Prevalence of Asymptomatic CoronaryArtery Disease in Men with Vasculogenic Erectile Dysfunction: A Prospective Angiographic Study

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1 European Urology European Urology 48 (2005) Prevalence of Asymptomatic CoronaryArtery Disease in Men with Vasculogenic Erectile Dysfunction: A Prospective Angiographic Study Charalambos Vlachopoulos*, Konstantinos Rokkas, Nikolaos Ioakeimidis, Constadina Aggeli, Andreas Michaelides, Georgios Roussakis, Charalambos Fassoulakis, Athanasios Askitis, Christodoulos Stefanadis Cardiovascular Diseases and Sexual Health Unit, 1st Department of Cardiology, Athens Medical School, Hippokration Hospital, Athens, Greece Accepted 1 August 2005 Available online 24 August 2005 Abstract Objectives: Erectile dysfunction (ED) shares common risk factors with coronary artery disease (CAD). It has been suggested that ED may be considered a clinical manifestation of a generalized vascular disease affecting also the penile arteries. The aim of this prospective study was to evaluate angiographically the incidence of asymptomatic CAD in men with ED of vascular origin. Methods: Fifty consecutive asymptomatic men, aged years, with non-psychogenic and non-hormonal ED were comprehensively evaluated using medical history and examination, exercise treadmill test and stress echocardiography. Patients who had positive one or both of the two non-invasive procedures were referred for coronary arteriography in order to document CAD and evaluate the severity of the disease. Results: The mean time interval between the onset of ED and cardiological assessment was 25 months (range 1 66). Smoking (32 patients/64%), hypertension (31 patients/62%) and hyperlipidemia (26 patients/52%) were the most common risk factors. Moreover, 35 men (70%) had two or more risk factors. Twelve patients (24%) with ED had positive one or both of the two non-invasive procedures and one patient presented with acute myocardial infarction before he completed the non-invasive investigation. Coronary arteriography performed in ten patients (in nine with positive one or both of the two non-invasive procedures [while the other three refused], and in the patient with acute myocardial infarction) demonstrated that one patient had three-vessel disease, two patients had two-vessel disease and six patients had single-vessel disease. Conclusions: A considerable proportion (9/47 or 19%) of patients with ED of vascular origin has angiographically documented silent CAD. These findings support the strategy that patients with ED should undergo further cardiovascular evaluation. # 2005 Elsevier B.V. All rights reserved. Keywords: Coronary arteriography; Coronary artery disease; Erectile dysfunction; Exercise stress testing 1. Introduction It has been suggested that erectile dysfunction (ED) may be considered a clinical manifestation of a generalized vascular disease affecting also the penile * Corresponding author. Tel ; Fax: address: cvlachop@otenet.gr (C. Vlachopoulos). arteries. Indeed, ED shares many common risk factors with coronary artery disease (CAD) including aging, hypertension, diabetes mellitus, hypercholesterolaemia and smoking [1 4]. Endothelial dysfunction is a common underlying abnormality in ED and vascular disease [5 8]. ED is common in patients with CAD. Studies have shown that a significant proportion (42 75%) of patients /$ see front matter # 2005 Elsevier B.V. All rights reserved. doi: /j.eururo

2 C. Vlachopoulos et al. / European Urology 48 (2005) with CAD have ED [9 15]. Furthermore, it has been shown that the degree of ED is related to the extent of CAD [11,16] and ED is more frequent in diabetic patients with silent CAD than in those without CAD [17]. Interestingly enough, retrospective analysis has suggested that ED becomes evident prior to coronary artery disease in almost 70% of cases [9]. The aim of the present study was to assess prospectively the incidence of asymptomatic coronary artery disease determined angiographically in patients who present with ED of vascular origin. 2. Methods 2.1. Patients Fifty consecutive patients who were evaluated at the Cardiovascular and Sexual Health Clinic of the 1st Department of Cardiology of Athens Medical School for symptoms of erectile dysfunction and did not have a history or a clinical presentation of current cardiovascular disease comprised the study population. Patients were aged (59 11) years and were screened for sociodemographic data and risk factors for CAD, including smoking, diabetes, hypertension and hyperlipidemia. Diagnosis of hypertension was set if resting blood pressure was 140 (systolic) and/or 90 (diastolic) mmhg, of hypercholesterolaemia if total cholesterol level was 190 mg/dl (5 mmol/l) and LDL cholesterol level was 115 mg/dl (3 mmol/l), and of diabetes if plasma glucose level was 125 mg/dl (7.0 mmol/l; fasting) and 200 mg/dl (11.1 mmol/l; 2 hours after a 75 mg oral glucose load). Informed consent was obtained from each patient after explaining the nature of the tests, risks and benefits and alternative choices Evaluation of erectile dysfunction All patients were invited to complete a 5-item brief form of the International Index of Erectile Function (IIEF) [18], the Sexual Health Inventory for Men (SHIM) [19]. Following, all patients were evaluated by comprehensive medical and sexual history and physical examination. Special emphasis was put upon the onset of ED and medications, including b-adrenergic antagonists and diuretics. Patients with SHIM score less than 21 were submitted to hormonal testing and to penile color duplex Doppler ultrasonography using 20 mg intracavernous prostaglandin E1 and audiovisual stimulation [20,21]. Men with hormonal, neurogenic, anatomic, or psychogenic ED were excluded from the study. ED was defined as mild (SHIM score 17 21), mild to moderare (11 16), moderate (8 10) and severe (7 or less). Arteriogenic ED was diagnosed when peak systolic velocity was less than 35 cm/s Assessment of the incidence and extent of asymptomatic coronary artery disease All patients were referred for further assessment by exercise treadmill stress test and stress echocardiography. Exercise treadmill stress test was performed for detection of CAD and for assessment of cardiovascular efficacy during exercise and risk stratification of patients. Stress echocardiography, a feasible and accurate technique for the identification and localization of CAD [22], was added to the investigation to increase the sensitivity in the detection of CAD and to locate the responsible vessel(s). Stress echocardiography obtains optimal diagnostic accuracy in patients with a moderate risk of CAD such as those in our population [23]. Furthermore, it has been shown that patients with ED who have a negative stress echocardiography study are at low risk for cardiac death for 2 years following the stress study [24]. If at least one of these tests was positive, the patients were referred for coronary angiography for documentation and assessment of the severity of possible CAD. In two patients who were overweight dobutamine stress echocardiography was carried out alone. b-adrenergic antagonists and calcium channel blockers were discontinued for at least 48 h before the non-invasive tests Exercise treadmill test Exercise testing was carried out according to the multistage Bruce protocol [25]. An exercise test result was considered positive if there was (a) a horizontal or down-sloping ST segment depression of at least 1 mm, 60 ms beyond the J point or (b) an up-sloping ST-segment depression of 1.5 mm or greater, 80 ms beyond the J point, or (c) an ST-segment elevation of at least 1mm. An exercise electrocardiogram (ECG) was considered negative (based on STsegment changes) when the patient achieved at least 85% of the maximal predicted heart rate in the absence of ischemic ST-segment changes [26]. Two independent investigators who were unaware of the angiographic findings carried out the interpretation. Intra-observer and inter-observer variability for ST-segment changes were and mm respectively Echocardiographic studies All echocardiograms were recorded by commercially available equipment Philips (Sonos 5500, Andover, Massachusetts) ultrasound system, with a second harmonic MHz transducer to optimize endocardial border visualization. Dobutamine infusion was initiated at a dose of 10 mg/kg/min and increased up to mg/kg/ min every 3 minutes. Atropine (up to 2 mg) was administrated intravenously if the test end point was not reached. Continuous monitoring of ECG and blood pressure was performed throughout the infusion. Images were recorded on both videotape and digital format for later analysis. To match myocardial segments with coronary distribution, anterior wall, anterior septum, and apex were assigned to the left anterior descending coronary artery (LAD), the lateral wall to the circumflex artery (LCx), and the inferoposterior wall and inferior septum to the right coronary artery (RCA). An independent investigator who had no knowledge of patient data interpreted wall motion using the 16-segments as normal, hypokinetic, akinetic, or dyskinetic. A positive test for wall motion was defined as new or worsening wall motion abnormality in two or more contiguous segments during stress Coronary angiography Coronary angiography was performed using the standard Judkins technique. Significant coronary artery disease was defined as 50% reduction of the luminal diameter of any of the three coronary arteries or their major branches. All angiograms were reviewed by two independent observers who were unaware of the results of exercise stress test and stress echocardiography. 3. Results 3.1. Risk factors and ED characteristics The clinical and demographic characteristics of the patients, as well as their drug therapy are shown in Table 1. Table 2 shows erectile function characteristics

3 998 C. Vlachopoulos et al. / European Urology 48 (2005) Table 1 Patient population clinical characteristics and drug therapy a All patients (n = 50) w/o CAD (n = 38) CAD (n =9) Age (years) BMI (kg/m 2 ) Systolic BP (mmhg) Diastolic BP (mmhg) Total cholesterol (mg/dl) (mmol/l) HDL (mg/dl) (mmol/l) Diabetes, n (%) 10 (20) 6 (16) 3 (33) Hypertension, n (%) 31 (62) 23 (61) 6 (67) Hypercholesterolemia, n (%) 26 (52) 20 (53) 4 (44) Smoking, n (%) 32 (64) 27 (71) 3 (33) Family history, n (%) 7 (14) 5 (13) 2 (22) Obesity, n (%) 20 (40) 17 (45) 3 (33) >2 risk factors, n (%) 35 (70) 26 (68) 7 (78) Drug therapy b-blockers, n (%) 4 (8) 4 (11) ACE inhibitors, n (%) 15 (30) 8 (21) 1 (11) Diuretics, n (%) 7 (14) 4 (11) 3 (33) Calcium antagonists, n (%) 9 (18) 8 (21) 1 (11) Statins, n (%) 8 (16) 4 (11) 3 (33) Aspirin, n (%) 5 (10) 2 (5) 2 (22) Biguanides, n (%) 7 (14) 2 (5) 3 (33) Sulfonylureas, n (%) 6 (12) 2 (5) 2 (22) a Three patients with positive non-invasive test(s) who refused to undergo coronary angiography were not included in CAD and w/o CAD columns. Data are expressed as mean SD. ACE: angiotensin-converting enzyme; BMI: body mass index; BP: blood pressure; CAD: coronary artery disease; w/o CAD: without coronary artery disease. and penile Doppler data of the study population. There was no statistical difference in peak systolic velocity between patients with and without coronary artery disease. The mean time interval between the onset Table 2 Erectile dysfunction characteristics and penile doppler results a All patients (n = 50) w/o CAD (n = 38) CAD (n =9) ED duration SHIM score Mild, n (%) 9 (18) 9 (24) Mild-moderate, n (%) 11 (22) 6 (16) 5 (56) Moderate, n (%) 14 (28) 10 (26) 2 (22) Severe, n (%) 16 (32) 13 (34) 2 (22) PSV (cm/s) a Three patients with positive non-invasive test(s) who refused to undergo coronary angiography were not included in CAD and w/o CAD columns. Data are expressed as mean SD. CAD: coronary artery; ED: erectile dysfunction; PSV: peak systolic velocity; SHIM: sexual health inventory for men; w/o CAD: without coronary artery disease. of ED and cardiological assessment was 25 months (range 1 66) Non invasive procedures The flow chart of patients is shown in Fig. 1. One patient presented with acute myocardial infarction before he completed the non-invasive investigation and coronary arteriography was performed during hospitalization. Ten patients had a positive exercise stress test due to ischemic ECG changes. Stress echocardiography was positive in nine patients. Three of these patients experienced chest pain during the test. In one patient with induced wall motion abnormalities the test was interrupted due non-sustained ventricular tachycardia. Twelve patients had positive one or both of the two non-invasive procedures Coronary arteriography One patient with positive both of the two noninvasive procedures and two patients with positive one of the procedures (one exercise treadmill test and one stress echocardiography) refused to undergo coronary arteriography. Coronary arteriography performed in the remaining nine patients with positive non-invasive tests and in the patient with myocardial infarction demonstrated that one patient had 3-vessel disease, two patients had 2-vessel disease (left anteriordiagonal-left circumflex artery and diagonal-right coronary artery) and six patients had 1-vessel disease (one left anterior descending, one proximal left anterior descending and ectasia, one right coronary, and three patients circumflex artery) (Fig. 2). One patient had coronary arteries with no significant stenosis. Five patients were referred for medical treatment because the lesions were deemed unsuitable for invasive therapy, and the remaining four patients were referred for invasive treatment. 4. Discussion 4.1. Clinical implications Our study is practically the only, to the best of our knowledge, to assess angiographically and in a prospective and systematic way the incidence of asymptomatic CAD in patients with vasculogenic erectile dysfunction. The considerable proportion (19%) of asymptomatic CAD in these patients reinforces the concept that ED is a part of a generalized vascular disease and may be its first clinical presentation. Furthermore, it supports the strategy that ED patients should be aggressively treated for cardiovascular risk

4 C. Vlachopoulos et al. / European Urology 48 (2005) Fig. 1. Flow-chart of patients. factors. Accordingly, ED should routinely be assessed in subjects with a clustering of risk factors and once the condition is diagnosed these patients are at a high priority for further cardiovascular assessment Association between erectile dysfunction and coronary artery disease: Background Common pathophysiological background suggests that ED and CAD are linked. Indeed, the two condi- Fig. 2. Right anterior oblique projections of patients with positive angiographic results. (A). Stenoses in the middle segment of the left anterior descending (black arrow), the diagonal (white arrow), and in the distal left circumflex (open arrow) artery. (B). Stenosis (arrow) and ectasia in the proximal segment of the left anterior descending artery.

5 1000 C. Vlachopoulos et al. / European Urology 48 (2005) tions share common risk factors [1 4] and a common pathogenetic pathway that includes endothelial dysfunction (early stages) [5 8] and obstructive vascular changes (late stages). Furthermore, there is clinical evidence that ED and CAD are closely associated. Previous studies have shown that a significant proportion (42 75%) of patients with CAD have concomitant ED [9 15]. In the more recent ones [9 11], in which the incidence was 49 75%, erectile dysfunction was documented with the use of IIEF-5 or IIEF- Erectile Function Domain tests. It has been shown also that ED is a predictor for acute myocardial infarction [27] and that patients at the age of with cavernous arterial insufficiency are at higher estimated cardiovascular risk [28] compared to those without. Furthermore, the degree of ED is related to the extent of CAD [11,16], and ED is more frequent in diabetic patients with silent CAD than in those without [17]. Retrospective analysis has suggested that ED becomes evident prior to coronary artery disease in almost 70% of cases [9]. Prospective studies investigating the incidence of silent CAD in patients with ED yielded results ranging from 8 to 56% [29 33]. In the three of these studies [29 31], non-invasive investigation of CAD was employed, whereas in the fourth [32] there is no clear definition as to the methods used. The only study with angiographic documentation of CAD was a preliminary study [33], in which a 48% (20 out of 42 patients) incidence of CAD was noted in a population with an unfavorable risk profile. The incidence of CAD in this latter study was 56% with non-invasive assessment. According to Montorsi and Montorsi artery-size hypothesis [34,35], the likelihood of a ED patient to have concomitant CAD is not high since a certain degree of disease progression is needed to compromise further the lumen of a larger (i.e. coronary) artery for symptoms to be elicited. Our results showing a considerable percentage of concomitant CAD are not necessarily in contrast to this hypothesis because the mean ED duration in our patients was relatively long (mean 28 months [range 9 66] in the patients with angiographically documented CAD), thus allowing time for disease progression. Thus, our results reflect the incidence of silent CAD at the time the patient is seeking medical advice for ED, which is very important from the clinical standpoint Issues for further investigation An important issue to be addressed is whether ED is an independent risk factor for CAD in addition to the established ones. To this end, angiographic evaluation of a control group, i.e. a group of patients with similar risk factors profile and no vasculogenic ED would be ideal. At present, comparisons can be made indirectly with published data in the literature keeping in mind confounders such as different risk profile (including age). According to these studies, the prevalence of CAD determined angiographically in coronary asymptomatic patients ranges from 1.34 to 4.5% [36 40]. The more recent of those included data from a large cohort of patients who underwent diagnostic coronary arteriography during ablation therapy for cardiac arrhythmias and showed a 3.8% prevalence of CAD in coronary asymptomatic patients [40]. It should be noted however, that this latter study included patients with a less unfavorable risk profile than our patients. Moreover, since data on erectile function status are not available for this study (or for other similar studies), it cannot be inferred whether these patients constitute a normal (regarding erectile function) reference population to compare with. An important issue that deserves further investigation is how earlier the clinical manifestation of ED precedes the clinical manifestation of CAD. Close follow-up studies of patients with ED who initially had negative cardiovascular tests should help address this issue. The absence of obstructive coronary lesions as determined by angiography does not rule out the risk of acute coronary events, since non-obstructive coronary plaques with a lipid-rich core and thin fibrous cup are vulnerable and prone to rupture. Specially designed studies are needed to define the association between ED and type of coronary clinical syndrome [41] Limitations Three patients with positive non-invasive test(s) refused to undergo coronary angiography. Thus, our results may slightly underestimate the true incidence of asymptomatic CAD. Indeed, should these 3 patients were proven to have CAD, this incidence could be as high as 24%. Extrapolations to the general population with ED or to subpopulations with different risk factors profile should be made with caution. 5. Conclusions According to our study, 19% of patients with ED of vascular origin have angiographically documented silent CAD. These findings suggest that patients with ED should be considered at increased risk for CAD and

6 C. Vlachopoulos et al. / European Urology 48 (2005) have high priority for further cardiovascular assessment and for aggressive treatment of cardiovascular risk factors. Routinely asking middle-aged men about their erectile function provides the opportunity to identify and assess undiagnosed cardiovascular disease. Further, large-scale studies are warranted to assess the exact incidence of silent CAD in patients with ED of vascular origin and to assess how early ED precedes the clinical manifestation of CAD. Acknowledgement There was no funding for the study. References [1] Feldman HA, Goldstein I, Hatzichristou DG, Krane RJ, Mc Kinlay JB. Impotence and its medical and psychosocial correlates: results of the Massachusetts Male Aging Study. J Urol 1994;151: [2] Aranda P, Ruilope LM, Cavlo C, Luque M, Coca A, Miguel AG, for the Sildenafil Study Group. Erectile dysfunction in essential arterial hypertension and effects of sildenafil: Results of a Spanish national study. 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7 1002 C. Vlachopoulos et al. / European Urology 48 (2005) [30] Kim SW, Paick JS, Park DW, Chae IH, Hee Oh B. Potential predictors of asymptomatic ischemic heart disease in patients with vasculogenic erectile dysfunction. Urology 2001;58: [31] Shamloul R, Ghanem HM, Salem A, Elnashaar A, Elnaggar W, Darwish H, et al. Correlation between penile duplex findings and stress electrocardiography in men with erectile dysfunction. Int J Impot Res 2004;16: [32] El Sakka AI, Morsy AM. Screening for ischemic heart disease in patients with erectile dysfunction: Role of penile Doppler ultrasonography. Urology 2004;64: [33] Pritzker MR. The penile stress test: a window to the hearts of man. Circulation 1999;100(Suppl I):I-171. [34] Montorsi P, Montorsi F, Schulman CC. Is erectile dysfunction the Tip of the Iceberg of a systemic vascular disorder? Eur Urol 2003;44: [35] Montorsi P, Ravagnani PM, Galli S, Rotatori F, Briganti A, Salonia A, et al. Common grounds for erectile dysfunction and coronary artery disease. Curr Opin Urol 2004;14: [36] Gensini GG, Kelly AE. Incidence and progression of coronary artery disease. Arch Intern Med 1972;129: [37] Erikssen J, Enge I, Forfang K, Storstein O. False positive diagnostic tests and coronary angiographic findings in 105 presumably healthy males. Circulation 1976;54: [38] Froelicher VF, Thompson AJ, Longo MR, Triebswasser Jh, Lancaster MC. Value of exercise testing for screening asymptomatic men for latent coronary artery disease. Prog Cardiovasc Dis 1976;18: [39] Davies B, Ashton WD, Rowlands DJ, el-sayed M, Wallace PC, Duckett K, et al. Association of conventional and exertional coronary heart disease risk factors in 5,000 apparently healthy men. Clin Cardiol 1996;19: [40] Enbergs A, Burger R, Reinecke H, Borggrefe M, Breithardt G, Kerber S. Prevalence of coronary artery disease in a general population without suspicion of coronary artery disease: angiographic analysis of subjects aged 40 to 70 years referred for catheter ablation therapy. Eur Heart J 2000;21: [41] Montorsi P, Rotatory F, Ravagnani P, Galli S, Veglia F, Briganti A, et al. Association between erectile dysfunction and coronary artery disease. Role of coronary clinical presentation and extent of vessel involvement. The COBRA trial. J Sex Med 2005;2(suppl 1):6, (abstr). Editorial Comment G. Jackson, London, UK gjcardiol@talk21.com The link between erectile dysfunction and vascular disease, and in particular coronary artery disease, is now well established [1]. This study is particularly interesting because of its prospective nature. We have a lot of retrospective data linking ED to both stable coronary patients and those presenting acutely but only Mark Pritzker s abstract in 1999 previously examined the link prospectively [2]. The current study of 50 consecutive asymptomatic men aged years identified a significant number of cardiovascular risk factors overall and positive non-invasive tests for ischaemia in twelve (24%). Of the 10 who underwent angiography only 1 had no obstructive lesion but without intravascular ultrasound plaques cannot be excluded and it is subclinical lipid rich plaques that rupture causing an acute event [3]. The two year delay to presentation is a concern not only with regard to relationship issues but reducing cardiovascular risk. In a study of asymptomatic type 2 diabetic patients ED was present in 33.8% with CAD and 4.7% without CAD and ED predicted CAD independently of the classical risk factors [4]. Vlachopoulos and colleagues reinforce the concept that a man with ED is a cardiac case until proved otherwise. I agree we need a large scale trial evaluating ED and CAD risk but importantly we need to know if we identify increased risk can we reduce or prevent a subsequent event by aggressive cardiovascular risk reduction. Pritzker regarded ED as a window to the hearts of man we need to look through the window and see if we can use ED as a signal for vascular disease prevention [5]. References [1] Jackson G. Erectile dysfunction and cardiovascular disease. Int J Clin Pract 1999;53: [2] Pritzker MR. The penile stress test: a window to the hearts of man. Circulation 1999;100(Suppl 1): [3] Montorsi P, Montorsi F, Schulman CC. Is erectile dysfunction the Tip of the Iceberg of a systemic vascular disorder? Eur Urol 2003;44: [4] Gazzaruso C, Giordanetti S, De Amici E, et al. Relationship between erectile dysfunction and silent ischemia in apparently uncomplicated type 2 diabetic patients. Circulation 2004;110:22 6. [5] Jackson G. Erectile dysfunction, like diabetes, should be considered a cardiovascular equivalent. Int J Clin Pract 2005;59:507. Editorial Comment Piero Montorsi, Milan, Italy piero.montorsi@unimi.it Atherosclerosis is a systemic disorder that should involve at the same time and to the same extent many vascular circulations. However, patients rarely complain at the same time of vascular symptoms coming from different arterial beds. This is likely the results of the different artery size supplying various circulations. Thus, penile circulation (small size arteries) should be involved earlier than coronary circulation (intermediate size arteries) that in turns should be involved earlier than carotid or femoral circulations (large size arteries) [1]. If true, every patient with erectile dysfunction (ED) due to significant vascular obstruction (let s for a moment forget the early phase of endothelial dysfunction) should be investigated for latent coronary artery disease (CAD). If found, ED should be rightly considered as an early marker (the tip of the iceberg ) of a systemic vascular disorder. The key point is: what is the target of cardiologic evaluation in patient with ED

8 C. Vlachopoulos et al. / European Urology 48 (2005) without CV history? Should we search for underlying obstructive or non-obstructive coronary involvement? While the former is a logical and widely investigated target, the latter might be less intuitive for non-cardiologists (why should we be worried about a nonobstructing, not flow-limiting vascular disease?) although it has been shown to better predict coronary events. The paper by Vlachopoulos et al. in this issue of European Urology is an example of a study targeting obstructive CAD. Authors found that almost 20% of ED patients without a CV history do have angiographically detectable significant CAD ultimately requiring coronary revascularization, either percutaneous or surgical. While a small study not including a control arm without ED, the message is clear and significant given the high prevalence of ED among middle-aged men population [2]. Nevertheless, much more interest should be direct to the high proportion of patients with negative tests for obstructing CAD (80% in the present study). While the lack of myocardial ischemia under stress is an obvious favourable result, it does not necessarily mean these patients are not at risk of acute coronary events [3]. In fact, acute myocardial infarction is usually due to abrupt thrombotic occlusion of a non-obstructing plaque. Thus, ED patients without CV history need to be tested with alternative diagnostic options, such as intima-media thickness of carotid arteries by ultrasound or C-reactive protein plasma levels measurement, that have been found to predict coronary events in CAD patients [4,5]. References [1] Montorsi P, Montorsi F, Schulman C. Is erectile dysfunction the tip of the iceberg of a systemic vascular disorder? Eur Urol 2003;44: [2] Feldman HA, Goldstein I, Hatzichristou D, Krane RJ, McKinlay JB. Impotence and its medical and psychological correlates: results of the Massachusset Male Aging Study. J Urol 1994;151: [3] Montorsi P, Ravagnani P, Galli S, Rotatori F, Briganti A, Salonia A, et al. Common grounds for erectile dysfunction and coronary artery disease. Curr Opin Urol 2004;14: [4] O Leary. Polak JF, Kronmal RA, et al. Carotid-artery intima and media thickness as a risk factor for myocardial infarction and stroke in older men. New Engl J Med 1999;340: [5] Bassuk S, Rifai N, Ridker P. High-sensitive C-reactive protein: clinical importance. Curr Prob Cardiol 2004;29: