Causal associations of remnant cholesterol with cardiometabolic diseases and risk factors: a mendelian randomization analysis.
Causal associations of remnant cholesterol with cardiometabolic diseases and risk factors: a mendelian randomization analysis.
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DOI：
10.1186/s12933-023-01927-z
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发表时间：
2023-08-10
影响因子：
9.3
通讯作者：
Xu H
中科院分区：
文献类型：
--
作者：
Guan B;Wang A;Xu H
新出现的证据表明，残余胆固醇（RC）与心脏代谢疾病（CMD）的发病率增加密切相关。然而，因果关系尚未得到证实。我们的目的是使用两样本孟德尔随机化（MR）方法评估RC与CMD的因果关系和相关危险因素。RC、CMD和心脏代谢风险因素的汇总水平统计量来自主要来自英国生物库和FinnGen生物库的欧洲血统个体的已发表数据。单变量和多变量MR分析用于评估RC和CMD之间的因果关系。进行双向MR分析，以估计RC和心脏代谢危险因素之间的因果关系。主要MR方法采用逆方差加权法。单变量MR分析显示，遗传预测RC与缺血性心脏病、心肌梗死、心房颤动和扑动、外周动脉疾病和非风湿性瓣膜疾病的风险增高有因果关系（均P < 0.05）。多变量MR分析提供了RC对缺血性心脏病风险有害影响的令人信服的证据（P < 0.05）。双向MR分析显示RC与总胆固醇、甘油三酯、低密度脂蛋白胆固醇、高胆固醇血症双向因果相关（均P < 0.05）。然而，没有发现RC和代谢紊乱或其他心脏代谢危险因素之间的遗传关联。这项MR研究表明，遗传驱动的RC增加了几种CMD和心脏代谢风险因素的风险，表明靶向降低RC的治疗可能对CMD的一级预防有效。在线版本包含补充材料，可通过10.1186/s12933-023-01927-z获得。
Emerging evidence suggests that remnant cholesterol (RC) is strongly associated with an increased incidence of cardiometabolic diseases (CMD). However, the causality have not been confirmed. We aimed to evaluate the causal associations of RC with CMD and the relative risk factors using two-sample Mendelian randomization (MR) methods. Summary-level statistics of RC, CMD, and cardiometabolic risk factors were obtained from the published data from individuals with a predominantly European ancestry mainly from the UK Biobank and the FinnGen biobank. Univariable and multivariable MR analyses were used to evaluate the causal relationships between RC and CMD. A bidirectional MR analysis was performed to estimate the causality between RC and cardiometabolic risk factors. The main MR method was conducted using the inverse-variance weighted method. Univariable MR analyses showed that genetically predicted RC was causally associated with higher risk of ischemic heart disease, myocardial infarction, atrial fibrillation and flutter, peripheral artery disease, and non-rheumatic valve diseases (all P < 0.05). Multivariable MR analyses provided compelling evidence of the harmful effects of RC on the risk of ischemic heart disease (P < 0.05). Bidirectional MR analysis demonstrated that RC was bidirectionally causally linked to total cholesterol, triglycerides, low-density lipoprotein cholesterol, hypercholesterolemia (all P < 0.05). However, no genetic association was found between RC and metabolic disorders or the other cardiometabolic risk factors. This MR study demonstrates that genetically driven RC increases the risk of several CMD and cardiometabolic risk factors, suggesting that targeted RC-lowering therapies may be effective for the primary prevention of CMD. The online version contains supplementary material available at 10.1186/s12933-023-01927-z.
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影响因子：
5.3
作者：
de Vries, Jeroen K.;Balder, Jan W.;Smit, Andries J.
通讯作者：
Smit, Andries J.
影响因子：
16.2
作者：
Mordi IR;Lumbers RT;Palmer CNA;Pearson ER;Sattar N;Holmes MV;Lang CC;HERMES Consortium
通讯作者：
HERMES Consortium
影响因子：
37.8
作者：
Dale CE;Fatemifar G;Palmer TM;White J;Prieto-Merino D;Zabaneh D;Engmann JEL;Shah T;Wong A;Warren HR;McLachlan S;Trompet S;Moldovan M;Morris RW;Sofat R;Kumari M;Hyppönen E;Jefferis BJ;Gaunt TR;Ben-Shlomo Y;Zhou A;Gentry-Maharaj A;Ryan A;UCLEB Consortium; METASTROKE Consortium;Mutsert R;Noordam R;Caulfield MJ;Jukema JW;Worrall BB;Munroe PB;Menon U;Power C;Kuh D;Lawlor DA;Humphries SE;Mook-Kanamori DO;Sattar N;Kivimaki M;Price JF;Davey Smith G;Dudbridge F;Hingorani AD;Holmes MV;Casas JP
通讯作者：
Casas JP
DOI：
10.1161/atvbaha.116.308834
发表时间：
2017-05-01
影响因子：
8.7
作者：
Moens, Sophie J. Bernelot;Verweij, Simone L.;Kroon, Jeffrey
通讯作者：
Kroon, Jeffrey
影响因子：
16.2
作者：
Satoh, A;Adachi, H;Imaizumi, T
通讯作者：
Imaizumi, T