Association of HDL cholesterol efflux capacity with incident coronary heart disease events: a prospective case-control study.
Association of HDL cholesterol efflux capacity with incident coronary heart disease events: a prospective case-control study.
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DOI：
10.1016/s2213-8587(15)00126-6
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发表时间：
2015-07
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--
通讯作者：
Rader DJ
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作者：
Saleheen D;Scott R;Javad S;Zhao W;Rodrigues A;Picataggi A;Lukmanova D;Mucksavage ML;Luben R;Billheimer J;Kastelein JJ;Boekholdt SM;Khaw KT;Wareham N;Rader DJ
虽然高密度脂蛋白胆固醇浓度与冠心病风险呈强负相关，但提高高密度脂蛋白胆固醇的干预措施并不能降低冠心病风险。高密度脂蛋白胆固醇外排能力-高密度脂蛋白功能的一个典型指标-在调整高密度脂蛋白胆固醇后与冠心病相关，但其对冠心病发病风险的影响尚不确定。我们测量了胆固醇外排能力，并评估了其与血管危险因素和冠心病事件的关系，该样本来自前瞻性EPIC-Norfolk研究的25639名40-79岁的个体，于1993-97年评估并随访至2009年。 我们定量胆固醇流出能力在1745例冠心病患者和1749例对照参与者无任何心血管疾病的使用一个有效的离体放射性示踪剂测定，涉及胆固醇标记的J774巨噬细胞与apoB-耗尽血清从研究参与者的孵育。胆固醇外排能力与HDL胆固醇浓度（r= 0.40; p<0.0001）和apoA-I浓度（r= 0.22; p<0.0001）呈正相关。它与2型糖尿病呈负相关（r=-0统计18; p<0·0001），与饮酒呈正相关（r=0·12; p<0·0001）。在比较上三分位数和下三分位数的分析中，胆固醇外排能力与冠心病事件发生率显著负相关，与年龄、性别、糖尿病、高血压、吸烟和饮酒、腰臀比、BMI、LDL胆固醇浓度、甘油三酯对数和HDL胆固醇或apoA-I浓度无关（比值比0.64，95%CI 0.51 - 0.80）。经过类似的多变量调整后，胆固醇外排能力每SD变化的冠心病发病风险为0.80（95%CI 0.70 - 0.90）。高密度脂蛋白胆固醇流出能力可能提供一种替代机制，用于治疗调节高密度脂蛋白胆固醇浓度以外的高密度脂蛋白途径，以帮助降低冠心病风险。美国国立卫生研究院、英国医学研究理事会、英国癌症研究所。
Although HDL cholesterol concentrations are strongly and inversely associated with risk of coronary heart disease, interventions that raise HDL cholesterol do not reduce risk of coronary heart disease. HDL cholesterol efflux capacity—a prototypical measure of HDL function—has been associated with coronary heart disease after adjusting for HDL cholesterol, but its effect on incident coronary heart disease risk is uncertain. We measured cholesterol efflux capacity and assessed its relation with vascular risk factors and incident coronary heart disease events in a nested case-control sample from the prospective EPIC-Norfolk study of 25 639 individuals aged 40–79 years, assessed in 1993–97 and followed up to 2009. We quantified cholesterol efflux capacity in 1745 patients with incident coronary heart disease and 1749 control participants free of any cardiovascular disorders by use of a validated ex-vivo radiotracer assay that involved incubation of cholesterol-labelled J774 macrophages with apoB-depleted serum from study participants. Cholesterol efflux capacity was positively correlated with HDL cholesterol concentration (r=0·40; p<0·0001) and apoA-I concentration (r=0·22; p<0·0001). It was also inversely correlated with type 2 diabetes (r=–0·18; p<0·0001) and positively correlated with alcohol consumption (r=0·12; p<0·0001). In analyses comparing the top and bottom tertiles, cholesterol efflux capacity was significantly and inversely associated with incident coronary heart disease events, independent of age, sex, diabetes, hypertension, smoking and alcohol use, waist:hip ratio, BMI, LDL cholesterol concentration, log-triglycerides, and HDL cholesterol or apoA-I concentrations (odds ratio 0·64, 95% CI 0·51–0·80). After a similar multivariable adjustment the risk of incident coronary heart disease was 0·80 (95% CI 0·70–0·90) for a per-SD change in cholesterol efflux capacity. HDL cholesterol efflux capacity might provide an alternative mechanism for therapeutic modulation of the HDL pathway beyond HDL cholesterol concentration to help reduce risk of coronary heart disease. US National Institutes of Health, UK Medical Research Council, Cancer Research UK.