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This Quarter's Question

Two recent studies published by the Journal of the American College of Cardiology add to the growing body of evidence first established in the landmark study by Thompson indicating that erectile dysfunction (ED) predicts subsequent development of adverse cardiovascular events. Would you please briefly describe the Gazzaruso and Ma studies, and discuss the implications of these findings?

Response by Robert F. DeBusk, MD

Thompson et al studied 9457 men 55 years of age and older (mean, 62 y).¹ Of the 8063 men without cardiovascular disease (CVD) at baseline, 3816 (47%) had ED at study entry, and ED developed during the 7-year study period in 2760 (34%). Proportional hazard regression analysis showed that these men with ED were at significantly greater risk for any CVD than the men without ED (hazard ratio, 1.45; P<.001), with risk for transient ischemic attack highest at 1.92 (P=.02). The CVD risk associated with ED was similar to that of smoking or a family history of myocardial infarction.

Gazzaruso and colleagues demonstrated that ED was a significant predictor of cardiovascular morbidity and mortality in patients with type 2 diabetes and silent coronary artery disease (CAD), as determined angiographically.² The investigators explored whether therapy combining statins and phosphodiesterase type 5 (PDE5) inhibitors might decrease the incidence of major adverse cardiac events (MACE) among patients with CAD, diabetes, and ED. ED was assessed using the 5-item International Index of Erectile Function (IIEF-5) questionnaire and was considered to be present when the IIEF-5 score was ≤21.³ The end point was defined by the occurrence of MACE, including CAD death, sudden death, nonfatal myocardial infarction, death due to congestive heart failure, unstable angina, stroke or transient ischemic attack, and peripheral artery disease.²

There was a significant difference in ED prevalence between patients with MACE (61.2%) and those without (36.4%).² A lower rate of MACE in patients with both CAD and ED was associated with statin and PDE5 inhibitor use, as determined using Kaplan-Meier analysis. The percentage of patients treated with statins was significantly lower in the presence of MACE (40.8%) than not (65.7%). In addition, the percentage of patients with ED treated with statins was significantly lower in the presence of MACE (33.3%) than not (69.3%), suggesting that statins may protect against the development of MACE in patients with ED. The percentage of patients with ED treated with PDE5 inhibitors was significantly lower in the presence of MACE (20.0%) than not (43.2%). These results suggest the potential for PDE5 inhibitors to treat stable CAD, and the authors proposed that PDE5 inhibitors may help to prevent cardiovascular events.

Ma and colleagues examined the impact of ED to predict coronary heart disease (CHD) in a large cohort of men with type 2 diabetes who did not exhibit any clinical signs of CVD.⁴ Over the course of the study, the incidence of CHD events for men with ED was 19.7/1000 person-years compared with 9.5/1000 person-years in men without ED. Overall, 26% of the men reported ED symptoms, and ED was associated with older age, longer disease duration, higher blood pressure, and the presence of other microvascular complications. After adjustment for age, duration of diabetes, and other cardiovascular risk factors, the results also demonstrated that men with ED were at 1.6-fold increased risk for CHD events compared with those without ED. The authors posited that penile microcirculation was affected early by metabolic and hemodynamic factors, such as hyperglycemia, dyslipidemia, blood pressure, oxidative stress, and glycation end products. Because none of the men had preexisting CVD, this study strongly indicates that ED is an early marker of CHD in patients with diabetes. Consequently, Ma et al proposed identifying symptoms of ED in cardiovascular risk assessment.

References

1. Thompson IM, Tangen CM, Goodman PJ, Probstfield JL, Moinpour CM, Coltman CA.  Erectile dysfunction and subsequent cardiovascular disease.  JAMA. 2005;294(23):2996-3002.

2. Gazzaruso C, Solerte SB, Pujia A, et al. Erectile dysfunction as a predictor of cardiovascular events and death in diabetic patients with angiographically proven asymptomatic coronary artery disease: a potential protective role for statins and 5-phosphodiesterase inhibitors.  J Am Coll Cardiol. 2008;51(21):2040-2044.

3. Rosen RC, Cappelleri JC, Smith MD, Lipsky J, Peña BM. Development and evaluation of an abridged, 5-item version of the International Index of Erectile Function (IIEF-5) as a diagnostic tool for erectile dysfunction.  Int J Impot Res. 1999;11(6):319-326.

4. Ma RCW, So WY, Yang X, et al.  Erectile dysfunction predicts coronary heart disease in type 2 diabetes.  J Am Coll Cardiol. 2008;51(21):2045-2050.

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