Possibility of cholesteryl ester transfer protein inhibitors in the treatment of major adverse cardiovascular events caused by familial hypercholesterolemia through Mendelian randomization
XU Jun-wei
LI Xiang-yu
WANG Zhi
DONG Rong
LU Zhi-ping
Abstract：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.
Keywords：Familial hypercholesterolemiaLow-density lipoprotein cholesterolCholesteryl ester transfer protein inhibitorsHeart failure
Publication Date：2024-12-10
Online Publishing Date：2025-08-15(First online date of this platform, not the publication date of the document)
Pages：6( 1057-1062 )