Managing Concomitant Cardiac Disease and Erectile Dysfunction

OPTIMIZING THE MANAGEMENT OF ED Managing Concomitant Cardiac Disease and Erectile Dysfunction Richard A. Stein, MD Weill Cornell Medical Center, New York, NY and Brooklyn Hospital Center, Brooklyn, NY 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. [Rev Urol. 2002;4(suppl 3):S39–S47] © 2002 MedReviews, LLC Key words: Erectile dysfunction • Cardiovascular disease • Coitus • Myocardial infarction • Sildenafil citrate he physician caring for a patient with erectile dysfunction (ED) is often placed in the position of dealing with this clinical presentation in the context of cardiovascular disease. The association of ED and cardiovascular disease is greater than would be expected on the basis of age and gender alone. In the Massachusetts Male Aging Study,1 ED was associated with increasing age and several atherosclerotic vascular disease risk factors. An elevated low-density lipoprotein (LDL) T VOL. 4 SUPPL. 3 2002 REVIEWS IN UROLOGY S39 Managing Cardiac Disease and ED continued cholesterol or low high-density lipoprotein (HDL) cholesterol, diabetes mellitus, hypertension, or smoking at entry into the prospective cohort study was associated with a nearly 4-fold increase in the risk of developing ED for a single factor, and a greater likelihood of developing ED if multiple factors were present. Essentially, the risk factors for ED are the same as the risk factors for coronary artery disease (CAD). joint American College of Cardiology/ American Heart Association–sponsored expert panel consensus statement regarding the use of sildenafil in patients with cardiovascular disease4; 2) a statement on the use of sildenafil in the management of sexual dysfunction in patients with cardiovascular disease presented under the auspices of the Heart and Stroke Foundation of Canada and the Canadian Cardiovascular Society5; Essentially, the risk factors for ED are the same as the risk factors for coronary artery disease. Given these findings, it is not surprising that CAD is a powerful indicator of the presence of or development of ED, and the greater the extent of the heart disease the greater is the likelihood of ED. Dhabuwala and colleagues2 noted that 42% of their male patients who had a myocardial infarction (MI) reported ED. Greenstein and associates3 reported, in a study of 40 men with CAD, that patients with multi-vessel CAD were more likely to experience ED than were men with single-vessel disease. An additional consideration is the presence of occult (not known to the patient or the physician) CAD. Occult CAD increases with age, and studies of CAD by nuclear imaging have suggested that in patients at age 70 more than 33% of CAD is occult. In this context, the physician treating ED will confront cardiovascular disease as a “comorbidity" in a significant number of patients and must appropriately adapt the clinical evaluation to meet the patient presentation. Several documents, published in 1999, address aspects of the medical management of ED—in most cases the prescribing of sildenafil citrate in patients with known or suspected cardiac disease. These include 1) the S40 VOL. 4 SUPPL. 3 2002 and 3) the recommendations of the Princeton Consensus Panel for the management of sexual dysfunction in patients with cardiovascular disease.6 The latter document was drafted after the ACC/AHA consensus statement and addresses, in a focused manner, the evaluation of the ED patient with known or possible cardiovascular disease and the use of sildenafil. The basis for the evaluation and management of ED in the setting of cardiovascular disease, which is the focus of this review, is the knowledge base regarding the cardiovascular response to coitus, the risk of acute cardiovascular events during or following sexual activity, and the interaction of sildenafil, a phosphodiesterase 5 inhibitor, with this physiology and pathophysiology. The Cardiovascular Response to Sexual Activity The response of the cardiovascular system to coitus and other sexual activity has been the subject of a number of studies in the recent past. These studies have been conducted against the backdrop of a popular “mythology" in the lay and health care provider community concerning the intensity of the physiologic REVIEWS IN UROLOGY response to coitus and orgasm, and the belief that sexual activity represents a significant risk in patients with known or occult CAD. In part, this perception was fostered by the work of Bartlett,7 published in 1956, and Masters and Johnson,8 published in 1961. They were among the first to study heart rate (HR) and blood pressure (BP) in student couples engaging in coitus in a “private" laboratory room. Early Studies of the Physiological Response to Coitus Bartlett studied three couples engaged in coitus in an experimental room with wires going through the wall and the couples signaling the stages of coitus, intromission, orgasm, and withdrawal by hand-held buttons. They noted that peak heart rates occurred at orgasm and were a mean of 170/min. A follow-up study was performed with couples wearing mouthpieces that permitted the collection and analysis of expired air during coitus. Respiratory rates and tidal volumes were noted to increase in all subjects (the highest respiratory rate noted during orgasm was 60/min), and minute volumes were in the range expected during moderateto-severe exertion. Masters and Johnson measured heart rates and blood pressure and found that heart rates in males ranged from 140/min to 180/min. Blood pressure was measured via a “through-the-wall" sphygmomanometer tube, and mean values for systolic BP increased by 80 mm Hg and for diastolic BP by 50 mm Hg during coitus. The potentially confounding impact of performance anxiety, coitus among non–longterm sex partners, and having their data “watched" in the next room during the coitus, was not fully addressed, and these heart rates and blood pressures became the “working numbers" for the next several years. Managing Cardiac Disease and ED “At-Home" Studies and "RealWorld" Data on the Cardiac Response to Coitus In 1970, Herman Hellerstein and Ernst Friedman of the Cleveland Clinic published their findings on men who were enrolled in a cardiac rehabilitation program and were sexually active with their spouses.9 A total of 91 patients responded to a questionnaire regarding sexual frequency and symptoms, and 14 of these subjects engaged in coitus at home with their spouses (usual place, time, partner, position, and foreplay) while wearing 24 hour ambulatory EKG recorders. Hellerstein and Friedman noted significantly lower peak heart rates—a mean of 117.4/min, with a range of 90/min to 144/min at orgasm in 14 subjects—than were reported by Bartlett and by Masters and Johnson. The HellersteinFriedman patients were older (mean age, 47.5 years), and their cardiorespiratory fitness, assessed by the measurement of maximum oxygen consumption during maximal exercise–EKG testing, was similar to that reported for ambulatory, middle-aged normal subjects. Of interest is that the 24-hour ambulatory EKG recording often noted heart rates that exceeded those achieved at coitus when the patient was engaged in occupational or home recreational activities. Hellerstein and Friedman’s data is important to our understanding of the physiological response to coitus in the “usual" patient of interest—a middle-aged, normally active male who engages in coitus with a longterm, stable sex partner. Their finding of a peak heart rate—and by extrapolation, peak myocardial oxygen requirement (estimated from changes in the “double product" of HR  BP systolic)—that was well below maximum values and was frequently exceeded during daily activities, placed the cardiac response to coitus in the “real-world" range. Their measurement of minute oxygen consumption at coital heart rates denotes that coitus, in the usual manner in middle-aged men, imposes only a modest physiologic cost. Stein10 studied coital heart rates with ambulatory EKG recorders and maximum oxygen consumption with treadmill exercise–EKG testing in postmyocardial infarction men, before and after a 16-week bicycle ergometer exercise training program. Peak coital heart rates prior to exercise training were a mean of 127/min (range, 120–130/min). After the 16-week exercise program, a training effect was confirmed by an 11.5% increase coital heart rates in eight healthy adult males. This was of interest because clinicians were counseling post-MI patients to use a woman-ontop position on the assumption that it would be associated with a lower work level and a lower cardiac oxygen requirement. Their subjects triggered an automatic blood pressure machine prior to coitus and at orgasm. The subjects engaged in a total of 35 episodes of coitus with their spouses in their own homes. Peak coital heart rates (mean of 114/min with the man on top and 117/min with the woman on top) were not significantly changed with the position, as was the case with blood pressures (163/81 mm Hellerstein and Friedman noted significantly lower peak heart rates—a mean of 117.4/min, with a range of 90/min to 144/min at orgasm in 14 subjects—than were reported by Bartlett and by Masters and Johnson. in mean peak minute oxygen consumption. Peak coital heart rates fell modestly but significantly compared with the heart rates in a control group. A training effect is expected to reduce peak heart rates at given exercise levels, consequent to an enhanced oxygen-extraction capacity of the trained muscles, with a consequent reduction in the cardiac output requirement. The reduction in coital heart rates suggests that the heart rate achieved during coitus is responsive, at least in part, to the same demands as endurance training “aerobic" activities. The Impact of Coital Position Further measurements of heart rates at home were obtained, using ambulatory EKG recording, by Eleanor Nemec and colleagues from the University of Washington in Seattle.11 They studied the impact of coital position (man-on-top versus woman-on-top) on peak achieved Hg for the man on top, and 161/77 mm Hg for the woman on top) and double product (HR  BP systolic). The mean peak coital heart rates were 61% of the age-predicted maximum heart rates for their subjects. They noted that there is no physiologic rationale for counseling men to alter a man-on-top coital position. These studies, in contrast to the early studies of Masters and Johnson and Bartlett, measured the physiological response to coitus in as usual and noninstrumented a manner as possible. The strength of such data is the relevance of their findings to “real-life" coitus. The weakness of “at-home" measurements is that blood pressure depends on automatic cuff inflation, and sound discernment and timing is left to the subjects; thus, they may miss orgasm by important seconds. In addition, the measurement of peak oxygen consumption, the most definitive method of establishing coital workload and VOL. 4 SUPPL. 3 2002 REVIEWS IN UROLOGY S41 Managing Cardiac Disease and ED continued the percentage of peak exercise capacity represented by coitus, cannot be measured. Laboratory Evaluation of the Physiological Response to Coitus Bohlen and colleagues12 used a highly instrumented protocol in order to study, in the most comprehensive manner to date, the physiological response to coitus in the laboratory setting. Ten married couples participated in four sexual activities on different days in a “laboratory room," with data-recording tubes and cables passing through a wall. The men were young (mean age, 33.2 years) and very fit (VO2max was a mean of protocol included rest-baseline, foreplay, and stimulation-orgasm. The authors expressed VO2 in terms of METs (1 MET = 3.5 mL O2/kg/min). VO2 was only modestly increased during self- and partnerstimulation (1.7 and 1.8 METs), and it was 2.5 METs for woman-on-top and 3.3 METs for man-on-top coitus. The latter value represents a VO2 of 11.7 mL/kg/min, which, interestingly, is close to the same value obtained by Hellerstein and Friedman. The Bohlen data provide the most comprehensive evaluation of the physiological response to coitus available. The study is, however, limited in its application to clinical situations in In studies that compared heart rates during the day with those at peak sexual activity, there were usually several instances of higher values during daily activities than during peak coital activity. 54/mL/kg). Data collected included HR, BP, and VO2. The four sexual activities included coitus with the husband on top, coitus with the wife on top, noncoital stimulation of the husband by the wife, and self-stimulation by the husband alone. The stages of sexual activity that were recorded included 1) baseline resting, 2) foreplay, 3) stimulation, and 4) orgasm. Heart rates were noted to increase at each stage of sexual activity, with peak values occurring at orgasm. Mean peak heart rates at orgasm with self-stimulation and partner-stimulation were 102/min, with wife-on-top coitus were 120/min, and with husband-on-top coitus were 127/min. Double products (HR  BP systolic), reflecting myocardial oxygen demand, were approximately doubled with self-stimulation and partner-stimulation and were not significantly different from these values in either of the coital positions. Minute oxygen consumption obtained during the S42 VOL. 4 SUPPL. 3 2002 that the subjects were exceptionally fit young men, who were highly instrumented (including facemasks to collect expired air) during coitus that was performed in a “laboratory setting." The lower heart rates they noted most probably reflected the high level of fitness of their subjects, consistent with Stein’s data demonstrating a reduced peak coital heart rate after exercise training and consequent enhancement in VO2max. A concern regarding the relevance of the above-noted blood pressure data is that the time involved in inflating and slowly deflating the cuff to permit the identification of clear sounds may miss a very brief significant elevation in blood pressure. This is suggested from data collected by Stewart Mann and colleagues from Harrow, England.13 They utilized indwelling radial artery catheters to record continuous blood pressure for a 24-hour period in a significant number of untreated hypertensive REVIEWS IN UROLOGY patients. Eighteen of their subjects engaged in coitus during the recording period. Surprisingly high peak coital blood pressures were recorded (mean, 237/138 mm Hg). Their data raises the possibility that normal subjects or treated hypertensive patients may also have very brief, significant elevations in blood pressure. The physiological significance of such very brief elevation in blood pressure would be minor. Of greater concern is that this may create shear forces across an atherosclerotic plaque that could “trigger" plaque fracture or erosion and cause subsequent thrombus formation and acute MI. It is clear that multiple studies addressing heart rates and blood pressure during coitus and measuring or estimating workload and minute oxygen consumption have produced, by and large, consistent data. Peak coital heart rates were noted to be in the 114/min to 130/min ranges, with the higher values found in younger subjects, and the percentage of the age-predicted maximum was close to 60% in several studies. In studies that compared heart rates during the day with those at peak sexual activity, there were usually several instances of higher values during daily activities than during peak coital activity. Blood pressures rose approximately 40 mm Hg in both home-ambulatory and laboratory settings. The data presented by Mann and colleagues from the United Kingdom are a source of concern and suggest that a very transient, significant elevation (above 220 mm Hg) in systolic BP may accompany orgasm. Work loads measured in a laboratory setting with on-line minute oxygen consumption and those estimated by measurements performed during ergometer exercise to coital heart rates are remarkably similar, indicating a moderate 3-to-4 MET work load. Managing Cardiac Disease and ED Risk of Acute Cardiac Event Related to Coitus Of great concern to the patient and the clinician is the risk that coitus may trigger an acute cardiac event (eg, MI, sudden death, or the onset of unstable angina). The mechanism whereby an event or exposure could induce acute physiologic changes that might lead to an acute MI has become clear only in the last decade. It is now understood that most acute MIs are precipitated by hemodynamic forces that cause a vulnerable atherosclerotic plaque (one with a large cholesterol pool at the center, active lipid-filled inflammatory cells just below the surface, and impaired endothelial cells at the surface) to fracture at the edge or erode the surface at the top of the plaque. The resultant exposure of prothrombotic substances in the plaque to platelets and other thrombus-initiating material in the blood induces the formation of a thrombus rich in platelets and fibrin that can suddenly occlude the coronary artery. Data regarding the actual risk of MI associated with coitus was, until recently, very limited and was confounded by reporting bias. In 1993, M. Ueno, a Japanese pathologist, reported on 5559 cases of sudden death.14 Thirty-four of the cases were recorded as having occurred during or immediately after coitus; of these, 18 were determined at the autopsy and case evaluation to be cardiac in origin. The relatively low incidence of coitus reported as proximate to sudden death was noted (0.06%), but of particular interest was that 27 of the 34 cases occurred with coitus involving extramarital sex partners. The interpretation of this data in the United States was that extramarital sex was associated with a greater physiologic demand and greater risk of a cardiac event than was sex with a spouse. It seemed that we had finally arrived at a physiological and medical basis for marital fidelity! This concept was in line with the cultural mythology, supported by the reported deaths of prominent figures and television dramas in which characters had cardiac events during extramarital coitus. The most comprehensive analysis to date of the risk of an acute MI being “triggered" by coitus is the data from the Myocardial Infarction Onset Study.15 A total of 1774 patients were questioned, within 24 hours of an acute MI, with respect to their activities and possible “triggering" exposures in the several hours prior the relative risk of an MI. Exposure to anger was, however, much more frequent (daily) compared to the reported coital frequency, which averaged less than once a week. Data from the Framingham Heart Study16 showed that a 50-year-old man who is healthy and exercises regularly has an absolute risk of MI of 1 chance in a million per hour. When this is doubled to 2 in a million per hour for the two hours following coitus, and coitus occurs once a week, it has a negligible impact on annual risk (1.01% annual risk compared to 1.00% annual risk!) Indeed, the increase in risk attributed to Data regarding the actual risk of MI associated with coitus was, until recently, very limited and was confounded by reporting bias. to their MI. Additionally, they were questioned with regard to their activities and exposures during the same period of time 1 day prior to their infarct (a noninfarct day) and the frequency of these activities and exposures throughout the previous year. They found that only 27 (3%) of the 858 (48%) MI patients who were sexually active in the year prior to the MI reported sexual activity in the 2 hours prior to the infarction. They concluded that the relative risk of an MI occurring in the 2 hours after sexual activity was 2.5 (95% confidence interval, 1.7-3.7). Of interest is that the relative risk for patients with a prior history of an MI (2.9) was not significantly different from the risk for those with no cardiac history (2.5). The study also showed that regular exercise had a significant protective effect, and that exercise three times a week eliminated the increase in risk associated with coitus. When compared to other triggering events, coitus was found to be similar to anger in coitus was found to be far less than that associated with anger and unaccustomed physical exercise, and during the 2 to 4 hours after awakening associated with diurnal variation. Even in the patient who has a history of MI, where the absolute risk of a subsequent MI is 10 per million per hour, the doubling of this risk in the 2 hours after coitus 50 times a year has a negligible impact on annual risk. Based on the data from this study, physicians and patients can be reassured that in most cases sexual activity carries very little risk of precipitating a cardiac event. Of additional concern is the issue of coitus inducing symptomatic and life-threatening cardiac arrhythmia in the absence of atherosclerotic plaque rupture, which results in a thrombosis causing an MI or unstable angina. The data on cardiac arrhythmia associated with coitus is limited. In 1979, Johnston and Fletcher published their findings from ambulatory EKG recordings during at-home, usual-partner sexual activity. The VOL. 4 SUPPL. 3 2002 REVIEWS IN UROLOGY S43 Managing Cardiac Disease and ED continued 24 subjects studied included post-MI patients and post-coronary artery bypass graft (CABG) patients.17 The peak heart rates during coitus in the post-CABG patients were higher (90 to 118/min) than they were in the post-MI patients (74 to 108/min). Of interest is their finding that 12 of the 24 patients had arrhythmias associated with sexual activity; 5 of these During the exercise examination, patients with arrhythmia showed an 89% increase in ectopic beats. During intercourse, this occurred in only 11% of the patients, and most common arrhythmia in coitus was distinct in nature from the ambulatory EKG during other times. A complex arrhythmia was detected during coitus in 12% of the patients. The Stable angina patients usually have a functional reserve that exceeds the demands of coitus. patients developed arrhythmias only during coitus, not during the rest of the ambulatory EKG recording. Drory and colleagues from TelHashomer, Israel, addressed this issue in 88 male outpatients, ranging from 36 to 66 years of age, with stable coronary artery disease.18 Ambulatory EKG recordings included sexual activity and a near-maximum exercise test in all subjects. Arrhythmia was found during intercourse in 56% of the patients and during the exercise examination in 38% of the patients. authors concluded that in most patients existing rhythm disturbances were not exacerbated during coitus, and most arrhythmias noted during coitus were simple. Cardiovascular Risk Associated with the Use of Sildenafil Phase 3, placebo-controlled and post-marketing trials of sildenafil have demonstrated improvement in erectile function with a concomitant enhancement in sexual performance and satisfaction in a large percentage of appropriately treated patients. Sildenafil blocks the action of phosphodiesterase 5 in the smooth muscles that surround the penile arterial circulation. This results in a prolongation and enhancement of cyclic GMPmediated arterial dilatation, corpus cavernosum engorgement, and a penile erection induced by penileartery–produced nitric oxide. Studies have resolved initial concerns regarding the use of sildenafil in patients who are taking multiple antihypertensive medications and have demonstrated no increase in adverse clinical events among such patients. Moreover, studies addressing the use of sildenafil and coronary artery blood flow in normal and diseased coronary arteries have not revealed physiological alterations that would prompt clinical concerns. With the exception of the absolute contraindication to the concomitant use of sildenafil and nitrates, sildenafil has been found to be safe and effective. The concern, however, regarding the risk associated with coitus, made possible by the use of sildenafil, is small but real in selected patients. Main Points • Coronary artery disease (CAD) is a powerful indicator of the presence of erectile dysfunction (ED). The risk factors for ED are similar to those for CAD. • The physician must become familiar with the risks involved in treating men with ED and cardiovascular disease and be knowledgeable about the guidelines for safely undertaking sexual activity. • Early studies of peak heart rates and blood pressure during coitus led to the belief that sexual activity represents a significant risk in patients with CAD. Subsequent studies indicated that the heart rate during coitus was no higher than the rate during unaccustomed physical exercise or bouts of anger. • The absolute risk of myocardial infarction (MI) in a patient who has a history of MI has been found to be 10 per million per hour. The doubling of this risk in the 2 hours following coitus has a negligible impact on annual risk. Of greater concern is that very brief, significant elevations in blood pressure might create shear forces that could trigger plaque fracture or erosion, leading to thrombus formation. • Regular exercise has a significant protective effect and may prevent the increase in risk associated with coitus. • Studies of sildenafil citrate use in patients with a history of cardiovascular disease have found sildenafil to be safe and effective. An absolute contraindication, however, is the concomitant use of nitrates. • Physicians should be aware of the clinical guidelines for managing ED patients with a history of cardiovascular disease. The guidelines categorize patients as high risk, intermediate or indeterminate risk, and low risk. These guidelines permit the large portion of the patient population that is at low risk to initiate ED therapy and specify parameters to deal with higher risk patients. S44 VOL. 4 SUPPL. 3 2002 REVIEWS IN UROLOGY Managing Cardiac Disease and ED the risk of triggering an MI is real but very small in the 2 hours after coitus; the actual risk is less than that associated with episodes of anger or vigorous bouts of exercise which, in most instances, occur far more frequently then coitus does. It is clear, however, that this risk is increased in patients who are sedentary. The risk is also presumably of greater total magnitude in patients with unstable coronary presentations, reflecting most probably the presence of an increased number of vulnerable atherosclerotic plaques. Table 1 Clinical Management of Sexual Dysfunction in Patients with Cardiovascular Disease: Stratification of Patients into High, Low, and Intermediate Risk Categories Risk Category Parameters Low risk: sexual activity is not significant cardiac risk; sexual activity may be initiated with need for additional cardiac evaluation or studies A. Asymptomatic patients with <3 CHD risk factors (increased LDL cholesterol, reduced HDL cholesterol, hypertension, smoking, diabetes mellitus, positive family history), not including male gender B. Controlled hypertension C. Mild stable angina, evaluated and treated D. Post successful CABG E. Uncomplicated past MI F. Mild valvular disease G. Congestive heart failure (left ventricular dysfunction) NYHA Class I (symptoms of dyspnea only on vigorous activity) Intermediate or indeterminate risk: cardiac condition is uncertain or risk profile requires further testing or evaluation before sexual activity is resumed; based on testing patient may be assigned to low- or high-risk categories A. >3 CHD risk factors B. Moderate stable angina C. Recent MI (2–6weeks) D. Congestive heart failure (NYHA II) E. Noncardiac sequelae of atherosclerotic disease (eg, stroke, peripheral vascular disease). High risk: cardiac condition is severe or unstable and sexual activity may constitute significant risk; sexual activity should be deferred and the patient referred for further cardiologic evaluation and treatment A. Unstable or refractory angina B. Uncontrolled hypertension C. Congestive heart failure NYHA Class III/IV D. Recent MI (<2 weeks) E. High-risk arrhythmias F. Hypertrophic obstructive and other cardiomyopathies G. Moderate-to-severe valvular heart disease Stratification of ED Patients by Cardiac Risk Category The clinical guidelines for managing cardiovascular risk and sexual activity, derived from the recommendations of the Princeton Consensus Panel,6 are shown in Table 1. The guidelines classify patients with regard to cardiovascular status into low risk, intermediate risk, and high risk of cardiac events resulting from sexual activity. The guidelines were designed to permit the large portion of the relevant patient population that is at low risk to initiate ED therapy without unnecessary delay or expense and to defer resumption of sexual activity and treatment of ED in patients who require definitive treatment or further evaluation. Management Considerations for Classes of Low-Risk Patients CHD, coronary heart disease; LDL, low-density lipoprotein; HDL, high-density lipoprotein; CABG, coronary artery bypass graft; MI, myocardial infarction; NYHA, New York Heart Association. Data from DeBusk et al.6 Clinical Management of ED Patients with Comorbid Cardiovascular Diseases The data from the studies described above define the myocardial workload and the resultant myocardial oxygen demand for coitus as “moderate" in intensity. In fact, this workload is exceeded during activities of daily living in many patients. Additionally, • Some hypertensive medication induces ED, most importantly, blockers and diuretics. Clinical experience has shown that decreasing the dose or changing or discontinuing the -blocking drug or diuretic does not, in most instances, significantly enhance erectile function, and such patients should be considered for direct ED therapy with sildenafil. • Stable angina patients usually VOL. 4 SUPPL. 3 2002 REVIEWS IN UROLOGY S45 Managing Cardiac Disease and ED continued have a functional reserve that exceeds the demands of coitus. This should be confirmed by exercise–EKG testing. Antianginal medications (NOT INCLUDING NITRATES) can increase this functional reserve. • The success of coronary revascularization procedures may be evaluated by exercise–EKG testing and with imaging, if indicated. • Post-MI patients who are 6–8 weeks post-event and who are asymptomatic on post-MI stress testing, are at low risk and should be encouraged to resume sexual activity with ED treatment, if indicated. Exercise training will most probably reduce the small cardiac event risk of coitus in this patient group. gering an MI. With the availability of sildenafil, it is a clinically important requirement for physicians who treat sexual dysfunction to be familiar with this data as well as the guidelines for the safe resumption of sexual function in ED patients. Summary of Discussion Following Dr. Stein’s Presentation Discussion began with a direct question by Dr. Sadovsky to Dr. Stein: “So, since you can’t predict the patient who is going to have a plaque rupture with their sexual activity, what’s your final word? How do you advise a clinician to actually measure his patient’s risk of MI with sexual activity?" Dr. Stein acknowledged the fear among physicians that they might be sued by spouses of patients who died during coitus, that they would be held liable for giving the sildenafil and allowing sexual activity to begin. He added, “I think if you can show you followed acceptable guidelines, S46 VOL. 4 SUPPL. 3 2002 8. 9. 10. 11. References 1. 2. 3. 4. 5. Conclusions Studies have demonstrated that coitus requires a moderate level of cardiac workload and myocardial oxygen demand and carries a real but very small absolute risk of trig- 7. 6. Feldman HA, Goldstein I, Hatzichiristou DG, et al. Impotence and its medical and psychological correlates: results of the Massachusetts Male Aging Study. J Urol. 1994;151:54–61. Dabuwala CB, Kumar A, Pierce JM. Myocardial infarction and its influence on male sexual function. Arch Sex Behav. 1986;15:499–504. Greenstein A, Chen J, Miller H, et al. Does severity of ischemia coronary artery disease correlate with erectile dysfunction? Int J Impot Res. 1997;9:123–126. Cheitlin MD, Hutter AM, Brindis RG, et al. ACC/AHA Expert Consensus Document. Use of sidenafil (Viagra) in patients with cardiovascular disease. J Am Coll Cardiol. 1999;33:273–282. The Heart and Stroke Foundation of Canada and the Canadian Cardiovascular Society. A statement on the use of sildenafil in the management of sexual dysfunction in patients with cardiovascular disease. March 9, 1999. Available at: http://www.ccs.ca/society/position/viagra.cfm. Accessed February 21, 2002. DeBusk R, Drory Y, Goldstein I, et al. Management of sexual dysfunction in patients with cardiovascular disease: recommendations of the Princeton Consensus Panel. Am J Cardiol. 2000;86:175–181. you will be on better legal grounds in terms of reasonable medical safety." However, he added that one can never be perfectly confident that a patient will not have an MI, and there is no evidence that very elaborate testing is going to provide that absolute confidence. Dr. Stein continued, ED does predict people who go on to have heart attacks; the Massachusetts Male Aging Study data showed that impressively (see article text). Dr. Stein’s sense is that ED patients probably fit the profile of the early peripheral vascular disease or early cerebrovascular disease patient, where they have shown that they REVIEWS IN UROLOGY 12. 13. 14. 15. 16. 17. 18. Bartlett JR. Physiologic responses during coitus. J Appl Physiol. 1956;9:496–472. Masters WH, Johnson VE. Human Sexual Response. Boston: Little, Brown and Co; 1966. Hellerstein HK, Friedman EH. Sexual activity and the postcoronary patient. Arch Intern Med. 1970;125:987–999. Stein RA. The effect of exercise training on heart rate during coitus in the post myocardial infarction patient. Circulation. 1977;55:738–740. Nemec ED, Mansfield L, Kennedy JW. Heart rate and blood pressure responses during sexual activity in normal males. Am Heart J. 1976;92:274–277. Bohlen JG, Held JP, Sanderson MO, Patterson RP. Heart rate, rate-pressure product, and oxygen uptake during four sexual activities. Arch Intern Med. 1984;144:1745–1748. Mann S, Craig MWM, Gould B, Raftery EB. Coital blood pressure in hypertensives [abstract]. Circulation. 1980;62(suppl III):III–37. Ueno M. The so-called coition death. Nippon Hoigaku Zasshi [The Japanese Journal of Legal Medicine]. 1969;17:333–340. Muller JE, Mittleman MA, Maclure M, et al. Triggering myocardial infarction by sexual activity: low absolute risk and prevention by regular physical exertion. Determinants of Myocardial Infarction Onset Study Investigators. JAMA. 1996;275:1405–1409. Muller JE. Sexual activity as a trigger for cardiovascular events: what is the risk? Am J Cardiol. 1999;84(5B):2N–5N. Johnston BL, Fletcher GF. Dynamic electrocardiographic recording sexual activity in recent post-myocardial infarction and revascularization patients. Am Heart J. 1979;98:736–741. Drory Y, Fisman EZ, Shapira Y, Pines A. Ventricular arrhythmia during sexual activity in patients with coronary artery disease. Chest. 1996;109:922–924. have arterial atherosclerotic disease. Stein said he thinks it is always appropriate, with this population, to speak to patients in terms of riskfactor modification (lipid control, etc) and to encourage that. The study by Hellerstein and Friedman (see article text) was, Dr. Stein surmised, probably the beginning of physicians realizing that their patients should, in all instances, safely resume sexual activity. Those authors stated that the cardiac risk was low, and that patients’ heart rates were actually higher during the course of normal daily activities. Also, that study came out at about the time that physicians were beginning Managing Cardiac Disease and ED to realize that 60% of post-MI patients did not resume sexual activity. Sixty percent of patients, who were sexually active prior to MI, either didn’t resume at all, or resumed sexual activity at a far lower frequency than they had before the MI. Hence, Dr. Stein stressed the need for physicians to actively counsel, to overcome the public myth that sex after MI is dangerous. After the introduction of sildenafil, which made all physicians aware that they have to talk to their patients about sexual function, came another, similar wake-up call to cardiologists that they had to counter this public myth. The feeling among cardiologists, he said, is that if they didn’t mention it, that they were leaving the myth unopposed. “If I haven’t said to them, ‘You can safely and should resume sexual activity,’ they have a reasonable chance of thinking that sex is not safe after their MI." VOL. 4 SUPPL. 3 2002 REVIEWS IN UROLOGY S47