血脂与心力衰竭风险的因果关系及冠状动脉疾病的中介作用:一项孟德尔随机化研究

Causal Relationship Between Lipids and Heart Failure Risk and Mediating Effect of Coronary Artery Disease:A Mendelian Randomization Study

目的利用孟德尔随机化分析方法,探究血脂与心力衰竭风险之间的因果关系及冠状动脉疾病的潜在中介效应。方法主要采用逆方差加权方法,对欧洲人群中的血脂水平(包括甘油三酯、低密度脂蛋白胆固醇、高密度脂蛋白胆固醇、载脂蛋白A1和载脂蛋白B)与心力衰竭的因果关系进行单变量孟德尔随机化分析。此外,采用中介分析方法探究冠状动脉疾病的潜在中介效应。结果单变量孟德尔随机化分析结果显示,血脂与心力衰竭风险之间存在显著关联。其中甘油三酯(OR=1.15,95%CI 1.09~1.21)、低密度脂蛋白胆固醇(OR=1.15,95%CI 1.05~1.25)和载脂蛋白B(OR=1.16,95%CI 1.07~1.26)水平的升高与心力衰竭风险呈正相关。此外,高密度脂蛋白胆固醇(OR=0.88,95%CI 0.84~0.93)和载脂蛋白A1(OR=0.92,95%CI 0.87~0.97)水平的升高与心力衰竭风险呈负相关。敏感性分析验证了以上结果的稳健性。中介分析结果显示冠状动脉疾病在甘油三酯、低密度脂蛋白胆固醇、高密度脂蛋白胆固醇、载脂蛋白A1、载脂蛋白B与心力衰竭风险的因果关系中起到部分中介作用(分别为10.63%、16.72%、18.78%、16.14%和23.82%)。结论孟德尔随机化方法表明,甘油三酯、低密度脂蛋白胆固醇和载脂蛋白B水平升高会增加心力衰竭风险,而高密度脂蛋白胆固醇和载脂蛋白A1水平升高则可能降低该风险。冠状动脉疾病在这一因果联系中存在部分中介作用。

Objective A univariable Mendelian randomization(MR)analysis was conducted to explore the causal relationship between lipids and the risk of heart failure(HF)and the potential mediating effect of coronary artery disease(CAD).Methods The inverse-variance weighting was mainly applied for the MR analysis to examine the causal relationship between blood lipids(triglyceride,low-density lipoprotein cholesterol,high-density lipoprotein cholesterol,apolipoprotein A1 and apolipoprotein B)and HF in European population.Additionally,mediation analysis was conducted to investigate the potential mediating effect of CAD.Results The results of the univariable MR analysis revealed a significant association between blood lipids and the risk of HF.Elevated levels of triglyceride(OR=1.15,95%CI 1.09~1.21),low-density lipoprotein cholesterol(OR=1.15,95%CI 1.05~1.25)and apolipoprotein B(OR=1.16,95%CI 1.07~1.26)were significantly associated with increased risk of HF.In addition,this analysis showed that elevated high-density lipoprotein cholesterol(OR=0.88,95%CI 0.84~0.93)and apolipoprotein A1(OR=0.92,95%CI 0.87~0.97)were inversely associated with the risk of HF.Sensitivity analysis confirmed the robustness of these results.The results of the mediation analysis showed that CAD partially mediated the causal relationship between the above lipid indices(triglyceride,low-density lipoprotein cholesterol,high-density lipoprotein cholesterol,apolipoprotein A1 and apolipoprotein B)and the risk of HF(10.63%,16.72%,18.78%,16.14%and 23.82%,respectively).Conclusion MR indicates that elevated levels of triglyceride,low-density lipoprotein cholesterol and apolipoprotein B increase the risk of HF,whereas higher levels of high-density lipoprotein cholesterol and apolipoprotein A1 may reduce this risk.CAD partially mediates this causal relationship.