Central Haemodynamics and Prediction of Cardiovascular Events in Patients With Erectile Dysfunction.

BACKGROUND: We investigated whether central hemodynamics predict major adverse cardiovascular events (MACEs) in erectile dysfunction (ED) patients beyond traditional risk factors. METHODS: MACEs in relation to aortic pressures and augmentation index (AIx) were analyzed in 398 patients (mean age, 56 years) with ED but without established cardiovascular (CV) disease. RESULTS: During the mean follow-up period of 6.5 years, a total of 29 (6.5%) MACEs occurred. The adjusted relative risk of MACEs was 1.062 (95% confidence interval (CI), 1.016-1.116) for a 10-mm Hg increase of aortic systolic pressure, 1.119 (95% CI, 1.036-1.155) for a 10-mm Hg increase of aortic pulse pressure (PP), and 1.191 (95% CI, 1.056-1.372) for a 10% absolute increase of AIx. While aortic pressures and AIx did not significantly improve the C-statistic models, the calibration for all indices was satisfactory. Regarding reclassification, the integrated discrimination improvement index (IDI) indicated improvement in risk discrimination of the models that included AIx and aortic PP compared to the reference model in identifying MACEs (IDI = 0.0069; P = 0.024, and IDI = 0.0060; P = 0.036, respectively). The based on categories for 10-year coronary heart disease risk and adapted at 6.5 years overall net reclassification index showed marginal and indicative risk reclassification for AIx (15.7%, P = 0.12) and aortic PP (7.2%, P = 0.20) respectively. CONCLUSIONS: Our results show for the first time that higher central pressures and AIx are associated with increased risk for a MACE in ED patients without known CV disease. Considering the adverse prognostic role of central hemodynamics on outcomes, the present findings may explain part of the increased CV risk associated with ED.

Acute effect of sildenafil on inflammatory markers/mediators in patients with vasculogenic erectile dysfunction.

BACKGROUND: Erectile dysfunction (ED) is associated with an incremental inflammatory activation. Evidence suggests that chronic phosphodiesterase 5 (PDE-5) inhibition may have a favorable effect on inflammatory activation and surrogate markers of ED. The aim of this study is to investigate the acute effect of sildenafil on circulating pro-inflammatory markers/mediators in ED patients. METHODS: The study comprised a randomized, double-blind, crossover trial carried out on two separate arms: one with sildenafil 100mg, and one with placebo. Twenty-seven subjects participated in the study (seven in the pilot and 20 in the main phase). In the main phase, blood samples were collected at baseline and at 2 and 4h after sildenafil or placebo administration to determine fibrinogen, high sensitivity C-reactive protein (hsCRP), high sensitivity interleukin-6 (hsIL-6) and tumor necrosis factor α (TNF-α). RESULTS: Administration of sildenafil produced a significant sustained reduction of fibrinogen, hsCRP and hsIL-6 (maximal absolute response of -44mg/dl, 0.42mg/l and 0.68pg/ml at 4h). Likewise, TNF-α was acutely decreased after sildenafil (maximal response of -13pg/ml, 2h). The effect of sildenafil on fibrinogen, hsCRP and hsIL-6 and TNF-α was independent of the baseline values of these markers/mediators or the baseline testosterone level (all P<0.05). Soluble vascular cell adhesion molecule 1 (sVCAM-1) levels remained unchanged. CONCLUSIONS: The present study shows for the first time the acute effect of sildenafil administration on pro-inflammatory markers/mediators in men with vasculogenic ED. This finding may have important implications in ED patients who are considered to be at increased cardiovascular risk.