衰弱与心血管疾病的因果关联研究:两样本孟德尔随机化分析  

Causal association between frailty and cardiovascular diseases:a two-sample Mendelian randomization analysis Ren Gaocan

作　　者：任高灿 丁砚秋 闫子安 马晓昌[1,2] Ding Yanqiu;Yan Zi'an;Ma Xiaochang(Department of Cardiovascular Medicine,Xiyuan Hospital,China Academy of Chinese Medical Sciences,Beijing 100091,China.)

机构地区：[1]中国中医科学院西苑医院心血管科,北京100091 [2]国家中医心血管病临床医学研究中心,北京100091

出　　处：《中国循证心血管医学杂志》2025年第2期129-133,共5页Chinese Journal of Evidence-Based Cardiovascular Medicine

基　　金：国家重点研发计划项目(2018YFC1707404);中国中医科学院科技创新工程(CI2021A00904)。

摘　　要：目的衰弱是一种与年龄相关的多系统功能的下降状态,其与心血管疾病之间的关系受到广泛关注,但观察性研究尚未证明它们之间的因果关系。本研究旨在使用孟德尔随机化(MR)分析评估衰弱对心血管疾病的因果效应。方法利用全基因组关联研究(GWAS)数据进行分析,暴露因素为衰弱指数,结局变量为心肌梗死、心力衰竭、高血压、心房颤动、心脏瓣膜疾病。使用逆方差加权法(IVW)法为主要分析方法,另外采用MR-Egger法、加权中位数法、加权模式法进行孟德尔随机化分析,并进行水平多效性及异质性检验。结果IVW结果显示,衰弱与心肌梗死(OR=1.926,95%CI:1.687~2.65,P=7.29×10^(-8))、心力衰竭(OR=1.423,95%CI:1.222~1.624,P=6.01×10^(-4))、高血压(OR=2.173,95%CI:1.910~2.436,P=7.50×10^(-9))、心房颤动(OR=1.791,95%CI:1.415~2.167,P=2.38×10^(-3))发生风险升高有关,没有证据支持衰弱和心脏瓣膜疾病(OR=1.138,95%CI:0.917~1.359,P=2.52×10^(-1))之间的关联,未发现水平多效性及异质性,留一法结果显示结果稳健。反向MR分析,提示心血管疾病与衰弱的风险呈正相关。结论衰弱与心血管疾病之间存在双向因果关系,但衰弱并不会增加心脏瓣膜疾病风险。Objective To review the causal efficacy between frailty and cardiovascular diseases(CVD)by using Mendelian randomization(MS)analysis.Methods The analysis was carried out by using data of genomewide association study(GWAS).The exposure factor was frailty index,and outcome variables weremyocardial infarction(MI),heart failure(HF),hypertension,atrial fibrillation(AF)and valvular heart disease(VHD).Mendelian randomization(MS)analysis was carried out by using mainly inverse variance-weighted(IVW)and other methods including MR-Egger method,weighted median method and weighted mode method,and horizontal pleiotropy test and heterogeneity test were conducted.Results The results of IVW analysis showed that frailty was related to risk increases of MI(OR=1.926,95%CI:1.687~2.65,P=7.29×10^(-8)),HF(OR=1.423,95%CI:1.222~1.624,P=6.01×10^(-4)),hypertension(OR=2.173,95%CI:1.910~2.436,P=7.50×10^(-9))and AF(OR=1.791,95%CI:1.415~2.167,P=2.38×10^(-3)).There was no evidence to support the association between frailty and VHD(OR=1.138,95%CI:0.917~1.359,P=2.52×10^(-1)).There were no horizontal pleiotropy or heterogeneity observed.The results of left one method showed robustness.The results of reverse MR analysis indicated that CVD was positively correlated to frailty risk.Conclusion There is a bidirectional causal association between frailty and CVD,but frailty does not increase VHD risk.

关 键 词：衰弱 心血管疾病 孟德尔随机化 因果关系 

分 类 号：R543[医药卫生—心血管疾病]