Erectile dysfunction carries a 45% higher risk of cardiovascular disease

Erectile dysfunction is associated with a 45% higher risk of cardiovascular disease, a 55% higher risk of myocardial infarction and a 25% higher risk of death from any cause. That is why the American Urological Association's guideline instructs clinicians to counsel men that ED is a risk marker for underlying cardiovascular disease — the symptom is often the earliest visible sign of a vascular problem that has not yet produced chest pain. On treatment, the same guideline is strongly supportive of one option and explicitly sceptical of three of the ones most heavily marketed.

The cardiovascular association

An umbrella review published in BJU International pooled the systematic reviews and meta-analyses on ED and cardiovascular disease, searching six databases from inception to April 2020 and appraising each review with a standard checklist before inclusion [s1]. Its summary estimates put the risk in men with ED against men without at 1.45 for cardiovascular disease (95% CI 1.36 to 1.54), 1.50 for coronary heart disease (95% CI 1.37 to 1.64), 1.55 for myocardial infarction (95% CI 1.33 to 1.80), 1.36 for stroke (95% CI 1.26 to 1.46) and 1.25 for all-cause mortality (95% CI 1.18 to 1.32), all at P < 0.001 [s1]. The review's own interpretation is that ED and cardiovascular disease are two presentations of the same physiological phenomenon, and that ED normally precedes symptomatic cardiovascular disease [s1].

An earlier meta-analysis in Circulation: Cardiovascular Quality and Outcomes added the detail that makes this clinically usable. Across 14 longitudinal studies covering 92,757 participants with a mean follow-up of 6.1 years, the pooled relative risk for total cardiovascular events was 1.44 (95% CI 1.27 to 1.63), for myocardial infarction 1.62 (95% CI 1.34 to 1.96), for cerebrovascular events 1.39 (95% CI 1.23 to 1.57) and for all-cause mortality 1.25 (95% CI 1.12 to 1.39) [s2]. Cardiovascular mortality alone did not reach significance (1.19, 95% CI 0.97 to 1.46) [s2].

Two modifiers stand out. The relative risk was higher at younger ages, and higher in intermediate-risk populations than in high- or low-risk ones [s2]. And how ED was ascertained mattered: studies using a questionnaire found a relative risk of 1.61 (95% CI 1.38 to 1.86) against 1.27 (95% CI 1.18 to 1.37) for studies using a single question, a difference significant at P = 0.006 [s2].

The last point is a measurement finding disguised as a nuance. If asking properly produces a stronger association than asking casually, then a single throwaway question in a clinic is systematically diluting the signal.

What the guideline tells clinicians to do with that

The AUA guideline states as a clinical principle that men should be counselled that ED is a risk marker for underlying cardiovascular disease and other conditions that may warrant evaluation and treatment [s3]. It also directs that men presenting with ED undergo a thorough medical, sexual and psychosocial history, a physical examination and selective laboratory testing, and that morning serum total testosterone be measured [s3].

Association is not causation and the guideline does not claim otherwise. ED and vascular disease share risk factors — diabetes, smoking, hypertension, obesity — and the small arteries supplying the penis are among the first to show endothelial dysfunction. That is a plausible common-cause explanation, and it is exactly why the symptom is informative regardless of which way any arrow points.

What works

The guideline's strongest treatment recommendation is that men with ED should be informed about the option of an FDA-approved oral phosphodiesterase type 5 inhibitor, including its benefits and risks, unless contraindicated — a strong recommendation at evidence grade B [s3]. It adds that instructions should be provided to maximise efficacy, and that the dose should be titrated for optimal effect [s3].

The comparative evidence behind that class comes from a network meta-analysis of 118 randomised trials and 31,195 men [s4]. All the PDE5 inhibitors studied were superior to placebo for erectile function [s4]. Tadalafil and vardenafil ranked as the most effective agents across efficacy outcomes, and the conclusion was that tadalafil appears the most effective, followed by vardenafil [s4]. Avanafil was less effective than tadalafil (relative risk 0.61, 95% CI 0.33 to 0.90) and vardenafil (0.63, 95% CI 0.35 to 0.92) on one global assessment measure [s4]. On safety, the analysis found no major difference between agents [s4].

The guideline also lists non-drug options it says men should be informed about: vacuum erection devices, intraurethral alprostadil, intracavernosal injections and penile prosthesis implantation, each with benefits and burdens discussed [s3]. It says clinicians should counsel men with comorbidities affecting erectile function that lifestyle changes including diet and physical activity improve overall health and may improve erectile function [s3], and that referral to a mental health professional should be considered [s3].

What the guideline calls investigational

Three treatments sold heavily in commercial men's-health clinics are classified by name. Low- intensity extracorporeal shockwave therapy should be considered investigational [s3]. Intracavernosal stem cell therapy should be considered investigational [s3]. And platelet-rich plasma therapy should be considered experimental [s3].

Those are the guideline's own words about three services that are widely advertised at a price. The classification does not mean they do not work; it means the evidence available when the guideline was written did not establish that they do.

The point most likely to be missed

The useful thing here is not a treatment ranking. It is that a man reporting ED to a clinician is reporting a cardiovascular datapoint, and the guideline treats it as one. The association is strongest in exactly the men least likely to be flagged by conventional risk scoring — younger men, and men in the intermediate-risk band where a nudge changes management [s2].

This article is informational and is not medical advice. It does not recommend any treatment, and decisions about drugs, dosing and cardiovascular assessment belong with a reader and their clinician.

Sources

• Association of erectile dysfunction and cardiovascular disease: an umbrella review of systematic reviews and meta-analyses — BJU International, 2021-01-09
• Prediction of cardiovascular events and all-cause mortality with erectile dysfunction: a systematic review and meta-analysis of cohort studies — Circulation: Cardiovascular Quality and Outcomes, 2013-01-08
• Erectile Dysfunction: AUA Guideline — American Urological Association, 2018
• Comparative effectiveness and safety of oral phosphodiesterase type 5 inhibitors for erectile dysfunction: a systematic review and network meta-analysis — European Urology, 2013-01-31