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.
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.
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.
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).
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.
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).
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.
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We thank Chang Gung Memorial Hospital for financially supporting this research under Contract No. CMRPG 660051.
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Cite this article
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
- erectile dysfunction
- coronary artery disease
- metabolic syndrome
- International Index of Erectile Function
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