Background: The causal role of high-density lipoprotein (HDL) cholesterol in cardioprotection has been questioned by genetic and randomized studies. Novel measures that relate to HDL function may contribute new information to the prediction of cardiovascular risk. Apolipoprotein C-III (apoC-III) is a key regulator of lipoprotein metabolism. We investigated whether subspecies of HDL defined by apoC-III are associated with coronary heart disease (CHD).

Methods: We used immunoaffinity chromatography to measure the apoA-I concentrations of HDL that contains and lacks apoC-III in 2 prospective studies of adults free of CHD. In MESA (Multi-Ethnic Study of Atherosclerosis), 5657 participants (52% women, 52–72 years of age) were followed for risk of CHD from 2000 to 2002 through 2013. In a case-cohort study nested within the DCH study (Danish Diet, Cancer, and Health), 3642 participants (47% women, 51–64 years of age) were followed from 1994 to 1997 through 2010. Subsequently, we conducted a meta-analysis that combined these results with the previously published findings from 2 cohort studies that used similar laboratory methodology to measure lipoproteins, totaling 2997 incident cases.

Results: ApoC-III was found on 6% to 8% of apoA-I. The 2 HDL subspecies showed opposing associations, with risk of CHD in each of the individual cohorts and in the meta-analysis (P heterogeneity between the 2 subspecies <0.01). HDL that contains apoC-III was associated with a higher risk of CHD (pooled relative risk per standard deviation, 1.09; 95% confidence interval, 1.01–1.18), whereas HDL that lacks apoC-III was associated with lower risk (relative risk, 0.76; 95% confidence interval, 0.70–0.83). The relative risk for HDL lacking apoC-III was even more negative than the relative risk for total HDL (relative risk, 0.80; 95% confidence interval, 0.74–0.87).

Conclusions: Our findings from 4 prospective studies support the hypothesis that apoC-III may mark a subfraction of HDL that is associated with higher risk of CHD. New measures reflecting HDL structure and function may provide novel insights for cardiovascular risk that extend beyond traditional plasma HDL cholesterol concentrations.

中文翻译：

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由载脂蛋白C-III和四组人群冠心病定义的高密度脂蛋白亚种

背景：遗传和随机研究质疑高密度脂蛋白（HDL）胆固醇在心脏保护中的因果作用。与高密度脂蛋白功能有关的新措施可能为心血管风险的预测提供新的信息。载脂蛋白C-III（apoC-III）是脂蛋白代谢的关键调节剂。我们调查了由apoC-III定义的HDL亚型是否与冠心病（CHD）相关。

方法：在两项无冠心病成人的前瞻性研究中，我们使用免疫亲和色谱法测量了含有和缺乏apoC-III的HDL的apoA-I浓度。在2000年至2002年至2013年间，对5657名参与者（52％的女性，52-72岁）进行了5657名参与者（52％的女性，52-72岁）的MESA（动脉粥样硬化多民族研究）研究。从1994年至1997年至2010年，共有3642名参与者（47％的女性，年龄在51-64岁之间）接受了丹麦饮食，癌症和健康研究。随后，我们进行了荟萃分析，将这些结果与之前发表的研究结果相结合2项队列研究使用了相似的实验室方法测量脂蛋白，总共发生2997例事件。

结果：在apoA-I的6％至8％中发现了ApoC-III。2个HDL亚种显示出相反的关联，在每个队列和荟萃分析中都有CHD风险（2个亚种之间的P异质性<0.01）。含有apoC-III的HDL与冠心病的风险较高（每标准偏差合并相对风险为1.09； 95％置信区间为1.01-1.18），而缺乏apoC-III的HDL与较低的风险（相对风险， 0.76； 95％置信区间0.70-0.83）。缺乏apoC-III的HDL的相对风险甚至比总HDL的相对风险更负（相对风险，0.80； 95％置信区间，0.74-0.87）。

结论：我们从4项前瞻性研究中得出的结果支持以下假说，即apoC-III可能标志着HDL的亚部分，与CHD的较高风险有关。反映HDL结构和功能的新措施可能为心血管风险提供新颖见解，其范围已超出传统血浆HDL胆固醇浓度。