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Aims: Phosphodiesterase 5 inhibitors (PDE5i), which are widely used for the treatment of erectile dysfunction (ED), have been found to exhibit systemic vascular benefits by improving endothelial function. In this context, we sought to evaluate the effects of PDE5i on long-term cardiovascular outcomes and mortality., Methods and Results: A comprehensive search of electronic databases was conducted up to 30 May 2023. Cohort studies comparing PDE5i treatment at any dose with other ED treatment, placebo or no treatment and minimum follow-up duration of 6 months were considered eligible. The primary endpoints were: (1) major adverse cardiovascular events (MACE) and (2) all-cause mortality. Pooled risk ratios (RR) with 95% confidence intervals (CI) were calculated. Sixteen studies were included (1 257 759 subjects-10.5% treated with PDE5i). The majority of patients (99.4%) were men [median age 61.5 years (range 30-72.8)]. The median follow-up duration was 4.3 years (range 6 months-7.5 years). PDE5i use was associated with a significant reduction in the composite of MACE (RR 0.78, 95% CI 0.69-0.89). Moreover, the analysis of pooled data from 13 studies, demonstrated that the use of PDE5i was associated with a significantly lower risk of all-cause mortality (RR 0.70, 95% CI 0.56-0.87)., Conclusion: The use of PDE5i primarily in men with or without known coronary artery disease was associated with a lower risk for cardiovascular events and overall mortality. This information underlines that PDE5i could provide clinical benefit beyond ED treatment and could instigate the conduction of further, large-scale randomized clinical trials., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

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 β-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., (© 2021. Springer Nature Limited.)

: Sexual health is an integral part of overall health, and an active and healthy sexual life is an essential aspect of a good life quality. Cardiovascular disease and sexual health share common risk factors (arterial hypertension, diabetes mellitus, dyslipidemia, obesity, and smoking) and common mediating mechanisms (endothelial dysfunction, subclinical inflammation, and atherosclerosis). This generated a shift of thinking about the pathophysiology and subsequently the management of sexual dysfunction. The introduction of phosphodiesterase type 5 inhibitors revolutionized the management of sexual dysfunction in men. This article will focus on erectile dysfunction and its association with arterial hypertension. This update of the position paper was created by the Working Group on Sexual Dysfunction and Arterial Hypertension of the European Society of Hypertension. This working group has been very active during the last years in promoting the familiarization of hypertension specialists and related physicians with erectile dysfunction, through numerous lectures in national and international meetings, a position paper, newsletters, guidelines, and a book specifically addressing erectile dysfunction in hypertensive patients. It was noted that erectile dysfunction precedes the development of coronary artery disease. The artery size hypothesis has been proposed as a potential explanation for this observation. This hypothesis seeks to explain the differing manifestation of the same vascular condition, based on the size of the vessels. Clinical presentations of the atherosclerotic and/or endothelium disease in the penile arteries might precede the corresponding manifestations from larger arteries. Treated hypertensive patients are more likely to have sexual dysfunction compared with untreated ones, suggesting a detrimental role of antihypertensive treatment on erectile function. The occurrence of erectile dysfunction seems to be related to undesirable effects of antihypertensive drugs on the penile tissue. Available information points toward divergent effects of antihypertensive drugs on erectile function, with diuretics and beta-blockers possessing the worst profile and angiotensin receptor blockers and nebivolol the best profile.

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., (© American Journal of Hypertension, Ltd 2016. All rights reserved. For Permissions, please email: journals.permissions@oup.com)

Objective: Hypertension is associated with an abnormal penile blood flow. Reduced dynamic penile peak systolic velocity (D-PSV) correlates with adverse cardiovascular outcomes. The aim of this study is to investigate whether abnormal penile blood flow predicts major adverse cardiovascular events (MACE) in hypertensive men., Methods: In total, 298 hypertensive men (55 ± 9 y/o) without known cardiovascular disease or diabetes were evaluated for cavernous vascular disease severity by dynamic penile Doppler ultrasound. The whole population was divided into tertiles according to D-PSV reduction (low tertile <25 cm/s; middle tertile 25-35 cm/s; and high tertile >35 cm/s). Predictive performance was evaluated with calibration, discrimination, and reclassification., Results: During the mean follow-up period of 4.9 years, a total of 22 (7%) MACE occurred. D-PSV level was associated with MACE and the differences between the tertiles were significant (Mantel log-rank test: 6.54; P < 0.01). A Cox proportional hazard model showed that study participants in the lowest D-PSV tertile (<25 cm/s) had an approximately 3.5-fold higher MACE risk compared with those in the highest D-PSV tertile (>35 cm/s) after adjustment for age, systolic pressure, metabolic parameters, smoking, C-reactive protein, and testosterone levels. Low D-PSV did not significantly improve the C-statistic model (0.774 vs. 0.767; P = 0.44), whereas the calibration was satisfactory (Hosmer-Lemeshow X = 8.73, P = 0.30). When only intermediate-risk patients were evaluated, the risk reclassification beyond traditional risk factors resulted in a clinical net reclassification index of 9.2% that was marginally significant (P = 0.07). The integrated discrimination improvement index showed better performance of the model that included D-PSV compared with the reference model in identifying MACE (improvement index: 0.047, P = 0.038)., Conclusion: Low-penile blood flow predicts MACE in hypertensive patients free of clinical atherosclerosis. This predictive ability is independent of the severity of hypertension and decreased testosterone that is often present in such patients.

Background: Exercise stress testing (EST) is crucial to determine cardiovascular (CV) risk in men with erectile dysfunction (ED). Low exercise workload, a slower rate of recovery following exercise, and an impaired capacity to increase heart rate (HR) during exercise testing (chronotropic incompetence) are independent predictors of adverse CV outcomes. Aim of this study was to investigate the association between ED and EST parameters., Methods: A total of 180 ED patients and 50 men without ED underwent maximal EST. Exercise parameters including exercise capacity (metabolic equivalents, METS), peak exercise time, HR at six METS, peak exercise, HR recovery (HRR) at 1 and 2 minutes and chronotropic index (CI) were evaluated in all individuals. Endothelial function was evaluated with flow-mediated dilatation (FMD) of the brachial artery., Results: ED patients had lower peak exercise time and thus lower calculated exercise capacity (P < 0.001) and reduced CI (P < 0.01) compared to men without ED. There was a significant association of ED severity with duration of exercise, peak workload, HRR 2 minutes after exercise, and CI (all P < 0.05). There also was a positive relation of HRR and CI with FMD (all P < 0.05)., Conclusions: This study shows interrelationships between exercise capacity, HRR, CI, and ED. Abnormal HRR and CI are associated with systemic endothelial dysfunction. These findings imply pathophysiological links and may have important implications for the estimation of cardiovascular risk in ED patients., (© 2015 Wiley Periodicals, Inc.)

A number of circulating and imaging biomarkers are robustly associated with cardiovascular (CV) risk. The overall expectation from a biomarker in the erectile dysfunction (ED) setting is to enhance the optimal management of a man with this disorder but no clinical atherosclerosis. Evidence demonstrating that these biomarkers enhance risk prediction for individuals with ED is at this stage still limited for most of them. A better identification of the subsets of the ED population that require further risk stratification, as well as the initiation of randomized trials that will formally test the ability of biomarkers to predict CV risk, could make biomarker-guided prevention an attainable goal.

Erectile dysfunction (ED) has been found to frequently precedes the onset of coronary artery disease (CAD), representing an early marker of subclinical vascular disease, included CAD. Its recognition is, therefore, a "window opportunity" to prevent a coronary event by aggressive treatment of cardiovascular risk factors. The artery size hypothesis (ASH) has been proposed as a putative mechanism to explain the relationship between ED and CAD. Since atherosclerosis is a systemic disorder all major vascular beds should be affected to the same extent. However, symptoms at different points in the system rarely become evident at the same time. This is likely the result of smaller vessels (i.e. the penile artery) being able to less well tolerate the same amount of plaque when compared with larger ones (i.e. the coronary artery). If true, ED will develop before CAD. We present a case in which ED developed after a coronary event yet before a coronary recurrence potentially representing a late marker of vascular progression. Reasons for this unusual sequence are discussed as they might still fit the ASH.

Erectile dysfunction confers an independent risk for cardiovascular events and total mortality. Aortic pulse wave velocity (PWV) is an important predictor of cardiovascular events and all-cause mortality. We investigated whether PWV predicts major adverse cardiovascular events (MACEs) in patients with erectile dysfunction beyond traditional risk factors. MACEs in relation to PWV were analyzed with proportional hazards models in 344 patients (mean age, 56 years) without established cardiovascular disease. During a mean follow-up of 4.7 years (range, 1-8.5 years), 24 of 344 participants (7.0%) experienced a MACE. Subjects in the highest PWV tertile (>8.8 m/s) had a 4-fold higher risk of MACEs compared with those in the lowest PWV tertile (<7.6 m/s; adjusted hazard ratio, 3.97; P=0.035). A PWV value of 7.81 m/s was associated with a negative predictive value (ability to rule out MACE) of 98.1%. Addition of PWV to standard risk factor model yielded correct patient reclassification to higher or lower risk category by 27.6% (P=0.0332) in the whole cohort. Our results show that higher aortic stiffness is associated with increased risk for a MACE in patients with erectile dysfunction without known cardiovascular disease. Aortic PWV improves risk prediction when added to standard risk factors and may represent a valuable biomarker of prediction of cardiovascular disease risk in these patients., (© 2014 American Heart Association, Inc.)

Context: Erectile dysfunction (ED) is considered a vascular impairment that shares many risk factors with cardiovascular disease (CVD). A correlation between ED and CVD has been hypothesized, and ED has been proposed as an early marker of symptomatic CVD., Objective: To analyze the relationship between ED and CVD, evaluating the pathophysiologic links between these conditions, and to identify which patients would benefit from cardiologic assessment when presenting with ED., Evidence Acquisition: A systematic literature review searching Medline, Embase, and Web of Science databases was performed. The search strategy included the terms erectile dysfunction, cardiovascular disease, coronary artery disease, risk factors, pathophysiology, atherosclerosis, low androgen levels, inflammation, screening, and phosphodiesterase type 5 inhibitors alone or in combination. We limited our search to studies published between January 2005 and May 2013., Evidence Synthesis: Several studies reported an association between ED and CVD. The link between these conditions might reside in the interaction between androgens, chronic inflammation, and cardiovascular risk factors that determines endothelial dysfunction and atherosclerosis, resulting in disorders of penile and coronary circulation. Because penile artery size is smaller compared with coronary arteries, the same level of endothelial dysfunction causes a more significant reduction of blood flow in erectile tissues compared with that in coronary circulation. Thus ED could be an indicator of systemic endothelial dysfunction. From a clinical standpoint, because ED may precede CVD, it can be used as an early marker to identify men at higher risk of CVD events. ED patients at high risk of CVD should undergo detailed cardiologic assessment and receive intensive treatment of risk factors., Conclusions: ED and CVD should be regarded as two different manifestations of the same systemic disorder. ED usually precedes CVD onset, and it might be considered an early marker of symptomatic CVD., (Copyright © 2013 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Erectile dysfunction is common in the patient with cardiovascular disease. It is an important component of the quality of life and it also confers an independent risk for future cardiovascular events. The usual 3-year time period between the onset of erectile dysfunction symptoms and a cardiovascular event offers an opportunity for risk mitigation. Thus, sexual function should be incorporated into cardiovascular disease risk assessment for all men. A comprehensive approach to cardiovascular risk reduction (comprising of both lifestyle changes and pharmacological treatment) improves overall vascular health, including sexual function. Proper sexual counselling improves the quality of life and increases adherence to medication. This review explores the critical connection between erectile dysfunction and cardiovascular disease and evaluates how this relationship may influence clinical practice. Algorithms for the management of patient with erectile dysfunction according to the risk for sexual activity and future cardiovascular events are proposed.

Purpose: We established erectile dysfunction as an often neglected but valuable marker of cardiovascular risk, particularly in younger men and men with diabetes. We also reviewed evidence that lifestyle change, combined with informed prescribing of pharmacotherapies used to mitigate cardiovascular risk, can improve overall vascular health and sexual functioning in men with erectile dysfunction., Materials and Methods: We performed a PubMed® search for articles and guidelines pertinent to relationships between erectile dysfunction and cardiovascular disease, cardiovascular and all cause mortality, and pharmacotherapies for dyslipidemia and hypertension. The clinical guidance presented incorporates the current literature and the expertise of the multispecialty investigator group., Results: Numerous cardiovascular risk assessment tools exist but risk stratification remains challenging, particularly in patients at low or intermediate short-term risk. Erectile dysfunction has a predictive value for cardiovascular events that is comparable to or better than that of traditional risk factors. Interventional studies support lifestyle changes as a means of improving overall vascular health as well as sexual functioning. Statins, diuretics, β-blockers and renin-angiotensin system modifiers may positively or negatively affect erectile function. Furthermore, the phosphodiesterase type 5 inhibitors used to treat erectile dysfunction may have systemic vascular benefits., Conclusions: Erectile dysfunction treatment should be considered secondary to decreasing cardiovascular risk. However, informed prescribing may prevent worsening sexual function in men receiving pharmacotherapy for dyslipidemia and hypertension. As the first point of medical contact for men with erectile dysfunction symptoms, the primary care physician or urologist has a unique opportunity to identify those who require early intervention to prevent cardiovascular disease., (Copyright © 2013 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Erectile dysfunction (ED) carries an independent risk for cardiovascular (CV) events. We conducted a meta-analysis of all longitudinal studies for determining the ability of ED to predict risk of clinical events and to dissect factors influencing this ability., Methods and Results: We conducted a comprehensive search of electronic databases through July 2012. Longitudinal studies that reported relative risk (RR) estimates with 95% confidence intervals (CIs) were included. Of the 14 studies included (92 757 participants; mean follow-up, 6.1 years; 16 articles), 13 (14 articles) reported results on total CV events (91 831 individuals), 4 on CV mortality (34 761 individuals), 4 on myocardial infarction (35 523 individuals), 6 on cerebrovascular events (27 689 individuals), and 5 on all-cause mortality (17 869 individuals). The pooled RRs for the above-mentioned end points were 1.44 (95% CI, 1.27-1.63), 1.19 (95% CI, 0.97-1.46), 1.62 (95% CI, 1.34-1.96), 1.39 (95% CI, 1.23-1.57), and 1.25 (95% CI, 1.12-1.39), respectively, for men with versus without ED. The RR was higher in intermediate- compared with high- or low-CV-risk populations and with younger age. The RR for studies that diagnosed ED with the use of a questionnaire compared with a single question was higher (RR, 1.61; 95% CI, 1.38-1.86 versus RR, 1.27; 95% CI, 1.18-1.37, respectively; P=0.006)., Conclusions: ED is associated with increased risk of CV events and all-cause mortality. RR is higher at younger ages, in intermediate-risk groups, and when a questionnaire is used instead of a single question.

The Princeton Consensus (Expert Panel) Conference is a multispecialty collaborative tradition dedicated to optimizing sexual function and preserving cardiovascular health. The third Princeton Consensus met November 8 to 10, 2010, and had 2 primary objectives. The first objective focused on the evaluation and management of cardiovascular risk in men with erectile dysfunction (ED) and no known cardiovascular disease (CVD), with particular emphasis on identification of men with ED who may require additional cardiologic work-up. The second objective focused on reevaluation and modification of previous recommendations for evaluation of cardiac risk associated with sexual activity in men with known CVD. The Panel's recommendations build on those developed during the first and second Princeton Consensus Conferences, first emphasizing the use of exercise ability and stress testing to ensure that each man's cardiovascular health is consistent with the physical demands of sexual activity before prescribing treatment for ED, and second highlighting the link between ED and CVD, which may be asymptomatic and may benefit from cardiovascular risk reduction., (Copyright © 2012 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.)

Introduction: Erectile dysfunction (ED) is common and considered to be predominantly of vascular origin., Aim: To evaluate the link between ED and coronary artery disease (CAD) and provide a consensus report regarding evaluation and management., Methods: A committee of eight experts from six countries was convened to review the worldwide literature concerning ED and CAD and provide a guideline for management., Main Outcome Measure: Expert opinion was based on grading the evidence-based medical literature, widespread internal committee discussion, public presentation, and debate., Results: ED and CAD frequently coexist. Between 50-70% of men with CAD have ED. ED can arise before CAD is symptomatic with a time window of 3-5 years. ED and CAD share the same risk factors, and endothelial dysfunction is the common denominator. Treating ED in cardiac patients is safe, provided that their risks are properly evaluated., Conclusion: ED is a marker for silent CAD that needs to be excluded. Men with CAD frequently have ED that can be treated safely following guidelines.

Introduction: Phosphodiesterase type 5 (PDE5) inhibitors are widely used as first-line therapy for erectile dysfunction (ED). Their efficacy and safety combined with an increasing understanding of cyclic guanosine monophosphate (cGMP)-regulated mechanisms have triggered a number of attempts to determine their effects on the cardiovascular system and their potential benefits in cardiovascular conditions., Aim: To review and discuss recent findings regarding the cardiovascular effects of PDE5 inhibitors and to highlight current and future clinical applications beyond ED., Main Outcome Measures: Results of preclinical and clinical studies evaluating the cardiovascular effects of PDE5 inhibitors are analyzed and critically put into perspective., Methods: Extensive PubMed literature search reviewing relevant data on effects and mechanisms of PDE5 inhibitors on the cardiovascular system., Results: In recent years, extensive but very heterogeneous preclinical and clinical evidence has been reported. PDE5 inhibition has proven collateral benefits for a multitude of risk factors or diseases associated with or accompanying ED. However, these agents appear to have the potential of expanding their indications. To date, PDE5 inhibition has been shown to be effective for the treatment of idiopathic pulmonary artery hypertension, and sildenafil is approved for this indication. Importantly, accumulating data show that the therapeutic potential extends to the myocardium, the coronary and peripheral arteries, subliclinical inflammation, oxidative stress, thrombosis, neurological recovery, and pathways of fibrosis. Thus, the spectrum of patients who may benefit has expanded to include, for instance, patients with heart failure or coronary artery disease., Conclusions: PDE5 inhibitors are an exciting class of drugs with pleiotropic effects. Current or future PDE5 inhibitors are a conceptually attractive therapeutic strategy with potential clinical applications in a variety of cardiovascular conditions.

Objective: Erectile dysfunction is a predictor of cardiovascular risk with high prevalence in hypertensive men. We investigated whether erectile dysfunction is related to arterial structure and function in hypertensive patients., Methods: We evaluated arterial structural and functional characteristics and measured systemic endothelial/inflammatory markers in 52 hypertensive men with vasculogenic erectile dysfunction and in 34 hypertensive men with normal erectile function, matched for age, blood pressure, risk factors and treatment., Results: Hypertensive patients with erectile dysfunction had higher common carotid intima-media thickness (0.95 +/- 0.19 vs. 0.83 +/- 0.18 mm, P = 0.003) and carotid-femoral pulse-wave velocity (8.89 +/- 1.38 vs. 8.11 +/- 1.10 m/s, P = 0.007), lower flow-mediated dilation of the brachial artery (absolute values of 2.96 +/- 1.64 vs. 4.07 +/- 1.68%, P = 0.003) and a higher level of the systemic endothelial dysfunction marker asymmetric dimethylarginine (0.67 +/- 0.13 vs. 0.57 +/- 0.16 mumol/l, P = 0.003), and the inflammatory markers high-sensitivity C-reactive protein [2.03 (1.16-2.89) vs. 1.23 (0.67-1.90) mg/l, P = 0.029] and interleukin-6 (4.13 +/- 2.38 vs. 2.77 +/- 1.92 pg/ml, P = 0.011). Multivariable analysis adjusting for age, mean pressure, other risk factors and treatment showed independent associations between erectile dysfunction and parameters of arterial structure and function. In the erectile dysfunction group, there were no significant relationships between the severity of erectile dysfunction (as expressed by the Sexual Health Inventory for Men score) and the above arterial indices and level of circulating markers (all P = NS)., Conclusion: In hypertensive men, the presence but not the severity of vasculogenic erectile dysfunction is associated with subclinical atherosclerosis, impairment of arterial function and systemic endothelial and inflammatory activation.

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.

Objective: Erectile dysfunction (ED) may be the early clinical manifestation of a generalized vascular disease and carries an independent risk for cardiovascular events. Low-grade subclinical inflammation affects endothelial function and is involved in all stages of the atherosclerotic process. This review identifies potential pathophysiologic links among low-grade inflammation, ED, metabolic syndrome, and coronary artery disease (CAD) and presents the clinical implications in terms of ED diagnosis, assessment of patient risk, and therapy., Methods: A comprehensive evaluation was performed for available published data in full-length papers that were identified in MedLine up to July 2007., Results: Studies support an association between metabolic syndrome, ED, and increased inflammatory state. Increased circulating levels of inflammatory and endothelial-prothrombotic compounds are related to the presence and severity of ED. Specific inflammatory biomarkers and their combination appear to have the potential to aid ED diagnosis or exclusion. ED and CAD may confer a similar unfavorable impact on the inflammatory and prothrombotic state, whereas ED adds an incremental activation on top of CAD; these findings have important implications for cardiovascular risk. Lifestyle and risk factor modification, as well as pharmacologic therapy, are associated with anti-inflammatory effects., Conclusions: Low-grade systemic inflammation could be an important element of the association between metabolic syndrome, ED, and CAD. Its individualized assessment may be a valuable tool for ED diagnosis, risk assessment, and rationalized therapeutic approach especially in patients with ED who have metabolic syndrome and carry an intermediate risk for future cardiovascular events.

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 α (TNF-α). 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-α 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-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. [ABSTRACT FROM AUTHOR]

Background: Erectile dysfunction (ED) is an early manifestation of a generalized arterial disease. The association between penile vascular disease progression and total atherosclerotic burden was investigated using a classification that incorporates ultrasonographic assessments of intima media thickness (IMT) and plaques from both the carotid and femoral arteries. Methods: Sixty-five ED patients (mean age, 56 ± 10 yrs) were evaluated for cavernous vascular disease severity using penile Doppler ultrasound. Ultrasonographic assessments of IMT, lumen diameter, and plaques in the carotid and femoral arteries were evaluated, and patients were classified according to an ultrasound-based morphological system. Results: Based on the results of ultrasonic assessments, patients were divided into two groups-a high-score group and a low-score group. Patients in the high-score group had increased intima-media ( > 1.0 mm) and/or plaque in any of the four arteries. Patients in the low-score group had normal carotid and femoral IMT and an absence of plaques in all four arteries. While the two groups did not differ in blood pressure parameters, metabolic profile, and smoking status, high-score patients (n = 31) had significantly decreased age-adjusted peak systolic velocity (25.2 cm versus 32.3 cm/s, P < 0.01) and a longer duration of ED (3.8 years versus 2 years, P < 0.05), compared with low-score patients (n = 34). In the high-score group, score level was inversely correlated with peak systolic velocity after adjusting for age and systolic blood pressure (b= -0.322, P = 0.025). There also was a positive linear relation of ED duration with prevalence of high score (P < 0.05). Conclusions: In patients with vasculogenic ED, ultrasound findings of penile vasculature damage and longstanding ED correlate significantly with increasing carotid and femoral atherosclerotic burden. These data suggest a close interrelationship between progression of vasculogenic ED and peripheral atherosclerosis. [ABSTRACT FROM AUTHOR]

Although vardenafil is widely prescribed for erectile dysfunction (ED), its effect on arterial function is not defined. Aortic stiffness, aortic pressures, and wave reflections are predictors of cardiovascular risk. The investigators assessed the hypothesis that vardenafil acutely improves aortic stiffness, aortic pressures, and wave reflections in ED patients. Twelve ED patients (mean age 58 ± 9 years) received vardenafil 20 mg in a randomized, placebo-controlled, double-blind, 2-way crossover design. Aortic stiffness was evaluated with carotid–femoral pulse wave velocity (PWV); wave reflections and aortic pressures were evaluated with augmentation index (AIx) and systolic, diastolic, and pulse pressure of the aortic pressure waveform, respectively. PWV, aortic pressures, and AIx were measured at baseline and for 3 hours after vardenafil intake or placebo. PWV decreased significantly (by 0.7 m/s, P = .001), denoting a decrease in aortic stiffness. AIx decreased significantly (by 7%, P = .008), denoting a decreased effect of wave reflections from the periphery. Aortic pressures decreased significantly (all P < .05). Statin use at baseline significantly interacted with the effects of treatment on both PWV and AIx (P = .003 and P < .001, respectively). This study shows, for the first time, that vardenafil has a favorable acute effect on aortic stiffness and wave reflection in ED patients. [ABSTRACT FROM PUBLISHER]

Abstract: Background: Asymmetric dimethylarginine (ADMA), a selective endogenous nitric oxide synthase inhibitor, is elevated in many conditions associated with erectile dysfunction (ED), such as hypertension, diabetes, hyperlipidemia, and renal failure; it is also increased in men with coronary artery disease and ED. The dynamic penile colour Doppler ultrasound is considered the gold standard for the evaluation of penile vascular damage. Objective: We investigated whether the extent of ultrasonographically documented penile vascular disease is associated with higher ADMA levels. Design, setting, and participants: One hundred four consecutive ED patients (mean age: 56±9 yr) without manifest cardiovascular/atherosclerotic disease and 31 subjects with normal erectile function matched for age and traditional risk factors were studied. Measurements: We evaluated penile dynamic colour Doppler parameters of arterial insufficiency (peak systolic velocity) and veno-occlusive dysfunction (end diastolic velocity) and measured systemic inflammatory markers/mediators. Results and limitations: Compared to men without ED, ED patients had significantly higher ADMA levels (p <0.001). ADMA was significantly increased in patients with severe arterial insufficiency (PSV<25cm/s) compared to subjects with borderline insufficiency and men with normal penile arterial function (p <0.001, by analysis of variance). Multivariable analysis adjusting for age, mean pressure, other risk factors, high-sensitivity C-reactive protein, testosterone, and treatment showed independent inverse association between ADMA level and peak systolic velocity (p <0.01). The combination of higher ADMA level with arterial insufficiency showed greater impact on 10-yr risk of a cardiovascular event compared to either parameter alone. Conclusions: ADMA level is independently associated with ultrasonographically documented poor penile arterial inflow. This finding underlines the important role of ADMA as a marker of penile arterial damage and implies a contribution of this compound to the pathophysiology of generalised vascular disease associated with ED. [Copyright &y& Elsevier]

Abstract: Background: Endothelial dysfunction is a key event in the pathophysiology of erectile dysfunction (ED) and generalized vascular disease. C-type natriuretic peptide (CNP) is a paracrine molecule that effects endothelial integrity and vascular tone. Objective: To determine the role of CNP in men with vasculogenic ED. Design, setting, and participants: Fifty-two consecutive men (age: 57±10 yr) with nonpsychogenic and nonhormonal ED for >6 mo and free of cardiovascular disease who were referred to the Cardiovascular Diseases and Sexual Health Unit of our Department for evaluation of ED were compared with 31 subjects with normal erectile function matched for age, body mass index, and traditional risk factors. Measurements: Vasculogenic ED was diagnosed according to comprehensive history, physical examination, Sexual Health Inventory for Men (SHIM-5) scoring, hormonal testing, and penile color-Doppler ultrasound. Amino-terminal proCNP (NT-proCNP) was measured in plasma with enzyme-linked immunosorbent assay (ELISA). Results and limitations: Compared to controls, ED patients had significantly lower NT-proCNP levels (0.21±0.08pmol/l in ED patients vs 0.34±0.07pmol/l in control subjects; p <0.001). NT-proCNP levels were associated with erectile performance as expressed by SHIM-5 score (r =0.57; p <0.001), even after adjusting for confounders. There was also an inverse linear relationship between ED duration and NT-proCNP levels (p <0.05). In patients with arteriogenic ED, there was a positive correlation of NT-proCNP levels with peak systolic velocity (PSV) (r =0.51; p =0.01). Conclusions: CNP levels are associated with the presence, severity, and duration of ED. These findings provide further insight into the role of CNP in the pathophysiology of ED. [Copyright &y& Elsevier]

Aims Erectile dysfunction (ED) confers an independent cardiovascular risk. We investigated the role of low-grade inflammation and endothelial dysfunction in ED patients with or without coronary artery disease (CAD). [ABSTRACT FROM PUBLISHER]

Abstract: Objectives: Erectile dysfunction (ED) shares common risk factors with coronary artery disease (CAD). It has been suggested that ED may be considered a clinical manifestation of a generalized vascular disease affecting also the penile arteries. The aim of this prospective study was to evaluate angiographically the incidence of asymptomatic CAD in men with ED of vascular origin. Methods: Fifty consecutive asymptomatic men, aged 41–74 years, with non-psychogenic and non-hormonal ED were comprehensively evaluated using medical history and examination, exercise treadmill test and stress echocardiography. Patients who had positive one or both of the two non-invasive procedures were referred for coronary arteriography in order to document CAD and evaluate the severity of the disease. Results: The mean time interval between the onset of ED and cardiological assessment was 25 months (range 1–66). Smoking (32 patients/64%), hypertension (31 patients/62%) and hyperlipidemia (26 patients/52%) were the most common risk factors. Moreover, 35 men (70%) had two or more risk factors. Twelve patients (24%) with ED had positive one or both of the two non-invasive procedures and one patient presented with acute myocardial infarction before he completed the non-invasive investigation. Coronary arteriography performed in ten patients (in nine with positive one or both of the two non-invasive procedures [while the other three refused], and in the patient with acute myocardial infarction) demonstrated that one patient had three-vessel disease, two patients had two-vessel disease and six patients had single-vessel disease. Conclusions: A considerable proportion (9/47 or 19%) of patients with ED of vascular origin has angiographically documented silent CAD. These findings support the strategy that patients with ED should undergo further cardiovascular evaluation. [Copyright &y& Elsevier]