Interactions between erectile dysfunction, cardiovascular disease and cardiovascular drugs

Sexual health has a fundamental role in overall health and well-being, and a healthy and dynamic sex life can make an important contribution to a good quality of life. Sexual dysfunction, and especially erectile dysfunction (ED) in men, is highly prevalent in patients with cardiovascular disease (CVD). CVD and ED have shared risk factors and pathophysiological links, such as endothelial dysfunction, inflammation and low plasma testosterone levels. ED has been shown to be an independent and early harbinger of future CVD events, providing an important window to initiate preventive measures. Therefore, screening and diagnosing ED is essential for the primary and secondary prevention of CVD because the assessment of ED offers an easy and low-cost prognostic tool that is an alternative to other investigational cardiovascular biomarkers. Moreover, ED is a major contributing factor to the discontinuation of, or poor adherence to, cardiovascular therapy. Cardiovascular drugs have divergent effects on erectile function, with diuretics and beta-blockers having the worst profiles, and renin-angiotensin-aldosterone system inhibitors and nebivolol having the best profiles. Pharmacological treatment of ED has an equivocal effect on the risk of CVD, suggesting a complex interaction between ED and drugs for CVD. In this Review, we discuss how sexual function could be incorporated into the patient history taken by physicians treating individuals with CVD, not merely as part of the diagnostic work-up but as a means to pursue tangible and essential benefits in quality of life and cardiovascular outcomes. Cardiovascular disease (CVD) and erectile dysfunction (ED) have shared risk factors and mechanisms. Moreover, ED is an independent predictor of CVD events and is an adverse effect of some cardiovascular drugs. This Review discusses how sexual function should be considered when treating patients with CVD to improve quality of life and cardiovascular outcomes

Adalimumab decreases aortic stiffness independently of its effect in disease activity in patients with rheumatoid arthritis

Rheumatoid arthritis (RA) is associated with increased cardiovascular morbidity and mortality attributed to traditional cardiovascular risk factors and/or the chronic systemic inflammation. We investigated the effect of a TNF antagonist (adalimumab-ADA) on aortic stiffness in RA patients. We studied 18 RA patients with active disease despite therapy with disease modifying antirheumatic drugs (DMARDs), treated with ADA (alone or in combination with DMARDs) for 12 weeks. Disease activity markers as well as aortic stiffness indices (carotid-femoral pulse wave velocity-PWV, augmentation index-AIx), were measured at baseline and at the end of treatment. Eighteen RA patients treated with methotrexate (MTX) were included as controls. Patients were categorized as responders (decrease of Disease Activity Score-DAS28 > 1.2) or nonresponders. There was a statistically significant decrease in PWV (from 8.18 +/- 2.03 to 7.01 +/- 1.78 m/s, p = 0.00006) and DAS28 (from 6.65 +/- 1.22 to 4.69 +/- 1.46, p = 0.00007) in RA patients treated with ADA. The decrease in PWV was observed both in responders (n = 12) and nonresponders (n = 6). Multivariate analysis showed that the decrease of PWV was independent of changes in disease activity or other parameters. There was no significant change in PWV in patients treated with MTX (from 8.87 +/- 1.91 to 8.41 +/- 2.17, p = 0.29). No significant change in AIx or traditional cardiovascular risk factors was observed. Treatment with ADA significantly reduced aortic stiffness in RA patients regardless of their response to therapy. These findings imply a direct protective effect of ADA in vascular wall in RA patients

The Triad: Erectile Dysfunction - Endothelial Dysfunction - Cardiovascular Disease

Endothelial dysfunction is an important process in the development of atherosclerotic cardiovascular disease, while it is also a major pathophysiological mechanism underlying vasculogenic erectile dysfunction (ED). Expectedly, these two prevalent disorders are linked also at the clinical level: ED is common in patients with overt and silent coronary artery disease, while ED is increasingly being regarded as the early clinical manifestation of a generalized vascular disease and carries an independent risk for future cardiovascular events. The emerging awareness of ED as a barometer for cardiovascular disease offers a unique opportunity to enhance preventive vascular health in men. Lifestyle and risk factor modification, as well as pharmacologic therapy (both phosphodiesterase type-5 inhibitors and non-ED-targeting drugs), appear to confer additional benefit both in terms of ED treatment and overall cardiovascular risk; this benefit may be related, at least partly, to the improvement of endothelial function and anti-inflammatory effects. The present review identifies pathophysiologic links between endothelial dysfunction, ED and coronary artery disease, presents methodological aspects regarding penile and systemic endothelial function, and discusses the clinical implications in terms of diagnosis of ED, assessment of patient risk, and treatment

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 100 mg, 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 4 h after sildenafil or placebo administration to determine fibrinogen, high sensitivity C-reactive protein (hsCRP), high sensitivity interleukin-6 (hsIL-6) and tumor necrosis factor a (TNF-alpha). Results: Administration of sildenafil produced a significant sustained reduction of fibrinogen, hsCRP and hsIL-6 (maximal absolute response of -44 mg/dl, 0.42 mg/l and 0.68 pg/ml at 4 h). Likewise, TNF-alpha was acutely decreased after sildenafil (maximal response of -13 pg/ml, 2 h). The effect of sildenafil on fibrinogen, hsCRP and hsIL-6 and TNF-alpha 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. (C) 2014 Published by Elsevier Ireland Ltd