Services on Demand
- Cited by SciELO
- Access statistics
- Similars in SciELO
Print version ISSN 0066-782X
Arq. Bras. Cardiol. vol.99 no.4 São Paulo Oct. 2012 Epub Sep 04, 2012
Antonio Carlos Cordeiro; Carolina Christianini Mizzaci; Rafael Modesto Fernandes; Afrânio Galdino Araujo-Junior; Paulo Oliveira Cardoso; Lucas Velloso Dutra; Amanda Guerra Moraes Rego Sousa; Celso Amodeo
Instituto Dante Pazzanese de Cardiologia, São Paulo, SP - Brasil
BACKGROUND: Erectile Dysfunction (ED) is associated with increased risk of coronary artery disease (CAD).
OBJECTIVE: To evaluate the association between ED, determined by the Simplified International Index of Erectile Function (IIEF-5) and CAD.
METHODS: This was a cross-sectional cohort study that evaluated 263 hypertensive patients (55 [50-61] years). ED was assessed through the IIEF-5 and CAD by the history of previous myocardial revascularization and/or coronary angiography.
RESULTS: The IIEF-5 correlated with creatinine clearance [CrCl] (Rho = 0.23, p <0.001) and age (Rho = -0.22, p <0.001). Forty-two patients had CAD, and IIEF-5 was able to discriminate them (area under the ROC curve = 0.63, p = 0.006). Patients were divided into two groups: IIEF-5 < 20 (n = 140) and IIEF-5 > 20 (n = 123); those with lower IIEF-5 scores were older (57 [52-61] vs. 54 [45-60] years, p = 0.002), had higher prevalence of CAD (22% vs. 9%, p = 0.004), smoking (64% vs. 47%, p = 0.009) and use of calcium channel inhibitors (65% vs. 43.%, p = 0.001), as well as lower CrCl (67.3 [30.8 to 88.6] vs. 82.6 [65.9 - 98.2] ml/min, p <0.001). The IIEF-5 < 21 was associated with increased risk of CAD in the logistic regression, both univariate (RR = 2.89 [95%CI: 1.39 - 6.05]), and after adjusting for age, diabetes, CrCl, smoking, mean arterial pressure and use of antihypertensive drugs (RR = 2.59 [95% CI: 1.01 - 6.61]).
CONCLUSION: The IIEF-5 is associated with the diagnosis of CAD and its use can add information to cardiovascular risk staging in hypertensive patients.
Keywords: Erectile dysfunction; hypertension; coronary artery disease.
Erectile Dysfunction (ED), the incapacity to achieve and maintain a penile erection sufficient to have satisfactory sexual intercourse1 affects approximately 150 million men around the world2 and is associated with higher prevalence of cardiovascular risk factors, such as diabetes mellitus (DM)3, Systemic Arterial Hypertension (SAH), dyslipidemia, obesity, smoking and metabolic syndrome4-6. In Brazil, Moreira et al.7, in a multicenter study involving 1286 men aged 18 years and older, described the presence of some degree of ED in 46% of the participants.
Atherosclerosis is a major cause of ED, thus individuals who develop erectile dysfunction are at increased risk for developing other manifestations of atherosclerotic disease, such as Stroke and Coronary Artery Disease (CAD) 8-13, even after adjusting for factors traditionally related to cardiovascular disease14. Furthermore, there is evidence that the degree of ED is associated with CAD severity15.
The presence and severity of ED can be assessed using the International Index of Erectile Function (IIEF), a self-administered questionnaire consisting of 15 items, covering different areas related to sexual function (erection, orgasm, desire and satisfaction)16.
Rosen et al.17 developed a simplified version of the questionnaire, consisting of only five items (IIEF-5), which has been shown to be a practical tool for ED diagnosis and classification. Our objective was to evaluate the association between the presence of erectile dysfunction, as assessed by the IIEF-5, and the diagnosis of CAD in hypertensive patients.
Patients and methods
We performed a cross-sectional study that evaluated all men aged between 18 to 65 years, consecutively attended in the Section of Hypertension and Nephrology of Instituto Dante Pazzanese de Cardiologia (IDPC - outpatients clinic) between April 3 and May 31, 2010 and demonstrated interest in participating in the study by signing the informed consent form. The age range for inclusion is that necessary for the referral of patients to the Section of Hypertension and Nephrology IDPC outpatients clinic. The study was approved by the Ethics of Committee of IDPC.
After detailed clinical and cardiologic assessment, patients were asked to answer the self-administered questionnaire of the International Index of Erectile Function (IIEF-5)17. The IIEF-5 questionnaire score determined the presence and severity of ED: absent (> 21), mild (17-21), mild / moderate (12-16), moderate (8-11) and severe (<8)
All patients had weight and height measured at the time of consultation. Laboratory tests (glucose, creatinine, total cholesterol and triglycerides) performed at the Laboratory of IDPC and brought to the medical consultation, were considered in the analysis. Glomerular filtration rate was calculated by the Cockroft-Gault equation18, adjusted for body surface area. The mean arterial pressure (MAP), calculated by the formula "(systolic blood pressure + [2 * diastolic blood pressure]) / 3" was used in the analysis, as it is the best method of measuring tissue perfusion pressure. The CAD diagnosis was performed by reviewing medical records, based on the revascularization history (surgical/percutaneous) or presence of prior coronary lesion > 50% at the coronary angiography.
Data distribution analysis was performed using the Kolmogorov-Smirnov test. The analysis of the receiver-operating characteristic (ROC) was used to establish the value of IIEF-5 that best identified the presence of CAD. The variables were expressed as mean ± standard deviation, median (interquartile range, IQR) or as percentage, as appropriate. As many values were not normally distributed, Spearman's rank correlation (Rho) was used to determine correlations. Groups were compared by Mann-Whitney test or Chi-square analysis, as appropriate. Crude and adjusted logistic regression analyses were performed to evaluate the association between coronary artery disease and erectile dysfunction.
Based on literature data, where the proportion of erectile dysfunction was 47% in patients with CAD and 24% in controls19, the minimum sample size required for our results to have a significance level of 5% and test power of 90 % was calculated at 178 patients (89 per group). All probabilities of significance (p values) are two-tailed and values < 0.05 were considered statistically significant. Statistical analysis was performed using SPSS 13.0 software (SPSS Inc., Chicago IL, 2004).
We evaluated 263 patients with median age of 55 (50-61) years, whose demographic and clinical data are described in Table 1. One hundred and fifty-five patients (59%) had some degree of erectile dysfunction according to IIEF-5 questionnaire (Table 1 and Figure 1).
The IIEF-5 questionnaire was negatively correlated with age (rho = - 0.22, p < 0.001) and positively correlated with creatinine clearance (rho = 0.23, p <0.001), as shown in Table 2. Patients with a history of CAD had lower IIEF-5 (17 [8-21] vs. 21. [15-23], p = 0.006), Figure 2. The IIEF-5 questionnaire was able to discriminate individuals with a diagnosis of CAD (area under ROC curve = 0.63, p = 0.006), as shown in Figure 3, and "20" was the IIEF-5 score considered to be more appropriate for this purpose.
The patients were divided into two groups according to the IIEF-5 score (< 20 and > 20) and their clinical and demographic characteristics are described in Table 3. In summary, patients with lower IIEF-5 were older (57 years [52-61] vs. 54 years [45-60], p = 0.002), had a higher prevalence of CAD (22% vs. 9%, p = 0.004), smoking (64% vs. 47%, p = 0.009) and use of calcium channel inhibitors (65% vs. 43.%, p = 0.001), as well as a lower creatinine clearance (67.3 mL / min [30.8 to 88.6] vs. 82.6 mL / min [65.9 to 98.2], p <0.001).
The logistic regression analysis (Table 4) showed that IIEF-5 score < 20 was associated with the presence of CAD in both the univariate analysis (odds ratio = 2.89 [95%CI: 1.39-6.05]) and even after adjustments for potential confounders such as age, diabetes mellitus, kidney disease, smoking, mean arterial pressure, use of angiotensin-converting enzyme inhibitors / angiotensin II receptor blockers, diuretics, calcium channel blockers and beta blockers (odds ratio = 2.59 [95%CI: 1.01 - 6.61]).
The present study showed that hypertensive patients with IIEF-5 score < 20 have a 2.59-fold higher odds of presenting diagnosis of CAD, regardless of the presence of known cardiovascular risk factors (age, diabetes, kidney disease and smoking) and the use of antihypertensive drugs, known to be associated with the development of erectile dysfunction. Our results provide further evidence of the association between ED and CAD9,11,20-22.
ED is considered a clinical manifestation of vascular functional and structural alterations, resulting from widespread cardiovascular disease, with penile circulation being affected earlier due to the smaller diameter of the penile arteries, when compared to coronary, carotid and femoral arteries11. Thus, ED and CAD may be considered different manifestations of the same disease, which is highlighted by the fact that the risk factors associated with CAD are commonly found in patients with ED23, as well as by the correlation between ED degree and CAD severity24. In fact, we observed that patients with CAD, when compared to those with no history of coronary artery disease, had a significantly lower IIEF-5.
The stratification of cardiovascular risk is an essential step to establish BP goals to be achieved in hypertensive patients25. Thus, given that the prevalence of ED is extremely high in patients with CAD19,20, with the first being an independent risk predictor for the development of the latter, in addition to preceding it on average by three years20, it would be reasonable to perform ED screening in all patients with risk factors for cardiovascular disease development. However, as this is a self-reported condition, often purposely omitted and with no specific confirmatory tests available, the investigation of erectile dysfunction by cardiologists is usually neglected.
In this set, our results, by showing the independent association between the IIEF-5 questionnaire - a simple and easy-to-use tool to diagnose the presence and severity of ED17 - and the presence of CAD, highlight their usefulness in everyday routine of medical offices, where it can be applied even in waiting rooms, both for the identification of erectile dysfunction and also for cardiovascular risk stratification.
The prevalence of erectile dysfunction in our patients (59%) was higher than that described in other studies with the Brazilian population7,22,27,28, which may be attributed to the fact that our sample included only hypertensive patients29,30. We also emphasize that the cutoff of 20 for the IIEF-5 adopted in our analysis includes patients with mild ED according to the original classification17, which may be related to failure in the classification or higher prevalence of psychiatric and non-organic alterations as cause of ED in patients with borderline IIEF-5 score. Our study has limitations, including: a) its cross-sectional design, which only allows the establishment of associations, b) the small sample size; c) the lack of information regarding the antihypertensive dose used, and d) the fact that the CAD diagnosis was based only on clinical history and medical file review. However, the diagnosis of CAD is initially hypothesized based on the patient's medical history; in this sense, our study simulated the conditions experienced by clinicians in their daily routine.
The presence of erectile dysfunction is associated with increased risk of coronary artery disease. The use of the IIEF-5 score may add information to the cardiovascular risk stratification of patients assessed at the medical office.
Potential Conflict of Interest
No potential conflict of interest relevant to this article was reported.
Sources of Funding
There were no external funding sources for this study.
This article is the result of the Monograph for Conclusion of Medical Residence in Cardiology by Carolina Christianini Mizzaci, Rafael Modesto Fernandes, Afrânio Galdino de Araújo Junior, Paulo Oliveira Cardoso e Lucas Velloso Dutra, from Instituto Dante Pazzanese de Cardiologia - São Paulo, SP.
1. Hatzimouratidis K, Amar E, Eardley I, Giuliano F, Hatzichristou D, Montorsi F, et al. Guidelines on male sexual dysfunction: erectile dysfunction and premature ejaculation. Eur Urol. 2010;57(5):804-14. [ Links ]
2. Ayta IA, McKinlay JB, Krane RJ. The likely worldwide increase in erectile dysfunction between 1995 and 2025 and some possible policy consequences. BJU Int. 1999;84(1):50-6. [ Links ]
3. Burke JP, Jacobson DJ, McGree ME, Nehra A, Roberts RO, Girman CJ, et al. Diabetes and sexual dysfunction: results from the Olmsted County study of urinary symptoms and health status among men. J Urol. 2007;177(4):1438-42. [ Links ]
4. Bacon CG, Mittleman MA, Kawachi I, Giovannucci E, Glasser DB, Rimm EB. Sexual function in men older than 50 years of age: results from the health professionals follow-up study. Ann Intern Med. 2003;139(3):161-8. [ Links ]
5. Bal K, Oder M, Sahin AS, Karatas CT, Demir O, Can E, et al. Prevalence of metabolic syndrome and its association with erectile dysfunction among urologic patients: metabolic backgrounds of erectile dysfunction. Urology. 2007;69(2):356-60. [ Links ]
6. Saigal CS, Wessells H, Pace J, Schonlau M, Wilt TJ; Urologic Diseases in America Project. Predictors and prevalence of erectile dysfunction in a racially diverse population. Arch Intern Med. 2006;166(2):207-12. [ Links ]
7. Moreira ED Jr, Abdo CH, Torres EB, Lobo CF, Fittipaldi JA. Prevalence and correlates of erectile dysfunction: results of the Brazilian study of sexual behavior. Urology. 2001;58(4):583-8. [ Links ]
8. Bolona ER, Uraga MV, Haddad RM, Tracz MJ, Sideras K, Kennedy CC, et al. Testosterone use in men with sexual dysfunction: a systematic review and meta-analysis of randomized placebo-controlled trials. Mayo Clin Proc. 2007;82(1):20-8. [ Links ]
9. Elesber AA, Solomon H, Lennon RJ, Mathew V, Prasad A, Pumper G, et al. Coronary endothelial dysfunction is associated with erectile dysfunction and elevated asymmetric dimethylarginine in patients with early atherosclerosis. Eur Heart J. 2006;27(7):824-31. [ Links ]
10. Montorsi P, Ravagnani PM, Galli S, Rotatori F, Briganti A, Salonia A, et al. The artery size hypothesis: a macrovascular link between erectile dysfunction and coronary artery disease. Am J Cardiol. 2005;96(12B):19M-23M. [ Links ]
11. 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(3):512-8. [ Links ]
12. Thompson IM, Tangen CM, Goodman PJ, Probstfield JL, Moinpour CM, Coltman CA. Erectile dysfunction and subsequent cardiovascular disease. JAMA. 2005;294(23):2996-3002. [ Links ]
13. Vlachopoulos C, Aznaouridis K, Ioakeimidis N, Rokkas K, Vasiliadou C, Alexopoulos N, et al. Unfavourable endothelial and inflammatory state in erectile dysfunction patients with or without coronary artery disease. Eur Heart J. 2006;27(22):2640-8. [ Links ]
14. Araujo AB, Hall SA, Ganz P, Chiu GR, Rosen RC, Kupelian V, et al. Does erectile dysfunction contribute to cardiovascular disease risk prediction beyond the Framingham risk score? J Am Coll Cardiol. 2010;55(4):350-6. [ Links ]
15. Le NA. Inflammation, oxidative stress, and atherosclerosis. Curr Opin Lipidol. 2004;15(2):227-9. [ Links ]
16. Rosen RC, Riley A, Wagner G, Osterloh IH, Kirkpatrick J, Mishra A. The international index of erectile function (IIEF): a multidimensional scale for assessment of erectile dysfunction. Urology. 1997;49(6):822-30. [ Links ]
17. Rosen RC, Cappelleri JC, Smith MD, Lipsky J, Pena 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):319-26. [ Links ]
18. Cockcroft DW, Gault MH. Prediction of creatinine clearance from serum creatinine. Nephron. 1976;16(1):31-41. [ Links ]
19. Montorsi P, Ravagnani PM, Galli S, Rotatori F, Veglia F, Briganti A, 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(22):2632-9. [ Links ]
20. Montorsi F, Briganti A, Salonia A, Rigatti P, Margonato A, Macchi 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(3):360-4. [ Links ]
21. Dong JY, Zhang YH, Qin LQ. Erectile dysfunction and risk of cardiovascular disease meta-analysis of prospective cohort studies. J Am Coll Cardiol. 2011;58(13):1378-85. [ Links ]
22. Ortiz J, Ortiz ST, Monaco CG, Yamashita CH, Moreira MC, Monaco CA. [Erectile dysfunction: a marker for myocardial perfusion impairment?]. Arq Bras Cardiol. 2005;85(4):241-6. [ Links ]
23. Sullivan ME, Keoghane SR, Miller MA. Vascular risk factors and erectile dysfunction. BJU Int. 2001;87(9):838-45. [ Links ]
24. Salem S, Abdi S, Mehrsai A, Saboury B, Saraji A, Shokohideh V, et al. Erectile dysfunction severity as a risk predictor for coronary artery disease. J Sex Med. 2009;6(12):3425-32. [ Links ]
25. Sociedade Brasileira de Cardiologia, Sociedade Brasileira de Hipertensão, Sociedade Brasileira de Nefrologia. VI Diretrizes brasileiras de hipertensão. Arq Bras Cardiol. 2010;95(1 supl.1):1-51. [ Links ]
26. Rhoden EL, Teloken C, Sogari PR, Vargas Souto CA. The use of the simplified International Index of Erectile Function (IIEF-5) as a diagnostic tool to study the prevalence of erectile dysfunction. Int J Impot Res. 2002;14(4):245-50. [ Links ]
27. Moreira ED Jr, Bestane WJ, Bartolo EB, Fittipaldi JA. Prevalence and determinants of erectile dysfunction in Santos, southeastern Brazil. Sao Paulo Med J. 2002;120(2):49-54. [ Links ]
28. Reis MM, Abdo CH. Prevalence of erectile dysfunction as defined by the International Index of Erectile Function (IIEF) and self-reported erectile dysfunction in a sample of Brazilian men who consider themselves healthy. J Sex Marital Ther. 2010;36(1):87-100. [ Links ]
29. Doumas M, Douma S. Sexual dysfunction in essential hypertension: myth or reality? J Clin Hypertens (Greenwich). 2006;8(4):269-74. [ Links ]
30. Fogari R, Zoppi A. Effects of antihypertensive therapy on sexual activity in hypertensive men. Curr Hypertens Rep. 2002;4(3):202-10. [ Links ]
Mailing Address: Manuscript received January 11, 2012; manuscript revised January 13, 2012; accepted May 18, 2012.
Antonio Carlos Cordeiro
Instituto Dante Pazzanese de Cardiologia, Seção de Hipertensão e Nefrologia
Avenida Dr. Dante Pazzanese 500, Vila Mariana
Postal Code 04012-909, São Paulo, SP - Brazil
E-mail: email@example.com, firstname.lastname@example.org
Manuscript received January 11, 2012; manuscript revised January 13, 2012; accepted May 18, 2012.