Erectile dysfunction in the trajectory of cardiovascular disease

Cardiovascular disease (CVD) remains the leading cause of death in men. Both young and older men have considerable rates of cardiovascular events. Erectile dysfunction (ED) is common, afflicting more than half of men aged 40–70 years and greater than 70% of men over age 70. Robust evidence links the presence of ED with heightened risk of cardiovascular events. ¹ In a recent meta-analysis of prospective studies, men with ED had a higher relative risk of myocardial infarction, total CV events, and all-cause mortality. ² The clinical expression of ED frequently occurs prior to coronary artery disease, suggesting that ED may serve as a marker for subclinical vascular disease. Thus, there is potential clinical utility for cardiovascular prevention in increased detection and treatment of ED.

In addition to ED predicting CVD risk, vascular disease contributes to ED pathophysiology. ³ Cardiovascular risk factors predict the development of ED, suggesting a vascular component. ⁴ Even prior to the development of overt CVD, men with ED display evidence of vascular abnormalities. ⁵ The extent and type of subclinical vascular dysfunction present in ED has not been fully elaborated.

In the current issue of Vascular Medicine, Osondu and colleagues report their findings from a meta-analysis of the associations of ED with subclinical CVD. ⁶ There were 28 cross-sectional studies that evaluated ED as identified by an established questionnaire and markers of subclinical vascular alterations: flow-mediated dilation of the brachial artery and carotid intima–media thickness by ultrasound. The authors report that men with ED have impaired flow-mediated dilation, indicating endothelial dysfunction, and greater carotid intima–media thickness, indicating early atherosclerosis. Importantly, the association of endothelial dysfunction and carotid atherosclerosis persisted when adjusting for age, supporting the idea that ED may have particular clinical utility in younger patients who may lack more traditional cardiovascular risk factors. However, in the available studies included in the meta-analysis, coronary artery calcium scoring, a marker of coronary atherosclerosis, did not show consistent associations with ED.

The study findings advance our knowledge regarding the connection between ED and vascular dysfunction. The association of ED with endothelial dysfunction and early atherosclerosis provides evidence that ED may serve as a marker of early vascular disease that is easily ascertained by clinical history taking. The connection may reflect shared underlying mechanisms leading to ED and CVD. Similar pathophysiology contributes to both endothelial dysfunction and ED, including loss of nitric oxide bioavailability and increased inflammatory activation. ³ Thus, established risk-reduction therapies may have a benefit for men with low cardiovascular risk undergoing treatment for ED. ⁷ Interestingly, a recent nationwide Swedish cohort study of males less than 80 years old demonstrated that treatment for ED with PDE-5 inhibitors or alprostadil after a first myocardial infarction was associated with reduced mortality and heart failure admissions. ⁸

There are several remaining questions regarding ED and subclinical vascular dysfunction. Osondu and colleagues only evaluated cross-sectional cohort studies. There are no prospective cohort studies evaluating the temporal associations of ED, and subclinical vascular markers are lacking. Thus, it is not possible to ascertain whether ED is preceded by vascular dysfunction. The cause of ED was not evaluated in the included studies, so it remains possible that the associations would differ in vasculogenic and non-vasculogenic ED. In addition, there were inadequate studies to definitively determine whether ED is associated with coronary calcium, and there were no studies evaluating more sophisticated atherosclerosis markers, including coronary plaque by computed tomography (CT) scan or carotid plaque evaluation. Further, the relative clinical risk implications of ED and subclinical vascular measures cannot be determined in cross-sectional studies.

The optimal management of patients with ED prior to clinical CVD is not clear. The European Society of Cardiology 2016 guidelines give a level IIa recommendation but with class C evidence to consider cardiovascular risk assessment in men with ED. ⁹ Other expert groups have proposed stress test evaluation in men with ED and intermediate risk;^10,11 however, more clinical trial evidence is needed before implementing cardiovascular testing in men with ED without any clinical cardiovascular symptoms.

The present study emphasizes the relevance of ED to understanding the trajectory of CVD. A simple standardized ED screening may identify early vascular dysfunction. Similarly, vascular dysfunction may serve as a surrogate marker to evaluate the efficacy of cardiovascular targeted therapies in men with ED. The presence of ED portends a higher risk of future cardiovascular events, particularly in intermediate risk men, and may serve as an opportunity for intensification of cardiovascular risk prevention strategies. ² The findings add to the growing evidence supporting additional trials to determine the clinical impact of ED screening and the appropriate cardiovascular-directed evaluation and treatment of men with ED.