脂蛋白与冠状动脉疾病风险之间的因果关联——孟德尔随机化研究的系统评价和荟萃分析

Causal association between lipoproteins and risk of coronary artery disease-a systematic review and meta-analysis of Mendelian randomization studies.

作者信息

Yang Rongyuan, Wu Shirong, Zhao Zhen, Deng Xuanxuan, Deng Qiuying, Wang Dawei, Liu Qing

机构信息

State Key Laboratory of Traditional Chinese Medicine Syndrome, Guangdong Provincial Hospital of Traditional Chinese Medicine, Guangzhou, 510120, People's Republic of China.

The Second Clinical School of Medicine, Guangzhou University of Traditional Chinese Medicine, Guangzhou, 510120, People's Republic of China.

出版信息

Clin Res Cardiol. 2024 Feb 26. doi: 10.1007/s00392-024-02420-7.

DOI:10.1007/s00392-024-02420-7

PMID:38407584

Abstract

OBJECTIVE

To systematically evaluate the causal effect of lipoproteins to the risk of coronary artery disease (CAD) by systematic review and meta-analysis of the associated Mendelian randomization (MR) studies.

METHODS

This systematic review was registered in PROSPERO (ID CRD42023465430). Searches from the databases (e.g., PubMed, Embase, Cochrane, Web of Science) and non-database sources to collect MR studies. The search time frame was from the database inception to August 2023. After data extraction, quality evaluation was performed, and the meta-analysis with bias evaluation was carried out with RevMan software.

RESULTS

A total of 5,828,409 participants from 21 records were included. Quality and bias assessment was performed by evaluating the internal three assumptions of MR studies. Meta-analysis for the causal association between non-HDL lipoproteins and CAD showed a significantly positive association between LDL and CAD (OR 1.37, 95% CI 1.26-1.49; P < 0.001, I = 95%), apoB and CAD (OR 1.38, 95% CI 1.11-1.71; P = 0.003, I = 98%), and Lp(a) and CAD (OR 1.21, 95% CI 1.12-1.31; P < 0.001, I = 99%). Interestingly, although there was no statistical significance in the association between VLDL/apoA1 and CAD (both P > 0.05), the pooled non-HDL lipoproteins showed a significantly positive association with CAD (OR 1.28, 95% CI 1.22-1.34; P < 0.001, I = 99%). For the HDL lipoproteins, the pooled OR showed a significantly negative association with CAD (OR 0.84, 95% CI 0.72-0.98; P = 0.002, I = 72%). However, the protective effect of HDL on CAD diminished when analyzed together with apoA1 and/or apoB (both P > 0.05). The funnel plot did not show serious publication bias, and sensitivity analysis performed relatively well robustness of the causal association of LDL, apoB, Lp(a), and total cholesterol with CAD.

CONCLUSION

The present meta-analysis suggests an overall effect of causal association between lipoproteins and CAD. Most of the non-HDL lipoproteins (LDL, apoB, Lp(a)) promote CAD, while the protective effect of HDL in CAD still needs to be verified in the future.

摘要

目的

通过对相关孟德尔随机化（MR）研究进行系统评价和荟萃分析，系统评估脂蛋白对冠心病（CAD）风险的因果效应。

方法

本系统评价已在PROSPERO（ID CRD42023465430）注册。从数据库（如PubMed、Embase、Cochrane、Web of Science）和非数据库来源进行检索，以收集MR研究。检索时间范围为从数据库建立至2023年8月。数据提取后，进行质量评估，并使用RevMan软件进行带有偏倚评估的荟萃分析。

结果

共纳入来自21篇记录的5828409名参与者。通过评估MR研究的内部三个假设进行质量和偏倚评估。非高密度脂蛋白与CAD之间因果关联的荟萃分析显示，低密度脂蛋白与CAD之间存在显著正相关（比值比1.37，95%置信区间1.26 - 1.49；P < 0.001，I² = 95%），载脂蛋白B与CAD之间存在显著正相关（比值比1.38，95%置信区间1.11 - 1.71；P = 0.003，I² = 98%），以及脂蛋白(a)与CAD之间存在显著正相关（比值比1.21，95%置信区间1.12 - 1.31；P < 0.001，I² = 99%）。有趣的是，尽管极低密度脂蛋白/载脂蛋白A1与CAD之间的关联无统计学意义（P均> 0.05），但汇总的非高密度脂蛋白与CAD之间存在显著正相关（比值比1.28，95%置信区间1.22 - 1.34；P < 0.001，I² = 99%）。对于高密度脂蛋白，汇总的比值比显示与CAD存在显著负相关（比值比0.84，95%置信区间0.72 - 0.98；P = 0.002，I² = 72%）。然而，当与载脂蛋白A1和/或载脂蛋白B一起分析时，高密度脂蛋白对CAD的保护作用减弱（P均> 0.05）。漏斗图未显示严重的发表偏倚，敏感性分析表明低密度脂蛋白、载脂蛋白B、脂蛋白(a)和总胆固醇与CAD因果关联的稳健性相对较好。