Στυτική δυσλειτουργία και Στεφανιαία νόσος

Στυτική δυσλειτουργία και Στεφανιαία νόσος Χαράλαμπος Βλαχόπουλος Αναπληρωτής Καθηγητής Καρδιολογίας ΓΝΑ Ιπποκράτειο Υπεύθυνος Μονάδας Υπέρτασης

Στυτική δυσλειτουργία και Στεφανιαία Νόσος Σχέση με τη ΣΝ κλινική ή υποκλινική ΣΔ και καρδιαγγειακός κίνδυνος: το παράθυρο της ευκαιρίας Παθοφυσιολογικές παράμετροι Χειρισμός των ασθενών με ΣΔ Φαρμακολογική θεραπεία

In CAD patients: Prevalence of ED 46% -70% Diokno AC, et al., Arch Intern Med 1990 Wabrek AJ, et al., Arch Sex Behav 1980 Dhabuwala CB et al., Arch Sex Behav 1986 Tuttle WB et al., Am J Cardiol 1964 Initial studies Kloner R, et al. J Urol 2003 70% (53/76) Solomon H, et al. Am J Cardiol 2003* 65% (86/132) Montorsi F, et al. Eur Urol 2003* 49% (147/300) Foroutan SK, et al. Urol 2007 46% (186/401) Justo H, et al. Int J Impot Res 2010* 54% (66/123) * CAD documented by coronary angiography

Type of CAD presentation and ED ED rate significantly differs across patients with established CAD according to coronary clinical presentation and atherosclerosis burden: it is low in Acute Coronary Syndromes and 1-VD and high in Chronic CS Montorsi P, et al, Eur Heart J 2006

Vasculogenic ED and Silent CAD Vlachopoulos et al. Eur Urol 2005 Prospective Angiographic Study 50 patients The other side of the coin Asymptomatic for CAD 37 patients with negative non-invasive procedures for myocardial ischemia 9 patients with angiographically documented CAD + 3 patients with positive non-invasive procedures for myocardial ischemia 1 out of 5 men with ED had subclinical CAD

Erectile Dysfunction and Cardiovascular Events 92,754 participants mean follow-up >6 years Vlachopoulos et al. Circ Cardiovasc Qual Outcomes 2013 ED increased significantly and independently of traditional risk factors the risk of myocardial infarction, cerebrovascular events, and all-cause mortality by 62, 39 and 25% respectively and marginally the risk of CV mortality

ED-CAD: Time is of the essence Montorsi F, et al Eur Urol 2003 Montorsi P, et al Circulation 2005 Montorsi P, et al. Eur Heart J 2006 Hodges L et al Int J Clin Pract 2007 Shi H et al. Andrologia 2007 Foroutan SK, et al. Urol J 2007 Vlachopoulos C, et al. Eur Heart J 2009 (abstr) Patients (n) Type of CAD ED prevalence (%) ED prior to CAD (%) ED-CAD time interval (mos/range) 300 Unselected 49 67 38.8 (1-168) 249 1 st ACS 41 100 28±36 95 CCS 67 93 24 (12-36) 207 Unselected 66 55 60±60 467 Unselected 48 49 33 (2-87) 401 Unselected 46 42 23 (10-36) 103 Unselected 100 78 36.4 (4-174)

1 in 2 pts with HTN has Erectile Dysfunction

Erectile Dysfunction and Cardiovascular disease: Pathophysiological considerations Vlachopoulos C, et al. Curr Pharmacol Des 2008 Endothelial dysfunction and inflammation seem to be common denominators between ED and CVD

Erectile Dysfunction and Arterial Function Increased arterial stiffness Increased early atherosclerosis (IMT) Endothelial dysfunction (brachial FMD) Vlachopoulos C, et al., J Hypertens 2008

Predictive role of arterial stiffness in ED Stiff aorta: >2-fold increase in risk for cardiovascular events / allcause mortality JACC, March 30, 2010 344 pts 3.7 yrs f-u 4-fold increase of events in the higher aortic stiffness group Vlachopoulos C, et al. Hypertension 2014

Erectile Dysfunction and Low-Grade Inflammation mg/l 6 5 hscrp pg/ml 12 10 IL-6 4 8 3 6 2 1 no ED 4 2 no ED 0 N = 32 46 25 38 no CAD CAD ED 0 N = 32 46 25 38 no CAD CAD ED ED is associated with increased inflammatory burden in men without CAD (equivalent to that of CAD alone) For most markers, ED confers an incremental unfavorable impact when combined with CAD Vlachopoulos C, et al. Eur Heart J 2006 Vlachopoulos C, et al. Eur Urol 2007

Erectile Dysfunction and Testosterone Deficiency Basaria and Dobs, Circulation 2007 Testosterone plays an integral role in the common pathophysiology of ED and CVD

Low testosterone increases CV risk Healthy men Erectile Dysfunction 4. >19.5 nmol/l 1. <12.5 nmol/l Khaw K Circulation 2007 Hypertension Corona et al. J Sex Med 2010 CAD Vlachopoulos C et al Am J Hypertens 2013 Malkin CJ et al. Heart 2010

Management of ED patients Vlachopoulos et al. Eur Heart J 2013

Sexual Dysfunction and Cardiovascular Disease Double Shot!

Medications ED treatment PDE5 inhibitors Alprostadil Testosterone Therapy CAD treatment Nitrates Antihypertensive drug therapy α blockers Statins

PDE5 inhibitors: effect on cardiac diseases Vlachopoulos et al. Curr Pharmacol Des 2009

PDE-5 inhibitors: effect on CV risk PDE-5 inhibitors might reduce the occurrence of MACE among CAD diabetic patients with ED. Gazzaruso C, et al. J Am Coll Cardiol 2008

TRT and CV events: Risk and benefits vs 209 males, 74 y/o and high CV risk (CVD~50%, hypertension.~80 %, DM ~25%) 100 to 350 ng/dl (3.5 to 12.1 nmol/l) Testosterone gel or placebo gel 6 mo f-u 398 males, 61 y/o (CAD~20%, DM ~36%) <250 ng/dl (8.7 nmol/l) Testosterone IM (88.6%) or placebo gel 40.5 mo f-u Basaria et al. N Engl J Med 2010 Shores et al. J Clin Endocrin Metab 2012

Statins: Effect on erectile function 713 pts 11 studies Mean follow-up: 4.2 ± 1.8 months baseline LDL: 133.9 ± 17.5 mg/dl after statin therapy: 90.4 ± 18.6 mg/dl J Kostis and J Dobrzynski. J Sex Med 2014 increase in IIEF score by 3.4 points

b-blockers: Effect on erectile function Doumas M. Asian J Androl 2006

Συμπεράσματα Η πλειονότητα των ασθενών με ΣΝ έχει ΣΔ Η ΣΔ σχετίζεται με το κλινικό σύνδρομο της ΣΝ Η ΣΔ εμφανίζεται πριν τη ΣΝ στην πλειονότητα των ασθενών Η ΣΔ αυξάνει τον κίνδυνο για καρδιαγγειακά συμβάματα Η χαμηλή τεστοστερόνη σχετίζεται με αυξημένο καρδιαγγειακό κίνδυνο Η θεραπεία υποκατάστασης της τεστοστερόνης (όταν ενδείκνυται) μπορεί να μειώσει τον καρδιαγγειακό κίνδυνο. Χρειάζονται όμως μεγάλες τυχαιοποιημένες μελέτες.