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Number 28, 2005 |
Back to the Summary| Abstract
Erectile dysfunction and vascular disease commonly coexist. They share the same risk factors, and endothelial dysfunction is the common denominator. Erectile dysfunction may develop in an otherwise asymptomatic male and be an important predictor of subsequent acute or chronic cardiac events. It may therefore offer an opportunity for risk assessment and therapeutic intervention to reduce the chance of a subsequent cardiac presentation. Cardiac patients with erectile dysfunction need a careful assessment to judge the safety of sexual activity and their suitability for treatment of their erectile dysfunction. When correctly assessed and counseled, patients can safely enjoy sexual activity. Treatment of erectile dysfunction with phosphodiesterase type-5 inhibitors is safe and effective, provided the patient and their partner are advised as to their use and potential drug interactions, especially with nitrates. Keywords: Erectile dysfunction, sexual activity, cardiac patients |
Introduction
When advising cardiac patients concerning sexual activity, it is important to individualize the advice. Although we have a statistical framework that supports our recommendations, each person being advised will have, in addition to a general cardiac condition (eg, post myocardial infarction), varying degrees of restriction of effort – determined by the size of the infarction, for example. In addition, each person will have personal concerns regarding safety of sexual activity, treatment of erectile dysfunction, and their confidence in returning to normal activities, including sex. As we advise on sexual function and activity, we need to remember that these problems may have preceded the cardiac event, with important implications for personal relationships as a consequence.
Cardiovascular response to sexual activity
Several studies performed using ambulatory electrocardiography and blood pressure monitoring have compared the heart rate, electrocardiographic, and blood pressure responses to sexual activity with those to other normal daily activities [1]. The energy requirement during sexual intercourse is not excessive for couples in a long-standing relationship. The average peak heart rate is 110–130 beats/min and the peak systolic blood pressure 150–180 mm Hg, resulting in a rate–pressure product of 16 000–22 000. Expressed as a multiple of the metabolic equivalent of task units (METs) of energy expenditure in the resting state (MET = 1), sexual intercourse is associated with a work load of 2–3 MET before orgasm and 3–4 MET during orgasm. Younger couples, who are not usually the individuals we advise, may be more vigorous in their activity, expending 5–6 MET. The average duration of sexual intercourse is 5–15 min. Therefore, sexual intercourse is not an extreme or sustained cardiovascular stress for patients in a long-standing relationship who are comfortable with each other. Casual sexual intercourse, which must be separated from extramarital sexual intercourse with a long-standing ‘other partner’, may involve a greater cardiac workload because of lack of familiarity and age mismatch (usually older men with younger women), with different activities and expectations [2].
By using our knowledge of METs in the clinical setting, we can advise on sexual safety by comparing sexual intercourse with other activities. Some daily activities and their METs are shown in Table I.
Table I. Metabolic equivalent of task units (METs) as a guide to relating daily activity to sexual activity.
Using METs, sexual intercourse is equivalent to 3–4 min of the standard Bruce treadmill protocol. Where doubts exist as to the safety of sexual intercourse, an exercise test can help guide decision making. If a person can manage at least 4 min on the treadmill without significant symptoms, electrocardiogram (ECG) evidence of ischemia, a decrease in systolic blood pressure, or dangerous arrhythmias, it will be safe to advise on sexual activity [2,3]. Using ambulatory ECGs and bicycle exercise tests, Drory et al [4,5] studied 88 men with coronary artery disease (CAD) who were not receiving medication. On ambulatory ECGs, one-third of the men had ischemia during sexual intercourse and all had ischemia on the bicycle exercise ECG. All those who did not exhibit ischemia on the exercise test (n = 34) also had no ECG changes during sexual intercourse. All ischemic episodes during sexual intercourse were associated with an increasing heart rate, identifying a potentially important therapeutic role for drugs that decrease the heart rate (β-adrenoreceptor antagonists, verapamil, diltiazem).
If a patient is unable to perform an exercise test because of mobility problems, a pharmacological stress test should be utilized (e.g. dobutamine stress echocardiography).
A man who cannot achieve 3–4 MET should be further evaluated by angiography if appropriate [2].
Advice on METs in the clinical setting and relating this advice to sexual intercourse should also include advice on the avoidance of stress, a heavy meal, or excess alcohol consumption before sexual intercourse.
Positions
As long as the couple are not stressed by the sexual position they use, there is no evidence of increased cardiac stress to a man or woman. Man on top, woman on top, side to side, oral sex and masturbation are cardiologically equivalent. In homosexual relationships, other than casual, anal intercourse is not associated with increased cardiac stress, provided proper lubrication is used and amyl nitrate (‘poppers’) is not used in conjunction with a phosphodiesterase type-5 (PDE-5) inhibitor.
Cardiac risk
There is only a small risk of myocardial infarction associated with sexual activity. The relative risk of a myocardial infarct during the 2 h after sexual intercourse is shown in Table II [6]. The baseline absolute risk of a myocardial infarction during normal daily life is low – 1 chance in a million per hour for a healthy adult, and 10 chances in a million per hour for a patient with documented cardiac disease. Therefore, during the 2 h after sexual intercourse, the risk increases to 2.5 in a million for a healthy adult and 25 in a million for a patient with documented cardiac disease; importantly, there is no increased risk in those who are physically active.
Table II. Relative risk of myocardial infarction during the 2 h after sexual activity: physically fit equals sexually fit.
Coital sudden death is very rare. In three large studies, death related to sexual activity was 0.6% in Japan, 0.18% in Frankfurt, and 1.7% in Berlin. Extramarital sex was responsible for 75%, 75%, and 77% respectively, and the victims were men in 82%, 94%, and 93% of cases, respectively [1]. The partnership of an older man with a younger woman was the most common setting.
Vasculogenic erectile dysfunction
Vascular diseases are the most common cause of erectile dysfunction, with endothelial dysfunction now recognized as the common denominator (Figure 1) [8]. Erectile dysfunction and CAD share the same risk factors, which explains the endothelial link (Table III) [9]. However, before attributing erectile dysfunction to a purely vascular cause, it is important to evaluate the patient thoroughly, as other factors may be contributing to the problem or, occasionally, may be the cause. As men age, there may be comorbid conditions that need to be addressed (endocrine, cellular, neural, or iatrogenic such as drug treatment), and organic erectile dysfunction will have psychological consequences for which they require counseling and support.
Table III. Shared risk factors for coronary artery disease and erectile dysfunction (data from [9]).
- Cardiovascular drugs: thiazide diuretics, β-adrenoceptor antagonists, calcium channel antagonists, centrally acting agents (eg, methyl-dopa, clonidine, reserpine, ganglion blockers), digoxin, lipid-decreasing agents, angiotensin-converting enzyme inhibitors, and recreational drugs such as alcohol (ethanol), marijuana, amphetamines, cocaine, anabolic steroids, and heroin (diamorphine).
- Psychotropic drugs: major tranquilizers, anxiolytics and hypnotics, tricyclic antidepressants, selective serotonin reuptake inhibitors.
- Endocrine drugs: antiandrogens, estrogens, gonadotropin-releasing hormone analogs, testosterone.
- Others: cimetidine, ranitidine, metoclopramide, carbamazepine.
There is little evidence that changing cardiovascular drug therapy will restore erectile function, suggesting it is the underlying disease process that is more important. However, if there is a strong temporal relationship between the commencement of treatment and the onset of erectile dysfunction (2–4 weeks), it is logical to change the treatment if it is safe to do so. Antihypertensive agents, especially thiazide diuretics, are the most frequently incriminated, and a switch to angiotensin II receptor antiantagonists or α-adrenoceptor antagonists should be considered [10]. When drugs are prognostically important, such as β-adrenoceptor antagonists used after myocardial infarction, the decision to discontinue treatment should be approached with caution, and undertaken only after overall risks have been considered [3].
Erectile dysfunction and cardiovascular disease
The Massachusetts Male Aging Study [11] was a random-sample, cross-sectional, observational study in 1709 healthy men aged 40–70 years, undertaken to assess the impact of aging on a wide range of health-related issues. Fifty-two percent of respondents reported some degree of erectile dysfunction (17% mild, 25% moderate, 10% complete), and the prevalence increased with age. Cardiovascular disease was significantly associated with erectile dysfunction. The incidence was doubled in patients with hypertension and tripled in diabetic patients; in those with established coronary disease, it was quadrupled. Cigarette smoking increased the prevalence twofold for all these conditions, and a positive relationship was found between reduced high-density lipoprotein cholesterol concentrations and erectile dysfunction.
The association between hyperlipidemia and erectile dysfunction has been studied in apparently healthy men who complained of erectile dysfunction [12]. More than 60% had hyperlipidemia and 90% of these had evidence of penile arterial disease on Doppler ultrasound. Diabetes is commonly associated with erectile dysfunction, with a prevalence of 50% (range 27–70% depending on age and disease severity). The onset of erectile dysfunction usually occurs within the first 10 years of the diagnosis of diabetes [13].
Men older than 50 years who have established CAD have an incidence of erectile dysfunction of 40%; in those who have suffered myocardial infarction or vascular surgery, the incidence ranges from 39% to 64%, depending on diagnostic criteria [14].
Erectile dysfunction as a marker of vascular disease
As erectile dysfunction and vascular disease share the same risk factors, the possibility arises that erectile dysfunction in otherwise asymptomatic men may be a marker of silent vascular disease, especially CAD [15]. This has now been established to be the case and represents an important new means of identifying those at risk of vascular disease.
Pritzker [16] studied 50 men aged 40–60 years who were asymptomatic other than for erectile dysfunction, and had cardiovascular risk factors (several such factors were present in 80% of the group). Exercise ECG was abnormal in 28 of the men and subsequent coronary angiography in 20 men identified severe CAD in six, moderate two-vessel disease in seven, and significant single-vessel CAD in a further seven. In a study of 132 men attending for day-case angiography, 65% had experienced erectile dysfunction before their CAD had been diagnosed [17]. Erectile dysfunction also correlates with the severity of CAD, patients with single-vessel disease having less difficulty in obtaining an erection [18].
The smaller penile arteries (diameter 1–2 mm) suffer obstruction from plaque burden earlier than do the larger coronary (3–4 mm), carotid (5–7 mm), or iliofemoral (6–8 mm) arteries; hence erectile dysfunction may be symptomatic before the occurrence of a coronary event [19]. Addressing cardiovascular risk early after the presentation of erectile dysfunction, and aggressive intervention to reduce risk, may have long-term symptomatic and prognostic cardiac benefits [20]. Most acute coronary syndromes follow from the rupture of asymptomatic lipid-rich plaques, and erectile dysfunction may therefore be a marker for reducing the risk of this happening [21].
Billups and colleagues [22] have developed a risk assessment and management algorithm for primary care patients with erectile dysfunction, with the aim of facilitating early diagnosis, intervention, and prevention of cardiovascular disease.
Any asymptomatic man who presents with erectile dysfunction that does not have an obvious cause (eg, trauma) should be screened for vascular disease and have blood glucose, lipids, and blood pressure measured. Ideally, all patients at risk should undergo an elective exercise ECG to facilitate risk stratification [23].
Treating erectile dysfunction in patients with cardiovascular disease
Recognizing the need for advice on management of erectile dysfunction, two consensus panels (in the UK and the USA) have produced similar guidelines dividing cardiovascular risk into three practical categories, with recommendations for management [2,3]. The Princeton consensus guidelines have recently been updated (Table IV) [3]. It is recommended that all men with erectile dysfunction should undergo a full medical assessment (Figure 2). Baseline physical activity needs to be established, and cardiovascular risk graded as low, intermediate, or high. Most patients with low or intermediate cardiac risk can have their erectile dysfunction managed in the outpatient or primary care setting.
Table IV. Risk from sexual activity in cardiovascular diseases: Second Princeton Consensus Conference.
Phosphodiesterase type-5 inhibitors
To say that sildenafil has transformed the management of erectile dysfunction would be a substantial understatement. Its mechanism of action by blocking the degradation of cyclic guanosine 3′5′-monophosphate (cGMP) by PDE-5 promotes blood flow into the penis and the restoration of erectile function. Vardenafil and tadalafil have been added to this family of drugs [24,25]. Because their mechanism of action is the same, there is no reason to assume there will be any significant differences in their effectiveness in treating erectile dysfunction, but their half-life may be of cardiac clinical importance.
Hemodynamically, PDE-5 inhibitors have mild nitrate-like actions (sildenafil was originally intended to be a drug for the treatment of stable angina) [26]. As PDE-5 is present in smooth muscle cells throughout the vasculature and the nitric oxide/cGMP pathway is involved in the regulation of blood pressure, PDE-5 inhibitors have a modest hypotensive action. In healthy men, a single dose of sildenafil 100 mg transiently decreased blood pressure by an average of 10/7 mm Hg, with a return to baseline at 6 h after the drug was given. There was no effect on heart rate [26]. As nitric oxide is an important neurotransmitter throughout the vasculature and is involved in the regulation of vascular smooth muscle relaxation, a synergistic and clinically important interaction with oral or sublingual nitrates can occur, and a profound decrease in blood pressure can result. The mechanism involves a combination of increased formation of cGMP when nitrates activate guanylate cyclase, and decreased breakdown of cGMP as a result of the action of PDE-5 inhibitors. The concomitant administration of PDE-5 inhibitors and nitrates is thus contraindicated, and this recommendation also extends to other nitric oxide donors such as nicorandil. Clinical guidelines recommend that sublingual nitrate should be taken 12 h after the PDE-5 inhibitors sildenafil or vardenafil [3]; tadalafil, which has a longer half-life, ceases to react with nitrates only after 48 h [27]. Oral nitrates are not prognostically important drugs, and they can therefore be discontinued and, if necessary, alternative agents substituted [28]. After cessation of oral nitrate, and provided there has been no clinical deterioration, PDE-5 inhibitors can be used safely. It is recommended that the time interval before the use of a PDE-5 inhibitor be five half-lives, which equates to 5 days in the case of most popular once-daily oral nitrate agents.
Sildenafil
Sildenafil was the first oral treatment for erectile dysfunction and is the most extensively evaluated [26]. Overall success rates of 80% or more in patients with cardiovascular disease have been recorded, with no evidence of tolerance. Patients with diabetes, with or without additional risk factors, in whom the pathophysiology is more complex and extensive, have an average success rate of 60%. To date, randomized trials, open-label studies, and outpatient monitoring studies have not found the use of sildenafil to be associated with any excess risk of myocardial infarction, stroke, or mortality [29–31].
In patients with stable angina pectoris, there is no evidence of an ischemic effect caused by coronary steal, and in one large, double-blind, placebo-controlled exercise study, sildenafil 100 mg increased exercise time and diminished ischemia [32]. A study of the hemodynamic effects of sildenafil in men with severe CAD identified no adverse cardiovascular effects, and a potentially beneficial effect on coronary blood flow reserve [33]. Studies in patients with and without diabetes have demonstrated improved endothelial function acutely and after long-term oral administration, which may have implications beyond the treatment of erectile dysfunction [26]. Sildenafil has also been shown to attenuate the activation of platelet IIb/IIIa receptor activity [34]. Hypertensive patients receiving monotherapy or being treated with several drugs have experienced no increase in adverse events, with the exception of those receiving doxazosin, a non-selective α-adrenoceptor antagonist. Occasional postural effects have occurred with sildenafil when it was taken within 4 h of doxazosin 4 mg; advice to avoid this time interval is now in place. Sildenafil has also been proved to be effective in patients with heart failure who were deemed suitable for treatment of erectile dysfunction [35]; the incidence of erectile dysfunction in patients with heart failure is 80%, making this finding of major clinical importance. On average, the dose of sildenafil is 50 mg; 25 mg is advised initially for those older than 80 years, because of delayed excretion. A dose of 100 mg is invariably needed in patients with diabetes. An empty stomach and the avoidance of alcohol or cigarette smoking facilitate the effect of the drug. Sildenafil 100 mg has no adverse cardiac effects additional to those associated with the 50-mg dose, and should be routinely prescribed if, after four attempts, the 50-mg dose is not effective.
The short half-life of sildenafil makes it the drug of choice in patients with more severe cardiovascular disease, allowing early use of supportive treatment if an adverse clinical event occurs.
Tadalafil
Tadalafil also has been extensively evaluated in patients with cardiovascular disease, and has a safety and efficacy profile similar to that of sildenafil [36]. Studies have shown no adverse effects on cardiac contraction, ventricular repolarization, or ischemic threshold. A similar hypotensive effect has been recorded with a dose of doxazosin 8 mg, so caution is needed: as hypotension does not occur when the patient is in the supine position, and as tadalafil has a long half-life, it is suggested that tadalafil is taken in the morning and doxazosin in the evening. There is no interaction of tadalafil with the selective α-adrenoceptor antagonist, tamsulosin, which can, therefore, be prescribed as an alternative to doxazosin for benign prostate hypertrophy [37].
Because of its long half-life, tadalafil may not be the drug of first choice for patients with more complex cardiovascular disease. However, as 80% of patients with cardiovascular disease stratify as low risk, it does represent an alternative for the majority.
Vardenafil
Because vardenafil has a chemical structure very similar to that of sildenafil, it is not surprising that it has a similar clinical profile. One study has reported no impairment of exercise ability in patients with stable CAD receiving vardenafil 20 mg [38]. Similar clinical efficiency for all three agents has been observed in patients with diabetes.
Other treatments
When oral agents are not effective, intracavernous injection therapy, transurethral alprostadil, or a vacuum pump are alternatives, requiring specialized referral and advice [2,3]. There is no evidence of increased cardiovascular risk from the use of any of these therapeutic options. If surgical intervention with general anesthesia is being anticipated, a full cardiological risk evaluation is recommended.
Conclusion
Erectile dysfunction is common in patients with cardiovascular disease, and should be routinely inquired about. The cardiac risk of sexual activity in patients with cardiovascular disease is minimal in those who are correctly assessed. The restoration of a sexual relationship is a possibility for the majority of patients with cardiovascular disease and erectile dysfunction, by means of oral PDE-5 inhibitors, which have an excellent safety profile (provided the use of nitrates is avoided). Erectile dysfunction is both a marker for cardiovascular disease and its consequence; therefore, its identification (in the asymptomatic male) provides the opportunity to address other cardiovascular risk factors and detect silent but significant vascular pathology.
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