Familial aggregation of coronary heart disease: partial mediation by high density lipoproteins?

The potential explanation of coronary heart disease inheritance by the major coronary risk factors was explored in a random sample of 1044 males, aged 40-70 years, who formed part of the Jerusalem Lipid Research Clinic Prevalence Study. Standardised data were available on personal and family history, coronary risk factors, resting and exercise electrocardiography. Twelve percent of subjects had coronary heart disease (previous myocardial infarction or electrocardiographic changes) and 20% had a family history of heart attack before 60 years in first degree relatives. In the presence of a family history of heart attack, the mean level of high density lipoprotein-cholesterol (HDL-C) was 5 mg/dl lower in cases of coronary heart disease than in controls. No such difference existed in the absence of a family history of heart attack. In multiple logistic regression, HDL-C was a significant negative predictor of coronary heart disease presence, but only in subjects having a positive family history. A 1 standard deviation (10 mg/dl) increment in HDL-C was associated with a two-thirds reduction in heart disease risk. Other risk factors did not predict the occurrence of coronary heart disease to any significant extent in subjects with a positive family history of heart attack. In an overall logistic model combining family history with other risk factors, the significant predictors of heart disease were: age, total plasma cholesterol, hypertension, family history and HDL-C. The interaction term, family history X HDL-C, was also a significant negative predictor of heart disease.(ABSTRACT TRUNCATED AT 250 WORDS)     

Association of lipids, lipoproteins, apolipoproteins and paraoxonase enzyme activity with premature coronary artery disease

BACKGROUND AND DESIGN: The association of serum apolipoprotein (apo) A-I and apo B concentrations and paraoxonase (PON) enzyme activity with angiographically determined coronary artery disease (CAD) was investigated in Iranian non-diabetic patients with premature CAD and control participants in a sex- and age-matched case-control study. METHODS: The study population consisted of 59 non-diabetic patients with premature CAD and 55 CAD control participants. Premature CAD was defined as the presence of angiographically proven coronary stenosis (> or =50% involvement) in men and women younger than 55 and 65 years, respectively. Apolipoprotein concentrations were measured by immunoturbidometric assay and paraoxonase/arylesterase activities by spectrophotometric assay of p-nitrophenol/phenol production following addition of paraoxon/phenylacetate to serum. RESULTS: In CAD patients, increased concentrations of total cholesterol (215 +/- 43 compared with 193 +/- 43, P < 0.001), low-density lipoprotein cholesterol (137 +/- 46 compared with 116 +/- 39, P < 0.05) and apo B (102 +/- 24 compared with 84 +/- 17, P < 0.001) and a decreased ratio of apo A-I/apo B (1.7 +/- 0.4 compared with 2.0 +/- 0.6, P < 0.001) were observed compared to the control group. Other study variables were not significantly different between the two groups. On multiple logistic regression analysis, the only marker for discrimination between the CAD+ group and the CAD- control group was apo B level. CONCLUSIONS: In Iranian non-diabetic patients with premature CAD, the concentration of apo B is a better marker than traditional lipids in discriminating between CAD+ and CAD- patients. The lack of significant difference in PON activity between CAD patients and control participants supports the concept of interethnic variability in PON activity and gene polymorphism observed in other studies.     

Effect of long-term physical training on hemostasis in patients with coronary heart disease and non-insulin dependent diabetes

AIM: To study effects of 6-month physical training on some parameters of hemostasis in patients with coronary heart disease and non-insulin dependent diabetes (NIDDM). RESULTS: Long-term physical training resulted in lowering of fibrinogen level and increase of fibrinolytic activity assessed as euglobulin fraction clot lysis time, while factor VII activity remained unchanged. These changes were accompanied with elevation of total and high density lipoprotein cholesterol levels without any shifts in low density lipoprotein cholesterol and triglycerides. Most pronounced positive effect physical training exerted on results of a test with standard single fat load, which was used as a model of postprandial lipemia. Serum cortisol level significantly decreased after 6-month training, especially after fat load and subsequent physical exertion. CONCLUSION: In patients with combination of coronary heart disease and NIDDM long-term physical training was associated with decreased thrombogenicity of blood.     

Plasma insulin, serum lipids and lipoproteins in gall stone disease in non-insulin dependent diabetic subjects: a case control study.

Fasting insulin, lipids and lipoproteins were measured in 22 middle aged female non-insulin dependent diabetics with gall stone disease (cases) and in 22 non-insulin dependent diabetics without gall stone disease (controls). The groups were matched for sex, age, obesity, and fasting glucose concentrations. No differences were observed between the cases and controls in duration of diabetes, glycated haemoglobin A1, alcohol intake, smoking, use of cardiovascular drugs or a history of myocardial infarction. Diabetics with gall stone disease had higher fasting insulin concentrations (p less than 0.5), lower total (p less than 0.01) and low density lipoprotein cholesterol (p less than 0.01) and high density lipoprotein cholesterol (not statistically significant) concentrations than diabetics without gall stone disease. These changes in insulin, lipids and lipoproteins are similar to reported changes in non-diabetic subjects with gall stone disease. Therefore, they are characteristic for gall stone disease and not as such explanatory to an increased risk of gall stones in patients with non-insulin dependent diabetes.     

Chronic kidney disease,lipids and apolipoproteins,and coronary heart disease: The ARIC Study

Background

Chronic kidney disease (CKD) is associated with elevated apolipoprotein B to A-1 ratio (ApoB/A1). It is not known whether these markers are more strongly associated with the risk of coronary heart disease (CHD) in CKD compared to traditionally measured lipids and lipoprotein cholesterol ratios.

Methods

We studied the association of lipids and apolipoproteins including non-HDL-cholesterol to HDL-cholesterol ratio (NonHDLc/HDLc) and ApoB/A1 with incident CHD in 10,137 individuals free of CHD at baseline (visit four) in the Atherosclerosis Risk in Communities (ARIC) study. An estimated glomerular filtration rate of 15 to <60 ml/min/1.73 m² based on a cystatin C measurement was used to define CKD (Stage 3–4). Cox proportional hazards regression models were used to determine the association of lipids and apolipoprotein measurements with the risk of CHD in those with and without CKD after adjustment for demographic and known clinical cardiovascular risk factors.

Results

CKD was present in 1217 (12%) individuals free of CHD at baseline. The median follow-up time was 11.1 years. A CHD event developed in 498 out of 8920 individuals without CKD (incidence rate: 5.2 events per 1000 person-years) and in 138 out of 1217 individuals with CKD (incidence rate: 12.0 events per 1000 person–years; P < 0.001). Those with CKD had a lower concentration of ApoA1: median (in g/L) and interquartile range (IQR) = 1.40 (1.38–1.42) vs. 1.48 (1.47–1.49) P < 0.001; and a higher ApoB/A1 = 0.75 (0.73–0.77) vs. 0.71 (0.70–0.72) P < 0.001; than those without CKD (eGFR ≥ 60 ml/min/1.73 m²). Among individuals with CKD, ApoB/A1 and NonHDLc/HDLc were both associated with the risk of CHD: hazard ratios (HR) and 95% confidence intervals (CI) per one standard deviation increase = 1.22 (1.02–1.46) for ApoB/A1 and 1.30 (1.07–1.57) for NonHDLc/HDLc with no significant differences detected (P for interaction >0.1) when comparing these estimates to those of participants without CKD.

Conclusions

Although CKD is associated with a lower ApoA1 concentration and with a higher ApoB/A1, we found no evidence that these apolipoproteins are more strongly associated with CHD incidence in CKD compared to NonHDLc/HDLc.     

Association of low-density lipoprotein particle size and ratio of different lipoproteins and apolipoproteins with coronary heart disease

BACKGROUND: Worldwide coronary heart disease (CHD) is estimated to be the leading cause of death. Current knowledge about prevention of CHD is mainly derived from developed countries. Therefore, this study aimed to find out the association of CHD with ratios of different lipoproteins and apolipoproteins, LDL particle size, as well as different traditional risk factors in Asian Indian population in Eastern part of India. METHODS: Case-control study of 100 patients with CHD and 98 healthy controls were age and sex matched. After clinical evaluation, blood samples were collected for biochemical assays. RESULTS: Multivariate logistic regression analysis found apoB (OR 2.96; 95% CI 1.02-8.54), apoB/HDL-c (OR 4.14; 95% CI 1.33-12.83), nonHDL-c (OR 5.41; 95% CI 2.08-14.10), apoB/apoAI (OR 6.64; 95% CI 2.37-18.57), and LDL particle size (9.59; 95% CI 2.92-31.54) were independently associated with CHD. Area under the ROC curves derived from the model (AUROC 0.947; 95% CI 0.916-0.977) are significantly higher than any other variables. CONCLUSIONS: Findings from the multivariate analysis, apoB, apoB/HDL-c, nonHDL-c, apoB/apoAI, and LDL particle size are potent indicators and useful for diagnosis of predisposed CHD.     

Varied effects of dietary sucrose and cholesterol on serum lipids, lipoproteins and apolipoproteins in rhesus monkeys.

Serum lipid, lipoproteins, apolipoproteins and plasma insulin and glucose were studied in rhesus monkeys (Macaca mulatta) fed high sucrose diets (69%, w/w), with and without added cholesterol. When compared to basal diet, a high sucrose diet with no added cholesterol fed for 6 weeks increased serum total cholesterol and triglycerides by factors of 1.2 and 2.8, respectively. Cholesterol supplementation of sucrose diets increased the serum total cholesterol levels by a factor of 2.2 and decreased the serum triglycerides by 0.47. The serum cholesterol response to experimental diets was reflected predominantly in beta-lipoprotein and to a lesser extent in alpha-lipoprotein. Sucrose diets without cholesterol enriched the beta- and pre-beta-lipoproteins with triglycerides and protein at the expense of cholesterol. On the same diet, the protein content of alpha-lipoprotein increased at the expense of cholesterol and triglycerides. In contrast, dietary cholesterol decreased the triglyceride content and increased the cholesterol content of all the lipoprotein classes. Sucrose feeding seems to increase ApoB more than non-ApoB proteins. The proportion of ApoC-II relative to ApcoC-III increased in each animal on a sucrose diet; exogenous cholesterol further increased this trend. While sucrose diet decreased ApoA-I/ApoA-II ratios, cholesterol supplementation reversed this trend. Dietary sucrose increased the plasma glucose, insulin, and insulin-glucose ratios. The addition of cholesterol also tended to decrease plasma glucose and insulin levels. These observations indicate varied responses of serum lipoproteins and apoproteins to dietary sucrose with and without cholesterol supplementation.     

载脂蛋白E基因多态性与健康人群血脂谱改变的关系

目的 :研究载脂蛋白E(apoE)基因多态性与健康人群血脂谱改变的关系。方法 :随机选择 16 8例江苏地区无血缘关系健康汉族人群 ,用聚合酶链反应 限制性片段长度多态性技术检测其apoE基因型。分析各基因型及等位基因对血脂、载脂蛋白及脂蛋白 (a)的影响。结果 :apoE各等位基因血清总胆固醇 (TC)、低密度脂蛋白胆固醇 (LDL C)及apoB水平由高到低依次为ε4 >ε3>ε2 。ε2 等位基因具有明显的降低TC、LDL C和apoB的作用 ;而ε4 等位基因的作用正相反。结论 :apoE基因多态性是个体间血脂谱差异的独立遗传因素。     

Effects of rosuvastatin on lipids, lipoproteins and apolipoproteins in the dyslipidaemia of diabetes.

AIMS: To compare the effects of rosuvastatin and atorvastatin 10 and 20 mg on plasma lipid and lipoprotein profiles in patients with Type 2 diabetes mellitus and triglycerides < or = 6.0 mmol/l. METHODS: A double-blind, randomized, multicentre study to assess the effect of rosuvastatin and atorvastatin, at 10 mg/day for 8 weeks followed by 20 mg/day for a further 8 weeks, on low-density lipoprotein cholesterol (LDL-C), together with a range of secondary lipid and lipoprotein end points. RESULTS: Rosuvastatin reduced mean LDL-C levels from baseline over 16 weeks by 57.4%, while atorvastatin reduced mean LDL-C levels by 46.0% over the same period. The difference in LDL-C reduction between treatments was statistically significant (P < 0.001). Rosuvastatin also produced statistically significantly greater mean reductions from baseline in levels of total cholesterol, non-high-density lipoprotein cholesterol, apolipoprotein B and lipid ratios. More patients achieved European LDL-C (< 2.5 mmol/l) and total cholesterol (< 4.5 mmol/l) goals with rosuvastatin than with atorvastatin. Rosuvastatin was associated with a significantly (P < 0.049) greater mean percentage increase in glycated haemoglobin (HbA(1c)) from baseline compared with atorvastatin; however, patients in both treatment groups maintained good glycaemic control. Both rosuvastatin and atorvastatin were well tolerated. CONCLUSIONS: Greater reductions in LDL-C were achieved with rosuvastatin compared with equal doses of atorvastatin, enabling more patients with Type 2 diabetes to achieve European LDL-C goals.     

The effects of adrenocorticotrophic hormone and an equivalent dose of cortisol on the serum concentrations of lipids, lipoproteins, and apolipoproteins

Previous studies have shown a strong lipid-lowering effect of adrenocorticotrophic hormone (ACTH) in healthy individuals and in patients with different kinds of dyslipoproteinemia. The mechanism behind this effect has not been established and its direct ACTH-specific nature has been questioned. Therefore, the present study was performed. Thirty healthy young males were randomized into 3 groups of equal size: one group received ACTH1-24 1 mg IM, daily for 4 days, another group was treated with cortisol 150 mg ID (50 mg tid) daily for 4 days, whereas a control group was observed for 4 days. Fasting blood samples were collected before and after treatment or observation. The serum concentrations of cholesterol (12%, P < .05), low-density lipoprotein cholesterol (24%, P < .01), and apolipoprotein (apo) B (31%, P < .01) decreased significantly in the ACTH group but not in the cortisol and control groups. The statistical workup confirmed that only ACTH had a lowering effect on the apo B-containing lipoproteins. In contrast, the results indicated conformity between the treatment groups with respect to increases in the serum apo E concentrations. There were inconsistent changes in the serum concentrations of the triglycerides, high-density lipoprotein cholesterol, apo A, and lipoprotein(a). The main results were clear: the lowering effect of ACTH on the serum concentration of apo B-containing lipoproteins could not be ascribed to cortisol. These, in combination with previous in vitro results, indicated an ACTH-specific effect.     

Gemfibrozil therapy in primary type II hyperlipoproteinemia: effects on lipids, lipoproteins and apolipoproteins

Gemfibrozil lowers triglycerides, low density lipoprotein (LDL) and very low density lipoprotein (VLDL) cholesterol. It also promotes a significant increase of high density lipoprotein (HDL) cholesterol. It has been established that normalization of apolipoproteins is an important protective factor against atherosclerosis. The present report examines the effectiveness of 12 months of gemfibrozil treatment on plasma lipids and apolipoproteins in types IIa (VLDL 18 +/- 2 mg cholesterol/dL) and IIb (VLDL 58 +/- 7 mg cholesterol/dL) hypercholesterolemic patients. Gemfibrozil lowered plasma triglycerides, VLDL cholesterol and apolipoprotein B (apoB), increased HDL cholesterol and apoAI levels in both groups, and induced a very substantial reduction in LDL cholesterol in type IIa patients only. Even though HDL particles were enriched in cholesterol, indicating improvement in the reverse cholesterol transport and lower risk of atherosclerosis in both groups, it is important to note that production of cholesterol-poor LDL particles and reduction in LDL cholesterol and the LDL/HDL cholesterol ratio were observed only in the normotriglyceride group (type IIa). Due to the initially elevated concentration of plasma triglycerides and VLDL in type IIb patients and the increased catabolism of VLDL to LDL during gemfibrozil therapy, this drug has a more efficient regulating effect on LDL particles in type IIa compared with type IIb hyperlipidemia.     

Impaired protection against diabetes and coronary heart disease by high-density lipoproteins in Turks

The issue of whether or not incident type 2 diabetes mellitus and coronary heart disease (CHD) can be predicted by high-density lipoprotein (HDL) cholesterol in both sexes needs investigation. A representative sample of 3035 middle-aged Turkish adults free of CHD at baseline was studied with this purpose prospectively over a mean of 7.8 years. High-density lipoprotein cholesterol levels were found to be correlated in women positively with plasma fibrinogen and weakly with waist girth and C-reactive protein, and to be not correlated with fasting insulin. High-density lipoprotein cholesterol protected men against future CHD risk (for a 12-mg/dL increment: relative risk = 0.80 [95% confidence interval, 0.69-0.95]) after multivariable adjustment in logistic regression analyses for age, smoking status, physical activity grade, hypertension, abdominal obesity, diabetes, and lipid-lowering drugs. However, men were not protected against risk of diabetes. In women, HDL cholesterol was not associated with risk for CHD, whereas intermediate (40-60 mg/dL) compared with lower HDL cholesterol levels proved protective against risk of diabetes (relative risk = 0.57 [95% confidence interval, 0.36-0.90]) after adjustments that included apolipoprotein A-I tertiles. Yet higher serum concentrations failed to yield protection against diabetes. It was concluded that HDL particles confer partially lacking protection against cardiometabolic risk among Turks, and this impairment is modulated by sex. This highly important observation may result from a setting of prevailing chronic subclinical inflammation.     

Effect of mild aerobic exercise on serum lipids and apolipoproteins in patients with coronary artery disease

The effects of mild aerobic exercise on serum lipids, apolipoproteins and lecithin-cholesterol acyltransferase (LCAT) activity were examined in 11 male patients with coronary artery disease and 4 healthy male controls. The mild aerobic exercise program involved exercise intensity at 50% of maximal oxygen uptake, as determined from the blood lactate threshold, for 60 min periods 3 times per week for 10 weeks. Following mild aerobic exercise, serum levels of high density lipoprotein cholesterol (HDL-C) were increased significantly from 50 +/- 7 mg/dl to 59 +/- 11 mg/dl (p less than 0.05) with a simultaneous increase in apolipoprotein A-I (apo A-I) in normal controls. The LCAT activity was significantly increased from 65 +/- 22 nmol/ml/hr to 99 +/- 30 nmol/ml/hr in normal controls (p less than 0.05). Furthermore, maximal oxygen uptake (VO2max) was significantly increased in normal controls. In contrast, no significant changes were found in HDL-C, apo A-I, apo B, VO2max and body weight in patients with coronary artery disease. There was significant correlation between the initial HDL-C level and the change in HDL-C level following the exercise program in the combined group of normal controls and patients with coronary artery disease.     

血清脂蛋白与冠状动脉病变的关系

目的:探讨血清脂蛋白水平与冠脉病变程度之间的关系。方法:回顾性分析311例行选择性冠状动脉造影的患者,其中267例冠心病(CHD)患者分为稳定型心绞痛(SAP)和急性冠脉综合征(ACS)组,分别测定总胆固醇(TC)、三酰甘油(TG)、高密度脂蛋白胆固醇(HDL-C),低密度脂蛋白胆固醇(LDL-C),载脂蛋白AI(Apo-AI),载脂蛋白B(Apo-B),脂蛋白a(Apoa),计算出LDL/HDL-C和TG/HDL。比较各组血清脂蛋白水平的差异及与冠状动脉病变程度的相关性,并与44例冠脉造影正常组比较。结果:CHD组HDL-C、Apo-AI较对照组显著降低;ACS组较SAP组HDL-C、Apo-AI显著降低(P0.01)。血浆Apo-B水平越高,患者冠状动脉病变血管数越多。结论:HDL-C、Apo-AI与冠脉病变程度具有负相关关系;而Apo-B水平与冠状动脉硬化范围呈正相关。