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Published on: October 22, 2014
Causal association of cardiovascular disease with erectile dysfunction: a two-sample bidirectional Mendelian
Miaoyong Ye1, Jiaxing Chen2, Jianxiong Ma3
1Department of Urology, The First People's Hospital of Wenling, Wenling, Zhejiang Province, China.
Insights
Cardiovascular diseases like ischemic stroke and heart failure are causally linked to erectile dysfunction. However, erectile dysfunction does not increase the risk of cardiovascular disease.
Area of Science:
- Cardiovascular medicine
- Genetics
- Urology
Background:
- Observational studies suggest a link between cardiovascular diseases (CVD) and erectile dysfunction (ED), but the causal relationship remains unclear.
- CVD encompasses conditions such as ischemic stroke (IS), heart failure (HF), myocardial infarction (MI), and coronary heart disease (CHD).
Purpose of the Study:
- To investigate the potential bidirectional causal association between various cardiovascular diseases and erectile dysfunction using Mendelian randomization (MR).
Main Methods:
- Utilized genome-wide association study data from European ancestry populations for CVD (1,711,875–977,323 participants) and ED (223,805 participants).
- Employed univariate MR (UVMR) and multivariate MR (MVMR) analyses, including inverse variance-weighting (IVW), weighted median, and MR-Egger methods, to assess causal effects.
- Explored potential mediation pathways for IS, HF, and CHD on ED, and vice versa.
Main Results:
- UVMR indicated significant associations between IS, HF, and CHD with ED.
- MVMR confirmed a significant causal effect of IS on ED, even after accounting for other CVD risk factors.
- Genetic susceptibility to ED did not show a causal effect on the risk of developing CVD.
Conclusions:
- Genetic predisposition to ischemic stroke, heart failure, and coronary heart disease is causally associated with erectile dysfunction.
- Findings suggest that ED in patients with IS, HF, and CHD may stem from underlying cardiovascular pathology, informing targeted prevention and intervention strategies.
Background:
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.
Objectives:
We explored the potential bidirectional association between CVD and ED by Mendelian randomization (MR).
Methods:
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.
Results:
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.
Conclusions:
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.
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