Possibility of cholesteryl ester transfer protein inhibitors in the treatment of major adverse cardiovascular events caused by familial hypercholesterolemia through Mendelian randomization
Possibility of cholesteryl ester transfer protein inhibitors in the treatment of major adverse cardiovascular events caused by familial hypercholesterolemia through Mendelian randomization
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
Key words
Familial hypercholesterolemia/Low-density lipoprotein cholesterol/Cholesteryl ester transfer protein inhibitors/Heart failure
维普
万方数据