Introduction

Cardiovascular disease is a leading cause of death and disability in men. Erectile dysfunction, a common problem in men as they age, may also help drive them to seek medical attention in the absence of other cardiovascular symptoms. The link between erectile dysfunction and cardiovascular disease, while now well established, has been previously characterized primarily by shared risk factors.^1-4 A number of risk factors are shared by erectile dysfunction and cardiovascular disease, including age,⁵ sedentary lifestyle, obesity, smoking, hypercholesterolemia, metabolic syndrome,⁶ insulin resistance,⁷ hypertension,^8,9 and diabetes.⁸ The common pathophysiologic bases for erectile dysfunction and cardiovascular disease are believed to include endothelial dysfunction,¹⁰ inflammation,¹¹ and low testosterone.^10,12 The most common organic (medical) etiology of erectile dysfunction is vasculogenic. Numerous studies in men with clinically evident cardiovascular disease have established erectile dysfunction as an independent risk marker for cardiovascular disease^4,13 and shown that erectile dysfunction frequently precedes coronary artery disease,^14-17 peripheral arterial disease,¹⁸ and stroke.¹⁵ Erectile dysfunction symptoms appear approximately two to five years before the onset of cardiovascular symptoms,^14,19-21 and more severe erectile dysfunction has been correlated with greater atherosclerotic burden;¹⁷ extent of coronary artery disease;^14,22 and risk of coronary artery disease,^15,16 peripheral artery disease,¹⁸ and major cardiovascular events.²³

An emerging paradigm indicates that erectile dysfunction is in fact an independent marker of cardiovascular disease risk.⁴ Thus, the presence of erectile dysfunction may provide the opportunity for cardiovascular disease risk mitigation in men with otherwise unrecognized cardiovascular disease. The importance of evaluating cardiovascular risk in men with erectile dysfunction is now a critical factor for overall early stage management of cardiovascular disease, especially in younger men (aged 30 - 60 years). This brief article focuses on the evaluation of cardiovascular risk in men with erectile dysfunction but no known cardiovascular disease.

Recommendations for Evaluation of CV Risk in Men With Erectile Dysfunction but No Known CVD

Erectile dysfunction is now a well-established, independent marker for cardiovascular disease risk,⁴ and all men should be questioned about their sexual history and functioning as part of the initial assessment of cardiovascular disease risk. Initial inquiry for erectile dysfunction can be done by asking a simple question such as "Have you noticed any change over the past month in your ability to get or maintain a rigid erection suitable for satisfactory intercourse?" Another option is to use a short scored validated questionnaire such as the Brief International Index of Erectile Function (IIEF-5) to assess for erectile dysfunction severity.²⁴ For all men with erectile dysfunction, particularly those with vasculogenic erectile dysfunction, initial risk stratification should be based on some type of cardiovascular risk score to estimate the 10-year risk for myocardial infarction or coronary death. In the past, the Framingham Risk Score^25,26 or SCORE was recommended but future studies will likely utilize the 2013 Prevention Guidelines ASCVD Risk Estimator. The following may be used to identify men whose cardiovascular risk may exceed that estimated by a risk score calculator: a thorough history; physical examination (including measures of visceral adiposity); assessment of erectile dysfunction severity and duration; evaluation of fasting plasma glucose; resting electrocardiogram; serum creatinine (estimated glomerular filtration rate) and albumin:creatinine ratio; plasma lipid levels (total, low density lipoprotein, and HDJ cholesterol and triglyceride values) and presence or absence of the metabolic syndrome.²⁶ The British Society of Sexual Medicine,²⁷ Third International Consultation on Sexual Medicine,²⁸ and Princeton III Consensus,²⁶ all recommend that total testosterone levels be measured as a potential cause of erectile dysfunction, particularly in those for whom phosphodiesterase type 5 inhibitors have failed. Although there are no generally accepted lower limits of normal total testosterone, there is general agreement that total testosterone >350 ng/dL (12 nmol/L) does not usually require substitution and, based on data from young hypogonadal men, those with total testosterone <230 ng/dL (8 nmol/L) could be considered as candidates for testosterone treatment if they are symptomatic and appropriately monitored.²⁹ Given the evidence that treatment of obstructive sleep apnea can improve erectile function,^30,31 along with observational studies suggesting treatment of obstructive sleep apnea may improve cardiovascular outcomes,^32,33 healthcare providers should also consider evaluating patients with erectile dysfunction for sleep apnea. Based on results of the above-mentioned clinical assessments, the provider may encourage lifestyle changes (e.g., diet, exercise, smoking cessation), which are likely to reduce cardiovascular risk and improve erectile function.^34,35 Interventions to control specific cardiovascular risk factors (e.g., hypertension, diabetes, hyperlipidemia, obstructive sleep apnea) may also be appropriate. Men who appear to be at high risk for cardiovascular events should be referred to a cardiologist. Men who appear to be at intermediate-risk men with vasculogenic erectile dysfunction and no overt cardiovascular disease undergo further noninvasive evaluation of cardiovascular risk using exercise stress testing, carotid intima-media thickness or coronary artery calcium scoring. Recently, in a comparison of the ability of six risk markers (coronary artery calcium scoring, carotid intima-media thickness, ankle-brachial index, brachial flow–mediated dilation, high-sensitivity C-reactive protein, and family history of coronary heart disease) to improve prediction of incident coronary heart disease/cardiovascular disease in patients at intermediate risk (Framingham 10-year risk, >5%–<20%) enrolled in the Multi-Ethnic Study of Atherosclerosis, coronary artery calcium scoring provided superior improvements in risk estimation versus the other risk markers.³⁶ Neither the most appropriate order of testing nor the prognostic superiority of one test over another has been established but both topics are the focus of ongoing research to determine the best approach to evaluate men with erectile dysfunction for subclinical vascular disease as part of the overall risk assessment. At this time, these tests should be selected based on clinical judgment, availability, and cost.

Conclusion

Vasculogenic erectile dysfunction should be regarded as a harbinger of silent or future cardiovascular disease. Thus, strategies that aid in the identification and characterization of erectile dysfunction may also be clinically useful for assessing and managing cardiovascular risk. In men with organic erectile dysfunction believed to be vasculogenic in etiology, cardiovascular risk should be further evaluated through assessment of traditional risk factors and noninvasive methods to detect subclinical cardiovascular disease. Cardiovascular risk stratification is now an essential component of clinical management in all men with vasculogenic erectile dysfunction.

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References

1. Bacon CG, Mittleman MA, Kawachi I, et al. A prospective study of risk factors for erectile dysfunction. J Urol 2006;176:217-221.
2. Bacon CG, Mittleman MA, Kawachi I, et al. Sexual function in men older than 50 years of age: results from the health professionals follow-up study. Ann Intern Med 2003;139:161-168.
3. Fung MM, Bettencourt R, Barrett-Connor E. Heart disease risk factors predict erectile dysfunction 25 years later: the Rancho Bernardo Study. J Am Coll Cardiol 2004;43:1405-1411.
4. Miner M, Nehra A, Jackson G, et al. All Men with Vasculogenic Erectile Dysfunction Require a Cardiovascular Workup. Am J Med 2014;127:174-82.
5. Feldman HA, Goldstein I, Hatzichristou DG, Krane RJ, McKinlay JB. Impotence and its medical and psychosocial correlates: results of the Massachusetts Male Aging Study. J Urol 1994;151:54-61.
6. Hatzimouratidis K, Amar E, Eardley I, et al. Guidelines on male sexual dysfunction: erectile dysfunction and premature ejaculation. Eur Urol 2010;57:804-814.
7. Guay A, Jacobson J. The relationship between testosterone levels, the metabolic syndrome (by two criteria), and insulin resistance in a population of men with organic erectile dysfunction. J Sex Med 2007;4(4 Pt 1):1046-1055.
8. Seftel AD, Sun P, Swindle R. The prevalence of hypertension, hyperlipidemia, diabetes mellitus and depression in men with erectile dysfunction. J Urol 2004;171(6 Pt 1):2341-2345.
9. Sun P, Swindle R. Are men with erectile dysfunction more likely to have hypertension than men without erectile dysfunction? A naturalistic national cohort study. J Urol 2005;174:244-248.
10. Guay AT. ED2: erectile dysfunction = endothelial dysfunction. Endocrinol Metab Clin North Am 2007;36:453-463.
11. Vlachopoulos C, Aznaouridis K, Ioakeimidis N, et al. Unfavourable endothelial and inflammatory state in erectile dysfunction patients with or without coronary artery disease. Eur Heart J 2006;27:2640-2648.
12. Yassin AA, Akhras F, El-Sakka AI, Saad F. Cardiovascular diseases and erectile dysfunction: the two faces of the coin of androgen deficiency. Andrologia 2011;43:1-8.
13. Bohm M, Baumhakel M, Teo K, et al. Erectile dysfunction predicts cardiovascular events in high-risk patients receiving telmisartan, ramipril, or both: The ONgoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial/Telmisartan Randomized AssessmeNt Study in ACE iNtolerant subjects with cardiovascular Disease (ONTARGET/TRANSCEND) Trials. Circulation 2010;121:1439-1446.
14. Montorsi P, Ravagnani PM, Galli S, et al. Association between erectile dysfunction and coronary artery disease. Role of coronary clinical presentation and extent of coronary vessels involvement: the COBRA trial. Eur Heart J 2006;27:2632-2639.
15. Ponholzer A, Temml C, Obermayr R, Wehrberger C, Madersbacher S. Is erectile dysfunction an indicator for increased risk of coronary heart disease and stroke? Eur Urol 2005;48:512-518; discussion 517-518.
16. Salem S, Abdi S, Mehrsai A, et al. Erectile dysfunction severity as a risk predictor for coronary artery disease. J Sex Med 2009;6:3425-3432.
17. Solomon H, Man JW, Wierzbicki AS, Jackson G. Relation of erectile dysfunction to angiographic coronary artery disease. Am J Cardiol 2003;91:230-231.
18. Polonsky TS, Taillon LA, Sheth H, et al. The association between erectile dysfunction and peripheral arterial disease as determined by screening ankle-brachial index testing. Atherosclerosis 2009;207:440-444.
19. Montorsi F, Briganti A, Salonia A, et al. Erectile dysfunction prevalence, time of onset and association with risk factors in 300 consecutive patients with acute chest pain and angiographically documented coronary artery disease. Eur Urol 2003;44:360-364; discussion 364-365.
20. Baumhakel M, Bohm M. Erectile dysfunction correlates with left ventricular function and precedes cardiovascular events in cardiovascular high-risk patients. Int J Clin Pract 2007;61:361-366.
21. Hodges LD, Kirby M, Solanki J, O'Donnell J, Brodie DA. The temporal relationship between erectile dysfunction and cardiovascular disease. Int J Clin Pract 2007;61:2019-2025.
22. Greenstein A, Chen J, Miller H, et al. Does severity of ischemic coronary disease correlate with erectile function? Int J Impot Res. 1997;9(3):123-126.
23. Hall SA, Shackelton R, Rosen RC, Araujo AB. Sexual activity, erectile dysfunction, and incident cardiovascular events. Am J Cardiol 2010;105:192-197.
24. Rosen RC, Cappelleri JC, Smith MD, et al. 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;11:319-26.
25. Greenland P, Alpert JS, Beller GA, et al. 2010 ACCF/AHA guideline for assessment of cardiovascular risk in asymptomatic adults: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Circulation 2010;122:e584-636.
26. Nehra A, Jackson G, Miner M, et al. The Princeton III Consensus Recommendations for the Management of Erectile Dysfunction and Cardiovascular Disease. Mayo Clin Proc 2012;87:766-778.
27. Hackett G, Kell P, Ralph D, et al. British Society for Sexual Medicine guidelines on the management of erectile dysfunction. J Sex Med 2008;5:1841-1865.
28. Buvat J, Maggi M, Gooren L, et al. Endocrine aspects of male sexual dysfunctions. J Sex Med 2010;7(4 Pt 2):1627-1656.
29. Corona G, Monami M, Boddi V, et al. Low testosterone is associated with an increased risk of MACE lethality in subjects with erectile dysfunction. J Sex Med 2010;7(4 Pt 1):1557-1564.
30. Shin HW, Park JH, Park JW, et al. Effects of Surgical vs. Nonsurgical Therapy on Erectile Dysfunction and Quality of Life in Obstructive Sleep Apnea Syndrome: A Pilot Study. J Sex Med 2013;10:2053-9
31. Khafagy AH, Khafagy AH. Treatment of obstructive sleep apnoea as a therapeutic modality for associated erectile dysfunction. Int J Clin Pract 2012;66:1204-1208.
32. Doherty LS, Kiely JL, Swan V, McNicholas WT. Long-term effects of nasal continuous positive airway pressure therapy on cardiovascular outcomes in sleep apnea syndrome. Chest 2005;127:2076-2084.
33. Marin JM, Carrizo SJ, Vicente E, Agusti AG. Long-term cardiovascular outcomes in men with obstructive sleep apnoea-hypopnoea with or without treatment with continuous positive airway pressure: an observational study. Lancet 2005;365:1046-1053.
34. Gupta BP, Murad MH, Clifton MM, et al. The effect of lifestyle modification and cardiovascular risk factor reduction on erectile dysfunction: a systematic review and meta-analysis. Arch Intern Med 2011;171:1797-1803.
35. Harte CB, Meston CM. Association between smoking cessation and sexual health in men. BJU Int 2012;109:888-896.
36. Yeboah J, McClelland RL, Polonsky TS, et al. Comparison of novel risk markers for improvement in cardiovascular risk assessment in intermediate-risk individuals. JAMA 2012;308:788-795.

Keywords: Erectile Dysfunction, Cardiovascular Diseases

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