AHMED T. AHMED, M.D.*; GAMILA M. ALI, M.D.**; AHMED A. HWARY, M.D.** and LAILA K. ABD EL-KREAM, M.Sc.***

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1 Med. J. Cairo Univ., Vol. 84, No. 1, March: , Study of Carotid Intimal Medial Thickness by Ultrasonography as A Marker of Subclinical Atherosclerosis in Males with Vasculogenic Erectile Dysfunction AHMED T. AHMED, M.D.*; GAMILA M. ALI, M.D.**; AHMED A. HWARY, M.D.** and LAILA K. ABD EL-KREAM, M.Sc.*** The Departments of Diagnostic Radiology*, Cardiology**, Suez Canal University Hospital and the Department of Cardiology, Ismailia General Hospital*** Abstract Purpose: To evaluate the possibility of considering measured Carotid Intima-Media Thickness (C-IMT) in patients with arteriogenic Erectile Dysfunction (ED) as a marker for prediction of subclinical atherosclerosis, and furthermore Coronary Artery Disease (CAD) as well. Patients and Methods: A total of eligible 74 male with arteriogenic erectile dysfunction and similar normal ones older than 35 years, were subjected in our case-control study; sampled in a simple random manner. All patients underwent laboratory assessment of total serum cholesterol, Low Density Lipoproteins (LDL-c), High Density Lipoproteins (HDL-c) and serum triglycerides, ECG, transthoracic echocardiography, exercise stress test and B-mode ultrasonography with color Doppler arterial flow pattern of the Carotid arteries to assess the Intima-Media Thickness (C-IMT). Patients with ED underwent penile color Doppler examination and calcified upon the International Index of Erectile Function-5 (IIEF-5). Results: We found a high statistically significant difference between the two studied groups in having abnormal C-IMT along the whole carotid tree bilaterally; as: 78.4% of the case group (58 subjects) had an abnormal C-IMT in comparison with 12.2% in the control group (9 subjects), with ( p=0.000). We also found that erectile dysfunction, low HDL and high TG are independent predictors for carotid atherosclerosis with (p=0.000, & 0.048) respectively. However, other factors as age, smoking, hypertension, diabetes, high cholesterol and high LDL are not independent predictors for carotid atherosclerosis. Conclusion: Men with ED but without clinical arteriosclerosis may have increased carotid artery IMT. That increased C-IMT may identify men with ED and associated VRFs who should aggressively correct VRFs to decrease the future risk of acute cardiovascular events. Therefore, the presence of ED in men with known VRFs may help in identifying, by ultrasonographic determination of common carotid artery IMT, patients with an increased risk of future vascular events that deserve a more aggressive treatment. Correspondence to: Dr. Ahmed T. Ahmed, The Department of Diagnostic Radiology, Suez Canal University Hospital Key Words: Erectile dysfunction Carotid intima media thickness Subclinical atherosclerosis. Introduction ATHEROSCLEROSIS can no longer be considered a disease of the developed world, because myocardial infarction and stroke are increasingly prevalent worldwide, across all socioeconomic strata. By 2025, cardiovascular mortality on a worldwide scale will likely surpass that of every major disease group, including infection, cancer, and trauma [1,2]. It is a condition affecting largeand medium-sized arteries. It leads to the formation of atherosclerotic plaques which may eventually disrupt the blood flow to target organs [2], and although it usually manifests in later life, its early phases are present in teenagers and young adults [3]. There is an accumulating evidence that erectile dysfunction may be just another manifestation of cardiovascular disease [4,5]. Erectile Dysfunction (ED) is defined as the persistent inability to achieve or maintain an erection sufficient for satisfactory sexual performance. It is estimated to affect approximately 49.4% of men aged 40 to 88 years [6]. The risk of erectile dysfunction is related to many factors, including age, smoking, diabetes, heart disease, depression, and hypertension [7,8]. Because cardiovascular disease and erectile dysfunction share etiologies as well as pathophysiology (endothelial dysfunction), and because of evidence that the degree of erectile dysfunction correlates with severity of cardiovascular disease, it has been postulated that erectile dysfunction is a sentinel symptom in patients with occult cardiovascular disease [9]. Intimal-media thickening of common carotid arteries is a risk factor for severe erectile dysfunction 311

2 312 Study of C-IMT by Ultrasonography as A Marker of Subclinical Atherosclerosis in men with Vascular Risk Factors (VRFs) but no clinical evidence of atherosclerosis [10]. Thus, carotid atherosclerosis measurements also reflect the degree of coronary and systemic arterial injury in a given individual. By examining the carotid artery wall rather than the lumen, risk prediction with carotid ultrasound identifies an earlier stage of atherosclerosis than standard duplex carotid imaging [11]. Erectile dysfunction is often associated with atherosclerotic plaque buildup. Impotence can be an early warning sign of cardiovascular disease. According to the National Institute of Diabetes and Digestive and Kidney Diseases; about 5 percent of forty-year-old men and between 15 to 25 percent of sixty-five-year-old men experience erectile dysfunction. In addition, when smoking is part of the picture, the odds of erectile dysfunction increase even further [9]. "Preclinical or subclinical atherosclerosis" is an early stage of atherosclerotic disease. The term indicates that something is beginning to change" in vascular walls. The damage is still minimal, and can still potentially be corrected. Carotid artery ultrasonography and measures of Carotid Intimal- Media Thickness (C-IMT) are emerging technologies that may be useful in identifying a patient who may benefit from more aggressive preventive therapy [12]. Recent data have improved our understanding of the application of C-IMT as a screening tool for cardiovascular disease. This non-invasive, reproducible, inexpensive and radiation-free screening test provides a measurement that can place an individual into a higher or lower risk category, thus allowing for appropriate implementation of preventive strategies [13]. The objective of this study was to measure the possibility of considering arteriogenic ED via C- IMT estimation as a marker for prediction of subclinical atherosclerosis, and furthermore CAD as well. Patients and Methods This case-control study enrolled 74 male with arteriogenic erectile dysfunction and similar normal ones older than 35 years; in case group; the patients were found in age range between 37 to 68 years old (mean age was 47.2 ±8.4 years), with almost similarity in control group as the age range from 37 to 66 years old (mean age was 47.9 ±8.4 years). They were sampled in a simple random manner. For the case group, males with arteriogenic ED were referred from andrology out-clinic in Suez Canal University Hospital and Ismailia General Hospital during 2014, while males of the control group were selected from patients who visited other out-clinics in Suez Canal University Hospital and Ismailia General Hospital with a complaint other than ED. The patients in case and control groups were subjected based upon specific inclusion and exclusion criteria. Inclusion criteria for the case group, males with age >35 years [14], stable marriage with a heterosexual relationship for six months or longer and arteriogenic ED diagnosed by International Index of Erectile Function (IIEF) and Penile Color Doppler. The control group shared the same inclusion criteria except for that patients did not have ED. Both groups shared the same exclusion criteria that included known history of Diabetes Mellitus (DM), coronary arterial diseases, stroke and peripheral arterial diseases, hypertension, hyperlipidemia, prostate and/or penile surgery, genital anatomy deformity, hyperprolactinemia, hypogonadism and major psychiatric disorder not well controlled with therapy (including schizophrenia and major depression) and also patients refusing to participate in the study after fully explaining everything to them. Preliminary diagnosis of diabetes mellitus, hypertension, hyperlipidemia, and cardiac diseases was based on medical history, medications and results of prior health investigations. All study participants were investigated in detail to finally indicate presence or absence of the abovementioned disorders. Only newly diagnosed cases after enrollment in the study were included. A medical history was obtained from the eligible subjects in both groups; they also underwent clinical examination. Diagnosis of hypertension was set if resting blood pressure was 140 (systolic) and/or 90 (diastolic) mmhg {BP was measured according to the Joint National Committee 7 (JNC 7) guidelines of BP measurement} in 3 separate sessions [15]. Hypercholesterolemia was diagnosed according to 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) if total cholesterol level was 200mg/dl, LDL cholesterol level was 130mg/dl and HDL cholesterol level was <35 mg/dl [16]. High triglycerides blood level was diagnosed if the level of triglycerides in blood was 160mg/dl [17].

3 Ahmed T. Ahmed, et al. 313 Diagnosis of DM was considered when plasma glucose level 126mg/dl (fasting) and 200mg/dl (2 hours after a 75mg oral glucose load) [18]. Presence of CHD-related events was defined as a past history of myocardial infarction, hospital admissions with heart failure, revascularization, or chest pain with abnormal electrocardiogram or stress test. Presence of stroke was defined as history of admission with typical neurological symptoms with or without recovery. Peripheral arterial disease was defined clear prior diagnosis based on symptoms, signs and/or investigations or a history of previous revascularization procedures. Examination technique and study variables: The eligible subjects in both groups were evaluated after an informed signed consent was obtained from all participants, for subclinical atherosclerosis parameters throughout electrocardiography (ECG), transthoracic echocardiography, Carotid Intima- Media Thickness measurement (C-IMT) and exercise stress test. The framingham risk score was calculated for all for next 10 years CAD risk estimation [19]. Only the eligible subjects in the case group underwent a Penile Color Doppler examination to rule in arteriogenic ED only and the International Index of Erectile Function 5 (IIEF-5) was applied to them. Erectile dysfunction will be defined as a score of 21 on a 25-point scale [20-22]. Penile color Doppler examination: Penile Doppler studies were performed using a 10-MHz linear array transducer (AU-5, Esaoti, Italy). Measurements included Peak Systolic Velocity (PSV), End-Diastolic Velocity (EDV), and resistance index (RI= PSV-EDV/PSV). All patients received 10 to 20µg of intracavernosal prostaglandin E-1, and measurements were performed at 5 to 20min. with interval of 5min. after injection to determine the PSV, EDV, and RI. Erectile dysfunction was defined as vascular in origin if PSV is <35cm/s; EDV <5cm/s, and RI is <0.9 [23]. Electrocardiography (ECG): Resting ECG was done for all study subjects and assessed for any abnormalities. Detection of ECG abnormalities was carried out using Minnesota Code [22]. Trans-thoracic echocardiography: This study was carried out using the commercially available echocardiographic equipment (Vivid-7e2/GE), which equipped with a 2.5-Mhz transducer. The ejection fraction, diastolic function and left ventricular mass index were measured based upon the following (Table 1). Carotid Intima Media Thickness Measurement (C-IMT): All the study subjects underwent B-Mode/ ultrasonography and color Doppler arterial flow pattern of the carotid arteries to assess the intimamedia thickness using Philips Medical System/ HD11 with a 10MHZ Transducer (linear array probe). The scans were performed for the far wall of six carotid segments: The right and left common carotid arteries, carotid bifurcations, and internal carotid arteries. When the ultrasound beam was at right angles to the carotid walls, two white lines were seen in normal vessels, particularly on the posterior wall. The first corresponds to the blood/intima boundary; the second to the outer media/adventitia region Fig. (1). Normally this is less than 0.8mm [23]. Exercise treadmill test: Exercise testing was carried out according to the multistage Modified Bruce Protocol. An exercise test result will be considered positive if there is (A) A horizontal or down-sloping ST segment depression of at least 1mm, 60ms beyond the J point or (B) An up-sloping ST-segment depression of 1.5mm or greater, 80ms beyond the J point, or (C) An ST-segment elevation of at least 1mm. An Exercise Electrocardiogram (ECG) was considered negative (based on ST segment changes) when the patient achieved at least 85% of the maximal predicted heart rate in the absence of ischemic STsegment changes [25]. Results The results of our study concern with evaluation of subclinical atherosclerosis parameters, relations between subclinical atherosclerosis, different vascular risk factors and predictors of carotid atherosclerosis. The demographic features of our study represented eligible 74 male patients with arteriogenic ED and a similar number of normal control ones, with age more than 35 years. For the case group, age ranged from 37 to 68 years (mean age 47.2 ± 8.4 years). For the control group, age ranged from 37 to 66 years (mean age 47.9 ±8.4 years), and so, there was no statistically significant difference as regard the age between the two studied groups (p>0.05). The penile color Doppler parameters among case group subjects showed that there were 1 1

4 314 Study of C-IMT by Ultrasonography as A Marker of Subclinical Atherosclerosis patients (14.8%) who had mild ED, 59 patients (79.8%) who had moderate ED and 4 patients (5.4%) who had severe ED. There was a high statistically significant difference between the two studied groups in having abnormal increase C-IMT along the whole carotid tree bilaterally; as: 78.4% of the case group (58 subjects) has an abnormal C-IMT in comparison with 12.2% in the control group (9 subjects) with (p=0.000 and Odds ratio=29.91) (Table 2). The relation of electrocardiographic findings to C-IMT among the two studied groups showed no statistically significant difference between the two studied groups as regard resting ECG and stress ECG (p>0.5). While the relation of the echocardiographic parameters to the C-IMT findings among the two studied groups showed a statistically significant correlation between the increased C-IMT in ED patients and LVMI and DD (p<0.05). As regards the relations between the C-IMT and the CVRFs among the two studied groups, there was a high statistically significant correlation between the increased C-IMT in ED patients and the different CVRFs in comparison to the control group (p<0.05 and Odds ratio >2) (Table 3). Regarding the correlation between the lipid profile and C-IMT in the two studied groups there was a statistically significant correlation between C-IMT in ED patients and the levels of total S. cholesterol, LDL-c, HDL-c & S. triglycerides ( p< 0.05) in comparison to the control group (Table 4). The Framingham Risk Score (FRS) application among the whole study population (case and control groups) showed no statistically significant difference of Framingham risk score among the two studied groups (p=0.575). The correlation between C-IMT in ED patients and the low risk Framingham Risk Score was statistically significant in comparison to the control group (p<0.05) (Table 5). A logistic regression analysis of the risk factors for carotid atherosclerosis among the studied population was done, to determine factors that can be used as a predictor for carotid atherosclerosis. It showed that erectile dysfunction, low HDL and high TG are independent predictors for carotid atherosclerosis (p=0.000, and 0.048) respectively. However, other factors as age, smoking, hypertension, diabetes, high cholesterol and high LDL are not independent predictors for carotid atherosclerosis (Table 6). Table (1): Reference parameters for tran-thoracic echocardiography. Ejection Fraction (EF) [22] Left Ventricular Mass Index (LVMI) [22] Diastolic Function [23] Normal 55% Normal g/m 2 Grade 1 - Diastolic Dysfunction (DD): Reversed E/A ratio (impaired relaxation) Mildly abnormal 45-54% Mildly abnormal g/m 2 Grade 2 - DD: Pseudo-normalized pattern Moderately abnormal 30-44% Moderately abnormal g/m 2 Grade 3 - DD: Reversible restrictive pattern Severely abnormal <30% Severely abnormal 13 1 g/m 2 Grade 4 - DD: Irreversible restrictive pattern Table (2): C-IMT measurements among the studied groups. C-IMT N. % Mean SD± p-value Odds ratio Case Group + Ve ED: Positive Negative Control Group Ve ED: Positive Negative Table (3): Relation between the C-IMT and coronary risk factors in both groups. C-IMT values Coronary risk factors Case Group +Ve ED Control Group Ve ED p-value (Odds) + % % + % % Smokers (49.71) Mean BP (hypertensive) (48) Diabetics BMI ( 25) (22.15)

5 Ahmed T. Ahmed, et al. 315 Table (4): Relation between the C- IMT and laboratory findings in both groups. C-IMT values Lab. parameters description Case Group +Ve ED Control Group Ve ED p-value + % % + % % Total serum cholesterol (mg/dl): Normal Abnormal (LDL) Low-Density Lipoprotein (mg/dl): Low risk Moderate risk High risk (HDL) High-Density Lipoprotein (mg/dl): Desirable level Moderate risk High risk Triglycerides (mg/dl): Normal Abnormal Table (5): Relation between the C-IMT and the framingham risk score in both groups. C-IMT values Framingham risk score* Case Group +Ve ED Control Group Ve ED p-value + % % + % % Very low risk (<10%) Low risk (<15%) Moderate risk (15-20%) *: No patients found in high risk score (>20%). Table (6): The linear logistic regression for the risk factors of carotid AS among the whole sample. Risk factors Coefficient Confidence limit p- value Lower Upper Smoking HTN DM Age Erectile dysfunction High cholesterol (>200) High LDL (>100) Low HDL (<40) High TG (>150) Subcutaneous tissue Jugular vein Near wall Lumen Far wall Fig. (1): Ultrasound image showing measurement of near and far wall C-IMT in the distal 1cm of the CCA [24]. Discussion ED was once considered primarily a condition of psychogenic origin, but medical and physical influences are gaining greater relevance as correlates of ED in recent years. The prevalence of ED increases with age. After controlling for age, chronic medical conditions such as diabetes, arterial hypertension and associated treatments are frequent correlates of ED [26]. ED also shares several atherogenic risk factors with Coronary Heart Disease (CHD) including cigarette smoking, unfavorable lipid levels, obesity and sedentary behavior [27]. Many studies have been done trying to evaluate the C-IMT in males with vasculogenic ED as a marker of vascular damage in the absence of clinical atherosclerosis (subclinical atherosclerosis); as in

6 316 Study of C-IMT by Ultrasonography as A Marker of Subclinical Atherosclerosis Massimo Bocchio et al., 2005 [10]. Also to evaluate the prevalence of carotid and femoral atherosclerotic lesions in ED patients; as in Foresta et al., 2008 [28]. Moreover, to evaluate ED as an early sign of vascular dysfunction by assessing arterial stiffness in erectile dysfunction patients; as in Shih- Tai Chang et al., [29]. These studies revealed that C-IMT associated with arteriogenic ED in men with VRFs was the only clinical correlate of unrecognized atherosclerosis of carotid arteries. Through the results of our study, we share some points of correlation with previous studies done to evaluate arteriogenic Erectile Dysfunction (ED) as a marker for detecting subclinical atherosclerosis in males with ED as well as carotid intima media thickness. In a study done by Massimo Bocchio et al., [10] to evaluate the intima-media thickening of the common carotid arteries as a risk factor for severe ED; in men with vascular risk factors but no clinical evidence of atherosclerosis which included 270 men with ED. We shared some results as Massimo Bocchio et al., as; they found carotid IMT score in the whole study was negatively correlated with SHIM score, while a positive correlation was found between C-IMT score and age (p<.00001), BMI (p=0.0002), plasma fasting glucose (p<0.0001), serum HbA1c (p<0.0001), LDL-c (p=0.177) and CRP levels (p<0.0001). But there was a statistically insignificant correlation with HDL-c. There were some points of difference with our study concerning demography; that smaller number of patients were included in our study and all men were divided into two groups, a case group (patients with ED) and a control group (men without ED). Other points of differences with our study concerning methodology are as the following: I- In Massimo Bocchio et al., the severity of ED was determined by using the SHIM. Unlike our study, we used the IIEF-5 score and the penile Doppler examination to exclude other causes of ED rather than arteriogenic ED, so more specific and relevant results concerning arteriogenic ED could be obtained in our study. II- In Massimo Bocchio et al., venous blood samples for determination of FBS, HbA1c, C- reactive protein, LDL-c and HDL-c were obtained. While in our study, venous blood samples were obtained for determination of FBS, PPBS, total s. cholesterol, s. triglycerides, LDL-c and HDL-c. III- All patients included in our study underwent resting ECG, stress ECG, echocardiography, as well as, carotid Doppler but we also differ in the C-IMT cut off point 0.8mm or greater [27] but the C-IMT cut off point used by Massimo Bocchio et al., was 0. 1 mm or greater that represents a strong point in our study as we can detect any minimal increased C-IMT. The logistic regression analysis of the risk factors for carotid atherosclerosis that was done by Massimo Bocchio et al., showed that an increased measure of each VRF, including aging, was associated with a trend of increased risk, but only a carotid IMT score of 1.00mm or greater had significantly increased the risk of severe ED (odds ratio 2.6), and that increased measures of age and BMI had a confounding effect on the relation between carotid IMT and the risk of severe ED (odds ratio 2. 1) while in our study we found that erectile dysfunction, low HDL and high TG are independent predictors for carotid atherosclerosis with (p=0.000, and 0.048) respectively. However, other factors as age, smoking, hypertension, diabetes, high cholesterol and high LDL are not independent predictors for carotid atherosclerosis. The study by Massimo Bocchio et al., revealed that 17.7% of men with ED were associated with VRFs (39 of 220), and only 1 man of 50 with no VRFs had an increased C-IMT score (1mm or greater). In all these patients; ED was the only clinical correlate of diffuse, unrecognized vascular damage that was associated with a documented future risk of acute vascular events. Which is a matching point with our study; that it is possible to consider arteriogenic ED and C-IMT estimation as a marker for prediction of subclinical atherosclerosis, and furthermore CAD as well. In another larger study that included numeral patients done by Foresta et al., [28] which evaluated the prevalence of carotid and femoral atherosclerotic lesions (increased IMT or presence of plaques) in ED patients. We shared a lot of features concerning methodology with Foresta et al., as both groups (patients and control) underwent complete medical and sexual history, physical examination, systolic and diastolic BP, laboratory investigations including: FBS, s. total cholesterol and s. triglycerides, carotid and femoral arteries Doppler as well as penile Doppler. Foresta et al., used the following formula: Pathologic PSV < (0.7X age) in order to state arteriogenic etiology of ED, but in our study erectile dysfunction were being defined as vascular in origin if PSV is <35cm/s. So, their data are more

7 Ahmed T. Ahmed, et al. 317 relevant as recently, the age significantly influences the PSV cut-off values. Unlike a study by Foresta et al., which considered normal CIMT <0.9mm, whereas mm CIMT was defined as increased thickness, but in our study C-IMT <0.8mm was considered normal that represents strong point in our study? Foresta et al., found that the prevalence of pathologic IMT in ED patients (Group 1) was not significantly different with respect to controls (18.0% versus %) and this is a point of difference with our study, as we found a high statistically significant difference between the two studied groups ( p=0.000 and Odds ratio=29.91). As regards CVRFs, we shared some results with Foresta et al., as; they found that only the prevalence of diabetes was significantly higher in ED group than in controls (p<0.05), and in our study, there was also an insignificant correlation between ED and all CVRFs except for the mean diastolic BP (p=0.029), the mean BMI (>25) ( p= 0.005), LDL-c (p=0.023) & HDL-c (p=0.007). The logistic regression analysis of the risk factors for carotid atherosclerosis that was done by Foresta et al., confirmed the statistically significant higher prevalence of atherosclerotic lesions and diabetes in ED patients with respect to controls. Unlike our study, we found that erectile dysfunction; low HDL and high TG are independent predictors for carotid atherosclerosis with ( p=0.000, and 0.048) respectively. However, other factors as age, smoking, hypertension, diabetes, high cholesterol and high LDL are not independent predictors for carotid atherosclerosis. In Shih-Tai Chang et al., [29] to evaluate the association among different criteria for assessing arterial stiffness and cardiovascular risk factors in ED patients. We shared the same method for determining the severity of ED as Shih-Tai Chang et al., which was the IIEF-5 score. They showed that 22.5% had mild ED, 16.5% had moderate ED and 60% had severe ED. Our study showed that 12.2% had mild ED, 66.2% had moderate ED and 21.6% had severe ED. There were points of difference with our study concerning methodology; C-IMT cut off point was 1.00mm in Shih-Tai Chang et al., Unlike our study, also all entire patients group in our study underwent penile Doppler to exclude any other causes of ED rather than the arteriogenic etiology that represents strong points in our study. The results of this study revealed that no significant difference was observed in the values of IMT, except in patients with diabetes mellitus compared to those without diabetes mellitus. Shih- Tai Chang et al., showed that type II diabetes mellitus is an independent determinant for C-IMT which was a point of difference with our study as we found that diabetes mellitus is not independent predictor for carotid atherosclerosis. Our results also revealed that there was a significant correlation between C-IMT and ED patients with diabetes mellitus and there was a significant correlation between C-IMT and ED patients with hypertension, smoking, BMI >25 and hyperlipidemia. Also, ED, low HDL and high TG are independent predictors for carotid atherosclerosis with (p=0.000, and 0.048) respectively. Finally, we found that increased IMT of carotid arteries indicative of preclinical arteriosclerosis was associated with an increased risk of severe ED in men with no clinical evidence of vascular disease, and it was found in a relevant proportion of men with ED and VRFs unaware of the presence of diffuse vascular damage. Which was more directed and specific results compared to Shih-Tai Chang et al., study. Our study had some limitations, firstly; we had a small sample size. Secondly, more parameters were needed for more accurate assessment of vascular damage or arterial stiffness such as, brachial mediated vasodilatation. Although, these results in our series and the other literatures are promising, future studies with a larger number of patients are needed to verify our findings in other lower risk populations. Conclusions: Men with ED but without clinical arteriosclerosis may have increased carotid artery IMT. The increase C-IMT may identify men with ED and associated VRFs who should aggressively correct VRFs to decrease the future risk of acute cardiovascular events. Therefore, the presence of ED in men with known VRFs may help in identifying, by ultrasonographic determination of common carotid artery IMT, patients with an increased risk of future vascular events that deserve a more aggressive treatment. References 1- YUSUF S., HAWKEN S., OUNPUU S., et al.: Effect of potentially modifiable risk factors associated with myocardial infarction in 52 countries (the INTERHEART study): Case-control study. Lancet, 364: 937, 2004.

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