Aortic stenosis intricacies beyond the valve: A bidirectional Mendelian randomization study.

Aims: Numerous observational studies have reported an association between calcific aortic valve stenosis (CAVS) and an increased risk of other cardiovascular diseases (CVDs). However, the potential causal association is uncertain.

Methods and results: A bidirectional Mendelian randomization (MR) analysis was performed to confirm the causal association between CAVS and the risk of seven common CVDs. The meta-analysis was used to estimate the combined causal effect with multiple MR results. The MR analysis indicated that genetically predicted CAVS is associated with the increased risk of heart failure (odds ratio [OR] = 1.064; 95% confidence interval [CI] [1.008, 1.123]; P = 0.025), large-artery stroke (OR = 1.256; 95% CI [1.112, 1.418]; P < 0.001), cardioembolic stroke (OR = 1.228; 95% CI [1.117, 1.349]; P < 0.001) and atrial fibrillation (OR = 1.100; 95% CI [1.061, 1.140]; P < 0.001) without heterogeneity and pleiotropy. Genetically predicted hypertension (FinnGen: OR = 1.170; 95% CI [1.055, 1.297]; P = 0.003 and UK Biobank: OR = 2.456; 95% CI: 1.571, 3.840; P = 8.16 × 10^-5) increased the risk of CAVS.

Conclusions: This comprehensive MR study revealed the causal relationship between genetically predicted CAVS and the increased risk of various CVDs and the causal relationship between hypertension and CAVS risk. Given the harmful causal impact of CAVS on adverse cardiovascular events, it is crucial to prioritize the prevention and management of CVD in individuals with CAVS. Blood pressure management is an effective preventive intervention.