan, Kim Wei; Ismail, Maznah; Mohd Esa, Norhaizan; Imam, Mustapha Umar; Ooi, Der Jiun; Khong, Nicholas M H

2018-02-21

Kenaf is one of the important commercial fiber crops worldwide and defatted kenaf seed meal (DKSM) is a secondary by-product from the kenaf industry. Thus, efforts to turn this low-cost agricultural waste into value-added functional food ingredients will definitely bring advantageous impacts to the community health, environment and economy. The present study was aimed to investigate the cardioprotective properties of DKSM and its phenolics-saponins rich extract (PSRE) in diet-induced hypercholesterolemic rat model. Hypercholesterolemia was induced in Sprague-Dawley rats via atherogenic diet feeding and dietary interventions were conducted by incorporating DKSM (15% and 30%) and equivalent levels of PSRE (2.3% and 4.6%, respectively, equivalent to the total content of phenolics and saponins in DKSM groups) into the atherogenic diets. After 10 weeks of DKSM and PSRE supplementation, the hepatosomatic index, hepatosteatosis, serum lipid profile, Castelli risk indexes as well as hepatic and renal functions of hypercholesterolemic rats were significantly improved (p 0.05), but superiorly upregulated by PSRE (p < 0.05). The combined results showed that hypercholesterolemia and the atherogenic risk in rats were effectively attenuated by DKSM and PSRE supplementation, possibly via modulations of multiple vital processes in hepatic cholesterol metabolism. Furthermore, phenolics and saponins may be the bioactives conferring DKSM and PSRE with their anti-hypercholesterolemic properties. In conclusion, DKSM and PSRE are prospective cardioprotective functional food ingredients for hypercholesterolemic individuals.

Phytosterol capsules and serum cholesterol in hypercholesterolemia: a randomized controlled trial.

Science.gov (United States)

Ottestad, Inger; Ose, Leiv; Wennersberg, Marianne H; Granlund, Linda; Kirkhus, Bente; Retterstøl, Kjetil

2013-06-01

Phytosterols are recommended in combination with diet therapy to reduce elevated LDL-cholesterol level. Meta-analyses indicate a 10% reduction in LDL-cholesterol from intake of approximately 2 g phytosterols/d incorporated into fat-based foods. However, the cholesterol lowering effect from capsules containing phytosterols is less documented. The pre-specified primary endpoint of the present study was to investigate the effect of capsules with phytosterols on circulating LDL-cholesterol in patients with mild to moderate hypercholesterolemia. In a double-blinded, randomized, placebo-controlled crossover study, 41 men and women were randomized into two four-weeks intervention periods with softgel capsules containing either phytosterols (2.0 g/d) or sunflower oil. There was a three-weeks washout period between the intervention periods. No significant difference in total- or LDL-cholesterol between the phytosterol and the placebo period were observed after four weeks intervention (0.0 mmol/L (95%CI: -0.3 to 0.2), P = 0.74 and -0.1 mmol/L (95%CI: -0.3 to 0.1), P = 0.32, respectively). Daily intake of capsules containing 2 g phytosterols did not reduce total- or LDL-cholesterol significantly in a highly relevant target group for the use of phytosterol products. The present results may emphasize the importance of choosing a suitable dosage-delivery system in order to achieve optimal cholesterol lowering effect. The study was registered at www.clinicaltrials.gov, IDno:NCT00485095. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Effect of dietary intervention and lipid-lowering treatment on brachial vasoreactivity in patients with ischemic heart disease and hypercholesterolemia

DEFF Research Database (Denmark)

Søndergaard, Eva; Møller, Jacob E; Egstrup, Kenneth

2003-01-01

BACKGROUND: The "Mediterranean" diet and statin treatment have both independently been shown to improve survival and reduce the risk of cardiovascular events in patients with ischemic heart disease (IHD), but no studies have evaluated the effect of this combination on endothelial function. We...... factors and vessel size (P =.02; beta = -2.66 [-4.91; -0.41]). CONCLUSION: Dietary intervention with the Mediterranean diet and statin treatment improve FMD in the brachial artery in patients with IHD and hypercholesterolemia to a greater degree than statin treatment alone....... therefore sought to evaluate the effect of the combination dietary intervention and lipid-lowering treatment on brachial vasoreactivity. METHODS: A total of 131 consecutive patients with documented IHD and a serum cholesterol level > or =5 mmol/L (193 mg/dL) were randomized to receive Mediterranean dietary...

Relative risk for cardiovascular atherosclerotic events after smoking cessation: 6–9 years excess risk in individuals with familial hypercholesterolemia

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Kastelein John JP

2006-10-01

Full Text Available Abstract Background Smoking history is often di- or trichotomized into for example "never, ever or current smoking". However, smoking must be treated as a time-dependent covariate when lifetime data is available. In particular, individuals do not smoke at birth, there is usually a wide variation with respect to smoking history, and smoking cessation must also be considered. Methods Therefore we analyzed smoking as a time-dependent risk factor for cardiovascular atherosclerotic events in a cohort of 2400 individuals with familial hypercholesterolemia who were followed from birth until 2004. Excess risk after smoking-cessation was modelled in a Cox regression model with linear and exponential decaying trends. The model with the highest likelihood value was used to estimate the decay of the excess risk of smoking. Results Atherosclerotic events were observed in 779 patients with familial hypercholesterolemia and 1569 individuals had a smoking history. In the model with the highest likelihood value the risk reduction of smoking after cessation follows a linear pattern with time and it appears to take 6 to 9 years before the excess risk is reduced to zero. The risk of atherosclerotic events due to smoking was estimated as 2.1 (95% confidence interval 1.5; 2.9. Conclusion It was concluded that excess risk due to smoking declined linearly after cessation in at least six to nine years.

Managing hypercholesterolemia and preventing cardiovascular events in elderly and younger Chinese adults: focus on rosuvastatin.

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Wang, Zhen; Ge, Junbo

2014-01-01

Coronary heart disease (CHD) is the leading cause of death worldwide. The efficacy and safety of statins in primary and secondary prevention of CHD is confirmed in several large studies, and rosuvastatin is the latest statin on market. We review the published literature on rosuvastatin in Chinese people. The pharmacokinetics of rosuvastatin in Chinese is somewhat different from that in Caucasians, but this does not influence the linear relationship between dosage and efficacy and with no drug accumulation. Rosuvastatin 5-20 mg/day is effective and safe in decreasing low-density lipoprotein cholesterol in both younger and elderly patients with hypercholesterolemia, even in very elderly patients. Rosuvastatin also shows anti-inflammatory and anti-atherosclerosis features, such as reducing carotid intima-media thickness and plaque area. Rosuvastatin can also improve the prognosis of Chinese CHD patients, such as in the case of acute myocardial infarction. Its adverse-event rate is low and comparable to other statins. In conclusion, rosuvastatin is effective and safe for younger or elderly Chinese patients.

Lead nitrate-induced development of hypercholesterolemia in rats: sterol-independent gene regulation of hepatic enzymes responsible for cholesterol homeostasis.

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Kojima, Misaki; Masui, Toshimitsu; Nemoto, Kiyomitsu; Degawa, Masakuni

2004-12-01

Changes in the gene expressions of hepatic enzymes responsible for cholesterol homeostasis were examined during the process of lead nitrate (LN)-induced development of hypercholesterolemia in male rats. Total cholesterol levels in the liver and serum were significantly increased at 3-72 h and 12-72 h, respectively, after LN-treatment (100 micromol/kg, i.v.). Despite the development of hypercholesterolemia, the genes for hepatic 3-hydroxy-3-methylglutaryl-CoA reductase (HMGR) and other enzymes (FPPS, farnesyl diphosphate synthase; SQS, squalene synthase; CYP51, lanosterol 14alpha-demethylase) responsible for cholesterol biosynthesis were activated at 3-24 h and 12-18 h, respectively. On the other hand, the gene expression of cholesterol 7alpha-hydroxylase (CYP7A1), a catabolic enzyme of cholesterol, was remarkably suppressed at 3-72 h. The gene expression levels of cytokines interleukin-1beta (IL-1beta) and TNF-alpha, which activate the HMGR gene and suppress the CYP7A1 gene, were significantly increased at 1-3 h and 3-24 h, respectively. Furthermore, gene activation of SREBP-2, a gene activator of several cholesterogenic enzymes, occurred before the gene activations of FPPS, SQS and CYP51. This is the first report demonstrating sterol-independent gene regulation of hepatic enzymes responsible for cholesterol homeostasis in LN-treated male rats. The mechanisms for the altered-gene expressions of hepatic enzymes in LN-treated rats are discussed.

Anti-atherosclerotic effect of Cynodon dactylon extract on experimentally induced hypercholesterolemia in rats.

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Pashaie, Belal; Hobbenaghi, Rahim; Malekinejad, Hassan

2017-01-01

Cynodon dactylon (Bermuda grass) is a perennial plant traditionally used as an herbal medicine in many countries. In the present study, anti-atherosclerotic property of ethanolic extract of C. dactylon was investigated in the experimentally induced hypercholesterolemia in rats. In this study, 36 male Wistar rats were selected and allocated into six groups (n = 6). The control group received a normal diet, sham group received a high cholesterol diet (HCD; 1.50% cholesterol and 24.00% fat) and other groups received a HCD and ethanolic extract of C. dactylon at low (100 mg kg -1 ), moderate (200 mg kg -1 ) and maximum (400 mg kg -1 ) doses via gavages. The last group received atorvastatin (10 mg kg -1 ) through gavage with a HCD. The study period for all groups was six months. At the end of this period, parameters including total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) were assessed in the blood samples. Additionally, histopathological and immunohistochemical examinations on coronary and aorta arteries sections were performed. The results showed an increase in vessels wall thickness and proliferation of smooth muscle cells in the HCD group, while these pathological changes were not seen in C. dactylon -treated groups. Treatment of HCD animals with C. dactylon positively changed lipid profile by lowering of TC, TG and LDL-C. The results indicate that C. dactylon prevents from early atherosclerotic changes in the vessels wall.

My Approach to the Patient With Familial Hypercholesterolemia

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Safarova, Maya S.; Kullo, Iftikhar J.

2017-01-01

Familial hypercholesterolemia (FH), a relatively common Mendelian genetic disorder, is associated with a dramatically increased lifetime risk of premature atherosclerotic cardiovascular disease due to elevated plasma low-density lipoprotein cholesterol (LDL-C) levels. The diagnosis of FH is based on clinical presentation or genetic testing. Early identification of patients with FH is of great public health importance because preventive strategies can lower the absolute lifetime cardiovascular risk and screening can detect affected relatives. However, low awareness, detection, and control of FH pose hurdles in the prevention of FH-related cardiovascular events. Of the estimated 0.65 million to 1 million patients with FH in the United States, less than 10% carry a diagnosis of FH. Based on registry data, a substantial proportion of patients with FH are receiving no or inadequate lipid-lowering therapy. Statins remain the mainstay of treatment for patients with FH. Lipoprotein apheresis and newly approved lipid-lowering drugs are valuable adjuncts to statin therapy, particularly when the LDL-C–lowering response is suboptimal. Monoclonal antibodies targeting proprotein convertase subtilisin/kexin type 9 provide an additional approximately 60% lowering of LDL-C levels and are approved for use in patients with FH. For homozygous FH, 2 new drugs that work independent of the LDL receptor pathway are available: an apolipoprotein B antisense oligonucleotide (mipomersen) and a microsomal triglyceride transfer protein inhibitor (lomitapide). This review attempts to critically examine the available data to provide a summary of the current evidence for managing patients with FH, including screening, diagnosis, treatment, and surveillance. PMID:27261867

Roles of the WHHL Rabbit in Translational Research on Hypercholesterolemia and Cardiovascular Diseases

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Tsutomu Kobayashi

2011-01-01

Full Text Available Conquering cardiovascular diseases is one of the most important problems in human health. To overcome cardiovascular diseases, animal models have played important roles. Although the prevalence of genetically modified animals, particularly mice and rats, has contributed greatly to biomedical research, not all human diseases can be investigated in this way. In the study of cardiovascular diseases, mice and rats are inappropriate because of marked differences in lipoprotein metabolism, pathophysiological findings of atherosclerosis, and cardiac function. On the other hand, since lipoprotein metabolism and atherosclerotic lesions in rabbits closely resemble those in humans, several useful animal models for these diseases have been developed in rabbits. One of the most famous of these is the Watanabe heritable hyperlipidemic (WHHL rabbit, which develops hypercholesterolemia and atherosclerosis spontaneously due to genetic and functional deficiencies of the low-density lipoprotein (LDL receptor. The WHHL rabbit has been improved to develop myocardial infarction, and the new strain was designated the myocardial infarction-prone WHHL (WHHLMI rabbit. This review summarizes the importance of selecting animal species for translational research in biomedical science, the development of WHHL and WHHLMI rabbits, their application to the development of hypocholesterolemic and/or antiatherosclerotic drugs, and future prospects regarding WHHL and WHHLMI rabbits.

Non-invasive diagnostic methods for atherosclerosis and use in assessing progression and regression in hypercholesterolemia

International Nuclear Information System (INIS)

Tsushima, Motoo; Fujii, Shigeki; Yutani, Chikao; Yamamoto, Akira; Naitoh, Hiroaki.

1990-01-01

We evaluated the wall thickening and stenosis rate (ASI), the calcification rate (ACI), and the wall thickening and calcification stenosis rate (SCI) of the lower abdominal aorta calculated by the 12 sector method from simple or enhanced computed tomography. The intra-observer variation of the calculation of ASI was 5.7% and that of ACI was 2.4%. In 9 patients who underwent an autopsy examination, ACI was significantly correlated with the rate of the calcification dimension to the whole objective area of the abdominal aorta (r=0.856, p<0.01). However, there were no correlations between ASI and the surface involvement or the atherosclerotic index obtained by the point-counting method of the autopsy materials. In the analysis of 40 patients with atherosclerotic vascular diseases, ASI and ACI were also highly correlated with the percentage volume of the arterial wall in relation to the whole volume of the observed artery (r=0.852, p<0.0001) and also the percentage calcification volume (r=0.913, p<0.0001) calculated by the computed method, respectively. The percentage of atherosclerotic vascular diseases increased in the group of both high ASI (over 10%) and high ACI (over 20%). We used SCI as a reliable index when the progression and regression of atherosclerosis was considered. Among patients of hypercholesterolemia consisting of 15 with familial hypercholesterolemia (FH) and 6 non-FH patients, the change of SCI (d-SCI) was significantly correlated with the change of total cholesterol concentration (d-TC) after the treatment (r=0.466, p<0.05) and the change of the right Achilles' tendon thickening (d-ATT) was also correlated with d-TC (r=0.634, p<0.005). However, no correlation between d-SCI and d-ATT was observed. In conclusion, CT indices of atherosclerosis were useful as a noninvasive quantitative diagnostic method and we were able to use them to assess the progression and regression of atherosclerosis. (author)

Protective effects of Allium sativum against defects of hypercholesterolemia on pregnant rats and their offspring.

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El-Sayyad, Hassan I; Abou-El-Naga, Amoura M; Gadallah, Abdelalim A; Bakr, Iman H

2010-06-10

Sixty fertile female and male albino rats of Wistar strain (I male/ 3 females) were used in the present study. The females were divided into four groups of ten rats each. Group 1 received water and standard feeds for thirty-four days. Group 2 was fed with a cholesterol-containing diet (1%) for two weeks prior to onset of gestation and maintained administration till parturition, produce atherosclerosis (34 days). Group 3 received intragastric administration of 100mg homogenate of garlic (Allium sativum)/kg body weight for three weeks prior to onset of gestation as well as throughout the gestation period. Group 4 intragastrically administered garlic for one week of group B and maintained with combined garlic-treatment for the mentioned period. At parturition, the pregnant were sacrificed and serum total cholesterol (TCL), triglycerides (TG), HDL, LDL and creatine kinase activity (CK) were determined. The total numbers of offspring were recorded and examined morphological for congenital abnormalities. Biopsies of heart and dorsal aorta of both pregnant and their offspring (1 day-age) were processed for investigation at light and transmission electron microscopy. The skeleton of the newborn of different experimental groups were stained with alizarin red s and mor-phometric assessment of mandibular and appendicular bone length. The study revealed that the myocardium of atherosclerotic mother exhibited leuhkocytic inflammatory cell infiltration associated with necrosis, eosinophilia of myocardiai fibers, and edema of blood vessels. Ultrastructural studies revealed swelling of mitochondria, disruption of cristae in the myocardiai muscle fibers. The dorsal aorta possessed accumulation of extra-cellular lipid in intima lining of endothelium. The collagenous fibrils in the tunica adventitia became fragile and loosely separated from each other. Numerous foamy lipid loaden cells were detected within the tunica intima causing deterioration of the elastic fibers, resulting in

2017 Position Paper of the Italian Society for Cardiovascular Prevention (SIPREC) for an Updated Clinical Management of Hypercholesterolemia and Cardiovascular Risk: Executive Document.

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Volpe, Massimo; Volpe, Roberto; Gallo, Giovanna; Presta, Vivianne; Tocci, Giuliano; Folco, Emanuela; Peracino, Andrea; Tremoli, Elena; Trimarco, Bruno

2017-09-01

The benefits achieved by implementing cardiovascular prevention strategies in terms of reduced incidence of atherosclerotic diseases and mortality are accepted, worldwide. In particular, the clinical management of hypercholesterolemia has a fundamental role for all preventive strategies, both in primary and secondary prevention, at each stage of cardiovascular risk. Since the net clinical benefit of lipid-lowering therapy largely depends on baseline individual cardiovascular risk profile, the assessment of individual risk is essential to establish type and intensity of both preventive and therapeutic strategies. Thus, the real challenge in a setting of clinical practice is not only to identify whom to treat among individuals at low-to-moderate risk, but mostly how much and how long to treat high or very-high risk patients. This manuscript, which reflects concepts and positions that have been published in a more extensive document of the Italian Society for Cardiovascular Prevention (SIPREC), deals with the diagnostic and therapeutic management of patients with dyslipidaemia, with an evidence-based approach adapted and updated from recent guidelines of the European Society of Cardiology and very recent results of randomized clinical trials. The purpose is to suggest a multidimensional and integrated actions aimed at eliminating or minimizing the impact of cardiovascular diseases and their related disabilities and mortality in patients with hypercholesterolemia.

The role of black rice (Oryza sativa L.) in the control of hypercholesterolemia in rats.

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Salgado, Jocelem Mastrodi; Oliveira, Anderson Giovanni Candido de; Mansi, Débora Niero; Donado-Pestana, Carlos M; Bastos, Candido Ricardo; Marcondes, Fernanda Klein

2010-12-01

Cardiovascular disease is a serious public health problem; it is the first "cause of death" in Brazil and in developed countries. Thus, it is essential to search for alternative sources such as some functional foods to prevent and control the risks of this disease. The purpose of this study was to evaluate the lipidemic parameters in hypercholesterolemic rats fed diets containing black rice variety IAC 600 or unrefined rice. Adult male Wistar rats (Rattus norvegicus var. albinos) were used, weighing about 200-220 g. The animals were divided into four groups: the first received a control casein diet, the second received hypercholesterolemic diet, and the other two groups, after induction of hypercholesterolemia, received the test diets, the first containing 20% black rice and the second 20% unrefined, for 30 days. It was observed that diet containing black rice reduced the level of plasma cholesterol, triglycerides, and low-density lipoprotein. For high-density lipoprotein values, the diet that provided an increase in the levels was the black rice. The diet containing black rice was more effective in controlling the lipidemia in rats compared with the whole rice diet.

Managing hypercholesterolemia and preventing cardiovascular events in elderly and younger Chinese adults: focus on rosuvastatin

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Wang Z

2013-12-01

Full Text Available Zhen Wang, Junbo GeDepartment of Cardiology, Zhongshan Hospital, Shanghai, People's Republic of ChinaAbstract: Coronary heart disease (CHD is the leading cause of death worldwide. The efficacy and safety of statins in primary and secondary prevention of CHD is confirmed in several large studies, and rosuvastatin is the latest statin on market. We review the published literature on rosuvastatin in Chinese people. The pharmacokinetics of rosuvastatin in Chinese is somewhat different from that in Caucasians, but this does not influence the linear relationship between dosage and efficacy and with no drug accumulation. Rosuvastatin 5–20 mg/day is effective and safe in decreasing low-density lipoprotein cholesterol in both younger and elderly patients with hypercholesterolemia, even in very elderly patients. Rosuvastatin also shows anti-inflammatory and antiatherosclerosis features, such as reducing carotid intima-media thickness and plaque area. Rosuvastatin can also improve the prognosis of Chinese CHD patients, such as in the case of acute myocardial infarction. Its adverse-event rate is low and comparable to other statins. In conclusion, rosuvastatin is effective and safe for younger or elderly Chinese patients.Keywords: rosuvastatin, Chinese, younger, elderly

Benefits of blackberry nectar (Rubus spp.) relative to hypercholesterolemia and lipid peroxidation Beneficios del néctar de mora (Rubus spp.) en relación con la hipercolesterolemia y la peroxidación lipídica

OpenAIRE

P. R. Ferreira de Araujo; V. da Silva Santos; A. Rodrigues Machado; C. Gevehr Fernandes; J. A. Silva; R. da Silva Rodrigues

2011-01-01

Introduction: In humans, the normal metabolic activity produces free radicals that constantly, along with other risk factors, including hypercholesterolemia may be responsible for the onset of degenerative diseases. Some bioactive compounds present in blackberry (Rubus spp.) have the ability to act as natural antioxidants can make the food to minimize effects on the body caused by reactive oxygen species. Objective: This study verified the benefits of blackberry nectar through the quantificat...

Hypercholesterolemia is associated with the apolipoprotein C-III (APOC3 genotype in children receiving HAART: an eight-year retrospective study.

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Carlos A Rocco

Full Text Available Polymorphisms in apolipoprotein genes have shown to be predictors of plasma lipid levels in adult cohorts receiving highly active antiretroviral therapy (HAART. Our objective was to confirm the association between the APOC3 genotype and plasma lipid levels in an HIV-1-infected pediatric cohort exposed to HAART. A total of 130 HIV-1-infected children/adolescents that attended a reference center in Argentina were selected for an 8-year longitudinal study with retrospective data collection. Longitudinal measurements of plasma triglycerides, total cholesterol, HDL-C and LDL-C were analyzed under linear or generalized linear mixed models. The contribution of the APOC3 genotype at sites -482, -455 and 3238 to plasma lipid levels prediction was tested after adjusting for potential confounders. Four major APOC3 haplotypes were observed for sites -482/-455/3238, with estimated frequencies of 0.60 (C/T/C, 0.14 (T/C/C, 0.11 (C/C/C, and 0.11 (T/C/G. The APOC3 genotype showed a significant effect only for the prediction of total cholesterol levels (p<0.0001. However, the magnitude of the differences observed was dependent on the drug combination (p = 0.0007 and the drug exposure duration at the time of the plasma lipid measurement (p = 0.0002. A lower risk of hypercholesterolemia was predicted for double and triple heterozygous individuals, mainly at the first few months after the initiation of Ritonavir-boosted protease inhibitor-based regimens. We report for the first time a significant contribution of the genotype to total cholesterol levels in a pediatric cohort under HAART. The genetic determination of APOC3 might have an impact on a large portion of HIV-1-infected children at the time of choosing the treatment regimens or on the counter-measures against the adverse effects of drugs.

Coronary and peripheral endothelial function in HIV patients studied with positron emission tomography and flow-mediated dilation: relation to hypercholesterolemia

Energy Technology Data Exchange (ETDEWEB)

Lebech, Anne-Mette [Copenhagen University Hospital, Department of Infectious Diseases, Hvidovre (Denmark); Hvidovre University Hospital, Department of Infectious Diseases, Hvidovre (Denmark); Kristoffersen, Ulrik Sloth; Kjaer, Andreas [Rigshospitalet University Hospital, Department of Clinical Physiology, Nuclear Medicine and PET, Copenhagen (Denmark); University of Copenhagen, Cluster for Molecular Imaging, Copenhagen (Denmark); Wiinberg, Niels; Petersen, Claus Leth [Frederiksberg University Hospital, Department of Clinical Physiology and Nuclear Medicine, Frederiksberg (Denmark); Kofoed, Kristian; Andersen, Ove [Copenhagen University Hospital, Department of Infectious Diseases, Hvidovre (Denmark); Copenhagen University Hospital, Clinical Research Unit, Hvidovre (Denmark); Hesse, Birger [Rigshospitalet University Hospital, Department of Clinical Physiology, Nuclear Medicine and PET, Copenhagen (Denmark); Gerstoft, Jan [Rigshospitalet University Hospital, Department of Infectious Diseases, Copenhagen (Denmark)

2008-11-15

The mechanisms underlying increased cardiovascular risk in HIV patients in antiretroviral therapy (ART) are not known. Our aim was to study the endothelial function of the coronary arteries by cardiac perfusion positron emission tomography (PET), in HIV patients with normal or high cholesterol levels. Flow mediated dilation (FMD) of the brachial artery and circulating endothelial markers were also assessed. HIV patients in ART with total cholesterol {<=} 5.5 mmol/L (215 mg/dL; n = 13) or total cholesterol {>=} 6.5 mmol/L (254 mg/dL; n = 12) and healthy controls (n = 14) were included. {sup 13}NH{sub 3} perfusion PET, FMD, and measurement of plasma levels of E-Selectin, ICAM-1, VCAM-1, tPAI-1, and hs-CRP were performed. Baseline myocardial perfusion and the coronary flow reserve measured by PET (3.2 {+-} 0.3, 3.2 {+-} 0.3 and 3.0 {+-} 0.3; ns) was similar in HIV patients with normal or high total cholesterol and controls. FMD did not differ between the groups and was 4.6 {+-} 1.1%, 5.1 {+-} 1.2%, and 4.6 {+-} 0.8%, respectively. Increased levels of plasma E-Selectin, ICAM-1, tPAI-1, and hs-CRP were found in HIV patients when compared to controls (p < 0.05). E-Selectin and ICAM-1 levels were higher in HIV patients receiving protease inhibitors (PI) compared to those not receiving PI (p < 0.05). None of the measured endothelial biomarkers differed between the normal and high cholesterol HIV groups. In ART-treated HIV patients with a low overall cardiovascular risk, no sign of endothelial dysfunction was found not even in hypercholesterolemic patients. Also, the increased level of plasma endothelial markers found in HIV patients was not related to hypercholesterolemia. (orig.)

Low-density lipoprotein apheresis in a pediatric patient of familial hypercholesterolemia: Primi experientia from a tertiary care center in North India

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Kanchan Dogra

2017-01-01

Full Text Available Familial hypercholesterolemia (FH is an autosomal dominant disorder due to mutation of apolipoprotein-B receptor gene causing severe dyslipidemia. Lifestyle modification and medical treatment attenuate the disease progression, but as these fail to control the blood cholesterol levels, low-density lipoprotein (LDL apheresis comes forth as a treatment option. To the best of our knowledge, the following is the very first case of pediatric FH being treated by LDL-apheresis to be reported from India. A severely malnourished female child presented with yellowish skin lesions over different parts of the body, viz., bilateral Achilles tendon, both knees, elbows, both pinnae, and outer canthus of both eyes. She had a strong family history of borderline hypercholesterolemia and was diagnosed as a case of FH. She was maintained on diet modification. LDL-apheresis was planned as the cholesterol levels were not controlled with the diet modificationt. However, unavailability of an appropriate kit in India for LDL-apheresis led to the use of the modified PL1 kit meant for therapeutic plasma exchange procedures. We conducted two sessions of LDL-apheresis. After the first session, the LDL-cholesterol (LDL-C level fell by 75.9% and the total cholesterol fell by 73.5%. A second procedure led to a decline in total cholesterol level by 18.6% and LDL-C by 19.46%. Subsequently, she was advised diet modification and statin therapy with regular follow-up after every 6 months. Thus, the cascade filtration technique is a safe and effective treatment option for removing the undesired lipoproteins.

Detecting familial hypercholesterolemia by serum lipid profile screening in a hospital setting: Clinical, genetic and atherosclerotic burden profile.

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Scicali, R; Di Pino, A; Platania, R; Purrazzo, G; Ferrara, V; Giannone, A; Urbano, F; Filippello, A; Rapisarda, V; Farruggia, E; Piro, S; Rabuazzo, A M; Purrello, F

2018-01-01

Familial hypercholesterolemia (FH) is underdiagnosed and public cholesterol screening may be useful to find new subjects. In this study, we aim to investigate the prevalence of FH patients in a hospital screening program and evaluate their atherosclerotic burden using intima-media thickness (IMT). We screened 1575 lipid profiles and included for genetic analysis adults with a low-density lipoprotein (LDL) cholesterol >190 mg/dL and triglycerides 160 mg/dL and triglycerides 8 it was 100%. Mean IMT was higher in FH patients compared to non FH (0.73 [0.61-0.83] vs 0.71 [0.60-0.75] mm, p 190 mg/dL and corneal arcus (p < 0.01 and p < 0.001, respectively). A hospital screening was useful to detect FH subjects with increased atherosclerosis. Also, next-generation sequencing was able to detect new FH mutations. Copyright © 2017 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.

Protective Effects of Setarud (IMODTM on Development of Diet-Induced Hypercholesterolemia in Rabbits

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MH Shahhosseiny

2008-09-01

Full Text Available Background: A new herbal drug setarud (IMODTM containing selenium, carotene, and flavonoids, was expected to have positive effects on lipid metabolism and liver functions, due to the nature of its primary components. This study was designed to determine effectiveness of the drug in reducing the risk of development of diet-induced hypercholesterolemia in laboratory animals. Methods: Two groups of male rabbits (n=10 per group as: intact and control groups on regular chow, were fed a high-cholesterol diet, and two experimental groups were maintained on the same diet and treated with different daily doses (0.02 g/kg and 0.04 g/kg of setarud (brand name IMOD®, Pars Roos, Iran. The treatment groups were then compared with the intact and control groups and with one another for the effects of the drug which was determined by changes in blood sugar, serum lipid levels, and liver function tests. Results: Results showed that drug had important benefits in alleviating the impact of high-cholesterol diet on serum lipids and liver function markers in drug-treated groups relative to hyperlipidemic controls (p < 0.001. A more favorable modification of total cholesterol and triglyceride levels and the atherogenic index was found in animals, which received 0.04 g/kg drug, as compared to the 0.02 g/kg dose group (p < 0.05. Assessment of serum total protein, albumin, transaminases, and bilirubin levels showed that no changes in liver function of control and drug-treated animals during the period of the study. Conclusion: From the results of this study it may concluded that setarud has dose-dependent positive effects on liver and lipid metabolism and may acts as an effective anti-hyperglycemic agent.

Selected spices and their combination modulate hypercholesterolemia-induced oxidative stress in experimental rats

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Gloria A Otunola

2014-01-01

Full Text Available BACKGROUND: Effect of aqueous extracts of Allium sativum (garlic, Zingiber officinale (ginger, Capsicum fructensces (cayenne pepper and their mixture on oxidative stress in rats fed high Cholesterol/high fat diet was investigated. Rats were randomly distributed into six groups (n = 6 and given different dietary/spice treatments. Group 1 standard rat chow (control, group 2, hypercholesterolemic diet plus water, and groups 3, 4, 5, 6, hypercholesterolemic diet with 0.5 ml 200 mg · kg-1 aqueous extracts of garlic, ginger, cayenne pepper or their mixture respectively daily for 4 weeks. RESULTS: Pronounced oxidative stress in the hypercholesterolemic rats evidenced by significant (p < 0.05 increase in MDA levels, and suppression of the antioxidant enzymes system in rat's liver, kidney, heart and brain tissues was observed. Extracts of spices singly or combined administered at 200 mg.kg-1 body weight significantly (p < 0.05 reduced MDA levels and restored activities of antioxidant enzymes. CONCLUSIONS: It is concluded that consumption of garlic, ginger, pepper, or their mixture may help to modulate oxidative stress caused by hypercholesterolemia in rats.

Hypercholesterolemia Induced by a PCSK9 Gain-of-Function Mutation Augments Angiotensin II-Induced Abdominal Aortic Aneurysms in C57BL/6 Mice-Brief Report.

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Lu, Hong; Howatt, Deborah A; Balakrishnan, Anju; Graham, Mark J; Mullick, Adam E; Daugherty, Alan

2016-09-01

Gain-of-function mutations of PCSK9 (proprotein convertase subtilisin/kexin type 9) lead to hypercholesterolemia. This study was to determine whether infection of normocholesterolemic mice with an adeno-associated viral (AAV) vector expressing a gain-of-function mutation of mouse PCSK9 increased angiotensin II (AngII)-induced abdominal aortic aneurysms. In an initial study, male C57BL/6 mice were injected intraperitoneally with either an empty vector or PCSK9 gain-of-function mutation (D377Y). AAV at 3 doses and fed a saturated fat-enriched diet for 6 weeks. Two weeks after AAV injection, mice were infused with AngII for 4 weeks. Plasma PCSK9 concentrations were increased dose dependently in mice injected with AAV containing PCSK9D377Y mutation and positively associated with elevations of plasma cholesterol concentrations. Infection with intermediate and high doses of PCSK9D377Y.AAV led to equivalent increases of maximal width of abdominal aortas in C57BL/6 mice infused with AngII. Therefore, the intermediate dose was used in subsequent experiments. We then determined effects of PCSK9D377Y.AAV infection on 5 normolipidemic mouse strains, demonstrating that C57BL/6 mice were the most susceptible to this AAV infection. PCSK9D377Y.AAV infected male C57BL/6 mice were also compared with age-matched male low-density lipoprotein receptor(-/-) mice. Although plasma cholesterol concentrations were lower in mice infected with PCSK9D377Y.AAV, these mice had equivalent abdominal aortic aneurysmal formation, compared to low-density lipoprotein receptor(-/-) mice. In a separate study, reduced plasma PCSK9 concentrations by PCSK9 antisense oligonucleotides in male low-density lipoprotein receptor(-/-) mice did not influence AngII-induced abdominal aortic aneurysms. AAV-mediated infection with a mouse PCSK9 gain-of-function mutation is a rapid, easy, and efficient approach for inducing hypercholesterolemia and promoting abdominal aortic aneurysms in C57BL/6 mice infused with Ang

A comparative study of efficacy of atorvastatin, rosuvastatin, and atorvastatin + fibrates as lipid lowering agents

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Karunasree Nagarur; Yamini Vadlamannati; Narasimha Rao Raja

2016-01-01

Background: Hypercholesterolemia patients are at high risk of coronary heart disease. National cholesterol education programme (NCEP) Adult Treatment Panel III guidelines provide the option of aggressively lowering Low-density cholesterol in them. Presently the standard therapy of hypercholesterolemia is by HMG co-A reductase inhibitors. Present study shows that Rosuvastatin is better than Atorvastatin, Atorvastatin and Fibrate is better than Atorvastatin monotherapy in management of hypercho...

The detection of heterozygous familial hypercholesterolemia in Ireland.

LENUS (Irish Health Repository)

O'Kane, Maurice J

2012-05-01

Heterozygous familial hypercholesterolemia (HeFH) is an autosomal dominant condition with a population prevalence of 1 in 500, and is associated with significant cardiovascular morbidity and mortality. It may be caused by mutations in the low-density lipoprotein (LDL) receptor, apolipoprotein B100 (Apo B100), or proprotein convertase subtilisin\\/kexin type 9 (PCSK9) genes, with over 1,000 causative mutations described. Statin therapy in HeFH is considered effective and safe. Audit data suggest that approximately 80% of the putative HeFH population remains unidentified and, therefore, there is a need to develop a strategy for the identification of affected individuals so that early lipid-lowering treatment may be offered. There is good evidence showing the effectiveness and acceptability of HeFH screening programs in Europe. The authors describe a protocol for an all island approach to HeFH detection in the Republic of Ireland\\/Northern Ireland. Index cases will be identified by opportunistic screening using the Simon Broome, or Make Early Diagnosis to Prevent Early Death (MedPed) and World Health Organization (WHO) criteria. Patients identified as "definite," "probable," or "possible" HeFH criteria will be offered genetic testing. The authors expect causative mutations to be identified in approximately 80% of patients with "definite" HeFH but in only approximately 20% of patients with "possible" HeFH. Cascade screening will be undertaken in first-degree relatives of the index case using genetic testing (where a causative mutation has been identified), or otherwise using LDL cholesterol concentration. The establishment of a HeFH screening program on an all-island basis will require: expansion of the existing molecular genetics diagnostic services, the establishment of a cohort of nurses\\/genetic counselors, a HeFH database to support cascade testing, the development of a network of lipid clinics (in a primary or secondary care setting), and an educational

Budget Impact Analysis of PCSK9 Inhibitors for the Management of Adult Patients with Heterozygous Familial Hypercholesterolemia or Clinical Atherosclerotic Cardiovascular Disease.

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Mallya, Usha G; Boklage, Susan H; Koren, Andrew; Delea, Thomas E; Mullins, C Daniel

2018-01-01

The aim of this study was to assess the budget impact of introducing the proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) alirocumab and evolocumab to market for the treatment of adults with heterozygous familial hypercholesterolemia or clinical atherosclerotic cardiovascular (CV) disease requiring additional lowering of low-density lipoprotein cholesterol (LDL-C). A 3-year model estimated the costs of lipid-modifying therapy (LMT) and CV events to a hypothetical US health plan of 1 million members, comparing two scenarios-with and without the availability of PCSK9i as add-on therapy to statins. Proportions of patients with uncontrolled LDL-C despite receiving statins, and at risk of CV events, were estimated from real-world data. Total undiscounted annual LMT costs (2017 prices, including PCSK9i costs of $14,563.50), dispensing and healthcare costs, including the costs of CV events, were estimated for all prevalent patients in the target population, based on baseline risk factors. Maximum PCSK9i utilization of 1-5% over 3 years according to risk group (following the same pattern as current ezetimibe use), and 5-10% as a secondary scenario, were assumed. Total healthcare budget impacts per target patient (and per member) per month for years 1, 2 and 3 were $3.62($0.10), $7.22($0.20) and $10.79($0.30), respectively, assuming 1-5% maximum PCSK9i utilization, and $15.81($0.44), $31.52($0.88) and $47.12($1.31), respectively, assuming 5-10% utilization. Results were sensitive to changes in model timeframe, years to maximum PCSK9i utilization and PCSK9i costs. The budget impact of PCSK9i as add-on therapy to statins for patients with hypercholesterolemia is relatively low compared with published estimates for other specialty biologics. Drug cost rebates and discounts are likely to further reduce budget impact.

Potential role of proteasome on c-jun related signaling in hypercholesterolemia induced atherosclerosis

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Erdi Sozen

2014-01-01

Full Text Available Atherosclerosis and its complications are major causes of death all over the world. One of the major risks of atherosclerosis is hypercholesterolemia. During atherosclerosis, oxidized low density lipoprotein (oxLDL regulates CD36-mediated activation of c-jun amino terminal kinase-1 (JNK1 and modulates matrix metalloproteinase (MMP induction which stimulates inflammation with an invasion of monocytes. Additionally, inhibition of proteasome leads to an accumulation of c-jun and phosphorylated c-jun and activation of activator protein-1 (AP-1 related increase of MMP expression. We have previously reported a significant increase in cluster of differentiation 36 (CD36 mRNA levels in hypercholesterolemic rabbits and shown that vitamin E treatment prevented the cholesterol induced increase in CD36 mRNA expression. In the present study, our aim is to identify the signaling molecules/transcription factors involved in the progression of atherosclerosis following CD36 activation in an in vivo model of hypercholesterolemic (induced by 2% cholesterol containing diet rabbits. In this direction, proteasomal activities by fluorometry and c-jun, phospo c-jun, JNK1, MMP-9 expressions by quantitative RT-PCR and immunoblotting were tested in aortic tissues. The effects of vitamin E on these changes were also investigated in this model. As a result, c-jun was phosphorylated following decreased proteasomal degradation in hypercholesterolemic group. MMP-9 expression was also increased in cholesterol group rabbits contributing to the development of atherosclerosis. In addition, vitamin E showed its effect by decreasing MMP-9 levels and phosphorylation of c-jun.

Spectrum of mutations in homozygous familial hypercholesterolemia in India, with four novel mutations.

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Setia, Nitika; Saxena, Renu; Arora, Anjali; Verma, Ishwar C

2016-12-01

Homozygous familial hypercholesterolemia (FH) is a rare but serious, inherited disorder of lipid metabolism characterized by very high total and LDL cholesterol levels from birth. It presents as cutaneous and tendon xanthomas since childhood, with or without cardiac involvement. FH is commonly caused by mutations in three genes, i.e. LDL receptor (LDLR), apolipoprotein B (ApoB) and PCSK9. We aimed to determine the spectrum of mutations in cases of homozygous FH in Asian Indians and evaluate if there was any similarity to the mutations observed in Caucasians. Sixteen homozygous FH subjects from eleven families were analyzed for mutations by Sanger sequencing. Large rearrangements in LDLR gene were evaluated by multiplex ligation probe dependent amplification (MLPA) technique. Ten mutations were observed in LDLR gene, of which four mutations were novel. No mutation was detected in ApoB gene and common PCSK9 mutation (p.D374Y). Fourteen cases had homozygous mutations; one had compound heterozygous mutation, while no mutation was detected in one clinically homozygous case. We report an interesting "Triple hit" case with features of homozygous FH. The spectrum of mutations in the Asian Indian population is quite heterogeneous. Of the mutations identified, 40% were novel. No mutation was observed in exons 3, 9 and 14 of LDLR gene, which are considered to be hot spots in studies done on Asian Indians in South Africa. Early detection followed by aggressive therapy, and cascade screening of extended families has been initiated to reduce the morbidity and mortality in these patients. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Demonstration of functional low-density lipoprotein receptors by protein blotting in fibroblasts from a subject with homozygous receptor-negative familial hypercholesterolemia

International Nuclear Information System (INIS)

Semenkovich, C.F.; Ostlund, R.E. Jr.; Yang, J.; Reaban, M.E.

1985-01-01

We report the detection of low-density lipoprotein (LDL) receptors by the technique of receptor blotting in fibroblasts from a patient with homozygous familial hypercholesterolemia (FHC) previously classified as ''receptor negative.'' Solubilized receptors were electrophoresed, transferred to nitrocellulose paper, treated with LDL followed by radiolabeled antibody to LDL, and visualized by autoradiography. GM 2000 FHC fibroblasts revealed LDL receptors with an apparent molecular weight of approximately 140,000, the same as in normal cells. LDL receptor activity by blotting in GM 2000 cells was greatly diminished in comparison with normal cells, but was calcium dependent. Receptor activity was also detectable by conventional monolayer binding and degradation assays. Thus, GM 2000 cells have profoundly diminished LDL receptor activity, but retain the genetic capacity to make LDL receptor material of normal molecular weight that is capable of binding LDL. Previous studies have demonstrated the presence of trace amounts of immunoreactive LDL receptor protein in fibroblasts from some receptor-negative FHC homozygotes. These studies are extended by demonstrating the ability of this material to bind LDL

Familial Hypercholesterolemia: Cascade Screening in Children and Relatives of the Affected.

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Setia, Nitika; Saxena, Renu; Sawhney, J P S; Verma, Ishwar C

2018-05-01

Familial Hypercholesterolemia (FH) is an inherited disorder of lipid metabolism characterized by very high low density lipoprotein (LDL) cholesterol since birth, resulting in premature atherosclerosis and coronary artery disease (CAD). Cascade screening of children and family members of proven FH individuals can identify more subjects who have high LDL cholesterol or the family mutation and appropriate intervention can reduce their risk of atherosclerosis and prevent its complications. Cascade screening by molecular testing, was carried out in 133 family members, comprising 24 children, of 31 probands with FH having a pathogenic mutation in LDLR/ApoB gene. Lipid profiles were obtained in 44 family members including 11 children. Of 133 family members tested, 88 (66.1%) were identified to carry the family mutation. Twelve of these were children below 18 y of age and 76 were adults. CAD was present in 15 (11.2%) family members and 63(47.4%) family members, including nine children, were already on Lipid Lowering Therapy. Cascade screening led to identification of 88 new cases, with a pathogenic mutation, who were at a very high risk of developing premature CAD. The authors identified 12 children with family specific mutation, out of which 9 were initiated on low dose statin therapy. Four homozygous children were treated with high dose statins because of substantially increased risk of CAD. Cascade screening, therefore, proved to be a successful initiative towards primary prevention of CAD in India.

Combination of opium smoking and hypercholesterolemia augments susceptibility for lethal cardiac arrhythmia and atherogenesis in rabbit.

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Najafipour, Hamid; Joukar, Siyavash

2012-09-01

Opium consumption is increasing in some eastern societies, where it is grown. We investigated the effect of opium smoking on plasma atherogenic index and incidence of lethal cardiac arrhythmia, i.e. ventricular tachycardia (VT) and ventricular fibrillation (VF) in rabbits. Animals were divided into two-, normo- and hyper-cholesterolemic main groups fed with normal or high cholesterol diet prior and during short-term and long-term exposure to opium smoke. Then, isoproterenol (3mg/kg, i.p.) was injected to induce cardiac ischemia and animals were followed for 3h for counting of lethal arrhythmia incidence. Long-term opium smoking significantly increased the plasma atherogenic index. In ischemic hearts, opium smoking along with hypercholesterolemia significantly enhanced the incidence of fatal arrhythmia. This vulnerability was not mediated by changes in QT interval. These data suggest that opium smoking, especially in hypercholesterolemic conditions, can be a predisposing factor for atherogenesis and lethal arrhythmia. Copyright © 2012 Elsevier B.V. All rights reserved.

Prebiotic and Synbiotic Modifications of Beta Oxidation and Lipogenic Gene Expression after Experimental Hypercholesterolemia in Rat Liver

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Claudia C. Alves

2017-10-01

Full Text Available Background and aims: Non-alcoholic fatty liver disease (NAFLD is characterized by the presence of fat in hepatocytes because of decreased β-oxidation and increased lipogenesis. Prebiotics, probiotics, and synbiotic have modulatory effects on intestinal microbiota and may influence the gut-liver axis. Our aim was to evaluate the effects of prebiotic, probiotics, and synbiotic on liver histopathology and gene expression related to β-oxidation and lipogenesis after hypercholesterolemia.Methods: Wistar male adult rats (n = 40 were submitted to hypercholesterolemic conditions (HPC (60 days. On Day 30 of HPC, rats were subdivided in 5 groups: negative control (NC: without HPC + Gv (distilled water; positive control (PC: with HPC + Gv (distilled water; prebiotic (PRE: HPC + Gv with prebiotic (Fiber FOS®; probiotic (PRO: HPC + Gv with probiotic strains Gv (Probiatop®; and synbiotic (SYN: HPC + Gv with synbiotic (Simbioflora®. All rats were sacrificed on Day 30 post-treatment. Blood was collected to verify total serum cholesterol, and liver tissue was sampled to verify histopathological changes and gene expression. Gene expression related to ß-oxidation (PPAR-α and CPT-1 and lipogenesis (SREBP-1c, FAS and ME was evaluated in liver tissue using RT-qPCR.Results: PC had higher cholesterol levels when compared to NC. PRE and SYN rats had lower cholesterol levels than PC. PC rats showed more histopathological changes than NC rats; PRE and SYN rats showed fewer alterations than PC rats. PPAR-α was expressed at higher levels in SYN and PC rats compared with PRE and PRO rats. CPT-1 expression was similar in all groups. SREBP-1c was expressed at higher levels in PC rats compared with NC rats; levels were lower in SYN rats compared with PRO rats; levels were lower in PRE rats compared with PC and PRO rats. FAS was expressed at lower levels in PRE rats compared with SYN rats. ME expression was lower in PC rats compared with NC rats.Conclusion: Prebiotic and

Dietary models for inducing hypercholesterolemia in rats

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Sheyla Leite Matos

2005-03-01

Full Text Available The present work aimed at finding a dietetical model capable of promoting the highest hypercholesterolemia without affecting the development of the rats. Sixty female Fisher rats were divided into five groups. The first one was fed a control diet; the remaining four were fed hypercholesterolemic diets with cholesterol and different contents of soybean oil, starch, casein, micronutrients and fiber and, consequently, different caloric values. After eight weeks animals were evaluated in relation to growth, fecal excretion, liver weight and fat, cholesterol and its fractions, serum biochemical parameters and sistolic pressure and compared with controls. The best result was obtained with the diet containing 25 % soybean oil, 1.0 % cholesterol, 13 % fiber and 4,538.4 Kcal/Kg, since it promoted an increase in LDL-cholesterol, a decrease in the HDL fraction and affected less the hepatic function of the animals.Modelos animais têm sido usados para investigar a relação entre desordens no metabolismo do colesterol e a aterogênese. A estratégia utilizada a fim de induzir hipercolesterolemia (dietas com alto teor de gordura e com colesterol adicionado leva à redução de sua ingestão pelos animais, o que induz desnutrição. O presente trabalho objetivou encontrar um modelo dietético capaz de promover a maior hipercolesterolemia, sem afetar o desenvolvimento dos animais. Sessenta ratas Fisher foram divididas em cinco grupos. O primeiro foi alimentado com uma dieta controle; os quatros restantes receberam dietas hipercolesterolêmicas, com colesterol e diferentes teores de óleo de soja, amido, caseína, micronutrientes e fibra e, conseqüentemente, diferentes valores calóricos. Após oito semanas os animais foram avaliados em relação ao crescimento, excreção fecal, peso e teor de gordura do fígado, colesterol e suas frações, parâmetros bioquímicos séricos e pressão sistólica. Os melhores resultados foram obtidos com a dieta contendo 25

Systematic review and metaanalysis of statins for heterozygous familial hypercholesterolemia in children: evaluation of cholesterol changes and side effects.

LENUS (Irish Health Repository)

O'Gorman, Clodagh S

2012-02-01

Heterozygous familial hypercholesterolemia (heFH) affects 1 in 500 individuals. Evidence supports the low-density lipoprotein (LDL)-lowering effect of statins for adults with heFH. However, there are concerns regarding the treatment children with heFH. By performing a systematic review and metaanalysis of the published literature, this study aimed to evaluate the efficacy and safety of statins used for children with heFH. A systematic review was performed by searching multiple medical databases and citations to identify reports of randomized controlled trials of statins used to treat children with heFH. The trials were retrieved, reviewed, and subjected to metaanalysis. The search yielded 2,174 titles. Of the 63 studies retrieved and reviewed, 56 were excluded, 7 were included in the systematic review, and 4 were included in the metaanalysis. Significant heterogeneity was detected. The metaanalysis showed significant LDL lowering, high-density lipoprotein (HDL) cholesterol elevation, and increases in height and weight with statins. The metaanalysis could not be performed for many side effects of statins, but individual trials showed no significant side effects. Quality assessment showed methodologic concerns, with potential for bias. For example, six trials analyzed statin effects without intention to treat despite such a stated intention. Metaanalysis shows significant LDL lowering with statin treatment. Further studies, including epidemiologic and multicenter studies, are required.

Stimulation of cholesteryl ester synthesis in mouse peritoneal macrophages by cholesterol-rich very low density lipoproteins from the Watanabe heritable hyperlipidemic rabbit, an animal model of familial hypercholesterolemia

International Nuclear Information System (INIS)

Kita, T.; Yokode, M.; Watanabe, Y.; Narumiya, S.; Kawai, C.

1986-01-01

Cholesterol-rich very low density lipoproteins (VLDL) from the homozygous Watanabe heritable hyperlipidemic (WHHL) rabbit induced marked cholesteryl ester accumulation in mouse peritoneal macrophages. This WHHL rabbit, an animal model of human familial hypercholesterolemia, has severe hypercholesterolemia, cutaneous xanthomas, and fulminant atherosclerosis due to the deficiency of the low density lipoprotein (LDL) receptor. When incubated with mouse peritoneal macrophages, the VLDL from WHHL rabbit (WHHL-VLDL) stimulated cholesteryl [ 14 C]oleate synthesis 124-fold more than did VLDL from the normal Japanese White rabbit (control-VLDL). The enhancement in cholesteryl ester synthesis and accumulation of WHHL-VLDL was due to the presence of a high affinity binding receptor site on the macrophage cell surface that mediated the uptake and lysosomal degradation of WHHL-VLDL. Competition studies showed that the uptake and degradation of 125 I-WHHL-VLDL was inhibited by unlabeled excess WHHL-VLDL and beta-migrating VLDL (beta-VLDL), but not LDL. Furthermore, the degradation of WHHL-VLDL was not blocked by either fucoidin, polyinosinic acid, or polyguanylic acid, potent inhibitors of the acetylated (acetyl)-LDL binding site, or by acetyl-LDL. These results suggest that macrophages possess a high affinity receptor that recognizes the cholesterol-rich VLDL present in the plasma of the WHHL rabbit and that the receptor which mediates ingestion of WHHL-VLDL seems to be the same as that for beta-VLDL and leads to cholesteryl ester deposition within macrophages. Thus, the uptake of the cholesterol-rich VLDL from the WHHL rabbit by macrophages in vivo may play a significant role in the pathogenesis of atherosclerosis in the WHHL rabbit

Monocytes of patients with familial hypercholesterolemia show alterations in cholesterol metabolism

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Soufi Muhidien

2008-11-01

Full Text Available Abstract Background Elevated plasma cholesterol promotes the formation of atherosclerotic lesions in which monocyte-derived lipid-laden macrophages are frequently found. To analyze, if circulating monocytes already show increased lipid content and differences in lipoprotein metabolism, we compared monocytes from patients with Familial Hypercholesterolemia (FH with those from healthy individuals. Methods Cholesterol and oxidized cholesterol metabolite serum levels of FH and of healthy, gender/age matched control subjects were measured by combined gas chromatography – mass spectroscopy. Monocytes from patients with FH and from healthy subjects were isolated by antibody-assisted density centrifugation. Gene expression profiles of isolated monocytes were measured using Affymetrix HG-U 133 Plus 2.0 microarrays. We compared monocyte gene expression profiles from FH patients with healthy controls using a Welch T-test with correction for multiple testing (p Results Using microarray analysis we found in FH patients a significant up-regulation of 1,617 genes and a down-regulation of 701 genes compared to monocytes from healthy individuals. These include genes of proteins that are involved in the uptake, biosynthesis, disposition, and cellular efflux of cholesterol. In addition, plasma from FH patients contains elevated amounts of sterols and oxysterols. An increased uptake of oxidized as well as of native LDL by FH monocytes combined with a down-regulation of NPC1 and ABCA1 explains the lipid accumulation observed in these cells. Conclusion Our data demonstrate that circulating FH monocytes show differences in cell physiology that may contribute to the early onset of atherosclerosis in this disease.

Animal magnetocardiography using superconducting quantum interference device gradiometers assisted with magnetic nanoparticle injection: A sensitive method for early detecting electromagnetic changes induced by hypercholesterolemia

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Wu, C. C.; Hong, B. F.; Wu, B. H.; Yang, S. Y.; Horng, H. E.; Yang, H. C.; Tseng, W. Y. Isaac; Tseng, W. K.; Liu, Y. B.; Lin, L. C.; Lu, L. S.; Lee, Y. H.

2007-01-01

In this work, the authors used a superconducting quantum interference device (SQUID) magnetocardiography (MCG) system consisted of 64-channel low-transition-temperature SQUID gradiometers to detect the MCG signals of hepercholesterolemic rabbits. In addition, the MCG signals were recorded before and after the injection of magnetic nanoparticles into the rabbits' ear veins to investigate the effects of magnetic nanoparticles on the MCG signals. These MCG data were compared to those of normal rabbits to reveal the feasibility for early detection of the electromagnetic changes induced by hypercholesterolemia using MCG with the assistance of magnetic nanoparticle injection.

Discriminative ability of LDL-cholesterol to identify patients with familial hypercholesterolemia: a cross-sectional study in 26,406 individuals tested for genetic FH.

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Huijgen, Roeland; Hutten, Barbara A; Kindt, Iris; Vissers, Maud N; Kastelein, John J P

2012-06-01

Screening for familial hypercholesterolemia (FH) within affected families is often based on cutoff values for low-density lipoprotein cholesterol (LDL-C). However, the diagnostic accuracy of LDL-C levels is influenced by the magnitude of the LDL-C overlap between FH patients and unaffected relatives. The purpose of the current study was to assess to what extent this overlap is influenced by the severity of specific FH mutations. Individuals were eligible if they underwent family screening for FH between 2003 and 2010. The entire cohort was then compared with those who were investigated for the presence of the most severe mutations (class 1). The area under the receiver operating characteristics curve and the sensitivity of the 90th percentile of LDL-C were calculated for both cohorts. We included 26 406 individuals, of whom 9169 (35%) carried an FH-causing mutation. In the entire cohort at baseline, mean LDL-C was 4.63 ± 1.44 mmol/L for FH carriers (n=5372) and 2.96 ± 0.96 mmol/L for unaffected relatives (n=15 148); P<0.001. The corresponding operating characteristics curve (95% CI) was 86.6% (85.9%-87.2%), and the cutoff level of LDL-C above the 90th percentile showed a sensitivity of 68.5%. The operating characteristics curve and sensitivity significantly improved when the 5933 individuals tested for class 1 mutations were assessed separately; 96.2% (95.3%-97.1%) and 91.3%, respectively. In summary, the overlap in terms of LDL-C levels between those with molecularly proven FH and unaffected relatives is to a large extent because of the high prevalence of modestly severe LDL-receptor mutations in the Netherlands.

Anxiety, depression, and health-related quality of life in heterozygous familial hypercholesterolemia: A systematic review and meta-analysis.

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Akioyamen, Leo E; Genest, Jacques; Shan, Shubham D; Inibhunu, Happy; Chu, Anna; Tu, Jack V

2018-06-01

Heterozygous familial hypercholesterolemia (FH) is a common genetic disease predisposing affected individuals to a high risk of cardiovascular disease. Yet, considerable uncertainty exists regarding its impact on psychosocial wellbeing. We performed a systematic review and meta-analysis of the association between FH and symptoms of anxiety and depression, and health-related quality of life (HRQL). We searched MEDLINE, EMBASE, Global Health, the Cochrane Library, PsycINFO, and PubMed for peer-reviewed literature published in English between January 1, 1990 and January 1, 2018. Quantitative and qualitative studies were eligible if they included patients with confirmed FH and evaluated its association with symptoms of anxiety or depression, or HRQL. We performed a narrative synthesis of studies, including thematic analysis of qualitative studies, and where data permitted, random-effects meta-analysis reporting standardized mean differences (SMD) and 95% confidence intervals. We found 10 eligible studies measuring HRQL, depression and anxiety. Random-effects meta-analysis of 4 (n = 4293) and 5 studies (n = 5098), respectively, showed that patients with FH had slightly lower symptoms of anxiety (SMD: -0.29 [95% CI: -0.53, -0.04]) and mental HRQL (SMD: -0.10 [95% -0.20, -0.00]) relative to general population controls. No significant differences existed in depressive symptoms (SMD: 0.04 [95% CI: -0.12, 0.19]) or physical HRQL scores (SMD: 0.02 [95% CI: -0.09, 0.12]). Our systematic review suggests that patients with FH may report small but measurable differences in anxiety symptoms and mental HRQL. Copyright © 2018 Elsevier Inc. All rights reserved.

Hypercholesterolemia increases plasma saturated and n-6 fatty acids altering prostaglandin homeostasis and promotes endothelial dysfunction in rabbits.

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Medina, M; Alberto, M R; Sierra, L; Van Nieuwenhove, C; Saad, S; Isla, M I; Jerez, S

2014-07-01

The present study evaluated the plasma fatty acid levels and the vascular prostaglandin (PG) release in a rabbit model of early hypercholesterolemia with endothelial dysfunction. Rabbits were fed either a control diet (CD) or a diet containing 1 % cholesterol (HD) for 5-6 weeks. The level of fatty acids was measured in plasma. The levels of PG and nitric oxide (NO) released from the aorta were also determined. Vascular morphology of the aorta was characterized by intima and media thickness measurements. The rabbits fed with HD had higher levels of arachidonic acid (ARA) and lower levels of oleic acid. The linoleic acid level was unchanged. PGI(2) and NO were diminished and PGF(2α) levels, the PGI(2)/TXA(2) ratio and the intima/media ratio were increased in rabbits fed with HD. In conclusion, feeding HD for a short period increased ARA plasma levels and unbalanced release of vasodilator/vasoconstrictor PG redirected the pathway to vasoconstrictor metabolite release. These lipid metabolism alterations in addition to the reduced NO levels and the moderate changes in the vascular morphology contributed to the endothelial dysfunction in this animal model. Therefore, the present findings support the importance of early correction or prevention of high cholesterol levels to disrupt the endothelial dysfunction process that leads to cardiovascular disease.

Prescription and adherence to statins of patients with coronary artery disease and hypercholesterolemia

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Mansur Antonio P.

2001-01-01

Full Text Available OBJECTIVE: Statins have proved to be safe and effective in the secondary prevention of coronary artery disease, but the level of prescription and the reasons for nonadherence to treatment in many coronariopathy treatment centers has not been determined. The purpose of this study was to identify reasons for nonadherence to statin therapy. METHODS: We analyzed 207 consecutive patients with coronary artery disease and hypercholesterolemia (total cholesterol > or = 200mg/dL or LDL - cholesterol > or = 130mg/dL. Patients' average age was 61.7±10 year; 111 (53.6% male were and 94 (46.6% were female. We analyzed the level of prescription and adherence to treatment with statins. RESULTS: Statins were prescribed for 139 (67% patients, but only 85 (41% used the drug. In spite of being indicated, statins were not prescribed in 68 (33% patients. Of 54 (26% patients, nonadherent to statins, 67% did not use the drug due to its high cost, 31% due to the lack of instruction, and only 2% due to side effects. Total cholesterol (260.3±42.2 vs 226.4±51.9; p<0.0001 and LDL cholesterol (174.6±38.1 vs 149.6±36.1; p<0.0001 were lower in patients on medication. HDL-cholesterol increased from 37.6±9.6 to 41.5±12.9mg/dL (p=0.02, and triglycerides were not modified in patients using statins. CONCLUSION: The prescription of statins in patients with coronary artery disease and dyslipidemia is high; however, its adherence is far from satisfactory, due to the high cost of the medication. Reduction in total cholesterol and LDL cholesterol levels did not reach the targets recommended by the Brazilian Consensus on Dyslipidemia.

IDENTIFICATION OF PATIENTS WITH FAMILIAL HYPERCHOLESTEROLEMIA IN THE RUSSIAN POPULATION USING THE EXAMPLE OF MOSCOW CITY AND MOSCOW REGION

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I. V. Sergienko

2018-01-01

Full Text Available Aim. To estimate the prevalence of familial hypercholesterolemia (FH in a sample of Moscow city and Moscow region patients with hypercholesterolemia (HCh based on lipid spectrum and instrumental methods.Material and methods. The study included two samples of patients (age >18 years, with total cholesterol (TCh level ≥7.5 mmol/l and/or low-density lipoprotein (LDL cholesterol level ≥4.9 mmol/l. First sample (n=60 was included to determine secondary hyperlipidemia frequency in newly diagnosed HCh, with measurement of thyroid hormone, glucose and glycated hemoglobin (HbA1c levels. Patients of the second sample (n=432 from Russian registry of FH (RuFH were studied by drug therapy assessment, lipid profile measurements, calculation of FH probability according to Dutch and British criteria, carotids duplex scanning (CDS, cardiac perfusion single-photon emission computed tomography (SPECT/CT using rest/stress protocol.Results. The incidence of secondary dyslipidemia due to diabetes or hypothyroidism in patients with severe HCh was 18.3%. Monotherapy with atorvastatin (34.2% or rosuvastatin (31.8%, combined therapy with statins and other lipid-lowering drugs (24.4% prevails in the structure of lipidlowering therapy in patients with severe HCh. The frequency of "definite" FH according to Dutch criteria in HCh patients was 15.3%, "probable" – 18.1%. Patients with definite FH diagnosis showed higher level of TCh (p<0.001, LDL cholesterol (p<0.001, proprotein convertase subtilisin/kexin type 9 (p<0.001, lower high-density lipoprotein (HDL; p=0.02, and triglycerides (p<0.001. At that HDL cholesterol levels differed only in patients treated with lipid-lowering drugs. Patients with lipid-lowering therapy had significantly higher values of total stenosis percent, the number of plaques, intima-media complex thickness (p<0.001. Patients with lipid-lowering therapy with a definite and probable FH diagnosis had significantly worse values of CDS parameters

Protective Effect of T. violacea Rhizome Extract Against Hypercholesterolemia-Induced Oxidative Stress in Wistar Rats

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Olorunnisola Sinbad Olorunnisola

2012-05-01

Full Text Available The present study examines the effect of methanolic extract of T. violacea rhizomes on high cholesterol (2% diet fed rats (HCD. At the end of 4 weeks, serum total protein, albumin, reduced glutathione (GSH, and markers of oxidative stress viz., catalase (CAT, superoxide dismutase (SOD, thiobarbituric acid reactive substances (TBARS—a marker of lipid peroxidation, glutathione-S-transferase (GST and glutathione peroxidase (GPx in the serum, aorta, liver and heart of HCD and normal rats were assessed and compared. A significant (p < 0.05 elevation in TBARS, and a reduction (p < 0.05 in serum total protein, albumin, GSH and antioxidant enzyme activities was observed in tissues of HCD fed rats compared with the normal group. Co-administration of crude extracts of T. violacea rhizomes protected the liver, heart, serum and aorta against HCD-induced lipid peroxidation in a dose dependant manner. The activities of the extract (500 mg/kg compared favorably with gemfibrozil. The extracts also protected against HCD-induced reduction in serum total protein, GSH and restored the activities of antioxidant tissues (liver, heart and aorta enzymes to near normal values. This result suggested that consumption of T. violacea rhizome may help to protect against hypercholesterolemia- induced oxidative stress diseases in the heart and liver.

Prevalence and management of familial hypercholesterolemia in patients with coronary artery disease: The heredity survey.

Science.gov (United States)

Faggiano, Pompilio; Pirillo, Angela; Griffo, Raffaele; Ambrosetti, Marco; Pedretti, Roberto; Scorcu, Giampaolo; Werren, Marika; Febo, Oreste; Malfatto, Gabriella; Favretto, Giuseppe; Sarullo, Filippo; Antonini-Canterin, Francesco; Zobbi, Gianni; Temporelli, Pierluigi; Catapano, Alberico L

2018-02-01

Familial hypercholesterolemia (FH) is a genetic disorder characterized by high levels of low density lipoprotein cholesterol (LDL-C) predisposing to premature cardiovascular disease. Its prevalence varies and has been estimated around 1 in 200-500. The Heredity survey evaluated the prevalence of potential FH and the therapeutic approaches among patients with established coronary artery disease (CAD) or peripheral artery disease (PAD) in which it is less well documented. Data were collected in patients admitted to programs of rehabilitation and secondary prevention in Italy. Potential FH was estimated using Dutch Lipid Clinic Network (DLCN) criteria. Potential FH was defined as having a total score≥6. Among the 1438 consecutive patients evaluated, the prevalence of potential FH was 3.7%. The prevalence was inversely related to age, with a putative prevalence of 1:10 in those with Definite FH (DLCN score>8) had the highest percentages of patients after an ACS (75% vs 52.5% in the whole study population). At discharge, most patients were on high intensity statin therapy, but despite this, potential FH group still had a higher percentage of patients with LDL-C levels not at target and having a distance from the target higher than 50%. Among patients with established coronary heart disease, the prevalence of potential FH is higher than in the general population; the results suggest that a correct identification of potential FH, especially in younger patients, may help to better manage their high cardiovascular risk. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

Severe hypertriglyceridemia and hypercholesterolemia accelerating renal injury: a novel model of type 1 diabetic hamsters induced by short-term high-fat / high-cholesterol diet and low-dose streptozotocin.

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He, Liang; Hao, Lili; Fu, Xin; Huang, Mingshu; Li, Rui

2015-04-11

Hyperlipidemia is thought to be a major risk factor for the progression of renal diseases in diabetes. Recent studies have shown that lipid profiles are commonly abnormal early on type 2 diabetes mellitus (T2DM) with diabetic nephropathy. However, the early effects of triglyceride and cholesterol abnormalities on renal injury in type 1 diabetes mellitus (T1DM) are not fully understood and require reliable animal models for exploration of the underlying mechanisms. Hamster models are important tools for studying lipid metabolism because of their similarity to humans in terms of lipid utilization and high susceptibility to dietary cholesterol and fat. Twenty-four male Golden Syrian hamsters (100-110 g) were rendered diabetes by intraperitoneal injections of streptozotocin (STZ) on consecutive 3 days at dose of 30 mg/kg, Ten days after STZ injections, hamsters with a plasma Glu concentration more than 12 mmol/L were selected as insulin deficient ones and divided into four groups (D-C, D-HF, D-HC, and D-HFHC), and fed with commercially available standard rodent chow, high-fat diet, high-cholesterol diet, high-fat and cholesterol diet respectively, for a period of four weeks. After an induction phase, a stable model of renal injury was established with the aspects of early T1DM kidney disease, These aspects were severe hypertriglyceridemia, hypercholesterolemia, proteinuria with mesangial matrix accumulation, upgraded creatinine clearance, significant cholesterol and triglyceride deposition, and increasing glomerular surface area, thickness of basement membrane and mesangial expansion. The mRNA levels of sterol regulatory element binding protein-1c, transforming growth factors-β, plasminogen activator inhibitor-1, tumor necrosis factor-α and interleukin-6 in the D-HFHC group were significantly up-regulated compared with control groups. This study presents a novel, non-transgenic, non-surgical method for induction of renal injury in hamsters, which is an important

Association between dyslipidemia and chronic kidney disease: a cross-sectional study in the middle-aged and elderly Chinese population.

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Liu, Dong-Wei; Wan, Jia; Liu, Zhang-Suo; Wang, Pei; Cheng, Gen-Yang; Shi, Xue-Zhong

2013-04-01

Dyslipidemia, a well-known risk factor for cardiovascular disease, is common in patients with kidney disease. Recent studies discerned that dyslipidemias play a critical role in renal damage progression in renal diseases, but the association between dyslipidemias and chronic kidney disease (CKD) in the general population remains unknown. Thus, we assessed whether the growing prevalence of dyslipidemia could increase the risk of CKD. A total of 4779 middle-aged and elderly participants participated in this study. Dyslipidemias were defined by the 2007 Guidelines in Chinese Adults. Incident CKD was defined as albuminuria and/or reduced estimated glomerular filtration rate (eGFR, dyslipidemia and albuminuria/reduced eGFR. Participants with hypercholesterolemia exhibited a greater prevalence of albuminuria and reduced eGFR (10.0% vs. 6.1%, P = 0.001; 4.0% vs. 2.4%, P = 0.028, respectively). Both hypercholesterolemia and low high density lipoprotein cholesterol (HDL-C) were independently associated with albuminuria (odds ratio (OR) 1.49; 95% confidence interval (CI) 1.08 - 2.07 and OR 1.53; 95%CI 1.13 - 2.09, respectively). The multivariable adjusted OR of reduced eGFR in participants with hypercholesterolemia was 1.65 (95%CI 1.03 - 2.65). As the number of dyslipidemia components increased, so did the OR of CKD: 0.87 (95%CI 0.65 - 1.15), 1.29 (95%CI, 0.83 - 2.01), and 7.87 (95%CI, 3.75 - 16.50) for albuminuria, and 0.38 (95%CI 0.21 - 0.69), 1.92 (95%CI 1.14 - 3.25), and 5.85 (95%CI 2.36 - 14.51) for reduced eGFR, respectively. Our findings indicate that dyslipidemias increase the risk of CKD in the middle-aged and elderly Chinese population. Hypercholesterolemia plays an important role in reducing total eGFR. Both low HDL-C and hypercholesterolemia are associated with an increased risk for albuminuria.

Episomal Nonviral Gene Therapy Vectors Slow Progression of Atherosclerosis in a Model of Familial Hypercholesterolemia

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Alastair G Kerr

2016-01-01

Full Text Available Familial hypercholesterolemia (FH is a life-threatening genetic disorder characterized by elevated levels of plasma low-density lipoprotein cholesterol (LDL-cholesterol. Current attempts at gene therapy for FH have been limited by the use of strong heterologous promoters which lack genomic DNA elements essential for regulated expression. Here, we have combined a minigene vector expressing the human LDLR cDNA from a 10 kb native human LDLR locus genomic DNA promoter element, with an efficient miRNA targeting 3-hydroxy-3-methylgutaryl-coenzyme A reductase (Hmgcr, to further enhance LDLR expression. We show that the combined vector suppresses endogenous Hmgcr transcripts in vivo, leading to an increase in LDLR transgene expression. In a diet-induced Ldlr-/- mouse model of FH, we show that administration of the combined vector reduces atherogenic plasma lipids by ≃32%. Finally, we demonstrate that our episomal nonviral vectors are able to reduce atherosclerosis by ≃40% after 12 weeks in vivo. Taken together, the vector system we describe exploits the normal cellular regulation of the LDLR to provide prolonged expression of LDLR through targeted knockdown of Hmgcr. This novel gene therapy system could act alone, or in synergy with current therapies that modulate intracellular cholesterol, such as statins, greatly enhancing its therapeutic application for FH.

The management of hypercholesterolemia in patients with coronary artery disease: guidelines for primary care.

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Vogel, R A

1998-01-01

More than 10 million individuals in the United States currently have symptomatic coronary artery disease (CAD). Asymptomatic CAD is even more prevalent. CAD in the United States is responsible for approximately 1.5 million myocardial infarctions, 500,000 deaths, and a total economic burden in excess of $120 billion annually. Fortunately, CAD is preventable in many individuals. Our understanding of CAD has steadily progressed throughout the 20th century, and now several lines of evidence support the importance of cholesterol in both the genesis and management of coronary atherosclerosis. Following identification of the presence of cholesterol in atheromas, Anitschkov early this century demonstrated that atherosclerotic lesions can be induced in susceptible animals by high-saturated-fat and cholesterol diets. These lesions regressed when low-fat and cholesterol diets were resumed. In the 1970s and 1980s, findings from the landmark Framingham Heart, Seven Countries, and Multiple Risk Factor Intervention Trial studies firmly established that hypercholesterolemia was a major risk factor for cardiovascular morbidity and mortality. During the 1980s and 1990s, 21 of 22 angiographic trials demonstrated reduced progression of coronary and/or carotid artery disease using lifestyle, drug, and surgical means for reducing cholesterol. The later trials commonly employed hydroxymethylglutaryl coenzyme A reductase inhibitors (statins), reflecting increasing clinical use of these drugs. In 1988, the Adult Treatment Panel of the National Cholesterol Education Program (NCEP) published guidelines on testing and treating hypercholesterolemic patients, which outlined a more aggressive approach to cholesterol lowering than was currently in practice. Since 1994, five large cardiovascular event trials and a large angiographic trial have shown that aggressive cholesterol lowering reduces both cardiac morbidity and mortality, largely substantiating the NCEP guidelines. Although important

The Impact of Lipoprotein-Associated Oxidative Stress on Cell-Specific Microvesicle Release in Patients with Familial Hypercholesterolemia

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M. H. Nielsen

2016-01-01

Full Text Available Objective. Microvesicles (MVs are small cell-derived particles shed upon activation. Familial hypercholesterolemia (FH particularly when associated with Achilles tendon xanthomas (ATX predisposes to atherosclerosis, possibly through oxLDL-C interaction with the CD36 receptor. To investigate the hypothesis that MVs derived from cells involved in atherosclerosis are increased in FH and that CD36 expressing MVs (CD36+ MVs may be markers of oxLDL-C-induced cell activation, cell-specific MVs were measured in FH patients with and without ATX and their association with atherogenic lipid profile was studied. Approach and Results. Thirty FH patients with and without ATX and twenty-three controls were included. Plasma concentrations of MVs and CD36+ MVs derived from platelets (PMVs, erythrocytes (ErytMVs, monocytes (MMVs, and endothelial cells (EMVs, as well as tissue factor-positive cells (TF+ MVs, were measured by flow cytometry. Total MVs, MMVs, EMVs, ErytMVs, and TF+ MVs were significantly increased in FH patients, compared to controls. CD36+ MVs derived from endothelial cells and monocytes were significantly higher in FH patients and oxLDL-C predicted all the investigated cell-specific CD36+ MVs in FH patients with ATX. Conclusions. MVs derived from cells involved in atherosclerosis were increased in FH and may contribute to elevated atherothrombosis risk. The increased cell-specific CD36+ MVs observed in FH may represent markers of oxLDL-C-induced cell activation.

Polymorphisms of the low-density lipoprotein receptor gene in Brazilian individuals with heterozygous familial hypercholesterolemia

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L.A. Salazar

2000-11-01

Full Text Available Familial hypercholesterolemia (FH is a metabolic disorder inherited as an autosomal dominant trait characterized by an increased plasma low-density lipoprotein (LDL level. The disease is caused by several different mutations in the LDL receptor gene. Although early identification of individuals carrying the defective gene could be useful in reducing the risk of atherosclerosis and myocardial infarction, the techniques available for determining the number of the functional LDL receptor molecules are difficult to carry out and expensive. Polymorphisms associated with this gene may be used for unequivocal diagnosis of FH in several populations. The aim of our study was to evaluate the genotype distribution and relative allele frequencies of three polymorphisms of the LDL receptor gene, HincII1773 (exon 12, AvaII (exon 13 and PvuII (intron 15, in 50 unrelated Brazilian individuals with a diagnosis of heterozygous FH and in 130 normolipidemic controls. Genomic DNA was extracted from blood leukocytes by a modified salting-out method. The polymorphisms were detected by PCR-RFLP. The FH subjects showed a higher frequency of A+A+ (AvaII, H+H+ (HincII1773 and P1P1 (PvuII homozygous genotypes when compared to the control group (P<0.05. In addition, FH probands presented a high frequency of A+ (0.58, H+ (0.61 and P1 (0.78 alleles when compared to normolipidemic individuals (0.45, 0.45 and 0.64, respectively. The strong association observed between these alleles and FH suggests that AvaII, HincII1773 and PvuII polymorphisms could be useful to monitor the inheritance of FH in Brazilian families.

Assessment of physicians' awareness and knowledge of familial hypercholesterolemia in Saudi Arabia: Is there a gap?

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Batais, Mohammed Ali; Almigbal, Turky H; Bin Abdulhak, Aref A; Altaradi, Hani B; AlHabib, Khalid F

2017-01-01

The scarcity of familial hypercholesterolemia (FH) cases reported in Saudi Arabia might be indicative of a lack of awareness of this common genetic disease among physicians. To assess physicians' awareness, practice, and knowledge of FH in Saudi Arabia. This is a cross-sectional study conducted among physicians at four tertiary hospitals in Riyadh, Saudi Arabia between March 2016 and May 2016 using a self-administered questionnaire. A total of 294 physicians completed the survey (response rate 90.1%). Overall, 92.9% of the participants have poor knowledge of FH while only 7.1% have acceptable knowledge. The majority (68.7%) of physicians rated their familiarity with FH as average or above average, and these had higher mean knowledge scores than participants with self-reported below average familiarity (mean 3.4 versus 2.6) (P knowledge scores compared to those without FH patients in their care (3.5 versus 2.9) (P = 0.006). In addition, there were statistically significant differences between physicians' mean knowledge scores and their ages, levels of training, and years in practice. Moreover, a substantial deficit was identified in the awareness of various clinical algorithms to diagnose patients with FH, cascade screening, specialist lipid services, and the existence of statin alternatives, such as proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors. A substantial deficit was found in the awareness, knowledge, practice, and detection of FH among physicians in Saudi Arabia. Extensive educational programs are required to raise physician awareness and implement best practices; only then can the impact of these interventions on FH management and patient outcome be assessed.

Frequency and clinical and molecular aspects of familial hypercholesterolemia in an endocrinology unit in Ciudad Bolívar, Venezuela.

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Lima-Martínez, Marcos M; Paoli, Mariela; Vázquez-Cárdenas, Alejandra; Magaña-Torres, María Teresa; Guevara, Ornella; Muñoz, María Carolina; Parrilla-Alvarez, Alberto; Márquez, Yuliangelys; Medeiros, Ana; Bourbon, Mafalda

2017-10-01

To assess the frequency and the clinical, biochemical, and molecular aspects of familial hypercholesterolemia (FH) in subjects attending an endocrinology unit. An observational, descriptive study evaluating 3,140 subjects attending the endocrinology unit of Centro Médico Orinoco in Ciudad Bolívar, Venezuela, from 7 January 2013 to 9 December 2016. The index cases were selected using the Dutch Lipid Clinic Network criteria. Plasma lipid levels were measured, and a molecular analysis was performed by DNA sequencing of the LDLR and APOB genes. Ten (0.32%) of the 3,140 study patients had clinical and biochemical characteristics consistent with FH. All but one were female. Three had first-degree relatives with prior premature coronary artery; and none had a personal history of this condition. Three patients were obese; three had high blood pressure; and no one suffered from diabetes. Three patients had a history of tendon xanthomas, and one of corneal arcus. LDL-C levels ranged from 191 to 486mg/dL. Two patients were on statin therapy. The genetic causes of FH were identified in four patients, and were LDLR gene mutations in three of them and an APOB gene mutation in exon 26 in the other. Approximately, one out of every 300 people attending this endocrinology unit in those four years had FH, and LDLR gene mutations were the most prevalent cause. Copyright © 2017 SEEN. Publicado por Elsevier España, S.L.U. All rights reserved.

Effect of microalga Spirulina platensis (Arthrospira platensis on hippocampus lipoperoxidation and lipid profile in rats with induced hypercholesterolemia

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Telma Elita Bertolin

2009-10-01

Full Text Available Studies have been conducted on microalga Spirulina platensis (Arthrospira platensis due to its therapeutic potential in several areas, including the capacity for preventing and decreasing the damages caused by hyperlipidemia and the antioxidant activity. The aim of the study was to evaluate the effect of microalga Spirulina platensis on hippocampus lipoperoxidation and lipid profile in rats with induced hypercholesterolemia during 60 days. The measurement of hippocampus lipoperoxidation did not demonstrate significant difference (p>0.05 when Spirulina platensis was added to hypercholesterolemic diet. The evaluation of lipid profile showed that the administration of the microalga in therapeutic and preventive ways led to a significant protective effect (pA microalga Spirulina platensis (Arthrospira platensis vem sendo fonte de pesquisas devido a evidências de seu potencial terapêutico em diversas áreas, dentre elas a capacidade de prevenção e diminuição dos danos causados por dislipidemias e sua atividade antioxidante. Objetivou-se avaliar o efeito da microalga Spirulina platensis sobre a lipoperoxidação no hipocampo e perfil lipídico sérico em ratos com hipercolesterolemia induzida durante 60 dias. A dosagem da lipoperoxidação no hipocampo não demonstrou diferença significativa (p>0,05 quando Spirulina platensis foi adicionada na dieta hipercolêsterolemica. A avaliação do perfil lipídico demonstrou que a administração da microlaga de forma terapêutica e preventiva demonstrou efeito significativo (p<0,05 na proteção do desenvolvimento de hipercolesterolemia.

Effects of Docosahexaenoic Acid Supplementation on Blood Pressure, Heart Rate, and Serum Lipids in Scottish Men with Hypertension and Hypercholesterolemia

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Miki Sagara

2011-01-01

Full Text Available To investigate the effects of daily supplementation with docosahexaenoic acid (DHA on coronary heart disease risks in 38 middle-aged men with hypertension and/or hypercholesterolemia in Scotland, a five-week double-blind placebo-controlled dietary supplementation with either 2 g of DHA or active placebo (1 g of olive oil was conducted. Percent composition of DHA in plasma phospholipids increased significantly in DHA group. Systolic and diastolic blood pressure and heart rate decreased significantly in DHA group, but not in placebo group. High-density lipoprotein cholesterol (HDL-C increased significantly, and total cholesterol (TC/HDL-C and non-HDL-C/HDL-C ratios decreased significantly in both groups. There was no change in TC and non-HDL-C. We conclude that 2 g/day of DHA supplementation reduced coronary heart disease risk factor level improving blood pressure, heart rate, and lipid profiles in hypertensive, hypercholesterolemic Scottish men who do not eat fish on a regular basis.

Use of next-generation sequencing to detect LDLR gene copy number variation in familial hypercholesterolemia.

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Iacocca, Michael A; Wang, Jian; Dron, Jacqueline S; Robinson, John F; McIntyre, Adam D; Cao, Henian; Hegele, Robert A

2017-11-01

Familial hypercholesterolemia (FH) is a heritable condition of severely elevated LDL cholesterol, caused predominantly by autosomal codominant mutations in the LDL receptor gene ( LDLR ). In providing a molecular diagnosis for FH, the current procedure often includes targeted next-generation sequencing (NGS) panels for the detection of small-scale DNA variants, followed by multiplex ligation-dependent probe amplification (MLPA) in LDLR for the detection of whole-exon copy number variants (CNVs). The latter is essential because ∼10% of FH cases are attributed to CNVs in LDLR ; accounting for them decreases false negative findings. Here, we determined the potential of replacing MLPA with bioinformatic analysis applied to NGS data, which uses depth-of-coverage analysis as its principal method to identify whole-exon CNV events. In analysis of 388 FH patient samples, there was 100% concordance in LDLR CNV detection between these two methods: 38 reported CNVs identified by MLPA were also successfully detected by our NGS method, while 350 samples negative for CNVs by MLPA were also negative by NGS. This result suggests that MLPA can be removed from the routine diagnostic screening for FH, significantly reducing associated costs, resources, and analysis time, while promoting more widespread assessment of this important class of mutations across diagnostic laboratories. Copyright © 2017 by the American Society for Biochemistry and Molecular Biology, Inc.

Endothelial NLRP3 inflammasome activation and arterial neointima formation associated with acid sphingomyelinase during hypercholesterolemia

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Saisudha Koka

2017-10-01

Full Text Available The NLRP3 inflammasome has been reported to be activated by atherogenic factors, whereby endothelial injury and consequent atherosclerotic lesions are triggered in the arterial wall. However, the mechanisms activating and regulating NLRP3 inflammasomes remain poorly understood. The present study tested whether acid sphingomyelinase (ASM and ceramide associated membrane raft (MR signaling platforms contribute to the activation of NLRP3 inflammasomes and atherosclerotic lesions during hypercholesterolemia. We found that 7-ketocholesterol (7-Keto or cholesterol crystal (ChC markedly increased the formation and activation of NLRP3 inflammasomes in mouse carotid arterial endothelial cells (CAECs, as shown by increased colocalization of NLRP3 with ASC or caspase-1, enhanced caspase-1 activity and elevated IL-1β levels, which were markedly attenuated by mouse Asm siRNA, ASM inhibitor- amitriptyline, and deletion of mouse Asm gene. In CAECs with NLRP3 inflammasome formation, membrane raft (MR clustering with NADPH oxidase subunits was found remarkably increased as shown by CTXB (MR marker and gp91phox aggregation indicating the formation of MR redox signaling platforms. This MR clustering was blocked by MR disruptor (MCD, ROS scavenger (Tempol and TXNIP inhibitor (verapamil, accompanied by attenuation of 7-Keto or ChC-induced increase in caspase-1 activity. In animal experiments, Western diet fed mice with partially ligated left carotid artery (PLCA were found to have significantly increased neointimal formation, which was associated with increased NLRP3 inflammasome formation and IL-1β production in the intima of Asm+/+ mice but not in Asm-/- mice. These results suggest that Asm gene and ceramide associated MR clustering are essential to endothelial inflammasome activation and dysfunction in the carotid arteries, ultimately determining the extent of atherosclerotic lesions.

Prevalence, management, and outcomes of familial hypercholesterolemia in patients with acute coronary syndromes in the Arabian Gulf.

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Al-Rasadi, Khalid; Al-Zakwani, Ibrahim; Alsheikh-Ali, Alawi A; Almahmeed, Wael; Rashed, Wafa; Ridha, Mustafa; Santos, Raul D; Zubaid, Mohammad

2018-02-14

Information on the epidemiology of familial hypercholesterolemia (FH) in the Arabian Gulf region, which has an elevated rate of consanguinity and type II diabetes, is scarce. To assess the prevalence of FH, its management, and impact on atherosclerotic cardiovascular disease (ASCVD) outcomes in a multicenter cohort of Arabian Gulf patients with acute coronary syndrome (ACS). Patients (N = 3224) hospitalized with ACS were studied. FH was diagnosed using the Dutch Lipid Clinic Network criteria. A composite endpoint of nonfatal myocardial infarction, stroke, transient ischemic attack, and mortality between the "probable/definite" and the "unlikely" FH patients was assessed after 1 year. Analyses were performed using univariate and multivariate statistical techniques. At admission, the proportion of "probable/definite", "possible", and "unlikely" FH in ACS patients was 3.7% (n = 119), 28% (n = 911), and 68% (n = 2194), respectively. Overall, 54% (n = 1730) of patients had diabetes, whereas 24% (n = 783) were current smokers. The "probable/definite" FH group was younger (50 vs 63 years; P definite" FH cohort had worse lipid control (13% vs 23%; P < .001) and presented with a greater association with the composite ASCVD endpoint when compared with the "unlikely" FH group (odds ratio: 1.85; 95% confidence interval: 1.01-3.38; P = .047) after multivariable adjustment. In Arabian Gulf citizens, FH was common in ACS patients, was undertreated, and was associated with a worse 1-year prognosis. Copyright © 2018 National Lipid Association. Published by Elsevier Inc. All rights reserved.

Physalis peruviana pomace suppresses highcholesterol diet-induced hypercholesterolemia in rats

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Ramadan, M. F.

2012-10-01

Full Text Available Physalis peruviana (goldenberry is a promising fruits that can be an ingredient in several functional foods. No reports are available on the effect of the administration of goldenberry pomace on different aspects of the plasma lipid profile in experimental animals. According to the chemical composition of the fruit pomace which includes high levels of bioactive compounds, the hypothesis was that feeding Physalis peruviana pomace may have health-promoting and hypercholesterolemic impacts on rats fed a high cholesterol diet (HCD. Therefore, the objective of this study was to investigate the effect of feeding goldenberry pomace on hypercholesterolemia by analyzing the changes in lipid profiles in HCD fed rats. The chemical composition, lipid profiles (fatty acids, tocopherols and sterols and phenolic contents of the fruit pomace were determined. Generally, rats fed the fruit pomace showed lower levels of total cholesterol (TC, total triacylglycerol (TAG and total low density lipoprotein (LDL cholesterol as well as higher levels of high density lipoprotein (HDL cholesterol in comparison with animals fed HCD and cholesterol free diets (CFD. Histological examinations of the liver and kidney were also studied. The results demonstrated that goldenberry pomace consumption provides overall beneficial effects on reversing HCD associated detrimental changes.Physalis peruviana (aguaymanto es un fruto prometedor que puede ser parte de diferentes alimentos funcionales. No hay datos disponibles sobre el efecto de la administración del orujo de aguaymanto sobre diferentes aspectos del perfil de lipídos plasmáticos en animales de experimentación. De acuerdo con la composición química del orujo de la fruta que incluye altos niveles de compuestos bioactivos, se demostró la hipótesis de que la alimentación con orujo de Physalis peruviana puede tener efectos saludables y sobre la hipercolesterolemia en ratas alimentadas con una dieta alta en colesterol (HCD

MRI at 3 Tesla detects no evidence for ischemic brain damage in intensively treated patients with homozygous familial hypercholesterolemia

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Schmitz, Stephan A.; O' Regan, Declan P.; Fitzpatrick, Julie; Hajnal, Joseph V. [Hammersmith Hospital Campus, Imaging Sciences Department, MRC Clinical Sciences Centre, Faculty of Medicine, Imperial College, London (United Kingdom); Neuwirth, Clare; Potter, Elizabeth; Tosi, Isabella; Naoumova, Rossi P. [MRC Clinical Sciences Centre, Clinical Research Facility, London (United Kingdom); Hammersmith Hospital, Lipid Clinic, London (United Kingdom)

2007-11-15

Homozygous familial hypercholesterolemia (FH) is considered a model disease for excessive plasma cholesterol levels. Patients with untreated homozygous FH have a markedly increased risk for premature atherosclerosis. The frequency and extent of ischemic brain damage detectable by high-field magnetic resonance imaging (MRI) after long-term intensive treatment are unknown. In a case control study, five patients with homozygous FH (one male and four females; mean age: 23.6 {+-} 9.2, range: 12-36 years; mean pre-treatment serum total cholesterol level: 26.9 {+-} 3.24 mmol/L; all patients with documented atherosclerotic plaques in the carotid arteries) and five age- and sex-matched healthy controls were studied. All patients had been on maximal lipid-lowering medication since early childhood, and four of them were also on treatment with low-density lipoprotein (LDL) apheresis at bi-weekly intervals. Brain MRI was performed at 3 Tesla field strength with fluid-attenuated T2-weighted inversion recovery and T1-weighted spin-echo MR pulse sequences and subsequently evaluated by two independent readers. The maximal lipid-lowering treatment reduced the total serum cholesterol by more than 50% in the patients, but their serum concentrations were still 3.6-fold higher than those found in the controls (11.9 {+-} 4.2 vs. 4.5 {+-} 0.5 mmol/L; p < 0.0047). No brain abnormality was observed in any of the patients with homozygous FH. Homozygous FH patients on intensive cholesterol-lowering therapy have no evidence of ischemic brain damage at 3 Tesla MRI despite the remaining high cholesterol levels. (orig.)

MRI at 3 Tesla detects no evidence for ischemic brain damage in intensively treated patients with homozygous familial hypercholesterolemia

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Schmitz, Stephan A.; O'Regan, Declan P.; Fitzpatrick, Julie; Hajnal, Joseph V.; Neuwirth, Clare; Potter, Elizabeth; Tosi, Isabella; Naoumova, Rossi P.

2007-01-01

Homozygous familial hypercholesterolemia (FH) is considered a model disease for excessive plasma cholesterol levels. Patients with untreated homozygous FH have a markedly increased risk for premature atherosclerosis. The frequency and extent of ischemic brain damage detectable by high-field magnetic resonance imaging (MRI) after long-term intensive treatment are unknown. In a case control study, five patients with homozygous FH (one male and four females; mean age: 23.6 ± 9.2, range: 12-36 years; mean pre-treatment serum total cholesterol level: 26.9 ± 3.24 mmol/L; all patients with documented atherosclerotic plaques in the carotid arteries) and five age- and sex-matched healthy controls were studied. All patients had been on maximal lipid-lowering medication since early childhood, and four of them were also on treatment with low-density lipoprotein (LDL) apheresis at bi-weekly intervals. Brain MRI was performed at 3 Tesla field strength with fluid-attenuated T2-weighted inversion recovery and T1-weighted spin-echo MR pulse sequences and subsequently evaluated by two independent readers. The maximal lipid-lowering treatment reduced the total serum cholesterol by more than 50% in the patients, but their serum concentrations were still 3.6-fold higher than those found in the controls (11.9 ± 4.2 vs. 4.5 ± 0.5 mmol/L; p < 0.0047). No brain abnormality was observed in any of the patients with homozygous FH. Homozygous FH patients on intensive cholesterol-lowering therapy have no evidence of ischemic brain damage at 3 Tesla MRI despite the remaining high cholesterol levels. (orig.)

The Effects of Beta-Glucan Rich Oat Bread on Serum Nitric Oxide and Vascular Endothelial Function in Patients with Hypercholesterolemia

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Faezeh Tabesh

2014-01-01

Full Text Available Introduction. Oats are high in soluble fibers and effective in reducing the risk of cardiovascular diseases (CVD. We assessed the effects of beta-glucan from oat bran on serum nitric oxide (NO endothelial function in patients with hypercholesterolemia. Method. Sixty hypercholesterolemic patients were randomly divided to receive an experimental bread rich in beta-glucan from oat bran (intervention or bread rich in wheat fiber (control for four weeks. All subjects had the same diet for two-week baseline period and hypocaloric diet for four weeks of intervention. Serum NO concentration and flow-mediated dilation (FMD were determined before and after the experiment. Results. Mean age of the participants was 51.1 ± 9.3 years and 65% (n=39 were female. After intervention, serum NO concentration increased by 50.2 ± 19.8 μmol/lit in the intervention group (P=0.017, but no change was observed in the control group (17.5 ± 27.5 μmol/lit; P=0.530. No change of FMD was observed in the intervention (0.48 ± 0.78%; P=0.546 or in the control group (0.59 ± 0.92%; P=0.533. Conclusion. Consumption of oat bread for four weeks increases serum NO concentration but has no effect on FMD. Further studies are warranted in this regard.

Two Years after Molecular Diagnosis of Familial Hypercholesterolemia: Majority on Cholesterol-Lowering Treatment but a Minority Reaches Treatment Goal

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Huijgen, Roeland; Kindt, Iris; Verhoeven, Sjoerd B. J.; Sijbrands, Eric J. G.; Vissers, Maud N.; Kastelein, John J. P.; Hutten, Barbara A.

2010-01-01

Background The risk of premature cardiovascular disease in patients with familial hypercholesterolemia (FH) can be profoundly reduced by cholesterol-lowering therapy, and current guidelines for FH advocate ambitious low-density lipoprotein cholesterol (LDL-C) goals. In the present study, we determined whether these goals are reflected in current clinical practice once FH has been diagnosed. Methodology/Principal Findings In 2008, we sent questionnaires to all subjects (aged 18–65 years) who were molecularly diagnosed with FH in the year 2006 through the screening program in the Netherlands. Of these 1062 subjects, 781 completed the questionnaire (46% males; mean age: 42±12 years; mean LDL-C at molecular diagnosis (baseline): 4.1±1.3 mmol/L). The number of persons that used cholesterol-lowering therapy increased from 397 (51%) at baseline to 636 (81%) after diagnosis. Mean treated LDL-C levels decreased significantly to 3.2±1.1 mmol/L two years after diagnosis. Only 22% achieved the LDL-C target level of ≤2.5 mmol/L. Conclusions/Significance The proportion of patients using cholesterol-lowering medication was significantly increased after FH diagnosis through genetic cascade screening. The attained LDL-C levels were lower than those reported in previous surveys on medication use in FH, which could reflect the effect of more stringent lipid target levels. However, only a minority of the medication users reached the LDL-C target. PMID:20169164

Subjects with molecularly defined familial hypercholesterolemia or familial defective apoB-100 are not being adequately treated.

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Trond P Leren

2011-02-01

Full Text Available To study whether subjects with a molecular genetic diagnosis of familial hypercholesterolemia (FH or familial defective apoB-100 (FDB are being adequately treated.A questionnaire regarding medical history was sent to 2611 subjects who had been provided with a molecular genetic diagnosis of FH or FDB, and a blood sample was obtained for lipid measurements.956 (36.6% of the 2611 subjects participated. The mean age for starting lipid-lowering therapy was 33.4 (±12.1 years. Among those below 18 years of age, only 20.4% were on lipid-lowering drugs, whereas 89.1% of those aged 18 and above were on lipid-lowering drugs. The mean levels of total serum cholesterol and LDL-cholesterol were 5.7 (±1.5 mmol/l and 3.9 (±1.3 mmol/l, respectively. Among those who were on lipid-lowering drugs, 29.0% and 12.2% had levels of LDL cholesterol below 3.0 mmol/l and 2.6 mmol/l, respectively. Only 47.3% of the 956 subjects were considered as being adequately treated largely due to a failure to titrate their drug regimens. From the use of cholesterol-years score, lipid-lowering therapy must start before the age of 20 in order to prevent the subjects from contracting premature coronary heart disease.The majority of FH/FDB subjects are being diagnosed late in life and are not being adequately treated. In order to prevent them from contracting premature coronary heart disease, it is key that levels of LDL cholesterol are normalized from a young age and that sufficient doses of lipid-lowering drugs are being used.

Pharmacological activity of the hydroalcoholic extract from Hovenia dulcis thunberg fruit and the flavonoid dihydromyricetin during hypercholesterolemia induced in rats

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Juliana Tensol Pinto

2014-12-01

Full Text Available Cerebrovascular accidents and coronary artery disease are the leading causes of cardiovascular mortalities in Brazil and high levels of LDL cholesterol are one of the main risk factors. In this context, several plant extracts and natural substances have shown promise as cholesterol-lowering. The objective of this study was to evaluate the potential of the hydroalcoholic extract of the fruit of H. dulcisand of dihydromyricetin in cholesterol reduction in hypercholesterolemic rats. Forty-two Wistar male rats were distributed into seven groups of six animals that received diets supplemented with 1% cholesterol and 0.3% cholic acid, with the exception of the control group, which received conventional diets. Animals were treated with oral suspensions containing: atorvastatin 1.0 mg/kg; H. dulcisextract at 50.0 and 100.0 mg/kg and dihydromyricetin at 25.0 and 50.0 mg/kg vehicle (control group. The following biochemical markers were evaluated; total cholesterol, HDL-C, LDL-C, triglycerides, AST, ALT, and alkaline phosphatase. The hypercholesterolemic diet was effective in inducing hypercholesterolemia, increasing total cholesterol by 112.7% relative to the control group. The treatments with two doses of the extract proved to be promising hypocholesterolemic agents, as they were able to substantially reduce total cholesterol and LDL-C, without significantly altering triglycerides, hepatic transaminases, and alkaline phosphatase, thereby encouraging the studies with the plant H. dulcis. The groups treated with the flavonoid dihydromyricetin, although they showed a significant reduction in total cholesterol and LDL-C, and found increases in triglycerides and hepatic transaminases, which is unwanted in the context of hypercholesterolaemia.

Cholesterol lowering effect of a soy drink enriched with plant sterols in a French population with moderate hypercholesterolemia

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Bard Jean-Marie

2008-10-01

Full Text Available Abstract Background Plant sterols are an established non-pharmacological means to reduce total and LDL blood cholesterol concentrations and are therefore recommended for cholesterol management by worldwide-renown health care institutions. Their efficacy has been proven in many types of foods with the majority of trials conducted in spreads or dairy products. As an alternative to dairy products, soy based foods are common throughout the world. Yet, there is little evidence supporting the efficacy of plant sterols in soy-based foods. The objective of this study was to investigate the effect of a soy drink enriched with plant sterols on blood lipid profiles in moderately hypercholesterolemic subjects. Methods In a randomized, placebo-controlled double-blind mono-centric study, 50 subjects were assigned to 200 ml of soy drink either enriched with 2.6 g plant sterol esters (1.6 g/d free plant sterol equivalents or without plant sterols (control for 8 weeks. Subjects were instructed to maintain stable diet pattern and physical activity. Plasma concentrations of lipids were measured at initial visit, after 4 weeks and after 8 weeks. The primary measurement was the change in LDL cholesterol (LDL-C. Secondary measurements were changes in total cholesterol (TC, non-HDL cholesterol (non-HDL-C, HDL cholesterol (HDL-C and triglycerides. Results Regular consumption of the soy drink enriched with plant sterols for 8 weeks significantly reduced LDL- C by 0.29 mmol/l or 7% compared to baseline (p 96%, and products were well tolerated. Conclusion Daily consumption of a plant sterol-enriched soy drink significantly decreased total, non-HDL and LDL cholesterol and is therefore an interesting and convenient aid in managing mild to moderate hypercholesterolemia.

The theoretical advantage of affinity membrane-based immunoadsorption therapy of hypercholesterolemia

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Green, P.; Odell, R.; Schindhelm, K.

1996-01-01

Full text: Therapy of hypercholesterolemia using immunoadsorption of Low Density Lipoprotein (LDL) to a gel substrate is a current clinical technique (Bosch T., Biomat., Art. Cells and Immob. Biotech, 20: 1165- 1169, 1992). Recently, Affinity Membranes have been proposed as an alternate substrate for immunoadsorption (Brandt S and others, Bio Technology, 6:779-782, 1988). Potentially, the overall rate of adsorption to a membrane may be faster than to a gel because of the different geometry (ibid). This implies that for the same conditions, a membrane-based device will have a higher Number of Transfer Units, more efficient adsorption and a smaller device size than a gel. To test this hypothesis, we calculated two key theoretical design parameters: Separation Factor, R, and the Number of Transfer Units, N, for a functioning clinical-scale affinity membrane device: R=K d /K d +C 0 . Kd: Equilibrium Dissociation Constant (M) and Co: Feed Concentration (M) N=k a Q max V m /F. ka: Intrinsic reaction rate constant (M -1 min -1 ), Qmax: Substrate capacity (M), Vm: Membrane volume (m1) and F: Flow Rate (m1 min -1 ). We assumed 1 hr treatment time during which 1 plasma volume (3L) is treated, hence F=50 (m1 min -1 ). If we assume 2/3 of LDL is removed from an initial level of 3 g/L, we can calculate an average feed concentration Co = 2 g / L. There is some data available in the literature for typical values of Kd (10 -8 M) and ka ( 10 3 M -1 s -1 to 3 x 10 5 M -1 s -1 ) (Olsen WC and others, Molec. Immun: 26: 129-136, 1989). Since the intrinsic reaction kinetics may vary from very slow (10 3 M) to very fast (3 x 10 5 M), the Number of Transfer Units, N may vary from small (2) to large (650). Hence for a membrane device, we must select the antibody with the fastest reaction, ka, and highest capacity (Qmax) otherwise, there may be no advantage in a membrane-based device over a gel-based device

CRISPR Correction of a Homozygous Low-Density Lipoprotein Receptor Mutation in Familial Hypercholesterolemia Induced Pluripotent Stem Cells.

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Omer, Linda; Hudson, Elizabeth A; Zheng, Shirong; Hoying, James B; Shan, Yuan; Boyd, Nolan L

2017-11-01

Familial hypercholesterolemia (FH) is a hereditary disease primarily due to mutations in the low-density lipoprotein receptor (LDLR) that lead to elevated cholesterol and premature development of cardiovascular disease. Homozygous FH patients (HoFH) with two dysfunctional LDLR alleles are not as successfully treated with standard hypercholesterol therapies, and more aggressive therapeutic approaches to control cholesterol levels must be considered. Liver transplant can resolve HoFH, and hepatocyte transplantation has shown promising results in animals and humans. However, demand for donated livers and high-quality hepatocytes overwhelm the supply. Human pluripotent stem cells can differentiate to hepatocyte-like cells (HLCs) with the potential for experimental and clinical use. To be of future clinical use as autologous cells, LDLR genetic mutations in derived FH-HLCs need to be corrected. Genome editing technology clustered-regularly-interspaced-short-palindromic-repeats/CRISPR-associated 9 (CRISPR/Cas9) can repair pathologic genetic mutations in human induced pluripotent stem cells. We used CRISPR/Cas9 genome editing to permanently correct a 3-base pair homozygous deletion in LDLR exon 4 of patient-derived HoFH induced pluripotent stem cells. The genetic correction restored LDLR-mediated endocytosis in FH-HLCs and demonstrates the proof-of-principle that CRISPR-mediated genetic modification can be successfully used to normalize HoFH cholesterol metabolism deficiency at the cellular level.

Attainment of LDL Cholesterol Treatment Goals in Children and Adolescents With Familial Hypercholesterolemia. The SAFEHEART Follow-up Registry.

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Saltijeral, Adriana; Pérez de Isla, Leopoldo; Alonso, Rodrigo; Muñiz, Ovidio; Díaz-Díaz, José Luis; Fuentes, Francisco; Mata, Nelva; de Andrés, Raimundo; Díaz-Soto, Gonzalo; Pastor, José; Pinilla, José Miguel; Zambón, Daniel; Pinto, Xavier; Badimón, Lina; Mata, Pedro

2017-06-01

Little is known about the characteristics of persons with familial hypercholesterolemia (FH) younger than 18 years, the lipid-lowering therapy used in these patients, and the lipid goals reached in real life. Our aim was to evaluate the achievement of low-density lipoprotein cholesterol (LDL-C) treatment goals in FH patients younger than 18 years enrolled in a large national registry. We analyzed patients younger than 18 years enrolled in a large ongoing registry of molecularly-defined patients with FH in Spain. The attainment of guideline-recommended plasma LDL-C goals at entry and follow-up was analyzed in relation to the use of lipid-lowering therapy. We enrolled 392 individuals younger than 18 years. Of these, 217 were molecularly-diagnosed FH patients and had a complete follow-up. The median follow-up time was 4.69 years (interquartile range, 2.48-6.38 years), 68.2% of FH patients were on statins, and 41.5% patients had LDL-C < 130mg/dL. Statin use was the only predictor of LDL-C goal attainment. This study shows that a high proportion of FH patients younger than 18 years have high LDL-C levels and fail to achieve recommended LDL-C targets. Statin use was the only independent predictor of LDL-C goal achievement. No safety concerns were detected during follow-up. These results indicate that many FH patients are not adequately controlled and that there is still room for treatment improvement. Copyright © 2016 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.

Sitagliptin/Simvastatin: a first combination tablet to treat type 2 diabetes and hypercholesterolemia – a review of its characteristics

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Ramadan WH

2015-02-01

Full Text Available Wijdan H Ramadan, Wissam K Kabbara Department of Pharmacy Practice, School of Pharmacy, Lebanese American University, Byblos, Lebanon Background: The purpose of this study was to review the current literature and information on the combination product Juvisync™ (sitagliptin + simvastatin, which was approved by the US Food and Drug Administration in October 2011. Methods: PubMed (2001–2014 was searched for primary and review articles on sitagliptin, simvastatin, or the combination product. Drug manufacturing data and product labeling were also used. Studies of simvastatin, sitagliptin, or the combination were screened and analyzed to include relevant and recent papers. Selected English language trials were limited to those with human subjects and included both safety and efficacy outcomes. Results: When compared with glipizide as add-on therapy to metformin, sitagliptin was noninferior but had lower rates of hypoglycemia and weight gain. In addition, when compared with insulin glargine, sitagliptin was less effective in decreasing glycosylated hemoglobin, but was associated with significantly lower rates of hypoglycemia. Further, trials have shown a beneficial effect of using statins in patients with diabetes mellitus with regard to decreasing cardiovascular risk, regardless of baseline lipid levels or the presence of a cardiac disease. Both medications have also demonstrated an acceptable side effect profile. However, caution is needed when coadministering with any drug that may increase simvastatin levels to reduce the risk of myopathy and rhabdomyolysis. Conclusion: Juvisync should be used in patients requiring both sitagliptin and simvastatin. Both agents have shown good efficacy and acceptable safety profiles. Sitagliptin is a good option for diabetic patients to improve glycemic control with a lower risk of hypoglycemia and weight gain. Keywords: simvastatin, sitagliptin, Juvisync™, diabetes mellitus, hypercholesterolemia

Gugulipid causes hypercholesterolemia leading to endothelial dysfunction, increased atherosclerosis, and premature death by ischemic heart disease in male mice.

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Andrea Leiva

Full Text Available For proper cholesterol metabolism, normal expression and function of scavenger receptor class B type I (SR-BI, a high-density lipoprotein (HDL receptor, is required. Among the factors that regulate overall cholesterol homeostasis and HDL metabolism, the nuclear farnesoid X receptor plays an important role. Guggulsterone, a bioactive compound present in the natural product gugulipid, is an antagonist of this receptor. This natural product is widely used globally as a natural lipid-lowering agent, although its anti-atherogenic cardiovascular benefit in animal models or humans is unknown. The aim of this study was to determine the effects of gugulipid on cholesterol homeostasis and development of mild and severe atherosclerosis in male mice. For this purpose, we evaluated the impact of gugulipid treatment on liver histology, plasma lipoprotein cholesterol, endothelial function, and development of atherosclerosis and/or ischemic heart disease in wild-type mice; apolipoprotein E knockout mice, a model of atherosclerosis without ischemic complications; and SR-B1 knockout and atherogenic-diet-fed apolipoprotein E hypomorphic (SR-BI KO/ApoER61h/h mice, a model of lethal ischemic heart disease due to severe atherosclerosis. Gugulipid administration was associated with histological abnormalities in liver, increased alanine aminotransferase levels, lower hepatic SR-BI content, hypercholesterolemia due to increased HDL cholesterol levels, endothelial dysfunction, enhanced atherosclerosis, and accelerated death in animals with severe ischemic heart disease. In conclusion, our data show important adverse effects of gugulipid intake on HDL metabolism and atherosclerosis in male mice, suggesting potential and unknown deleterious effects on cardiovascular health in humans. In addition, these findings reemphasize the need for rigorous preclinical and clinical studies to provide guidance on the consumption of natural products and regulation of their use in the

Cholesterol contributes to dopamine-neuronal loss in MPTP mouse model of Parkinson's disease: Involvement of mitochondrial dysfunctions and oxidative stress.

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Rajib Paul

Full Text Available Hypercholesterolemia is a known contributor to the pathogenesis of Alzheimer's disease while its role in the occurrence of Parkinson's disease (PD is only conjecture and far from conclusive. Altered antioxidant homeostasis and mitochondrial functions are the key mechanisms in loss of dopaminergic neurons in the substantia nigra (SN region of the midbrain in PD. Hypercholesterolemia is reported to cause oxidative stress and mitochondrial dysfunctions in the cortex and hippocampus regions of the brain in rodents. However, the impact of hypercholesterolemia on the midbrain dopaminergic neurons in animal models of PD remains elusive. We tested the hypothesis that hypercholesterolemia in MPTP model of PD would potentiate dopaminergic neuron loss in SN by disrupting mitochondrial functions and antioxidant homeostasis. It is evident from the present study that hypercholesterolemia in naïve animals caused dopamine neuronal loss in SN with subsequent reduction in striatal dopamine levels producing motor impairment. Moreover, in the MPTP model of PD, hypercholesterolemia exacerbated MPTP-induced reduction of striatal dopamine as well as dopaminergic neurons in SN with motor behavioral depreciation. Activity of mitochondrial complexes, mainly complex-I and III, was impaired severely in the nigrostriatal pathway of hypercholesterolemic animals treated with MPTP. Hypercholesterolemia caused oxidative stress in the nigrostriatal pathway with increased generation of hydroxyl radicals and enhanced activity of antioxidant enzymes, which were further aggravated in the hypercholesterolemic mice with Parkinsonism. In conclusion, our findings provide evidence of increased vulnerability of the midbrain dopaminergic neurons in PD with hypercholesterolemia.

Cholesterol contributes to dopamine-neuronal loss in MPTP mouse model of Parkinson's disease: Involvement of mitochondrial dysfunctions and oxidative stress.

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Paul, Rajib; Choudhury, Amarendranath; Kumar, Sanjeev; Giri, Anirudha; Sandhir, Rajat; Borah, Anupom

2017-01-01

Hypercholesterolemia is a known contributor to the pathogenesis of Alzheimer's disease while its role in the occurrence of Parkinson's disease (PD) is only conjecture and far from conclusive. Altered antioxidant homeostasis and mitochondrial functions are the key mechanisms in loss of dopaminergic neurons in the substantia nigra (SN) region of the midbrain in PD. Hypercholesterolemia is reported to cause oxidative stress and mitochondrial dysfunctions in the cortex and hippocampus regions of the brain in rodents. However, the impact of hypercholesterolemia on the midbrain dopaminergic neurons in animal models of PD remains elusive. We tested the hypothesis that hypercholesterolemia in MPTP model of PD would potentiate dopaminergic neuron loss in SN by disrupting mitochondrial functions and antioxidant homeostasis. It is evident from the present study that hypercholesterolemia in naïve animals caused dopamine neuronal loss in SN with subsequent reduction in striatal dopamine levels producing motor impairment. Moreover, in the MPTP model of PD, hypercholesterolemia exacerbated MPTP-induced reduction of striatal dopamine as well as dopaminergic neurons in SN with motor behavioral depreciation. Activity of mitochondrial complexes, mainly complex-I and III, was impaired severely in the nigrostriatal pathway of hypercholesterolemic animals treated with MPTP. Hypercholesterolemia caused oxidative stress in the nigrostriatal pathway with increased generation of hydroxyl radicals and enhanced activity of antioxidant enzymes, which were further aggravated in the hypercholesterolemic mice with Parkinsonism. In conclusion, our findings provide evidence of increased vulnerability of the midbrain dopaminergic neurons in PD with hypercholesterolemia.

Imputation of Baseline LDL Cholesterol Concentration in Patients with Familial Hypercholesterolemia on Statins or Ezetimibe.

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Ruel, Isabelle; Aljenedil, Sumayah; Sadri, Iman; de Varennes, Émilie; Hegele, Robert A; Couture, Patrick; Bergeron, Jean; Wanneh, Eric; Baass, Alexis; Dufour, Robert; Gaudet, Daniel; Brisson, Diane; Brunham, Liam R; Francis, Gordon A; Cermakova, Lubomira; Brophy, James M; Ryomoto, Arnold; Mancini, G B John; Genest, Jacques

2018-02-01

Familial hypercholesterolemia (FH) is the most frequent genetic disorder seen clinically and is characterized by increased LDL cholesterol (LDL-C) (>95th percentile), family history of increased LDL-C, premature atherosclerotic cardiovascular disease (ASCVD) in the patient or in first-degree relatives, presence of tendinous xanthomas or premature corneal arcus, or presence of a pathogenic mutation in the LDLR , PCSK9 , or APOB genes. A diagnosis of FH has important clinical implications with respect to lifelong risk of ASCVD and requirement for intensive pharmacological therapy. The concentration of baseline LDL-C (untreated) is essential for the diagnosis of FH but is often not available because the individual is already on statin therapy. To validate a new algorithm to impute baseline LDL-C, we examined 1297 patients. The baseline LDL-C was compared with the imputed baseline obtained within 18 months of the initiation of therapy. We compared the percent reduction in LDL-C on treatment from baseline with the published percent reductions. After eliminating individuals with missing data, nonstandard doses of statins, or medications other than statins or ezetimibe, we provide data on 951 patients. The mean ± SE baseline LDL-C was 243.0 (2.2) mg/dL [6.28 (0.06) mmol/L], and the mean ± SE imputed baseline LDL-C was 244.2 (2.6) mg/dL [6.31 (0.07) mmol/L] ( P = 0.48). There was no difference in response according to the patient's sex or in percent reduction between observed and expected for individual doses or types of statin or ezetimibe. We provide a validated estimation of baseline LDL-C for patients with FH that may help clinicians in making a diagnosis. © 2017 American Association for Clinical Chemistry.

Induction of sustained hypercholesterolemia by single adeno-associated virus-mediated gene transfer of mutant hPCSK9.

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Roche-Molina, Marta; Sanz-Rosa, David; Cruz, Francisco M; García-Prieto, Jaime; López, Sergio; Abia, Rocío; Muriana, Francisco J G; Fuster, Valentín; Ibáñez, Borja; Bernal, Juan A

2015-01-01

Patients with mutations in the proprotein convertase subtilisin/kexin type 9 (PCSK9) gene have hypercholesterolemia and are at high risk of adverse cardiovascular events. We aimed to stably express the pathological human D374Y gain-of-function mutant form of PCSK9 (PCSK9(DY)) in adult wild-type mice to generate a hyperlipidemic and proatherogenic animal model, achieved with a single systemic injection with adeno-associated virus (AAV). We constructed an AAV-based vector to support targeted transfer of the PCSK9(DY) gene to liver. After injection with 3.5×10(10) viral particles, mice in the C57BL/6J, 129/SvPasCrlf, or FVB/NCrl backgrounds developed long-term hyperlipidemia with a strong increase in serum low-density lipoprotein. Macroscopic and histological analysis showed atherosclerotic lesions in the aortas of AAV-PCSK9(DY) mice fed a high-fat-diet. Advanced lesions in these high-fat-diet-fed mice also showed evidence of macrophage infiltration and fibrous cap formation. Hepatic AAV-PCSK9(DY) infection did not result in liver damage or signs of immunologic response. We further tested the use of AAV-PCSK9(DY) to study potential genetic interaction with the ApoE gene. Histological analysis of ApoE(-/-) AAV-PCSK9(DY) mice showed a synergistic response to ApoE deficiency, with aortic lesions twice as extensive in ApoE(-/-) AAV-PCSK9(DY)-transexpressing mice as in ApoE(-/-) AAV-Luc controls without altering serum cholesterol levels. Single intravenous AAV-PCSK9(DY) injection is a fast, easy, and cost-effective approach, resulting in rapid and long-term sustained hyperlipidemia and atherosclerosis. We demonstrate as a proof of concept the synergy between PCSK9(DY) gain-of-function and ApoE deficiency. This methodology could allow testing of the genetic interaction of several mutations without the need for complex and time-consuming backcrosses. © 2014 American Heart Association, Inc.

Can Multiple Lifestyle Behaviours Be Improved in People with Familial Hypercholesterolemia? Results of a Parallel Randomised Controlled Trial

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Broekhuizen, Karen; van Poppel, Mireille N. M.; Koppes, Lando L.; Kindt, Iris; Brug, Johannes; van Mechelen, Willem

2012-01-01

Objective To evaluate the efficacy of an individualised tailored lifestyle intervention on physical activity, dietary intake, smoking and compliance to statin therapy in people with Familial Hypercholesterolemia (FH). Methods Adults with FH (n = 340) were randomly assigned to a usual care control group or an intervention group. The intervention consisted of web-based tailored lifestyle advice and face-to-face counselling. Physical activity, fat, fruit and vegetable intake, smoking and compliance to statin therapy were self-reported at baseline and after 12 months. Regression analyses were conducted to examine between-group differences. Intervention reach, dose and fidelity were assessed. Results In both groups, non-significant improvements in all lifestyle behaviours were found. Post-hoc analyses showed a significant decrease in saturated fat intake among women in the intervention group (β = −1.03; CI −1.98/−0.03). In the intervention group, 95% received a log on account, of which 49% logged on and completed one module. Nearly all participants received face-to-face counselling and on average, 4.2 telephone booster calls. Intervention fidelity was low. Conclusions Individually tailored feedback is not superior to no intervention regarding changes in multiple lifestyle behaviours in people with FH. A higher received dose of computer-tailored interventions should be achieved by uplifting the website and reducing the burden of screening questionnaires. Counsellor training should be more extensive. Trial Registration Dutch Trial Register NTR1899 PMID:23251355

LDL-cholesterol lowering effect of a new dietary supplement: an open label, controlled, randomized, cross-over clinical trial in patients with mild-to-moderate hypercholesterolemia.

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Magno, S; Ceccarini, G; Pelosini, C; Jaccheri, R; Vitti, J; Fierabracci, P; Salvetti, G; Airoldi, G; Minale, M; Saponati, G; Santini, F

2018-05-24

Hypercholesterolemia is a major risk factor for cardiovascular disorders and requires specific intervention through an adequate lifestyle (diet and physical exercise) and, if necessary, an appropriate drug treatment. Lipid-lowering drugs, although generally efficacious, may sometimes cause adverse events. A growing attention has been devoted to the correction of dyslipidemias through the use of dietary supplements. The aim of this study was to assess the lipid-lowering activity and safety of a dietary supplement containing monacolin K, L-arginine, coenzyme Q10 and ascorbic acid, named Argicolina (A), compared to a commercially available product containing monacolin K and coenzyme Q10, Normolip 5 (N). This was a single center, controlled, randomized, open-label, cross-over clinical study enrolling 20 Caucasian outpatients aged 18-75 years with serum LDL-C between 130 and 180 mg/dL. Patients assumed two different dietary supplements (A and N) both containing monacolin K 10 mg for 8 weeks each, separated by a 4-week wash-out period. Evaluated parameters were: Total cholesterol (Tot-C), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), triglycerides (TG), fasting blood glucose, aspartate aminotransferase, alanine aminotransferase, creatinekinase, gamma-glutamyl-transpeptidase, brachial arterial pressure and heart rate, measured at the start and at the end of each treatment period. Safety was monitored through the study. LDL-C decreased by 23.3% during treatment with N (p ascorbic acid also produces a significant reduction of triglycerides without significant effects on HDL. ClinicalTrials.gov ID: NCT03425630 .

Acute consumption of walnuts and walnut components differentially affect postprandial lipemia, endothelial function, oxidative stress, and cholesterol efflux in humans with mild hypercholesterolemia.

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Berryman, Claire E; Grieger, Jessica A; West, Sheila G; Chen, Chung-Yen O; Blumberg, Jeffrey B; Rothblat, George H; Sankaranarayanan, Sandhya; Kris-Etherton, Penny M

2013-06-01

Walnut consumption improves cardiovascular disease risk; however, to our knowledge, the contribution of individual walnut components has not been assessed. This study evaluated the acute consumption of whole walnuts (85 g), separated nut skins (5.6 g), de-fatted nutmeat (34 g), and nut oil (51 g) on postprandial lipemia, endothelial function, and oxidative stress. Cholesterol efflux (ex vivo) was assessed in the whole walnut treatment only. A randomized, 4-period, crossover trial was conducted in healthy overweight and obese adults (n = 15) with moderate hypercholesterolemia. There was a treatment × time point interaction for triglycerides (P < 0.01) and increased postprandial concentrations were observed for the oil and whole walnut treatments (P < 0.01). Walnut skins decreased the reactive hyperemia index (RHI) compared with baseline (P = 0.02) such that a difference persisted between the skin and oil treatments (P = 0.01). The Framingham RHI was maintained with the oil treatment compared with the skins and whole nut (P < 0.05). There was a treatment effect for the ferric reducing antioxidant potential (FRAP) (P < 0.01), and mean FRAP was greater with the oil and skin treatments compared with the nutmeat (P < 0.01). Cholesterol efflux increased by 3.3% following whole walnut consumption in J774 cells cultured with postprandial serum compared with fasting baseline (P = 0.02). Walnut oil favorably affected endothelial function and whole walnuts increased cholesterol efflux. These 2 novel mechanisms may explain in part the cardiovascular benefits of walnuts.

Study of pomegranate (Punica granatum L. peel extract containing anthocyanins on fatty streak formation in the renal arteries in hypercholesterolemic rabbits

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Fatemeh Sharifiyan

2016-01-01

Conclusion: The results of this study indicate that consumption of pomegranate peel extract containing anthocyanins (polyphenol content 1 g/kg diet despite of a significant increase in serum antioxidant capacity cannot protect the kidneys from hypercholesterolemia-induced damages during the treatment period.

Anti-hypercholesterolemic effect of Saccharomyces boulardii in the hamster.

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Girard, Philippe; Pansart, Yannick; Verleye, Marc

2014-01-01

Hypercholesterolemia is a major risk factor for coronary artery disease and probiotics have been suggested as tools to manage elevated cholesterol levels. The present study investigated the ability of the biotherapeutic agent Saccharomyces boulardii (Sb-Biocodex) to reduce the hypercholesterolemia induced by a 0.1% cholesterol-enriched diet in the hamster. In a first experiment, chronic oral treatment with S. boulardii at 12 × 10(10) CFU/kg (3 g/kg) twice a day was started from the beginning of the cholesterol diet and continued for 14 days ('preventive protocol'). In the second experiment, S. boulardii was given 14 days after the beginning of the cholesterol diet when hypercholesterolemia had developed and continued for an additional 14 days ('curative protocol'). In the preventive protocol, administration of the yeast significantly reduced hypercholesterolemia (14%) induced by the cholesterol-enriched diet compared to the group receiving only the cholesterol diet. In the curative protocol, S. boulardii significantly reduced hypercholesterolemia (12%) induced by the cholesterol-enriched diet, too. Moreover, the yeast significantly decreased the serum triglyceride increase by 39%. S. boulardii possesses anti-hypercholesterolemic properties in the hamster worthy of further evaluation in clinical studies. © 2014 S. Karger AG, Basel.

Relationship between Lipid Phenotypes, Overweight, Lipid Lowering Drug Response and KIF6 and HMG-CoA Genotypes in a Subset of the Brisighella Heart Study Population

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Sabrina Angelini

2017-12-01

Full Text Available The existence of genetic traits might explain the susceptibility to develop hypercholesterolemia and the inter-individual differences in statin response. This study was performed to evaluate whether individuals’ polymorphisms in HMG-CoA and KIF6 genes are independently associated with hypercholesterolemia, other lipid-associated traits, and statin response in unselected individuals enrolled in the Brisighella heart study (Survey 2012. A total of 1622 individuals, of which 183 under statin medication, were genotyped for a total of five polymorphisms (KIF6 rs20455, rs9471077, rs9462535; HMG-CoA rs3761740, rs3846662. The relationships between the five loci and clinical characteristics were analyzed. The principal basic parameters calculated on 12 h fasting blood included total cholesterol (TC, High Density Lipoprotein Cholesterol (HDL-C, Low-Density Lipoprotein Cholesterol (LDL-C, and triglycerides (TG. Hypercholesterolemia was defined as a TC >200 mg/dL or use of lipid-lowering medication. 965 individuals were characterized by hypercholesterolemia; these subjects were significantly older (p < 0.001, with body mass index (BMI and waist circumference significantly higher (p < 0.001 compared to the others. HMG-CoA rs3846662 GG genotype was significantly over-represented in the hypercholesterolemic group (p = 0.030. HMG-CoA rs3846662 genotype was associated with the level of TC and LDL-C. Furthermore, in the same subset of untreated subjects, we observed a significant correlation between the KIF6 rs20455 and HDL-C. KIF6 variants were associated with a significantly lower (rs20455 or higher (rs9471077 and rs9462535 risk of obesity, in males only. No association between responsiveness to statins and the polymorphisms under investigation were observed. Our results showed associations between HMG-CoA rs3846662 and KIF6 rs20455 and lipid phenotypes, which may have an influence on dyslipidemia-related events. Moreover, this represents the first study

Increase in peripheral oxidative stress during hypercholesterolemia is not reflected in the central nervous system: evidence from two mouse models.

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Ding, Tao; Yao, Yeumang; Praticò, Domenico

2005-05-01

In recent years oxidative stress has been widely implicated as a pathogenetic mechanism of several diseases, and a variety of indices and assays have been developed to assess this phenomenon in complex biological systems. Most of these biomarkers can be measured virtually in every biological fluid and tissue, providing us with the opportunity to assess their formation at local site of oxidative injury. However, despite their widespread use, it is still not completely clear how their peripheral formation correlates with the levels measured in the central nervous system. For this reason, we utilized two well-characterized animal models of chronic peripheral oxidative stress, low-density lipoprotein receptor (LDLR)-deficient and C57BL/6 mice on a high fat diet. After 8 weeks on the diet, we assessed isoprostane, marker of lipid peroxidation, and carbonyls, marker of protein oxidation, in several organs of these animals. Compared with animals on chow, mice on the high fat diet showed a significant increase in both biomarkers in plasma, heart, aorta and liver but not in brain tissues. This observation was confirmed by the selective accumulation of radioactivity in the peripheral organs but not in the brains of mice injected with tritiated isoprostane. Our findings indicate that in hypercholesterolemia the peripheral formation of oxidative products does not contribute to their levels found in the central nervous system.

Ten years of lipoprotein apheresis for familial hypercholesterolemia in Malaysia: A creative approach by a cardiologist in a developing country.

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Khoo, Kah Lin; Page, Michael M; Liew, Yin Mei; Defesche, Joep C; Watts, Gerald F

2016-01-01

Familial hypercholesterolemia (FH) leads to premature coronary artery disease and aortic stenosis, with undertreated severe forms causing death at a young age. Lipoprotein apheresis (LA) is often required for lowering low-density lipoprotein cholesterol levels in severe FH. The objective of this study was to present the first experiences with LA in Malaysia, between 2004 and 2014. We retrospectively collected data from patient records to assess the effectiveness, adverse effects, patient quality of life, and costs associated with an LA service for genetically confirmed homozygous and heterozygous FH. We treated 13 women and 2 men aged 6 to 59 years, 10 with homozygous and 5 with heterozygous FH, all on maximally tolerated cholesterol-lowering drug therapy, for a total of 65 patient-years. Acute lowering of low-density lipoprotein cholesterol post apheresis was 56.3 ± 7.2%, with time-averaged mean lowering of 34.9 ± 13.9%. No patients experienced any cardiovascular events during the period of receiving LA. Patients receiving LA experienced few side effects and enjoyed reasonable quality of life, but inability to continue treatment was frequent because of cost. LA for severe FH can be delivered effectively in the short term in developing nations, but costs are a major barrier to sustaining this mode of treatment for this high-risk group of patients. New drug therapies for FH, such as the proprotein convertase subtilisin/kexin type 9 inhibitors, microsomal triglyceride transfer protein inhibitors, and apolipoprotein-B100 antisense oligonucleotides may allow improved care for these patients, but costs and long-term safety remain as issues to be addressed. Copyright © 2016 National Lipid Association. Published by Elsevier Inc. All rights reserved.

Global loss of acetylcholinesterase activity with mitochondrial complexes inhibition and inflammation in brain of hypercholesterolemic mice.

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Paul, Rajib; Borah, Anupom

2017-12-20

There exists an intricate relationship between hypercholesterolemia (elevated plasma cholesterol) and brain functions. The present study aims to understand the impact of hypercholesterolemia on pathological consequences in mouse brain. A chronic mouse model of hypercholesterolemia was induced by giving high-cholesterol diet for 12 weeks. The hypercholesterolemic mice developed cognitive impairment as evident from object recognition memory test. Cholesterol accumulation was observed in four discrete brain regions, such as cortex, striatum, hippocampus and substantia nigra along with significantly damaged blood-brain barrier by hypercholesterolemia. The crucial finding is the loss of acetylcholinesterase activity with mitochondrial dysfunction globally in the brain of hypercholesterolemic mice, which is related to the levels of cholesterol. Moreover, the levels of hydroxyl radical were elevated in the regions of brain where the activity of mitochondrial complexes was found to be reduced. Intriguingly, elevations of inflammatory stress markers in the cholesterol-rich brain regions were observed. As cognitive impairment, diminished brain acetylcholinesterase activity, mitochondrial dysfunctions, and inflammation are the prima facie pathologies of neurodegenerative diseases, the findings impose hypercholesterolemia as potential risk factor towards brain dysfunction.

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.

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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.

Oxidized low-density lipoprotein in children with familial hypercholesterolemia and unaffected siblings: effect of pravastatin.

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Rodenburg, Jessica; Vissers, Maud N; Wiegman, Albert; Miller, Elizabeth R; Ridker, Paul M; Witztum, Joseph L; Kastelein, John J P; Tsimikas, Sotirios

2006-05-02

To assess the role of oxidized phospholipids (OxPLs) in children with familial hypercholesterolemia (FH) and the effect of pravastatin. Oxidized phospholipids are a major component of oxidized low-density lipoprotein (OxLDL) and are bound to lipoprotein (a) [Lp(a)]. The significance of OxPL markers in children is unknown. Children with FH were randomized to placebo (n = 88) or pravastatin (n = 90) after instruction on American Heart Association step II diet. Unaffected siblings (n = 78) served as controls. The OxPL content on apolipoprotein B-100 (apoB) detected by antibody E06 (OxPL/apoB ratio), immunoglobulin (Ig)G and IgM immune complexes per apoB (IC/apoB) and on all apoB particles (total apoB-IC = IC/apoB multiplied by plasma apoB levels), autoantibodies to malondialdehyde (MDA)-low-density lipoprotein (LDL), Lp(a), and apoB levels were measured at baseline and after two years of treatment. Compared with unaffected siblings, children with FH had significantly lower levels of OxPL/apoB but higher levels of IgG and IgM total apoB-IC and IgM MDA-LDL autoantibodies. From baseline to two-year follow-up, compared with placebo pravastatin treatment resulted in a greater mean percentage change in apoB (-18.7% vs. 0.3%; p = 0.001), total IgG apoB-IC (-31.9% vs. -12.2%; p vs. 13.2%; p = 0.001). Interestingly, pravastatin also resulted in higher OxPL/apoB (48.7% vs. 29.3%; p = 0.028) and Lp(a) levels (21.9% vs. 10.7%; p = 0.044). Compared with unaffected siblings, children with FH are characterized by elevated levels of apoB-IC and IgM MDA-LDL autoantibodies. Compared with placebo, pravastatin led to a greater reduction in apoB-IC but also to a greater increase in OxPL/apoB and Lp(a), which may represent a novel mechanism of mobilization and clearance of OxPL.

Identification of a point mutation in growth factor repeat C of the low density lipoprotein-receptor gene in a patient with homozygous familial hypercholesterolemia

International Nuclear Information System (INIS)

Soutar, A.K.; Knight, B.L.; Patel, D.D.

1989-01-01

The coding region of the low density lipoprotein (LDL)-receptor gene from a patient (MM) with homozygous familial hypercholesterolemia (FH) has been sequenced from six overlapping 500-base-pair amplified fragments of the cDNA from cultured skin fibroblasts. Two separate single nucleotide base changes from the normal sequence were detected. The first involved substitution of guanine for adenine in the third position of the codon for amino acid residue Cys-27 and did not affect the protein sequence. The second mutation was substitution of thymine for cytosine in the DNA for the codon for amino acid residue 664, changing the codon from CCG (proline) to CTG (leucine) and introducing a new site for the restriction enzyme PstI. MM is a true homozygote with two identical genes, and the mutation cosegregated with clinically diagnosed FH in his family in which first cousin marriages occurred frequently. LDL receptors in MM's skin fibroblasts bind less LDL than normal and with reduced affinity. Thus this naturally occurring single point mutation affects both intracellular transport of the protein and ligand binding and occurs in growth factor-like repeat C, a region that has not previously been found to influence LDL binding

HYPOLIPEDEMIC EFFECT OF CYNODON DACTYLON ON HISTOPATHOLOGICAL STUDY AND DNA FRAGMENTATION ANALYSIS IN EXPERIMENTALLY INDUCED HYPERCHOLESTEREMIC RATS

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C. Selva Kumar

2011-01-01

Hypercholesteremia is one of the risk factors for coronary artery disease. The present study highlights the efficacy of Ayurvedic herbal formulation Cynodon dactylon (Bermuda grass) on histopathological study and DNA fragmentation analysis in experimentally induced hypercholesteremic rats. Four groups of rats were employed namely control, hypercholesterolemia rats (4% Cholesterol＋1% cholic acid), Cynodon dactylon treatment in hypercholesteremic rats and Cynodon dactylon alone treated rats. Re...

Lipoprotein-associated phospholipase A2 mass and activity in children with heterozygous familial hypercholesterolemia and unaffected siblings: effect of pravastatin.

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Ryu, Sung Kee; Hutten, Barbara A; Vissers, Maud N; Wiegman, Albert; Kastelein, John J P; Tsimikas, Sotirios

2011-01-01

Lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) is an independent risk factor of cardiovascular disease and a target of treatment. Lp-PLA(2) levels in children have not been previously reported. The effect of statin therapy on Lp-PLA(2) mass and activity in children with familial hypercholesterolemia (FH) is also not known. Lp-PLA(2) mass and activity levels were measured at baseline and after 2 years in 178 children with FH randomized to pravastatin or placebo and in 78 unaffected and untreated siblings. At the end of the randomized period, all FH children were then placed on pravastatin for an additional 2 years, and Lp-PLA(2) mass and activity levels were correlated with changes in carotid intima-media thickness during 4 years of follow-up. Baseline levels of Lp-PLA(2) mass and activity were significantly greater in children with FH compared with unaffected siblings (mass: 240.3 ± 41.6 vs 222.1 ± 36.5 ng/mL, P = .002; activity: 205.7 ± 41.6 vs 124.3±23.0 nmol/min/mL, P vs 231.5 ± 34.8 ng/mL, P = .001) and activity (178.8 ± 37.3 vs 206.2 ± 33.5 nmol/min/mL, P children with heterozygous FH compared with unaffected siblings and are significantly reduced by pravastatin therapy. Copyright © 2011 National Lipid Association. Published by Elsevier Inc. All rights reserved.

Prevalence of middle cerebral artery stenosis in asymptomatic subjects of more than 40 years age group: a transcranial Doppler study.

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Sada, Sujay; Reddy, Yugandhar; Rao, Sampath; Alladi, Suvarna; Kaul, Subash

2014-01-01

Middle cerebral artery (MCA) disease is the most common vascular lesion in stroke. Transcranial Doppler (TCD) is a non-invasive bedside screening method for assessing cerebral blood flow. To investigate the prevalence of MCA stenosis in asymptomatic but high-risk individuals for stroke. Prospective study between December 2011 and December 2013. Vascular risk factors considered included: hypertension (HTN), diabetes mellitus, smoking, alcohol consumption, coronary artery disease (CAD), peripheral vascular disease (PVD), hypercholesterolemia and obesity. TCD was performed with portable machine through the temporal windows by use of a standardized protocol. Of the 427 subjects, 374 were analyzed; males 264 (70.6%) and females 110 (29.4%). Mean age was 54.2 ± 7.6 years. The frequency of the risk factors was: HTN 287 (76.7%), diabetes 220 (58.8%), CAD 120 (32.1%), hypercholesterolemia 181 (48.4%), smoking 147 (39.3%), alcohol 99 (26.5%), obesity 198 (52.9%) and PVD 8 (2.1%). Of the 374 subjects, 27 (7.2%) had intracranial arterial stenosis and the rest had normal intracranial arteries. On univariate analysis, subjects with higher age, HTN, CAD, smoking and hypercholesterolemia had higher risk of having intracranial arterial stenosis (P < 0.05). Multivariate analysis showed HTN and CAD are independent risk factors for intracranial arterial stenosis. Overall prevalence of intracranial arterial stenosis is 7.2% in high-risk population sample from Hyderabad in South India. HTN and CAD are independent risk factors for the development of intracranial arterial stenosis.

White Matter Hyperintensities on T2-Weighted MRI Images among DNA-Verified Older Familial Hypercholesterolemia Patients

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Hyttinen, L. (Dept. of Internal Medicine, North Karelia Central Hospital, Joensuu (Finland)); Autti, T.; Soljanlahti, S. (Medical Imaging Center, Helsinki Univ. Central Hospital, Helsinki (Finland)); Rauma, S. (Dept. of Radiology, North Karelia Central Hospital, Joensuu (Finland)); Vuorio, A.F. (Dept. of Medicine, Univ. of Helsinki, Helsinki (Finland)); Strandberg, T.E. (Dept. of Health Sciences/Geriatrics, Univ. of Oulu, Oulu (Finland))

2009-04-15

Background: Familial hypercholesterolemia (FH) is a genetic disorder, causing an increased risk of coronary heart disease (CHD) if untreated. Silent brain infarctions and white matter hyperintensities (WMHIs) observed on T2-weighted magnetic resonance images (MRI) are associated with increased risk for stroke and myocardial infarction. Age is a strong predictor of WMHIs. Purpose: To use MRI to assess the presence of clinically silent brain lesions in older FH patients, and to compare the occurrence and size of these lesions in older FH patients with middle-aged FH patients and healthy controls. Material and Methods: A total of 43 older (age = 65 years) FH patients with the same FH North Karelia mutation, living in Finland, were identified. In this comprehensive cohort, 1.5T brain MRI was available for 33 individuals (age 65-84 years, M/F 9/24, mean duration of statin treatment 15.3 years). This group was divided into two age categories: 65-74 years (FHe1 group, n=23) and 75-84 years (FHe2 group, n=10). Infarcts, including lacunas, and WMHIs on T2-weighted images were recorded. Data from brain MRI were compared to those of a group of middle-aged FH patients with CHD (n=19, age 48-64 years) and with middle-aged healthy controls (n=29, age 49-63 years). Results: Only two (6%) of the older FH patients had clinically silent brain infarcts detected by MRI. The amount of large WMHIs (>5 mm in diameter) was similar in the FHe1 group compared with the groups of middle-aged FH patients and healthy controls, even though the FHe1 group was 13 years older. The total amount of WMHIs and the amount of large WMHIs were greatest in the FHe2 group. Conclusion: FH patients aged 65 to 74 years receiving long-term statin treatment (15 years) did not have more WMHIs on brain MRI compared to middle-aged FH patients and healthy controls.

White Matter Hyperintensities on T2-Weighted MRI Images among DNA-Verified Older Familial Hypercholesterolemia Patients

International Nuclear Information System (INIS)

Hyttinen, L.; Autti, T.; Soljanlahti, S.; Rauma, S.; Vuorio, A.F.; Strandberg, T.E.

2009-01-01

Background: Familial hypercholesterolemia (FH) is a genetic disorder, causing an increased risk of coronary heart disease (CHD) if untreated. Silent brain infarctions and white matter hyperintensities (WMHIs) observed on T2-weighted magnetic resonance images (MRI) are associated with increased risk for stroke and myocardial infarction. Age is a strong predictor of WMHIs. Purpose: To use MRI to assess the presence of clinically silent brain lesions in older FH patients, and to compare the occurrence and size of these lesions in older FH patients with middle-aged FH patients and healthy controls. Material and Methods: A total of 43 older (age = 65 years) FH patients with the same FH North Karelia mutation, living in Finland, were identified. In this comprehensive cohort, 1.5T brain MRI was available for 33 individuals (age 65-84 years, M/F 9/24, mean duration of statin treatment 15.3 years). This group was divided into two age categories: 65-74 years (FHe1 group, n=23) and 75-84 years (FHe2 group, n=10). Infarcts, including lacunas, and WMHIs on T2-weighted images were recorded. Data from brain MRI were compared to those of a group of middle-aged FH patients with CHD (n=19, age 48-64 years) and with middle-aged healthy controls (n=29, age 49-63 years). Results: Only two (6%) of the older FH patients had clinically silent brain infarcts detected by MRI. The amount of large WMHIs (>5 mm in diameter) was similar in the FHe1 group compared with the groups of middle-aged FH patients and healthy controls, even though the FHe1 group was 13 years older. The total amount of WMHIs and the amount of large WMHIs were greatest in the FHe2 group. Conclusion: FH patients aged 65 to 74 years receiving long-term statin treatment (15 years) did not have more WMHIs on brain MRI compared to middle-aged FH patients and healthy controls

Bioavailability assessment of hydroxymethylglutaryl coenzyme A reductase inhibitor utilizing pulsatile drug delivery system: a pilot study.

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Taha, Ehab I

2016-09-01

Chronotherapy or pulsatile drug delivery system could be achieved by increasing drug plasma concentration exactly at the time of disease incidence. Cholesterol synthesis shows a circadian rhythm being high at late night and early in the morning. Simvastatin (SIM) inhibits hydroxymethylglutaryl coenzyme A reductase, which is responsible for cholesterol synthesis. In this study, SIM lipid-based formulation filled in gelatin capsules and coated with aqueous Eudragit® S100 dispersion was prepared for chronotherapeutic treatment of hypercholesterolemia. The pharmacokinetic parameters of SIM capsules were studied in human volunteers after a single oral dose and compared with that of Zocor® tablets as a reference in a randomized cross-over study. Pharmacokinetic parameters such as AUC 0-∞ , C max , T max , t 1/2 and elimination rate constant were determined from plasma concentration-time profile for both formulations. The tested formulation had the ability to delay drug absorption and provide higher drug concentrations from 3 up to 10 h after oral administration compared to that of commercial tablets. The data in this study revealed that the prepared formulation could be effective in chronotherapeutic treatment of hypercholesterolemia. Moreover, the tested formulation was found to enhance SIM bioavailability by 29% over the reference tablets.

Disease: H00155 [KEGG MEDICUS

Lifescience Database Archive (English)

Full Text Available H00155 Familial hypercholesterolemia; Autosomal dominant hypercholesterolaemia Fam...n receptor. Other forms of this disorder include hypercholesterolemia caused by mutation of APOB or PCSK9 ge...amilial autosomal recessive hypercholesterolemia. ICD-10: E78.0 MeSH: D006937 OMI

Study of pomegranate (Punica granatum L.) peel extract containing anthocyanins on fatty streak formation in the renal arteries in hypercholesterolemic rabbits.

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Sharifiyan, Fatemeh; Movahedian-Attar, Ahmad; Nili, Nafiseh; Asgary, Sedigheh

2016-01-01

The influence of the supplementation of pomegranate peel extract containing anthocyanins on atherosclerotic plaque formation induced by hypercholesterolemia was investigated in renal arteries in rabbits. After the determination of polyphenol and anthocyanin's content of P. granatum peel hydroalcoholic extract, 30 male rabbits were randomly divided into three groups. They were fed basic diet, hypercholesterolemic diet and hypercholesterolemic diet along with P. granatum peel extract (polyphenolic content for each rabbit 1 g/kg diet) for 2 month. Blood samples were collected at the begging, middle and end of the study in order to measure lipid concentration and oxidative and antioxidative status variables, and renal arteries were taken for the assessment of atherosclerotic plaques at the end of the study. The results reveal that P. granatum peel extract significantly increases serum antioxidant capacity in the extract recipient group in comparison with hypercholesterolemic control (P 0.05). The results of this study indicate that consumption of pomegranate peel extract containing anthocyanins (polyphenol content 1 g/kg diet) despite of a significant increase in serum antioxidant capacity cannot protect the kidneys from hypercholesterolemia-induced damages during the treatment period.

The effect of an apolipoprotein A-I-containing high-density lipoprotein-mimetic particle (CER-001) on carotid artery wall thickness in patients with homozygous familial hypercholesterolemia: The Modifying Orphan Disease Evaluation (MODE) study.

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Hovingh, G Kees; Smits, Loek P; Stefanutti, Claudia; Soran, Handrean; Kwok, See; de Graaf, Jacqueline; Gaudet, Daniel; Keyserling, Constance H; Klepp, Heather; Frick, Jennifer; Paolini, John F; Dasseux, Jean-Louis; Kastelein, John J P; Stroes, Erik S

2015-05-01

Patients with homozygous familial hypercholesterolemia (HoFH) are at extremely elevated risk for early cardiovascular disease because of exposure to elevated low-density lipoprotein cholesterol (LDL-C) plasma levels from birth. Lowering LDL-C by statin therapy is the cornerstone for cardiovascular disease prevention, but the residual risk in HoFH remains high, emphasizing the need for additional therapies. In the present study, we evaluated the effect of serial infusions with CER-001, a recombinant human apolipoprotein A-I (apoA-I)-containing high-density lipoprotein-mimetic particle, on carotid artery wall dimensions in patients with HoFH. Twenty-three patients (mean age 39.4 ± 13.5 years, mean LDL-C 214.2 ± 81.5 mg/dL) with genetically confirmed homozygosity or compound heterozygosity for LDLR, APOB, PCSK9, or LDLRAP1 mutations received 12 biweekly infusions with CER-001 (8 mg/kg). Before and 1 hour after the first infusion, lipid values were measured. Magnetic resonance imaging (3-T magnetic resonance imaging) scans of the carotid arteries were acquired at baseline and after 24 weeks to assess changes in artery wall dimensions. After CER-001 infusion, apoA-I increased from 114.8 ± 20.7 mg/dL to 129.3 ± 23.0 mg/dL. After 24 weeks, mean vessel wall area (primary end point) decreased from 17.23 to 16.75 mm(2) (P = .008). A trend toward reduction of mean vessel wall thickness was observed (0.75 mm at baseline and 0.74 mm at follow-up, P = .0835). In HoFH, 12 biweekly infusions with an apoA-I-containing high-density lipoprotein-mimetic particle resulted in a significant reduction in carotid mean vessel wall area, implying that CER-001 may reverse atherogenic changes in the arterial wall on top of maximal low-density lipoprotein-lowering therapy. This finding supports further clinical evaluation of apoA-I-containing particles in patients with HoFH. Copyright © 2015 Mosby, Inc. All rights reserved.

Risk factors for benign prostatic enlargement: The role of lifestyle habits at younger age. The #Controllati2017 initiative study group.

Science.gov (United States)

Mirone, Vincenzo; Carrieri, Giuseppe; Morgia, Giuseppe; Carmignani, Luca; Vespasiani, Giuseppe; Parazzini, Fabio; Artibani, Walter

2017-12-31

The risk factors for benign prostatic enlargement (BPE) are not well understood and particularly few data are available from Italian population. This was an observational cross sectional study aimed to examine the association between several risk factors and BPE. During the "#Controllati2017" initiative, men aged 18 years or more were invited to attend participating urologic centers for a free of charge visit for counseling about urologic or andrologic conditions. Each participating man underwent a physical examination including digital rectal examination (DRE). Further he was asked about his medical history, urologic symptoms, sexual activity and related problems. Diagnosis of BPE was made by the urologist after DRE. Out of the 1902 [mean age 54 years (SD 12, range 18-92)] considered men, a total of 603 subjects (31.7%) had diagnosis of BPE. The diagnosis of BPE increased from 9.3% in men aged 60 years. A history of hypertension, diabetes, heart diseases, hypercholesterolemia and hypertriglyceridemia were all significantly associated with an increased risk of BPE in the total series and, although not always in a statistically significant way, in strata of age. Physical activity (PA) was significantly associated with a decreased risk of BPE. We have further analyzed the risk of BPE in men with one or more of the identified risk factors (i.e. hypertension, diabetes, heart disease, hypercholesterolemia, hypertriglyceridemia and low PA): the risk of BPE increased with number of risk factors reported by the subjects. The estimated risk were higher among younger men. In our study a history of hypertension, diabetes, heart disease, hypercholesterolemia and hypertriglyceridemia increased the risk and physical activity lowered the risk of BPE. This risk profile was observed also in men aged < 50 years.

The Effect of Seaweed Eucheuma cottonii on Superoxide Dismutase (SOD Liver of Hypercholesterolemic Rats

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TUTIK WRESDIYATI

2008-09-01

Full Text Available Intracellular antioxidant superoxide dismutase (SOD was reported decreased in the liver and kidney of hypercholesterolemic rats. This study was conducted to observe the effect of seaweed Eucheuma cottonii powder on the profile of blood cholesterol and the level of SOD in liver tissues of hypercholesterolemic rats by using immunohistochemical technique. Twenty male Wistar rats were used for this study. Those rats were divided into four groups; (i negative control group (A, (ii hypercholesterolemia group treated by 5% seaweed powder (B, (iii hypercholesterolemia group treated by 10% seaweed powder (C, and (iv Positive control group or hypercholesterolemia group (D. The experiment was carried out for 35 days. Hypercholesterolemia condition (> 130 mg/dl, except group A, was achieved by feeding the rats with commercial diet containing 1% cholesterol. Drinking water was given ad libitum for 40 days. The results showed that seaweed powder decreased the total cholesterol, low density lipoprotein (LDL, triglyceride, and increased the level of high density lipoprotein (HDL and SOD status in the liver tissues of hypercholesterolemic rats. The treatment of 10% seaweed powder gave better results than that of 5%. These results suggested that dietary fiber such in the seaweed powder has antioxidant activity.

Predicting Self-Management Behaviors in Familial Hypercholesterolemia Using an Integrated Theoretical Model: the Impact of Beliefs About Illnesses and Beliefs About Behaviors.

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Hagger, Martin S; Hardcastle, Sarah J; Hingley, Catherine; Strickland, Ella; Pang, Jing; Watts, Gerald F

2016-06-01

Patients with familial hypercholesterolemia (FH) are at markedly increased risk of coronary artery disease. Regular participation in three self-management behaviors, physical activity, healthy eating, and adherence to medication, can significantly reduce this risk in FH patients. We aimed to predict intentions to engage in these self-management behaviors in FH patients using a multi-theory, integrated model that makes the distinction between beliefs about illness and beliefs about self-management behaviors. Using a cross-sectional, correlational design, patients (N = 110) diagnosed with FH from a clinic in Perth, Western Australia, self-completed a questionnaire that measured constructs from three health behavior theories: the common sense model of illness representations (serious consequences, timeline, personal control, treatment control, illness coherence, emotional representations); theory of planned behavior (attitudes, subjective norms, perceived behavioral control); and social cognitive theory (self-efficacy). Structural equation models for each self-management behavior revealed consistent and statistically significant effects of attitudes on intentions across the three behaviors. Subjective norms predicted intentions for health eating only and self-efficacy predicted intentions for physical activity only. There were no effects for the perceived behavioral control and common sense model constructs in any model. Attitudes feature prominently in determining intentions to engage in self-management behaviors in FH patients. The prominence of these attitudinal beliefs about self-management behaviors, as opposed to illness beliefs, suggest that addressing these beliefs may be a priority in the management of FH.

High prevalence of non-communicable diseases and associated risk factors amongst adults living with HIV in Cambodia.

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Pheak Chhoun

Full Text Available With rapid expansion of antiretroviral therapy for HIV, there are rising life expectancies among people living with HIV. As a result, co-morbidity from non-communicable diseases in those living and aging with HIV is increasingly being reported. Published data on this issue have been limited in Cambodia. The aim of this study was to determine the prevalence of diabetes mellitus, hypertension and hypercholesterolemia and associated risk factors in adults living with HIV in Cambodia.This cross-sectional study was conducted in five provinces of Cambodia from May-June 2015. Information was obtained on socio-demographic and clinical characteristics through face-to-face interviews using a structured questionnaire, and anthropometric and biochemical measurements were performed. Diabetes mellitus was diagnosed with fasting blood glucose ≥126 mg/dl, hypertension with systolic blood pressure ≥140 mmHg and/or diastolic blood pressure ≥ 90 mmHg and hypercholesterolemia with fasting blood cholesterol ≥190 mg/dl. Multivariable logistic regression analyses were used to explore risk factors.The study sample included 510 adults living with HIV; 67% were female, with a mean age of 45 (standard deviation = 8 years. Of these, 8.8% had diabetes mellitus, 15.1% had hypertension and 34.7% had hypercholesterolemia. Of the total participants with non-communicable diseases (n = 244, 47.8% had one or more diseases, and 75% were not aware of their diseases prior to the study: new disease was diagnosed in 90% of diabetes mellitus, 44% of hypertension and 90% of hypercholesterolemia. Single disease occurred in 81%, dual disease in 17% and triple disease in 2%. In adjusted analyses, those consuming 1 serving of fruit compare to 2 servings as significantly with diabetes mellitus, those eating 1 serving of fruit compare to 2 servings and using lard for cooking were significantly associated with hypertension, and those being unemployed, having monthly income less than 100

Deletion in the first cysteine-rich repeat of low density lipoprotein receptor impairs its transport but not lipoprotein binding in fibroblasts from a subject with familial hypercholesterolemia

International Nuclear Information System (INIS)

Leitersdorf, E.; Hobbs, H.H.; Fourie, A.M.; Jacobs, M.; Van Der Westhuyzen, D.R.; Coetzee, G.A.

1988-01-01

The ligand-binding domain of the low density lipoprotein (LDL) receptor is composed of seven cysteine-rich repeats, each ∼ 40 amino acids long. Previous studies showed that if the first repeat of the ligand-binding domain (encoded by exon 2) is deleted, the receptor fails to bind an anti-LDL receptor monoclonal antibody (IgG-C7) but continues to bind LDL with high affinity. Cultured fibroblasts from a Black South African Xhosa patient (TT) with the clinical syndrome of homozygous familial hypercholesterolemia demonstrated high-affinity cell-surface binding of 125 I-labeled LDL but not 125 I-labeled IgG-C7. previous haplotype analysis, using 10 restriction fragment length polymorphic sites, suggested that the patient inherited two identical LDL receptor alleles. The polymerase chain reaction technique was used to selectively amplify exon 2 of the LDL receptor gene from this patient. Sequence analysis of the amplified fragment disclosed a deletion of six base pairs that removes two amino acids, aspartic acid and glycine, from the first cysteine-rich ligand binding repeat. The mutation creates a new Pst I restriction site that can be used to detect the deletion. The existence of this mutant allele confirms that the epitope of IgG-C7 is located in the first cysteine-rich repeat and that this repeat is not necessary for LDL binding. The mutant gene produced a normally sized 120-kilodalton LDL receptor precursor protein that matured to the 160-kilodalton form at less than one-fourth the normal rate

Design and baseline characteristics of the simvastatin and ezetimibe in aortic stenosis (SEAS) study

DEFF Research Database (Denmark)

Rossebø, Anne B; Pedersen, Terje R; Allen, Christopher

2007-01-01

Aortic valve stenosis and atherosclerotic disease have several risk factors in common, in particular, hypercholesterolemia. Histologically, the diseased valves appear to have areas of inflammation much like atherosclerotic plaques. The effect of lipid-lowering therapy on the progression of aortic...

Hospital admission for hyperemesis gravidarum: a nationwide study of occurrence, reoccurrence and risk factors among 8.2 million pregnancies

OpenAIRE

Fiaschi, Linda; Nelson-Piercy, Catherine; Tata, Laila J.

2016-01-01

STUDY QUESTION: What are the maternal risk factors for hyperemesis gravidarum (HG) hospital admission, readmission and reoccurrence in a following pregnancy?\\ud SUMMARY ANSWER: Young age, less socioeconomic deprivation, nulliparity, Asian or Black ethnicity, female fetus, multiple pregnancy, history of HG in a previous pregnancy, thyroid and parathyroid dysfunction, hypercholesterolemia and Type 1 diabetes are all risk factors for HG.\\ud WHAT IS KNOWN ALREADY: Women with Black or Asian ethnic...

Understanding the evolution of multimorbidity: evidences from the North West Adelaide Health Longitudinal Study (NWAHS.

Directory of Open Access Journals (Sweden)

Guillaume Ruel

Full Text Available OBJECTIVE: The aim of this study is to describe the evolution of multimorbidity. STUDY DESIGN AND SETTING: Data from 1854 South Australians who participated in the North West Adelaide longitudinal Health Study (NWAHS was collected between baseline (2000-2002 and follow-up (2008-2010. Status for eight chronic diseases (CDs was determined by biomedical measurement or self-report. Chronic disease (CD mean age of occurrence and order of appearance was investigated. RESULTS: The prevalence of multimorbidity increased from 32% to 64% during the 7.8±1.1 years of follow-up. The estimated mean age of onset of a new CD was significantly older for hypertension, cardiovascular disease (CVD and chronic obstructive pulmonary disease (COPD and younger for hypercholesterolemia, asthma and other mental problem. Hypercholesterolemia was more likely to develop as a first than as a subsequent CD (39%vs.16%, p<0.0001 while CVD (1%vs.5%, p<0.0001, diabetes (5%vs.11%, p<0.001 and COPD (6%vs.16%, p<0.0001 were less likely. The presence of mood disorders at baseline was associated with an increased risk of developing other mental disorders (36%vs.12%, p<0.0001, diabetes (18%vs.9%, p<0.01 and asthma (30%vs.21%, p<0.05. CONCLUSION: Longitudinal data could be used to study the evolution of multimorbidity and could provide information on CDs mean age of occurrence, order of appearance and impact on the development of future CDs.

Studies on Tl-201 single photon emission computed tomography (SPECT) of myocardium in patients with ischemic heart disease

International Nuclear Information System (INIS)

Igarashi, Takeki; Yokoi, Toshio; Ueda, Mitsuru; Horimoto, Masashi; Funayama, Naoki; Takenaka, Takashi; Tasho, Teruo; Tsutsuji, Yuko; Oi, Tsuyoshi

1985-01-01

Seventy-six patients with IHD were divided into 2 groups, A) angina pectoris (n=50) and B) previous myocardial infarction(n=26). Each group was classified into three subgroups, without considering hypertension, that is 1) without complication, 2) with hypercholesterolemia, and 3) with diabetes mellitus. We studied and compared the findings of ECG, Echocardiogram (ECHO) and Emission CT (ECT) in these patients at rest. In the previous myocardial infarction group (Group B), we could find 100% ischemic patterns on ECG, 100% asynergy of either IVS or the posterior wall on ECHO and higher percentages of various grade of perfusion defects on ECT compared with group A. In group A, the percentages of perfusion defects were similar in three subgroups. But interestingly, in the hypercholesterolemic group, we could find diffuse moth-eaten like low perfusion areas on ECT. Further study is required whether this finding is peculiar for angina pectoris with hypercholesterolemia or an artifact on ECT. The percentage of ischemic patterns on ECG was lower than in the other groups. In angina pectoris with diabetes mellitus, asynergy in ECHO finding was a significantly higher percentage, compared with other groups. We believe, that ECG, ECHO and ECT are of compensatory importance in the diagnosis of patients with IHD. (author)

Familial hypercholesterolemia

Science.gov (United States)

... and Tests A physical exam may show fatty skin growths called xanthomas and cholesterol deposits in the eye (corneal arcus). The health care provider will ask questions about your personal and family medical history. There may be: A strong family history of ...

Antihyperlipidemic Activities of Common Garden Peony ( Paeonia lactifl ora Pall.

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Tserenlkham Tserendejid

2013-12-01

Full Text Available We studied different extracts of aboveground and underground parts of Paeonia lactifl ora Pall.in experiment. For doing so this research needs to start up with total cholesterol. Total cholesterol is a direct cholesterol measurement that measures all cholesterol molecules in the blood, including low density lipoproteins (LDL, high density lipoproteins (HDL, and very low density lipoproteins (VLDL. The serum total cholesterol (TC and low density lipoproteins (LDL levels were signifi cantly different in the experimentally-induced hypercholesterolemia rats. Effect on serum triglyceride (TG level compared to control group, simvastatin and hypercholesterolemia diet (HD, but almost all were similar with simvastatin. Effect on serum high density lipoproteins (HDL level compared between those. Extracts (PL1, PL2 were lower, almost the same with hypercholesterolemia diet (HD.

Blood lipid of preadolescent boys of well-to-do families

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Muzief Munir

2017-02-01

Full Text Available Coronary heart disease is presently one of the leading causes of death In adults in many countries, including in Indonesia. It is well known that elevated levels of cholesterol in children are closely associated with hypercholesterolemia and coronary heart disease in adult life. This study was conducted in an attempt to find a preliminary insight of the magnitude of the problem of hypercholesterolemia In children In Indonesia as a developing country. The blood lipid levels of 54 preadolescent boys from well-Io-do families were analyzed. Two-third of those children were shown to have elevated blood cholesterol level, and even one third or 16 out of 54 preadolescents boys investigated suffered from hypercholesterolemia. We conclude that elevated blood cholesterol level is frequently found among large-framed and obese Indonesian children.

Diet and Age Interactions with Regards to Cholesterol Regulation and Brain Pathogenesis

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Romina M. Uranga

2010-01-01

Full Text Available Cholesterol is an essential molecule for brain homeostasis; yet, hypercholesterolemia and its numerous complications are believed to play a role in promoting multiple aspects of brain pathogenesis. An ever increasing number of individuals in modern Western Society are regularly consuming diets high in fat which promote the development of hypercholesterolemia. Additionally, modern societies are becoming increasingly aged, causing a collision between increased hypercholesterolemia and increased aging, which will likely lead to the development of increased pathological conditions due to hypercholesterolemia, thereby promoting deleterious neurochemical and behavioral changes in the brain. Lastly, while beneficial in controlling cholesterol levels, the long-term use of statins itself may potentially promote adverse effects on brain homeostasis, although specifics on this remain largely unknown. This review will focus on linking the current understanding of diet-induced hypercholesterolemia (as well as statin use to the development of oxidative stress, neurochemical alterations, and cognitive disturbances in the aging brain.

The potential of pigeon pea (Cajanus cajan) beverage as an anti-diabetic functional drink

Science.gov (United States)

Ariviani, S.; Affandi, D. R.; Listyaningsih, E.; Handajani, S.

2018-01-01

The number of patients with diabetes continues to increase. Diabetes complications might induce serious diseases such as kidney, nervous, cardiovascular diseases and stroke. Diabetic complications can be prevented by keeping blood glucose and cholesterol at normal levels. This study aims to determine the potential of pigeon pea beverage for lowering glucose and total cholesterol plasma levels and increasing the antioxidant status of diabetic-hypercholesterolemia rats. The research was conducted using 18 Sprague Dawley male rats aged 3 months old with an average body weight of 154 g. The rats were divided into three groups: normal group, D-H group (diabetic-hypercholesterolemia group), and pigeon pea beverage group. The results showed that pigeon pea beverage diet showed hypoglycemic and hypocholesterolemic activities, and could improve the antioxidant status of diabetic-hypercholesterolemia rats. Plasma glucose and total cholesterol levels of diabetic-hypercholesterolemia rats decreased 33.86% and 19.78% respectively. The improvement of the plasma antioxidant status was indicated by the decrease of plasma MDA (malondialdehyde) level, reaching 37.16%. The research result provides an alternative to diabetes management by using the local bean as an anti-diabetic functional drink.

Hypercholesterolemia, Stroke And Statins

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Prabhakar S

2005-01-01

Full Text Available The link between serum cholesterol levels and the incidence of stroke still remain to be established. There are conflicting reports from a series of observational cohort studies. However, clinical trials with HMG CoA reductase inhibitors (also called statins have shown that cholesterol lowering therapy used in the primary and secondary prevention of myocardial infarction significantly reduced cardiovascular events including strokes. Meta analysis of trials with statins have shown a relative risk reduction in stroke of 12 to 48% in patients with coronary heart disease after MI. It has been postulated that the clinical action of statins is the result of pleiotropic / antiatherogenic effects rather than simply a reduction in cholesterol. The putative beneficial effect of statins in stroke involve blocking of macrophage and platelet activation, improvement of endothelial cell vasomotor function, enhancement of endothelial fibrinolytic function, immunosuppressive and anti-inflammatory action, inhibition of smooth muscle cell proliferation and particularly enhancement of endothelial nitric oxide synthase (eNOS.

Metabolic syndrome and the risk of urothelial carcinoma of the bladder: a case-control study

International Nuclear Information System (INIS)

Montella, Maurizio; Di Maso, Matteo; Crispo, Anna; Grimaldi, Maria; Bosetti, Cristina; Turati, Federica; Giudice, Aldo; Libra, Massimo; Serraino, Diego; La Vecchia, Carlo; Tambaro, Rosa; Cavalcanti, Ernesta; Ciliberto, Gennaro; Polesel, Jerry

2015-01-01

The Metabolic syndrome (MetS) is an emerging condition worldwide, consistently associated with an increased risk of several cancers. Some information exists on urothelial carcinoma of the bladder (UCB) and MetS. This study aims at further evaluating the association between the MetS and UCB. Between 2003 and 2014 in Italy, we conducted a hospital-based case-control study, enrolling 690 incident UCB patients and 665 cancer-free matched patients. The MetS was defined as the presence of at least three of the four selected indicators: abdominal obesity, hypercholesterolemia, hypertension, and diabetes. Odds ratios (ORs) and corresponding 95 % confidence intervals (CIs) for MetS and its components were estimated through multiple logistic regression models, adjusting for potential confounders. Patients with MetS were at a 2-fold higher risk of UCB (95 % CI:1.38–3.19), compared to those without the MetS. In particular, ORs for bladder cancer were 2.20 (95 % CI:1.42–3.38) for diabetes, 0.88 (95 % CI: 0.66-1.17) for hypertension, 1.16 (95 % CI: 0.80-1.67) for hypercholesterolemia, and 1.63 (95 % CI:1.22–2.19) for abdominal obesity. No heterogeneity in risks emerged across strata of sex, age, education, geographical area, and smoking habits. Overall, 8.1 % (95 % CI: 3.9-12.4 %) of UCB cases were attributable to the MetS. This study supports a positive association between the MetS and bladder cancer risk

Influence of maternal hypercholesterolemia and phytosterol intervention during gestation and lactation on dyslipidemia and hepatic lipid metabolism in offspring of Syrian golden hamsters.

Science.gov (United States)

Liu, Jie; Iqbal, Aadil; Raslawsky, Amy; Browne, Richard W; Patel, Mulchand S; Rideout, Todd C

2016-10-01

Although there is a normal physiological rise in maternal lipids during pregnancy, excessive maternal hyperlipidemia during pregnancy increases cardiovascular disease risk for both the mother and offspring. There are limited safe lipid-lowering treatment options for use during pregnancy, therefore, we evaluated the influence of maternal phytosterol (PS) supplementation on lipid and lipoprotein metabolism in mothers and progeny. Female Syrian golden hamsters were randomly assigned to three diets throughout prepregnancy, gestation, and lactation (n = 6/group): (i) Chow (Chow), (ii) chow with 0.5% cholesterol (CH), and (iii) chow with 0.5% CH and 2% PS (CH/PS). Compared with newly weaned pups from Chow dams, pups from dams fed the CH-enriched diet demonstrated increases (p < 0.05) in total-C, LDL-C, HDL-C, and total LDL and VLDL particle number. Pups from CH-fed mothers also exhibited higher hepatic CH concentration and differential mRNA expression pattern of CH regulatory genes. Pups from PS-supplemented dams demonstrated reductions (p < 0.05) in serum total-C, non-HDL-C, and LDL-C but also increased triglycerides compared with pups from CH-fed dams. Maternal PS supplementation reduced (p < 0.05) hepatic CH and increased the abundance of HMG-CoAr and LDLr protein in newly weaned pups compared with the CH group. Results suggest that maternal PS supplementation is largely effective in normalizing CH in pups born to mothers with hypercholesterolemia, however, the cause and long-term influence of increased triglyceride is not known. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Cholesterol lowering effect of a commercial margarine in hypercholesterolemic adults: a review of the scientific literature.

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Raquel Bernácer

2013-03-01

Full Text Available Introduction: the hypercholesterolemia is a growing problem, responsible of one fifth of coronary events in Spain. It is considered that plant sterols (PS could play an important role in their treatment.Objective: we review the role of a range of functional foods with added PS (including specific studies using Flora pro•activ in adults with hypercholesterolemia.Methods: we performed a review of the literature in the PubMed database to locate human studies that have evaluated the role of Flora pro•activ or PS fortified foods with a similar composition. We also have been consulted the European Food Safety Authority (EFSA database.Results: Flora pro•activ demonstrated in rigorous scientific studies to lower cholesterol in adults with hypercholesterolemia. Two servings of Flora pro•activ (1.5 g PS are needed to observe this effect. Lowering cholesterol with Flora pro•activ (2 servings / day oscillate as EFSA notes, between 7 and 10%. This effect is observed after 2-3 weeks. Its composition allows to make health claims about lowering cholesterol as is described for the European Union. The cholesterol-lowering efficacy of PS enriched foods that are not margarine, mayonnaise, salad dressings or dairy products is under-researched. With few exceptions, the use of fortified foods with PS is safe.Conclusions: the current scientific evidence justify the promotion of the use of PS to lower LDL cholesterol in adults with hypercholesterolemia.

Can vascular risk factors influence number and size of cerebral metastases? A 3D-MRI study in patients with different tumor entities.

Science.gov (United States)

Nagel, Sandra; Berk, Benjamin-Andreas; Kortmann, Rolf-Dieter; Hoffmann, Karl-Titus; Seidel, Clemens

2018-02-01

There is increasing evidence that cerebral microangiopathy reduces number of brain metastases. Aim of this study was to analyse if vascular risk factors (arterial hypertension, diabetes mellitus, smoking, and hypercholesterolemia) or the presence of peripheral arterial occlusive disease (PAOD) can have an impact on number or size of brain metastases. 200 patients with pre-therapeutic 3D-brain MRI and available clinical data were analyzed retrospectively. Mean number of metastases (NoM) and mean diameter of metastases (mDM) were compared between patients with/without vascular risk factors (vasRF). No general correlation of vascular risk factors with brain metastases was found in this monocentric analysis of a patient cohort with several tumor types. Arterial hypertension, diabetes mellitus, hypercholesterolemia and smoking did not show an effect in uni- and multivariate analysis. In patients with PAOD the number of BM was lower than without PAOD. This was the case independent from cerebral microangiopathy but did not persist in multivariate analysis. From this first screening approach vascular risk factors do not appear to strongly influence brain metastasation. However, larger prospective multi-centric studies with better characterized severity of vascular risk are needed to more accurately detect effects of individual factors. Copyright © 2018 Elsevier B.V. All rights reserved.

Polymorphism in APOB associated with increased low-density lipoprotein levels in both genders in the general population

DEFF Research Database (Denmark)

Benn, Marianne; Nordestgaard, Børge G; Jensen, Jan S

2005-01-01

Rare mutations in APOB cause hypercholesterolemia. Whether common polymorphisms in APOB have similar effects remains controversial.......Rare mutations in APOB cause hypercholesterolemia. Whether common polymorphisms in APOB have similar effects remains controversial....

Phaleria macrocarpa Boerl. (Thymelaeaceae Leaves Increase SR-BI Expression and Reduce Cholesterol Levels in Rats Fed a High Cholesterol Diet

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Yosie Andriani

2015-03-01

Full Text Available In vitro and in vivo studies of the activity of Phaleria macrocarpa Boerl (Thymelaeaceae leaves against the therapeutic target for hypercholesterolemia were done using the HDL receptor (SR-BI and hypercholesterolemia-induced Sprague Dawley rats. The in vitro study showed that the active fraction (CF6 obtained from the ethyl acetate extract (EMD and its component 2',6',4-trihydroxy-4'-methoxybenzophenone increased the SR-BI expression by 95% and 60%, respectively. The in vivo study has proven the effect of EMD at 0.5 g/kgbw dosage in reducing the total cholesterol level by 224.9% and increasing the HDL cholesterol level by 157% compared to the cholesterol group. In the toxicity study, serum glutamate oxalate transaminase (SGOT and serum glutamate pyruvate transaminase (SGPT activity were observed to be at normal levels. The liver histology also proved no toxicity and abnormalities in any of the treatment groups, so it can be categorized as non-toxic to the rat liver. The findings taken together show that P. macrocarpa leaves are safe and suitable as an alternative control and prevention treatment for hypercholesterolemia in Sprague Dawley rats.

An analysis of the effects of smoking and other cardiovascular risk factors on obliteration rates after arteriovenous malformation radiosurgery

International Nuclear Information System (INIS)

Bhatnagar, Ajay; Flickinger, John C.; Kondziolka, Douglas; Niranjan, Ajay; Lunsford, L. Dade

2001-01-01

Purpose: To assess the relationships of smoking and other cardiovascular disease risk factors (hypertension, diabetes, hypercholesterolemia, and gender) to rates of radiosurgery-induced obliteration of arteriovenous malformations (AVM). Methods and Materials: We evaluated follow-up imaging and clinical data in 329 AVM patients who received gamma knife radiosurgery at the University of Pittsburgh between 1987 and 1994. There were 113 smokers, 29 hypertensives, 5 diabetics, 4 hypercholesterolemics, 159 male patients, and 170 female patients. All patients had regular clinical or imaging follow-up for a minimum of 3 years after radiosurgery. Results: Multivariate analysis showed that smoking had no effect on AVM obliteration (p>0.43). Hypertension, diabetes, and hypercholesterolemia had no discernible effect on AVM obliteration in this study (p>0.78). However, females aged 12-49 had a statistically significant lower in-field obliteration rate than males (78% vs. 89%, p=0.0102). Conclusion: Smoking has no effect on AVM obliteration. Hypertension, diabetes, and hypercholesterolemia had no discernible effect in this study. Further study is needed to establish whether estrogen has a vascular protective effect that could partially limit radiosurgical AVM obliteration, as suggested by this study

EST Table: DC540266 [KAIKOcDNA[Archive

Lifescience Database Archive (English)

Full Text Available ar to Low density lipoprotein receptor adapter protein 1 (Autosomal recessive hypercholesterolemia protein) ... similar to Low density lipoprotein receptor adapter protein 1 (Autosomal recessive hypercholesterolemia protein) isoform 1 [Tribolium castaneum] FS929848 dpe- ...

How do patients at risk portray candidates for coronary heart disease? A qualitative interview study

DEFF Research Database (Denmark)

Frich, J.C.; Malterud, K.; Fugelli, P.

2007-01-01

OBJECTIVE: To explore how patients at risk of coronary heart disease (CHD) portray candidates for CHD. DESIGN: Qualitative interview study. SETTING: Norway. SUBJECTS: A total of 20 men and 20 women diagnosed with heterozygous familial hypercholesterolemia (FH) recruited through a lipid clinic. MAIN...... considered their notions to be valid for assessing people's risk of CHD, others questioned how valid their notions were. CONCLUSION: Doctors should recognize that distancing is a way patients cope with risk and that such a strategy may have psychological and moral reasons. When communicating about risk...

Thirteen Week Oral Toxicity Study of WR242511 in Rats. Volume 1

Science.gov (United States)

1994-01-14

hypercholesterolemia and hypertriglyceridemia seen in high dose females, as previously discussed. Heptatobiliary changes were suggested by significant elevations in...lung (alveolar histiocytosis) lesions. Severe thymic lymphocyte depletion was also observed in these animals where the thymus could be identified...this animal, but it was attributed to the severe and diffuse chronic-active inflammation. As indicated above, treatment-related histopathologic

Overweight and factors associated in civil servants from Southern Brazil

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Eliane Cristina de Andrade Gonçalves

2016-07-01

Full Text Available DOI: http://dx.doi.org/10.5007/1980-0037.2016v18n3p277   This study aimed to estimate the prevalence of overweight and investigate its association with sociodemographic factors, physical activity level, hypercholesterolemia, and diabetes in civil servants of a university in the state of Paraná, Brazil. The research was conducted with 339 civil servants aged above 18 years. Overweight was analyzed by self-reported body mass index. Physical activity level was evaluated using a questionnaire. Sociodemographic data (sex, age, economic status, educational level, marital status, and working hours and information on the chronic diseases of interest (hypercholesterolemia and diabetes were obtained from self-report. The association between overweight and the other variables was investigated using binary logistic regression. The prevalence of overweight was 50.6%. The groups most susceptible to overweight were: male civil servants (OR: 2.04; CI: 1.30-3.22, those less than 12 years of education (OR: 2.46; CI: 1.43-4.23, who were insufficiently active (OR: 1.64; CI: 1.03-2.60, and those with hypercholesterolemia (OR: 2.28; CI: 1.32-3.96. This study concluded that more than a half of the sample was overweight and that this condition was associated with male sex, educational level below 12 years, insufficient physical activity, and hypercholesterolemia.

Prevalence and correction of hypothyroidism in a large cohort of patients referred for dyslipidemia

NARCIS (Netherlands)

Diekman, T.; Lansberg, P. J.; Kastelein, J. J.; Wiersinga, W. M.

1995-01-01

Treatment of hypercholesterolemia can reduce the risk of developing premature atherosclerosis. The hypercholesterolemia caused by hypothyroidism is potentially reversible by thyroid hormone replacement therapy. We determined the prevalence of hypothyroidism in patients referred to a university lipid

EST Table: FS936166 [KAIKOcDNA[Archive

Lifescience Database Archive (English)

Full Text Available ar to Low density lipoprotein receptor adapter protein 1 (Autosomal recessive hypercholesterolemia protein) ... similar to Low density lipoprotein receptor adapter protein 1 (Autosomal recessive hypercholesterolemia protein) isoform 1 [Tribolium castaneum] FS929848 fwgP ...

EST Table: BY921544 [KAIKOcDNA[Archive

Lifescience Database Archive (English)

Full Text Available ar to Low density lipoprotein receptor adapter protein 1 (Autosomal recessive hypercholesterolemia protein) ... similar to Low density lipoprotein receptor adapter protein 1 (Autosomal recessive hypercholesterolemia protein) isoform 1 [Tribolium castaneum] FS929848 ovS0 ...

Population prevalence and control of cardiovascular risk factors: what electronic medical records tell us.

Science.gov (United States)

Catalán-Ramos, Arantxa; Verdú, Jose M; Grau, María; Iglesias-Rodal, Manuel; del Val García, José L; Consola, Alicia; Comin, Eva

2014-01-01

To analyze the prevalence, control, and management of hypertension, hypercholesterolemia, and diabetes mellitus type 2 (DM2). Cross-sectional analysis of all individuals attended in the Catalan primary care centers between 2006 and 2009. History of cardiovascular diseases, diagnosis and treatment of hypertension, hypercholesterolemia, DM2, lipid profile, glycemia and blood pressure data were extracted from electronic medical records. Age-standardized prevalence and levels of management and control were estimated. Individuals aged 35-74 years using primary care databases. A total of 2,174,515 individuals were included (mean age 52 years [SD 11], 47% men). Hypertension was the most prevalent cardiovascular risk factor (39% in women, 41% in men) followed by hypercholesterolemia (38% and 40%) and DM2 (12% and 16%), respectively. Diuretics and angiotensin-converting enzyme inhibitors were most often prescribed for hypertension control (women treated). Hypercholesterolemia was controlled (low-density lipoprotein cholesterol women with no history of cardiovascular disease, despite lipid-lowering treatment, primarily (90%) with statins. The percentage of women and men with DM2 and with glycated hemoglobin DM2 were adequately controlled; hypercholesterolemia control was particularly low. Copyright © 2013 Elsevier España, S.L. All rights reserved.

EST Table: FS929848 [KAIKOcDNA[Archive

Lifescience Database Archive (English)

Full Text Available DICTED: similar to Low density lipoprotein receptor adapter protein 1 (Autosomal recessive hypercholesterolemia...1| PREDICTED: similar to Low density lipoprotein receptor adapter protein 1 (Autosomal recessive hypercholesterolemia protein) isoform 1 [Tribolium castaneum] FS929848 fwgP ...

Drug: D10335 [KEGG MEDICUS

Lifescience Database Archive (English)

Full Text Available lipidemic agent Therapeutic category: 2189 ATC code: C10AX14 Heterozygous familial hypercholesterolemia [DS:...H00155] ... monoclonal antibody Treatment of hypercholesterolemia PCSK9 [HSA:255738] [KO:K13050] ... CAS: 1245916-14-6 PubChem: 172232429 ...

Mutation G805R in the transmembrane domain of the LDL receptor gene causes familial hypercholesterolemia by inducing ectodomain cleavage of the LDL receptor in the endoplasmic reticulum

Directory of Open Access Journals (Sweden)

Thea Bismo Strøm

2014-01-01

Full Text Available More than 1700 mutations in the low density lipoprotein receptor (LDLR gene have been found to cause familial hypercholesterolemia (FH. These are commonly divided into five classes based upon their effects on the structure and function of the LDLR. However, little is known about the mechanism by which mutations in the transmembrane domain of the LDLR gene cause FH. We have studied how the transmembrane mutation G805R affects the function of the LDLR. Based upon Western blot analyses of transfected HepG2 cells, mutation G805R reduced the amounts of the 120 kDa precursor LDLR in the endoplasmic reticulum. This led to reduced amounts of the mature 160 kDa LDLR at the cell surface. However, significant amounts of a secreted 140 kDa G805R-LDLR ectodomain fragment was observed in the culture media. Treatment of the cells with the metalloproteinase inhibitor batimastat largely restored the amounts of the 120 and 160 kDa forms in cell lysates, and prevented secretion of the 140 kDa ectodomain fragment. Together, these data indicate that a metalloproteinase cleaved the ectodomain of the 120 kDa precursor G805R-LDLR in the endoplasmic reticulum. It was the presence of the polar Arg805 and not the lack of Gly805 which led to ectodomain cleavage. Arg805 also prevented γ-secretase cleavage within the transmembrane domain. It is conceivable that introducing a charged residue within the hydrophobic membrane lipid bilayer, results in less efficient incorporation of the 120 kDa G805R-LDLR in the endoplasmic reticulum membrane and makes it a substrate for metalloproteinase cleavage.

Chocolate and Health-Related Quality of Life: A Prospective Study

Science.gov (United States)

Balboa-Castillo, Teresa; López-García, Esther; León-Muñoz, Luz M.; Pérez-Tasigchana, Raúl F.; Banegas, José Ramón; Rodríguez-Artalejo, Fernando; Guallar-Castillón, Pilar

2015-01-01

Background Chocolate consumption has been associated with a short-term reduction in blood pressure and cholesterol, and improvement of insulin sensitivity; however, participants could not be aware of presenting hypertension or hypercholesterolemia. Moreover, the effect of chocolate on mental health is uncertain. This study assessed the association of regular chocolate consumption with the physical (PCS) and mental (MCS) components of health-related quality of life (HRQL). Materials and methods We analyzed data from a cohort of 4599 individuals recruited in 2008–2010 and followed-up once prospectively to January 2013 (follow-up mean: 3.5 years). Regular chocolate consumption was assessed at baseline with a validated diet history. HRQL was assessed with the SF-12 v.2 at baseline and at follow-up. Analyses were performed with linear regression and adjusted for the main confounders, including HRQL at baseline. Results At baseline, 72% of the study participants did not consume chocolate, 11% consumed ≤10 g/day and 17% >10 g/day. Chocolate consumption at baseline did not show an association with PCS and MCS of the SF-12 measured three years later. Compared to those who did not consume chocolate, the PCS scores were similar in those who consumed ≤10g/day (beta: -0.07; 95% confidence interval (95% CI): -0.94 to 0.80) and in those who consumed >10g/day (beta: 0.02; 95% CI:-0.71 to 0.75); corresponding figures for the MCS were 0.29; 95% CI: -0.67 to 1.26, and -0.57; 95%CI: -1.37 to 0.23. Similar results were found for sex, regardless of obesity, hypertension, hypercholesterolemia, diabetes or depression. Conclusions No evidence was found of an association between chocolate intake and the physical or mental components of HRQL. PMID:25901348

Chocolate and health-related quality of life: a prospective study.

Directory of Open Access Journals (Sweden)

Teresa Balboa-Castillo

Full Text Available Chocolate consumption has been associated with a short-term reduction in blood pressure and cholesterol, and improvement of insulin sensitivity; however, participants could not be aware of presenting hypertension or hypercholesterolemia. Moreover, the effect of chocolate on mental health is uncertain. This study assessed the association of regular chocolate consumption with the physical (PCS and mental (MCS components of health-related quality of life (HRQL.We analyzed data from a cohort of 4599 individuals recruited in 2008-2010 and followed-up once prospectively to January 2013 (follow-up mean: 3.5 years. Regular chocolate consumption was assessed at baseline with a validated diet history. HRQL was assessed with the SF-12 v.2 at baseline and at follow-up. Analyses were performed with linear regression and adjusted for the main confounders, including HRQL at baseline.At baseline, 72% of the study participants did not consume chocolate, 11% consumed ≤10 g/day and 17% >10 g/day. Chocolate consumption at baseline did not show an association with PCS and MCS of the SF-12 measured three years later. Compared to those who did not consume chocolate, the PCS scores were similar in those who consumed ≤10 g/day (beta: -0.07; 95% confidence interval (95% CI: -0.94 to 0.80 and in those who consumed >10 g/day (beta: 0.02; 95% CI:-0.71 to 0.75; corresponding figures for the MCS were 0.29; 95% CI: -0.67 to 1.26, and -0.57; 95%CI: -1.37 to 0.23. Similar results were found for sex, regardless of obesity, hypertension, hypercholesterolemia, diabetes or depression.No evidence was found of an association between chocolate intake and the physical or mental components of HRQL.

Chocolate and health-related quality of life: a prospective study.

Science.gov (United States)

Balboa-Castillo, Teresa; López-García, Esther; León-Muñoz, Luz M; Pérez-Tasigchana, Raúl F; Banegas, José Ramón; Rodríguez-Artalejo, Fernando; Guallar-Castillón, Pilar

2015-01-01

Chocolate consumption has been associated with a short-term reduction in blood pressure and cholesterol, and improvement of insulin sensitivity; however, participants could not be aware of presenting hypertension or hypercholesterolemia. Moreover, the effect of chocolate on mental health is uncertain. This study assessed the association of regular chocolate consumption with the physical (PCS) and mental (MCS) components of health-related quality of life (HRQL). We analyzed data from a cohort of 4599 individuals recruited in 2008-2010 and followed-up once prospectively to January 2013 (follow-up mean: 3.5 years). Regular chocolate consumption was assessed at baseline with a validated diet history. HRQL was assessed with the SF-12 v.2 at baseline and at follow-up. Analyses were performed with linear regression and adjusted for the main confounders, including HRQL at baseline. At baseline, 72% of the study participants did not consume chocolate, 11% consumed ≤10 g/day and 17% >10 g/day. Chocolate consumption at baseline did not show an association with PCS and MCS of the SF-12 measured three years later. Compared to those who did not consume chocolate, the PCS scores were similar in those who consumed ≤10 g/day (beta: -0.07; 95% confidence interval (95% CI): -0.94 to 0.80) and in those who consumed >10 g/day (beta: 0.02; 95% CI:-0.71 to 0.75); corresponding figures for the MCS were 0.29; 95% CI: -0.67 to 1.26, and -0.57; 95%CI: -1.37 to 0.23. Similar results were found for sex, regardless of obesity, hypertension, hypercholesterolemia, diabetes or depression. No evidence was found of an association between chocolate intake and the physical or mental components of HRQL.

Prevalence, awareness, treatment and control of dyslipidemia in older persons in urban and rural population in the Astana region, Kazakhstan.

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Supiyev, Adil; Nurgozhin, Talgat; Zhumadilov, Zhaxybay; Peasey, Anne; Hubacek, Jaroslav A; Bobak, Martin

2017-08-11

Despite high cardiovascular mortality in Central Asian republics of the former Soviet Union, there is limited information about major risk factors, including blood lipids. We investigated the prevalence of impaired concentrations of blood lipids, the awareness, treatment and control of hypercholesterolemia, and factors associated with these indicators in urban and rural populations in Kazakhstan. We conducted a cross-sectional study of random urban and rural population samples (the state capital Astana and Akmol village). Men and women aged 50-74 years were examined; a total of 954 adults participated (response rate 59%). Serum concentrations of total, LDL and HDL cholesterol and triglycerides and a range of other cardiovascular risk factors were measured. The overall prevalence of hypercholesterolemia (total cholesterol ≥6.2 mmol/l) was 37%; among subjects with hypercholesterolemia, 57% were aware of their condition, 41% took medication and 23% had total cholesterol <6.2 mmol/l (4.5% <5 mmol/l). The prevalence, awareness, treatment, and control of hypercholesterolemia were all higher in the urban than the rural area. Similarly, the proportions of subjects with impaired concentrations of specific lipids fractions were also considerably higher in the urban population. Most associations with other covariates were in the expected direction. This study found relatively high prevalence of dyslipidemia in the Kazakh population, and the blood lipid profile was less favourable in the urban area. These pronounced urban-rural differences may be related to urbanization, the associated nutrition transition and to access to health care.

Cholesterol, Cholesterol-Lowering Medication Use, and Breast Cancer Outcome in the BIG 1-98 Study

DEFF Research Database (Denmark)

Borgquist, Signe; Giobbie-Hurder, Anita; Ahern, Thomas P

2017-01-01

on cholesterol levels and hypercholesterolemia per se may counteract the intended effect of aromatase inhibitors. Patients and Methods The Breast International Group (BIG) conducted a randomized, phase III, double-blind trial, BIG 1-98, which enrolled 8,010 postmenopausal women with early-stage, hormone receptor......-positive invasive breast cancer from 1998 to 2003. Systemic levels of total cholesterol and use of CLM were measured at study entry and every 6 months up to 5.5 years. Cumulative incidence functions were used to describe the initiation of CLM in the presence of competing risks. Marginal structural Cox proportional...

Dyslipidemia, Diet and Physical Exercise in Children on Treatment With Antiretroviral Medication in El Salvador: A Cross-sectional Study.

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Sonego, Michela; Sagrado, Maria José; Escobar, Gustavo; Lazzerini, Marzia; Rivas, Estefanie; Martín-Cañavate, Rocio; Pérez de López, Elsy; Ayala, Sandra; Castaneda, Luis; Aparicio, Pilar; Custodio, Estefanía

2016-10-01

Dyslipidemias are common in HIV-infected children, especially if treated with protease inhibitors, but there are few data on how to treat dyslipidemias in this population. We estimated the dyslipidemia prevalence and its association with treatment, diet and physical exercise in children on antiretroviral treatment at the El Salvador reference center for pediatric HIV care (CENID). Information was gathered regarding socio-demographic characteristics, treatment, diet and physical activity of 173 children aged 5-18 years and receiving antiretroviral therapy. Triglycerides, total cholesterol, low-density lipoprotein (LDL-C), high-density lipoprotein (HDL-C), viral load and CD4 T-lymphocytes were measured. Abnormal concentrations were defined as triglycerides ≥130 mg/dL in 10- to 18-year olds and ≥100 mg/dL in diet and physical exercise. Of the 173 children, 83 (48%) had hypertriglyceridemia and 25 (14.5%) hypercholesterolemia. High LDL-C concentrations were observed in 17 children (9.8%) and low HDL-C in 38 (22%). Treatment with protease inhibitors was significantly associated with hypertriglyceridemia [prevalence ratio (PR) 2.8; 95% confidence interval (CI): 2.0-3.8] and hypercholesterolemia (PR 9.0; 95% CI: 3.6-22.2). Higher adherence to a "high fat/sugar diet" was associated with hypercholesterolemia (PR 1.6; 95% CI: 1.1-2.3) and high LDL-C (PR 1.7; 95% CI: 1.0-2.9). Compared with those exercising exercising ≥7 times were less likely to have low HDL-C (PR = 0.4; 95% CI: 0.2-0.7). These results suggest that a healthy diet and exercise habits can contribute to controlling some aspects of the lipid profile in this population.

Study of hypocholesterolemic activity of Algerian Pistacia lentiscus leaves extracts in vivo

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Mohammed Cheurfa

Full Text Available Abstract Plants are a large source of new bioactive molecules with therapeutic potentials. However, only a small amount of worldwide plants have been phytochemically investigated. The aqueous and ethanolic extracts of Pistacia lentiscus L., Anacardiaceae, leaves were evaluated for hypocholesterolemic activity in vivo. In this study, hypercholesterolemia was induced in animals by feeding them high cholesterol (1% food. The extracts of P. lentiscus were orally administered at a dose of 200 mg/kg body weight along with a high cholesterol diet for thirty successive days. Lipid parameters such as total cholesterol, triacylglyceride, low density lipoprotein, very low density lipoprotein and high density lipoprotein were measured in the plasma. Total phenol and flavonoid contents were also evaluated. Flavonoid content was found to be more present in the ethanolic extract (8.218 ± 0.009 mg of QE/g compared to the aqueous extract (3.107 ± 0.014 mg of QE/g. The administration of P. lentiscus extracts produced a significant decrease in total cholesterol, triacylglyceride and low density lipoprotein-cholesterol (154.6 ± 18.10, 71.2 ± 4.38 and 99.36 ± 18.77 mg/dl respectively in the ethanolic extract, while the aqueous extract showed a significant decrease in total cholesterol and triacylglyceride (203.6 ± 9.18 and 97.6 ± 3.57 mg/dl respectively. The results of the investigation demonstrated that P. lentiscus leaf extract has hypocholesterolemic properties and might be used for the prevention of hypercholesterolemia associated disorders.

Vascular Risk Factors as Treatment Target to Prevent Cognitive Decline

NARCIS (Netherlands)

Richard, Edo; Moll van Charante, Eric P.; van Gool, Willem A.

2012-01-01

Epidemiological studies have consistently shown that vascular risk factors including hypertension, diabetes, obesity, hypercholesterolemia, smoking, and lack of physical exercise are associated with an increased risk of cognitive decline and dementia. Neuroradiological and neuropathological studies

Hierarchical analysis of cardiovascular risk factors in relation to the development of acute coronary syndromes, in different parts of Greece: the CARDIO2000 study.

Science.gov (United States)

Panagiotakos, Demosthenes B; Pitsavos, Christos; Chrysohoou, Christine; Stefanadis, Christodoulos

2008-01-01

During 2000 to 2002, 700 men (59 +/- 10 years) and 148 women (65 +/- 9 years) patients with first event of an ACS were randomly selected from cardiology clinics of Greek regions. Afterwards, 1078 population-based, age-matched and sex-matched controls were randomly selected from the same hospitals. The frequency ratio between men and women in the case series of patients was about 4:1, in both south and north Greek areas. Hierarchical classification analysis showed that for north Greek areas family history of coronary heart disease, hypercholesterolemia, hypertension, diabetes (explained variability 35%), and less significantly, dietary habits, smoking, body mass index, and physical activity status (explained variability 4%) were associated with the development of ACS, whereas for south Greek areas hypercholesterolemia, family history of coronary heart disease, diabetes, smoking, hypertension, dietary habits, physical activity (explained variability 34%), and less significantly body mass index (explained variability <1%), were associated with the development of the disease.

Gout and rheumatoid arthritis, both to keep in mind in cardiovascular risk management: A primary care retrospective cohort study.

Science.gov (United States)

Janssens, Hein J E M; Arts, Paul G J; Schalk, Bianca W M; Biermans, Marion C J

2017-01-01

To assess in one time window cardiovascular risks for both patients with gout and patients with rheumatoid arthritis in a Dutch primary care population. Retrospective matched cohort study with data from the electronic health records of 51 Dutch general practices. Participants were patients aged 30 years or older with an incident diagnosis of gout (n=2655) or rheumatoid arthritis (n=513), and matched non-disease controls (n=7891 and n=1850 respectively). At disease incidence date, patients and controls were compared for prevalence of hypertension, diabetes mellitus, hypercholesterolemia, and prior cardiovascular diseases. Patients without prior cardiovascular disease were followed for a first cardiovascular disease, and compared to controls using Kaplan-Meier survival curves and Cox proportional hazard analyses. Compared to controls, gout patients suffered more from hypertension (44.8%), diabetes (20.1%), hypercholesterolemia (13.7%), and prior cardiovascular disease (30%) (P0.05). After adjustment, both gout and rheumatoid arthritis patients without prior cardiovascular disease were more likely to get a cardiovascular disease: hazard ratio (95% confidence interval) 1.44 (1.18 to 1.76), and 2.06 (1.34 to 3.16) respectively. This primary care study indicates that gout and rheumatoid arthritis are both independent risk factors for cardiovascular diseases, rheumatoid arthritis to some greater extent, whereas gout patients at first diagnosis had already an increased cardiovascular risk profile. It gives strong arguments for implementation of both rheumatic diseases in primary care guidelines on cardiovascular risk management. Copyright © 2016 Société française de rhumatologie. Published by Elsevier SAS. All rights reserved.

Low density lipoprotein receptors: preliminary results on 'in vivo' study

International Nuclear Information System (INIS)

Lupattelli, G.; Virgolini, I.; Li, S.R.; Sinzinger, H.

1991-01-01

Plasmatic levels of low density lipoproteins (LDL) are regulated by the receptor pathway and most LDL receptor are located in the liver. A receptor defect due to genetic mutations of the LDL receptor gene is the cause of familial hypercholesterolemia (F.H.), a disease characterized by high cholesterol levels and premature atherosclerosis. Injections of autologous radiolabelled LDL, followed by hepatic scintiscanning, can be used to obtain 'in vivo' quantification of hepatic receptor activity, both in normal and hypercholesterolemic patients. In this study we observe no hepatic increase of radioactivity in patients affected by F.H., confirming the liver receptor defect. Scintigraphy is a non-invasive technique which can be used to diagnose this disease and to monitor the efficiacy of hypolipidemic therapy. (Authors)

Sitosterolemia: a review and update of pathophysiology, clinical spectrum, diagnosis, and management

Directory of Open Access Journals (Sweden)

Eun-Gyong Yoo

2016-03-01

Full Text Available Sitosterolemia is an autosomal recessive disorder characterized by increased plant sterol levels, xanthomas, and accelerated atherosclerosis. Although it was originally reported in patients with normolipemic xanthomas, severe hypercholesterolemia have been reported in patients with sitosterolemia, especially in children. Sitosterolemia is caused by increased intestinal absorption and decreased biliary excretion of sterols resulting from biallelic mutations in either ABCG5 or ABCG8, which encode the sterol efflux transporter ABCG5 and ABCG8. Patients with sitosterolemia show extreme phenotypic heterogeneity, ranging from almost asymptomatic individuals to those with severe hypercholesterolemia leading to accelerated atherosclerosis and premature cardiac death. Hematologic manifestations include hemolytic anemia with stomatocytosis, macrothrombocytopenia, splenomegaly, and abnormal bleeding. The mainstay of therapy includes dietary restriction of both cholesterol and plant sterols and the sterol absorption inhibitor, ezetimibe. Foods rich in plant sterols include vegetable oils, wheat germs, nuts, seeds, avocado, shortening, margarine and chocolate. Hypercholesterolemia in patients with sitosterolemia is dramatically responsive to low cholesterol diet and bile acid sequestrants. Plant sterol assay should be performed in patients with normocholesterolemic xanthomas, hypercholesterolemia with unexpectedly good response to dietary modifications or to cholesterol absorption inhibitors, or hypercholesterolemia with poor response to statins, or those with unexplained hemolytic anemia and macrothrombocytopenia. Because prognosis can be improved by proper management, it is important to find these patients out and diagnose correctly. This review article aimed to summarize recent publications on sitosterolemia, and to suggest clinical indications for plant sterol assay.

Cardiovascular Risk Factors and Ethnicity Are Independent Factors Associated with Lower Urinary Tract Symptoms.

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Jasmine Lim

Full Text Available To determine the lower urinary tract symptoms (LUTS profile and factors affecting its degree of severity including cardiovascular risk profile, age, ethnicity, education level and prostate volume in a multiethnic Asian setting.We conducted a cross-sectional study of 1021 men aged 40-79 years with no clinical evidence of prostate cancer, prostate surgery or 5α-reductase inhibitor treatment of known prostate conditions. The severity of LUTS was assessed using the International Prostate Symptom Score (IPSS. Potential factors associated with LUTS including age, ethnicity, education, history of hypertension, diabetes and hypercholesterolemia, height, weight, and prostate volume were evaluated using univariable and multivariable analyses.There were 506 (50% men found to have moderate-to-severe LUTS attaining an IPSS above 7. Overall, nocturia (45.5% was the most frequently reported symptom. Multivariable analysis showed that age, ethnicity, prostate volume and history of hypertension and hypercholesterolemia were independent factors associated with severity of LUTS (p < 0.05. Considering individual lower urinary tract symptoms, we found a strong association of storage symptom with history of hypertension and hypercholesterolemia. Malay men were significantly bothered by post micturition symptom compared to their Chinese and Indian counterparts. Stratified analyses of LUTS demonstrated a mutually exclusive cardiovascular risk factors profile defined by ethnicity.Severity of LUTS varies between different ethnicities across all age groups. In addition to age and prostate volume, ethnicity and cardiovascular risk factors including hypertension and hypercholesterolemia may also need to be taken into account in managing men with LUTS.

Evaluation of Cardiovascular Risk Factors and Restless Legs Syndrome in Women and Men: A Preliminary Population-Based Study in China.

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Liu, Yuqiong; Liu, Gangqiong; Li, Ling; Yang, Jing; Ma, Shengli

2018-03-15

Many studies have investigated the association between restless legs syndrome (RLS) and cardiovascular risk factors, leading to conflicting results. Therefore, the aim of the current study was to determine whether RLS is associated with cardiovascular risk factors and disease. This cross-sectional study included 5,324 consecutive subjects who visited the Physical Examination Center of The First Affiliated Hospital of Zhengzhou University for their yearly routine physical examination. Participants underwent a face-to-face interview with a neurologist for the assessment of RLS, based on the International Restless Legs Study Group criteria. They also completed a questionnaire related to cardiovascular risk factors and other health-related and demographic information. Logistic regression was used to assess which of the demographic and cardiovascular risk factors increased the odds of RLS. Then, unadjusted and adjusted models were designed to determine whether RLS was associated with increased odds of cardiovascular disease, coronary artery disease, or hypertension. RLS was observed in 9.2% of the participants. Multivariable logistic regression models, which included the covariates age, sex, body mass index, smoking status, hypercholesterolemia, and Pittsburgh Sleep Quality Index score (dichotomized at 5), demonstrated that female sex (odds ratio [OR]: 2.42, 95% confidence interval [CI]: 1.99-2.95), smoking (OR: 1.96, 95% CI: 1.31-2.92), high cholesterol (OR: 1.30, 95% CI: 1.03-1.64), and PSQI score > 5 (OR: 5.61, 95% CI: 2.14-14.69) are significantly associated with RLS. Additionally, RLS was associated with hypertension, after adjusting for age, sex, body mass index, smoking, hypercholesterolemia, Pittsburgh Sleep Quality Index score > 5, diabetes, anemia, and decreased renal function. RLS is associated with the prevalence of hypertension but not with that of cardiovascular disease or coronary artery disease. © 2018 American Academy of Sleep Medicine.

Short- and long-term influence of diet and simvastatin on brachial artery endothelial function

DEFF Research Database (Denmark)

Jensen, Lisette Okkels; Thayssen, Per; Petersen, Knud Erik

2006-01-01

BACKGROUND: Endothelium-dependent dilation (EDD) has often been studied in patients with hypercholesterolemia without overt coronary atherosclerosis where an improvement after statin treatment has been documented within few weeks. The aim of the study was to assess the short-term effect of diet...

Research

African Journals Online (AJOL)

abp

2014-01-31

Jan 31, 2014 ... Hypercholesterolemia correlated significantly with age and sex. Conclusion: Our study showed a ... work is properly cited. Pan African Medical .... to sex. References. 1. Facing the facts: the impact of chronic disease in Africa.

Learning about Familial Hypercholesterolemia

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... Care Genomic Medicine Working Group New Horizons and Research Patient Management Policy and Ethics Issues Quick Links for Patient Care Education All About the Human Genome Project Fact Sheets Genetic Education Resources for ...

Effects of diet-induced hypercholesterolemia on amyloid ...

Indian Academy of Sciences (India)

2012-10-27

Oct 27, 2012 ... A central hypothesis in the study of Alzheimer's disease (AD) is the accumulation and aggregation of β-amyloid ... protein (APP) and estrogen has been implicated in the pre- .... inant in HCL in the intensity of the expression was lower ..... estrogen replacement therapy of the Women's Health Initiative.

Efficacy of 5MG and 10MG rosuvastatin in type-2 diabetes mellitus with hypercholesteroalemia

International Nuclear Information System (INIS)

Ullah, F.; Rahim, F.; Rahman, S.U.; Ashfaq, M.; Afridi, A.K.

2015-01-01

Background: Coronary Heart Disease (CHD) is the most important complication and the leading cause of death in patients with type 2 diabetes mellitus (T2DM). Hypercholesterolemia is an important modifiable risk factor for CHD. Statins are the first line drugs for the treatment of hypercholesterolemia in DM. Comparative studies between different statins are available but different doses of the same statin have not been compared in our population. The objective of this study is to compare mean reduction in serum LDL-C level after using 5mg and 10mg of rosuvastatin among T2DM patients with hypercholesterolemia. This study will help finding lowest effective dose of rosuvastatin to achieve internationally set low density lipoprotein cholesterol (LDL-C) goals. Method: A total of 82 patients with T2DM having fasting LDL-C levels equal or more than 100mg/dl were randomly allocated into two groups with 41 patients in each group. Baseline fasting serum LCL-C levels were obtained in all patients. Group A received 5mg while group B received 10mg of rosuvastatin daily at night. After 6 weeks, fasting LDL-C levels were obtained and analysed to compare the mean±SD reduction of LDL-C levels in both groups. Results: Baseline mean±SD LDL-C levels in group A and group B were 134.12±30.02 and 143.49±32.01 respectively (p 0.176). Follow up mean ± SD LDL-C levels were 81.59±28.47 and 83.24±36.06 respectively (p 0.818). Mean ± SD reduction in LDL-C levels from baseline levels in group A and group B were 52.51±19.49 and 60.20±24.09 (p 0.116). Conclusion: Rosuvastatin 5mg is as effective as 10mg in reducing the LDL-C levels in type 2 diabetic patients with hypercholesterolemia. (author)

Lipid profile frequency and the prevalence of dyslipidaemia from ...

African Journals Online (AJOL)

Hypercholesterolemia correlated significantly with age and sex. Conclusion: Our study showed a relatively low request rate for lipid profile and a high prevalence of dyslipidaemia hence the importance of conducting a major study on the prevalence of dyslipidaemia and associated factors in the Senegalese population.

Association between depression and anxiety symptoms and major atherosclerosis risk factors in patients with chest pain

International Nuclear Information System (INIS)

Vural, M.; Satiroglu, Oe.; Goeksel, I.; Akbas, B.; Karabay, Oe.

2007-01-01

Psychological variables, such as depression and anxiety, are known as independent risk factors for coronary artery disease (CAD), suggesting the interaction of psychological and physiological factors in the development of CAD. In the present study, we analyzed the possible association between depressive and anxiety symptoms and major atherosclerotic risk factors in patients with chest pain warranting coronary angiography. The patients without CAD (n=159) and those with CAD (n=155) were evaluated for the severity of depression and anxiety by the symptom scales; high scores indicate severe symptoms. Age, male/female ratio, prevalence of diabetes mellitus (DM), and depression level were significantly higher in the CAD group. Among a total of 314 patients with chest pain, the mean depression score was higher in patients with DM (16.01±8.12 vs 13.01±9.6, p=0.01) and those with hypercholesterolemia (15.43±9.61 vs 12.53±9.61, p=0.02). The mean anxiety score was also higher in patients with DM (20.81±12.85 vs 16.51±12.09, p=0.008), hypercholesterolemia (20.67±13.11 vs 15.29±11.36, p=0.002), or hypertension (20.74±12.94 vs 14.1±10.8, p=0.001). Thus, DM and hypercholesterolemia are associated with depression and anxiety, while hypertension is only related to anxiety. In contrast, smoking and family history of atherosclerosis are not related to depression and anxiety scores. These results suggest depression and anxiety symptoms may contribute to the development and progression of CAD, especially in patients with DM or hypercholesterolemia. (author)

Influence of Soy Lecithin Administration on Hypercholesterolemia

OpenAIRE

Mourad, Amouni Mohamed; de Carvalho Pincinato, Eder; Mazzola, Priscila Gava; Sabha, Maricene; Moriel, Patricia

2010-01-01

Recent studies suggest that lecithin-rich diet can modify cholesterol homeostasis and hepatic lipoprotein metabolism. Considering the phytotherapeutic impact of lecithin, this work hypothesizes that lecithin administration in hypercholesterolemic patients may reduce cholesterol concentrations by increasing biliary secretion. Total cholesterol and LDL were evaluated after soy lecithin administration in hypercholesterolemic patients. One soy lecithin capsule (500 mg/RP-Sherer) was administrated...

Red Cabbage Microgreens Lower Circulating Low-Density Lipoprotein (LDL), Liver Cholesterol, and Inflammatory Cytokines in Mice Fed a High-Fat Diet.

Science.gov (United States)

Huang, Haiqiu; Jiang, Xiaojing; Xiao, Zhenlei; Yu, Lu; Pham, Quynhchi; Sun, Jianghao; Chen, Pei; Yokoyama, Wallace; Yu, Liangli Lucy; Luo, Yaguang Sunny; Wang, Thomas T Y

2016-12-07

Cardiovascular disease (CVD) is the leading cause of death in the United States, and hypercholesterolemia is a major risk factor. Population studies, as well as animal and intervention studies, support the consumption of a variety of vegetables as a means to reduce CVD risk through modulation of hypercholesterolemia. Microgreens of a variety of vegetables and herbs have been reported to be more nutrient dense compared to their mature counterparts. However, little is known about the effectiveness of microgreens in affecting lipid and cholesterol levels. The present study used a rodent diet-induced obesity (DIO) model to address this question. C57BL/6NCr mice (n = 60, male, 5 weeks old) were randomly assigned to six feeding groups: (1) low-fat diet; (2) high-fat diet; (3) low-fat diet + 1.09% red cabbage microgreens; (4) low-fat diet + 1.66% mature red cabbage; (5) high-fat diet + 1.09% red cabbage microgreens; (6) high-fat diet + 1.66% mature red cabbage. The animals were on their respective diets for 8 weeks. We found microgreen supplementation attenuated high-fat diet induced weight gain. Moreover, supplementation with microgreens significantly lowered circulating LDL levels in animals fed the high-fat diet and reduced hepatic cholesterol ester, triacylglycerol levels, and expression of inflammatory cytokines in the liver. These data suggest that microgreens can modulate weight gain and cholesterol metabolism and may protect against CVD by preventing hypercholesterolemia.

Atherosclerotic Plaque Destabilization in Mice: A Comparative Study.

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Helene Hartwig

Full Text Available Atherosclerosis-associated diseases are the main cause of mortality and morbidity in western societies. The progression of atherosclerosis is a dynamic process evolving from early to advanced lesions that may become rupture-prone vulnerable plaques. Acute coronary syndromes are the clinical manifestation of life-threatening thrombotic events associated with high-risk vulnerable plaques. Hyperlipidemic mouse models have been extensively used in studying the mechanisms controlling initiation and progression of atherosclerosis. However, the understanding of mechanisms leading to atherosclerotic plaque destabilization has been hampered by the lack of proper animal models mimicking this process. Although various mouse models generate atherosclerotic plaques with histological features of human advanced lesions, a consensus model to study atherosclerotic plaque destabilization is still lacking. Hence, we studied the degree and features of plaque vulnerability in different mouse models of atherosclerotic plaque destabilization and find that the model based on the placement of a shear stress modifier in combination with hypercholesterolemia represent with high incidence the most human like lesions compared to the other models.

The toxicity of very prolonged courses of PEGasparaginase or Erwinia asparaginase in relation to asparaginase activity, with a special focus on dyslipidemia

NARCIS (Netherlands)

W.H. Tong (Wing); R. Pieters (Rob); H.A. de Groot-Kruseman (Hester A.); W.C.J. Hop (Wim); J. Boos (Joachim); W.J.E. Tissing (Wim); I.M. van der Sluis (Inge)

2014-01-01

textabstractWe prospectively studied the incidence and clinical course of hypertriglyceridemia and hypercholesterolemia during very prolonged use of asparaginase in relation to levels of asparaginase activity in children with acute lymphoblastic leukemia. We also evaluated the incidence of

The toxicity of very prolonged courses of PEGasparaginase or Erwinia asparaginase in relation to asparaginase activity, with a special focus on dyslipidemia

NARCIS (Netherlands)

Tong, Wing H.; Pieters, Rob; de Groot-Kruseman, Hester A.; Hop, Wim C. J.; Boos, Joachim; Tissing, Wim J. E.; van der Sluis, Inge M.

2014-01-01

We prospectively studied the incidence and clinical course of hypertriglyceridemia and hypercholesterolemia during very prolonged use of asparaginase in relation to levels of asparaginase activity in children with acute lymphoblastic leukemia. We also evaluated the incidence of pancreatitis,

Polymorphisms of uric transporter proteins in the pathogenesis of gout in a Chinese Han population.

Science.gov (United States)

Wan, W; Xu, X; Zhao, D B; Pang, Y F; Wang, Y X

2015-03-30

In this study, we analyzed single nucleotide polymorphisms (SNP) in urate transporter genes to examine the pathogenesis of gout. We conducted a 1:1-matched case-control study that included 110 patients with acute gout attacks as the patient group and 110 healthy age- and gender-matched subjects as the control group. Clinical parameters were recorded and blood biochemistry tests were conducted for both groups. Multivariate logistic regression analysis was used to analyze the data. Hyperuricemia, hypercholesterolemia, and hypertriglyceridemia were found to be the main risk factors for the onset of gout, with relative risks of 29.2 (P 0.05). The risk factors of gout were hyperuricemia, hypercholesterolemia, hypertriglyceridemia, and the T/T genotype of the rs2231142 locus in the ABCG2 gene; expression of the G/G genotype may be a protective factor against gout development.

Hypertension and related risk factors in type 2 diabetes mellitus (DM ...

African Journals Online (AJOL)

Results: During the study it was found out that 61.2%of DM patients had hypertension, 56.4% obesity, 33.5% hypercholesterolemia and 38.9% hypertriglyceredemia. In the study, hypertension was associated with age, sex, type of DM, body mass index (BMI) and hypertriglyceredemia. Conclusion: The study found out that ...

Walking versus running for hypertension, cholesterol, and diabetes mellitus risk reduction.

Science.gov (United States)

Williams, Paul T; Thompson, Paul D

2013-05-01

To test whether equivalent energy expenditure by moderate-intensity (eg, walking) and vigorous-intensity exercise (eg, running) provides equivalent health benefits. We used the National Runners' (n=33 060) and Walkers' (n=15 945) Health Study cohorts to examine the effect of differences in exercise mode and thereby exercise intensity on coronary heart disease (CHD) risk factors. Baseline expenditure (metabolic equivant hours per day [METh/d]) was compared with self-reported, physician-diagnosed incident hypertension, hypercholesterolemia, diabetes mellitus, and CHD during 6.2 years follow-up. Running significantly decreased the risks for incident hypertension by 4.2% (Pdiabetes mellitus by 12.1% (Phypertension; and (3) 43.5%, 44.1%, 47.7%, and 68.2% from running, and 34.1%, 44.2% and 23.6% from walking for diabetes mellitus (walking >5.4 METh/d excluded for too few cases). The risk reductions were not significantly different for running than walking for diabetes mellitus (P=0.94), hypertension (P=0.06), or CHD (P=0.26), and only marginally greater for walking than running for hypercholesterolemia (P=0.04). Equivalent energy expenditures by moderate (walking) and vigorous (running) exercise produced similar risk reductions for hypertension, hypercholesterolemia, diabetes mellitus, and possibly CHD.

VARIABILITY IN LEVELS OF LOW-DENSITY LIPOPROTEINS CHOLESTEROL IN PATIENTS WITH FAMILIAL HYPERCHOLESTEROLEMIA DEPENDING ON AGE AND SEX AND ITS IMPORTANCE IN THE DIAGNOSIS OF THIS DISEASE

Directory of Open Access Journals (Sweden)

V. А. Korneva

2017-01-01

Full Text Available Aim. To study the ranges of low density lipoprotein (LDL cholesterol depending on the age and gender of patients with familial hypercholesterolemia (FHC by an example of a sample of patients living in the Republic of Karelia.Material and methods. Parameters of lipid spectrum of 219 patients (aged 52.5±1.7 years; males 38.3% with heterozygous FHC were studied before the start of statin therapy. Definite FHC was diagnosed in 102 patients. Lipid profile was estimated by enzymatic calorimetric method. The diagnosis of FHC was established according to the criteria of The Dutch Lipid Clinic Network.  Genetic analysis was performed in 102 patients (46.6%; pathogenic mutation in the LDL receptor was identified in 21 patients. The control group consisted of 539 people with the excluded diagnosis of FHC (aged 46.8±0.8 years; males 53.8%.Results. We determined the level of LDL cholesterol (LDLC associated with increased frequency of mutations of the LDL receptor in patients with definite FHC; mutation frequency was 3 times higher when LDLC level was more than 6.5 mmol/L. We revealed the following characteristic intervals of the LDLC levels in patients with a definite FHC: up to 20 years old – 4.8-6.2 mmol/l; in patients of 20-29 years old – 5.9-8.2 mmol/l; in the age range of 30-39 years the upper value of the LDLC levels reached 9.6 mmol/l; in individuals of 40-49 years old a stabilization, "plateau", was observed – LDLC level did not differ significantly compared to the previous decade, and was 5.4-9.0 mmol/l. In the age range  of 50-59 years the upper LDLC level was up to 11.4 mmol/l. Similar indicators were identified in patients aged 60-69 years. Patients older than 70 years with a definite FHC an upper level of LDLC was higher and reached 12.5 mmol/l. Tendency to increase in the characteristic values of LDLC with age was observed both in men and in women. Specific age-related trends  for men (an increase from a plateau by the age of 50

Aliskiren inhibits atherosclerosis development and improves plaque stability in APOE*3Leiden.CETP transgenic mice with or without treatment with atorvastatin

NARCIS (Netherlands)

Kühnast, S.; Hoorn, J.W.A. van der; Hoek, A.M. van den; Havekes, L.M.; Liau, G.; Jukema, J.W.; Princen, H.M.G.

2012-01-01

Objective: Aliskiren is the first commercially available, orally active, direct renin inhibitor approved to treat hypertension. The renin-angiotensin system has been shown to be a significant contributor to the development of hypercholesterolemia-induced atherosclerosis. The aim of this study was to

Local heart irradiation of ApoE(-/-) mice induces microvascular and endocardial damage and accelerates coronary atherosclerosis

NARCIS (Netherlands)

Gabriels, Karen; Hoving, Saske; Seemann, Ingar; Visser, Nils L.; Gijbels, Marion J.; Pol, Jeffrey F.; Daemen, Mat J.; Stewart, Fiona A.; Heeneman, Sylvia

2012-01-01

Radiotherapy of thoracic and chest-wall tumors increases the long-term risk of radiation-induced heart disease, like a myocardial infarct. Cancer patients commonly have additional risk factors for cardiovascular disease, such as hypercholesterolemia. The goal of this study is to define the

Predictive genetic testing for cardiovascular diseases: Impact on carrier children

NARCIS (Netherlands)

Meulenkamp, Tineke M.; Tibben, Aad; Mollema, Eline D.; Van Langen, Irene M.; Wiegman, Albert; De Wert, Guido M.; De Beaufort, Inez D.; Wilde, Arthur A. M.; Smets, Ellen M. A.

2008-01-01

We studied the experiences of children identified by family screening who were found to be a mutation carrier for a genetic cardiovascular disease (Long QT Syndrome (LQTS), Hypertrophic Cardiomyopathy (HCM), Familial Hypercholesterolemia (FH)). We addressed the (a) manner in which they perceive

Laypersons' understanding of relative risk reductions: randomised cross-sectional study

DEFF Research Database (Denmark)

Sorensen, Lene; Gyrd-Hansen, Dorte; Kristiansen, Ivar S

2008-01-01

of a representative sample (n = 1,519) of lay people with mean age 59 (range 40-98) years in Denmark. In addition to demographic information, respondents were asked to consider a hypothetical drug treatment to prevent heart attack. Its effectiveness was randomly presented as RRR of 10, 20, 30, 40, 50 or 60 percent......, and half of the respondents were presented with quantitative information on the baseline risk of heart attack. The respondents had also been asked whether they were diagnosed with hypercholesterolemia or had experienced a heart attack. RESULTS: In total, 873 (58%) of the respondents consented...

[Perception of cardiovascular risk in an outpatient population of the Madrid Community].

Science.gov (United States)

Pérez-Manchón, D; Álvarez-García, G M; González-López, E

2015-01-01

Cardiovascular diseases are responsible for the largest burden of global mortality. The study of the degree of knowledge of their population risk factors and cardiovascular risk is a priority preventive strategy. A cross-sectional study with 369 people was performed. The sociodemographic variables were cardiovascular risk and perception as well as physical and anthropometric factors. The risk was stratified with the SCORE table. A total of 49.6% were men and 50.4% were women. The proportion of diagnosis was 23.8% in HTA, 39% in hypercholesterolemia, 31.4% in smoking, 26.3% in obesity and 4.6% in diabetes. Concordance between perceived and real cardiovascular risk was very weak. The population has good knowledge about diabetes and acceptable knowledge about hypertension, and hypercholesterolemia but knowledge in prediabetic states and perception of the associated cardiovascular risk is low. Copyright © 2014 SEHLELHA. Published by Elsevier Espana. All rights reserved.

Clinical Usefulness of serum total cholesterol as an index of hypothyroidism in patients after cervical radiation

International Nuclear Information System (INIS)

Iguma, Yoko; Iwai, Chikako; Okuyama, Masako; Futami, Takahiro; Inui, Ken-ichi; Asato, Ryo

2003-01-01

Cervical radiation therapy is often applied to patients with head and neck cancers because radiation has a high sensitivity to these cancers and permits the preservation of functions and physical form. However, it has been shown that various complications can result from radiation therapy. We have encountered some patients who showed hypercholesterolemia resulting from cervical radiation. Therefore, we have paid close attention to the relationship between hypercholesterolemia after cervical radiation and hypothyroidism. Thyroid hormone tests in these patients with hypercholesterolemia after cervical radiation showed high thyroid stimulating hormone (TSH) and low free thyroxine (fT 4 ), indicating the presence of hypothyroidism. After administration of levothyroxine Na, their fT 4 levels increased and both TSH levels and serum total cholesterol levels decreased. In conclusion, in patients who have received cervical radiation, we recommend monitoring serum total cholesterol periodically to detect hypothyroidism easily before the appearance of its symptoms. (author)

Clinical Usefulness of serum total cholesterol as an index of hypothyroidism in patients after cervical radiation

Energy Technology Data Exchange (ETDEWEB)

Iguma, Yoko; Iwai, Chikako; Okuyama, Masako; Futami, Takahiro; Inui, Ken-ichi [Kyoto Univ. (Japan). Hospital; Asato, Ryo [Kyoto Univ. (Japan). Graduate School of Medicine

2003-02-01

Cervical radiation therapy is often applied to patients with head and neck cancers because radiation has a high sensitivity to these cancers and permits the preservation of functions and physical form. However, it has been shown that various complications can result from radiation therapy. We have encountered some patients who showed hypercholesterolemia resulting from cervical radiation. Therefore, we have paid close attention to the relationship between hypercholesterolemia after cervical radiation and hypothyroidism. Thyroid hormone tests in these patients with hypercholesterolemia after cervical radiation showed high thyroid stimulating hormone (TSH) and low free thyroxine (fT{sub 4}), indicating the presence of hypothyroidism. After administration of levothyroxine Na, their fT{sub 4} levels increased and both TSH levels and serum total cholesterol levels decreased. In conclusion, in patients who have received cervical radiation, we recommend monitoring serum total cholesterol periodically to detect hypothyroidism easily before the appearance of its symptoms. (author)

Asymptomatic carotid artery stenosis in patients with severe peripheral vascular diseases

Directory of Open Access Journals (Sweden)

Rasoul Mirsharifi

2009-04-01

Full Text Available

• BACKGROUND: The prevalence of carotid artery stenosis (CAS in the  eneral population is not high enough to justify screening programs. This study was done to determine the prevalence of asymptomatic carotid artery stenosis (ACAS among patients with severe peripheral vascular disease (PVD.
• METHODS: Between March 2005 and February 2006, 54 consecutive  atients with severe PVD admitted at a vascular surgery unit and underwent carotid duplex scanning in a prospective study. A  uestionnaire was used to collect data concerning known risk factors. Significant CAS was defined as a stenosis of 70% or greater.
• RESULTS: The mean age was 62.5 years (51-72. Out of 54 patients, 2 (3.7% had an occluded internal carotid artery. Significant CAS was found in 9 (16.7% and its presence was correlated with diabetes, hypertension, hypercholesterolemia, hypertriglyceridemia, coronary artery disease, severity of symptoms, ankle-brachial index, and carotid bruit. On multivariate analysis, only hypercholesterolemia and carotid bruit seemed to have independent influence.
• CONCLUSION: The prevalence of significant ACAS is higher among  atients with severe PVD. This patient population may indicate a  uitable subgroup for screening of ACAS, especially when hypercholesterolemia and carotid bruit are present.
• KEYWORDS: Carotid artery stenosis, duplex ultrasound scanning, peripheral vascular disease, carotid endarterectomy,
• cerebrovascular accident.

High-risk drinking is associated with dyslipidemia in a different way, based on the 2010-2012 KNHANES.

Science.gov (United States)

Kwon, Yu-Jin; Kim, Sung-Eun; Park, Byoung-Jin; Bae, Jang-Whan; Kang, Hee-Taik

2016-05-01

The Alcohol Use Disorders Identification Test (AUDIT) questionnaire is a simple and useful method for the early detection of hazardous and harmful drinking. In this study, we examined the association between alcohol drinking pattern and dyslipidemia in Korean adults. This cross-sectional study included 14,308 participants who took part in the 2010-2012 Korean National Health and Nutrition Examination Survey. We categorized alcohol drinking patterns into three groups. We classified dyslipidemia into hypercholesterolemia, hypertriglyceridemia, hypo-HDL-cholesterolemia, hyper-LDL-cholesterolemia, and hyper-non-HDL-cholesterolemia. Of those who participated, 25.1% of men and 4.8% of women were high-risk drinkers. Compared with the low-risk group, Odd Ratios for hypercholesterolemia and hypertriglyceridemia in the high-risk group were 1.198 (1.001-1.434) and 1.979 (1.622-2.413) for men. Odd Ratios for hypo-HDL-cholesterolemia in the high-risk group was 0.351 (0.279-0.441) in men and 0.413 (0.291-0.586) in women. Compared with the low-risk participants, the high-risk group was associated with higher prevalence and increased risk for hyper-LDL-cholesterolemia in both sexes (1.541 [1.467-1.913] for men and 1.631 [1.034-2.575] for women). High-risk drinking was associated with higher risk for hypertriglyceridemia and hyper-LDL-cholesterolemia in both sexes and hypercholesterolemia in men but lower risk for hypo-HDL-cholesterolemia in both sexes. Copyright © 2016 Elsevier B.V. All rights reserved.

RED ROSELLA TEA AND AVOCADO AS SIMVASTATIN THERAPY SUPPORT REDUCE TOTAL CHOLESTEROL

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Budi Artini

2017-06-01

Full Text Available Introduction: Hypercholesterolemia is a condition characterized by high levels of total cholesterol in the blood. Many studies have proven that steeping tea rosella and flesh of an avocado can reduce total cholesterol levels. This study was conducted to determine the effectiveness of therapy companion rosella tea and  avocado in lowering total cholesterol levels in hypercholesterolemia clients. Method: This type of research is a quasi-experimental study with pre-post test control group design. The population study was a client with hypercholesterolemia in the working area of menganti health centers. First sample group consisted of nine respondents received the drug Simvastatin 10 mg and rosella tea consumed as much as 2 g 1x / day. The second group consisted of nine respondents received the drug Simvastatin 10 mg and avocado meat weighing 330 grams were consumed 1x / day. The control group consisted of 11 respondents have a drug Simvastatin 10 mg oral 1x daily at night before bed. All groups examined total cholesterol levels before treatment and after treatment on day 15. Result: The results of one-way ANOVA test showed a significant difference between before and after treatment in the first group (p=0,001 and second group (p= 0,005, and there is no significant difference before and after treatment in the control group (p= 0,248. The difference between the three groups showed p= 0.025. Conclusion: The conclusion of this study is giving rosella tea and avocado has the same effectiveness in lowering total cholesterol levels so that health workers can suggest the use of rosella tea and avocado as a companion therapy to reduce total cholesterol level.

Characterization of the hyperlipidemia resulting from exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin

International Nuclear Information System (INIS)

Edwards, D.A.

1984-01-01

This research characterized the hyperlipidemia found in male Sprague-Dawley rats upon exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Initial experiments were done to determine the lowest dosage which would produce a consistent hyperlipidemia. The dosage chosen was 10 μg/kg TCDD. The time point at which hyperlipidemia appeared most significant and which was used in later experiments was seven days after administration of TCDD. Rats exhibited a significant hypercholesterolemia from day one through day 20 after exposure to TCDD. This hypercholesterolemia was characterized by quantitative increases in circulating lipoproteins and their components. The relative concentrations of the lipoprotein classes did not change nor did the concentrations of the lipoprotein classes did not change nor did the distribution of cholesterol in the lipoprotein classes. Studies of the metabolism of VLDL, intermediate density lipoprotein (IDL), and LDL in TCDD-treated animals were done. Studies of biosynthesis of lipoproteins, which involved injections of Triton WR 1339 and 3 H-leucine, revealed that TCDD-treated animals synthesized cholesterol, triacylgylcerol, and VLDL more rapidly than the pair-fed controls. Catabolic studies using 3 H-leucine indicated no significant differences in the catabolism of VLDL, IDL, or LDL in TCDD-treated and pair-fed control rats. Thus, a sub-lethal dose of 10 μg/kg TCDD produced a prolonged hypercholesterolemia and hyperlipoproteinemia in male Sprague-Dawley rats which appeared to be the result of increased VLDL synthesis. Therefore, TCDD exposure is an apparent risk factor for the development of atherosclerosis

Short-Term Red Wine Consumption Promotes Differential Effects on Plasma Levels of High-Density Lipoprotein Cholesterol, Sympathetic Activity, and Endothelial Function in Hypercholesterolemic, Hypertensive, and Healthy Subjects

Science.gov (United States)

Andrade, Ana CM; Cesena, Fernando HY; Consolim-Colombo, Fernanda M; Coimbra, Silmara R; Benjó, Alexandre M; Krieger, Eduardo M; da Luz, Protasio Lemos

2009-01-01

OBJECTIVES: To compare the metabolic, hemodynamic, autonomic, and endothelial responses to short-term red wine consumption in subjects with hypercholesterolemia or arterial hypertension, and healthy controls. METHODS: Subjects with hypercholesterolemia (n=10) or arterial hypertension (n=9), or healthy controls (n=7) were given red wine (250 mL/night) for 15 days. Analyses were performed before and after red wine intake. RESULTS: Red wine significantly increased the plasma levels of HDL-cholesterol in the controls, but not in the other groups. The effects on hemodynamic measurements were mild, non-significantly more prominent in healthy subjects, and exhibited high interindividual variability. Across all participants, mean blood pressure decreased 7 mmHg (p <0.01) and systemic vascular resistance decreased 7% (p = 0.05). Heart rate and cardiac output did not significantly change in any group. Red wine enhanced muscle sympathetic fibular nerve activity in hypercholesterolemic and hypertensive patients, but not in controls. At baseline, brachial artery flow-mediated dilation was impaired in patients with hypercholesterolemia and arterial hypertension; red wine restored the dilation in the hypercholesterolemic group but not in the hypertensive group. CONCLUSIONS: Red wine elicits different metabolic, autonomic, and endothelial responses among individuals with hypercholesterolemia or arterial hypertension and healthy controls. Our findings highlight the need to consider patient characteristics when evaluating the response to red wine. PMID:19488610

HPMC supplementation reduces abdominal fat content, intestinal permeability, inflammation, and insulin resistance in diet-induced obese mice

Science.gov (United States)

Cationic hydroxyethyl cellulose (cHEC) , was fed to hamsters to determine if this new soluble fiber had an effect on hypercholesterolemia and dyslipidemia associated with cardiovascular disease. In this study, Golden Syrian hamsters were supplemented with 3-8% cHEC or microcrystalline cellulose (MC...

Endothelial cell death and intimal foam cell accumulation in the coronary artery of infected hypercholesterolemic minipigs

DEFF Research Database (Denmark)

Birck, Malene Muusfeldt; Saraste, Antti; Hyttel, Poul

2013-01-01

Apoptosis of endothelial cells (ECs) has been suggested to play a role in atherosclerosis. We studied the synergism of hypercholesterolemia with Chlamydia pneumoniae and influenza virus infections on EC morphology and intimal changes in a minipig model. The coronary artery was excised at euthanasia...

Plasma copper status in hypercholesterolemic patients | Oluwatosin ...

African Journals Online (AJOL)

African Journal of Biomedical Research ... Most of these earlier studies have been predominantly in experimental models; very few reports have examined human subjects. ... These data support some previous reports that hypercholesterolemia is associated with decrease Cu status and this may be manipulated to control ...

Hearing Impairment and Undiagnosed Disease: The Potential Role of Clinical Recommendations

Science.gov (United States)

Marlow, Nicole M.; Malaty, John; Jo, Ara; Tanner, Rebecca J.; Beau de Rochars, Valery M.; Carek, Peter J.; Mainous, Arch G., III

2017-01-01

Purpose: The objective of this study was to use cross-sectional, nationally representative data to examine the relationship between self-reported hearing impairment and undetected diabetes, hypertension, hypercholesterolemia, and chronic kidney disease. Method: We analyzed the National Health and Nutrition Examination Survey for the years…

Cardiovascular disease in patients with genotyped familial hypercholesterolemia in Norway during 1994-2009, a registry study.

Science.gov (United States)

Mundal, Liv; Veierød, Marit B; Halvorsen, Thomas; Holven, Kirsten B; Ose, Leiv; Iversen, Per Ole; Tell, Grethe S; Leren, Trond P; Retterstøl, Kjetil

2016-12-01

Background Familial hypercholesterolaemia increases the risk for cardiovascular disease. The primary aim of the present study was to describe sex differences in incidence and prevalence of cardiovascular disease leading to hospitalisation in a complete cohort of genotyped familial hypercholesterolaemia patients. Design and methods In this registry study data on 5538 patients with verified genotyped familial hypercholesterolaemia were linked to data on all Norwegian cardiovascular disease hospitalisations, and hospitalisations due to pre-eclampsia/eclampsia, congenital heart defects and diabetes. Results During 1994-2009 a total of 1411 of familial hypercholesterolaemia patients were hospitalised, and ischaemic heart disease was reported in 90% of them. Mean (SD) age at first hospitalisation and first re-hospitalisation was 45.1 (16.5) and 47.6 (16.3) years, respectively, with no sex differences ( P = 0.66 and P = 0.93, respectively). More men (26.9%) than women (24.1%) with familial hypercholesterolaemia were hospitalised ( P = 0.02). The median (25th-75th percentile) number of hospital admissions was four (two to seven) per familial hypercholesterolaemia patient, with no sex differences ( P = 0.87). Despite having familial hypercholesterolaemia at the time of hospitalisation, the diagnosis of familial hypercholesterolaemia was registered in only 45.7% of the patients at discharge. Conclusion Most cardiovascular disease hospitalisations were due to ischaemic heart disease. Familial hypercholesterolaemia patients were first time hospitalised at age 45.1 years, with no significant sex differences in age, which are important novel findings. The awareness and registration of the familial hypercholesterolaemia diagnosis during the hospital stays were disturbingly low.

Analysis of prothrombotic and vascular risk factors in patients with nonarteritic anterior ischemic optic neuropathy.

Science.gov (United States)

Salomon, O; Huna-Baron, R; Kurtz, S; Steinberg, D M; Moisseiev, J; Rosenberg, N; Yassur, I; Vidne, O; Zivelin, A; Gitel, S; Davidson, J; Ravid, B; Seligsohn, U

1999-04-01

To determine whether genetic or acquired thrombophilias and other risk factors are associated with nonarteritic anterior ischemic optic neuropathy (NAION). Retrospective case-control study. Sixty-one patients with NAION diagnosed between 1984 and 1997. Ninety consecutive patients who visited the Eye Institute made up the control group. Protein C, protein S, antithrombin III, lupus anticoagulant, and three recently described prothrombotic polymorphisms (i.e., factor V G1691A, factor II G20210A, and methylenetetrahydrofolate reductase [MTHFR] C677T) were analyzed. In addition, risk factors for arteriosclerotic vascular disease were assessed. Parameters of thrombophilia. None of the thrombophilic markers (genetic and acquired) constituted a significant risk factor for NAION. Ischemic heart disease, hypercholesterolemia, and diabetes mellitus were discerned as risk factors for NAION with odds ratios of 2.9 (95% confidence interval [CI], 1.3-6.4), 2.6 (95% CI, 1.2-5.5), and 2.3 (95% CI, 1.1-4.8), respectively. Multiple logistic regression analysis indicated that ischemic heart disease and hypercholesterolemia exerted an additive risk for NAION with a combined odds ratio of 4.5 (95% CI, 1.4-14.5). However, none of these risk factors statistically predicted second eye involvement. NAION was not found to be associated with thrombophilic risk factors, yet it was related to ischemic heart disease, hypercholesterolemia, and diabetes mellitus.

Agmatine ameliorates atherosclerosis progression and endothelial dysfunction in high cholesterol-fed rabbits.

Science.gov (United States)

El-Awady, Mohammed S; Suddek, Ghada M

2014-06-01

The aim of this work was to explore possible effects of agmatine, an endogenous inhibitor of inducible nitric oxide synthase (iNOS), against hypercholesterolemia-induced lipid profile changes and endothelial dysfunction. Hypercholesterolemia was induced by feeding rabbits with a high-cholesterol diet (HCD, 0.5%) for 8 weeks. Another HCD-fed group was orally administered agmatine (10 mg/kg/day) during weeks 5 through 8. Serum lipid profile, malondialdehyde (MDA), nitric oxide (NO) and lactate dehydrogenase (LDH) were determined. Aorta was isolated to analyse vascular reactivity, atherosclerotic lesions and intima/media (I/M) ratio. HCD induced a significant increase in serum total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), triglycerides and high-density lipoprotein cholesterol (HDL-C). Agmatine administration significantly decreased HCD-induced elevations in serum TC and LDL-C, MDA, LDH and NO while significantly increased HDL-C levels. Additionally, agmatine significantly protected against HCD-induced attenuation of rabbit aortic endothelium-dependent relaxation to acetylcholine. HCD and agmatine did not significantly influence aortic endothelium-independent relaxation to sodium nitroprusside. Moreover, agmatine significantly reduced the elevation in aortic atherosclerotic lesion area and I/M ratio. This study is the first to reveal that agmatine has the ability to ameliorate hypercholesterolemia-induced lipemic-oxidative and endothelial function injuries possibly by its antioxidant potential and/or iNOS inhibition. © 2014 Royal Pharmaceutical Society.

Antihypercholesterolemic activity of ethanolic extract of Buchholzia ...

African Journals Online (AJOL)

Background: Hypercholesterolemia is a condition characterised with high level of cholesterol in the blood. Objectives: The effect of ethanolic extract of Buchholzia coriacea (EEBC) on the lipid profile levels and extent of lipid peroxidation in hypercholesterolemic albino rats was investigated in this study. Methods: Thirty ...

Case series

African Journals Online (AJOL)

abp

2014-01-20

Jan 20, 2014 ... Page number not for citation purposes. 1. Stroke in young adults: about 128 cases ... hypercholesterolemia, history of cigarette smoking, contraceptive intake treatment, alcohol intake, sexual ..... Carolei A, Marini C, Ferranti E, Frontoni M, Prencipe M, Fieschi. C. A prospective study of cerebral ischemia in ...

The effect of quince leaf ( Cydonia oblonga miller) decoction on ...

African Journals Online (AJOL)

Current medical literature lacks any evidence of the protective effects of quince leaf on testes. Therefore, the aim of the present study was to assess the effect of quince (Cydonia oblonga Miller) leaf decoction on testicular injury and impaired spermatogenesis induced by hypercholesterolemia in rabbits. Eleven mature New ...

Adenosine-induced coronary flow reserve in Watanabe heritable hyperlipidemic rabbits

Energy Technology Data Exchange (ETDEWEB)

Shimada, Kazuhiro; Yoshida, Katsuya [Chiba Univ. (Japan). School of Medicine; Tadokoro, Hiroyuki [and others

2000-12-01

The Watanabe heritable hyperlipidemic (WHHL) rabbit develops coronary atherosclerosis and hypercholesterolemia because of a genetic deficiency of low-density lipoprotein receptors and is therefore a good animal model for studying the relationships of coronary atherosclerosis, hypercholesterolemia and coronary flow reserve. The aim of the present study was to assess myocardial perfusion at baseline and during adenosine infusion (0.2 mg{center_dot}kg{sup -1}{center_dot}min{sup -1}) in 8 WHHL rabbits (13.8{+-}0.5 months) with {sup 13}N-ammonia, small-animal positron emission tomography (PET) and colored microspheres. Results were compared with those from 6 age-matched Japanese white rabbits. Plaque distribution was also examined in the extramural coronary arteries. All 8 WHHL rabbits had coronary plaques, with 6 showing multiple plaques. Mean global myocardial blood flow (ml{center_dot}min{sup -1}{center_dot}g{sup -1}) did not differ significantly between control and WHHL groups both at baseline (3.67{+-}0.72 vs 4.26{+-}1.12 ml{center_dot}min{sup -1}{center_dot}g{sup -1}, p=NS) and with adenosine (7.92{+-}2.00 vs 9.27{+-}2.91 ml{center_dot}min{sup -1}{center_dot}g{sup -1}, p=NS), nor did coronary flow reserve (2.16{+-}0.37 vs 2.18{+-}0.41, p=NS). None showed evidence of regional perfusion abnormalities by visual and semiquantitative analyses of PET images. It was concluded that WHHL rabbits preserve adenosine-induced coronary flow reserve despite coronary atherosclerosis and hypercholesterolemia, suggesting that a compensatory mechanism develops in this animal model. (author)

Adenosine-induced coronary flow reserve in Watanabe heritable hyperlipidemic rabbits

International Nuclear Information System (INIS)

Shimada, Kazuhiro; Yoshida, Katsuya; Tadokoro, Hiroyuki

2000-01-01

The Watanabe heritable hyperlipidemic (WHHL) rabbit develops coronary atherosclerosis and hypercholesterolemia because of a genetic deficiency of low-density lipoprotein receptors and is therefore a good animal model for studying the relationships of coronary atherosclerosis, hypercholesterolemia and coronary flow reserve. The aim of the present study was to assess myocardial perfusion at baseline and during adenosine infusion (0.2 mg·kg -1 ·min -1 ) in 8 WHHL rabbits (13.8±0.5 months) with 13 N-ammonia, small-animal positron emission tomography (PET) and colored microspheres. Results were compared with those from 6 age-matched Japanese white rabbits. Plaque distribution was also examined in the extramural coronary arteries. All 8 WHHL rabbits had coronary plaques, with 6 showing multiple plaques. Mean global myocardial blood flow (ml·min -1 ·g -1 ) did not differ significantly between control and WHHL groups both at baseline (3.67±0.72 vs 4.26±1.12 ml·min -1 ·g -1 , p=NS) and with adenosine (7.92±2.00 vs 9.27±2.91 ml·min -1 ·g -1 , p=NS), nor did coronary flow reserve (2.16±0.37 vs 2.18±0.41, p=NS). None showed evidence of regional perfusion abnormalities by visual and semiquantitative analyses of PET images. It was concluded that WHHL rabbits preserve adenosine-induced coronary flow reserve despite coronary atherosclerosis and hypercholesterolemia, suggesting that a compensatory mechanism develops in this animal model. (author)

How does the impact of a community trial on cardio-metabolic risk factors differ in terms of gender and living area? Findings from the Isfahan healthy heart program

Directory of Open Access Journals (Sweden)

Nizal Sarrafzadegan

2012-01-01

Full Text Available Objective: To assess the impact of gender and living area on cardiovascular risk factors in the context of a comprehensive lifestyle intervention program. Design: Data from independent sample surveys before (2000--2001 and after (2007 a community trial, entitled the Isfahan Healthy Heart Program (IHHP were used to compare differences in the intervention area (IA and reference area (RA by gender and living area. Setting: The interventions targeted the population living in Isfahan and Najaf-Abad counties as IA and Arak as RA. Participants: Overall, 12 514 individuals who were more than 19 years of age were studied at baseline, and 9570 were studied in postintervention phase. Interventions: Multiple activities were conducted in connection with each of the four main strategies of healthy nutrition, increasing physical activity, tobacco control, and coping with stress. Main Outcomes: Comparing serum lipids levels, blood pressure, blood glucose and obesity indices changes between IA and RA based on sex and living areas during the study. Results: In IA, while the prevalence of hypertension declined in urban and rural females (P < 0.05. In IA, the prevalence of hypercholesterolemia and hypertriglyceridemia decreased in both females and males of urban and rural areas except for hypercholesterolemia in rural males (P < 0.01. In RA, the significant changes include both decrease in the hypercholesterolemia among rural males (P < 0.001 and hypertriglyceridemia in urban females (P < 0.01, while hypertriglyceridemia was significantly increased in rural females (P < 0.01. Conclusions: This comprehensive community trial was effective in controlling many risk factors in both sexes in urban and rural areas. These findings also reflect the transitional status of rural population in adopting urban lifestyle behaviors.

Comparison Between the Effects of the Alcholic Extract of Mellissia Officinalis and Atorvastatin on Serum Levels of Thyroid Hormones in Hypercholesterolemic Male Rats

Directory of Open Access Journals (Sweden)

Ali Zarei

2013-08-01

Full Text Available Background: Consumption of unsaturated fats reduces the serum level of lipids and leptin. Thyroid hormones and leptin play pivotal roles in metabolism and their amounts are inter-related. This study was done to compare the effects of Mellissia officinalis extract and atorvastatin on the serum levels of thyroid hormones in hypercholesterolemia rats.Materials and Methods: Consumption of unsaturated fats reduces the serum level of lipids and leptin. Thyroid hormones and leptin play pivotal roles in metabolism and their amounts are inter-related. This study was done to compare the effects of Mellissia officinalis extract and atorvastatin on the serum levels of thyroid hormones in hypercholesterolemia rats.Results: The results showed that in experimental groups receiving the plant extract and atorvastatin, the concentration of thyroid hormones increased, whereas the amount of the thyroid-stimulating hormone showed a significant decrease (p<0.05.Conclusion: Mellissia officinalis extract decreases TSH but it increases T3 and T4. Further studies are required for applying this extract to the treatment of hyperthyroidism.

Effect of a long-chained fructan Raftiline HP on blood lipids and spontaneous atherosclerosis in low density receptor knockout mice

DEFF Research Database (Denmark)

Mortensen, Alicja; Poulsen, Morten; Frandsen, Henrik Lauritz

2002-01-01

The effect of a long-chained fructan Raftiline HP on spontaneous hypercholesterolemia and atherosclerosis was studied in 40 LDLR-/- male mice receiving isocaloric, balanced in fat content, purified diets with 0 or 10% Raftiline HP, for 16 weeks. The feed intake was comparable (3.9 v. 3.8 g/day) b...

Randomized comparison of deliverability and in-hospital complications in implantation of BxSonic(R), Express(R), and Flexmaster(R) coronary stents

DEFF Research Database (Denmark)

Thuesen, Leif; Galløe, Anders; Thayssen, Per

2005-01-01

in a native coronary artery were included in the study. There were 494 (664) patients (treated lesions) in the BxSonic(R), 499 (657) in the Express(R) and 500 (658) in the Flexmaster(R) groups. The groups were well matched with regard to age, sex, diabetes, smoking, hypercholesterolemia, hypertension...

Effects of oat and wheat bread consumption on lipid profile, blood sugar, and endothelial function in hypercholesterolemic patients: A randomized controlled clinical trial

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Amir Momenizadeh

2014-09-01

Full Text Available BACKGROUND: Increased lipid profile after each meal can disturb the endothelial function. The present study assessed the effects of bread supplemented with oat bran on serum lipids and endothelial dysfunction in patients with hypercholesterolemia. METHODS: This clinical trial was conducted on 60 isolated hypercholesterolemic patients. The subjects were randomly allocated to either intervention (consuming at least five daily servings of oat bread with 6 g beta-glucan or control (receiving at least five servings of wheat bread. Anthropometric indicators, fasting blood sugar and lipid profiles ere measured at baseline and after 6 weeks (in the end of the intervention. Endothelial function was assessed using flow-mediated dilation (FMD. Within the group and between group differences were investigated using paired t-test and Student’s t-test, respectively. RESULTS: Oat bread consumption could significantly reduce total cholesterol (P = 0.029. A significant increase in baseline and after ischemia brachial artery diameters at the end of the study was seen. However, it did not have a significant effect on FMD (P = 0.825. In the control group, none of the measured indices had changed significantly at the end of the study. Finally, only the mean change of brachial artery diameter after ischemia and baseline brachial artery diameter were significantly higher in the intervention group than in the control group (P = 0.036 and P = 0.012 respectively. CONCLUSION: Oat bread with beta-glucan could successfully reduce cholesterol levels. Furthermore, in this study oat bread did not reduce FMD more than wheat bread. Since hypercholesterolemia is a proven risk factor for endothelial dysfunction, hypercholesterolemic patients can hence be advised to eat oat bread.   Keywords: Bread, Diet, Flow-Mediated Dilation, Hypercholesterolemia 

The Effect of the Cholesterol Levels on Noise-Induced Hearing Loss.

Science.gov (United States)

Demir, Mehmet Gokhan; Aydin, Sedat

2018-01-01

Introduction  Noise-induced hearing loss (NIHL), which is one of the most common occupational diseases among industrialized populations, is associated with longstanding exposure to high levels of noise. The pathogenesis of NIHL is not clear, but some genes and their activity at the tissue level have been investigated. Hypercholesterolemia, which can disturb the microcirculation, can be one of the underlying pathologies in hearing loss. Objective  To investigate the relationship between NIHL and hypercholesterolemia. Methods  The study group was selected among workers who had an occupational exposure of 85 dB of noise for at least 10 years. The audiologic assessment was recorded at seven frequencies (500 Hz, 1,000 Hz, 2,000 Hz, 3,000 Hz, 4,000 Hz, 6,000 Hz and 8,000 Hz). A total of 456 workers were included in the study and divided into two groups: the control group (252 patients) and the NIHL group (204 patients). After the audiologic measurement, blood samples were taken and investigated for blood cholesterol levels. According to these results, the groups were compared. Results  Both groups were similarly distributed regarding age and occupational exposure time ( p  > 0.05). We could not detect any association between cholesterol levels and noise-induced hearing loss ( p   0.05). Conclusion  Noise-induced hearing loss is still a common occupational problem that can be prevented by hearing conservation programs and occupational health and safety training. Still, we know little about the relationship between NIHL and hypercholesterolemia. According to our findings, we cannot detect any relationship. Controlled studies and studies with human individuals can be made possible in the future with diagnostic innovations in tissue imaging and tissue microcircular sampling.

Educational Health Disparities in Cardiovascular Disease Risk Factors: Findings from Jamaica Health and Lifestyle Survey 2007–2008

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Trevor S. Ferguson

2017-05-01

Full Text Available ObjectivesSocioeconomic disparities in health have emerged as an important area in public health, but studies from Afro-Caribbean populations are uncommon. In this study, we report on educational health disparities in cardiovascular disease (CVD risk factors (hypertension, diabetes mellitus, hypercholesterolemia, and obesity, among Jamaican adults.MethodsWe analyzed data from the Jamaica Health and Lifestyle Survey 2007–2008. Trained research staff administered questionnaires and obtained measurements of blood pressure, anthropometrics, glucose and cholesterol. CVD risk factors were defined by internationally accepted cut-points. Educational level was classified as primary or lower, junior secondary, full secondary, and post-secondary. Educational disparities were assessed using age-adjusted or age-specific prevalence ratios and prevalence differences obtained from Poisson regression models. Post-secondary education was used as the reference category for all comparisons. Analyses were weighted for complex survey design to yield nationally representative estimates.ResultsThe sample included 678 men and 1,553 women with mean age of 39.4 years. The effect of education on CVD risk factors differed between men and women and by age group among women. Age-adjusted prevalence of diabetes mellitus was higher among men with less education, with prevalence differences ranging from 6.9 to 7.4 percentage points (p < 0.05 for each group. Prevalence ratios for diabetes among men ranged from 3.3 to 3.5 but were not statistically significant. Age-specific prevalence of hypertension was generally higher among the less educated women, with statistically significant prevalence differences ranging from 6.0 to 45.6 percentage points and prevalence ratios ranging from 2.5 to 4.3. Similarly, estimates for obesity and hypercholesterolemia suggested that prevalence was higher among the less educated younger women (25–39 years and among more educated older

Clinical study of the relationship between arteriosclerosis obliterans (ASO) and cerebral infarction

International Nuclear Information System (INIS)

Iwamoto, Toshihiko; Sasaki, Akinori; Yanagawa, Kiyotaka; Mitsugi, Yasushi

1991-01-01

To clarify the relationship between arteriosclerosis obliterans (ASO) and cerebral infarction (CI), brain CT was performed and the risk factors for atherosclerosis were assessed. Thirty-five male and 5 female patients with intermittent claudication and/or leg ulceration were angiographically diagnosed as having ASO. According to CT findings, these patients were divided into three groups [no low-density areas (NLDA), hemorrhage, and infarction (CI)]. CI was subdivided as lacunar, cortical, and watershed infarction. Thirteen patients were in the NLDA group and 26 in the CI group (17 lacunar, 3 cortical and 6 mixed infarcts), indicating a CI incidence of 65%. Comparing the risk factors of the CI group with those of the NLDA group, hypertension (53.8%), diabetes (34.6%), and cigarette smoking (69.2%) was often seen in the CI group, although hypercholesterolemia (53.8%) and ischemic heart disease (42.3%) was the same in both groups. Multivariate analysis revealed that smoking had the strongest effect on the occurrence of CI in ASO patients. Furthermore, the number of combined risk factors (hypertension, diabetes, smoking, hypercholesterolemia) had a significant positive correlation with cortical infarction. As to the chronological relationship between the onset of ASO and CI, CI was present in 14 of 27 ASO patients on CT when the ischemic leg symptoms appeared, while symptomatic cortical infarction preceded ASO in 5 patients. CI patients increased gradually over a decade to 26 out of 40, among whom 16 patients with lacunae had silent infarcts. These findings suggested that ASO is frequently associated with CI, not only due to atherosclerosis of the main trunks of the cerebral vessels, but also due to arteriolosclerosis of the perforating arteries. (author)

THE ROLE OF LIPOTROPIC THERAPY IN PATIENTS WITH CHRONIC ISCHEMIC HEART DISEASE BEFORE AND AFTER CORONARY REVASCULARIZATION

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R. N. Adzhiev

2013-01-01

Full Text Available Review of large of trials that prove the positive impact of high-dose lipid-lowering therapy on the prognosis in patients with ischemic heart disease (IHD are presented. The data on the efficacy of the lipid profile correction by lipid apheresis in patients with hypercholesterolemia that is refractory to optimal medical therapy are showed. The results of the large trials (LIPS, ARMYDA, NAPLES II, ARMYDA-RECAPTURE, Post-CABG, TNT and meta-analyzes on the role of statins, prescribed before and after coronary artery bypass surgery and stenting, in reducing the risk of early and late cardiac events and the need for repeat myocardial revascularization are analyzed. The issue of therapeutic apheresis should be considered in cases of refractory hypercholesterolemia according to ESC/EAS Guidelines for the management of dyslipidaemias (2011. The tendency to reduction in the risk of stent restenosis and vein graft lesions after lipid apheresis is found in very high risk patients with IHD and refractory hypercholesterolemia that underwent coronary stenting or bypass surgery.

THE ROLE OF LIPOTROPIC THERAPY IN PATIENTS WITH CHRONIC ISCHEMIC HEART DISEASE BEFORE AND AFTER CORONARY REVASCULARIZATION

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R. N. Adzhiev

2015-09-01

Full Text Available Review of large of trials that prove the positive impact of high-dose lipid-lowering therapy on the prognosis in patients with ischemic heart disease (IHD are presented. The data on the efficacy of the lipid profile correction by lipid apheresis in patients with hypercholesterolemia that is refractory to optimal medical therapy are showed. The results of the large trials (LIPS, ARMYDA, NAPLES II, ARMYDA-RECAPTURE, Post-CABG, TNT and meta-analyzes on the role of statins, prescribed before and after coronary artery bypass surgery and stenting, in reducing the risk of early and late cardiac events and the need for repeat myocardial revascularization are analyzed. The issue of therapeutic apheresis should be considered in cases of refractory hypercholesterolemia according to ESC/EAS Guidelines for the management of dyslipidaemias (2011. The tendency to reduction in the risk of stent restenosis and vein graft lesions after lipid apheresis is found in very high risk patients with IHD and refractory hypercholesterolemia that underwent coronary stenting or bypass surgery.

High plasma concentrations of asymmetric dimethylarginine inhibit ischemic cardioprotection in hypercholesterolemic rats

International Nuclear Information System (INIS)

Landim, M.B.P.; Dourado, P.M.M.; Casella-Filho, A.; Chagas, A.C.P.; Luz, P.L. da

2013-01-01

A low concentration of nitric oxide associated with a high concentration of asymmetric dimethylarginine (ADMA) can explain the lack of ischemic cardioprotection observed in the presence of hypercholesterolemia. The objective of the present study was to evaluate the effect of hypercholesterolemia on ischemic pre- and postconditioning and its correlation with plasma concentrations of ADMA. Male Wistar rats (6-8 weeks old) fed a 2% cholesterol diet (n = 21) for 8 weeks were compared to controls (n = 25) and were subjected to experimental myocardial infarction and reperfusion, with ischemic pre- and postconditioning. Total cholesterol and ADMA were measured in plasma before the experimental infarct and the infarct area was quantified. Weight, total cholesterol and plasma ADMA (means ± SE; 1.20 ± 0.06, 1.27 ± 0.08 and 1.20 ± 0.08 vs 0.97 ± 0.04, 0.93 ± 0.05 and 0.97 ± 0.04 µM) were higher in animals on the hypercholesterolemic diet than in controls, respectively. Cardioprotection did not reduce infarct size in the hypercholesterolemic animals (pre: 13.55% and post: 8% compared to 7.95% observed in the group subjected only to ischemia and reperfusion), whereas infarct size was reduced in the animals on a normocholesterolemic diet (pre: 8.25% and post: 6.10% compared to 12.31%). Hypercholesterolemia elevated ADMA and eliminated the cardioprotective effects of ischemic pre- and postconditioning in rats

High plasma concentrations of asymmetric dimethylarginine inhibit ischemic cardioprotection in hypercholesterolemic rats

Energy Technology Data Exchange (ETDEWEB)

Landim, M.B.P.; Dourado, P.M.M.; Casella-Filho, A.; Chagas, A.C.P.; Luz, P.L. da [Unidade de Aterosclerose, Instituto do Coração, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP (Brazil)

2013-05-10

A low concentration of nitric oxide associated with a high concentration of asymmetric dimethylarginine (ADMA) can explain the lack of ischemic cardioprotection observed in the presence of hypercholesterolemia. The objective of the present study was to evaluate the effect of hypercholesterolemia on ischemic pre- and postconditioning and its correlation with plasma concentrations of ADMA. Male Wistar rats (6-8 weeks old) fed a 2% cholesterol diet (n = 21) for 8 weeks were compared to controls (n = 25) and were subjected to experimental myocardial infarction and reperfusion, with ischemic pre- and postconditioning. Total cholesterol and ADMA were measured in plasma before the experimental infarct and the infarct area was quantified. Weight, total cholesterol and plasma ADMA (means ± SE; 1.20 ± 0.06, 1.27 ± 0.08 and 1.20 ± 0.08 vs 0.97 ± 0.04, 0.93 ± 0.05 and 0.97 ± 0.04 µM) were higher in animals on the hypercholesterolemic diet than in controls, respectively. Cardioprotection did not reduce infarct size in the hypercholesterolemic animals (pre: 13.55% and post: 8% compared to 7.95% observed in the group subjected only to ischemia and reperfusion), whereas infarct size was reduced in the animals on a normocholesterolemic diet (pre: 8.25% and post: 6.10% compared to 12.31%). Hypercholesterolemia elevated ADMA and eliminated the cardioprotective effects of ischemic pre- and postconditioning in rats.

Bayesian statistic methods and theri application in probabilistic simulation models

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Orietta Zaniolo

2006-03-01

Full Text Available Significant advances in the management of hypercholesterolemia have been made possible by the development of statins, 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA reductase inhibitors. More recently, statins have demonstrated benefit in primary and secondary prevention of cardiovascular disease also in patients without hypercholesterolemia. Therefore statins help to reduce the impact of cardiovascular disease on morbility, mortality and social costs. Statins inhibit HMG-CoA reductase competitively, reduce LDL levels more than other cholesterol-lowering drugs, and lower triglyceride levels in hypertriglyceridemic patients. Prescribing statins as first line therapy in management of hypercholesterolemia as a part of a more comprehensive prevention program of cardiovascular disease is widely recommended by international guidelines (e.g. National Cholesterol Education Program - NCEP - Adult Treatment Panel - ATP- III reports. Currently in Italy there are five available statins: atorvastatin, fluvastatin, pravastatin, rosuvastatin and simvastatin; each of them presents some differences in physical and chemical characteristics (solubility, pharmacokinetics (absorption, proteic binding, metabolism and excretion and pharmacodinamics (pleiotropic effects. Compared to other statins, fluvastatin extended-release (RP 80 mg provides an equal efficacy in lowering total cholesterol and low-density lipoprotein cholesterol (LDL-C, with an important action on triglyceride (TG levels and superior increases in HDL-C levels, reducing the incidence of major adverse cardiac events (MACE. Aim of this study is to outline an updated therapeutic and pharmacoeconomic profile of fluvastatin, particularly regarding extended-release (RP 80 mg formulation.

Bone marrow endothelial progenitors augment atherosclerotic plaque regression in a mouse model of plasma lipid lowering

Science.gov (United States)

Yao, Longbiao; Heuser-Baker, Janet; Herlea-Pana, Oana; Iida, Ryuji; Wang, Qilong; Zou, Ming-Hui; Barlic-Dicen, Jana

2012-01-01

The major event initiating atherosclerosis is hypercholesterolemia-induced disruption of vascular endothelium integrity. In settings of endothelial damage, endothelial progenitor cells (EPCs) are mobilized from bone marrow into circulation and home to sites of vascular injury where they aid endothelial regeneration. Given the beneficial effects of EPCs in vascular repair, we hypothesized that these cells play a pivotal role in atherosclerosis regression. We tested our hypothesis in the atherosclerosis-prone mouse model in which hypercholesterolemia, one of the main factors affecting EPC homeostasis, is reversible (Reversa mice). In these mice normalization of plasma lipids decreased atherosclerotic burden; however, plaque regression was incomplete. To explore whether endothelial progenitors contribute to atherosclerosis regression, bone marrow EPCs from a transgenic strain expressing green fluorescent protein under the control of endothelial cell-specific Tie2 promoter (Tie2-GFP+) were isolated. These cells were then adoptively transferred into atheroregressing Reversa recipients where they augmented plaque regression induced by reversal of hypercholesterolemia. Advanced plaque regression correlated with engraftment of Tie2-GFP+ EPCs into endothelium and resulted in an increase in atheroprotective nitric oxide and improved vascular relaxation. Similarly augmented plaque regression was also detected in regressing Reversa mice treated with the stem cell mobilizer AMD3100 which also mobilizes EPCs to peripheral blood. We conclude that correction of hypercholesterolemia in Reversa mice leads to partial plaque regression that can be augmented by AMD3100 treatment or by adoptive transfer of EPCs. This suggests that direct cell therapy or indirect progenitor cell mobilization therapy may be used in combination with statins to treat atherosclerosis. PMID:23081735

Edible bird’s nest attenuates procoagulation effects of high-fat diet in rats

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Yida Z

2015-07-01

Full Text Available Zhang Yida,1,2 Mustapha Umar Imam,1 Maznah Ismail,1,3 Norsharina Ismail,1 Zhiping Hou1 1Laboratory of Molecular Biomedicine, Institute of Bioscience, Universiti Putra Malaysia, Serdang, Selangor, Malaysia; 2Cardiology Department, Affiliated Hospital of Chengde Medical University, Chengde, Hebei, People’s Republic of China; 3Faculty of Medicine and Health Sciences, Department of Nutrition and Dietetics, Universiti Putra Malaysia, Serdang, Selangor, Malaysia Abstract: Edible bird’s nest (EBN is popular in Asia, and has long been used traditionally as a supplement. There are, however, limited evidence-based studies on its efficacy. EBN has been reported to improve dyslipidemia, which is closely linked to hypercoagulation states. In the present study, the effects of EBN on high-fat diet- (HFD- induced coagulation in rats were evaluated. Rats were fed for 12 weeks with HFD alone or in combination with simvastatin or EBN. Food intake was estimated, and weight measurements were made during the experimental period. After sacrifice, serum oxidized low-density lipo­protein (oxLDL, adiponectin, leptin, von willibrand factor, prostacyclin, thromboxane and lipid profile, and whole blood coagulation indices (bleeding time, prothrombin time, activated partial thromboplastin time, red blood count count, and platelet count were estimated. Furthermore, hepatic expression of coagulation-related genes was evaluated using multiplex polymerase chain reaction. The results indicated that EBN could attenuate HFD-induced hypercholesterolemia and coagulation similar to simvastatin, partly through transcriptional regulation of coagulation-related genes. The results suggested that EBN has the potential for lowering the risk of cardiovascular disease-related hypercoagulation due to hypercholesterolemia. Keywords: edible bird’s nest, coagulation, high-fat diet, hypercholesterolemia, nutrigeno­mics

Vascular risk factors, cognitve decline, and dementia

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E Duron

2008-04-01

Full Text Available E Duron, Olivier HanonBroca Hospital, Paris, FranceAbstract: Dementia is one of the most important neurological disorders in the elderly. Aging is associated with a large increase in the prevalence and incidence of degenerative (Alzheimer’s disease and vascular dementia, leading to a devastating loss of autonomy. In view of the increasing longevity of populations worldwide, prevention of dementia has turned into a major public health challenge. In the past decade, several vascular risk factors have been found to be associated with vascular dementia but also Alzheimer’s disease. Some longitudinal studies, have found significant associations between hypertension, diabetus mellitus, and metabolic syndrome, assessed at middle age, and dementia. Studies assessing the link between hypercholesterolemia, atrial fibrillation, smoking, and dementia have given more conflicting results. Furthermore, some studies have highlighted the possible protective effect of antihypertensive therapy on cognition and some trials are evaluating the effects of statins and treatments for insulin resistance. Vascular risk factors and their treatments are a promising avenue of research for prevention of dementia, and further long-term, placebo-controlled, randomized studies, need to be performed.Keywords: dementia, hypertension, diabetus mellitus, hypercholesterolemia, metabolic syndrome

Progression to impaired glucose regulation and diabetes in the population-based Inter99 study

DEFF Research Database (Denmark)

Engberg, Susanne; Vistisen, Dorte; Lau, Cathrine

2009-01-01

Objective: To estimate the progression rates to impaired glucose regulation (impaired fasting glucose or impaired glucose tolerance) and diabetes in the Danish population-based Inter99 study and in a high-risk subpopulation, separately. Research Design and Methods: From a population-based primary...... glucose regulation using the current World Health Organization classification criteria were calculated for the first time in a large European population-based study. The progression rates to diabetes show the same pattern as seen in the few similar European studies....... prevention study, the Inter99 study, 4,615 individuals without diabetes at baseline and with relevant follow-up data were divided into a low- and a high-risk group based on a risk estimate of ischemic heart disease or the presence of risk factors (smoking, hypertension, hypercholesterolemia, obesity...... estimated directly from baseline to 5-year follow-up for all the participants, and from baseline through 1- and 3-, to 5-year follow-up for the high-risk individuals, separately. Results: In the combined low- and high-risk group, 2.1 per 100 person-years progressed from normal glucose tolerance to impaired...

Reaction of lymph nodes of irradiated rats to alimentary lipid loading

International Nuclear Information System (INIS)

Tryasuchev, P.M.; Chirkina, I.A.; Ol'shanikova, V.V.; Chirkin, A.A.

1998-01-01

The transformation of the hepatic and mesenteric lymph nodes of rats received 2,5%, 5%, or 10% cholesterol load during one month has been studied by histological methods.The second step included studying the influence of 2,5%, 5%, or 10% cholesterol load combined with external gamma irradiation with 0,04 R/h. Many lymph nodes have demonstrated in biochemical tests destructive changes after maximal hypercholesterolemia

Effect of γ irradiation on the activity of lecithin-cholesterol acyltransferase in plasma of the rat

International Nuclear Information System (INIS)

Dousset, N.; Douste-Blazy, L.

1975-01-01

Plasma cholesterol and lecithin-cholesterol-acyl-transferase activity are studied in irradiated rats. Ionizing radiations cause an increase of cholesterol levels in plasma, concerning mainly ester fraction. Lecithin-cholesterol-acyltransferase activity in plasma of irradiated rats is lowered 48 hours after exposure. This decreased rate of LCAT is probably the consequence of the post-irradiation hypercholesterolemia [fr

Effect of vitamin E supplementation on serumic levels of lipids and lipoproteins in cholesterol-fed male rat

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M.H Khayat Nouri

2008-11-01

Full Text Available Hypercholesterolemia is one of the risk factors of cardiovascular diseases. High blood cholesterol affects the general health and increases the mortality rate of cardiovascular diseases. High levels of cholesterol in the diet increases LDL levels and decreases the activity of LDL receptors in the liver. Oxidation of vascular LDL lipoproteins increases the development of atherosclerosis. Previous studies have indicated that consumption of antioxidants decreases hypercholesterolemia. This study evaluates the effect of vitamin E supplementation on blood lipid levels in high cholesterol-fed rats. In this experimental study, three groups of male rats (n=10 for each group were used. The control group received basic diet and one of the other two groups received a diet containing one percent cholesterol and while the other received the same diet plus vitamin E supplement (2500 IU/kg in dry matter of the diet for one month. After determining the values of TC, LDL, VLDL, HDL and TG the results indicated that in rats fed with 1% cholesterol apart from HDL and VLDL the other lipids had increased significantly compared with the control group (p

Survey on risk factors for chronic diseases in college students - doi:10.5020/18061230.2007.p168

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Vívian Saraiva Veras

2012-01-01

Full Text Available The study proposed to identify the risk factors for diabetes mellitus (DM, systemic arterial hypertension (HAS and cardiovascular diseases (DCV in college students of a private institution in the city of Fortaleza. Two hundred students joined in the study, being submitted to an evaluation survey, in which were obtained data on: sex, age, history of tobacco use, alcoholism, sedentariness and family antecedents of DM, HAS, hypercholesterolemia and ischemic event. Those that presented three or more risk factors for DM, HAS and DCV being then, directed for accomplishment of anthropometric evaluation, capillary glucose measure and measurement of arterial pressure. The sample consisted of 172 students (128F/44M. The results pointed out that 121 (70.3% of the students did not practice physical activities, 124 (72.1% of the subjects presented family antecedents for DM, 131 (76.2% for HAS, 104 (60.5% for hypercholesterolemia and 91 (52.9% for previous ischemic event, 43 (25% presented overweight and 10 (5.9% first-degree obesity, 30 (17.5% had arterial pressure ? 130/60 mmHg. The results indicate the need for educational programs in the studied institution aiming at health education and prevention of chronic diseases.

A Hamster Model of Diet-Induced Obesity for Preclinical Evaluation of Anti-Obesity, Anti-Diabetic and Lipid Modulating Agents.

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Louise S Dalbøge

Full Text Available Unlike rats and mice, hamsters develop hypercholesterolemia, and hypertriglyceridemia when fed a cholesterol-rich diet. Because hyperlipidemia is a hallmark of human obesity, we aimed to develop and characterize a novel diet-induced obesity (DIO and hypercholesterolemia Golden Syrian hamster model.Hamsters fed a highly palatable fat- and sugar-rich diet (HPFS for 12 weeks showed significant body weight gain, body fat accumulation and impaired glucose tolerance. Cholesterol supplementation to the diet evoked additional hypercholesterolemia. Chronic treatment with the GLP-1 analogue, liraglutide (0.2 mg/kg, SC, BID, 27 days, normalized body weight and glucose tolerance, and lowered blood lipids in the DIO-hamster. The dipeptidyl peptidase-4 (DPP-4 inhibitor, linagliptin (3.0 mg/kg, PO, QD also improved glucose tolerance. Treatment with peptide YY3-36 (PYY3-36, 1.0 mg/kg/day or neuromedin U (NMU, 1.5 mg/kg/day, continuously infused via a subcutaneous osmotic minipump for 14 days, reduced body weight and energy intake and changed food preference from HPFS diet towards chow. Co-treatment with liraglutide and PYY3-36 evoked a pronounced synergistic decrease in body weight and food intake with no lower plateau established. Treatment with the cholesterol uptake inhibitor ezetimibe (10 mg/kg, PO, QD for 14 days lowered plasma total cholesterol with a more marked reduction of LDL levels, as compared to HDL, indicating additional sensitivity to cholesterol modulating drugs in the hyperlipidemic DIO-hamster. In conclusion, the features of combined obesity, impaired glucose tolerance and hypercholesterolemia in the DIO-hamster make this animal model useful for preclinical evaluation of novel anti-obesity, anti-diabetic and lipid modulating agents.

Fatores de risco de aterosclerose na infância. Um estudo epidemiológico Risk factors of atherosclerosis in children. An epidemiologic study

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Zoffi Roberto S. Gerber

1997-10-01

Full Text Available OBJETIVO: Obter um perfil dos fatores de risco coronário em uma amostra populacional pediátrica da cidade de Bento Gonçalves, RS, no período de maio/90 a junho/91. MÉTODOS: Foram estudados 1501 escolares de 6 a 16 anos incompletos, visando a detecção dos níveis séricos de colesterol total, lipoproteínas, triglicerídeos, bem como a avaliação da pressão arterial e da história familiar de doença cardiovascular isquêmica e obesidade. RESULTADOS: Foram detectadas 420 (27,98% crianças com hipercolesterolemia, sendo que 75 (5% apresentavam hipertensão arterial sistólica e 48 (3,20% hipertensão arterial diastólica. A história familiar foi importante quando positiva, porém, sua ausência não excluia a presença de fatores de risco para a aterosclerose. A hipertrigliceridemia foi encontrada em 136 (9,06% escolares e a LDL-colesterol elevada em 155 (10,33%, mostrando forte associação com hipercolesterolemia. Apresentaram índice de massa corporal acima de percentil 95, não mostrando uma maior prevalência de hipercolesterolemia, 111 crianças. CONCLUSÃO: Os fatores de risco para a aterosclerose estão presentes na infância e deveriam ser pesquisados independentemente do nível socioeconômico, da história familiar, da idade e do sexo, devendo o pediatra ser um dos responsáveis por esta investigação.PURPOSE: To obtain a profile of risk factors for coronary atherosclerosis in a pediatric population from Bento Gonçalves, Rio Grande do Sul, from May 1990 to June 1991. METHODS: One thousand five hundred and one children with ages from 6 to 15 years were studied to assess serum cholesterol levels and their association with other risk factors, such as arterial hypertension, obesity and family history of cardiovascular disease. RESULTS: Four hundred and twenty (27.98% children showed cholesterol levels over 180mg%; 75 (5% had systolic hypertension and 48 (3.20% diastolic hypertension. The family history was important to search

Hypocholesterolemic Effect and In Vitro Pancreatic Lipase Inhibitory Activity of an Opuntia ficus-indica Extract.

Science.gov (United States)

Padilla-Camberos, Eduardo; Flores-Fernandez, Jose Miguel; Fernandez-Flores, Ofelia; Gutierrez-Mercado, Yanet; Carmona-de la Luz, Joel; Sandoval-Salas, Fabiola; Mendez-Carreto, Carlos; Allen, Kirk

2015-01-01

Cholesterol control is fundamental for prevention of cardiovascular disorders. In this work, the hypocholesterolemic activity of an aqueous Opuntia ficus-indica extract (AOE) was tested in triton-induced mice. The inhibitory activity on pancreatic lipase enzyme was evaluated in vitro by the same extract. Furthermore, polyphenol content of the extract was evaluated. Hypercholesterolemia was induced in three groups of mice by intraperitoneal administration of Triton WR-1339. After induction of hypercholesterolemia, the groups were treated with an AOE (500 mg/kg) and saline solution and the positive control group with orlistat, respectively. Cholesterol levels were measured 24 h later in peripheral blood. The levels of blood cholesterol after administration of AOE significantly decreased compared to negative control. The inhibitory activity of AOE on pancreatic lipase enzyme was evaluated at concentrations from 60 to 1000 μg/mL. The AOE inhibited the pancreatic lipase with an IC50 = 588.5 μg/mL. The AOE had a high content of polyphenolic compounds. These results show that AOE is able to prevent hypercholesterolemia by pancreatic lipase inhibition, in part due to its polyphenolic compounds.

Hypocholesterolemic Effect and In Vitro Pancreatic Lipase Inhibitory Activity of an Opuntia ficus-indica Extract

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Eduardo Padilla-Camberos

2015-01-01

Full Text Available Cholesterol control is fundamental for prevention of cardiovascular disorders. In this work, the hypocholesterolemic activity of an aqueous Opuntia ficus-indica extract (AOE was tested in triton-induced mice. The inhibitory activity on pancreatic lipase enzyme was evaluated in vitro by the same extract. Furthermore, polyphenol content of the extract was evaluated. Hypercholesterolemia was induced in three groups of mice by intraperitoneal administration of Triton WR-1339. After induction of hypercholesterolemia, the groups were treated with an AOE (500 mg/kg and saline solution and the positive control group with orlistat, respectively. Cholesterol levels were measured 24 h later in peripheral blood. The levels of blood cholesterol after administration of AOE significantly decreased compared to negative control. The inhibitory activity of AOE on pancreatic lipase enzyme was evaluated at concentrations from 60 to 1000 μg/mL. The AOE inhibited the pancreatic lipase with an IC50 = 588.5 μg/mL. The AOE had a high content of polyphenolic compounds. These results show that AOE is able to prevent hypercholesterolemia by pancreatic lipase inhibition, in part due to its polyphenolic compounds.

Effect of Rice Bran Oil on the Lipid Profile of Mild-Moderate Hypercholesterolemic Male Aged 19-55 year

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Noor Diah Erlinawati

2017-09-01

Full Text Available Introduction: Adult individuals in Indonesia showed changes in diet and lack of physical activity, therefore increasing the risk of hypercholesterolemia and obesity. One of nutritional therapy for hypercholesterolemia is rice bran oil, which contains active substances that works synergistically in controlling lipid profile. The substances are gamma-orzanol, phytosterols, and vitamin E isomers (tocotrienol and tocopherol. Methods: A clinical trial was conducted for 4 weeks in City Hall of Jakarta on 20 males, age 19–55 years old, with mild-moderate hypercholesterolemia, to assess lipid profile improvement of the supplementation of rice bran oil 45 ml/days compared to 15 ml/days without changing eating patterns. Results: After 4 weeks of intervention, there was significant difference in total cholesterol level between both groups (p = 0.049. In the group that received 45 ml/days of rice bran oil, total cholesterol level decreased 14%, and in the group of 15 ml/days total cholesterol level decreased 7.8%. The reduction of LDL and triglycerides and the increase of HDL were not significantly different between both groups (p >0,05. There was no significant changes of body weight in both groups. Conclusion: This study showed that consumption of  45 ml/days rice bran oil led to better improvements in lipid profiles compare to 15 ml/days. It has been demonstrated that gamma oryzanol and plant sterols in rice bran oil have the capability to remove cholesterol from bile salt micelles, thus decreasing cholesterol absorption in intestine.

Influence of socio-economic and lifestyle factors on overweight and nutrition-related diseases among Tunisian migrants versus non-migrant Tunisians and French

Directory of Open Access Journals (Sweden)

Delpeuch Francis

2007-09-01

Full Text Available Abstract Background Migrant studies in France revealed that Mediterranean migrant men have lower mortality and morbidity than local-born populations for non-communicable diseases (NCDs. We studied overweight and NCDs among Tunisian migrants compared to the population of the host country and to the population of their country of origin. We also studied the potential influence of socio-economic and lifestyle factors on differential health status. Methods A retrospective cohort study was conducted to compare Tunisian migrant men with two non-migrant male groups: local-born French and Tunisians living in Tunisia, using frequency matching. We performed quota sampling (n = 147 based on age and place of residence. We used embedded logistic regression models to test socio-economic and lifestyle factors as potential mediators for the effect of migration on overweight, hypertension and reported morbidity (hypercholesterolemia, type-2 diabetes, cardiovascular diseases (CVD. Results Migrants were less overweight than French (OR = 0.53 [0.33–0.84] and had less diabetes and CVD than Tunisians (0.18 [0.06–0.54] and 0.25 [0.07–0.88]. Prevalence of hypertension (grade-1 and -2 and prevalence of hypercholesterolemia were significantly lower among migrants than among French (respectively 0.06 [0.03–0.14]; 0.04 [0.01–0.15]; 0.11 [0.04–0.34] and Tunisians (respectively OR = 0.07 [0.03–0.18]; OR = 0.06 [0.02–0.20]; OR = 0.23 [0.08–0.63]. The effect of migration on overweight was mediated by alcohol consumption. Healthcare utilisation, smoking and physical activity were mediators for the effect of migration on diabetes. The effect of migration on CVD was mediated by healthcare utilisation and energy intake. No obvious mediating effect was found for hypertension and hypercholesterolemia. Conclusion Our study clearly shows that lifestyle (smoking and cultural background (alcohol are involved in the observed protective effect of migration.

[Acute myocardial infarction in Djibouti: 2-year prospective study].

Science.gov (United States)

Maurin, O; Massoure, P L; de Regloix, S; Topin, F; Sbardella, F; Lamblin, G; Kaiser, E

2012-01-01

Acute myocardial infarction (AMI) is a life-threatening emergency. In Africa, the increasing prevalence of cardiovascular risk factors is leading to an epidemiological transition. No data have yet been reported about AMI in Djibouti. This study prospectively included all patients with acute coronary syndrome and persistent ST segment elevation admitted to the emergency department of Bouffard Military Hospital in Djibouti from January 2009 through December 2010. It analyzed their clinical data and management. The study included 35 patients. Their mean age was 52 ± 11 years [range: 29-76]. The sex ratio was 7.7 (men/women). Cardiovascular risk factors were: hypercholesterolemia (83%), tobacco use (60%), khat chewing (57%), diabetes (49%), hypertension (46%), and heredity (20%). AMI was anterior in 40% of cases. Fifteen patients (43%) arrived within 12 hours after the onset of symptoms (average 5 hours); thrombolysis was successful for 11 of them (73%). Seven patients (20%) died over the entire follow-up (11.3 ± 9 months), 5 within the first month. Mortality was significantly associated with diabetes (pDjibouti are 10 to 15 years younger than in Western countries. Their high level of cardiovascular risk is remarkable. Khat use did not significantly affect prognosis. The high mortality rate was similar to rates reported before the percutaneous coronary angioplasty era.

[Prevalence of cardiovascular risk factors in urban and rural communities in the Wilaya of Tlemcen (Algeria): A comparative study].

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Boukli Hacène, L; Khelil, M-A; Chabane Sari, D; Meguenni, K; Meziane Tani, A

2017-08-01

In Algeria, few studies have been conducted to determine the prevalence of genetic and environmental risk factors of cardiovascular diseases as a function of residence. The objective of this study was therefore to determine the prevalence of cardiovascular risk factors according to sex and age in urban and rural communities in the Wilaya of Tlemcen (Algeria). A population survey was conducted on a representative sample of 864 individuals aged 20years and over, among inhabitants in urban and rural communes in the Wilaya of Tlemcen. Each subject answered the questionnaire on cardiovascular risk factors, underwent a physical examination and had a blood sample drawn. The prevalence of hypercholesterolemia was 6.6%, it was found to be higher in urban areas (8.4%) than in rural areas (4.6%). The prevalence of low HDL cholesterol levels was higher in urban (28.8%) than rural (23.9%) areas. The prevalence of family history of cardiovascular disease did not differ between the two sexes and between urban (15.7%) and rural (14.0%) areas. The prevalence of hypertension was higher in urban (28.0%) than in rural (16.8%) areas, and was highest among women aged 65 years or older in urban areas (67.3%) and in rural areas (66.6%). The prevalence of diabetes was higher among women living in urban areas (21.4%) compared with rural areas (15.4%). Obesity was much more frequent among women than among men in urban areas (24.7% in women and 9.5% in men) and in rural areas (28.3% in women and 8.3% in men). The prevalence of smoking was 45.8% for men and with no significant variations between urban areas and rural areas. The prevalence of cardiovascular risk factors according to sex and age in the two communes are high in two communes in the Wilaya of Tlemcen. However, the prevalence of hypertension, hypercholesterolemia and diabetes were higher in women in urban than in rural areas. This finding focuses attention on the need for measures to reduce the prevalence of these cardiovascular

Polymorphism in Apoprotein-C III gene and coronary heart disease

International Nuclear Information System (INIS)

Hussain, Syed S.; Buraiki, J.; Dzimiri, N.; Butt, Abdul Isalm; Vencer, L.; Basco, M.C.; Khan, B.

1999-01-01

The aim of this study was to look into the association, if any, apoprotein-CIII variant allele with hypertriglyceridemia, hypercholesterolemia and coronary heart disease (CHD). The prevalence of a C to G substitution in the 3 untranslated regions of apoprotein-CIII was studied in a sample of 92 angiographed Saudi subjects, consisting of 65 males and 27 females. The subjects were genotyped by amplification followed by digestion of the gene fragment containing the polymorphic site with Sac I restriction enzyme. The variant allele of apoprotein-CIII was found to be associated neither with hypertriglyceridemia nor with hypercholesterolemia. However, a significant association of this allele (P<0.01) was found with coronary heart disease, independent of other risk factors such as smoking, diabetes and hypertension. An estimation of odds ratio using logistic regression with various risk factors in the model showed that the individuals with this rare allele were 3.4 times more at risk of developing coronary disease. This estimation of risk held even after analyzing a subset of individuals above 45 years of age. While the association between apoprotein-CIII variant allele and dyslipidemia could not be established in this study, the relationship between this marker and CHD was highlighted in the studied subjects. (author)

Polymorphism in Apoprotein-C III gene and coronary heart disease

Energy Technology Data Exchange (ETDEWEB)

Hussain, Syed S; Buraiki, J; Dzimiri, N; Butt, Abdul Isalm; Vencer, L; Basco, M C; Khan, B [Dept. of Biological and Medical Research, Cardiovascular diseases and Biomedical Statistics and Scientific Computing, King Faisal Specialist Hospital and Research Centre, Riyadh (Saudi Arabia)

1999-07-01

The aim of this study was to look into the association, if any, apoprotein-CIII variant allele with hypertriglyceridemia, hypercholesterolemia and coronary heart disease (CHD). The prevalence of a C to G substitution in the 3 untranslated regions of apoprotein-CIII was studied in a sample of 92 angiographed Saudi subjects, consisting of 65 males and 27 females. The subjects were genotyped by amplification followed by digestion of the gene fragment containing the polymorphic site with Sac I restriction enzyme. The variant allele of apoprotein-CIII was found to be associated neither with hypertriglyceridemia nor with hypercholesterolemia. However, a significant association of this allele (P<0.01) was found with coronary heart disease, independent of other risk factors such as smoking, diabetes and hypertension. An estimation of odds ratio using logistic regression with various risk factors in the model showed that the individuals with this rare allele were 3.4 times more at risk of developing coronary disease. This estimation of risk held even after analyzing a subset of individuals above 45 years of age. While the association between apoprotein-CIII variant allele and dyslipidemia could not be established in this study, the relationship between this marker and CHD was highlighted in the studied subjects. (author)

Risk communication between general practitioners and patients with hypercholesterolemia

DEFF Research Database (Denmark)

Hansen, Bo; Kirkegaard, Pia; Lauritzen, Torsten

  Purpose: It is important that the general practitioners (GPs) are able to intervene to reduce risk of disease. One of the key points in doing so is effective risk communication that decreases uncertainty about choice of treatment and gives the patients a greater understanding of benefits......, and psychological well-being.    Methods: 40 GPs receive training in risk communication. Each GP selects 7 patients with elevated cholesterol. These patients are informed about the opportunity to receive preventive pharmacological treatment. Another 280 patients receive the same opportunity from 40 GPs without...... their psychological well-being.   Conclusion: This randomised intervention study will produce new knowledge about the effect of training GPs in risk communication....

H2O2 Treatment of HUVECs Facilitates PKC Mediated Thr495 Phosphorylation on eNOS when Pre-treated with High Glucose Levels

DEFF Research Database (Denmark)

Guterbaum, Thomas J; Braunstein, Thomas H; Fossum, Anna

2015-01-01

Objective: Metabolic syndrome entails hypertension, hyperglycemia, obesity and hypercholesterolemia. This syndrome increases the risk of cardiovascular disease and diabetes. Hyperglycemia during coronary reperfusion is associated with a poor prognosis. Contrastingly, targeting correction of hyper......Objective: Metabolic syndrome entails hypertension, hyperglycemia, obesity and hypercholesterolemia. This syndrome increases the risk of cardiovascular disease and diabetes. Hyperglycemia during coronary reperfusion is associated with a poor prognosis. Contrastingly, targeting correction....... The presence of reactive oxygen species (ROS) in both mitochondria and cytoplasm was measured by fluorescence activated cell sorting (FACS). Phosphorylation of endothelial nitric oxide synthase (eNOS) on threonine 495 (Thr495) and serine 1177 (Ser1177) was assessed by western blotting. Short-term (20 hours...

Prevention of Alzheimer disease: The roles of nutrition and primary care.

Science.gov (United States)

Bane, Tabitha J; Cole, Connie

2015-05-15

Risk factors for developing Alzheimer disease include hypercholesterolemia, hypertension, obesity, and diabetes. Due to lack of effective treatments for Alzheimer disease, nutrition and primary prevention becomes important.

High blood cholesterol levels

Science.gov (United States)

Cholesterol - high; Lipid disorders; Hyperlipoproteinemia; Hyperlipidemia; Dyslipidemia; Hypercholesterolemia ... There are many types of cholesterol. The ones talked about most are: ... lipoprotein (HDL) cholesterol -- often called "good" cholesterol ...

Protective effects of Morus alba leaves extract on ocular functions of pups from diabetic and hypercholesterolemic mother rats.

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El-Sayyad, H I H; El-Sherbiny, M A; Sobh, M A; Abou-El-Naga, A M; Ibrahim, M A N; Mousa, S A

2011-01-01

Phytotherapy is frequently considered to be less toxic and free from side effects than synthetic drugs. Hence, the present study was designed to investigate the protective use of crude water extract of Morus alba leaves on ocular functions including cataractogenesis, biochemical diabetic and hypercholesterolemic markers, retinal neurotransmitters and retinopathy of rat pups maternally subjected to either diabetes and/or hypercholesterolemia. Application of crude water extract of Morus alba resulted in amelioration of the alterations of maternal serum glucose, LDL, HDL, total cholesterol and creatine phosphokinase activity as well as retinal neurotransmitters including acetylcholine (ACE), adrenaline (AD), nor-adrenaline (NAD), serotonin (5-HT), histamine (HS), dopamine (DA) and gamma amino butyric acid (GABA). The retina of pups of either diabetic and/or hypercholesterolemia mothers exhibited massive alterations of retinal neurotransmitters. The alterations of retinal neurotransmitters were correlated with the observed pathological alterations of retinal pigmented epithelium, photoreceptor inner segment and ganglion cells and increased incidence of DNA fragmentation and apoptosis cell death. However, protection with Morus alba extract led to amelioration of the pathological alterations of retinal neurons and estimated neurotransmitters. Furthermore, a striking incidence of cataract was detected in pups of either diabetic and/or hypercholesterolemic mothers. Highest cataractogenesis was observed in pups of combined -treated groups. Our data indicate that experimental maternal diabetes alone or in combination with hypercholesterolemia led to alteration in the ocular structures of their pups, with an increasing incidence of cataract and retinopathy, and the effects of the extract might be attributed to the hypoglycaemic, antihypercholesterolemic and anti-oxidative potential of flavonoids, the major components of the plant extract.

APOE and CETP TaqIB polymorphisms influence metabolic responses to Hibiscus sabdariffa L. and Gynostemma pentaphyllum Makino tea consumption in hypercholesterolemic subjects.

Science.gov (United States)

Jeenduang, Nutjaree; Sangkaew, Boonnisa; Chantaracha, Pacharee; Chanchareonsri, Sirada; Plyduang, Thunyaluk; Thitdee, Wanida; Samae, Cathaleeya; Pitumanon, Wacharaporn

2017-03-01

Hibiscus sabdariffa L. (HS) and Gynostemma pentaphyllum Makino (GP) have been used as traditional medicines to treat diabetes and hypercholesterolemia. Nevertheless, there is interindividual variation in the metabolic responses to HS and GP consumption. This may be due to genetic factors. The aim of this study was to investigate the effects of HS and GP tea consumption on anthropometric data, fasting blood glucose (FBG), and lipid concentrations in hypercholesterolemia subjects with different genotypes of the APOE and CETP TaqIB polymorphisms. Forty-eight subjects with hypercholesterolemia were given either HS or GP tea for 30 days. Anthropometric and biochemical variables were determined, and APOE and CETP TaqIB polymorphisms were analyzed using the polymerase chain reaction- restriction fragment length polymorphism (PCR-RFLP). E4 (p=0.008) and homozygous B1B1 (p=0.010) carriers had significantly decreased HDL-C concentrations after HS consumption; in addition, B2 carriers who consumed HS showed significantly decreased triglyceride (TG) concentrations (p=0.039). Regarding GP consumption, non-E4 carriers had significantly decreased HDL-C (p=0.009) and FBG (p=0.042) concentrations. Furthermore, B2 carriers had significantly decreased total cholesterol (TC) (p=0.045), HDL-C (p=0.004), and FBG (p=0.026) concentrations. HS consumption may have beneficial effects with respect to TG concentrations in the B2 carriers, but it may adversely affect HDL-C concentrations in homozygous B1B1 and E4 carriers. In contrast, GP consumption may have favorable effects on TC and FBG concentrations but not on HDL-C concentrations for B2 and/or non-E4 carriers.

The role of diabetes mellitus in the clinical presentation and prognosis of Bell palsy.

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Riga, Maria; Kefalidis, George; Danielides, Vasilios

2012-01-01

Bell palsy is considered to be an entrapment neuropathy resulting from inflammation, edema, and strangulation. Diabetes, hypertension, and hypercholesterolemia have all been related to microangiopathies. However, the relationship between the frequency, severity, and recovery course of Bell palsy in patients with these pathologies is a matter of controversy. Fifty-six patients with Bell palsy were evaluated according to the House-Brackmann grading system a few days after the onset of the disease and 6 months later and correlated to their hypertension, hypercholesterolemia, and diabetes records. Diabetes was evaluated by the use of serum glycosylated hemoglobin (HbA1c). The 20 patients with abnormal HbA1c values were more frequently diagnosed with Bell palsy of grade V/VI (P = .008; odds ratio, 4.7; 95% CI, 1.4-15.2). However, their House-Brackmann scores were not found to be worse at the 6-month follow-up visit (P = .9). No correlations were found for hypertension and hypercholesterolemia. A relationship between the severity of Bell palsy and abnormal HbA1c values seems to be demonstrated. However, the prognosis of these patients does not seem to be worse because at the 6-month follow-up visit they present similar scores to nondiabetic patients.

Cardiovascular risk in minority and underserved women in Appalachian Tennessee: a descriptive study.

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Pearson, Tamera Lea

2010-04-01

The purposes of this study were to translate current knowledge regarding cardiovascular risk factors, screening, and prevention to a disparate population of women and to ascertain the cardiovascular health status and risk factors in a sample of minority and underserved Appalachian women. Demographic data were collected from a voluntary sample of women from a disparate population living in Appalachian Tennessee. A coronary risk profile recorded family health history, personal health history, and lifestyle habits affecting risk for cardiovascular disease. Physiologic measurements included body mass index, blood pressure, fasting glucose, cholesterol levels, ankle brachial index, and carotid artery stenosis. Women in Appalachia Tennessee from a disparate population have high risks for heart disease and stroke. This is a critical time to address any modifiable risk factors and aggressively treat underlying cardiovascular diseases such as hypertension and hypercholesterolemia. Nurse practitioners (NPs) often provide primary care to women who may not be aware of their cardiovascular risks or actual disease. NPs can ensure that their practice incorporates primary and secondary cardiovascular prevention through screening, individual health education, and aggressive evidence-based treatment plans for women.

Maximal thickness of the normal human pericardium assessed by electron-beam computed tomography

International Nuclear Information System (INIS)

Delille, J.P.; Hernigou, A.; Sene, V.; Chatellier, G.; Boudeville, J.C.; Challande, P.; Plainfosse, M.C.

1999-01-01

The purpose of this study was to determine the maximal value of normal pericardial thickness with an electron-beam computed tomography unit allowing fast scan times of 100 ms to reduce cardiac motion artifacts. Electron-beam computed tomography was performed in 260 patients with hypercholesterolemia and/or hypertension, as these pathologies have no effect on pericardial thickness. The pixel size was 0.5 mm. Measurements could be performed in front of the right ventricle, the right atrioventricular groove, the right atrium, the left ventricle, and the interventricular groove. Maximal thickness of normal pericardium was defined at the 95th percentile. Inter-observer and intra-observer reproducibility studies were assessed from additional CT scans by the Bland and Altman method [24]. The maximal thickness of the normal pericardium was 2 mm for 95 % of cases. For the reproducibility studies, there was no significant relationship between the inter-observer and intra-observer measurements, but all pericardial thickness measurements were ≤ 1.6 mm. Using electron-beam computed tomography, which assists in decreasing substantially cardiac motion artifacts, the threshold of detection of thickened pericardium is statistically established as being 2 mm for 95 % of the patients with hypercholesterolemia and/or hypertension. However, the spatial resolution available prevents a reproducible measure of the real thickness of thin pericardium. (orig.)

Dietary nitrate improves vascular function in patients with hypercholesterolemia: a randomized, double-blind, placebo-controlled study123

Science.gov (United States)

Velmurugan, Shanti; Gan, Jasmine Ming; Rathod, Krishnaraj S; Khambata, Rayomand S; Ghosh, Suborno M; Hartley, Amy; Van Eijl, Sven; Sagi-Kiss, Virag; Chowdhury, Tahseen A; Curtis, Mike; Kuhnle, Gunter GC; Wade, William G; Ahluwalia, Amrita

2016-01-01

Background: The beneficial cardiovascular effects of vegetables may be underpinned by their high inorganic nitrate content. Objective: We sought to examine the effects of a 6-wk once-daily intake of dietary nitrate (nitrate-rich beetroot juice) compared with placebo intake (nitrate-depleted beetroot juice) on vascular and platelet function in untreated hypercholesterolemics. Design: A total of 69 subjects were recruited in this randomized, double-blind, placebo-controlled parallel study. The primary endpoint was the change in vascular function determined with the use of ultrasound flow-mediated dilatation (FMD). Results: Baseline characteristics were similar between the groups, with primary outcome data available for 67 patients. Dietary nitrate resulted in an absolute increase in the FMD response of 1.1% (an ∼24% improvement from baseline) with a worsening of 0.3% in the placebo group (P nitrate group, showing a trend (P = 0.06) to improvement in comparison with the placebo group. Dietary nitrate also caused a small but significant reduction (7.6%) in platelet-monocyte aggregates compared with an increase of 10.1% in the placebo group (P = 0.004), with statistically significant reductions in stimulated (ex vivo) P-selectin expression compared with the placebo group (P nitrate were detected. The composition of the salivary microbiome was altered after the nitrate treatment but not after the placebo treatment (P nitrate treatment; of those taxa present, 2 taxa were responsible for >1% of this change, with the proportions of Rothia mucilaginosa trending to increase and Neisseria flavescens (P nitrate treatment relative to after placebo treatment. Conclusions: Sustained dietary nitrate ingestion improves vascular function in hypercholesterolemic patients. These changes are associated with alterations in the oral microbiome and, in particular, nitrate-reducing genera. Our findings provide additional support for the assessment of the potential of dietary nitrate as a

Avascular necrosis of the femoral head in HIV infected patients

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Marcos Almeida Matos

Full Text Available Avascular necrosis (AVN of the femoral head is an emerging complication in HIV infected patients. It has been suggested that the increased incidence of AVN in this population may be caused by an increased prevalence of predisposing factors for osteonecrosis, including protease inhibitors, hyperlipidemia, corticosteroid use, alcohol and intravenous drug abuse. The aim of this study was to assess the risk factors for avascular necrosis developing in the femoral head of HIV infected individuals. This study consisted of meta-analysis of the secondary data extracted from current literature. The selected articles allowed two study groups to be drawn up for comparison. Group 1 comprised 324 individuals infected by the HIV virus, who did not present femoral head AVN. Group 2 comprised 32 HIV positive patients, who presented femoral head AVN. The parameters used for analysis were as follows: age, gender, sexual preference, use of intravenous drugs, time of diagnosis, CD4+ cell count, use of antiretroviral agents and duration, serum cholesterol and serum triglycerides. The present study found a statistically significant association between hypertriglyceridemia, hypercholesterolemia, sexual preference and intravenous drug abuse. The authors concluded that femoral head osteonecrosis is associated with hyperlipidemia (hypercholesterolemia and hypertriglyceridemia and intravenous drug abuse. This study supports the hypothesis that protease inhibitors play a role in the development of osteonecrosis through a tendency to cause hyperlipidemia.

Prevalence of Canine Obesity, Obesity-Related Metabolic Dysfunction, and Relationship with Owner Obesity in an Obesogenic Region of Spain

OpenAIRE

Montoya-Alonso, J. Alberto; Bautista-Casta?o, Inmaculada; Pe?a, Cristina; Su?rez, Lourdes; Juste, M. Candelaria; Tvarijonaviciute, Asta

2017-01-01

The main objective of this study was to evaluate the prevalence of canine obesity and obesity-related metabolic dysfunction (ORMD) in the obesogenic area in Spain. The prevalence of overweight/obesity among owners of obese pets was also evaluated. In the sample population studied (93 client-owned dogs), 40.9% of dogs presented obesity (body condition score 7–9/9), 40.9% of dogs presented hypertension, 20.4% of dogs presented fasting hypertriglyceridemia, 20.4% fasting hypercholesterolemia, an...

Gangguan Peredaran Darah Otak di Indonesia (Faktor-faktor Risiko dan Prevalensi pada Usia Lanjut)

OpenAIRE

Mardjono, Mahar

1993-01-01

Cerebrovascular accidents are mayor causes of death and disability in developed countries and are also increasing in developing countries like Indonesia. It is strongly related to hypertension, diabetes and ischemic heart disease which are prevalent in older age groups. A study of 2092 cases of cerebrovascular accidents in Indonesia in 1980 revealed that the most frequent risk factors were hypertension (68.5%), diabetes (20%), obesity (15%), hypercholesterolemia (13%), and hyperuricemia (7%)....

Echocardiographic evaluation of the arterial stiffness in healthy subjects and hypertensive patients under 60 years

International Nuclear Information System (INIS)

Valiente Mustelier, Juan; Suarez Vazquez, Leisy; Cabrera Rego, Julio Oscar; Gandarilla Sarmientos, Julio Cesar

2011-01-01

We conducted a cross-sectional study that included 83 patients (healthy, n=43; hypertensive, n=40) assisted in the external consultation of the National Cardiology and Cardiovascular Surgery Institute, from April to October, 2009. We included clinical (age, sex, personal antecedents of smoking habit, obesity, hypercholesterolemia, arterial hypertension) and echocardiographic (diastolic function, arterial stiffness index [β], pressure strain elastic modulus [Ep], arterial compliance, local pulse wave velocity [LPWV]) variables

Disease: H01742 [KEGG MEDICUS

Lifescience Database Archive (English)

Full Text Available diabetes, and a family history of early CAD. It has been reported that an autosomal dominant form of CAD is...s are associated with CAD, including hypercholesterolemia, hypertension, obesity,

Prevalence and management of cardiovascular risk factors in Portuguese living in Portugal and Portuguese who migrated to Switzerland.

Science.gov (United States)

Alves, Luís; Azevedo, Ana; Barros, Henrique; Vollenweider, Peter; Waeber, Gérard; Marques-Vidal, Pedro

2015-03-31

Information regarding the health status of migrants compared to subjects who remain in the country of origin is scarce. We compared the levels and management of the main cardiovascular risk factors between Portuguese living in Porto (Portugal) and Portuguese migrants living in Lausanne (Switzerland). Cross-sectional studies conducted in Porto (EPIPorto, 1999 to 2003, n = 1150) and Lausanne (CoLaus, 2003 to 2006, n = 388) among subjects aged 35-65 years. Educational level, medical history and time since migration were collected using structured questionnaires. Body mass index, blood pressure, cholesterol and glucose levels were measured using standardized procedures. Portuguese living in Lausanne were younger, more frequently male and had lower education than Portuguese living in Porto. After multivariate adjustment using Poisson regression, no differences were found between Portuguese living in Porto or in Lausanne: prevalence rate ratio (PRR) and (95% confidence interval) for Portuguese living in Lausanne relative to Portuguese living in Porto: 0.92 (0.71 - 1.18) for current smoking; 0.78 (0.59 - 1.04) for obesity; 0.81 (0.62 - 1.05) for abdominal obesity; 0.82 (0.64 - 1.06) for hypertension; 0.88 (0.75 - 1.04) for hypercholesterolemia and 0.92 (0.49 - 1.73) for diabetes. Treatment and control rates for hypercholesterolemia were higher among Portuguese living in Lausanne: PRR = 1.91 (1.15 - 3.19) and 3.98 (1.59 - 9.99) for treatment and control, respectively. Conversely, no differences were found regarding hypertension treatment and control rates: PRR = 0.98 (0.66 - 1.46) and 0.97 (0.49 - 1.91), respectively, and for treatment rates of diabetes: PRR = 1.51 (0.70 - 3.25). Portuguese living in Lausanne, Switzerland, present a similar cardiovascular risk profile but tend to be better managed regarding hypercholesterolemia than Portuguese living in Porto, Portugal.

[Classical cardiovascular risk factors: predictive value and treatment of the elderly. The rocky road to evidence-based medicine].

Science.gov (United States)

Thomas, H P

2001-04-01

Coronary heart disease and cerebrovascular disease are still the most common causes of death in Western countries. A number of risk factors have been identified in young and middle-aged adults, such as dyslipidemia, hypertension and diabetes. Their prevalence and importance, however, are less clear in the elderly. In terms of dyslipedemia it is questionable whether hypercholesterolemia is a definite risk factor. On the other hand, mortality can be reduced by lowering LDL cholesterol, but the benefit in the oldest old is not yet known. Systolic blood pressure rises with age and is discussed controversely as a potential risk factor in the elderly. Some large trials could show a clear relationship between high blood pressure while others did not see any association. Similar to the treatment of hypercholesterolemia, antihypertensive drugs showed beneficial effects in elderly people until the age of 80. But the treatment of the oldest old cannot be recommended in general. Diabetes and impaired glucose tolerance are some of the most common diseases in elderly people. They are considered to be an important risk factor until the age of 75. Their role in the oldest old is still under debate. Until now, we do not know anything about possible treatment effects because of the lack of controlled trials. Elderly people seem to have a risk profile different from younger people; especially in extreme ages the predictive role of classical risk factors is unclear. On the other hand, drug treatment could reduce mortality and morbidity in patients with hypercholesterolemia or hypertension. There are no studies which investigated the effects of blood glucose control in the elderly. The collection of sufficient data is a geriatric challange in order to decide whether treatment is useful or not.

Central Nervous System Demyelination and Remyelination is Independent from Systemic Cholesterol Level in Theiler's Murine Encephalomyelitis.

Science.gov (United States)

Raddatz, Barbara B; Sun, Wenhui; Brogden, Graham; Sun, Yanyong; Kammeyer, Patricia; Kalkuhl, Arno; Colbatzky, Florian; Deschl, Ulrich; Naim, Hassan Y; Baumgärtner, Wolfgang; Ulrich, Reiner

2016-01-01

High dietary fat and/or cholesterol intake is a risk factor for multiple diseases and has been debated for multiple sclerosis. However, cholesterol biosynthesis is a key pathway during myelination and disturbances are described in demyelinating diseases. To address the possible interaction of dyslipidemia and demyelination, cholesterol biosynthesis gene expression, composition of the body's major lipid repositories and Paigen diet-induced, systemic hypercholesterolemia were examined in Theiler's murine encephalomyelitis (TME) using histology, immunohistochemistry, serum clinical chemistry, microarrays and high-performance thin layer chromatography. TME-virus (TMEV)-infected mice showed progressive loss of motor performance and demyelinating leukomyelitis. Gene expression associated with cholesterol biosynthesis was overall down-regulated in the spinal cord of TMEV-infected animals. Spinal cord levels of galactocerebroside and sphingomyelin were reduced on day 196 post TMEV infection. Paigen diet induced serum hypercholesterolemia and hepatic lipidosis. However, high dietary fat and cholesterol intake led to no significant differences in clinical course, inflammatory response, astrocytosis, and the amount of demyelination and remyelination in the spinal cord of TMEV-infected animals. The results suggest that down-regulation of cholesterol biosynthesis is a transcriptional marker for demyelination, quantitative loss of myelin-specific lipids, but not cholesterol occurs late in chronic demyelination, and serum hypercholesterolemia exhibited no significant effect on TMEV infection. © 2015 International Society of Neuropathology.

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African Journals Online (AJOL)

Dr Olaleye

Hypercholesterolemia is a metabolic derangement that can ... and the presence of other diseases such as diabetes and ... intolerance, obesity, diabetes and metabolic syndromes. (Rothad et ..... contractile function of in situ canine left ventricle.

Psoriasis og aterotrombotisk sygdom

DEFF Research Database (Denmark)

Ahlehoff, Ole; Gislason, Gunnar H; Skov, Lone

2010-01-01

Psoriasis and atherosclerosis share immunoinflammatory mechanisms and patients with psoriasis may carry an excess of cardiovascular risk factors (hypercholesterolemia, hypertension, obesity, metabolic syndrome, diabetes mellitus, smoking etc.) and increased risk of atherothrombotic disease...

Clinical effectiveness of garlic (Allium sativum).

Science.gov (United States)

Pittler, Max H; Ernst, Edzard

2007-11-01

The objective of this review is to update and assess the clinical evidence based on rigorous trials of the effectiveness of garlic (A. sativum). Systematic searches were carried out in Medline, Embase, Amed, the Cochrane Database of Systematic Reviews, Natural Standard, and the Natural Medicines Comprehensive Database (search date December 2006). Our own files, the bibliographies of relevant papers and the contents pages of all issues of the review journal FACT were searched for further studies. No language restrictions were imposed. To be included, trials were required to state that they were randomized and double blind. Systematic reviews and meta-analyses of garlic were included if based on the results of randomized, double-blind trials. The literature searches identified six relevant systematic reviews and meta-analysis and double-blind randomized trials (RCT) that were published subsequently. These relate to cancer, common cold, hypercholesterolemia, hypertension, peripheral arterial disease and pre-eclampsia. The evidence based on rigorous clinical trials of garlic is not convincing. For hypercholesterolemia, the reported effects are small and may therefore not be of clinical relevance. For reducing blood pressure, few studies are available and the reported effects are too small to be clinically meaningful. For all other conditions not enough data are available for clinical recommendations.

Protein-losing enteropathy in systemic lupus erythematosus: 12 years experience from a Chinese academic center.

Science.gov (United States)

Chen, Zhen; Li, Meng-Tao; Xu, Dong; Yang, Hong; Li, Jing; Zhao, Jiu-Liang; Zhang, Heng-Hui; Han, Shao-Mei; Xu, Tao; Zeng, Xiao-Feng

2014-01-01

Protein-losing enteropathy (PLE) is a complication in some systemic lupus erythematosus (SLE) patients that is often misdiagnosed. With this study, we provide insight into clinical characteristics, laboratory characteristics, diagnostic tests, risk factors, treatment, and prognosis of the disease. A retrospective, case-control study was performed in 44 patients with SLE-related PLE (PLE group) and 88 patients with active SLE (control group) admitted to our care from January 2000-January 2012. Risk factors for SLE-related PLE were examined, and we analyzed the accuracy of single and combined laboratory characteristics in discriminating SLE-related PLE from active SLE. Serum albumin and C3 levels were measured as outcome during and after treatment with corticosteroids and immunosuppressive agents. The PLE group had lower mean serum albumin and 24-hour urine protein levels, higher mean total plasma cholesterol levels, and greater frequencies of anti-SSA and SSB seropositivity compared with the control group. Anti-SSA seropositivity, hypoalbuminemia, and hypercholesterolemia were independent risk factors for SLE-related PLE. The simultaneous presence of serum albumin (PLE. SLE-related PLE should be considered when an SLE patient presents with generalized edema, anti-SSA antibody seropositivity, hypercholesterolemia, severe hypoalbuminemia, and low 24-hour urine protein levels. Aggressive treatment for lupus might improve prognosis.

[Dyslipidemias in school-age chilean children: prevalence and associated factors].

Science.gov (United States)

Barja Yáñez, Salesa; Arnaiz Gómez, Pilar; Villarroel Del Pino, Luis; Domínguez de Landa, Angélica; Castillo Valenzuela, Oscar; Farías Jofré, Marcelo; Mardones Santander, Francisco

2015-05-01

Dyslipidemias are a key cardiovascular risk factor, and are increased since early childhood. The objective of this study was to describe the prevalence, characteristics of dyslipidemias and associated factors in a population of Chilean children. Cross-sectional study done in school-age children from Santiago, Chile (2009-2011). Parents answered questions about family medical history and children answered questions about physical activity. Anthropometry was performed and in a blood sample (12 hours fast) lipid profile, glycemia and insulinemia were measured. We recruited 2900 euglycemic children, 11.4 ± 0.97 years old, 52% girls. According to BMI, 22.5% were overweight and 15,3% had obesity. Considering recommended cut-off points for lipids, 69.3% were in acceptable range, 19.2% at risk and 11.5% at high cardiovascular risk. In total, 32% of the population had any clinical form of dyslipidemia: Isolated hypertriglyceridemia (9.4%), low HDL-C (7.6%), isolated hypercholesterolemia (4.9%), atherogenic dyslipidemia (6.24%) and mixed dyslipidemia (3.9%). Except for isolated hypercholesterolemia, dyslipidemias were more frequent in girls (globally 36.2% vs. 27.4%, pdyslipidemia, and the principal determinant was weight excess. Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.

Lentinus edodes promotes fat removal in hypercholesterolemic mice.

Science.gov (United States)

Yang, Hyun; Hwang, Inho; Kim, Sun; Hong, Eui-Ju; Jeung, Eui-Bae

2013-12-01

Lentinus (L.) edodes (shiitake mushroom) is used as a traditional medicine in Asia. One of the components of L. edodes , eritadenine (an adenosine analog alkaloid), has been shown to reduce cholesterol levels. The hypocholesterolemic action of eritadenine appears to be achieved through the modification of hepatic phospholipid metabolism. In the present study, the effects of L. edodes in a mouse model of hypercholesterolemia were investigated. Hypercholesterolemia was induced by the consumption of a high-fat diet (HFD). The animals were divided into six groups, which were fed a normal diet, HFD alone, HFD containing eritadenine [10 mg/kg of body weight (BW)] or HFD with 5, 10 or 20% L. edodes , respectively, for 4 weeks (from 5 to 9 weeks of age). The mice in the six groups had similar BW gains. Total serum cholesterol (T-CHO), low-density lipoprotein (LDL) and triglyceride (TG) levels were increased in the HFD-fed group compared with those in the normal diet group. However, the levels of high-density lipoprotein (HDL) were not significantly altered. In mice treated with L. edodes (5, 10 or 20%), the T-CHO, LDL and TG serum levels were reduced in a dose-dependent manner. The mRNA expression of cholesterol 7-α-hydroxylase 1 (CYP7A1) was decreased in hypercholesterolemic mice and increased by eritadenine and L. edodes (5, 10 and 20%) supplementation. In liver tissues, it was observed that lipid accumulation was reduced by treatment with eritadenine and L. edodes . In addition, it was revealed that the formation of atherosclerotic plaques due to the HFD was also suppressed by eritadenine and L. edodes . The results of the study indicated that the consumption of an HFD may inhibit CYP7A1 expression in the liver by increasing serum T-CHO, LDL and TG levels. L. edodes may help regulate lipid metabolism, suggesting that this fungus ameliorates hypercholesterolemia in mice by regulating CYP7A1 expression in the liver.

Resveratrol Protects and Restores Endothelium-Dependent Relaxation in Hypercholesterolemic Rabbit Corpus Cavernosum.

Science.gov (United States)

Murat, Nergiz; Korhan, Peyda; Kizer, Onur; Evcim, Sinem; Kefi, Aykut; Demir, Ömer; Gidener, Sedef; Atabey, Neşe; Esen, Ahmet Adil

2016-01-01

Oxidative stress dependent-decrease in nitric oxide (NO) bioavailability plays an integral role in hypercholesterolemia-induced erectile dysfunction (ED). Resveratrol has been demonstrated to exert beneficial effects against oxidative stress and improve NO bioavailability. The protective and restorative potentials of resveratrol on endothelium-dependent relaxations were evaluated in hypercholesterolemic rabbit corpus cavernosum (CC). Hypercholesterolemia was induced by administering 2% cholesterol diet (CD) (w/w) to the rabbits for 6 weeks. Two different protocols were applied to test the effects of resveratrol on hypercholesterolemia-induced ED. In Protocol-1 (P1), resveratrol was administrated to the rabbits simultaneously with CD in order to evaluate the protective effect, and for Protocol-2 (P2), resveratrol was administrated for 6 weeks after termination of CD in order to evaluate the restorative effect. Endothelium-dependent relaxations of CC were evaluated by using organ bath studies. In order to elucidate the possible molecular mechanisms, we measured endothelial NO synthase (eNOS) and phosphovasodilator-stimulated phosphoprotein (VASP) expressions and activations, NADPH oxidase, superoxide dismutase (SOD), and catalase (CAT) and glutathione peroxidase (GPx) activity in cavernosal tissues obtained at the end of the study. Resveratrol showed an improvement in the endothelium-dependent relaxation responses in vitro. We demonstrated significantly increased activatory-phosphorylation (p[S1177]-eNOS) and activated phosphovasodilator-stimulated phosphoprotein (phospho-VASP) levels, but reduced phosphorylation (p[T495]-eNOS) of eNOS and NADPH oxidase activity in the resveratrol-administered HC animals compared with hypercholesterolemic control rabbits in the P1. In the P2, resveratrol exhibited an improvement in endothelium-dependent relaxation responses and more pronounced effects on eNOS activation. Resveratrol administration, either simultaneously with HC diet

Eflucimibe. Pierre Fabre/Eli Lilly.

Science.gov (United States)

Burnett, John R

2003-03-01

Eflucimibe is an acyl coenzyme A:cholesterol acyltransferase inhibitor under development by Pierre Fabre SA and Eli Lilly & Co for the potential treatment of hypercholesterolemia and atherosclerosis. Phase II clinical trials commenced during 2002.

Rhabdomyolysis and Acute Kidney Injury Associated with Hypothyroidism and Statin Therapy

Directory of Open Access Journals (Sweden)

Pyoung Ahn

2013-12-01

Full Text Available Rhabdomyolysis is a syndrome involving the breakdown of skeletal muscle that causes myoglobin and other intracellular proteins to leak into the circulatory system, resulting in organ injury including acute kidney injury. We report a case of statin-induced rhabdomyolysis and acute kidney injury that developed in a 63-year-old woman with previously undiagnosed hypothyroidism. Untreated hypothyroidism may have caused her hypercholesterolemia requiring statin treatment, and it is postulated that statin-induced muscle injury was aggravated by hypothyroidism resulting in her full-blown rhabdomyolysis. Although this patient was successfully treated with continuous venovenous hemofiltration and L-thyroxin replacement, rhabdomyolysis with acute kidney injury is a potentially life-threatening disorder. Physicians must pay special attention to the possible presence of subclinical hypothyroidism when administering statins in patients with hypercholesterolemia.

Nutritional habits & cardiovascular disease

OpenAIRE

Sampaio, Hélia; Capitão, Sandra; Ferro-Lebres, Vera

2010-01-01

An elevated predominance of the risk factors associated to the illnesses of the circulatory system, particurily hypercholesterolemia and arterial hypertension aim for a special attention to its prevention. This way, the composition of the digested food daily can influence the sprouting of Cardiovascular Disease (CVD), which has shown association between the risk factors and the things we consume. The present study had an objective to identify the influential factors of social economics...

Drug: D10557 [KEGG MEDICUS

Lifescience Database Archive (English)

Full Text Available de: C10AX13 Homozygous familial hypercholesterolemia [DS:H00155 H01383] ... Monoclonal antibody PCSK9 [HSA:255738] [KO:K13050] ... CAS: 1256937-27-5 1420806-15-0 PubChem: 254741519 ...

Dietary pattern classifications with nutrient intake and health-risk factors in Korean men.

Science.gov (United States)

Lee, Ji Eun; Kim, Jung-Hyun; Son, Say Jin; Ahn, Younjhin; Lee, Juyoung; Park, Chan; Lee, Lilha; Erickson, Kent L; Jung, In-Kyung

2011-01-01

This study was performed to identify dietary patterns in Korean men and to determine the associations among dietary patterns, nutrient intake, and health-risk factors. Using baseline data from the Korean Health and Genome Study, dietary patterns were identified using factor analysis of data from a validated food-frequency questionnaire, and associations between these dietary patterns and health-risk factors were analyzed. Three dietary patterns were identified: 1) the "animal-food" pattern (greater intake of meats, fish, and dairy products), 2) the "rice-vegetable" pattern (greater intake of rice, tofu, kimchi, soybean paste, vegetables, and seaweed), and 3) the "noodle-bread" pattern (greater intake of instant noodles, Chinese noodles, and bread). The animal-food pattern (preferred by younger people with higher income and education levels) had a positive correlation with obesity and hypercholesterolemia, whereas the rice-vegetable pattern (preferred by older people with lower income and educational levels) was positively associated with hypertension. The noodle-bread pattern (also preferred by younger people with higher income and education levels) had a positive association with abdominal obesity and hypercholesterolemia. This study identifies three unique dietary patterns in Korean men, which are independently associated with certain health-risk factors. The rice-vegetable dietary pattern, modified for a low sodium intake, might be a healthy dietary pattern for Korean men. Copyright © 2011 Elsevier Inc. All rights reserved.

Maximal thickness of the normal human pericardium assessed by electron-beam computed tomography

Energy Technology Data Exchange (ETDEWEB)

Delille, J.P.; Hernigou, A.; Sene, V.; Chatellier, G.; Boudeville, J.C.; Challande, P.; Plainfosse, M.C. [Service de Radiologie Centrale, Hopital Broussais, Paris (France)

1999-08-01

The purpose of this study was to determine the maximal value of normal pericardial thickness with an electron-beam computed tomography unit allowing fast scan times of 100 ms to reduce cardiac motion artifacts. Electron-beam computed tomography was performed in 260 patients with hypercholesterolemia and/or hypertension, as these pathologies have no effect on pericardial thickness. The pixel size was 0.5 mm. Measurements could be performed in front of the right ventricle, the right atrioventricular groove, the right atrium, the left ventricle, and the interventricular groove. Maximal thickness of normal pericardium was defined at the 95th percentile. Inter-observer and intra-observer reproducibility studies were assessed from additional CT scans by the Bland and Altman method [24]. The maximal thickness of the normal pericardium was 2 mm for 95 % of cases. For the reproducibility studies, there was no significant relationship between the inter-observer and intra-observer measurements, but all pericardial thickness measurements were {<=} 1.6 mm. Using electron-beam computed tomography, which assists in decreasing substantially cardiac motion artifacts, the threshold of detection of thickened pericardium is statistically established as being 2 mm for 95 % of the patients with hypercholesterolemia and/or hypertension. However, the spatial resolution available prevents a reproducible measure of the real thickness of thin pericardium. (orig.) With 6 figs., 1 tab., 31 refs.

Atherosclerotic plaque volume and composition in symptomatic carotid arteries assessed with multidetector CT angiography; relationship with severity of stenosis and cardiovascular risk factors

International Nuclear Information System (INIS)

Rozie, S.; Weert, T.T. de; Monye, C. de; Homburg, P.J.; Tanghe, H.L.J.; Lugt, A. van der; Dippel, D.W.J.

2009-01-01

The purpose of this study was to examine the volume and the composition of atherosclerotic plaque in symptomatic carotid arteries and to investigate the relationship between these plaque features and the severity of stenosis and the presence of cardiovascular risk factors. One hundred patients with cerebrovascular symptoms underwent CT angiography. We measured plaque volume (PV) and the relative contribution of plaque components (calcifications, fibrous tissue, and lipid) in the symptomatic artery. The contribution of different components was measured as the number of voxels within defined ranges of HU values (calcification >130 HU, fibrous tissue 60-130 HU, lipid core <60 HU). Fifty-seven patients had atherosclerotic plaque in the symptomatic carotid artery. The severity of stenosis and PV were moderately correlated. Age and smoking were independently related to PV. Patients with hypercholesterolemia had significantly less lipid and more calcium in their plaques than patients without hypercholesterolemia. Other cardiovascular risk factors were not significantly related to PV or plaque composition. Luminal stenosis of the carotid artery partly reflects the amount of atherosclerotic carotid disease. Plaque volume and plaque composition are associated with cardiovascular risk factors. (orig.)

Atherosclerotic plaque volume and composition in symptomatic carotid arteries assessed with multidetector CT angiography; relationship with severity of stenosis and cardiovascular risk factors

Energy Technology Data Exchange (ETDEWEB)

Rozie, S.; Weert, T.T. de; Monye, C. de; Homburg, P.J.; Tanghe, H.L.J.; Lugt, A. van der [Erasmus MC, University Medical Center Rotterdam, Departments of Radiology, Rotterdam (Netherlands); Dippel, D.W.J. [Erasmus MC, University Medical Center Rotterdam, Department of Neurology, PO Box 2040, Rotterdam (Netherlands)

2009-09-15

The purpose of this study was to examine the volume and the composition of atherosclerotic plaque in symptomatic carotid arteries and to investigate the relationship between these plaque features and the severity of stenosis and the presence of cardiovascular risk factors. One hundred patients with cerebrovascular symptoms underwent CT angiography. We measured plaque volume (PV) and the relative contribution of plaque components (calcifications, fibrous tissue, and lipid) in the symptomatic artery. The contribution of different components was measured as the number of voxels within defined ranges of HU values (calcification >130 HU, fibrous tissue 60-130 HU, lipid core <60 HU). Fifty-seven patients had atherosclerotic plaque in the symptomatic carotid artery. The severity of stenosis and PV were moderately correlated. Age and smoking were independently related to PV. Patients with hypercholesterolemia had significantly less lipid and more calcium in their plaques than patients without hypercholesterolemia. Other cardiovascular risk factors were not significantly related to PV or plaque composition. Luminal stenosis of the carotid artery partly reflects the amount of atherosclerotic carotid disease. Plaque volume and plaque composition are associated with cardiovascular risk factors. (orig.)

Population prevalence and control of cardiovascular risk factors: What electronic medical records tell us

Directory of Open Access Journals (Sweden)

Arantxa Catalán-Ramos

2014-01-01

Conclusions: Hypertension was the most prevalent cardiovascular risk factor in the Catalan population attended at primary care centers. About two thirds of individuals with hypertension or DM2 were adequately controlled; hypercholesterolemia control was particularly low.

Journal of Biosciences | Indian Academy of Sciences

Indian Academy of Sciences (India)

HPLC analysis reveals the presence of beta amyloid in the OVX and HCL mice brain. Congo red staining analysis revealed the extent of amyloid deposition in OVX and hypercholesterolemia mice brain. ... Journal of Biosciences | News ...

Olea europaea Linn (Oleaceae) Fruit Pulp Exhibits ...

African Journals Online (AJOL)

such as total cholesterol (TC), triglycerides (TG), high-density lipoprotein (HDL) and low-density ... Keywords: Olea europaea, cholesterol, Hypercholesterolemia, Lipid metabolism, Peroxisome .... ethanol (EtOH) at 1:10 ratio (w/v) for 2 h in a.

Lead induced dyslipidemia: The comparative effects of ascorbate ...

African Journals Online (AJOL)

The blood lipid profiles were determined spectrophotometrically. Lead exposure resulted in significant dyslipidemia (p < 0.05), characterized by 50% hypercholesterolemia and hypertriglyceridemia and 132% hyperphospholipidemia (plasma) while in the red blood cells, hypocholesterolemia and hypophospholipidemia ...

Effect of blood UV-irradiation on the development of alimentary cholesterol atherosclerosis in rabbits (preliminary data)

International Nuclear Information System (INIS)

Chernigovskaya, S.V.; Yanushkene, T.S.

1986-01-01

In-house and literature data on possible effect of autotransfusion of UV-irradiated blood (AUVIB) on the development of hypercholesterolemia in rabbits and degree of ateriosclerotic change manifestation in the aorta of the animals are discussed

Disease: H01635 [KEGG MEDICUS

Lifescience Database Archive (English)

Full Text Available iglyceride (TG), or both, is the most common form of dyslipidemia. Hyperlipidemia...rtriglyceridemia; Mixed dyslipidemia Dyslipidemia is a condition characterized by either an increase or decr... H01635 Hyperlipidemia, including: Hyperlipoproteinemia; Hypercholesterolemia; Hype

Prevalence and correlates of coronary heart disease: first population-based study in Lebanon.

Science.gov (United States)

Zeidan, Rouba Karen; Farah, Rita; Chahine, Mirna N; Asmar, Roland; Hosseini, Hassan; Salameh, Pascale; Pathak, Atul

2016-01-01

Lebanon is experiencing a growing epidemic of coronary heart diseases (CHDs), as most low- and middle-income countries currently are. However, this growth can be attenuated if effective preventive strategies are adopted. To provide the first national population-based prevalence of CHD and to describe the profile of Lebanese adults with prevalent CHD. We carried out a cross-sectional study using a multistage cluster sample across Lebanon. We interviewed residents aged 40 years and older using a questionnaire that captured the presence of CHDs and their risk factors (RFs). Our study showed that 13.4% of the Lebanese population aged ≥40 years suffer from a prevalent CHD. CHD seemed to appear more prematurely than in developed countries, and males seemed to be more subject to CHD than females until a certain age. CHD was associated with older age, male sex, a lower economic situation, hypercholesterolemia, hypertension, having a family history of premature cardiovascular diseases, and suffering from diabetes. However, smoking and waist circumference did not seem to have an independent effect on CHD, but rather an effect mediated by biological RFs. This is the first nationwide endeavor conducted in Lebanon to assess the prevalence of CHD. This study also confirms the relevance of the classic RFs of CHD and their applicability to the Lebanese population, thus allowing for prevention strategies.

Genetics and genomics of cholesterol and polyunsaturated fatty acid metabolism in relation to coronary heart disease risk

NARCIS (Netherlands)

Lu Yingchang (Kevin), Y.

2011-01-01

Background

Coronary heart disease (CHD) continues to be a leading cause of morbidity and mortality among adults worldwide. Deregulated lipid metabolism (dyslipidemia) that manifests as hypercholesterolemia, hypertriglyceridemia, low high-density-lipoprotein (HDL)

Antioxidants: real medicines?

African Journals Online (AJOL)

Repro

MAIN TOPIC. 66 C M E Fe b ru ... been subject to widespread orthodox examination .... min E, vitamin C, β-carotene, and perhaps ... Plasma protein thiols which provide sulphydryl [-SH] groups. • Melatonin ..... hypercholesterolemia. J Am Coll.

Thematic review series: patient-oriented research. What we have learned about VLDL and LDL metabolism from human kinetics studies.

Science.gov (United States)

Parhofer, Klaus G; Barrett, P Hugh R

2006-08-01

Lipoprotein metabolism is the result of a complex network of many individual components. Abnormal lipoprotein concentrations can result from changes in the production, conversion, or catabolism of lipoprotein particles. Studies in hypolipoproteinemia and hyperlipoproteinemia have elucidated the processes that control VLDL secretion as well as VLDL and LDL catabolism. Here, we review the current knowledge regarding apolipoprotein B (apoB) metabolism, focusing on selected clinically relevant conditions. In hypobetalipoproteinemia attributable to truncations in apoB, the rate of secretion is closely linked to the length of apoB. On the other hand, in patients with the metabolic syndrome, it appears that substrate, in the form of free fatty acids, coupled to the state of insulin resistance can induce hypersecretion of VLDL-apoB. Studies in patients with familial hypercholesterolemia, familial defective apoB, and mutant forms of proprotein convertase subtilisin/kexin type 9 show that mutations in the LDL receptor, the ligand for the receptor, or an intracellular chaperone for the receptor are the most important determinants in regulating LDL catabolism. This review also demonstrates the variance of results within similar, or even the same, phenotypic conditions. This underscores the sensitivity of metabolic studies to methodological aspects and thus the importance of the inclusion of adequate controls in studies.

Evaluation of probiotic potential of lactic acid bacteria to reduce in vitro cholesterol

OpenAIRE

Clementina Cueto; Stephania Aragón

2012-01-01

Daily consumption of probiotics reduce levels of serum cholesterol by up to 3%, which is significant to prevent hypercholesterolemia, a risk factor for cardiovascular disease and cause of mortality. The genus Lactobacillus is used in industry as a probiotic and some species reduce serum cholesterol by two mechanisms, the adsorption of cholesterol and the production of the enzyme bile salt hydrolase, which vary according to species. The aim of the study was to assess the ability of probiotic b...

Antiatherogenic Effect of Camellia japonica Fruit Extract in High Fat Diet-Fed Rats

OpenAIRE

Lee, Hyun-Ho; Paudel, Keshav Raj; Jeong, Jieun; Wi, An-Jin; Park, Whoa-Shig; Kim, Dong-Wook; Oak, Min-Ho

2016-01-01

Hypercholesterolemia is a well-known etiological factor for cardiovascular disease and a common symptom of most types of metabolic disorders. Camellia japonica is a traditional garden plant, and its flower and seed have been used as a base oil of traditional cosmetics in East Asia. The present study was carried out to evaluate the effect of C. japonica fruit extracts (CJF) in a high fat diet- (HFD-) induced hypercholesterolemic rat model. CJF was administered orally at three different doses: ...

[The polymetabolic syndrome. The experiences of the DRECE study. Dieta y Riesgo de Enfermedades Cardiovasculares en España].

Science.gov (United States)

Gutiérrez Fuentes, J A

1995-01-01

Different risk factors frequent in NIDDM predispose to suffer an early atherosclerosis. Among these and beside lipidic disorders (hypercholesterolemia, hypertriglyceridemia and low HDL-cholesterol levels), hyperinsulinemia and/or insulin resistance, obesity and arterial hypertension are placed. In Spain, 135,000/year deaths from cardiovascular diseases (42% of total deaths) are produced. To plan a preventive strategy requires the knowledge and previous analysis among the population of the situation with regard to risk factors. In order to know in Spain the actual prevalence of cholesterol and other lipidic fractions and their relationship with different dietetic habits and other cardiovascular risk factors, a study on "Diet and Cardiovascular Risk Diseases in Spain": DRECE, was performed. Remains to be explained in the mediterranean countries the low incidence of coronary morbid/mortality, in spite of a high fat consume and cholesterol levels. In this direction, the role of a few micronutrients and other common elements in our diet, some of them with antioxidant properties, may have as protector agents in the atherosclerotic ischemic heart disease process, acquires interest.

AMERICAN ASSOCIATION OF CLINICAL ENDOCRINOLOGISTS AND AMERICAN COLLEGE OF ENDOCRINOLOGY GUIDELINES FOR MANAGEMENT OF DYSLIPIDEMIA AND PREVENTION OF CARDIOVASCULAR DISEASE - EXECUTIVE SUMMARYComplete Appendix to Guidelines available at http://journals.aace.com.

Science.gov (United States)

Jellinger, Paul S; Handelsman, Yehuda; Rosenblit, Paul D; Bloomgarden, Zachary T; Fonseca, Vivian A; Garber, Alan J; Grunberger, George; Guerin, Chris K; Bell, David S H; Mechanick, Jeffrey I; Pessah-Pollack, Rachel; Wyne, Kathleen; Smith, Donald; Brinton, Eliot A; Fazio, Sergio; Davidson, Michael; Zangeneh, Farhad; Bush, Michael A

2017-04-02

Endocrinology ACS = acute coronary syndrome AHA = American Heart Association ASCVD = atherosclerotic cardiovascular disease ATP = Adult Treatment Panel apo = apolipoprotein BEL = best evidence level CKD = chronic kidney disease CPG = clinical practice guidelines CVA = cerebrovascular accident EL = evidence level FH = familial hypercholesterolemia HDL-C = high-density lipoprotein cholesterol HeFH = heterozygous familial hypercholesterolemia HIV = human immunodeficiency virus HoFH = homozygous familial hypercholesterolemia hsCRP = high-sensitivity C-reactive protein LDL-C = low-density lipoprotein cholesterol Lp-PLA 2 = lipoprotein-associated phospholipase A 2 MESA = Multi-Ethnic Study of Atherosclerosis MetS = metabolic syndrome MI = myocardial infarction NCEP = National Cholesterol Education Program PCOS = polycystic ovary syndrome PCSK9 = proprotein convertase subtilisin/kexin type 9 T1DM = type 1 diabetes mellitus T2DM = type 2 diabetes mellitus TG = triglycerides VLDL-C = very low-density lipoprotein cholesterol.

The spectrum of statin therapy in hyperlipidemic children

NARCIS (Netherlands)

Rodenburg, J.; Vissers, M. N.; Trip, M. D.; Wiegman, A.; Bakker, H. D.; Kastelein, J. J. P.

2004-01-01

The recommended therapy of hypercholesterolemia in children consists of dietary modification and bile acid-binding resins. Unfortunately, the lipid-lowering efficacy of bile acid-binding resins is modest, and moreover, long-term compliance is poor because of side effects. In contrast,

Inhibition of the isoprenoid biosynthesis pathway; detection of intermediates by UPLC-MS/MS

NARCIS (Netherlands)

Henneman, Linda; van Cruchten, Arno G.; Kulik, Willem; Waterham, Hans R.

2011-01-01

The isoprenoid biosynthesis pathway provides the cell with a variety of compounds which are involved in multiple cellular processes. Inhibition of this pathway with statins and bisphosphonates is widely applied in the treatment of hypercholesterolemia and metabolic bone disease, respectively. In

Association of IL-6 and CRP gene polymorphisms with obesity and metabolic disorders in children and adolescents

Directory of Open Access Journals (Sweden)

Pâmela F. Todendi

2015-06-01

Full Text Available Activation of adipose tissue inflammation is associated with obesity caused by lipid accumulation in adipocytes. Through this activation, proinflammatory cytokines, such as Interleukin-6 (IL-6 and C-reactive protein (CRP seem to influence metabolic disorders. The present study evaluated whether polymorphisms in the CRP (rs1205 and IL-6 (rs1800795, rs2069845 genes are associated with the development of metabolic disorders in children and adolescents. A cross-sectional study was performed, consisting of 470 students from the municipality of Santa Cruz do Sul, Brazil, aged 7-17 years. Body mass index (BMI was classified according to overweight and obesity. Genotyping was performed by real-time Polymerase Chain Reaction(PCR. Anthropometric characteristics, biochemical markers, immunological markers and blood pressure were assessed. Descriptive statistics, chi-square and logistic regression were used for the analyses. No association was detected between the rs1800795 polymorphism and the assessed variables. Individuals with the risk genotype in the rs1205 gene were associated with the risk of developing hypercholesterolemia (OR 2.79; CI 1.40, 5.57; p = 0.003. Carriers of the risk genotype in the rs2069845 gene are associated with the risk of developing obesity (OR 3.07; CI 1.08, 8.72; p = 0.03. The polymorphism rs2069845 was associated with obesity and rs1205 was associated with the risk of developing hypercholesterolemia in Brazilian schoolchildren.

Association of Paraoxonase-1 Q192R (rs662 Single Nucleotide Variation with Cardiovascular Risk in Coffee Harvesters of Central Colombia

Directory of Open Access Journals (Sweden)

Fernando Siller-López

2017-01-01

Full Text Available Paraoxonase 1 (PON1, a high-density lipoprotein-associated antioxidant enzyme, hydrolyzes several organophosphate pesticides and oxidized lipids. The PON1 Q192R polymorphism affects the catalytic efficiency and is considered a risk factor for pesticide intoxication and cardiovascular disease (CVD but the association is not consistent between individuals or populations. We aimed to study the association of PON1 Q192R polymorphism with CVD risk in coffee harvesters of central Colombia. Demographics were collected from 205 subjects via standardized questionnaires. Lipid profiles and serum butyrylcholinesterase (BChE were measured by standard procedures. The calculated 10-year atherosclerotic CVD (ASCVD risk was used as the cardiovascular risk estimate. Q192R genotype was determined by real-time PCR. Prevalence of hypertension, hypercholesterolemia, and the 10-year ASCVD risk was 33%, 62%, and 22%, respectively. BChE levels were no indicative of recent pesticide exposure, although a positive correlation was observed with BChE and hypercholesterolemia. The Q192R genotype frequencies were 38% (QQ, 44% (QR, and 18% (RR. We found an association of the 192Q genotype with hypertension. The results of this study signal the importance to evaluate the influence and potential interactions of BChE and PON1 192Q allele with known genetic and environmental factors implicated in the pathogenesis of CVD.

[Prevalence of ischemic cardiopathy risk factors on the island of Lanzarote].

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Rodríguez Pérez, J C; Calonge Ramírez, S; Bichara Antanios, G

1993-06-05

As a fruit of complex interaction of factors, coronary atherosclerosis constitutes the first cause of death in the developed countries. With the aim of studying the risk factors of ischemic cardiopathy in a natural adult population (30-64 years) from Lanzarote (Canary Islands) a representative sample of 600 individuals was studied with participation of 70% being obtained. The prevalences obtained were the following: established arterial hypertension (systolic: 160 mmHg and/or diastolic 95 mmHg) 24%; hypercholesterolemia (cholesterol: 6.5 mmol) 25%; diabetes (basal glucose: 7.8 mmol) 6.1%; hypertriglyceridemia (triglycerides 2.3 mmol) 12%; cholesterol (lipids and high density lipoproteinemia HDL) lower than 0.90 mmol in males 19% and lower than 1.16 mmol in females 36%; male smoking habit 53%; female smoking habit 15%; obesity (Quetelet index: 30) male 19%, females 35%, family history of ischemic cardiopathy (prior to 60 years of age) 14%; use of oral contraceptives in premenopausic females 13%; left ventricular growth in hypertensive individuals 7.4%. The prevalence of cardiovascular risk factors is high for arterial hypertension, diabetes, hypercholesterolemia, male smoking habit and female obesity. These results demonstrate an unfavorable profile for cardiovascular risk in the population of Lanzarote and it is reasonable to assume that this may be due to the great socioeconomic growth which has taken place on the island over the last decade.

Genetics of Dyslipidemia and Ischemic Heart Disease.

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Sharma, Kavita; Baliga, Ragavendra R

2017-05-01

Genetic dyslipidemias contribute to the prevalence of ischemic heart disease. The field of genetic dyslipidemias and their influence on atherosclerotic heart disease is rapidly developing and accumulating increasing evidence. The purpose of this review is to describe the current state of knowledge in regard to inherited atherogenic dyslipidemias. The disorders of familial hypercholesterolemia (FH) and elevated lipoprotein(a) will be detailed. Genetic technology has made rapid advancements, leading to new discoveries in inherited atherogenic dyslipidemias, which will be explored in this review, as well as a description of possible future developments. Increasing attention has come upon the genetic disorders of familial hypercholesterolemia and elevated lipoprotein(a). This review includes new knowledge of these disorders including description of these disorders, their method of diagnosis, their prevalence, their genetic underpinnings, and their effect on the development of cardiovascular disease. In addition, it discusses major advances in genetic technology, including the completion of the human genome sequence, next-generation sequencing, and genome-wide association studies. Also discussed are rare variant studies with specific genetic mechanisms involved in inherited dyslipidemias, such as in the proprotein convertase subtilisin/kexin type 9 (PCSK9) enzyme. The field of genetics of dyslipidemia and cardiovascular disease is rapidly growing, which will result in a bright future of novel mechanisms of action and new therapeutics.

[Prevalence of hyperlipidemia and possible risk factors in rural Chinese adults: cohort study of health population in Yuhuan rural].

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Su, Meifang; Fu, Chaowei; Li, Songtao; Ying, Xuhua; He, Na; Jiang, Qingwu

2013-09-01

To examine the prevalence of hyperlipidemia and its related factors in adults in rural Yuhuan, China. A cross-sectional study was carried out as a baseline study of Rural Yuhuan Health Population Cohort in all communities in Yuhuan County, Zhejiang Province, China. A total of 118,571 subjects aged 35 years old or above participated in this study. The trained health/medical workers collected the general information, health conditions and so on by the face-to-face interview. Totally, 5 ml blood samples were taken. Hyperlipidemia was defined as blood triglyceride > or = 1.70 mmol/L and/or total cholesterols > or = 5.18 mmol/L. SPSS 16.0 was used for statistical analysis. Data of the fifth China population census 2000 was used as the standard population. Among 118,571 eligible subjects, the averages of blood triglyceride and total cholesterols were (1.71 +/- 14.42) mmol/L and (5.48 +/- 40.25 ) mmol/L, respectively, and there was a statistical difference in gender on blood triglyceride (t = 4.163, P education levels, smoking, alcohol consumption and body mass index were significantly related to hyperlipidemia. Hyperlipidemia, especial hypercholesterolemia, was common in adults aged 35 years old or above living in rural China.

Isolated Diastolic Hypertension among Adults in Saudi Arabia: Prevalence, Risk Factors, Predictors and Treatment. Results of a National Survey

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Abdalla Abdelwahid Saeed

2016-02-01

Full Text Available Background: In the past, diastolic hypertension was the main criterion for treatment, but currently, systolic pressure is the main criterion because it was thought that Isolated Diastolic Hypertension (IDH is not associated with complications. Studies later revealed that IDH carries significant risks. Quantifying the magnitude and risk factors of IDH in the community is essential for all intervention strategies. Aims: This study aims to determine the prevalence, risk factors, predictors, treatment modalities and lifestyle practices of IDH adult patients in the Kingdom of Saudi Arabia (KSA. Study Design: Cross-sectional study. Methods: A community-based cross-sectional study using STEPwise approach among adults using a multistage, stratified, cluster random sample was carried out. Data were collected using questionnaires which included socio-demographics, blood pressure, biochemical, anthropometric measurements and lifestyle practices. Statistical analysis included calculating means and standard deviations, proportions, univariate and multiple logistic regression analysis. Results: Of a total 4562 subjects, 180 (3.95% suffered from IDH, which was significantly related to age, gender, employment, smoking, diabetes mellitus, obesity and hypercholesterolemia. More than 93% were using some form of treatment, with 77.2% on prescribed drugs, 63% using diet, and 23% using exercise. Significant predictors of IDH were retirement and hypercholesterolemia. Conclusion: IDH is associated with some sociodemographic characteristics and co-morbidity. Given the risk of cardiovascular disease associated with IDH, the findings of this study emphasize the need for diagnosing the disease in middle-aged persons focusing on the modifiable risk factors of IDH.

Exercise electrocardiogram testing in two brothers with different outcome – a case study exercise testing in master cyclists

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Rüst CA

2013-06-01

Full Text Available Christoph Alexander Rüst,1 Beat Knechtle,1,2 Thomas Rosemann11Institute of General Practice and Health Services Research, University of Zurich, Zurich, Switzerland; 2Gesundheitszentrum St Gallen, St Gallen, SwitzerlandAbstract: The cases of two brothers training and competing as master cyclists and both preparing for a cycling tour are presented. The older brother aged 66 years went first to the primary care physician and presented with an asymptomatic depression in the exercise stress test of the ST segment in V5 and V6 during recovery after complete exhaustion. Coronary angiography revealed a multi vessel coronary artery disease and he underwent bypass surgery. One year later, he successfully completed his planned cycling tour of ~600 km in seven stages and covering ~12,000 m of total ascent. The younger brother aged 59 years went a few months later to the primary care physician and also performed asymptomatic exercise stress testing without changes in the ST segments. Unfortunately, 2 months later he suffered a cardiac arrest during his cycling tour and survived following immediate successful cardiopulmonary resuscitation on the road by his cycling colleagues. Immediate invasive coronary arteriography showed a complete stenosis of the trunk of arteria coronaria sinistra (left coronary artery, a 40%–50% stenosis of ramus circumflexus, and a 20% stenosis of arteria coronaria dextra (right coronary artery. The left coronary artery was dilated and he continued cycling 2 months later. In both brothers, familial hypercholesterolemia was the main cardiovascular risk factor for the multi vessel coronary artery disease. A negative exercise electrocardiogram in siblings with an increased risk for coronary artery disease seemed not to exclude an advanced multi vessel coronary artery disease. In master athletes with asymptomatic exercise electrocardiogram but a positive family history, further examinations should be performed in order to detect

Olive oil-diet improves the simvastatin effects with respect to sunflower oil-diet in men with increased cardiovascular risk: a preliminary study.

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Sánchez-Muniz, F J; Bastida, S; Gutiérrez-García, O; Carbajal, A

2009-01-01

Concomitant intake of statins together with certain foods may affect their therapeutic effects. The purpose of this preliminary study was to determine the modulating effect of two culinary oils on the hypolipemic effect of statins. Twenty-five men with severe hypercholesterolemia and high estimate cardiovascular risk (> 20% according to the Adult Treatment Panel III of USA National Institutes of Health, ATP-III) were enrolled in an observational follow-up study to test lipoprotein profile changes after ix month 20-mg/d Simvastatin treatment. Thirteen volunteers using sunflower oil as the habitual culinary fat, and 12 using olive oil, were selected by non-probabilistic incidental sampling. Volunteers consent in follow their habitual diets and to maintain diet characteristics throughout the study. Diet was evaluated through the study by three 24-h recalls and a food frequency questionnaire. The energy contribution of fat (P = 0.019) and MUFA (P alcohol (P = 0.005) was higher in the sunflower oil-group. TC/HDL-cholesterol and the ATP-III 10-year risk percent decreased more (P alcohol intakes were adjusted. Data suggest that although Simvastatin is a very effective hypolipemic drug, olive oil-diets in preference to sunflower oil-diets must be consumed in patients with high cardiovascular risk.

Physical, psychological and occupational consequences of job burnout: A systematic review of prospective studies

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Melanda, Francine Nesello; Mesas, Arthur Eumann; González, Alberto Durán; Gabani, Flávia Lopes

2017-01-01

Burnout is a syndrome that results from chronic stress at work, with several consequences to workers’ well-being and health. This systematic review aimed to summarize the evidence of the physical, psychological and occupational consequences of job burnout in prospective studies. The PubMed, Science Direct, PsycInfo, SciELO, LILACS and Web of Science databases were searched without language or date restrictions. The Transparent Reporting of Systematic Reviews and Meta-Analyses guidelines were followed. Prospective studies that analyzed burnout as the exposure condition were included. Among the 993 articles initially identified, 61 fulfilled the inclusion criteria, and 36 were analyzed because they met three criteria that must be followed in prospective studies. Burnout was a significant predictor of the following physical consequences: hypercholesterolemia, type 2 diabetes, coronary heart disease, hospitalization due to cardiovascular disorder, musculoskeletal pain, changes in pain experiences, prolonged fatigue, headaches, gastrointestinal issues, respiratory problems, severe injuries and mortality below the age of 45 years. The psychological effects were insomnia, depressive symptoms, use of psychotropic and antidepressant medications, hospitalization for mental disorders and psychological ill-health symptoms. Job dissatisfaction, absenteeism, new disability pension, job demands, job resources and presenteeism were identified as professional outcomes. Conflicting findings were observed. In conclusion, several prospective and high-quality studies showed physical, psychological and occupational consequences of job burnout. The individual and social impacts of burnout highlight the need for preventive interventions and early identification of this health condition in the work environment. PMID:28977041

Estrogen and phytoestrogens: Effect on eNOS expression and in vitro vasodilation in cerebral arteries in ovariectomized Watanabe heritable hyperlipidemic rabbits

DEFF Research Database (Denmark)

Lund, Claus O.; Mortensen, Alicja; Nilas, Lisbeth

2007-01-01

Objectives: To evaluate the effect of estrogen replacement therapy or soy isoflavones supplement on endothelium-dependent relaxation in vitro and gene expression of endothelial nitric oxide synthase (eNOS) in cerebral arteries in a rabbit model of human hypercholesterolemia. Study design: Thirty...... cholesterol was significantly higher at termination in the SoyLife(R) group (P lipoprotein (LDL) cholesterol was comparable in all treatment groups. Neither treatment influenced the endothelium-dependent responses to carbamylcholine chloride or L-NAME or the endothelium...

The Effect of Pumpkin on GLP-1 and HOMA-β in Hypercholesterolemic Rats

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Sunarti

2016-03-01

Full Text Available Background and aim: High fat and fructose diet may impair β cell function through oxidative stress that is induced by subsequent hypercholesterolemia. The β cell function is usually quantified by homeostatic model assessment beta-cell function (HOMA-β. Oxidative stress may be decreased by β-carotene from pumpkin (Cucurbita maxima. This study aimed to evaluate the effects of pumpkin powder on glucagon-like peptide-1 (GLP-1 level and HOMA-β in rats with high fat and fructose diet.