胆固醇酯转移蛋白抑制剂治疗家族性高胆固醇血症引起不良心血管事件的可能性分析  

Possibility of cholesteryl ester transfer protein inhibitors in the treatment of major adverse cardiovascular events caused by familial hypercholesterolemia through Mendelian randomization

作　　者：徐俊伟 李翔宇 王治 董荣 陆治平 XU Jun-wei;LI Xiang-yu;WANG Zhi;DONG Rong;LU Zhi-ping(Department of Cardiology,Nanjing Chest Hospital,The Affiliated Brain Hospital of Nanjing Medical University,Nanjing 210029,China;Department of Cardiology,Yancheng Number 1 People’s Hospital,Yancheng 224006,China)

机构地区：[1]南京医科大学附属脑科医院南京市胸科医院心血管内科,江苏省南京市210029 [2]盐城市第一人民医院心血管内科

出　　处：《中国心血管病研究》2024年第12期1057-1062,共6页Chinese Journal of Cardiovascular Research

基　　金：江苏省自然科学基金面上项目(BK20211019);南京医科大学科技发展基金(NMUB2020229)。

摘　　要：目的基于孟德尔随机化探索家族性高胆固醇血症与心衰及心源性死亡的因果关系,并探究胆固醇酯转移蛋白(CETP)抑制剂治疗家族性高胆固醇血症引起的心力衰竭(心衰)及心源性死亡的可能性。方法使用公开的的全基因组关联研究(GWAS)数据,筛选与家族性高胆固醇血症、低密度脂蛋白胆固醇水平密切相关且独立的单核苷酸多态性(single nucleotide polymorphisms,SNPs)作为工具变量(IVs),分别运用逆方差加权法(IVW)进行两样本孟德尔随机化分析。结果两样本孟德尔随机化的IVW结果显示,家族性高胆固醇血症与心衰(OR=1.09,95%CI 1.05~1.13,P<0.0001)和心源性死亡(OR=1.0007,95%CI 1.0001~1.0011,P=0.007)的危险性升高有因果关系。此外,药物靶点孟德尔随机化研究的结果显示,长期使用CETP抑制剂与心衰(OR=0.62,95%CI 0.46~0.83,P=0.001)和心源性死亡(OR=0.996,95%CI 0.992~1.000,P=0.06)的危险性降低有关。结论家族性高胆固醇血症与心衰、心源性死亡存在因果关系,使用CETP抑制剂可以通过降低低密度脂蛋白胆固醇水平来降低心衰和心源性死亡的危险。Objective To explore the causal relationship between familial hypercholesterolemia and heart failure as well as cardiovascular death using Mendelian randomization(MR),and to investigate the potential therapeutic effects of cholesteryl ester transfer protein(CETP)inhibitors on heart failure and cardiovascular death caused by familial hypercholesterolemia.Methods Utilizing publicly available genome-wide association study(GWAS)data,single nucleotide polymorphisms(SNPs)closely and independently associated with familial hypercholesterolemia and low-density lipoprotein cholesterol levels were selected as instrumental variables(IVs).Two-sample Mendelian randomization analyses were conducted using the inverse variance-weighted(IVW)method.Results The IVW results of the two-sample MR indicated a causal relationship between familial hypercholesterolemia and an increased risk of heart failure(OR=1.09,95%CI 1.05-1.13,P<0.0001)and cardiovascular death(OR=1.0007,95%CI 1.0001-1.0011,P=0.007).Additionally,results from drug-target MR studies revealed that long-term use of CETP inhibitors was associated with a decreased risk of heart failure(OR=0.62,95%CI 0.46-0.83,P=0.001)and cardiovascular death(OR=0.996,95%CI 0.992-1.000,P=0.06).Conclusion There is a causal relationship between familial hypercholesterolemia and heart failure as well as cardiovascular death.The use of CETP inhibitors can reduce the risk of heart failure and cardiovascular death by lowering low-density lipoprotein cholesterol levels.

关 键 词：家族性高胆固醇血症 低密度脂蛋白胆固醇 胆固醇酯转移蛋白抑制剂 心力衰竭 

分 类 号：R589.2[医药卫生—内分泌]