Erectile dysfunction as a predictor of cardiovascular disease

Although it has been recognized that erectile dysfunction (ED) and coronary artery disease share many of the same risk factors--smoking, dyslipidemia, diabetes and hypertension--just in the past few years several new studies now suggest that ED is an important early marker of the presence of coronary artery disease. Recent analyses suggest that ED symptoms occur prior to coronary artery disease symptoms and may be a predictor of future major cardiovascular events. Some of these new studies also suggest that ED is an independent risk factor for predicting cardiovascular events--that is independent of other well-established risk factors. Taken together, these new studies suggest that when a patient presents with ED, the patient should be questioned about cardiac health and cardiovascular risk factors. If cardiovascular risk factors are identified, they should be worked up and aggressively treated--as treatment of these risk factors may be life-saving.     

Erectile dysfunction and cardiovascular diseases

Erection is a vascular phenomenon under a psychologic control in a hormonal environment. Erectile dysfunction is defined as the inability to obtain and to maintain sufficient erection for satisfactory intercourse. Organic erectile dysfunction results mainly from vascular problems due to atherosclerosis, a process that begins during childhood, and becomes clinically evident from middle age. Endothelial dysfunction is the first step of atherosclerosis. As the endothelial cells recover the sinusoid spaces in the cavernous tissue and because common risk factors for atherosclerosis have been frequently found in patients with erectile dysfunction, it is logical that vascular impotence presents the same pathophysiology of the other vascular diseases. They share a similar pathogenic involvement of nitric oxide pathway leading to impairment of endothelium dependent vasodilatation and structural vascular abnormalities. Circulating markers of endothelial cell damage have been reported in patients with erectile dysfunction while they have not yet presented any other vascular pathology. Endothelial progenitor cells of bone marrow origin that play a role in promoting endothelial repair are also reduced in vascular abnormalities.As penile arteries have the smallest diameter in the vascular network and because atherosclerosis is a systemic disease, erectile dysfunction could be a sentinel symptom of a more generalized vascular pathology. Modifications of reversible causes or risk factors at the base of the pathogenesis of atherosclerosis remain the first approach toward improving endothelial function and associated with chronic exposure to PDE5-I, they could improve or even cure ED and could avoid fatal cardiovascular attacks in the future.     

Erectile dysfunction and cardiovascular risk factors

There are numerous causes of erectile dysfunction (ED), including psychogenic, organic,and mixed psychogenic/organic. Among the organic causes the most common include vascular, neurogenic, endocrine, structural, drug-induced, and others. Some have estimated that nearly one half of all causes of ED in men over 50 years of age are vascular in nature. This article reviews cardiovascular risk factors of ED.     

Erectile dysfunction as a marker for vascular disease

A body of evidence from basic science and clinical research is emerging to provide a compelling argument for endothelial dysfunction as a central etiologic factor in the development of atherosclerosis and systemic vascular diseases (hypertension, dyslipidemia, diabetes, ischemic heart disease, stroke, or claudication). Erectile dysfunction (ED) is another prevalent vascular disorder that, like cardiovascular disease, is now thought to be caused by endothelial dysfunction. In fact, a burgeoning literature is now available that suggests that ED may be an early marker for atherosclerosis, cardiovascular risk, and subclinical systemic vascular disease. The emerging awareness of ED as a barometer for vascular health and occult cardiovascular disease represents a unique opportunity for primary prevention of vascular disease in all men. Although the implications of this relationship for primary and secondary prevention of cardiovascular disease are not fully appreciated, the available literature makes a strong argument for the role of ED as an early marker for the development of significant cardiovascular risk factors and cardiovascular disease.     

Microalbuminuria as an early marker for cardiovascular disease

Excretion of albumin in the urine is highly variable, ranging from nondetectable quantities to milligrams of albumin and even grams of albumin. Microalbuminuria is defined as low levels of urinary albumin excretion of 30 to 300 mg/d. Microalbuminuria is highly prevalent; in hypertensive and diabetic populations, its prevalence varies from 10 to 40%. It is interesting that microalbuminuria also is found frequently in seemingly healthy individuals (5 to 7%). The variable excretion of albumin in the urine is related to the risk for the individual to develop cardiovascular (CV) disease: Absence or very low levels of albuminuria is associated with low CV risk, whereas the CV risk increases markedly with increasing amount of albumin in the urine (even within the now considered normal range). The predictive power of urinary albumin levels for CV risk is independent of other CV risk factors and not only is present in individual with diabetes and/or hypertension but also in healthy individuals. Treatments that lower albuminuria are associated with CV protection, as demonstrated in randomized, controlled trials of patients with diabetes as well as in patients with hypertension. There is preliminary evidence that albuminuria lowering is CV protective in healthy individuals with an elevated albumin excretion rate. Differences between individuals in their level of albumin excretion are already observed at a very early age (just after birth). In fact, the interindividual variability seems to be relatively constant in the first 5 decades of life, indicating that microalbuminuria is not necessarily a consequence of vascular damage at later age. Higher levels of urinary albumin seem to reflect the ordinary interindividual variability in (renal and systemic) endothelial function. Experimental data show that between strains and even within strains, rats at young age show a remarkable difference in individual endothelial function, and this is strongly related to the susceptibility of that rat to organ damage. In conclusion, albuminuria seems to be a sensitive marker very early in life for the susceptibility of an individual to CV disease. It therefore may be an ideal target for early primary prevention using CV-protective therapy regimens.     

Erectile dysfunction in heart disease patients

Atherosclerosis is a general health problem that not only affects the coronary arteries but also (in men) the penile arteries, thus contributing to organic causes of erectile dysfunction (ED) in heart disease patients. These organic causes are intertwined with psychological and pharmacological causes because medication prescribed for heart disease patients may also cause ED. The incidence of ED after myocardial infarction ranges from 38 to 78%. As sexual intercourse involves physical exertion, the medical history, ventricular function determined through echocardiography, and stress testing are used to classify patients into various groups where coital activity represents a greater or lesser cardiovascular risk. The energy requirements for intercourse are not high, ranging from 3.7 metabolic equivalents (METs) of energy expenditure at resting state during the preorgasmic phase to 5 METs during orgasm. The Bruce protocol for exercise stress testing is a six-stage protocol with changes in the slope and speed of the treadmill. As a general rule, a patient who completes the first two stages of the Bruce protocol has a functional capacity greater than 7 METs, which is considered sufficient for sexual intercourse. The physician or cardiologist concerned should institute first-line treatment with oral drugs according to the indications listed below. If sexual activity is not contraindicated, the treatment of choice for ED in heart disease patients is oral therapy with sildenafil, except in those cases in which its use is contraindicated. Specific recommendations are discussed.     

Erectile dysfunction

The past several years have witnessed a veritable revolution in our understanding and management of erectile dysfunction. Although surgical implants in the form of penile prostheses continue to be an important part of treatment of end-stage cases, the largest change has been brought about by the introduction of oral medications, such as sildenafil (Viagra). This review addresses the etiology, epidemiology, diagnosis, and treatment of erectile dysfunction in light of the remarkable advances in the field.     

Erectile dysfunction

In Spain, based on the IIEF, 19% of males between 25 and 70 years old present some degree of erectile dysfunction (ED). Therefore, around 2,000,000 Spanish men present this condition and could require medical attention for it. Here, we present an up-date of the most important aspects of erectile dysfunction (pathophysiology, diagnosis and treatment). We review, in detail, the oral treatments and future drugs that are presently in the premarketing experimental phase. Diagnostic and therapeutic management of the patient with erectile dysfunction should be individualized, taking into account the goals of each patient. It is highly recommendable to carry out a basic assessment (comprehensive clinical history, physical examination, recommended lab testing). If previously undiagnosed diseases are discovered (diabetes, arteriosclerosis, etc.) these should be treated and modifiable risk factors should be corrected. There are numerous therapeutic options for the treatment of erectile dysfunction. Replacement therapy with testosterone should only be used in males with ED and low levels of this hormone, under medical supervision. At present, first line treatment consists of the administration of oral drugs (sildenafil, apomorphine). There are two new PDE 5 inhibitors (tadalafil and vardenafil) that will be released on the market 2003, which will provide better selectivity. Moreover, several drugs for oral administration are in the initial phases of research that will facilitate erection via a direct penile action. When oral drugs are contraindicated, are not effective or when they are unpopular with the patient, the second line of treatment is intracavernous injection. Prostaglandin E1 is the initial drug of choice in patients using intracavernous autoinjection for the first time and has a high efficacy. Implantation of a penis prosthesis and penile revascularisation are appropriate for highly selected patients. Psychotherapy can be an option for men with ED of psychogenic origin, either as a monotherapy or combined with sildenafil or apomorphine.     

Erectile dysfunction

PURPOSE: Male sexual health has taken on increased importance as the United States population ages, develops coexisting medical conditions and undergoes interventions that can affect sexual function. We characterized the burden and severity of disease, treatment patterns and economic consequences of erectile dysfunction. MATERIALS AND METHODS: The analytical methods used to generate these results were described previously. RESULTS: Erectile dysfunction was self-reported by almost 1 of 5 men and it increased with age. Erectile dysfunction may have been more commonly reported in Hispanic men and in those with a history of diabetes, obesity, smoking and hypertension. In most databases black American men had rates of use for office visits and inpatient hospital care that were twice those of other racial groups, although these rates were not controlled for comorbid conditions or other regional and socioeconomic factors. The use of diagnostic tests markedly decreased, while pharmacological therapy, especially with oral phosphodiesterase-5 inhibitors, markedly increased. Penile implant surgery continued to be performed with most patients electing inflatable devices. Extrapolating from the population based estimates of erectile dysfunction prevalence and current use trends showed that the cost of treatment nationwide could reach $15 billion if all men sought treatment. CONCLUSIONS: The burden of disease due to erectile dysfunction in the United States will increase with the aging of the male population, increasing prevalence of comorbid conditions, expanded treatment seeking behavior and costs of pharmaceutical therapy. Accurate estimates of economic cost will require better understanding of pathogenesis, treatment seeking behavior, patient preference for therapies, success of treatments and relative satisfaction with oral pharmacotherapy and penile implants.     

Glomerular proteinuria as an early sign of renal-transplant rejection

The introduction of cyclosporin gave rise to an additional problem in the surveillance of renal transplant patients, namely the differentiation between cyclosporin toxicity and acute transplant rejection. The development of assays for specific proteins in urine has produced a non-invasive solution to this problem. In 55 renal transplant patients the following proteins were determined daily in 24 h-urine samples: IgG, transferrin (TF), albumin, beta 2-microglobulin (beta 2-MG), retinol binding protein (RBP), alpha 1-microglobulin (alpha 1-MG) and alpha 1-antitrypsin (alpha 1-AT). All proteins were determined quantitatively using immunoluminometric assays and 10 microliters urine in dilutions from 1:1-1:100. The urinary protein excretion was related to the actual creatinine clearance as this index gave the best differentiation between normal and abnormal status. In 24 h-urine, intraindividual peaks of IgG, TF and albumin were seen regularly in acute rejection episodes. However, a peak in the "tubular" proteins (RBP, beta 2-MG, alpha 1-MG) could not be detected. After effective treatment of the rejection episode, the renal function improved and the protein excretion returned to prerejection episode levels. In bacterial infection of the urogenital tract, urinary alpha1-AT levels rose. They returned to normal after successful antibiotic treatment. In two cases of cyclosporin toxicity neither glomerular nor tubular proteins were excreted in abnormal amounts when compared with transplant patients without complications, the only changes being an increase in serum creatinine as a result of reduced renal function.     

The flexion-adduction test: an early sign of hip disease

This report introduces the flexion-adduction test as an additional diagnostic technique for hip pathology in children and young adults. Losses of flexion-adduction, internal rotation, abduction and total flexion arc are all individually assessed in patients with confirmed hip pathology. The findings suggest that the "flexion-adduction" test is a simple, but sensitive, clinical procedure to detect the early signs of hip disease in older children and young adults. Although abduction and internal rotation are reportedly the most commonly restricted movements in frequent hip pathologies such as irritable hip, Legg-Calve-Perthes disease and slipped epiphysis, we believe that the loss of flexion-adduction is often the first affected range of movement. A statistical analysis of 87 cases from 1994 to 1997 is presented wherein the clinical loss of flexion-adduction provided the initial suggestion of underlying hip pathology, and concludes that the loss of internal rotation, abduction and flexion arc are not statistically reliable tests for clinically diagnosing pathology individually. Often, despite a positive flexion-adduction test, the other ranges of movements remained unaffected or minimally affected in children and young adults with varying hip diseases, later confirmed through subsequent physical examinations or investigations. A thorough explanation of the flexion-adduction test is provided.     

Erectile dysfunction in patients with coronary artery disease

Recent studies suggest that erectile dysfunction (ED) may be an early marker of endothelial dysfunction and coronary artery disease (CAD). Conversely, patients with CAD commonly have ED. The phosphodiesterase 5 (PDE5) inhibitors are very effective for the treatment of ED in patients with CAD. Numerous studies show that this class of drugs is in general safe in patients with stable CAD and these agents do not exacerbate ischemia in men with CAD undergoing exercise stress testing. Analysis of placebo-controlled trials did not show an increase in cardiovascular events among men receiving PDE5 inhibitors, and post-marketing surveillance studies with sildenafil did not observe an increase in cardiovascular events compared to expected age-matched rates. Organic nitrates remain a contraindication for PDE5 inhibitors and alpha blockers have precautions/contraindications depending upon specific drugs. The Princeton Consensus Guidelines (soon to be updated) suggest a logical approach to the patient with CAD seeking therapy for sexual dysfunction.