APOA-1 RATIO AND CARDIOVASCULAR RISK IMPROVEMENT: A TADALAFIL PLEIOTROPIC EFFECT?

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Severe erectile dysfunction as an independent risk factor for coronary artery disease

Decrease ApoB/ApoA-1ratio and cardiovascular risk improvement: A tadalafil pleiotropic effect?

Salem S.1, Mehrsai A.1, Abdi S.2, Saraji A.1, Pourmand G.1

Roumeguere T.1, Zouaoui Boudjeltia K.2, Hauzeur C.3, Schulman C.1, Ducobu J.2, Vanhaeverbeek M.2, Wespes E.3

Urology Research Center Medical Sciences University of Tehran, Dept. of Urology, Tehran, Iran, 2Iran University of Medical Sciences, Dept. of Cardiology, Tehran, Iran

1

Introduction & Objectives: Erectile dysfunction (ED) is now beginning to be considered as an early manifestation of a subclinical systemic vascular disorder and may be an index of subclinical coronary artery disease (CAD). Recognizing ED as a sign of early endothelial dysfunction could have a huge impact on preventive healthcare by providing a clinical method for physicians to identify patients at the early stage prior to the development of CAD or other adverse vascular events. Our aim was to evaluate whether ED is a predicting factor for CAD while adjusting for other common risk factors. Material & Methods: From 2005 to 2007, 183 patients with documented CAD and 134 participants without CAD were enrolled in this case-control study at our referral center. The prevalence of ED and the distribution of CAD risk factors (age, smoking, lipid profile, hypertension, obesity and diabetes mellitus) were evaluated. The 5-item International Index of Erectile Function (IIEF-5) was used to evaluate the presence and the severity of ED. The uni- and multivariate logistic regression analysis were performed to assess the effect of classic risk factors and ED severity on CAD; calculating odds ratio (OR) and 95% confidence interval (CI). Adjustments were made for potential confounding factors including age, hypertension, diabetes, dyslipidemia and smoking. Results: The mean age and prevalence of ED in CAD positive and negative groups were 60.3±6 vs. 45.3±5 and 88.5% vs. 64.2%, P<0.05 respectively. In comparison to unadjusted variables, a statistically significant difference was found for all risk factors (except total cholesterol and LDL levels) and also ED prevalence between CAD positive and negative groups. In the logistic regression analysis, the adjusted OR for age, diabetes, hypertension, hypercholesterolemia, and smoking demonstrated a significant confounding effect. Our results also revealed a significant association between severe ED and CAD (OR: 2.22, 95% CI: 1.11-6.03; P<0.05). Moreover, the findings demonstrated that patients suffering from ED for a longer period of time were at the greater risk of subclinical CAD.

1 Hôpital Erasme Univ. Clinic Brussels, Dept. of Urology, Brussels, Belgium, 2Chu Charleroi Ulb, Laboratory of Experimental Medicine Unit 222, Charleroi, Belgium, 3 Chu Charleroi Ulb, Dept. of Urology, Charleroi, Belgium

Introduction & Objectives: Recognition of erectile dysfunction (ED) as an early sign of systemic cardiovascular disease offers an opportunity for prevention. Cardiac risk assessment may deserve measurement of Apoliporotein B/ Apolipoprotein A-1 ratio. An elevated ApoB/ApoA-1 ratio is a risk factor for future coronary artery disease. ApoA-1 production which is recognized as a cardioprotective lipid fraction is down regulated by NFκB activation in vitro. Because inhibition of phosphodiesterases (PDEs) 5, 6 and 9 negatively attenuates NFκB translocation/activation, tadalafil, a selective PDE 5 inhibitor used for treatment of ED could present some interesting pleiotropic effects. The objective of this open study is to test the hypothesis that tadalafil treatment could decrease serum ApoB/ApoA-1 ratio. Material & Methods: 10 healthy men without any complain of ED or known cardiovascular risk factors were administered tadalafil 10 mg intake on alternate days for 4 weeks. Lipid profile with total Cholesterol, HDL-cholesterol, LDLcholesterol, triglycerides, ApoA-1 and ApoB, was assessed at baseline (T0), after 2 weeks (T1), at the end of the treatment period (T2) and after 2 weeks of wash-out follow up (T3). Results: ApoB/ApoA ratio was significantly decreased during treatment (mean+/SEM, T0: 0.80±0.11, T1: 0.64±0.06, T2: 0.65±0.06; p<0.05) and remained lower after wash-out (T3: 0.67±0.05; p= 0.08). Serum ApoA-1 (mg/dl) increased but not significantly during the treatment period (152±8.8, 165±7.9, 169±6, 153±7, p= 0.26) and ApoB (mg/dl) significantly decreased (117±10.8, 103±8.4, 106±9.9, 102±8.6, p= 0.03). HDL and LDL cholesterol were unchanged.

Conclusions: This study suggests that ED could be considered as a surrogate marker which can predict the occurrence of CAD. Moreover, severe ED could be mentioned as an independent risk factor in addition to the established ones. However, further cohort studies are warranted to test this hypothesis.

Conclusions: This preliminary study showed the interest of PDE 5 inhibitors to decrease the cardiac risk factor ApoB/ApoA-1 ratio. Randomised controlled studies with longer follow up are needed to confirm those results and to define the right schedule and dosage for maintenance therapy.





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5-years longitudinal changes of testosterone and DHEAS in 75yrs old men: Results of the VITA-study

Rapid ejaculation and attention deficiency hyperactivity disorder

Ponholzer A.1, Jungwirth S.2, Tragl K.H.2, Madersbacher S.1, Fischer P.3

Adayener C.1, Semiz B.2, Ates F.1, Akyol I.1, Soydan H.1, Basoglu C.2, Baykal V.1

1 Donauspital, Dept. of Urology, Vienna, Austria, 2Donauspital, Lbi of Aging Research, Vienna, Austria, 3Donauspital, Dept. of Psychiatry, Vienna, Austria

Introduction & Objectives: Despite the broad discussion on late onset hypogonadism (LOH) and its management, little is known on the natural history of androgen serum levels, particularly in elderly men. Aim of this study was therefore to address this issue in a population based cohort of 75 yrs old men. Material & Methods: The Vienna Transdanube Aging study (VITA) is a longitudinal, population-based study that included men aged 75-76 yrs living in a well-defined area in Vienna. The main purpose of this study is identifying risk-factors and predictors for incident Alzheimer’s disease. Testosterone and DHEAS were determined at baseline and at 5yrs follow-up. LOH was defined as total serum testosterone <350ng/dl. Results: Baseline and 5 yrs follow-up data were available of 146 men. Baseline characteristics were as follows: age: 75.7+0.4 yrs (mean+SD; range: 74.9 yrs-76.8 yrs), BMI: 26.8+2.8, diabetes: 19.9%, hypertension: 30.1%, hypercholesteraemia: 31.5%. Testosterone serum levels were 429 ng/dl at baseline and declined slightly to 416ng/dl 5 yrs later. At baseline, LOH defined by a total testosterone (<350ng/dl) was present in 30.8%, after 5 yrs this percentage increased to 35.6%. Of men with LOH at baseline (n=45), 29% had normal testosterone values after 5 yrs. De novo LOH developed in 17% over 5 years (3.4%/year). DHEAS was 83+51mg/dl at baseline and 80+85 mg/ dl after 5 yrs. The percentage of men with low DHEA-serum levels (<50 mg/dl) was 30% at baseline and 39% 5 yrs thereafter. Conclusions: This longitudinal study of a population-based 75 yrs old cohort indicates only minor changes of testosterone and DHEAS. About one third of men with LOH experience spontaneous remission over 5 years.

1 Gulhane Military Medical Faculty, Haydarpasa Hospital, Dept. of Urology, Istanbul, Turkey, 2Gulhane Military Medical Faculty, Haydarpasa Hospital, Dept. of Psychiatry, Istanbul, Turkey

Introduction & Objectives: Rapid ejaculation (RE) is the most frequent sexual dysfunction in elderly men. The relation between RE and attention deficiency hyperactivity disorder (ADHD) which has a incidence of 5-10% in school boys and 4% in adults has never been investigated. Material & Methods: A total of 38 men complained with RE were studied. Medical histories, body mass index (BMI), routine biochemical analysis, tiroid function tests, follicule stimulan hormone (FSH), luteinizan hormone (LH), prolactine (PRL), free and total testosterone (fT and T) were recorded. All patients answered the 10 questions in Althof and Rosen’s Index of Premature Ejaculation and filled Wender Utah and Conner’s adult ADHD index form. The data was compared with 27 men who don’t have RE. Results: ADHD was found in 16 of the 38 patients with RE (42.1%). However only one case was having ADHD in control group (3.7%). First sexual intercourse age, frequency of intercourse, BMI, tiroid function tests, routine biochemical results and the ejaculation time was not found to be correlated. Conclusions: The relation between ADHD and RE was studied for the first time. A close relation was found between two disorders. Future studies on the common factors of these two disorders may change the things we know about etiology and the treatment of RE.

Eur Urol Suppl 2009;8(4):173