CVD and Sexual Dysfunction

1. CVD and Sexual Dysfunction Melvin Cheitlin MD Jonathan Abrams MD Nancy Houston-Miller RN

2. Nitric oxide release in sexual stimulation CNS erotic stimulation Neural transmission Penile endothelial cells NITRIC OXIDE

3. Role of cyclic-GMP in penile erection smooth muscle relaxation vessel dilatation nitric oxide Blood filling lacunae in corpus cavernosum pushing against tunica albuginea cyclic-GMP obstruction of venous outflow

4. Sildenafil inhibits the enzyme PDE-5 Sildenafil citrate Nitric oxide X phosphodiesterase-5 Cyclic GMP X

5. Sildenafil side effects Sildenafil citrate specific for phosphodiesterase-5 (PDE-5) in penis selectivity for PDE-6 in retina (responsible for visual side effects) drop in systolic pressure 8-10 mm Hg drop in diastolic pressure 5-6 mm Hg erection tenable only when accompanied by stimulation of nitric oxide (ie, erotic stimulation)

6. Sildenafil and vasodilatation Sildenafil citrate normally SLOW vasodilation no increase in HR no sympathetic response no increase in cardiac output no increase in contractility BUT interacts with organic nitrates to produce significant hypotension

7. Sildenafil, original studies • No differences in MI or death were seen between those on placebo versus sildenafil in studies of > 3700 people. • The following subjects were excluded: • - patients with stroke or MI within 6 months • - patients with unstable angina, CHF • - patients with uncontrolled diabetes or BP > 150/110 or < 90/50 • patients with severe renal or hepatic disease

8. Sildenafil, original studies • Less than 25% of patients in these studies were over 65 years. • Patients with hypertension in the original safety trials were typically on simple regimens to control their blood pressure. • The effect of sildenafil on patients with hypertension and who are on multiple medications is not known.

9. Physical burden of sexual activity • General energy expenditure in sexual activity is 3-7 metabolic equivalents (METS), comparable to mild to moderate physical activity. • This expenditure depends on baseline status and differences in fitness levels. • Use stress testing to risk stratify certain patient populations (eg, recent MI, hospitalization for unstable angina, CHF, multiple drugs for HTN…).

10. Risk for acute MI during sexual activity • There exists a 2-fold increase in risk for MI within 2-3 hours following sexual activity. • The baseline risk of having an MI during sex is very low, less than 1% in terms of all infarctions. • The risk factors for coronary artery disease and erectile dysfunction are comparable. • When in doubt, stress test prior to resumption of sex or de novo sex in sedentary men at risk.

11. The use of both nitrates and sildenafil results in hypotension Nitrates Sildenafil citrate + - Nitric oxide phosphodiesterase-5 Cyclic GMP - HYPOTENSION

12. The concomitant use of sildenafil and nitrates is contraindicated. All men presenting with acute coronary syndromes must be asked if they’ve used Viagra within the preceding 24 hours. All patients given Viagra must be repeatedly told not to take nitrates.

13. Discussing sexual history with patients • As late as 1996, less than 1/3 of patients received sexual counseling at the time of MI, while up to 85% of patients appear willing to talk to their physician about sex. • When health-care professionals neglect to discuss their patients’ sexual history, patients experience: • - conflicts in relationships • - diminished quality of life • - decreased frequency of sexual activity

14. Key points in counseling a patient on sexual activity • In clinically low-risk individuals, risk of AMI is 1% per year. • By including sex at a frequency of once per week, then the risk of AMI is 1.01% per year. • In high risk patients having sex once per week, the risk of AMI is 1.2% per year. Provide information on the risks of sexual activity.

15. Key points in counseling a patient on sexual activity • Generally, in first 2-6 weeks after AMI it is safe to resume sexual activity. • Up to 80% of patients NOT provided this information are fearful in the first 6 months while resuming activity. Provide information on when to resume sexual activity.

16. Key points in counseling a patient on sexual activity Transition to full sexual participation may involve masturbation so that patients feel more comfortable resuming sexual intercourse. Patients should be aware of their environment, avoiding sexual activity in association with heavy meals, alcohol, temperature changes and fatigue.

17. Key points in counseling a patient on sexual activity • This workload is not significantly different with regard to position during sex. • The sex act is not a steady-state workload, unlike treadmill testing. • Patients should be cautioned about warning signals such as chest discomfort and shortness of breath. Physicians and patients should be aware of energy costs ( 2.5-3 METS).

18. Key points in counseling a patient on sexual activity • Sildenafil is contraindicated in patients taking long acting nitrates. • Other side effects include impaired color discrimination, headache, flushing and rhinitis. • Concomitant use of certain medications is associated with increased plasma levels of sildenafil. Physicians should be aware of medications that may be of use in treating sexual dysfunction.

19. Sexual counseling in women with cardiovascular disease • Women have greater difficulty with psychosocial adjustment, higher levels of anxiety, depression and sleep disturbances after MI and the development of coronary artery disease. Up to 1/3 of women may not resume sexual function at all. • A need for counseling exists irrespective of marital status. • Many more studies are needed.

20. CVD and sexual dysfunction • “One of the biggest issues with physicians is the long list of things they have to discuss with patients. Unless we begin to cue them in some way, to bring this subject up, it’s another one that gets lost along the way. The issue of erectile dysfunction… has to be brought to the forefront.” • Nancy Houston-Miller • Associate Director • Stanford Cardiac Rehabilitation Program • Stanford University School of Medicine • Stanford, CA