Erectile Dysfunction and Coronary Artery Disease

It’s not surprising that doctors have wondered whether erectile dysfunction (ED) is a marker of coronary artery disease (CAD). After all both disorders result from impaired blood flow to the two involved organs. Because the penile artery is about one-third the diameter of the coronary artery, vascular disease affecting both these arteries might become symptomatic in the former before declaring itself in the latter. Thus ED might be a harbinger of heart disease. As ED and CAD have complicated pathophysiologies the association between them might be loose. But if the association could be documented interventions designed to arrest the progression of CAD could be started at an early stage thus preventing the disease from causing serious morbidity or premature mortality.

To this end, a group of investigators studied a cohort of white men from Minnesota. The study is limited by the narrow group examined, which is partly based on a self-report questionnaire, and examination of medical records. Its authors are aware of these limitations and include them in their discussion. This study was published in the February 2009 issue of the Mayo Clinic Proceedings – (A Population-Based, Longitudinal Study of Erectile Dysfunction and Future Coronary Artery Disease).

The paper’s authors conclude: that ED and CAD may be differing manifestations of a common underlying vascular pathology. When ED occurs in a younger man, it is associated with a marked increase in the risk of future cardiac events, whereas in older men, ED appears to be of little prognostic importance. Young men with ED may be ideal candidates for cardiovascular risk factor screening and medical intervention.

As I’ll show this conclusion, which may be correct, goes a little bit beyond what the data allow. I’ll ignore any limitations of the study’s design and only concentrate on the data.

When all the subjects studied are lumped together those with ED are about twice as likely to get CAD as a similar group without ED. HR stands for hazard ratio while CI is the confidence interval. If the CI does not straddle 1 the HR is significantly different from the control group. The further away from 1 the CI the greater the significance (typically defined as a P value = or <0.05). If the HR is greater than 1 the ED group is more likely to have CAD. Were it less than1 the ED group would be less likely to have CAD. The comorbidity adjusted data account for the influence of other risk factors that predispose to CAD – smoking, hypertension, diabetes, high cholesterol, etc. The data support a link between ED and CAD.

These data were interpreted as showing that ED at a younger age was associated with CAD, but as you can see  (click on the table for a clearer image) the HR straddles 1 in all the groups. Thus while these data suggest an association with ED and CAD in subjects 40-49 they are not statistically significant and do not justify the conclusion reached by these investigators even if it turns out later to be correct. The comorbidity adjusted data are not even close to statistical significance. Just for kicks look at the HR for the subjects over 70. If you want to over interpret data you could say they suggest that ED is associated with a decreased likelihood of CAD.

So where are we? Just where we started. We need more information. If this association between ED and CAD  could be definitively established we could use ED in the relatively young as a risk factor for CAD and start treatment designed to prevent vascular disease. However, we would first require another study demonstrating the safety and efficacy of such a prophylactic regimen before we could confidently prescribe it. To be clear, I’m talking about whether we should use ED as a cardiovascular risk factor in patients who lack any other risk factor. And if so, should we treat these patients? If other risk factors were present we would already have reason to treat.

The same issue of the Mayo Clinic Proceedings has another article, Erectile Dysfunction and Cardiovascular Disease: Efficacy and Safety of Phosphodiesterase Type 5 Inhibitors in Men With Both Conditions, which examines both the evidence that ties ED with cardiovascular disease and the safety of phosphodiesterase 5 (PDE5) inhibitors in patients who have a comorbid condition. This paper concludes that Erectile dysfunction and cardiovascular disease, especially CAD, share the same risk factors: smoking, high blood pressure, high cholesterol, and diabetes. These 2 conditions also share the same pathophysiology, mediated by endothelial dysfunction. Thus, ED may be an important risk marker of silent vascular disease in men with no cardiac symptoms, providing physicians with a unique opportunity to uncover and address underlying CAD in patients who present with ED. It is recommended that physicians screen these patients for vascular disease. Because ED is often associated with comorbid conditions such as diabetes, hypertension, or dyslipidemia, screening should also include measurements of blood glucose, lipids, and blood pressure.

It doesn’t tell what the physician should do with a patient who has ED and high lipids, but who has no other cardiovascular risk factors. Primary treatment of hyperlipidemia (ie treatment of patients with high cholesterols without CV disease or other risk factors) has not been shown to be of value, though many physicians treat it regardless. Is the combination of the two reasons enough to prescribe a statin?

There are three PDE5 inhibitors currently available – sildenafil (Viagra), tadalafil (Cialis), and vardenafil (Levitra). They work by selective inhibition of PDE5 in the corpus cavernosum of the penis. This in turn reduces degradation of NO which increases cGMP which then results in vasodilatation, increased penile blood flow, and an erection.

So is it safe to give these drugs to patients who already have CV disease? The available evidence which is well documented in this paper suggests it is. The safety profile of the three drugs available as well as that of their efficacy is the same.