Protective effect of apolipoprotein E2 on coronary artery disease in African Americans is mediated through lipoprotein cholesterol

We studied the relationship of apolipoprotein E (apoE) isoforms and coronary artery disease (CAD) in 224 African Americans and 326 Caucasians undergoing diagnostic coronary angiography. The presence of CAD was defined as >50% stenosis in at least one artery. ApoE allele frequencies were 0.12, 0.62, and 0.26 for epsilon 2, epsilon 3, and epsilon 4, respectively, in African Americans and 0.08, 0.78, and 0.14 for epsilon 2, epsilon 3, and epsilon 4, respectively, in Caucasians. Among African Americans, CAD was present in 9 of 34 epsilon 2 carriers (26%), significantly smaller (P < 0.05) in proportion compared with 39 of 82 epsilon 3 carriers and 43 of 92 epsilon 4 carriers (48% and 47%, respectively), suggesting a protective effect of the epsilon 2 allele. No such difference was seen in Caucasians. In African Americans but not Caucasians, LDL cholesterol was lower in epsilon 2 carriers than in epsilon 3 and epsilon 4 carriers (106 vs. 127 and 134 mg/dl, respectively; P < 0.005). After adjusting for lipid levels, the association between apoE2 and CAD was no longer significant. Thus, the protective effect of apoE2 seen in African Americans could be explained by a favorable lipid profile in epsilon 2 carriers, whereas in Caucasians, the absence of such a protective effect could be attributable to the lack of effect of apoE2 on the lipid profile.     

Association of Plasma Resistin Levels with Coronary Heart Disease in Women

Objective: To examine the association between plasma resistin levels and the presence of coronary heart disease (CHD) in women. Research Methods and Procedures: Plasma resistin levels were measured in a case‐control study including 185 women with angiographically confirmed CHD and 227 population‐based female controls from the Coronary Risk Factors for Atherosclerosis in Women (CORA) study. Results: After adjustment for age, smoking, family history of myocardial infarction, retirement, education, physical activity, menopausal status, hormone replacement use, BMI, hypertension, diabetes, and dyslipidemia, the odds ratio for CHD for women in the highest compared with lowest quintile of plasma resistin levels was 3.19 (95% confidence interval, 1.44 to 7.10; p log trend, 0.001). After additional adjustment for plasma C‐reactive protein levels, this association was substantially attenuated and no longer significant (odds ratio, 1.80; 95% confidence interval, 0.69 ti 4.69; p trend = 0.23). Discussion: These results suggest that plasma resistin levels are significantly associated with the presence of CHD in women; however, this association can largely be explained by concomitant inflammatory processes. Further studies are needed to determine the causal role of resistin in the development of CHD in humans.     

Assessment of Global Coronary Heart Disease Risk in Overweight and Obese African‐American Women

Objective : To examine, with the use of national guidelines, coronary heart disease (CHD) risk with increasing BMI for primary prevention in urban African‐American women. Research Methods and Procedures : Participants were recruited for CHD risk factor screening from 20 churches as part of a larger study of nutrition and fitness (Project Joy). All participants had a demographic, smoking and medical history assessment, and the following measurements were taken: weight, height, waist circumference, blood pressure, lipid levels, and glucose. Three methods of defining risk, the Framingham Point Scoring System, a count of risk factors, and the presence of the multiple metabolic syndrome, based on the National Cholesterol Education Program Adult Treatment Panel III Report and BMI classes established by the Clinical Guidelines, were used. Results : A total of 396 women were eligible. Participants were 40 to 80 years of age and had marked excess prevalence of overweight and obesity (84%); 55% were obese. There was a linear increase in risk factors as BMI increased. Lipids did not differ significantly among BMI classifications. Seventeen percent of women had multiple metabolic syndrome. Eight percent and 16% of women in the normal and overweight BMI classes, respectively, had two or more modifiable risk factors. There was no difference in number of modifiable risk factors among the obese classes. The Framingham Point Scoring System assigned a <10% risk of a hard CHD event in 10 years to 97% of the women. Discussion : National risk assessment guidelines for primary prevention of CHD may not be adequate for overweight and obese urban African‐American women and require further study.     

Systematic comparison of family history and polygenic risk across 24 common diseases

1. Download : Download high-res image (84KB)
2. Download : Download full-size image

     

Leucocyte copper, a marker of copper body status is low in coronary artery disease

To elucidate the relationship between leucocyte copper as a reliable, sensitive index of copper body status and extent of atherosclerosis in patients with Coronary Artery Disease (CAD) the present case-control study was carried out. 80 subjects were studied (23 females and 57 males), aged between 30-70, due to have a angiography. Individual angiograms were scored by combining the individual scores in all the major coronary arteries into one score of a scale 1.00 for patency to 0.00 for severe CAD. Serum and leucocyte copper and zinc were determined by GFAAS. No significant difference between patients with advanced CAD and relatively normal arteries were observed in the lipid profile and levels of plasma copper. Leucocyte copper had a significant link with the severity of atherosclerosis which was independent of sex. There was a linear relationship between the degree of decreasing leucocyte copper concentration and angiogram score. These findings give support to the hypothesis that marginal copper status, assessed by decreased leucocyte copper level, is associated with developing CAD.     

Dissecting the polygenic basis of atherosclerosis via disease-associated cell state signatures

1. Download : Download high-res image (126KB)
2. Download : Download full-size image

     

蝮蛇抗栓酶伍用刺五加对冠心病心率变异性的影响

目的探讨蝮蛇抗栓酶伍用刺五加对冠心病心率异性的影响。方法观察蝮蛇抗栓酶伍用刺五加对冠心病变异性的影响,并与对照组对比。结果治疗组ＳＤＮＮ、ＨＦ、ＬＦ／ＨＦ改变较对照组有显著差异性（Ｐ＜０．０１）。结论该方法能显著提高冠心病患者的心率变异性,对冠心病心源性猝死的预防有着重要意义。     

Polygenic risk prediction: why and when out-of-sample prediction R2 can exceed SNP-based heritability

1. Download : Download high-res image (216KB)
2. Download : Download full-size image

     

Polygenic transcriptome risk scores for COPD and lung function improve cross-ethnic portability of prediction in the NHLBI TOPMed program

1. Download : Download high-res image (130KB)
2. Download : Download full-size image

     

血浆及外周血中性粒细胞内髓过氧化物酶水平在冠心病临床诊断中的意义

目的:研究冠心病患者外周循环血中性粒细胞中髓过氧化物酶指数(MPXI)和血浆中髓过氧化物酶(MPO)浓度的改变及两者间相关性,探讨两者在冠心病临床诊断中的意义。方法:随机选取冠心病患者55例,按病情严重程度分为急性冠脉综征(ACS)组35例[包括不稳定心绞痛(UAP)组21例和急性心肌梗死(AMI)组14例]和稳定心绞痛(SAP)组20例,同时随机选取健康体检人员60例为正常对照组;采用ADVIA2120全自动血细胞分析仪检测MPXI,取血浆用ELISA法检测血浆MPO浓度。结果:ACS组MPXI(6.31±4.24)显著高于SAP组(3.38±2.14)和对照组(2.78±2.12),差异有统计学意义(P<0.05);SAP组MPXI高于正常对照组,差异无统计学意义(P>0.05)。ACS组血浆中MPO(1204.07±838.61 pmol/L)显著高于SAP组(755.97±426.23 pmol/L)和对照组(290.45±99.87 pmol/L),差异有统计学意义(P<0.05);SAP组MPO显著高于正常对照组,差异有统计学意义(P<0.05)。SAP组MPXI与MPO无相关性(r=0.424,P>0.05),ACS组MPXI与MPO呈负相关(r=-0.536,P<0.05)。结论:MPXI和MPO在冠心病的诊断中有意义,MPXI与血浆中MPO在ACS组中呈负相关。     

Polymorphisms at newly identified lipid-associated loci are associated with blood lipids and cardiovascular disease in an Asian Malay population

We conducted a cross-sectional study of Malay participants aged 40-80 years (n = 2,932) to examine the associations between polymorphisms at newly identified, lipid-associated loci with blood lipid levels and prevalent cardiovascular disease (CVD) in a Malay population in Asia. A polymorphism adjacent to the TRIB1 locus (rs17321515) was associated with elevated total cholesterol and LDL-cholesterol (LDL-C) after adjustment for age and sex (both P values <0.007) and with increased risk of coronary heart disease and CVD [odds ratio (OR) 1.23, 95% confidence interval (95% CI) 1.03-1.46; and OR 1.2, 95% CI 1.02-1.42, respectively] under an additive model of inheritance. In addition, using recessive models of inheritance, polymorphisms on chromosome 19 adjacent to the CILP2 and PBX4 loci (rs16996148) and on chromosome 1 at the GALNT2 locus (rs4846914) were associated with elevated HDL-C (P = 0.005) and lower LDL-C (P = 0.048), respectively. Although novel, the former is consistent with the association between this polymorphism and lower blood triglycerides observed in the initial studies conducted in populations of European ancestry. Neither showed statistically significant association with CVD. These observations should form the basis of further investigation to identify the causative polymorphisms at this locus, and also to understand the mechanistic roles that this protein may play in lipoprotein metabolism in Asians and other populations.     

步长稳心颗粒治疗冠心病合并心律失常临床观察

目的:观察步长稳心颗粒治疗冠心病合并心律失常的疗效。方法:选择98例门诊病人为观察对象,每次1包,每日三次,连续观察四周。结果:治愈51例,有效35例,总有效率87.7%。结论:步长稳心颗粒具有良好的抗心律失常的作用。     

Leptin and coronary heart disease risk: prospective case control study of British women

Objective: Prospective studies have shown a positive association between leptin concentrations and coronary heart disease (CHD) in men, but its effect in women is unclear. Our objective was to examine the association of serum leptin levels with CHD in a prospective study of women. Research Methods and Procedures: We conducted a prospective (4 year) case (N = 165) control (N = 335) study nested within a cohort of 4286 British women. Results: With mutual adjustment for each other and age, social class, smoking, and physical activity, leptin was positively associated with BMI, fasting insulin, total cholesterol, low‐density lipoprotein‐cholesterol, triglycerides, and hypertension and was inversely associated with homeostasis model assessment insulin sensitivity. Leptin was not associated with CHD risk (age‐adjusted relative risk for a doubling of leptin: 1.08 [95% confidence interval (CI): 0.91, 1.29]). This changed little with adjustment for childhood and adult social class, smoking, alcohol, and physical activity but attenuated to 1.00 (95% CI: 0.80, 1.26) with further adjustment for other metabolic risk factors (waist‐to‐hip ratio, low‐density lipoprotein‐cholesterol, triglycerides, C‐reactive protein, fasting insulin, hypertension). Discussion: We found no strong statistical evidence that leptin is associated with CHD risk in this study population of older British women. Further research is needed to compare associations of leptin with CHD in men and women and to determine whether the effect varies by gender.     

Four-point electrode measurement of impedance in the vicinity of bovine aorta for quasi-static frequencies

Results are presented here of experimental measurements using a four-point electrode technique to measure the complex impedance of bovine aorta submerged in Ringer's solution. Impedance measurements were taken at 250 microm intervals, ranging from 0 (the electrode directly on the surface of the tissue) to 10 mm. Frequencies ranged from 1 kHz to 10 MHz. Throughout this range, the measured impedance changed by an average of 400% when the electrode was 10 mm from the tissue as compared to when the electrode was in direct contact with the tissue. The change in impedance made it possible to determine when the electrode made contact with the arterial wall.     

载脂蛋白C-Ⅲ基因突变与冠心病

载脂蛋白C-III(apolipoprotein C-III,ApoC-III)是一种水溶性低分子蛋白质,主要分布于血浆高密度脂蛋白、极低密度脂蛋白和乳糜颗粒中。ApoC-III是脂蛋白代谢的重要调节因子,与高甘油三酯血症和冠状动脉粥样硬化性心脏病(coronary heart disease,CHD),即冠心病的进展相关联。ApoC-III基因的突变,可使血中脂质水平降低,起到明显的心脏保护作用,且对机体无不利影响。这就为研究特异性下调ApoC-III表达的疗法提供了可行性。这种有针对性的疗法对于降低冠心病相关的患病率和死亡率将是安全和有效的。     

冠状动脉粥样硬化性心脏病8号染色体基因扫描

冠状动脉粥样硬化性心脏病(Coronary heart disease,CHD)的全基因组扫描研究在世界各大研究中心展开,关于CHD易感基因位点的报道多集中于1号、3号、9号、11号、16号染色体,对8号染色体的研究报道甚少。在汉族人群中未见关于CHD的8号染色体的基因扫描研究。文章旨在查找汉族人群中CHD易感基因位点,选取8号染色体上间隔10 cM遗传距离的13个微卫星遗传位点,采用DNA混合池的方法对CHD患者组156例和正常对照组1 000例DNA样本进行基因扫描,经卡方检验分析患者组和对照组每个位点的等位基因频率差异。发现在患者组与对照组中D8S264位点(8p23.3-p23.2)及D8S285位点(8q12.1)的等位基因频率差异有统计学意义(P<0.05)。汉族人群中CHD患者8号染色体上8p23.3-p23.2、8q12.1区域可能存在CHD易感基因,需要进行候选基因突变筛查。     

Scavenger receptor Class B type I as a potential risk stratification biomarker and therapeutic target in cardiovascular disease

Cardiovascular disease (CVD) is the leading cause of mortality globally. There are few useful markers available for CVD risk stratification that has proven clinical utility. Scavenger receptor B type I (SR-BI) is a cell surface protein that plays a major role in cholesterol homeostasis through its interaction with high-density lipoprotein-cholesterol (HDL-C) esters (CE). HDL delivers CE to the liver through selective uptake by the SR-BI. SR-BI also regulates the inflammatory response. It has been shown that SR-BI overexpression has beneficial, protective effects in atherogenesis, and there is considerable interest in developing antiatherogenic strategies that involve SR-BI-mediated increases in reverse cholesterol transport through HDL and/or low-density lipoprotein. Further investigations are essential to explore the clinical utility of this approach. Moreover, there is growing evidence showing associations between genetic variants with modulation of SR-BI function that may, thereby, increase CVD risk. The aim of the current review was to provide an overview of the possible molecular mechanisms by which SR-BI may affect CVD risk, and the clinical implications of this, with particular emphasis on preclinical studies on genetic changes of SR-BI and CVD risk.