2024 年第 7 期 第 19 卷

高密度脂蛋白胆固醇脂质构成对多种冠心病风险的影响研究

The effect of high-density lipoprotein cholesterol lipid composition on the risk of multiple types of coronary atherosclerotic heart diseases

作者：李泽昆1马骁2杨俊体3

英文作者：Li Zekun1 Ma Xiao2 Yang Junti3

单位：1首都医科大学附属北京天坛医院急诊科，北京100070；2航空总医院天通苑门诊部，北京102218；3北京市垂杨柳医院医务处，北京100021

英文单位：1Department of Emergency Beijing Tiantan Hospital Capital Medical University Beijing 100070 China; 2Outpatient Department of Tiantongyuan Aviation General Hospital Beijing 102218 China; 3Medical Service Division Beijing Chuiyangliu Hospital Beijing 100021 China

关键词：冠心病（冠状动脉粥样硬化性心脏病）；高密度脂蛋白胆固醇；孟德尔随机化

英文关键词：Coronaryatheroscleroticheartdisease;High-densitylipoproteincholesterol;Mendelianrandomization

• 摘要：

• 目的 基于孟德尔随机化(MR)方法探索高密度脂蛋白胆固醇(HDL-C)脂质构成特征对多种冠心病(冠状动脉粥样硬化性心脏病)风险的影响。方法 根据MR研究的相关性、独立性和排他性假设，本研究从公开的全基因组关联研究数据中提取可以预测HDL-C脂质构成成分（比如HDL-C中的磷脂）的工具变量。用随机效应模型的拟方差加权法、MR-Egger法和MR-PRESSO法进行HDL-C脂质构成成分与冠状动脉粥样硬化及多种冠心病类型之间的因果推断。用Cochran′s Q法和MR-Egger截距法进行敏感度分析。结果 拟方差加权法提示外周HDL-C水平以及HDL-C中的总脂质、胆固醇酯、胆固醇和磷脂水平升高与冠心病、心肌梗死、不稳定型心绞痛和冠状动脉粥样硬化风险的降低存在显著相关性（均P＜0.05）；而HDL-C中的甘油三酯水平升高与冠心病、不稳定型心绞痛和冠状动脉粥样硬化风险升高存在显著相关性（均P＜0.05），与心肌梗死的风险无关（P＞0.05）。MR-Egger法和MR-PRESSO法所报告的结果支持上述拟方差加权法所报告的结果。虽然Cochran′s Q法在上述分析中报告了显著的异质性，但是本研究所使用的随机效应模型拟方差加权法可以克服这一不足从而得出可靠的结果。MR-Egger截距法在上述分析中均未发现显著的水平多效性。结论 HDL-C中的总脂质、磷脂和胆固醇成分在基因水平上对多种冠心病的发病起保护作用，而HDL-C中的甘油三酯成分则在基因水平上对除心肌梗死外的多种冠心病具有一定的致病作用。

• Objective To explore the effect of high-density lipoprotein cholesterol (HDL-C) composition on the risk of multiple types of coronary atherosclerotic heart disease based on Mendelian randomization (MR) method. Methods In accordance with the assumptions of relevance, independence, and exclusivity of MR Studies, instrumental variables were extracted from publicly available genome-wide association study data to predict the lipid composition of HDL-C, such as the phospholipids in HDL-C. Causal inference between HDL-C lipid composition and coronary atherosclerosis and various types of coronary atherosclerotic heart disease was carried out by using the random effects model pseudo-variance weighting method, MR-Egger method and MR-PRESSO method. Cochran′s Q method and MR-Egger intercept method were used for sensitivity analysis.Results  The increased levels of peripheral HDL-C, as well as the levels of total lipids, cholesterol esters, cholesterol, and phospholipids in HDL-C, were significantly associated with a reduced risk of coronary atherosclerotic heart disease, myocardial infarction, unstable angina, and coronary atherosclerosis(all P＜0.05). In contrast, increased triglyceride levels in HDL-C were significantly associated with increased risk of coronary atherosclerotic heart disease, unstable angina, and coronary atherosclerosis (all P＜0.05), but not myocardial infarction (P＞0.05). The results reported by the MR-Egger and MR-PRESSO methods support those reported by the pseudo-variance weighting method described above. Although the Cochran′s Q method reported significant heterogeneity in these analyses, the random-effects model pseudo-variance weighting method used in this study can overcome this limitation and provide reliable results. No significant level pleiotropy was found by the MR-Egger intercept method in any of the above analyses. Conclusion  The total lipid, phospholipid and cholesterol components of HDL-C play a protective role in the pathogenesis of multiple types of coronary atherosclerotic heart disease at the genetic level, while the triglyceride component of HDL-C plays a pathogenic role in the pathogenesis of many kinds of coronary atherosclerotic heart disease except myocardial infarction at the genetic level.