The effect of high-density lipoprotein cholesterol lipid composition on the risk of multiple types of coronary atherosclerotic heart diseases
Li Zekun
Ma Xiao
Yang Junti
Abstract：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.
Keywords：Coronary atherosclerotic heart diseaseHigh-density lipoprotein cholesterolMendelian randomization
Publication Date：2024-07-08
Online Publishing Date：2026-09-14(First online date of this platform, not the publication date of the document)
Pages：5( 970-974 )