HealthPeripheral Arterial Disease and Erectile Dysfunction: The Vascular Link

Peripheral Arterial Disease and Erectile Dysfunction: The Vascular Link

The overlap in cardiovascular risk factors for ED and PAD is quite similar. A few larger studies conducted in multispecialty clinics in the USA have reliably shown that men with ED have a higher prevalence of cardiovascular disease and its risk factors when compared to men without ED. High prevalence rates of ED were shown in men with a history of cardiovascular disease (50%), hypertension (61%), smoking (61%), and diabetes (64%). The increasing awareness of a link between ED and cardiovascular disease prompted the American Heart Association to make a Scientific Statement that it may be considered as a risk factor for silent coronary artery disease.

The impact of both ED and atypical leg symptoms due to PAD can have a significant effect on one’s quality of life. A man with ED and PAD may be unable to walk a short distance and thus may avoid sexual intercourse for fear that activity may precipitate leg pain. This, in turn, creates a homeostatic cycle where avoidance of physical activity leads to worsening physical function in both total distance walked and sexual ability.

In a certain subset of patients, typically diabetics, there may be no complaint of leg pain due to a neuropathy. Erectile dysfunction (ED) occurs when a man is unable to achieve and/or maintain an erection sufficient for sexual intercourse. It is a highly prevalent disorder that increases with age. Approximately 50% of men aged 40-70 years experience some degree of ED.

While the classic symptom of PAD is exertional calf, thigh, or buttock muscle pain which occurs during exercise and is relieved by rest (termed intermittent claudication), less than 50% of patients with PAD actually experience intermittent claudication. This prevalence of atypical leg symptoms is, in large part, responsible for the under-diagnosis of PAD in the primary care setting. Without a high index of suspicion and proper evaluation, many patients with PAD will progress to advanced ischemic stages and may ultimately require limb amputation.

PAD is estimated to affect between 8-12 million people in the United States. However, the majority of individuals with the disorder are asymptomatic or have atypical leg symptoms and are likely to seek medical help. They believe the symptoms are a normal part of aging.

Understanding Peripheral Arterial Disease

So, following the series of articles discussing PAD and erectile dysfunction, in which PAD is a cause of ED, we hope to form a better understanding of PAD and its implications. By doing so, we can take steps to better manage or prevent the progression of this debilitating disease.

The more you understand about your condition, the easier it will be to manage. However, the news about PAD is not all bad. The disease is often unrecognized or dismissed as normal aging, when in reality it is a sign of atherosclerosis. In many cases, this early diagnosis of PAD can be used as a warning of potentially preventing a future heart attack or stroke. By taking steps to improve health and lifestyle, the symptoms and progression of PAD can also be effectively treated.

A study in 2000 by the National Health and Nutrition Examination Survey (NHANES) found the prevalence of PAD to be 4.3% in the US. This study also showed that those suffering from PAD were likely to have co-existing CAD and a history of stroke. This demonstrates the seriousness of PAD; it is a common and often debilitating disease. Contributing a high financial cost on healthcare, it impairs functional status and reduces quality of life.

The most common cause of PAD is the fatty deposits in the inner lining of the artery. Fatty deposits cause the arteries to harden and narrow. This condition is called atherosclerosis. PAD is like coronary artery disease (CAD), but it occurs in the arteries which supply blood to the brain, arms, legs, and pelvis, as opposed to the arteries of the heart and brain. PAD also has stable coronary artery disease (CAD). This means those suffering from PAD have a higher risk of heart attack and stroke. High cholesterol, high blood pressure, smoking, diabetes, and age are the risk factors that affect both CAD and PAD.

Peripheral arterial disease can be simply defined as a circulation problem in which narrowed arteries reduce blood flow to your limbs. When you develop peripheral artery disease (PAD), your extremities, usually legs, don’t receive enough blood flow to keep up with demand. This causes symptoms, especially pain, with activity. Over time, the reduced blood flow can cause damage to the limbs. If severe enough, PAD can lead to the amputation of a foot or leg.

Causes of Peripheral Arterial Disease

The second most common cause of PAD is Buerger’s disease. This disease mainly affects the small and medium-sized arteries and veins in the arms and legs and is strongly associated with smoking. Buerger’s disease causes the vessels to constrict and reduces blood flow to the distal extremities. This can cause pain in the fingers and toes that may be followed by ulcers and infection of the extremities. If the impaired blood flow to the fingers and toes is not restored, the tissue in these areas will die and become gangrenous.

There are a variety of potential causes of PAD; however, atherosclerosis accounts for the vast majority of cases. Atherosclerosis occurs when plaque consisting of cholesterol, fat, calcium, and other substances in the blood builds up in the arteries, causing them to narrow and become less flexible. Plaque tends to accumulate at arterial branch points, and it can completely clog an artery, stopping the flow of blood to tissue nourished by that artery. Tissues deprived of an adequate blood supply of oxygen and nutrients will not function properly. Atherosclerosis is accelerated by certain risk factors, including high blood pressure, high cholesterol, tobacco use, diabetes, as well as a family history of premature heart disease. High blood levels of homocysteine, an amino acid larger amounts of which are associated with heart disease and other artery diseases, have also been linked to atherosclerosis. In addition, an increased level of lipoprotein small particle density is more strongly related to this disease than high levels of the traditional measure of LDL cholesterol. On the other hand, light to moderate alcohol consumption has been associated with a lower prevalence of PAD in a number of studies. A possible reason for the alcohol-PAD association is the increase in HDL-cholesterol, which is the result of alcohol consumption.

Symptoms and Diagnosis

The physical examination may be normal in patients with mild to moderate intermittent claudication. Decreased or absent pulses and/or decreased blood pressure in the affected limb(s), and the presence of a bruit over the femoral or popliteal artery, are suggestive of arterial insufficiency in a limb with no gross oedema, hair loss, or nail dystrophy. The presence of these latter abnormalities is usually indicative of more advanced disease. In severe ischaemia, the affected limb may exhibit muscle atrophy and decreased skin thickness with a shiny appearance, and there may be the development of ulcers or blackened, non-healing wounds. These latter findings are generally indicative of critical limb ischaemia and may signal the need for medical intervention to prevent limb loss. In this setting, it is important to differentiate between ischaemic and neurotrophic ulcers or wounds, which occur in the setting of diabetic neuropathy and are not related to arterial insufficiency. Duplex ultrasound scanning can provide additional information, helping to differentiate between these different types of wounds and the underlying pathophysiology.

The most frequent symptom of PAD in the lower extremities is a painful muscle calf or buttock muscle with exercise, alleviated by rest (termed intermittent claudication). The clinical event of critical limb ischaemia, defined as ischaemic pain at rest or a non-healing wound, is less common, occurring in approximately 1% of patients with PAD annually. On occasion, patients with PAD may be asymptomatic or have atypical leg fatigue or a feeling of heaviness with function, making the physical diagnosis of PAD challenging.

Treatment Options

It is important to reduce controllable risk factors for PAD in effort to halt progression of the disease. Lifestyle changes and medical management are effective ways to stop the advancement of PAD and improve symptoms of the disease.

Amputation: In severe cases of PAD, especially when critical limb ischemia has developed, amputation of the affected toe, foot, or leg may be the only option to remove dead tissue and reduce risk of infection.

Surgery: For some people with PAD, surgical intervention may be necessary. The most common procedure is an arterial bypass. This surgery involves using a healthy blood vessel from another part of the body to bypass the blocked artery. This allows for improved blood flow to the area being treated.

Angioplasty and stenting: Your doctor may perform a minimally invasive endovascular procedure to open a blocked artery. In angioplasty, the doctor inflates a small balloon inside the artery to widen the vessel, then deflates and removes the balloon. A stent is often placed during angioplasty to help keep the artery open. A stent is a small mesh tube that acts as a scaffold to provide support inside the artery. Some stents are coated with medication to help keep your artery open (drug-eluting stents).

Medical treatments: Several drugs are available for treating leg symptoms of PAD. These drugs include pentoxifylline, cilostazol, and statins. If you have PAD and high blood pressure, your doctor may prescribe an ACE inhibitor, such as ramipril.

Exploring Erectile Dysfunction

3.1 Causes of Erectile Dysfunction As with other cardiovascular diseases, the development of ED is primarily a vascular problem. In the Massachusetts Male Aging Study, 52% of subjects aged 40-70 had some degree of ED. There was a strong relationship between the presence of ED and the history of angina, myocardial infarction, or stroke. Compared to men without ED, men with ED had a 30% greater chance of having one of these diseases. An analysis of data from the Health Professionals Follow-up Study, involving 25,096 men aged 56-91, provided detailed information on the relationship between ED and the level of concomitant cardiovascular disease. The age-adjusted relative risk of developing ED for men with a history of cardiovascular disease was 1.5. A recent paper has detailed the extent of endothelial dysfunction in men with ED and no reported cardiovascular disease, concluding that ED is a sensitive indicator of endothelial dysfunction and subclinical atherosclerosis.

Erectile dysfunction (ED) may result from a variety of factors, including neurological, hormonal, arterial, and cavernosal abnormalities. Damage to the cavernous nerve is known to be a common and often undiscussed cause of ED. In men with diabetes, the prevalence of ED is strongly age-related. In a large multinational study, 68% of diabetic men aged 60-69 had ED. The severity of ED has been shown to correlate with the extent of peripheral neuropathy; men with the presence of a biodthesiometer measure indicative of more severe loss have significantly higher rates of ED.

Causes of Erectile Dysfunction

It is in the area of diseases of the arteries that the link between erectile dysfunction and peripheral arterial disease is most certain. Peripheral arterial disease is a manifestation of atherosclerotic narrowing of the arteries throughout the body. The same changes in arteries that cause heart disease can cause erection problems. Atherosclerosis often results in a partial or total blockage of the arteries leading to the penis, and prevents a man from having an erection. The same disease affecting the arteries in the heart is an early warning sign that a patient is at high risk of a heart attack, suggesting that the onset of erectile dysfunction in men with atherosclerosis may be an indicator of a cardiovascular event. J.M. Mock et al demonstrated that men with well-documented coronary heart disease were nearly 50% more likely to develop erectile dysfunction than men without the disease, further showing how closely erectile dysfunction is linked with diseases harming the heart and arteries.

Physical impotence can be caused by many conditions, including diabetes, diseases of the testes and pituitary gland, hypertension, heart and vascular disease, and other diseases. Hardening of the arteries, which restricts blood flow to the penis, is often the cause of this disorder. Reduced blood flow into the penis can be due to a number of conditions other than diseases of the arteries, and can be treated on the lines of surgery. This includes bypassing blocked or narrowed arteries with a vein from the leg. This can often be performed in younger patients where the problem is due to a specific injury to the pelvis, such as a fracture or a direct blow.

Symptoms and Diagnosis

Lastly, angiokeratomas of the penis can be used as a visible sign to gauge the symptoms of erectile dysfunction and the finding of chronic penile ischemia.

An additional procedure taken to determine ED is duplex Doppler ultrasonography. This information obtained from this test is a significant determinant in understanding the neurovascular aspect of erection. Blood flow to the penis can be determined by studying the peak systolic velocity and end diastolic velocity. A more advanced tool used to diagnose the condition of ED is penile angiography, and it is reserved for situations of diagnostic uncertainty or for those likely to undergo intracavernous injection testing or penile vascular surgery.

The most common tool to test for erection problems is biothesiometry. It measures penile vibration and is often used to distinguish between psychogenic and organic impotence. In a study involving male subjects without erectile dysfunction, it has been concluded that penile vibration threshold values were significantly higher in older men than in younger men, suggesting a decline in penile nerve function with aging. This testing also allowed comparison of the vibratory perception threshold, a determination of the integrity of the peripheral nervous system with the penile nervous system, between diabetics and non-diabetics.

A physical examination is necessary for every patient, emphasizing the identification of characteristic predisposing and precipitating factors in order to diagnose the exact cause/s of erectile dysfunction. These conditions may consist of diabetes, peripheral vascular disease, any neurologic disease, chronic renal failure, endocrine disorders, or hypogonadism.

Symptoms of ED can be broken down in simple terms. Failing to have an erection one time is not a significant symptom, but if it reoccurs, it is a sign that you may be suffering from erectile dysfunction. ED can also be defined as the inability to maintain an erection long enough to engage in sexual intercourse.

Treatment Options

Data from the Massachusetts Male Aging Study have estimated the prevalence of erectile dysfunction among 40- to 70-year-old men to be 52%. Discussing the problem with the patient and offering him a chance to seek treatment is the first step towards a better sex life. After ruling out a psychogenic explanation and documenting normal nocturnal erections through the course of a full erection and detumescence cycle at least two or three times using stamp test or RigiScan monitor, referral to a urologist is the next step. Often, however, the patient has already tried one or more of the available oral treatments with minimal success. It is important to determine if the problem truly is a lack of efficacy with the oral PDE5 inhibitors or if other conditions might be interfering. These same medications may be more effective if a man can increase his level of physical activity and improve his cardiovascular health to the point where PDE5 inhibitors alone are sufficient in treating the condition. The next step is diabetes optimization. Suboptimal glucose control is a major contributing factor for erectile dysfunction in men with diabetes. Implementing an aggressive treatment to control hyperglycemia means adequate glycemic and weight control with efficient management of atherosclerotic complications, microvascular and neuropathic disease. This is likely more effective for type 2 diabetics with less severe ED than those with type 1 diabetes whose ED is more severe and multifactorial. Nonetheless, it is an essential component of any diabetes management program and has been shown to either prevent the development of erectile dysfunction or slow its progression and be more likely to do so in men with good glycemic control.

The Vascular Link between Peripheral Arterial Disease and Erectile Dysfunction

Given the similarities between risk factors for PAD and those for CVD, including diabetes and metabolic syndrome, it is reasonable to expect that there is an association between ED and PAD. However, it is not known whether they share a common vascular etiology.

Similar findings have been reported from the Massachusetts Male Aging Study (MMAS), a longitudinal study of men aged 40 to 70 years. In the MMAS, data on the incidence rates of moderate to complete ED, taken from questionnaires, were compared between men with and without risk factors for symptomatic CVD. After adjusting for age and other risk factors, the relative risk of developing ED in men with the following risk factors was approximately 1.5 to 3.0 times higher compared with men without the risk factor. This study suggests that ED is particularly sensitive to CVD risk factors and that it may serve as a powerful early marker of CVD.

In multivariate analyses adjusting for age and other risk factors, men with diabetes had a twofold increase in the relative risk of ED compared with age-matched men without diabetes. High cholesterol and triglyceride levels, hypertension, and obesity were all associated with increased odds of experiencing ED. The investigators concluded that ED is highly prevalent and correlates with a cluster of CVD risk factors in men with diabetes.

Emerging evidence suggests that ED is an early surrogate marker of cardiovascular disease and a harbinger of systemic atherosclerosis. The most compelling evidence to support this hypothesis is the link between ED and CVD in men with diabetes. The Strong Heart Study included a case control sub-study at the time of a baseline visit in 1989 through 1991 in Oklahoma among Native Americans. The purpose of the erectile dysfunction (ED) sub-study of the Strong Heart Study (SHS) was to determine the prevalence and correlates of ED in Native Americans with and without diabetes.

Erectile dysfunction (ED) and peripheral arterial disease (PAD) share a number of risk factors, including hypertension, smoking, diabetes mellitus, and metabolic syndrome. Because of this association, investigators have sought to better understand whether ED and PAD are similar manifestations of systemic cardiovascular disease and whether they are caused by a common etiology.

Mechanisms and Pathophysiology

Penile erection is dependent on the relaxation of smooth muscle and penile arterial dilatation, and is a haemodynamic event. In contrast to the more familiar risk factors of age, diabetes, and hypertension that are associated with ED, the majority of men with ED associated with PAD are current or former smokers, frequently with a heavy smoking history. It is well established that smoking is the single most important risk factor for intermittent claudication and critical limb ischemia, the two most severe clinical manifestations of PAD. There is evidence to suggest that smoking may have specific effects on penile arterial structure and function, as we have recently demonstrated in a study comparing cavernosal artery ultrasound studies of non-diabetic smokers and non-diabetic non-smokers with and without a history of ED. Smokers with ED were found to have a significantly higher prevalence of cavernosal artery atherosclerosis and increased cavernosal artery intima media thickness when compared with non-diabetic non-smokers with no history of ED. This effect was also seen in non-diabetic smokers without ED when compared with non-diabetic non-smokers. The presence of atherosclerosis and greater intima media thickness of the cavernosal artery was also associated with an increased prevalence of abnormal penile vascular function, and it is likely that these findings are explained by a direct effect of smoking on the penile vasculature. Hostility and depressive symptoms have been associated with ED and are prevalent in men with PAD and established CHD. We have recently demonstrated that the presence of depression and particularly depressive symptoms are independent risk factors for vasculogenic ED and are strongly associated with abnormal penile vascular function. This is of fundamental importance to the question of the causal link between PAD and ED; if depression were an established risk factor for PAD, an alternative explanation for the association between PAD and ED might be that the same risk factors lead to the development of both PAD and ED. However, given that depression is not a risk factor for PAD, the association between depression and ED in men with PAD strongly suggests that there are pathophysiological processes induced by systemic atherosclerosis that affect penile vascular function.

Clinical Studies and Evidence

The Olmsted County Study of Urinary Symptoms and Health Status Among Men found similar results when the association between ED and concomitant cardiovascular disease was evaluated. This cross-sectional, community-based survey was conducted among a random sample of men living in Olmsted County, Minnesota. Erectile dysfunction was assessed by using the five-item version of the International Index of Erectile Function, and combined with other factors, such as patient age and comorbidities, to predict the presence of cardiovascular disease. It was concluded that ED is independently associated with increased risk of cardiovascular disease in middle-aged men. This study not only provides evidence of a strong link between ED and cardiovascular disease, but is also unique in that it focuses on an unselected population of men who were not seeking treatment for ED or cardiac symptoms.

During the course of the study, it was found that ED was significantly associated with both the prevalence and the incidence of IHD across all subgroups. Specifically, men with more severe ED had an increased relative risk of a major adverse cardiovascular event, defined as myocardial infarction, stroke, revascularisation or death, compared to men with lesser degrees of ED. While the etiological association between ED and IHD cannot be definitively established by this observational data, this study adds to the mounting evidence that severity of ED is a marker for undetected subclinical cardiovascular disease.

In the multinational, 12-week, randomised, placebo-controlled Erectile Dysfunction and Ischaemic Heart Disease (IHD) study, nearly 3000 men aged 35-75 years were screened for ED and cardiovascular risk factors. All participants then underwent exercise stress testing as a screen for IHD; those with a positive stress test, history of IHD or taking nitrates were not eligible for randomisation. Of the randomised subjects, 1515 had at least one risk factor for IHD and thus were considered to be at increased risk in this mixed primary and secondary prevention population.

The progression of CAD is a process that antedates symptomatology, a principle that has been confirmed by multiple studies assessing subclinical CAD in populations of men with ED. Subjects with vascular risk factors are at increased risk for silent CAD and may present with ED as their inaugural symptom of cardiovascular disease.

Implications for Treatment

The vascular association between ED and PAD raises the possibility that the risk factors and initiation mechanisms for atherosclerosis in one vascular bed could be addressed by prescribing interventions aimed at another target area of the vasculature. This theory has been supported by the known benefits of cardiovascular risk factor modification, such as smoking cessation, lipid lowering and anti-hypertensive therapies, and good glycemic control, upon both ED and PAD. However, the only randomized controlled trial of an ED intervention and a PAD outcome was the RUPED study, which showed that 6 weeks of sildenafil therapy in men with type 2 diabetes and ED produced a significant improvement in brachial artery flow compared with a placebo-controlled group. Although these results are encouraging and provide evidence of a systemic vascular effect of a known ED therapy, further research is still required to determine whether an improvement in ED symptoms can lead to a reduced incidence of clinical cardiovascular events or improvement in established PAD. The evidence showing that men with ED and no cardiac symptoms have a high prevalence of silent CAD suggests an opportunity for early identification of men at an increased cardiovascular risk. Using the non-invasive techniques of EPCU and penile color Doppler ultrasound, it may be possible to identify structural and functional abnormalities in the penile vasculature of borderline CAD patients before they develop symptomatic cardiovascular disease. This could allow initiation of preventative measures aimed at preserving cardiovascular and erectile function in a group of patients who may not otherwise be identified as being at risk.

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