Erectile dysfunction increases the risk of stroke: evidence from NHANES and Mendelian randomization analysis.

Background: Erectile dysfunction (ED) has been linked to cardiovascular disease (CVD), but the associations are inconsistent and causal relationships remain unclear. We combined National Health and Nutrition Examination Survey (NHANES) data with Mendelian randomization (MR) to investigate the association and potential causal effects of ED on CVD. Methods: ED in the NHANES and MR analyses was defined based on questionnaire responses, self-reported diagnosis, physician diagnosis, or use of ED medication. Based on the NHANES survey stratified by erectile status, we performed univariate analysis and logistic regression to assess the association between ED and CVD. Then MR analysis was performed to explore the causal relationship between ED and CVD. Exposure and outcome data were obtained from publicly available large-scale genome-wide association studies (GWAS). Inverse variance weighted (IVW) was used as the primary method to analyze causal relationships. All results are expressed as odds ratio (OR) and 95% confidence interval (CI). Results: A total of 3,624 participants were included in the observational study according to erectile function status. In the weighted cohort, 36.80% reported some degree of ED, with 12.33% sometimes able to achieve an erection and 6.09% never able to achieve an erection. After fully adjusting for covariates, never able to get and keep an erection was associated with increased risk of stroke (OR: 2.42; 95% CI: 1.20-4.91; P=0.03). MR analysis confirmed a genetic causal association between ED and large artery stroke (OR: 1.06; 95% CI: 1.00-1.11; P<0.05) and small vessel stroke (OR: 1.06; 95% CI: 1.04-1.09; P<0.001). Conclusions: Evidence from both NHANES and MR confirmed that ED was associated with increased risk of stroke.