Surveillance of cardiovascular risk factors for outpatients in different erectile dysfunction severity

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Abstract

We determined the association between the severity of erectile dysfunction (ED) and traditional cardiovascular risk factors, including metabolic syndrome (MS). A total of 141 ED patients were divided into three groups on the basis of ED severity, which was determined using the International Index of Erectile Function (IIEF) scores. The prevalence of MS among the ED patients was 32.6%. Significantly lower IIEF scores were noted in patients with MS than in patients without MS (7.6±6.4 vs 11.6±7.4, P=0.003). As assessed by the anthropometric indices of body mass index, waist circumference and waist-to-hip ratio, obesity was detected in 58.9, 54.6 and 32.6% of the patients, respectively. Of the 141 patients, 39 had mild, 24 had moderate and 78 had severe ED. Statistically significant differences were noted among the different ED severity groups with regard to the presence of hypertension, systolic blood pressure, presence of MS and number of MS components. Multivariate analysis showed that the odds ratio for high-low-density lipoprotein (LDL) cholesterol level in moderate and severe ED, determined with reference to mild ED, were 9.346 and 6.452, respectively. The presence of MS, number of MS components, and certain traditional cardiovascular risk factors, particularly high-LDL cholesterol level and hypertension, may influence the severity of ED.

Introduction

Erectile dysfunction (ED) is the recurrent or persistent inability to attain or maintain a penile erection consistent with satisfactory sexual intercourse. This is a common distracted problem that affects up to 10% of men aged between 40 and 70 years,1 and adversely affects the quality of life of men in middle and old age. The incidence and prevalence of ED are expected to show continuous increases; indeed, the projected prevalence for 2005 was approximately 322 million subjects.2 Previous studies have suggested that ED could be a reliable marker for cardiovascular diseases and that it plays an important role in vascular diseases. Further, several epidemiological studies have demonstrated that ED is more prevalent among men with atherosclerotic diseases, including coronary artery disease (CAD), than it is in the general population.3, 4, 5

It is now well established that many risk factors for CAD (hypertension, smoking, dyslipidemia, diabetes mellitus (DM) and lack of physical exercise) are also risk factors for ED;6, 7 at least one significant cardiovascular risk factor occurs in most ED patients.8, 9, 10 This could be attributed to the fact that both CAD and ED are characterized by endothelial dysfunction and injury.11, 12 These shared risk factors contribute to endothelial dysfunction and impede vasodilatation, thereby inhibiting the occurrence of normal erection.

Metabolic syndrome (MS) is a cluster of conditions, including DM or impaired glucose tolerance, hypertension, obesity and dyslipidemia, that is closely associated with cardiovascular morbidity and mortality.13, 14 As MS has been found to be associated with atherosclerotic ischemic heart disease, ED also shows a strong association with several classic risk factors for CAD, particularly DM, current smoking status and hypertension.15, 16 Therefore, MS and ED could be related.

However, although the relationship among cardiovascular risk factors, MS and ED has been established, there are currently no data available regarding differences in the severity of ED. The aim of this study was to investigate the effects of traditional cardiovascular risk factors on the severity of ED. In addition, the potential association between ED severity and MS was also evaluated.

Materials and methods

Between January 2006 and December 2007, 141 consecutive male outpatients with a clinical diagnosis of ED in our hospital visiting our urology clinic volunteered to participate into this prospective study. Informed consent was obtained from all the patients and the study protocol was approved by the local ethics committee. All the patients had been referred to the urology clinic with an initial diagnosis of functional ED. The patients were examined by urologists and their ED-related histories were recorded. The severity of ED was determined on the basis the International Index of Erectile Function (IIEF) scores.17 Questions 1–5 and 15 of the IIEF constitute the erectile function domain, which is used to assess global erectile function. Scoring the IIEF domain of erectile function allowed the classification of each patient as follows: absent of ED (26–30), mild ED (17–25), moderate ED (11–16) and severe ED (0–10).

Blood was collected for routine chemical analyses after an overnight fast, with the patients in the supine position. Standard blood tests, including serum fasting glucose level, and lipid profiles, were performed. All blood samples were collected at the same time of the day (between 0800 and 1000 hours). The blood samples were separated, and then frozen at −80 °C until required for analysis. The criteria for MS were adopted from The Third Report of the National Cholesterol Education Program Expert Panel on the Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adults Treatment Panel III, ATP III);18 the exception being that high waist circumference was defined as greater than 90 cm based on the norms for the Asian population. Patients who satisfied three or more criteria were considered to have MS.

The waist circumference was measured at a point midway between the lowest rib and the iliac crest in the standing position. Patients with a waist circumference of greater than 90 cm were considered to have a high waist circumference. The hip circumference was measured in the standing position in the plane of both major femoral trochanters. Body mass index (BMI) was calculated by dividing the body weight in kilograms by the height in meters squared (kg/m2). Patients with a BMI of 25 kg/m2 or more were considered as obese and having high BMI values. The waist-to-hip ratio (WHR) was calculated by dividing the waist circumference by the hip circumference. A WHR of 0.95 or more was considered to be high.

The χ2-test was employed to compare the following parameters: presence of DM, hypertension or MS; current smoking status; ED classification and distribution of dyslipidemia or obesity. The independent t-test was used to compare the ages and the biochemical and hormonal profiles of the patients with and without MS. The results were expressed as the mean±s.d. The nonparametric Kruskal–Wallis test was used to compare the ages, and the biochemical and hormone profiles of the three ED severity groups: mild, moderate and severe. Multivariate analysis using a nominal logistical regression was performed to identify the independent variables; their odds ratios (ORs) were derived from the nominal logistic model and the 95% confidence intervals (CI 95%) of the ORs were computed for the principal results. A P value equal to or less than 0.05 was considered to be statistically significant; the P value between 0.05 and 0.1 were considered to be indicative of a significant trend. All data were analyzed using the SPSS 14.0 for Windows statistical package.

Results

The baseline characteristics of the study patients are shown in Table 1. The mean ED duration was 2.4±2.8 years. Significantly lower IIEF scores were obtained in patients with MS as compared to patients without MS (7.6±6.4 vs 11.6±7.4, P=0.003). The incidence of traditional cardiovascular risk factors was high in these ED patients: DM (44.7%), hypertension (24.8%), cigarette smoking status (31.9%), hypercholesterolemia (32.6%), hypertriglyceridemia (35.5%), low-high-density lipoprotein (HDL) cholesterol levels (34.8%) and high-low-density lipoprotein (LDL) cholesterol levels (25.5%). As assessed by the anthropometric indices of BMI, waist circumference and WHR, obesity was detected in 58.9, 54.6 and 32.6% of patients, respectively.

Table 1 Demographic characteristics of patients

Variables between the patients with or without MS are shown in Table 2. The prevalence of MS was 32.6% (46/141). No differences were found with regard to age (55.1±9.3 vs 53.5±10.4 years, P=0.363), high sensitivity C-reactive protein (hs-CRP) levels (1.6±1.6 vs 1.5±2.1 mg l−1, P=0.572) and duration of ED (2.4±2.6 vs 2.3±3.0 years, P=0.941) between patients with and without MS. The IIEF scores were lower in the MS group than in the non-MS group (7.6±6.4 vs 11.6±7.4, P=0.003).

Table 2 Variables between patients with/without metabolic syndrome

Of the 141 patients, 39 (27.7%) had mild, 24 (17.0%) had moderate and 78 (55.3%) had severe ED. The characteristics of the patients in these three groups are listed in Table 3. Overall, no statistically significant differences were noted among the different ED severity groups, with the exception of the presence of hypertension (15.4, 12.5 and 33.3%, respectively; P=0.033), systolic blood pressure (125.8±14.5, 126.7±18.6 and 133.9±15.8 mm Hg, respectively; P=0.029), presence of MS (17.9, 25 and 42.3%, respectively; P=0.020) and number of MS components (1.6±1.1, 1.7±1.4 and 2.2±1.4, respectively; P=0.038). There appeared to be a statistically nonsignificant dose relationship between ED severity and following terms: duration of hypertension (1.1±2.8, 0.6±2.1 and 2.1±5.4 years, respectively; P=0.084), duration of DM (1.5±3.0, 2.1±3.5 and 3.3±4.8 years, respectively; P=0.058), hs-CRP level (1.6±2.8, 1.1±1.3 and 1.6±1.6 mg l−1, respectively; P=0.076) and high-LDL cholesterol levels (12.8, 33.3 and 29.5%, respectively; P=0.094); however, the P values were borderline nonsignificant (statistically trend). As shown in Figure 1, a positive correlation was noted between the number of MS components and the IIEF scores.

Table 3 Variables among patients in different erectile dysfunction severity
Figure 1
figure1

Positive correlation between the number of metabolic syndrome (MS) components and erectile dysfunction (ED) severity.

Nominal logistic regression showed that the OR of high-LDL cholesterol levels was 9.346 (95% CI: 1.618–55.556) in the case of moderate ED and 6.452 (95% CI: 1.577–26.316) in the case of severe ED referring to the mild ED when controlling duration of hypertension, systolic blood pressure, hs-CRP values, hypertriglyceridemia, hypercholesterolemia, low-HDL cholesterol levels and high waist girth. Meanwhile, when assessed with respect to patients with mild ED, the OR for the duration of DM in severe ED patients was 1.188 (95% CI: 1.020–1.383).

Discussion

MS, which constitutes many traditional cardiovascular risk factors, has been proved to have a strong relationship with CAD.13, 14 Similarly, it is now well known that ED is associated with the cardiovascular risk factors. Further, the degree of ED is related to the number and severity of the risk factors themselves.1, 19, 20 Recent studies have shown that the similar pathogenic involvement of the nitric oxide (NO) pathway leading to the early impairment of endothelium-dependent vasodilatation and late obstructive vascular changes is common to both ED and other vascular diseases.21, 22 In 2003, a pathophysiological mechanism, the ‘artery-size hypothesis,’ was proposed by Montorsi et al. to explain the link among ED, CAD, and stroke.23 Atherosclerosis, a systemic disorder, should theoretically affect all the major vascular beds simultaneously, and to the same extent. However, the involvement of multiple vessels is rarely clinically evident at the same time. The reason behind this could be that arteries with different sizes supply the various vascular beds: a plaque that significantly obstructs a small vessel may lodge in a larger vessel without interfering with the blood flow. Therefore, the occlusion of the cavernous arteries by atherosclerosis characterized by vascular damage, endothelial dysfunction, decrease in NO production, increase in NO degeneration, increase in advanced glycation end products resulting in NO scavenging, increase in the NO synthase inhibitor, free radial damage or a combination of these complex interactions, may partly explain the association between ED and MS.

Bansal et al.24 reported that the prevalence of MS in an ED population was 43%, but was only 24% in a matched control population. Similarly, Esposito et al.25 reported that in comparison with an age- and weight-matched control groups, patients with MS also exhibited an increased prevalence of ED. In our study, the prevalence rate of MS in ED patients was 32.6%. Further, among the potential cardiovascular risk factors, a high incidence of DM, hypertension, hypercholesterolemia, hypertriglyceridemia, low-HDL cholesterol level and high-LDL cholesterol level were noted in these ED outpatients. With regard to obesity classified according to different anthropometric indices, waist circumference, BMI and WHR were also high in our ED patients. These results partially indicate that ED patients have a potential risk of cardiovascular events due to the presence of traditional cardiovascular independent risk factors among a large proportion of ED patients.

There are conflicting reports regarding the relationship between ED severity and MS. Only a very few studies have examined the factors that affect the severity of disease in patients with ED. Esposito et al.25 have reported an increase in the prevalence of ED with an increase in the number of MS components. However, they did not investigate the correlation between ED severity, prevalence of MS and the number of MS components. Paick et al.26 concluded that MS may not influence the severity of ED in impotent men. In our study, the IIEF scores were relatively lower in patients with MS than in those without MS. Moreover, the prevalence of MS showed a significant inverse correlation with the ED severity. Furthermore, the ED severity also increased with the number of MS components. To our knowledge, there was lack of study to illustrate this issue.

Despite the reverse correlation effect of MS on the ED severity, the other traditional cardiovascular-independent risk factors showed no significant correlation, which impact the disease severity in men suffering from ED except the factor of the presence of hypertension. These observations are consistent with those of Paick et al.26 who concluded that MS was not correlated with ED severity. In our study, systolic blood pressure showed an inversely impact to the ED severity.

In patients with DM, ED has a multifactorial etiology, which involves glycation of elastic fibers, and failure of relaxation of the corpora cavernosa, multiple-drug treatment, dyslipidemia, peripheral vascular disease affecting the arterial and arteriolar inflow and advanced glycation end products leading to an increase in reactive oxidizing substances and a decrease in NO production.27 A retrospective analysis of a cohort of men with type 2 DM demonstrated that glycated hemoglobin (HbA1C) is an independent predictor of ED.28 We, nevertheless, failed to observe any significant correlation between ED severity and HbA1C levels. However, a statistical trend was observed between the ED severity and the duration of the presence of DM. This fact could be because of the insufficient number of patients.

Walczak et al.29 have previously reported that as many as 79% of men with ED are either overweight or obesity. Similarly, Derby et al.30 reported that overweight patients were at a greater risk of developing ED. However, the relationship between obesity and ED severity remains controversial. Kupelian et al.31 showed the predictive value—twofold increase in risk—of ED for MS in men with BMI <25. Heidler et al.32 reported that the WHR is independently associated with a decrease in the IIEF scores and Demir et al.33 demonstrated that the waist circumference was a new and independent metabolic risk factor for ED. However, in the present study, we found that none of the anthropometric indices of obesity were statistically correlated with the severity of ED.

In patients with dyslipidemia, the production of LDL cholesterol results in a reduction in endogenous NO synthethase.34 This adversely affects the activity and bioavailability of NO on the endothelial surface and may lead to impaired endothelium-based vasodilatation.35 Few previous studies have examined the association between ED severity and dyslipidemia. In our study, the nominal logistic regression showed high-LDL cholesterol levels statistically significant in the correlation with ED severity.

Many types of antihypertensive medications contribute to ED severity. Consequently, before scoring ED severity, patients with hypertension should receive no medication with thiazide diuretics, central-acting sympatholytic agents, or β-blockers, even though the role of these agents in worsening ED is still controversial.36 Besides, as the study population consists of men at a urologic clinic, there is a referral bias that might limit the overall generation of data presented. On the contrary, thinking about it in another way, this is the value of this manuscript for its being near to the real clinical practice world.

Accumulating evidence suggests that there exists a strong association between MS and ED. However, this needs to be confirmed through further larger epidemiological studies. Nevertheless, the positive correlation observed between the severity of ED and the prevalence of MS proportion and number of MS components is suggestive of a progressive burden of increasing cardiovascular risk on patients with ED. In conclusion, the presence of MS, the number of MS components and the presence of certain traditional cardiovascular risk factors, such as hypertension, systolic blood pressure, long duration of DM and hypertension, hs-CRP levels and high-LDL cholesterol levels may influence ED severity. Intensive medical treatment and lifestyle modifications are strongly recommended for patients who are at a risk of developing MS, and consequently ED.

References

  1. 1

    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.

  2. 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: 50–56.

  3. 3

    Gazzaruso C, Giordanetti S, De Amici E, Bertone G, Falcone C, Geroldi D et al. Relationship between erectile dysfunction and silent myocardial ischemia in apparently uncomplicated type 2 diabetic patients. Circulation 2004; 110: 22–26.

  4. 4

    Montorsi P, Montorsi F, Schulman CC . Is erectile dysfunction the ‘tip of the iceberg’ of a systemic vascular disorder? Eur Urol 2003; 44: 352–354.

  5. 5

    Cheitlin MD . Should the patient with coronary artery disease use sildenafil? Prev Cardiol 2003; 6: 161–165.

  6. 6

    El-Sakka AI, Morsy AM, Fagih BI, Nassar AH . Coronary artery risk factors in patients with erectile dysfunction. J Urol 2004; 172: 251–254.

  7. 7

    Feldman HA, Johannes CB, Derby CA, Kleinman KP, Mohr BA, Araujo AB et al. Erectile dysfunction and coronary risk factors: prospective results from the Massachusetts male aging study. Prev Med 2000; 30: 328–338.

  8. 8

    Greenstein A, Chen J, Miller H, Matzkin H, Villa Y, Braf Z . Does severity of ischemic coronary disease correlate with erectile function? Int J Impot Res 1997; 9: 123–126.

  9. 9

    Virag R, Bouilly P, Frydman D . Is impotence an arterial disorder? A study of arterial risk factors in 440 impotent men. Lancet 1985; 1: 181–184.

  10. 10

    Shabsigh R, Fishman IJ, Schum C, Dunn JK . Cigarette smoking and other vascular risk factors in vasculogenic impotence. Urology 1991; 38: 227–231.

  11. 11

    Conti CR, Pepine CJ, Sweeney M . Efficacy and safety of sildenafil citrate in the treatment of erectile dysfunction in patients with ischemic heart disease. Am J Cardiol 1999; 83: 29C–34C.

  12. 12

    Brunner H, Cockcroft JR, Deanfield J, Donald A, Ferrannini E, Halcox J, et al., Working Group on Endothelins and Endothelial Factors of the European Society of Hypertension. Endothelial function and dysfunction. Part II: Association with cardiovascular risk factors and diseases. A statement by the Working Group on Endothelins and Endothelial Factors of the European Society of Hypertension. J Hypertens 2005; 23: 233–246.

  13. 13

    Isomaa B, Almgren P, Tuomi T, Forsen B, Lahti K, Nissen M et al. Cardiovascular morbidity and mortality associated with the metabolic syndrome. Diabetes Care 2001; 24: 683–689.

  14. 14

    Mykkanen L, Zaccaro DJ, Wagenknecht LE, Robbins DC, Gabriel M, Haffner SM . Microalbuminuria is associated with insulin resistance in nondiabetic subjects: the insulin resistance atherosclerosis study. Diabetes 1998; 47: 793–800.

  15. 15

    Papamichael CM, Lekakis JP, Stamatelopoulos KS, Papaioannou TG, Alevizaki MK, Cimponeriu AT et al. Ankle-brachial index as a predictor of the extent of coronary atherosclerosis and cardiovascular events in patients with coronary artery disease. Am J Cardiol 2000; 86: 615–618.

  16. 16

    Johnson RJ, Kivlighn SD, Kim YG, Suga S, Fogo AB . Reappraisal of the pathogenesis and consequences of hyperuricemia in hypertension, cardiovascular disease, and renal disease. Am J Kidney Dis 1999; 33: 225–234.

  17. 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: 319–326.

  18. 18

    Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. Executive Summary of The Third Report of The National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, And Treatment of High Blood Cholesterol In Adults (Adult Treatment Panel III). JAMA 2001; 285: 2486–2497.

  19. 19

    Bortolotti A, Parazzini F, Colli E, Landoni M . The epidemiology of erectile dysfunction and its risk factors. Int J Androl 1997; 20: 323–334.

  20. 20

    Roumeguere T, Wespes E, Carpentier Y, Hoffmann P, Schulman CC . Erectile dysfunction is associated with a high prevalence of hyperlipidemia and coronary heart disease risk. Eur Urol 2003; 44: 355–359.

  21. 21

    Azadzoi KM, Goldstein I . Erectile dysfunction due to atherosclerotic vascular disease: the development of an animal model. J Urol 1992; 147: 1675–1681.

  22. 22

    Sullivan ME, Thompson CS, Dashwood MR, Khan MA, Jeremy JY, Morgan RJ et al. Nitric oxide and penile erection: is erectile dysfunction another manifestation of vascular disease? Cardiovasc Res 1999; 43: 658–665.

  23. 23

    Kloner RA, Mullin SH, Shook T, Matthews R, Mayeda G, Burstein S et al. Erectile dysfunction in the cardiac patient: how common and should we treat? J Urol 2003; 170: S46–S50.

  24. 24

    Bansal TC, Guay AT, Jacobson J, Woods BO, Nesto RW . Incidence of metabolic syndrome and insulin resistance in a population with organic erectile dysfunction. J Sex Med 2005; 2: 96–103.

  25. 25

    Esposito K, Giugliano F, Martedì E, Feola G, Marfella R, D’Armiento M et al. High proportions of erectile dysfunction in men with the metabolic syndrome. Diabetes Care 2005; 28: 1201–1203.

  26. 26

    Paick JS, Yang JH, Kim SW, Ku JH . Severity of erectile dysfunction in married impotent patients: interrelationship with anthropometry, hormones, metabolic profiles and lifestyle. Int J Urol 2007; 14: 48–53.

  27. 27

    Richardson D, Vinik A . Etiology and treatment of erectile failure in diabetes mellitus. Curr Diab Rep 2002; 2: 501–509.

  28. 28

    Romeo JH, Seftel AD, Madhun ZT, Aron DC . Sexual function in men with diabetes type 2: association with glycemic control. J Urol 2000; 163: 788–791.

  29. 29

    Walczak MK, Lokhandwala N, Hodge MB, Guay AT . Prevalence of cardiovascular risk factors in erectile dysfunction. J Gend Specif Med 2002; 5: 19–24.

  30. 30

    Derby CA, Mohr BA, Goldstein I, Feldman HA, Johannes CB, McKinlay JB . Modifiable risk factors and erectile dysfunction: can lifestyle changes modify risk? Urology 2000; 56: 302–306.

  31. 31

    Kupelian V, Shabsigh R, Araujo AB, O’Donnell AB, McKinlay JB . Erectile dysfunction as a predictor of the metabolic syndrome in aging men: results from the Massachusetts Male Aging Study. J Urol 2006; 176: 222–226.

  32. 32

    Heidler S, Temml C, Broessner C, Mock K, Rauchenwald M, Madersbacher S et al. Is the metabolic syndrome an independent risk factor for erectile dysfunction? J Urol 2007; 177: 651–654.

  33. 33

    Demir T, Demir O, Kefi A, Comlekci A, Yesil S, Esen A . Prevalence of erectile dysfunction in patients with metabolic syndrome. Int J Urol 2006; 13: 385–388.

  34. 34

    Vallance P, Chan N . Endothelial function and nitric oxide: clinical relevance. Heart 2004; 85: 342–350.

  35. 35

    Wheatcroft SB, Williams IL, Shah AM, Kearney MT . Pathophysiological implications of insulin resistance on vascular endothelial function. Diabet Med 2003; 20: 255–268.

  36. 36

    Rastogi S, Rodriguez JJ, Kapur V, Schwarz ER . Why do patients with heart failure suffer from erectile dysfunction? A critical review and suggestions on how to approach this problem. Int J Impot Res 2005; 17 (Suppl. 1): S25–S36.

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Acknowledgements

We thank Chang Gung Memorial Hospital for financially supporting this research under Contract No. CMRPG 660051.

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Correspondence to J-J Shee.

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Chang, S., Chu, C., Hsu, J. et al. Surveillance of cardiovascular risk factors for outpatients in different erectile dysfunction severity. Int J Impot Res 21, 116–121 (2009) doi:10.1038/ijir.2009.1

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Keywords

  • erectile dysfunction
  • coronary artery disease
  • metabolic syndrome
  • International Index of Erectile Function

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