Epidémiologie de la dysfonction érectile (2ème partie). Facteurs de risque

Epidemiological studies in the general population or target populations in several countries in the world have revealed a large number of risk factors for erectile dysfunction: diabetes mellitus, hypertension, smoking, dyslipidaemia, cardiovascular diseases, psychological disorders, certain medications, chronic renal failure, socioeconomic factors and lifestyle, obesity, lower urinary tract symptoms, poor health and bicycling. Cardiovascular risk factors are predictors of erectile dysfunction and erectile dysfunction is now considered to be a manifestation of vascular disease. Further studies are necessary to establish the pathophysiological mechanisms of certain risk factors and the possible value of preventive measures.     

Managing concomitant cardiac disease and erectile dysfunction

Early studies of peak heart rates and blood pressure during coitus led physicians to believe that sexual activity represents a significant risk to patients with cardiovascular disease. Subsequent studies indicated, however, that the heart rate during coitus was no higher than the rate during unaccustomed physical exercise or associated with anger. The absolute risk of myocardial infarction (MI) in a patient with a history of MI has been found to be 10 per million per hour, and the doubling of this risk in the 2 hours following coitus has a negligible impact on annual risk. Coronary artery disease (CAD) is a powerful indicator of the presence of erectile dysfunction (ED), and the risk factors for ED are similar to those for CAD. Studies of sildenafil citrate use in patients with a history of cardiovascular disease have found sildenafil to be safe and effective, except for an absolute contraindication in the concomitant use of nitrates. Physicians should become familiar with the clinical guidelines for classifying ED patients with a history of cardiovascular disease as high risk, intermediate or indeterminate risk, and low risk. The guidelines permit physicians MIlow risk while deferring the resumption of sexual activity among higher risk patients pending further evaluation.     

Farnesoid X receptor activation improves erectile dysfunction in models of metabolic syndrome and diabetes

The metabolic syndrome (MetS) is an insulin-resistant state characterized by a cluster of cardiovascular risk factors, including abdominal obesity, hyperglycemia, elevated blood pressure and combined dyslipidemia. In this review, we discuss the potential of farnesoid X receptor (FXR) agonists in the treatment of erectile dysfunction (ED), a multifactorial disorder often comorbid with MetS. FXR not only regulates lipid and glucose homeostasis but also influences endothelial function and atherosclerosis, suggesting a regulatory role for this hormone nuclear receptor in the cardiovascular complications associated with the MetS, including ED. MetS induces ED via several mechanisms, and in particular through endothelial dysfunction in penile vessels. In a high-fat diet rabbit model of MetS, a 3-month treatment with the potent and selective FXR agonist INT-747 restores endothelium-dependent relaxation in isolated cavernous tissue, normalizing responsiveness to acetylcholine and to electrical field stimulation. Accordingly, eNOS expression in the penis is greatly up-regulated by INT-747 treatment. Experiments in a rat model of chemically-induced type 1 diabetes further demonstrate that INT-747 treatment preserves erectile function induced by electrical stimulation of the cavernous nerve. These results add a new facet to the pleiotropic activities mediated by FXR, and reveal novel beneficial effects of FXR activation with potential clinical relevance. This article is part of a Special Issue entitled: Translating nuclear receptors from health to disease.     

Diabetes,obesity, and erectile dysfunction

Background: Diabetes mellitus (DM) and obesity affect large parts of the population in the United States and around the world. These disorders are among the most common risk factors for erectile dysfunction (ED), because of their effects on the vasculature and the hormonal milieu.Objective: This article reviews the current literature on the connection between DM, obesity, and ED.Methods: Using the search terms erectile dysfunction, endothelial dysfunction, hypogonadism, diabetes, and obesity, a systematic review of the available literature in the PubMed database was conducted. Relevant English-language publications (to August 2008) were identified.Results: ED is highly prevalent in men with both DM and obesity, and may act as a harbinger for cardiovascular disease (CVD) in this high-risk population. In addition to male hypogonadism and macrovascular disease, endothelial dysfunction is central to the connection between the metabolic syndrome and ED. Conversely, improved glycemic control and weight loss have been found to improve erectile function.Conclusion: ED is very prevalent in men with DM and obesity. It is increasingly being recognized as an early clinical indicator and motivator for patients with CVD. The role of pharmacologic ED treatments in improving endothelial function is currently being investigated.     

La dysfonction érectile, un marqueur précoce d’atteinte cardio-vasculaire

Erectile dysfunction (ED) affects approximately 100 million men in the world and 50% of men between the ages of 40 and 70 years. The commonest cause is a vascular disorder of penile arteries. ED may therefore be a an early marker of cardiovascular disease (CVD). The main arguments in favour of this assertion are primarily epidemiological, but also pathophysiological, as control of cardiovascular risk factors such as smoking, obesity and hypertension may prevent not only CVD, but also ED. This relationship is particularly strong in diabetic patients, in whom ED can be considered to be an element able to identify patients at risk of asymptomatic heart disease. From a pathophysiological point of view, small calibre penile vessels present signs of obstruction earlier than larger vessels because they are more sensitive to even minor haemodynamic changes. There is also a significant correlation between the severity of ED and the number of vessels affected in patients with coronary artery disease. Endothelial dysfunction is the common denominator underlying these diseases and therefore represents a major cause of ED. Preliminary studies have shown that PDE-5 inhibitors can reduce symptoms, improve exercise tolerance, and reduce endothelial dysfunction in patients after cardiac arrest and in diabetics. In the years to come, ED may therefore be added to the classical cardiovascular risk factors and could characterize a population with an increased risk of coronary artery disease.     

Pharmaco-écho-doppler pénien: méthodologie, critères diagnostiques et indications actuelles dans l’exploration d’une dysfonction érectile

Erectile dysfunction (ED) is a common multifactorial disease, whose organic or mixed origin is currently considered as dominant in men aged 50 years and older. Most ED classified as arterial are linked to endothelial dysfunction in relation to the key factors of cardiovascular risk. ED is an indicator of vascular health in general. It is also a predictor of cardiovascular events, including coronary heart disease. It has also been associated with lower peripheral arterial disease and stroke. The penile doppler ultrasound examination is actually used relatively infrequently in the management of ED, the etiologic factors being considered most often not necessary for the therapeutic management, but also because of the absence of standardization. Nonetheless, large recent studies have shown that the vascular nature of ED, basis on doppler parameters recorded after intracavernous injection of vasoactive drugs, strengthened the predictive value of ED on events and cardiovascular mortality, justifying a highest interest in this test.     

Erectile Dysfunction Severity as a Risk Marker for Cardiovascular Disease Hospitalisation and All-Cause Mortality: A Prospective Cohort Study

Background

Erectile dysfunction is an emerging risk marker for future cardiovascular disease (CVD) events; however, evidence on dose response and specific CVD outcomes is limited. This study investigates the relationship between severity of erectile dysfunction and specific CVD outcomes.

Methods and Findings

We conducted a prospective population-based Australian study (the 45 and Up Study) linking questionnaire data from 2006–2009 with hospitalisation and death data to 30 June and 31 Dec 2010 respectively for 95,038 men aged ≥45 y. Cox proportional hazards models were used to examine the relationship of reported severity of erectile dysfunction to all-cause mortality and first CVD-related hospitalisation since baseline in men with and without previous CVD, adjusting for age, smoking, alcohol consumption, marital status, income, education, physical activity, body mass index, diabetes, and hypertension and/or hypercholesterolaemia treatment. There were 7,855 incident admissions for CVD and 2,304 deaths during follow-up (mean time from recruitment, 2.2 y for CVD admission and 2.8 y for mortality). Risks of CVD and death increased steadily with severity of erectile dysfunction. Among men without previous CVD, those with severe versus no erectile dysfunction had significantly increased risks of ischaemic heart disease (adjusted relative risk [RR] = 1.60, 95% CI 1.31–1.95), heart failure (8.00, 2.64–24.2), peripheral vascular disease (1.92, 1.12–3.29), “other” CVD (1.26, 1.05–1.51), all CVD combined (1.35, 1.19–1.53), and all-cause mortality (1.93, 1.52–2.44). For men with previous CVD, corresponding RRs (95% CI) were 1.70 (1.46–1.98), 4.40 (2.64–7.33), 2.46 (1.63–3.70), 1.40 (1.21–1.63), 1.64 (1.48–1.81), and 2.37 (1.87–3.01), respectively. Among men without previous CVD, RRs of more specific CVDs increased significantly with severe versus no erectile dysfunction, including acute myocardial infarction (1.66, 1.22–2.26), atrioventricular and left bundle branch block (6.62, 1.86–23.56), and (peripheral) atherosclerosis (2.47, 1.18–5.15), with no significant difference in risk for conditions such as primary hypertension (0.61, 0.16–2.35) and intracerebral haemorrhage (0.78, 0.20–2.97).

Conclusions

These findings give support for CVD risk assessment in men with erectile dysfunction who have not already undergone assessment. The utility of erectile dysfunction as a clinical risk prediction tool requires specific testing. Please see later in the article for the Editors'' Summary     

Mitochondrial dysfunction in cardiovascular disease

Whereas the pathogenesis of atherosclerosis has been intensively studied and described, the underlying events that initiate cardiovascular disease are not yet fully understood. A substantial number of studies suggest that altered levels of oxidative and nitrosoxidative stress within the cardiovascular environment are essential in the development of cardiovascular disease; however, the impact of such changes on the subcellular or organellar components and their functions that are relevant to cardiovascular disease inception are less understood. In this regard, studies are beginning to show that mitochondria not only appear susceptible to damage mediated by increased oxidative and nitrosoxidative stress, but also play significant roles in the regulation of cardiovascular cell function. In addition, accumulating evidence suggests that a common theme among cardiovascular disease development and cardiovascular disease risk factors is increased mitochondrial damage and dysfunction. This review discusses aspects relating mitochondrial damage and function to cardiovascular disease risk factors and disease development.     

La dysfonction érectile au Congo : premières données sur la fréquence de ce motif de consultation et profil clinique au centre hospitalier universitaire de Brazzaville

Objective

To study risk factors and diagnostic investigations results of erectile dysfunction in urologic consultation in Brazzaville.

Method

It was a prospective study, which included 40 patients between 25 and 80 year-old seen for erectile dysfunction in the external urology-andrology consultation of the teaching hospital of Brazzaville, from December 2009 to August 2010. Information obtained from the investigation form included age, past history, risk factors, clinical and nonclinical characteristics and the international index of erectile function (IIEF-5) in its French translation. Epi Info software version 3.5.1 and SPSS 11.5 were used for data analysis. The Chi squared test was used to compare quantitative results and the analysis of variance (ANOVA) for qualitative results. The significance level was 0.05.

Results The frequency of erectile dysfunction was 14.7%, with an average age of 50.7 + 12.3 year-old (27?C77 years). The group 40 to 50 year-old was the most affected. The mean duration was 2.6 + 2.2 years (three months to nine years). Associated diseases were hypertension (22.5%) and diabetes (15%). The risk factors observed were alcoholism (75%), tobacco use (25%) and obesity (12.5%). The erectile dysfunction was severe in 47.5% of cases and severity was correlated with age. It was unbearable in 40% of cases

Conclusion

Erectile dysfunction was found in 14.7% of patients seen in urologic consultation. This number is underestimated because of modesty and taboos.     

Cardiovascular risk factors, erection disorders and endothelium dysfunction

Upon sexual stimulation, penile erection, occurring in response to the activation of pro-erectile autonomic pathways, is greatly dependent on adequate inflow of blood to the erectile tissue and requires coordinated arterial endothelium-dependent vasodilatation and sinusoidal endothelium-dependent corporal smooth muscle relaxation. Nitric oxide (NO) is the principal peripheral pro-erectile neurotransmitter which is released by both non-adrenergic, non-cholinergic neurons and the sinusoidal endothelium to relax corporal smooth muscle through the cGMP pathway. Any factors modifying the basal corporal tone, the arterial inflow of blood to the corpora, the synthesis/release of neurogenic or endothelial NO are prime suspects for being involved in the pathophysiology of erectile dysfunction (ED). In fact, conditions associated with altered endothelial function, such as ageing, hypertension, hypercholesterolemia and diabetes, may, by changing the balance between contractant and relaxant factors, cause circulatory and structural changes in penile tissues, resulting in arterial insufficiency and defect in smooth muscle relaxation and thus, ED. There is increasing evidence to suggest that ED is predominantly a vascular disease and may even be a marker for occult cardiovascular disease. Recent results illustrating the importance of endothelial dysfunction in the pathophysiology of different forms of experimental ED are discussed. These pathways may represent new potential treatment targets.     

Management of Erectile Dysfunction in the Hypogonadal Man: A Case-Based Review

Erectile dysfunction (ED) has emerged as an important marker of cardiovascular and overall health, independent of other known conventional risk factors. ED often precedes coronary artery disease in half of affected subjects, and could indicate the presence of cardiovascular pathology. The pathophysiology and role of androgens in sexual function are described, along with the relevant literature on the effects of aging in erectile and gonadal function. The concept of testosterone supplementation (TST) in men with ED is reviewed. The authors utilize clinical vignettes to discuss the appropriate management of two clinical cases of men at different life stages who have ED in the setting of hypogonadism and propose a treatment algorithm. In patients of all ages, proper identification of the underlying pathophysiology of decreased libido and erectile function is paramount in choosing between the use of TST, phosphodiesterase type 5 inhibitors, or both, in the management of these disorders.Key words: Erectile dysfunction, Testosterone supplementation, Hypogonadism, Phosphodiesterase type 5 inhibitorsErectile dysfunction (ED) has emerged as an important marker of cardiovascular and overall health, independent of other known conventional risk factors. Because ED often precedes coronary artery disease (CAD) in half of affected subjects, it may be considered a harbinger of indolent cardiovascular pathology.^1,2 The modulation of erectile function by testosterone is well known,^3,4 and in men with both hypogonadism and ED a treatment strategy necessitating management of both conditions is required.Phosphodiesterase type 5 inhibitors (PDE5i) and testosterone supplementation therapy (TST) are established treatment strategies for ED and hypogonadism, respectively. Using a PDE5i in combination with TST has the potential for improving efficacy in men with concurrent ED and hypogonadism compared with the use of either agent alone. However, in light of the recent evidence associating testosterone with cardiovascular risk in elderly men,^5,6 TST should be used judiciously in the management of ED in older men.     

Androgénothérapie: Quels sont les risques?

Androgens play an important biological role at all phases of a man’s life. The objective of treatment of androgen deficiency is to maintain physiological testosterone levels. Misuse and abuse of androgen as anabolic steroids are frequent in sportsmen and body-builders or for erectile dysfunction. The main concerns for the potential adverse effects of testosterone treatment are the prostate and the cardiovascular system (lipid metabolism). Liver function must also be monitored. There is no evidence, at the present time, that testosterone replacement therapy in hypogonadal men increases the risk of prostate cancer. Only sporadic cases have been reported. Because of the risk of stimulating an existing prostate cancer, each patient must be monitored every six months (PSA and DRE).     

Cardiovascular Risk Factors Have Larger Impact on Endothelial Function in Self-Reported Healthy Women than Men in the HUNT3 Fitness Study

Background

Several studies suggest that cardiovascular risk factors comprising the metabolic syndrome have larger effects on the development of cardiovascular disease in women than in men. A recent study in self-reported healthy subjects demonstrated a marked gender difference in endothelial dysfunction that may be an important precursor of manifest cardiovascular disease. The aim of the present study was to determine whether the association between endothelial function and cardiovascular risk factors is different in self-reported healthy women compared to self-reported healthy men.

Methods and Results

Associations between endothelial function (flow mediated dilation, FMD, of the brachial artery measured by ultrasound), anthropometric variables, peak oxygen uptake (VO_2peak), blood pressure, serum lipids, blood glucose and a questionnaire on general health and lifestyle including smoking status were studied by logistic and linear regression in 2 528 women and 2 211 men aged 20–89 years, free from self-reported cardiovascular disease. In women with hyperglycemia, endothelial dysfunction (FMD ≤0%) occurred twice as frequently as in male counterparts. The presence of the metabolic syndrome, high blood pressure and low VO_2peak increased the prevalence of endothelial dysfunction more in women than in men.

Conclusion

Endothelial dysfunction is more strongly associated with cardiovascular risk factors in self-reported healthy women than in self-reported healthy men. This finding could explain why the metabolic syndrome, and especially hyperglycemia, is associated with higher cardiovascular risk and a worse prognosis in women.     

Uric acid is a strong independent predictor of renal dysfunction in patients with rheumatoid arthritis

Introduction  

Recent evidence suggests that uric acid (UA), regardless of crystal deposition, may play a direct pathogenic role in renal disease. We have shown that UA is an independent predictor of hypertension and cardiovascular disease (CVD), and that CVD risk factors associate with renal dysfunction, in patients with rheumatoid arthritis (RA). In this study we investigated whether UA associates with renal dysfunction in patients with RA and whether such an association is independent or mediated through other comorbidities or risk factors for renal impairment.     

Endothelial progenitor cells: diagnostic and therapeutic considerations

Endothelial progenitor cells (EPCs) may be defined as adherent cells derived from peripheral blood- or bone marrow-derived mononuclear cells demonstrating acLDL uptake and isolectin-binding capacity. The number of circulating EPCs inversely correlates with the number of cardiovascular risk factors and is reduced in cardiovascular disease. This measurement may therefore serves as a surrogate marker for cardiovascular disease risk. EPC numbers can be modified by various means. However, the effectiveness of risk-factor modification on EPC number and function is currently unknown. Furthermore, EPCs may be used as a potential therapy for a variety of vascular disease states including ischaemia, restenosis and pulmonary hypertension. This review provides an update on multiple factors that affect EPC number as well as highlighting the potential use of EPCs as a novel marker of vascular dysfunction. Furthermore, potential gene- and/or EPC-based approaches to a number of vascular disease states are explored.     

Les dysfonctions érectiles chez le diabétique: Rôle des facteurs neurologiques

Objective

To assess the etiological factors of erectile dysfunction in male diabetics.

Material and methods

We have performed a prospective evaluation including 69 diabetic patients suffering from erectile dysfunction. Studied parameters including age, type and duration of diabetes, complications, treatments and associated risk factors were analysed. Comparison was done with a control group of 138 diabetic patients without erectile dysfunction.

Results

There was a significant difference between the diabetic with neurologic complications and the others without neuropathy (p=0.0004). The duration of the diabete was was another risk factor of erectile dysfunction (p=0.049)

Conclusion

We confirm various authors who demonstrated that diabetic impotence seems to be mainly neuropathic in etiology even though it was a multifactorial discomfort.     

Erectile dysfunction after myocardial infarction--myth or a real problem?

Erectile dysfunction is a common problem whose relation to cardiovascular diseases has scientifically been proved, but it has not been studied sufficiently in patients recovering from myocardial infarction. The objective of this study was to establish the frequency of erectile dysfunction in patients recovering from myocardial infarction. We examined 89 patients (aged 30 to 75 years) included in the program of cardiac rehabilitation after myocardial infarction. The results were compared with 91 healthy examinees of the same age. Even 82% of the patients who recovered from myocardial infarction have problems with erectile dysfunction, compared to 42.9% of healthy examinees. The prevalence of erectile dysfunction increases with the age in both groups. In the group of patients recovering from myocardial infarction aged 30 do 39 years, the erectile dysfunction decreased after 6 months, while in other age subgroups and between controls, there were no significant changes in erectile dysfunction prevalence during the analysed time period. We concluded that erectile dysfunction is a significant problem in patients recovering from myocardial infarction. It should be recognized on time in order to provide a better life quality for the patient with a multidisciplinary approach.     

Serum C‐reactive protein in the prediction of cardiovascular diseases: Overview of the latest clinical studies and public health practice

Cardiovascular disease is the most common cause of morbidity and mortality globally. Epidemiological studies using high‐sensitivity assays for serum C‐reactive protein have shown a consistent association between cardiovascular disease risk and serum C‐reactive protein concentrations. C‐reactive protein is a biomarker for inflammation, and has been established in clinical practice as an independent risk factor for cardiovascular disease events. There is evidence that serum C‐reactive protein is an excellent biomarker of cardiovascular disease and is also an independent and strong predictor of adverse cardiovascular events. Further characterization of the impact and influence of lifestyle exposures and genetic variation on the C‐reactive protein response to cardiovascular disease events may have implications for the therapeutic approaches to reduce cardiovascular disease events. This review summarizes the studies that have examined the association between serum C‐reactive protein and the risk of cardiovascular disease. We also discuss the impact of independent factors and C‐reactive protein genetic polymorphisms on baseline plasma C‐reactive protein levels.     

Is the association between optimistic cardiovascular risk perceptions and lower rates of cardiovascular disease mortality explained by biomarkers of systemic inflammation or endothelial function? A case-cohort study

Background  

More optimistic perceptions of cardiovascular disease risk are associated with substantively lower rates of cardiovascular death among men. It remains unknown whether this association represents causality (i.e. perception leads to actions/conditions that influence cardiovascular disease occurrence) or residual confounding by unmeasured factors that associate with risk perceptions and with physiological processes that promote cardiovascular disease (i.e. inflammation or endothelial dysfunction).     

Biomarkers of endothelial dysfunction,cardiovascular risk factors and atherosclerosis in rheumatoid arthritis

Cardiovascular event rates are markedly increased in rheumatoid arthritis (RA), and RA atherogenesis remains poorly understood. The relative contributions of traditional and nontraditional risk factors to cardiovascular disease in RA await elucidation. The present study comprises three components. First, we compared biomarkers of endothelial dysfunction (vascular cell adhesion molecule [VCAM]-1, intercellular adhesion molecule [ICAM]-1 and endothelial leucocyte adhesion molecule [ELAM]-1) in 74 RA patients and 80 healthy control individuals before and after controlling for traditional and nontraditional cardiovascular risk factors, including high-sensitivity C-reactive protein (hs-CRP), IL-1, IL-6 and tumor necrosis factor-α. Second, we investigated the potential role of an extensive range of patient characteristics in endothelial dysfunction in the 74 RA patients. Finally, we assessed associations between biomarkers of endothelial dysfunction and ultrasonographically determined common carotid artery intima–media thickness and plaque in RA. The three biomarkers of endothelial dysfunction, as well as hs-CRP, IL-1, IL-6 and tumor necrosis factor-α, were higher in patients than in control individuals (P < 0.0001). Patients were also older, exercised less and had a greater waist circumference, blood pressure and triglyceride levels (P ≤ 0.04). Five patients had diabetes. Differences in endothelial function were no longer significant between patients and controls (P = 0.08) only after both traditional and nontraditional cardiovascular risk factors were controlled for. In the 74 RA patients, IL-6 predicted levels of all three biomarkers (P ≤ 0.03), and rheumatoid factor titres and low glomerular filtration rate (GFR) both predicted levels of VCAM-1 and ICAM-1, independent of traditional cardiovascular risk factors (P ≤ 0.02). VCAM-1 was associated with common carotid artery intima–media thickness (P = 0.02) and plaque (P = 0.04) in RA. Patients had impaired endothelial function, less favourable traditional cardiovascular risk factor profiles, and higher circulating concentrations of hs-CRP and cytokines compared with healthy control individuals. Both traditional and nontraditional cardiovascular risk factors contributed to the differences in endothelial function between RA patients and healthy control individuals. IL-6, rheumatoid factor titres and low GFR were independently predictive of endothelial dysfunction in RA. Disease-modifying agents that effectively suppress both cytokine and rheumatoid factor production, and interventions aimed at preserving renal function may attenuate cardiovascular risk in RA.