Xiyuan Hospital, China Academy of Chinese Medical Sciences, 100091, Beijing, China.
National Clinical Research Center for Chinese Medicine Cardiology, 100091, Beijing, China.
Cardiovasc Diabetol. 2023 Aug 10;22(1):207. doi: 10.1186/s12933-023-01927-z.
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.
新出现的证据表明，残余胆固醇（RC）与心血管代谢疾病（CMD）的发病率增加密切相关。然而，其因果关系尚未得到证实。我们旨在使用两样本孟德尔随机化（MR）方法评估 RC 与 CMD 及相关风险因素的因果关系。
从以欧洲血统为主的个体（主要来自英国生物库和芬兰基因库）发表的研究中获取 RC、CMD 和心血管代谢危险因素的汇总水平统计数据。采用单变量和多变量 MR 分析来评估 RC 与 CMD 之间的因果关系。进行双向 MR 分析以估计 RC 与心血管代谢风险因素之间的因果关系。主要 MR 方法采用逆方差加权法进行。
单变量 MR 分析表明，遗传预测的 RC 与缺血性心脏病、心肌梗死、心房颤动和扑动、外周动脉疾病以及非风湿性瓣膜病的风险增加有关（均 P<0.05）。多变量 MR 分析提供了强有力的证据表明 RC 对缺血性心脏病风险有不良影响（P<0.05）。双向 MR 分析表明，RC 与总胆固醇、甘油三酯、低密度脂蛋白胆固醇、高胆固醇血症之间存在双向因果关系（均 P<0.05）。然而，RC 与代谢紊乱或其他心血管代谢危险因素之间没有遗传关联。
这项 MR 研究表明，遗传驱动的 RC 增加了几种 CMD 和心血管代谢风险因素的风险，这表明靶向 RC 降低疗法可能对 CMD 的一级预防有效。
