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HDL
Kinds of HDL Terms modified by HDL Selected AbstractsReverse cholesterol transport in type 2 diabetes mellitusDIABETES OBESITY & METABOLISM, Issue 6 2009K. C. B. Tan High-density lipoprotein (HDL) plays an important protective role against atherosclerosis, and the anti-atherogenic properties of HDL include the promotion of cellular cholesterol efflux and reverse cholesterol transport (RCT), as well as antioxidant, anti-inflammatory and anticoagulant effects. RCT is a complex pathway, which transports cholesterol from peripheral cells and tissues to the liver for its metabolism and biliary excretion. The major steps in the RCT pathway include the efflux of free cholesterol mediated by cholesterol transporters from cells to the main extracellular acceptor HDL, the conversion of free cholesterol to cholesteryl esters and the subsequent removal of cholesteryl ester in HDL by the liver. The efficiency of RCT is influenced by the mobilization of cellular lipids for efflux and the intravascular remodelling and kinetics of HDL metabolism. Despite the increased cardiovascular risk in people with type 2 diabetes, current knowledge on RCT in diabetes is limited. In this article, abnormalities in RCT in type 2 diabetes mellitus and therapeutic strategies targeting HDL and RCT will be reviewed. [source] Antidiabetic and toxicological evaluations of naringenin in normoglycaemic and NIDDM rat models and its implications on extra-pancreatic glucose regulationDIABETES OBESITY & METABOLISM, Issue 11 2008R. R Ortiz-Andrade Aim:, The present investigation was designed to determine the in vivo antidiabetic effect of naringenin (NG) in normoglycaemic and diabetic rat models through blood glucose (GLU) measurements following acute and subchronic time periods. Possible modes of action of NG were investigated and its acute toxicity determined. Methods:, Normoglycaemic and non-insulin-dependent diabetes mellitus (NIDDM) rat models were treated for acute and subchronic (5 days) time periods with 50 mg/kg/day of NG. Blood biochemical profiles were determined after 5 days of the treatment in normoglycaemic and NIDDM rats using commercial kits for GLU, triglycerides (TG), total cholesterol (CHOL) and high-density lipoprotein (HDL). In order to elucidate its antidiabetic mode of action, NG was administered intragastrically and an oral glucose tolerance test performed using GLU and sucrose (2 g/kg) as substrates. The inhibitory effect of a single concentration of NG (10 ,M) on 11,-hydroxysteroid dehydrogenase type 1 (11,-HSD1) activity in vitro was determined. Finally, the preclinical safety and tolerability of NG was determined by toxicological evaluation in mice and rats using Organization for Economic Cooperation and Development (OECD) protocols. Results:, Intragastrically administered NG (50 mg/kg) induced a significant decrease in plasma GLU in normoglycaemic and NIDDM rat models (p < 0.05) following acute and subchronic time periods. After 5 days of administration, NG produced significant diminished blood GLU and TG levels in streptozotocin,nicotinamide,induced diabetic rats. The administration of NG to normal rats significantly increased the levels of TG, CHOL and HDL (p < 0.05). NG (5 and 50 mg/kg) induced a total suppression in the increase of plasma GLU levels after administration of substrates (p < 0.01), but NG did not produce inhibition of ,-glucosidase activity in vitro. However, NG (10 ,M) was shown to inhibit 11,-HSD1 activity by 39.49% in a cellular enzyme assay. Finally, NG showed a Medium Lethal Dose LD50 > 5000 mg/kg and ranking at level five based on OECD protocols. Conclusion:, Our findings suggest that NG may exert its antidiabetic effect by extra-pancreatic action and by suppressing carbohydrate absorption from intestine, thereby reducing the postprandial increase in blood GLU levels. [source] Incidence of insulin resistance in obese subjects in a rural Japanese population: The Tanno and Sobetsu studyDIABETES OBESITY & METABOLISM, Issue 1 2005H. Ohnishi Objectives:, Although it is well known that obesity is closely related to insulin resistance, the incidence of the development of insulin resistance in people with obesity is not known. In this study, we investigated the incidence of insulin resistance in citizens of two rural communities in Japan. Subjects and methods:, The subjects were 102 men and 126 women over the age of 30 years selected from 1035 citizens who had undergone medical examinations in the towns of Tanno and Sobetsu, Hokkaido, in 1991 and 1998. Those who were on medication for hypertension, diabetes, hyperlipidaemia, coronary heart disease and cerebral vessel disease were excluded. The simple index to determine insulin resistance [i.e. homeostasis model assessment (HOMA-R) , 1.73] was used, and subjects who were determined to be positive for insulin resistance according to this index in 1991 were also excluded in order to determine the incidence of insulin resistance in subjects who had no abnormalities other than obesity. The systolic blood pressure (SBP), diastolic blood pressure, body mass index (BMI), triglyceride level, high-density lipoprotein level, blood sugar level, serum insulin value and HOMA-R were measured in all subjects in 1991 and in 1998. Moreover, the subjects were divided into two groups according to BMI, a normal group consisting of subjects with BMI < 25 and an obesity group consisting of subjects with BMI , 25. We also compared the incidences of insulin resistance in normal and obesity groups of subjects who were newly determined to be positive for insulin resistance on the basis of data obtained from medical examinations conducted in 1998. Results:, The incidence of insulin resistance was significantly higher in the obesity group than in the normal group (25.0 vs. 4.5%). The results of logistic regression analysis showed that obesity was closely related to insulin resistance and that the relative risk of development of insulin resistance adjusted for age, sex, SBP, FPG and HDL was 3.193 (95% CI 1.085,9.401). Conclusions:, The incidence of insulin resistance was significantly higher in the obesity group than in the normal group in this study, suggesting that improvement in obesity is important for prevention of the occurrence of type 2 diabetes or atherosclerotic disease based on insulin resistance. [source] Losartan modifies glomerular hyperfiltration and insulin sensitivity in type 1 diabetesDIABETES OBESITY & METABOLISM, Issue 6 2001S. Nielsen Aim: The effect of the angiotensin II receptor antagonist losartan on renal haemodynamics and insulin-mediated glucose disposal was examined in normotensive, normoalbuminuric type 1 diabetic patients using a double-blind, placebo-controlled, cross-over design. Methods: Diurnal blood pressure, glomerular filtration rate (GFR, determined using [125I]-iothalamate), renal plasma flow (RPF, determined using [131I]-hippuran) and urinary albumin excretion rate (UAE) were measured, and a hyperinsulinaemic, euglycaemic clamp with indirect calorimetry was performed in nine patients (age 30 ± 7 years (mean ±,s.d.), HbA1c 8.1 ± 1.1%) following 6 weeks' administration of either losartan 50 mg/day or placebo. Results: Diurnal blood pressure was significantly reduced after losartan compared with placebo (122/70 ± 11/8 vs. 130/76 ± 12/6 mmHg, p <,0.05). A significant decline in GFR (133 ± 23 vs. 140 ± 22 ml/min, p < 0.05) and filtration fraction (FF; GFR/RPF) (24.6 ± 3.5 vs. 26.2 ± 3.6%, p <,0.05) was observed in the losartan vs. placebo groups. RPF and UAE did not change. Isotopically determined glucose disposal rates were similar after losartan and placebo in the basal (2.61 ± 0.53 vs. 2.98 ± 0.93 mg/kg/min) and insulin-stimulated states (6.84 ± 2.52 vs. 6.97 ± 3.11 mg/kg/min). However, the glucose oxidation rate increased significantly after losartan vs. placebo in the basal state (1.72 ± 0.34 vs. 1.33 ± 0.18, mg/kg/min, p <,0.01) and during insulin stimulation (2.89 ± 0.75 vs. 2.40 ± 0.62 mg/kg/min, p <,0.03). Basal and insulin-stimulated non-oxidative glucose disposal tended to decrease after losartan; however, this was not significant. Endogenous glucose production and lipid oxidation were unchanged after treatment and similarly suppressed during hyperinsulinaemia. Glycaemic control, total cholesterol, high-density lipoprotein (HDL)-cholesterol and triglycerides were stable in both losartan and placebo groups. Conclusions: Losartan reduces blood pressure, glomerular hyperfiltration and FF, and improves basal and insulin-stimulated glucose oxidation in normotensive, normoalbuminuric type 1 diabetic patients. [source] Clustering of cardiovascular risk factors in type 2 diabetes mellitus: prognostic significance and trackingDIABETES OBESITY & METABOLISM, Issue 1 2001J. Kaukua Summary Aim Little attention has been paid to the prognostic significance and tracking effect of risk factor clusters characteristic of type 2 diabetes mellitus. We studied the clustering of eight cardiovascular risk factors (smoking, high body mass index, elevated systolic blood pressure, high serum, low density lipoprotein (LDL) cholesterol, high serum LDL triglycerides, low serum, high density lipoprotein (HDL) cholesterol, high fasting blood glucose and high plasma insulin concentration) and their effect on the prognosis and the tracking effect. Methods This study is a population-based prospective follow-up of newly diagnosed type 2 diabetic subjects (n = 133, aged 45,64 years) in Eastern Finland. The following end points were used: all-cause mortality, cardiovascular mortality, and incidences of first myocardial infarction and first stroke. Furthermore, we studied the ,tracking effect' of the risk factor clusters during the 10-year follow-up period. Results When the clustering of risk factors typical of type 2 diabetes mellitus was taken into account, all-cause mortality increased from 28.6% to 50.0% (p <,0.05) and cardiovascular disease mortality increased from 14.3% to 50.0% (p <,0.01) depending on the number of risk factors present. The incidence of first myocardial infarction increased from 0% to 40.0% (p <,0.05) as the number of risk factors increased from 0 to 5. In survivors, the proportion of individuals with no risk factors decreased and the proportion on individuals with three to four risk factors increased during the 10-year follow-up period despite the high mortality among the group with many risk factors. Conclusions The risk factor clusters among type 2 diabetic subjects are of great predictive value and when not aggressively treated, show a relentless increase despite selective mortality. [source] Prevalence of and risk factors for extracranial internal carotid artery stenosis in Korean Type 2 diabetic patientsDIABETIC MEDICINE, Issue 12 2006J. H. Park Abstract Aims The objectives of this study were to evaluate the prevalence of and risk factors for extracranial internal carotid artery stenosis in Type 2 diabetic patients. Methods This study included 406 patients aged 40,79 years with Type 2 diabetes (male 55.4%, female 44.6%). Both carotid arteries of each patient were examined by carotid duplex scanning. The duplex ultrasound criteria based on the North American Symptomatic Carotid Endarterectomy Trial (NASCET) measurement method were used for the identification of carotid stenosis. Results Extracranial internal carotid artery stenosis , 40% by velocity criteria was detected in 5.2% of the patients. The prevalence of carotid stenosis increased with advancing age: 1.0% at 40,49 years of age, 5.0% at 50,59 years, 7.3% at 60,69 years and 9.5% at 70,79 years. The degree of stenosis was > 70% in 42.9% of patients with stenosis, Bilateral stenosis was detected in 14% of patients. Of the patients with , 40% carotid stenosis, 33% had a decreased ankle-brachial index, 38% had a previous history of stroke, and only one patient (5%) had a documented history of coronary artery disease. Multivariate analysis, including variables determined to be significantly different by univariate analysis between patients with or without , 40% stenosis, indicated that age, systolic blood pressure and high-density lipoprotein (HDL)-cholesterol (inverse correlation) were independent risk factors associated with carotid stenosis. Conclusions Carotid duplex scanning is a useful strategy in identifying carotid stenosis in older Type 2 diabetic patients with high systolic blood pressure, or low levels of HDL cholesterol. The early identification and subsequent appropriate management of carotid stenosis, particularly in this group of patients, may facilitate efforts to reduce the incidence of macrovascular complications. [source] A multivariate logistic regression equation to screen for dysglycaemia: development and validationDIABETIC MEDICINE, Issue 5 2005B. P. Tabaei Abstract Aims To develop and validate an empirical equation to screen for dysglycaemia [impaired fasting glucose (IFG), impaired glucose tolerance (IGT) and undiagnosed diabetes]. Methods A predictive equation was developed using multiple logistic regression analysis and data collected from 1032 Egyptian subjects with no history of diabetes. The equation incorporated age, sex, body mass index (BMI), post-prandial time (self-reported number of hours since last food or drink other than water), systolic blood pressure, high-density lipoprotein (HDL) cholesterol and random capillary plasma glucose as independent covariates for prediction of dysglycaemia based on fasting plasma glucose (FPG) , 6.1 mmol/l and/or plasma glucose 2 h after a 75-g oral glucose load (2-h PG) , 7.8 mmol/l. The equation was validated using a cross-validation procedure. Its performance was also compared with static plasma glucose cut-points for dysglycaemia screening. Results The predictive equation was calculated with the following logistic regression parameters: P = 1 + 1/(1 + e,X) = where X = ,8.3390 + 0.0214 (age in years) + 0.6764 (if female) + 0.0335 (BMI in kg/m2) + 0.0934 (post-prandial time in hours) + 0.0141 (systolic blood pressure in mmHg) , 0.0110 (HDL in mmol/l) + 0.0243 (random capillary plasma glucose in mmol/l). The cut-point for the prediction of dysglycaemia was defined as a probability , 0.38. The equation's sensitivity was 55%, specificity 90% and positive predictive value (PPV) 65%. When applied to a new sample, the equation's sensitivity was 53%, specificity 89% and PPV 63%. Conclusions This multivariate logistic equation improves on currently recommended methods of screening for dysglycaemia and can be easily implemented in a clinical setting using readily available clinical and non-fasting laboratory data and an inexpensive hand-held programmable calculator. [source] Prevalence of the metabolic syndrome among the Inuit in Greenland.DIABETIC MEDICINE, Issue 11 2004A comparison between two proposed definitions Abstract Aims To estimate the prevalence of the metabolic syndrome among Greenland Inuit according to the World Health Organization (WHO) definition and the definition suggested by the National Cholesterol Education Program (NCEP). Methods From 1999 to 2001, 917 adult Inuit participated in a health survey in Greenland. The examination included a 75-g oral glucose tolerance test (OGTT). Body mass index (BMI), waist circumference, waist-to-hip ratio and blood pressure were measured. Plasma glucose, serum insulin, lipids and urine albumin/creatinine ratio were measured. The metabolic syndrome was diagnosed according to the WHO criteria 1999 and to the working definition suggested by the NCEP 2001. Results Using the WHO and the NCEP criteria, 20.7% and 17.9% of the participants had the metabolic syndrome, respectively. There was a moderate agreement between the two definitions, , = 0.56 (95% CI 0.51,0.61). Of those with the WHO metabolic syndrome, 37.9% did not have the NCEP syndrome, and 28.5% of those with the NCEP syndrome were not classified with the metabolic syndrome under the WHO criteria. Compared with the WHO syndrome, men with the NCEP syndrome had higher mean values of waist circumference, BMI and triglycerides, and lower mean values of high-density lipoprotein (HDL) cholesterol; among women, triglycerides were higher with the NCEP syndrome. Conclusion The metabolic syndrome is common among Inuit using either the WHO definition or the proposed NCEP definition. The classification disagreement is considerable and a universally accepted definition is needed. [source] The influence of the polymorphism in apolipoprotein B codon 2488 on insulin and lipid levels in a Danish twin populationDIABETIC MEDICINE, Issue 1 2002J. Bentzen Abstract Aims The apolipoprotein B codon 2488 polymorphism has been associated with the metabolism of lipoproteins in subjects with Type 2 diabetes. However, no data are available on the influence of the polymorphism on insulin or glucose metabolism. This study examines the impact of the polymorphism on parameters associated with the insulin resistance syndrome in Danish twins. Methods The effect of the polymorphism on lipid, glucose and insulin measures was studied in 548 same sex twins aged 55,74 years. Results The codon 2488 polymorphism influenced fasting triglyceride levels, as well as insulin, as measured at 120 min in an oral glucose tolerance test. Subjects with the genotype T2488T had 14% higher triglyceride levels (P = 0.02) and 31% higher insulin levels (P = 0.004) than subjects with genotype C2488C. In twins discordant for genotype, the T-allele was associated with higher levels of triglyceride (P = 0.04) and insulin (P = 0.02) and lower levels of HDL-cholesterol (P = 0.04). Conclusion The T-allele of the codon 2488 polymorphism influenced parameters related to the insulin resistance syndrome, i.e. increased levels of insulin, increased levels of triglyceride and decreased levels of HDL. As the polymorphism is silent, these effects must be mediated through linkage to other polymorphisms in apolipoprotein B or other genes on chromosome 2. [source] Glibenclamide improves postprandial hypertriglyceridaemia in Type 2 diabetic patients by reducing chylomicrons but not the very low-density lipoprotein subfraction levelsDIABETIC MEDICINE, Issue 10 2001I. Skrapari Abstract Aim, There are scarce data dealing with the degree of postprandial lipaemia after sulphonylurea administration. The aim of this study was to examine the effect of acute glibenclamide administration on postprandial lipaemia in Type 2 diabetic patients. Methods, Eight randomly selected Type 2 diabetic individuals, aged 43,65 years (mean, 54 years), who had never received any anti-diabetic drug, were included in the study. Each patient was given a 485 kcal mixed meal (45% fat, 40% carbohydrate and 15% protein) twice on separate days after an overnight fast: once with placebo and once with 5 mg glibenclamide, per os, in a random order. The two tests were performed with an interval of 7 days. Venous blood samples were drawn just before and 2 h, 4 h and 6 h after meal consumption. Total triglyceride levels in plasma, in chylomicrons (CM), in CM-deficient plasma, in very low-density lipoprotein (VLDL) subfractions (VLDL-1, VLDL-2) and in intermediate-density lipoprotein (IDL) were determined. Free fatty acid (FFA) and total cholesterol levels in plasma, as well as high-density lipoprotein (HDL) cholesterol and low-density lipoprotein (LDL) cholesterol levels in CM-deficient plasma, were also measured. Finally, serum glucose, insulin and C-peptide concentrations were measured in each sample. Results, As expected there was a significant decrease in postprandial glycaemia after glibenclamide administration compared to placebo (mean area under the curve values: AUC = 53.3 ± 18.2 and 69.1 ± 21.6 mm/h, P = 0.00009). In addition, the mean AUC values of insulin and C-peptide were significantly greater after drug administration. The AUC values of total plasma triglyceride and of CM triglyceride following glibenclamide administration were significantly lower compared to placebo, while the AUC values of postprandial triglyceride in CM-deficient plasma and of postprandial triglyceride in VLDL-1, VLDL-2 and IDL were not different after drug administration compared to placebo. Finally, no significant differences were noted in the AUC values of total cholesterol, LDL cholesterol, HDL cholesterol and plasma FFA levels after glibenclamide administration. Conclusions, These results demonstrate that glibenclamide administration improves postprandial hypertriglyceridaemia acutely by reducing postprandial triglycerides of intestinal origin. Diabet. Med. 18, 781,785 (2001) [source] Ethnicity and glycaemic control are major determinants of diabetic dyslipidaemia in MalaysiaDIABETIC MEDICINE, Issue 6 2001I. S. Ismail Abstract Aims To define the prevalence of dyslipidaemia in young diabetic patients in Peninsular Malaysia and the contributory factors of dyslipidaemia in these subjects. Methods This is a cross-sectional study involving 848 young diabetic patients from seven different centres, with representation from the three main ethnic groups. Clinical history and physical examination was done and blood taken for HbA1c, fasting glucose, total cholesterol, low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol and triglycerides. Results The overall lipids were suboptimal, worse in Type 2 diabetes mellitus (DM) patients compared with Type 1 DM patients. Of the Type 2 patients, 73.2% had total cholesterol >,5.20 mmol/l, 90.9% had LDL-cholesterol >,2.60 mmol/l, 52.6% had HDL-cholesterol <,1.15 mmol/l and 27.3% had serum triglycerides >,2.30 mmol/l. There were ethnic differences in the lipid levels with the Malays having the highest total cholesterol (mean 6.19 mmol/l), and the highest LDL-cholesterol (mean 4.16 mmol/l), while the Chinese had the highest HDL-cholesterol (geometric mean 1.24 mmol/l). Ethnicity was an important determinant of total, LDL- and HDL-cholesterol in Type 2 DM, and LDL- and HDL-cholesterol and triglycerides in Type 1 DM. Glycaemic control was an important determinant of total, LDL-cholesterol and triglycerides in both Type 1 and Type 2 DM. Waist,hip ratio (WHR) was an important determinant of HDL-cholesterol and triglycerides in both types of DM. Gender was an important determinant of HDL-cholesterol in Type 2 DM, but not in Type 1 DM. Socioeconomic factors and diabetes care facilities did not have any effect on the dyslipidaemia. Conclusions The prevalence of dyslipidaemia was high especially in Type 2 DM patients. Ethnicity, glycaemic control, WHR, and gender were important determinants of dyslipidaemia in young diabetic patients. Diabet. Med. 18, 501,508 (2001) [source] Microchip-based small, dense low-density lipoproteins assay for coronary heart disease risk assessmentELECTROPHORESIS, Issue 9 2008Hua Wang Abstract Small, dense low-density lipoprotein (sdLDL) has been accepted as an emerging cardiovascular risk factor, and there has been an increasing interest in analytical methods for sdLDL profiling for diagnosis. Serum sdLDL may be measured by different laboratory techniques, but all these methods are laborious, time-consuming, and costly. Recently, we have demonstrated that a low-temperature bonding of quartz microfluidic chips for serum lipoproteins analysis (Zhuang, G., Jin, Q., Liu, J., Cong, H. et al., Biomed. Microdevices 2006, 8, 255,261). In contrast to this previous study, we chose SDS as anionic surfactant to modify both lipoproteins and the channel surface to minimize lipoprotein adsorption and improve the resolution of lipoprotein separation. Two major LDL subclass patterns including large, buoyant LDL (lLDL), sdLDL, and high-density lipoprotein (HDL) were effectively separated with high reproducibility. RSD values of the migration time (min) and peak areas of standard LDL and HDL were 6.28, 4.02, 5.02, and 2.5%, respectively. Serum lipoproteins of 15 healthy subjects and 15 patients with coronary heart disease (CHD) were separated by microchip CE. No peaks of sdLDL were detected in serum samples of healthy subjects while sdLDL fractional peaks were observed in patients' entire serum samples. These results suggested that the microchip-based sdLDLs assay was a simple, rapid, and highly efficient technique and significantly improved the analysis of CHD risk factors. [source] The metabolic syndrome in overweight epileptic patients treated with valproic acidEPILEPSIA, Issue 2 2010Alberto Verrotti Summary Purpose:, To evaluate the presence of metabolic syndrome (MS) in children and adolescents treated with valproate (VPA). Methods:, One hundred fourteen patients (54 male and 60 female) were studied. These patients were followed from the beginning of therapy for at least 24 months; at the end of follow-up, 46 patients (40.4%) had a considerable increase in body weight, whereas the other patients (59.6%) remained with the same weight. The MS was defined as having at least three of the following: abdominal obesity, dyslipidemia, glucose intolerance, and hypertension. Results:, Forty-six patients developed obesity; 20 (43.5%) of 46 patients developed MS. Abnormal glucose homeostasis was identified in 45% of patients. High total serum cholesterol concentrations were noted in 10 (50%), high serum triglyceride concentrations in 7 (35%), and low high-density lipoprotein (HDL) in 15 (75%) of the 20 subjects with MS. However, there were no significant differences in the features of MS between boys and girls with MS. Conclusions:, Patients who gain weight during VPA therapy can develop MS with a possible risk of cardiovascular disease. [source] Inflammation reduces HDL protection against primary cardiac riskEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 6 2010James P. Corsetti Eur J Clin Invest 2010; 40 (6): 483,489 Abstract Background, We recently reported high high-density lipoprotein (HDL) cholesterol as a predictor of recurrent risk in a subgroup of postinfarction patients defined by hypercholesterolemia and high C-reactive protein (CRP) levels. We investigated whether a similar high-risk subgroup might exist for incident cardiovascular disease. Material and Methods, A graphical exploratory data analysis tool was used to identify high-risk subgroups in a male population-based cohort (n = 3405) from the prevention of renal and vascular end-stage disease study by generating 3-dimensional mappings of risk over the HDL-cholesterol/CRP domain with subsequent use of Kaplan,Meier analysis to verify high-risk. Within-subgroup risk was assessed using Cox proportional hazards regression and Kaplan,Meier analysis. Results, Mappings revealed two high-risk subgroups: a low HDL-cholesterol/high CRP subgroup and a high HDL-cholesterol/high CRP subgroup. The low HDL-cholesterol subgroup demonstrated a pattern of metabolic syndrome dyslipidemia contrasted with a predominantly unremarkable biomarker pattern for the high HDL-cholesterol subgroup. However, in the high HDL-cholesterol subgroup, CRP levels were higher than the low HDL-cholesterol subgroup; and within the high HDL-cholesterol subgroup, CRP predicted risk. Moreover, in the high HDL-cholesterol subgroup, risk was associated with lower triglyceride levels in conjunction with presumptively larger HDL particles. Conclusions, High HDL-cholesterol and high CRP levels define a subgroup of men at high-risk for incident cardiovascular disease. High HDL cholesterol-associated risk likely relates to impaired HDL particle remodelling in the setting of inflammation. This approach may facilitate identification of additional inflammation-related mechanisms underlying high HDL cholesterol-associated risk; and potentially influence management of such patients. [source] Expression of STAMP2 in monocytes associates with cardiovascular alterationsEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 6 2010Zhi-Hao Wang Eur J Clin Invest 2010; 40 (6): 490,496 Abstract Background, Metabolic and inflammatory pathways crosstalk at many levels. In this study, we aimed to investigate the expression of six-transmembrane protein of prostate 2 (STAMP2) in macrophages and tried to search for the association between the decreased STAMP2 expression, if any, and carotid atherosclerosis as well as cardiac adaptations. Materials and methods, A total of 97 unrelated Chinese subjects were recruited including 48 subjects with metabolic syndrome (MetS) and 49 controls. Clinical and biochemical characteristics were collected from subjects, with quantification of STAMP2 in monocyte/macrophages. All subjects underwent ultrasonography. Results, STAMP2 expression in macrophages was significantly decreased in MetS as compared with the control group (10·25 ± 9·20 vs. 15·20 ± 9·18, P = 0·009), especially in women patients. Partial correlation analysis showed that STAMP2 expression in macrophages correlated with BMI (r = ,0·375, P = 0·045), age (r = 0·414, P = 0·026) and HDL (r = 0·377, P = 0·044) after controlling for systolic blood pressure (SBP). Furthermore, STAMP2 expression was correlated with PI (r = ,0·454, P = 0·013), LVEF (r = ,0·503, P = 0·005), LA-ESR (r = ,0·424, P = 0·022), LA-S (r = 0·469, P = 0·010) and mitral E/A ratio (r = 0·492, P = 0·005) after controlling for SBP. Still, in multivariable analysis, STAMP2 expression was independently associated with IMTmean, PI and mitral E/A ratio. Conclusions, In MetS patients, especially women patients, STAMP2 expression was down-regulated in peripheral blood mononuclear cell, which was correlated with carotid atherosclerosis and cardiac adaptation. [source] CETP inhibition in cardiovascular risk management: a critical appraisalEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 2 2007R. P. F. Dullaart Abstract In view of the cardioprotective effect of high-density lipoproteins (HDL) and the limited effects of statin and fibrate therapy on HDL cholesterol, it is clinically relevant to test whether pharmacological treatment aimed at raising HDL lowers cardiovascular risk. Cholesteryl ester transfer protein (CETP) is a new therapeutic target, because the cholesteryl ester transfer process lowers HDL cholesterol and contributes to an atherogenic lipoprotein profile, particularly when plasma triglycerides are high. Clinical evidence suggests that coronary artery calcification as well as intima media thickness is positively related to plasma cholesteryl ester transfer, and that high plasma CETP concentration is associated with increased cardiovascular risk in hypertriglyceridaemia. However, CETP could also have anti-atherogenic potential, since it provides a potentially beneficial route for delivery of HDL-derived cholesteryl esters to the liver. In addition, CETP could also favourably stimulate peripheral cell cholesterol removal and enhance hepatic cholesterol uptake. Recent evidence suggests that a high CETP level may confer lower cardiovascular risk in the context of low triglycerides. At maximal doses, the CETP inhibitors JTT-705 and torcetrapib elicit a marked rise in HDL cholesterol of up to 34% and 91,106%, respectively. The effectiveness of these drugs on (intermediate) clinical outcome measures is currently being tested in large-scale phase III clinical trials, with torcetrapib being only evaluated in combination therapy with atorvastatin. When and how to use CETP inhibitors, e.g. in combination with a statin or a fibrate, is a major challenge. We propose that low HDL cholesterol in the context of high triglycerides, such as found in type 2 diabetes mellitus, could become an important indication area for this new class of drugs. [source] Serum paraoxonase activity in patients with type 1 diabetes compared to healthy controlsEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 4 2002B. Mackness Abstract Background The oxidation of low-density lipoprotein (LDL) is central to current theories on the initiation and progression of atherosclerosis. Type 1 diabetes is associated with an increase in oxidative stress, which may be responsible for the increased susceptibility to coronary heart disease seen in type 1 diabetes. High-density lipoprotein (HDL) associated paraoxonase (PON1) can retard the oxidation of LDL. Design Paraoxonase activity, concentration and genotype were therefore investigated in 152 people with type 1 diabetes and 282 healthy controls. These parameters were also investigated in the group with type 1 diabetes in relation to the presence of diabetic complications. Results Both PON1 activity and concentration were significantly lower by 16·7% and 19·2% (both P < 0·05) in the type 1 diabetes group. These differences were independent of the PON1 coding region polymorphisms. The distribution of PON1 activity and mass were the same in both populations, i.e. for the PON1-192 polymorphism RR > RQ > QQ and for the PON1-55 polymorphism LL > LM > MM. There were no differences in either the PON1 polymorphisms, PON1 activity and concentration in people with type 1 diabetes in the presence or absence of micro and macro vascular complications of diabetes. Conclusions Low PON1 activity may contribute to the increased atherosclerosis found in type 1 diabetes by reducing the ability of HDL to retard LDL oxidation despite the frequently-found increased HDL in type 1 diabetes when good glycaemic control is established. [source] PON1 L55M polymorphism is not a predictor of coronary atherosclerosis either alone or in combination with Q192R polymorphism in an Italian populationEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 1 2002M. Arca Abstract Background, The present study evaluated the role of the PON1 L55M polymorphism independently and in conjunction with the Q192R polymorphism on the risk of coronary atherosclerosis in an Italian population. Materials and methods, Three hundred and ninety-one subjects with significant coronary stenosis (> 50%) (coronary artery disease-positive; CAD+), 196 subjects with normal coronary arteries (< 10% stenosis) (CAD,) and 178 healthy controls were screened using a combination of polymerase chain reaction and restriction enzyme digestion. Results, In the pooled population, the frequencies of L and M alleles were 0·63 and 0·37, respectively; the most common haplotypes were QQ/LM (24·2%) and QR/LL (21·8%) and a strong linkage disequilibrium between L/55 and R/192 alleles was observed (D, = ,0·91; P < 0·0001). CAD+ subjects did not show any significant differences in the distribution of PON1,55 genotypes as compared to CAD, subjects and population controls (,2 = 1·5, P = 0·8). After controlling for other risk factors, the low-concentration M allele was not associated with a significant change of CAD risk (OR 1·02; 95% CI 0·80,1·29; P = 0·87). Moreover, the L55M polymorphism did not show any interaction with other risk factors such as smoking, diabetes, hypertension, low levels of high-density lipoprotein (HDL) or high ratios of low-density to high-density lipoproteins. The combination of L55M with the Q192R polymorphism did not show any effect on CAD risk. However, a marginal decrease in myocardial infarction risk was detected when QQ/MM carriers (OR 0·51; 95% CI 0·26,0·99; P = 0·048), but not LL/RR carriers, were compared with subjects not homozygous for an L or R allele. Conclusions, These findings did not indicate a major effect of the PON1 L55M polymorphism, either alone or in combination with the Q192R polymorphism, on CAD risk. Additional studies are needed for a better evaluation of the role of the 55/192 PON1 genotypes in combination on myocardial infarction risk. [source] Gender and age differences in the distribution of the HDL subclasses among the Chinese populationEUROPEAN JOURNAL OF LIPID SCIENCE AND TECHNOLOGY, Issue 4 2010Li Tian Abstract Background and aims: to analyze the gender and age differences in the distribution of the high-density lipoprotein (HDL) subclasses among the Chinese population, and to clarify the mechanism of these changes. Methods and results: the apoA-I contents of the plasma HDL subclasses were determined by 2-DE coupled with immunodetection in 324 men (including 186 normolipidemic subjects) and 186 women (including 114 normolipidemic subjects). The contents of pre,1 -HDL and HDL3 (HDL3c, HDL3b, HDL3a) were significantly lower, whereas the contents of HDL2a and HDL2b were higher for women than for men in the <50,years age group. Moreover, the contents of pre,1 -HDL and HDL3 were higher for female subjects; the HDL2a and HDL2b contents were lower for both female and male subjects in the 50,59, 60,69, and ,70,years age groups versus the subjects of the same gender in the <50,years age group. When compared to the normolipidemic premenopausal women, pre,1 -HDL, HDL3b, and HDL3a increased while HDL2b decreased significantly in normolipidemic men and postmenopausal women. Conclusions: the contents of the large-sized HDL particles HDL2b were higher, but the contents of the small-sized HDL particles (pre,1 -HDL, HDL3b, HDL3a) were lower for women versus men in the <50,years age group. Meanwhile, the gender difference in distribution of the HDL subclass narrowed obviously with advancing age. Moreover, the characteristics of the HDL subclass distribution profile for the normolipidemic postmenopausal women resembled those for the normolipidemic men. [source] Complete high-density lipoproteins in nanoparticle coronaFEBS JOURNAL, Issue 12 2009Erik Hellstrand In a biological environment, nanoparticles immediately become covered by an evolving corona of biomolecules, which gives a biological identity to the nanoparticle and determines its biological impact and fate. Previous efforts at describing the corona have concerned only its protein content. Here, for the first time, we show, using size exclusion chromatography, NMR, and pull-down experiments, that copolymer nanoparticles bind cholesterol, triglycerides and phospholipids from human plasma, and that the binding reaches saturation. The lipid and protein binding patterns correspond closely with the composition of high-density lipoprotein (HDL). By using fractionated lipoproteins, we show that HDL binds to copolymer nanoparticles with much higher specificity than other lipoproteins, probably mediated by apolipoprotein A-I. Together with the previously identified protein binding patterns in the corona, our results imply that copolymer nanoparticles bind complete HDL complexes, and may be recognized by living systems as HDL complexes, opening up these transport pathways to nanoparticles. Apolipoproteins have been identified as binding to many other nanoparticles, suggesting that lipid and lipoprotein binding is a general feature of nanoparticles under physiological conditions. [source] Biophysical characterization of the interaction of high-density lipoprotein (HDL) with endotoxinsFEBS JOURNAL, Issue 23 2002Klaus Brandenburg The interaction of bacterial endotoxins [lipopolysaccharide (LPS) and the ,endotoxic principle' lipid A], with high-density lipoprotein (HDL) from serum was investigated with a variety of physical techniques and biological assays. HDL exhibited an increase in the gel to liquid crystalline phase transition temperature Tc and a rigidification of the acyl chains of the endotoxins as measured by Fourier-transform infrared spectroscopy and differential scanning calorimetry. The functional groups of the endotoxins interacting with HDL are the phosphates and the diglucosamine backbone. The finding of phosphates as target groups is in accordance to measurements of the electrophoretic mobility showing that the zeta potential decreases from ,50 to ,60 mV to ,20 mV at binding saturation. The importance of the sugar backbone as further target structure is in accordance with the remaining negative potential and competition experiments with polymyxin B (PMB) and phase transition data of the system PMB/dephosphorylated LPS. Furthermore, endotoxin binding to HDL influences the secondary structure of the latter manifesting in a change from a mixed ,-helical/,-sheet structure to a predominantly ,-helical structure. The aggregate structure of the lipid A moiety of the endotoxins as determined by small-angle X-ray scattering shows a change of a unilamellar/inverted cubic into a multilamellar structure in the presence of HDL. Fluorescence resonance energy transfer data indicate an intercalation of pure HDL, and of [LPS],[HDL] complexes into phospholipid liposomes. Furthermore, HDL may enhance the lipopolysaccharide-binding protein-induced intercalation of LPS into phospholipid liposomes. Parallel to these observations, the LPS-induced cytokine production of human mononuclear cells and the reactivity in the Limulus test are strongly reduced by the addition of HDL. These data allow to develop a model of the [endotoxin]/[HDL] interaction. [source] Kinetics of tryptophan oxidation in plasma lipoproteins by myeloperoxidase-generated HOClFEBS JOURNAL, Issue 13 2000Andreas Jerlich The relative susceptibility of the apoprotein components of human lipoproteins [high-density lipoprotein (HDL) and low-density lipoprotein (LDL)] and their subclasses to oxidation by the myeloperoxidase/H2O2/Cl, system in vitro was studied by measuring the decrease in rate of tryptophan fluorescence. Whereas the lipoprotein-modification rate showed a saturation type of dependence on the concentration of myeloperoxidase, a biphasic dependence on the concentration of the lipoproteins was found. High concentrations of H2O2 were also found to inhibit tryptophan oxidation in LDL but to a lesser extent in HDL. The optimal rate of LDL and HDL modification was observed at pH 6.0. HDL was modified much more rapidly than LDL, which may be due to differences in size and different relative contents of protein and lipids per particle. No differences in rates of modification of LDL subclasses were observed, when the assays were standardized to equal LDL protein concentrations, but, when standardized to equal particle mass, an optimum at subclass 8 was found, which is probably due to differences in apolipoprotein B-100 conformation. It was concluded that HDL may have a beneficial effect in retarding LDL modification in inflammatory processes. [source] LPL polymorphism predicts stroke risk in menGENETIC EPIDEMIOLOGY, Issue 3 2002Alanna C. Morrison Abstract Variation in lipid levels has been associated with atherosclerotic vascular disease, including stroke. Genes contributing to interindividual variation in lipid levels may play a role in the etiology of stroke, either through their effects on lipid synthesis and metabolism or through separate pathways. For this reason, we sought to examine the association between polymorphisms in the lipoprotein lipase (LPL) and apolipoprotein E (APOE) genes and subclinical and clinical stroke in the Atherosclerosis Risk in Communities (ARIC) Study. Subclinical stroke was determined by cerebral magnetic resonance imaging (MRI). Subclinical cerebral infarct cases (n = 197) were compared to a stratified random sample identified from individuals participating in the MRI examination (n = 200). Incidence of clinical ischemic stroke was determined by following the ARIC cohort for an average of 7.5 years for potential cerebrovascular events; 218 validated clinical ischemic strokes were identified. A stratified random sample of the ARIC cohort (CRS, n = 964) was used as the comparison group for clinical cases. The LPL S291-carrying genotypes and APOE ,2- and ,4-carrying genotypes were not significantly associated with subclinical or clinical stroke. The LPL X447-containing genotypes were significantly associated with subclinical (odds ratio [OR], 4.32; 95% confidence interval [CI], 1.23,15.15; P = 0.020) and clinical stroke (hazard rate ratio [HRR], 2.57; 95% CI, 1.24,5.34; P = 0.01) in men, both by themselves and after adjustment for multiple stroke risk factors. The LPL S447X polymorphism is significantly associated with subclinical cerebral infarction and incident clinical ischemic stroke in men from a middle-aged American population. This association does not appear to be mediated by triglyceride, high-density lipoprotein (HDL)- and low-density lipoprotein (LDL)-cholesterol levels, or additional stroke risk factors. Genet. Epidemiol. 22:233,242, 2002. © 2002 Wiley-Liss, Inc. [source] New Beverage for Cardiovascular Health, Proposal Based on Oriental and Occidental Food Culture from a World-Wide Epidemiological StudyGERIATRICS & GERONTOLOGY INTERNATIONAL, Issue 2008Emilio Hideyuki Moriguchi Objectives: To investigate whether combined isoflavones and antioxidants in oriental and occidental drinks reduce the risk of cardiovascular disease (CVD) in high-risk Japanese immigrants living in Brazil. Materials and methods: From among over 100 Japanese immigrants thirty-seven females aged 45,60 years in Porto Alegre, Brazil, were randomized after informed consent into two groups to drink 200 ml of whole soy cell juice (S) containing 7.5 g soy protein and 10 mg of isoflavones (aglycone) in peach juice or placebo peach juice (P) with 80 Kcal for 12 weeks. Health survey including 24-hour urine (24 U) examination were carried out before the randomization and after the double blind placebo controlled intervention study. Results: Both weight and body mass index (BMI) were significantly (p < 0.05, 0.01) decreased from the baseline only in the S group. Systolic blood pressure (SBP) was decreased significantly (p < 0.05) from the baseline in the S group with elevated 24 U isoflavone excretion (>10 µmol), and there was a significant (p < 0.05) inter-group difference between the S and P groups after intervention. Total and low density lipoprotein (LDL)-cholesterol (C) decreased significantly (p < 0.05) in the S group from the baseline and there was a significant difference (p < 0.05) between the S and P groups after intervention. HbA1c and atherogenic index (non-high density lipoprotein (HDL)-C/HDL-C) were significantly (p < 0.05) decreased in both groups. Conclusions: Soy isoflavones combined with fruit antioxidants, the combination of which might potentiate local nitric oxide (NO) affect, decreased SBP, total cholesterol and LDL-C. Peach juice itself improved blood glucose levels and the atherogenic index of the high-risk Japanese population in Brazil. [source] P2Y13 receptor is critical for reverse cholesterol transport,HEPATOLOGY, Issue 4 2010Aurélie C. Fabre A major atheroprotective functionality of high-density lipoproteins (HDLs) is to promote "reverse cholesterol transport" (RCT). In this process, HDLs mediate the efflux and transport of cholesterol from peripheral cells and its subsequent transport to the liver for further metabolism and biliary excretion. We have previously demonstrated in cultured hepatocytes that P2Y13 (purinergic receptor P2Y, G protein,coupled, 13) activation is essential for HDL uptake but the potential of P2Y13 as a target to promote RCT has not been documented. Here, we show that P2Y13 -deficient mice exhibited a decrease in hepatic HDL cholesterol uptake, hepatic cholesterol content, and biliary cholesterol output, although their plasma HDL and other lipid levels were normal. These changes translated into a substantial decrease in the rate of macrophage-to-feces RCT. Therefore, hallmark features of RCT are impaired in P2Y13 -deficient mice. Furthermore, cangrelor, a partial agonist of P2Y13, stimulated hepatic HDL uptake and biliary lipid secretions in normal mice and in mice with a targeted deletion of scavenger receptor class B type I (SR-BI) in liver (hypomSR-BI,knockoutliver) but had no effect in P2Y13 knockout mice, which indicate that P2Y13 -mediated HDL uptake pathway is independent of SR-BI,mediated HDL selective cholesteryl ester uptake. Conclusion: These results establish P2Y13 as an attractive novel target for modulating RCT and support the emerging view that steady-state plasma HDL levels do not necessarily reflect the capacity of HDL to promote RCT. (HEPATOLOGY 2010) [source] Scavenger receptor class B type I is a key host factor for hepatitis C virus infection required for an entry step closely linked to CD81,HEPATOLOGY, Issue 6 2007Mirjam B. Zeisel Hepatitis C virus (HCV) is a major cause of chronic hepatitis worldwide. Scavenger receptor class B type I (SR-BI) has been shown to bind HCV envelope glycoprotein E2, participate in entry of HCV pseudotype particles, and modulate HCV infection. However, the functional role of SR-BI for productive HCV infection remains unclear. In this study, we investigated the role of SR-BI as an entry factor for infection of human hepatoma cells using cell culture,derived HCV (HCVcc). Anti,SR-BI antibodies directed against epitopes of the human SR-BI extracellular loop specifically inhibited HCVcc infection in a dose-dependent manner. Down-regulation of SR-BI expression by SR-BI,specific short interfering RNAs (siRNAs) markedly reduced the susceptibility of human hepatoma cells to HCVcc infection. Kinetic studies demonstrated that SR-BI acts predominately after binding of HCV at an entry step occurring at a similar time point as CD81,HCV interaction. Although the addition of high-density lipoprotein (HDL) enhanced the efficiency of HCVcc infection, anti,SR-BI antibodies and SR-BI,specific siRNA efficiently inhibited HCV infection independent of lipoprotein. Conclusion: Our data suggest that SR-BI (i) represents a key host factor for HCV entry, (ii) is implicated in the same HCV entry pathway as CD81, and (iii) targets an entry step closely linked to HCV,CD81 interaction. (HEPATOLOGY 2007.) [source] Quantifying anomalous intestinal sterol uptake, lymphatic transport, and biliary secretion in Abcg8,/, mice,,HEPATOLOGY, Issue 4 2007Helen H. Wang Sitosterolemia is caused by mutations in either ABCG5 or ABCG8, but simultaneous mutations of these genes have never been observed. To explore whether ABCG8, the sterol efflux (hemi-)transporter, plays a major role in determining intestinal absorption efficiency and hepatic secretion rates of cholesterol and sitostanol, we performed direct measurements of the absorption and lymphatic transport of these sterols in mice with chronic biliary and lymphatic fistulae, as well as the transport rates of radiolabeled cholesterol and sitostanol from plasma high-density lipoprotein (HDL) into bile in male Abcg8,/, and wild-type mice. We observed that the absorption and lymphatic transport rates of radiolabeled cholesterol and sitostanol were increased by ,40% and ,500%, respectively, in Abcg8,/, mice in the setting of constant intraduodenal infusion of micellar taurocholate and lecithin. Both strains displayed identical intestinal Npc1l1 expression levels and small intestinal transit rates. After 45 minutes of intraduodenal infusion, acute intestinal uptake rates of trace [14C]cholesterol and [3H]sitostanol were essentially similar in both groups of mice with intact biliary secretion. Furthermore, in wild-type mice, mass transport rate of [3H]sitostanol from plasma HDL into bile was significantly faster than that of [14C]cholesterol; however, no [3H]sitostanol and only traces of [14C]cholesterol were detected in bile of Abcg8,/, mice. Conclusion: Deletion of the Abcg8 gene alone significantly increases the mass of intestinal cholesterol and sitostanol absorption and reduces but does not eliminate hepatic secretion of cholesterol. Moreover, the mutation has no influence on acute uptake of cholesterol and sitostanol by the enterocyte nor small intestinal transit time. (HEPATOLOGY 2007;45:998,1006.) [source] Serum amyloid A has antiviral activity against hepatitis C virus by inhibiting virus entry in a cell culture system,HEPATOLOGY, Issue 6 2006Muriel Lavie Serum amyloid A (SAA) is an acute phase protein produced by the liver. SAA concentration increases markedly in the serum following inflammation and infection. Large increases in SAA concentration during the acute phase response suggest that SAA has a beneficial role in host defense. This study sought to determine the effect of SAA on hepatitis C virus (HCV) infectivity using retroviral particles pseudotyped with HCV envelope glycoproteins (HCVpp) and the recently developed cell culture system for HCV (HCVcc). SAA inhibited HCVpp and HCVcc infection in a dose-dependent manner by affecting an early step of the virus life cycle. Further characterization with HCVpp indicated that SAA blocks virus entry by interacting with the viral particle. In addition, the antiviral activity of SAA was strongly reduced when high-density lipoproteins (HDL) were coincubated with SAA. However, HDL had only a slight effect on the antiviral activity of SAA when HCVpp was first preincubated with SAA. Furthermore, analyses of SAA in sera of chronic HCV patients revealed the presence of variable levels of SAA with abnormally elevated concentrations in some cases. However, no obvious clinical correlation was found between SAA levels and HCV viral loads. In conclusion, our data demonstrate an antiviral activity for SAA and suggest a tight relationship between SAA and HDL in modulating HCV infectivity. (HEPATOLOGY 2006;44:1626,1634.) [source] Influence of angiotensin-converting enzyme I/D gene polymorphism on clinical and histological correlates of chronic hepatitis CHEPATOLOGY RESEARCH, Issue 8 2009Carlo Fabris Aim:, This study aimed to verify the relationship between the insertion,deletion (I/D) polymorphism of angiotensin-converting enzyme (ACE) and clinical and histological correlates of chronic hepatitis C. Methods:, Two-hundred and fifty-eight, treatment naive, unselected hepatitis C virus (HCV) RNA-positive patients and 210 controls were studied. ACE allelic variants were determined by polymerase chain reaction. Results:, Mean staging scores adjusted for age, body mass index (BMI) and alcohol consumption were: men, D/* = 2.283; men, I/I = 2.092; women, D/* = 2.241; and women, I/I = 3.283 (P = 0.028). Age-adjusted mean BMI were: men, D/* = 25.01; men, I/I = 24.87; women, D/* = 23.73; and women, I/I = 22.50 (P = 0.006). Age and BMI-adjusted mean low-density lipoprotein (LDL)/ high-density lipoprotein (HDL) cholesterol ratios were: men, D/* = 2.344; men, I/I = 2.283; women, D/* = 1.916; and women, I/I = 1.903 (P = 0.004). Histological grading correlated positively with triglycerides and negatively with HDL and LDL cholesterol (P < 0.0001). Conclusion:, Female ACE I/I homozygotes have higher liver fibrosis scores in comparison to D/* women and to men; moreover, they are leaner and have a lower LDL/HDL cholesterol ratio. These observations suggest a possible mutual influence between ACE polymorphism, serum lipid concentrations and outcome of chronic HCV infection. [source] Prevalence of risk factors for cardiovascular disease in HIV-infected patients over time: the Swiss HIV Cohort StudyHIV MEDICINE, Issue 6 2006TR Glass Objective Metabolic changes caused by antiretroviral therapy (ART) may increase the risk of coronary heart disease (CHD). We evaluated changes in the prevalence of cardiovascular risk factors (CVRFs) and 10-year risk of CHD in a large cohort of HIV-infected individuals. Methods All individuals from the Swiss HIV Cohort Study (SHCS) who completed at least one CVRF questionnaire and for whom laboratory data were available for the period February 2000 to February 2006 were included in the analysis. The presence of a risk factor was determined using cut-offs based on the guidelines of the National Cholesterol Education Program (NCEP ATP III), the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC7), the American Diabetes Association, and the Swiss Society for Cardiology. Results Overall, 8033 individuals completed at least one CVRF questionnaire. The most common CVRFs in the first completed questionnaire were smoking (57.0%), low high-density lipoprotein (HDL) cholesterol (37.2%), high triglycerides (35.7%), and high blood pressure (26.1%). In total, 2.7 and 13.8% of patients were categorized as being at high (>20%) and moderate (10,20%) 10-year risk for CHD, respectively. Over 6 years the percentage of smokers decreased from 61.4 to 47.6% and the percentage of individuals with total cholesterol >6.2 mmol/L decreased from 21.1 to 12.3%. The prevalence of CVRFs and CHD risk was higher in patients currently on ART than in either pretreated or ART-naive patients. Conclusion During the 6-year observation period, the prevalence of CVRFs remains high in the SHCS. Time trends indicate a decrease in the percentage of smokers and individuals with high cholesterol. [source] | |||||||||||||||||||||||||||||||||||||