美国哈佛大学研究人员5月16日报告说，他们完成的分析表明，单纯提高被称作“好胆固醇”的高密度脂蛋白胆固醇水平，并不能降低一个人患心脏病的风险。
高密度脂蛋白胆固醇和低密度脂蛋白胆固醇是人体中常见的两种胆固醇。前者能将血管中的血脂运到肝脏中处理掉，在一些观察性研究中，较高的“好胆固醇”水平与心脏病患病风险较低有关；而低密度脂蛋白胆固醇会把肝脏中的血脂运到血管里，诱发疾病，被称为“坏胆固醇”。
根据以往观察性研究的结论，由于遗传原因体内“好胆固醇”水平高的人患心脏病的风险应该较低，但哈佛大学研究人员的荟萃分析结果并非如此。利用孟德尔随机法，研究人员分析了20项包括两万多个心脏病病例及9.5万多名控制组对象的研究，其结果显示，“好胆固醇”水平高与患心脏病的风险并无关联。研究人员进一步分析14个仅与“好胆固醇”相关的基因变异后发现，“某些提高高密度脂蛋白水平的遗传机制不能降低心脏病患病风险”。
在16日发表在英国《柳叶刀》杂志网络版上的报告中，研究人员的结论是，“提高血浆高密度脂蛋白水平的（生活方式或药理学方面的）干预，并不能想当然地被认为能带来心脏病患病风险方面的相应益处”。
Plasma HDL cholesterol and risk of myocardial infarction: a mendelian randomisation study
Benjamin F Voight , Gina M Peloso , Marju Orho-Melander , Ruth Frikke-Schmidt DMSc
Background：High plasma HDL cholesterol is associated with reduced risk of myocardial infarction, but whether this association is causal is unclear. Exploiting the fact that genotypes are randomly assigned at meiosis, are independent of non-genetic confounding, and are unmodified by disease processes, mendelian randomisation can be used to test the hypothesis that the association of a plasma biomarker with disease is causal.
Methods：We performed two mendelian randomisation analyses. First, we used as an instrument a single nucleotide polymorphism (SNP) in the endothelial lipase gene (LIPG Asn396Ser) and tested this SNP in 20 studies (20 913 myocardial infarction cases, 95 407 controls). Second, we used as an instrument a genetic score consisting of 14 common SNPs that exclusively associate with HDL cholesterol and tested this score in up to 12 482 cases of myocardial infarction and 41 331 controls. As a positive control, we also tested a genetic score of 13 common SNPs exclusively associated with LDL cholesterol.
Findings：Carriers of the LIPG 396Ser allele (2·6% frequency) had higher HDL cholesterol (0·14 mmol/L higher, p=8×10−13) but similar levels of other lipid and non-lipid risk factors for myocardial infarction compared with non-carriers. This difference in HDL cholesterol is expected to decrease risk of myocardial infarction by 13% (odds ratio [OR] 0·87, 95% CI 0·84—0·91). However, we noted that the 396Ser allele was not associated with risk of myocardial infarction (OR 0·99, 95% CI 0·88—1·11, p=0·85). From observational epidemiology, an increase of 1 SD in HDL cholesterol was associated with reduced risk of myocardial infarction (OR 0·62, 95% CI 0·58—0·66). However, a 1 SD increase in HDL cholesterol due to genetic score was not associated with risk of myocardial infarction (OR 0·93, 95% CI 0·68—1·26, p=0·63). For LDL cholesterol, the estimate from observational epidemiology (a 1 SD increase in LDL cholesterol associated with OR 1·54, 95% CI 1·45—1·63) was concordant with that from genetic score (OR 2·13, 95% CI 1·69—2·69, p=2×10−10).
Interpretation：Some genetic mechanisms that raise plasma HDL cholesterol do not seem to lower risk of myocardial infarction. These data challenge the concept that raising of plasma HDL cholesterol will uniformly translate into reductions in risk of myocardial infarction.
Funding：US National Institutes of Health, The Wellcome Trust, European Union, British Heart Foundation, and the German Federal Ministry of Education and Research.
文献链接：https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(12)60312-2/fulltext
