Causal association of cardiovascular disease with erectile dysfunction: a two-sample bidirectional Mendelian randomization analysis.

Abstract

The association between cardiovascular diseases (CVD), including ischemic stroke (IS), heart failure (HF), myocardial infarction (MI), and coronary heart disease (CHD), and erectile dysfunction (ED) remains unclear from observational studies. We explored the potential bidirectional association between CVD and ED by Mendelian randomization (MR). Data from genome-wide association studies for CVD in individuals with European ancestry were obtained from several databases, with 1,711,875-977,323 participants, while that for ED included 223,805 participants. We conducted univariate MR (UVMR), inverse variance-weighting (IVW), weighted median, MR-Egger, and multivariate MR (MVMR) analyses to explore the bidirectional causal effects between CVD and ED. UVMR indicated that IS (odds ratios [OR]=1.34, 95% confidence interval [CI]: 1.08-1.21, P=0.007), HF (OR=1.36, 95% CI 1.07-1.74, P=0.013), and CHD (OR=1.15, 95% CI 1.09-1.18, P=0.022) were associated with ED. By MVMR, IS estimates remained significant after accounting for combining single nucleotide polymorphisms from CVDs (OR=1.42, 95%CI: 1.13-1.79, P=0.002). Moreover, the effect of a genetic susceptibility to IS on ED was not mediated by type 2 diabetes or triglycerides; that of HF was not mediated by type 2 diabetes, and that of CHD was not mediated by body mass index. Bidirectional analyses showed that genetic susceptibility to ED did not confer any increased CVD risk. Our results, based on MR, indicated that genetic susceptibility to IS, HF, and CHD was causally associated with ED. These findings can inform prevention and intervention strategies for ED in IS, HF, and CHD patients.