Association between blood pressure traits,hypertension,anti-hypertensive drugs and calcific aortic valve stenosis:a mende-lian randomization study
Wen-Hua LEI
Jia-Liang ZHANG
Yan-Biao LIAO
Yan WANG
Fei XU
Yao-Yu ZHANG
Yanjiani XU
Jing ZHOU
Fang-Yang HUANG
Mao CHEN
Department of Cardiology,West China Hospital,Sichuan University,No.37 Guoxue Street,Chengdu 610041,China;Laboratory of Cardiac Structure and Function,Institute of Cardiovascular Diseases,West China Hospital,Sichuan University,Chengdu,China
摘要：Background Hypertension is associated with an increased risk of calcific aortic valve stenosis(CAVS).However,the direction-ality of causation between blood pressure traits and aortic stenosis is unclear,as is the benefit of antihypertensive drugs for CAVS.
Methods Using genome-wide association studies(GWAS)summary statistics,we performed bidirectional two-sample univari-able mendelian randomization(UVMR)to assess the causal associations of systolic blood pressure(SBP),diastolic blood pressure(DBP),and pulse pressure(PP)with CAVS.Multivariable mendelian randomization(MVMR)was conducted to evaluate the dir-ect effect of hypertension on CAVS,adjusting for confounders.Drug target mendelian randomization(MR)and summary-level MR(SMR)were used to estimate the effects of 12 classes of antihypertensive drugs and their target genes on CAVS risk.Inverse variance weighting was the primary MR method,with sensitivity analyses to validate results.
Results UVMR showed SBP,DBP,and PP have causal effects on CAVS,with no significant reverse causality.MVMR con-firmed the causality between hypertension and CAVS after adjusting for confounders.Drug-target MR analyses indicated that calcium channel blockers(CCBs),loop diuretics,and thiazide diuretics via SBP lowering exerted protective effects on CAVS risk.SMR analysis showed that the CCBs target gene CACNA2D2 and ARBs target gene AGTR1 were positively associated with CAVS risk,while diuretics target genes SLC12A5 and SLC12A1 were negatively associated with aortic stenosis risk.
Conclusions Hypertension has a causal relationship with CAVS.Managing SBP in hypertensive patients with CCBs may pre-vent CAVS.ARBs might exert protective effects on CAVS independent of blood pressure reduction.The relationship between di-uretics and CAVS is complex,with opposite effects through different mechanisms.
机标关键词：hypertensionassociationpressurebetweentraitsstudybloodanti
论文发表日期：2025-03-28
在线出版日期：2025-08-15（本平台首次上网日期，不代表文献的发表时间）
页数：10( 351-360 )