Evidence is accumulating to support the concept that ED and CAD are differing manifestations of a common underlying vascular pathology. The presence of a number of common risk factors, the presence of several known pathophysiologic links, and a number of retrospective association studies have reinforced the idea that the link between ED and CAD is important and real. In the current study, we evaluated the association between the presence of ED and the development of future CAD by prospectively following up a cohort of community-dwelling men for a 10-year period from 1996 to 2005. After accounting for common cardiovascular risk factors, we found that ED was associated with an approximately 80% higher risk of subsequent CAD. This finding is comparable to the 65% increased risk predicted by Ponholzer et al10
and slightly stronger than the 45% increased risk observed after 5 years by Thompson et al.11
That ED precedes other manifestations of systemic atherosclerosis, such as CAD and cerebrovascular disease, may be partially explained by blood vessel size.16
The penile arteries are typically 1 to 2 mm in diameter, whereas the coronary arteries are 3 to 4 mm in diameter and the carotid arteries, 5 to 7 mm in diameter. Therefore, an atherosclerotic plaque of a given size should occlude and hemodynamically affect a penile artery earlier than a coronary or carotid artery. The essential idea is that smaller arteries plug earlier than larger arteries. The underlying assumption of this “vessel size” theory is that slow and progressive vascular occlusion is the underlying cause of both ED and CAD, an assumption that may not always be true. For instance, another pathophysiologic link between ED and CAD is endothelial dysfunction. Many patients with ED exhibit evidence of
inflammation and endothelial dysfunction independent of their CAD status.13,19
This finding suggests that nonocclusive coronary plaques in men with ED could also be worrisome because they may occur in the setting of a systemic malfunction of the vascular endothelium. This endothelial dysfunction can carry a heightened risk of future CAD events because it results in dysregulated intimal proliferation, inappropriate vasoconstriction, and a proinflammatory environment that causes plaque destabilization.17
The fact that ED and atherosclerotic vascular diseases share such a large number of common risk factors has led to the clinical consensus that most cases of organic ED are probably part of the spectrum of atherosclerotic vascular disease.31
In agreement with the findings of other studies,32
our findings showed that ED is more likely to develop among older men and among men with cardiovascular risk factors such as tobacco use, hypertension, and diabetes. In our study, age was by far the strongest predictor of ED, even after the effect of other important cardiovascular risk factors was taken into account. Aging is known to be a key factor in the development of vascular pathology. The repetitive pulsations to which the large central arteries are submitted over a patient's life span lead to fatigue and fracture of the vessels' elastic lamellae; therefore, the arteries become stiff.33
Arterial stiffness causes the systolic blood pressure to increase and the diastolic blood pressure to decrease. In addition to their negative effects on the myocardium, large-artery stiffness and the resulting systolic hypertension force the pressure waves of cardiac pulsation farther into the smaller arteries than is normally the case. Ultimately, small arteries such as the pudendal and penile arteries begin to degenerate, and end-organ ischemia results.33
Atherosclerosis is another form of vascular pathology that can affect the small arteries that supply the penis. This condition is distinct from the damage caused by age-related arterial stiffness in that it is associated with the formation of plaques in the arterial system that can either rupture or grow to occlude the blood vessel. Eaton et al34
observed an association between the levels of biomarkers of atherosclerosis and the level of erectile function. We observed strong associations between the development of ED and well-known risk factors for atherosclerosis, such as diabetes, smoking, and hypertension. These results should be interpreted carefully because we obtained only indirect measurement of these covariates by patient report. Other risk factors, such as dyslipidemia and hyperhomocysteinemia, were not evaluated because screening for these conditions was not uniform within our patient cohort. There has been some suggestion that actively addressing cardiovascular risk factors by initiating preventive measures such as a smoking cessation program35,36
or a weight-loss regimen,37
by treating hypertension,38
and by controlling blood glucose levels may contribute to reducing the risk of ED. Therefore, actively addressing common cardiovascular risk factors may provide both a cardiovascular and a sexual benefit. Other molecular mechanisms likely link ED to vascular diseases, and whether treating ED patients for vascular risk factors can reduce the burden of both ED and future cardiovascular disease remains to be determined.
The extent to which ED itself imparts an untoward cardiovascular risk is debatable. In the current study we observed that the effect of incident ED on future coronary risk was strongly affected by patient age. Although ED had relatively little impact on the development of incident cardiac events in men aged 70 years or older, we found that it resulted in a nearly 50-fold increase in the 10-year incidence density of heart disease in men aged 40 to 49 years (). This observation hints at the possibility that ED in young men may indeed be an early manifestation of a progressive systemic vasculopathy, preceding the development of coronary disease by decades. The long temporal association between ED and new cardiac events is important to underscore because it implies that studies must be designed with prolonged follow-up if any systemic sequelae of ED are to be found. Furthermore, the timing of events raises the possibility of a window of curability, whereby the progression of cardiac disease might be slowed or halted by some form of medical intervention.39
Because this hypothesis remains to be tested, young men with ED could be an ideal cohort for clinical trials of cardiovascular disease prevention.
Finally, we found that the predictive value of ED on incident CAD is attenuated after the analyses are adjusted for cardiovascular risk factors and that the predictive values of the cardiovascular risk factors are attenuated after the analyses are adjusted for ED. These observations suggest that ED and CAD may be part of a common underlying pathophysiologic pathway. However, the age effect is never completely accounted for by either ED or cardiovascular risk factors; this finding supports the notion that age-related vascular stiffening is distinct from atherosclerosis and that both are at play in elderly patients. Therefore, it is unclear to what degree preventive measures for atherosclerosis—such as anti-hypertensive treatment, weight loss, and smoking cessation—would benefit the older man whose vascular disease is probably already well established and is at least partly caused by nonatherosclerotic mechanisms.
The strengths of our study include active ascertainment of erectile status by validated biennial questionnaires specifically designed to measure diverse aspects of male sexual function. Additionally, because our study participants were randomly selected from a geographically fixed community, the study lacks many of the selection biases inherent in studies with a patient cohort recruited from physicians' clinics or from clinical trials. However, the strongly white composition of Olmsted County raises the possibility of race-specific ED effects that may not be generalizable to other ethnic groups. The socioeconomic profile and rural location of Olmsted County may also affect the study's generalizability to patients from other geographic areas within the United States. Although we were able to follow up our cohort of men for a substantial period to ascertain the development of erectile and cardiac disease, our study is limited in that the intermittent questioning of participants is an imperfect method of determining their continuous ED status. Additionally, we were not able to precisely categorize the cause of the self-reported ED, and we expect that some cases were psychogenic and lacked the physiologic associations with CAD that were previously described. Of note, some men in the study may have asymptomatic heart disease that has not yet manifested itself. With further longitudinal follow-up, many of these cases should become clinically apparent.