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Canary in the Coal Mine

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Canary in the Coal Mine

  1. 1. The Link Between Erectile and Cardiovascular Health: The Canary in the Coal Mine. Meldrum DR, et al. Amer J Cardiol 2011;108:599-606 Your name and title here
  2. 2. Erectile Dysfunction (ED) is strongly linked to C-V disease <ul><li>Men with ED develop coronary artery calcification at a younger age than controls, and have a reduced response to nitroglycerine (penile angina) 1 </li></ul><ul><li>A very strong correlation was found between penile systolic velocity and ischemic heart disease 2 </li></ul>1. Chiurlia E, et al: J Amer Coll Cardiol 2005;46:1502-6 2. Shamloul R, et al: Int J Impot Res 2004;16:235-7
  3. 3. ED is strongly linked to C-V disease <ul><li>There is a strong correlation of ED and the metabolic syndrome 1 </li></ul><ul><li>ED is correlated with a reduced HDL/cholesterol ratio 2 </li></ul><ul><li>Coronary risk factors predict later development of ED 3 </li></ul>1. Kupalian V, et al: J Urol 2006;176:222-6 2. Eaton CB, et al: Int J Impot Res 2007;19:218-25 3. Fung MM, et al: J Am Coll Cardiol 2004;14:1405-11
  4. 4. ED is strongly linked to C-V disease <ul><li>67% of men with angiographically proven coronary artery disease had experienced symptoms of ED an average of 39 months earlier 1 </li></ul><ul><li>“… a man with ED and no cardiac symptoms is a cardiac (or vascular) patient until proven otherwise.” 2 </li></ul>1. Montorsi F, et al: Eur Urol 2003;44:360-4 2. Jackson G: The second Princeton consensus on sexual dysfunction and cardiac risk: new guidelines for sexual medicine. J Sex Med 2006;3:28-36
  5. 5. Nitric Oxide and Flow Mediated Dilation * P < 0.001 ED NO ED * Chiurlia E, et al. J Am Coll Cardiol 2005;46:1503-1506
  6. 6. Nitric oxide (NO) and erectile function <ul><li>NO is the principle factor that mediates the effect of sexual arousal in causing engorgement of penile tissue and erection. </li></ul><ul><li>Nerve stimulation of human corpus cavernosum tissue indicated that NO was responsible for relaxation of the penile vasculature </li></ul><ul><li>NO caused smooth muscle relaxation through stimulation of cyclic GMP </li></ul>Rajfer J, Aronson WJ, Bush PA, Dorey FJ, Ignarro LJ: New Engl J Med 1992;326:90-4
  7. 7. Nitric oxide (NO) and erectile function <ul><li>Nitric oxide synthase exists as a neuronal enzyme (nNOS), where it functions as a neurotransmitter </li></ul><ul><li>It also exists as an endothelial enzyme, eNOS, where it acts as an autocrine factor for example by reducing senescence of the endothelium, and as a paracrine factor, diffusing into surrounding tissue where it inhibits platelet adhesion, prevents atherosclerosis, inhibits prolipheration of surrounding smooth muscle, and reduces vascular muscle tone. </li></ul>
  8. 8. The penis is “just” a collection of specialized blood vessels within a tough fibrous sheath Relaxation of the penile artery through nNOS causes filling of the sinusoids of the corpora cavernosa NO also relaxes the smooth muscle surrounding the sinusoids (eNOS) Sufficient distention against the fibrous sheath then closes off the penile veins, maintaining the erection
  9. 9. www.Erectile-Function.com
  10. 10. Viagra-like drugs can inadvertently cover up more serious vascular disease <ul><li>Inhibitors of PDE5 afford primarily symptomatic treatment by increasing cyclic-GMP, while not fully correcting the underlying problem of deficient nitric oxide (NO) production by unhealthy blood vessels (recent studies have established some beneficial vascular effects) </li></ul><ul><li>NO both stimulates cyclic-GMP and also reduces/prevents atherosclerosis and intra-arterial clotting, and reduces vascular tone and smooth muscle proliferation in artery/arteriolar walls </li></ul>
  11. 11. Physiology of Erectile Function* * www.Erectile-Function.com penile arteries anxiety, stress constrict sexual stimuli relax sinusoids fill veins are compressed erection lasts erection NO NO = Nitric Oxide NO
  12. 12. Biochemistry of Erectile Function* Meldrum DR, et al. Amer J Cardiol, e-pub 29 May, 2011 exercise, insulin, omega 3 fatty acids, calcium, folic acid, anti-oxidants, vitamin C, vitamin E, testosterone, weight reduction, moderate alcohol, PDE-5 inhibitors smoking, excessive alcohol, physical inactivity, dietary sugar, abdominal obesity, diabetes, hypertension, insulin resistance, decreased antioxidant defenses L-arginine (and indirectly from L-citrulline) NO Antioxidants, folic acid, omega 3 fats, Ca, vit. C&E, exercise, and testosterone promote Cyclic GMP promotes Viagra-like drugs inhibit erection Break-down by PDE5 inhibit
  13. 13. Sedentary or no alcohol moderate active alcohol
  14. 14. Cheng C, et al: Blood 2005;106:3691-8 Shear force induction of eNOS no shear force shear force
  15. 15. NO and decreased fasting insulin concentration Decrease in Fasting Insulin (uU/ml) r 2 = 0.68, p < 0.05 Roberts CK et al. Circulation 2002;106:2530-2
  16. 16. N I T R I C O XI D E FATTY ACIDS SUGARS alcohol? smoking obesity inactivity www.Erectile-Function.com
  17. 17. Sedentary or no alcohol moderate active alcohol
  18. 19. L-Arginine NITRIC OXIDE L-Citrulline Calcium Omega 3 fats Anti-oxidants Folic acid a a Moens AL, et al: Am J Heart Circ Physiol 2008;49:H1971-8 b van Mierlo LAJ, et al: J Hum Hypertens 2006;20:571-80 c Okuda Y, et al: Biochem Biophys Res Commun 1997;232:487-91 b c
  19. 21. L-Arginine NITRIC OXIDE L-Citrulline Calcium Omega 3 fats Anti-oxidants Folic acid pomegranate blackberries blueberries strawberries chocolate green tea red wine * * reference list under “resources” tab at www.erectile-function.com
  20. 22. Red cell reduced glutathione (umol/L) ED Control * P < 0.001 * Tagliabue M, et al: Int J Androl 2005;28:156-62
  21. 23. *† † * Vasodilatation due to cocoa (ml volume by PAT) Baseline Day 5 90 minutes L-NAME * P < 0.01 Fisher ND, et al: J Hypertens 2003;21:2281-6
  22. 24. Pycnogenol and ED placebo Stanislavov R,et al: J Sex Marital Ther 2003;29:207-13 80 mg 120 mg % improvement of ED
  23. 25. Low testosterone and ED <ul><li>Male hypogonadism has been correlated with ED and with the metabolic syndrome, and testosterone replacement not only improves ED, but gathering evidence has shown that it also improves various components of the metabolic syndrome, including a reduction of central adiposity and decreased insulin resistance. </li></ul>Stanworth RD, et al: Clin Interven Aging 2008;3:25-44
  24. 26. Impact of L-Arginine and pycnogenol on ED and circulating T placebo L-A/P placebo L-A/P * * * P < 0.001 Stanislavov R, et al: Int J Impot Res 2008;20:173-80
  25. 27. L-citrulline versus L-arginine 1.5 gm L-citrulline 3.2 gm L-arginine Hecker M, et al: Proc Natl Acad Sci 1990;87:8612-16 Schwedhelm E, et al: Br J Clin Pharmacol;2008;65:51-9
  26. 28. L-Arginine NITRIC OXIDE L-Citrulline calcium Omega 3 fats pycnogenol Folic acid N I R T I C O XI D E low fat low sugar weight loss www.Erectile-Function.com Ten steps to improved erectile and vascular health 1. Exercise increases NO by the shear forces of increased blood flow and increased insulin sensitivity 1.
  27. 29. L-Arginine NITRIC OXIDE L-Citrulline calcium Omega 3 fats pycnogenol Folic acid N I R T I C O XI D E low fat low sugar weight loss www.Erectile-Function.com Ten steps to improved erectile and vascular health 2. Omega-3 fats increase NO. Eat fatty fish and take fish oil to provide 500 to 1,000 mg daily 2.
  28. 30. L-Arginine NITRIC OXIDE L-Citrulline calcium Omega 3 fats pycnogenol Folic acid N I R T I C O XI D E low fat low sugar weight loss www.Erectile-Function.com Ten steps to improved erectile and vascular health 3. Folic acid in a co-factor in the synthesis of NO. Take 200 to 400 micrograms daily. 3.
  29. 31. L-Arginine NITRIC OXIDE L-Citrulline calcium Omega 3 fats pycnogenol Folic acid N I R T I C O XI D E low fat low sugar weight loss www.Erectile-Function.com Ten steps to improved erectile and vascular health 4. Increase intake of natural antioxidants 4.
  30. 32. L-Arginine NITRIC OXIDE L-Citrulline calcium Omega 3 fats pycnogenol Folic acid N I R T I C O XI D E low fat low sugar weight loss www.Erectile-Function.com Ten steps to improved erectile and vascular health 5. Decrease intake of sugar and fat. Cutting out all sugary drinks and fried foods would be an excellent plan. 5.
  31. 33. Effects of Cocoa and Sugar on Flow Mediated Dilation Faridi Z, et al. Am J Clin Nutr 2008;88:58-63 Meldrum DR, et al. Amer J Cardiol, e-pub 29 May, 2011
  32. 34. L-Arginine NITRIC OXIDE L-Citrulline calcium Omega 3 fats pycnogenol Folic acid N I R T I C O XI D E low fat low sugar weight loss www.Erectile-Function.com Ten steps to improved erectile and vascular health 6. Increase calcium intake with supplements as necessary to provide 1,200 mg daily. 6.
  33. 35. STRESS 7. Decrease stress. Ten steps to improved erectile and vascular health www.Erectile-Function.com
  34. 36. 8. Pay attention to your relationship with your partner. Ten steps to improved erectile and vascular health www.Erectile-Function.com
  35. 37. L-Arginine NITRIC OXIDE L-Citrulline calcium Omega 3 fats pycnogenol Folic acid N I R T I C O XI D E low fat low sugar weight loss www.Erectile-Function.com Ten steps to improved erectile and vascular health 9. Consider a stronger antioxidant (pycnogenol, 50-120 mg per day) and L-citrulline, 2 gm daily 9.
  36. 38. L-Arginine NITRIC OXIDE L-Citrulline calcium Omega 3 fats pycnogenol Folic acid N I R T I C O XI D E low fat low sugar weight loss www.Erectile-Function.com Ten steps to improved erectile and vascular health 10. Weight loss improves insulin sensitivity. Work at moderate weight loss (20-30 lb /year) 10.
  37. 39. Biochemistry of Erectile Function* *www.Erectile-Function.com caution! Antioxidants, folic acid, omega 3 fats, Ca, vit. C&E, exercise, and testosterone L-arginine (and indirectly from L-citrulline) smoking, excessive alcohol, physical inactivity, dietary sugar, abdominal obesity, diabetes, hypertension, insulin resistance, decreased antioxidant defenses NO promote Cyclic GMP promotes Viagra-like drugs inhibit erection Break-down by PDE5 inhibit
  38. 40. Tadadafil and Serum Oxidant Status TAS TOS PON-1 Tadalafil Baseline % difference from baseline Verit A, et al. Int J Impot Res 2010;22:115-9.
  39. 41. Tadalafil and Flow Mediated Dilation Rosano GMC et al. Eur Urol 2005;47:214022.
  40. 42. ED and Diabetes <ul><li>ED is 3 times as common in diabetics and is negatively correlated with better glycemic control and physical activity 1 . Therefore early aggressive treatment of diabetes, exercise, and antioxidant supplementation would be expected to particularly benefit these men. </li></ul><ul><li>ED predicts coronary artery disease (CAD) events in diabetic men with no evidence of coronary artery disease, and major cardiac events in men with type 2 diabetes who have established, asymptomatic CAD 2 . </li></ul>1. Giugliano F, et al. Int J Impot Res 2010;22:204-210 2. Meldrum DR, et al. Amer J Cardiol, e-pub 29 May, 2011
  41. 43. ED and Hypertension <ul><li>ED is two to three times more common in men with hypertension without diabetes or other medical conditions, and the incidence of ED increases with the duration and severity of elevated blood pressure 1 . </li></ul><ul><li>ED predicts a doubling of the risks of myocardial infarction and cardiac death in hypertensive men 2 . </li></ul><ul><li>All of the measures we have discussed that increase vascular NO will aid in blood pressure control 3 . </li></ul><ul><li>Doumas M, et al. J Androl 2006;27:469-77. </li></ul><ul><li>Bohm M, et al. Circulation 2010;121:1439-46. </li></ul><ul><li>3. Meldrum DR, et al. Amer J Cardiol, e-pub 29 May, 2011 </li></ul>
  42. 44. A B Losartan and Flow Mediated Dilation, Oxidative Stress Flammer AJ, et al. J Hypertens 2007;25:785-91.
  43. 45. ED as a Critical Warning Sign <ul><li>We have indicated that ED in men with diabetes or hypertension is an important warning sign for myocardial infarction and death. </li></ul><ul><li>ED can also be a very important danger sign in younger men with ED and no evidence of cardiac disease. When followed for 10 years, such men age 40-49 had a fifty-fold increase of CAD, including death, whereas the predictive value decreased with increasing age as expected (5.4-fold for ages 50 to 59 years, 2.2-fold for ages 60 to 69 years, and 1.3-fold for age 70 years and older. </li></ul>Inman BA, et al. Mayo Clin Proc 2009;84:108-113
  44. 46. www.Erectile-Function.com
  45. 47. How the Penis Works
  46. 48. Erectile Function and Exercise
  47. 49. Excess Weight and Erectile Function
  48. 50. Stress and E.F.
  49. 51. For Sexual Partners
  50. 52. Other Health Benefits
  51. 53. Self Assessment
  52. 54. Supplements
  53. 55. Forum www.Erectile-Function.com 102 Y/O
  54. 56. Sexual Dysfunction and Treatment of ED <ul><li>Female sexual satisfaction resulting from treatment of ED </li></ul><ul><li>38 women whose partners had ED had highly significant decreases of various indices of sexual satisfaction </li></ul><ul><li>Treatment of ED increased arousal and lubrication (p = 0.001, p = 0.002), and orgasm and satisfaction (p < 0.001) </li></ul>Cayan S et al: J Sex Marital Ther 2004;30:333-41
  55. 57. Meldrum DR, et al. Amer J Cardiol, e-pub 29 May, 2011

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