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Jacques Genest, Jr., MD FRCPC FACC Professor and Novartis Chair in Medicine, McGill University Director of the Division of...
In Vino Veritas: Are You MADD? Jacques Genest From the Cardiovascular Research Laboratories McGill University Health Centr...
<ul><li>Advisory Board, Speaker’s Bureau, Consultant, Grants </li></ul><ul><ul><li>sanofi-aventis </li></ul></ul><ul><ul><...
Alcohol and Heart Disease <ul><li>Questions </li></ul><ul><li>Epidemiology of alcohol drinking and mortality </li></ul><ul...
The Preparation of Beers Saccharomyces cerevisiae   Hordeum vulgare   (Barley) Beer preparation in Ancient Egypt + =
Fermentation of Grapes + = Yeast   Grape Wine Ethanol C
Epidemiology of Alcohol Drinking and All-Cause Mortality   <ul><li>Individual studies suggest benefit of alcohol drinking ...
Alcohol Dosing and Total Mortality in Men and in Women   <ul><li>Studies (n=34); 1,015,835 subjects and 94,533 deaths. </l...
Risk Factors and Risk of MI Smoking Diabetes Hypertension Abd. Obesity Psychol index Fruits/Veg Exercise (-) Alcohol (-) A...
Alcohol and the Heart
Alcohol and the Heart
Copyright restrictions may apply. Di Castelnuovo, A. et al. Arch Intern Med 2006;166:2437-2445. Relative risk of total mor...
What is a drink? <ul><li>10 g Ethanol = 1 drink </li></ul><ul><li>Wine (12.5% EtOH): 80 mL (!)    one glass 125-200 mL </...
Copyright restrictions may apply. Di Castelnuovo, A. et al. Arch Intern Med 2006;166:2437-2445. Relative risk of total mor...
In Bottle Sizes...Bigger is Better HALF-BOTTLE - 375 ml.  BOTTLE - Standard sized bottle. 750 ml.  MAGNUM - 1.5 L.  JEROBO...
Fermentation and Distillation shōchū (sobajōchū) buckwheat millet beer,  tongba millet rice baijiu, shōchū, soju  huangjiu...
yangmei jiu yangmei jiu Myrica rubra gouqi jiu gouqi jiu gouqi Urgwagwa, mbege, kasikisi bananas Tepache,  pineapples sliv...
Copyright restrictions may apply. Di Castelnuovo, A. et al. Arch Intern Med 2006;166:2437-2445. Relative risk of total mor...
Copyright restrictions may apply. Di Castelnuovo, A. et al. Arch Intern Med 2006;166:2437-2445. Relative risk of total mor...
Copyright restrictions may apply. Relative risk of total mortality (99% confidence interval) and alcohol intake in men and...
Geographic Differences? <ul><li>The available data does not allow to resolve the debate concerning the type of alcohol and...
Relative risk of total mortality (99% confidence interval) and alcohol intake stratified according to type of reference ca...
Alcohol and Heart Disease <ul><li>Epidemiology of alcohol drinking and mortality </li></ul><ul><li>Insights into possible ...
Alcohol and Risk Factors
(potential)  Mechanisms of Action <ul><li>Increase in HDL-C </li></ul><ul><li>Reduction in plasma viscosity </li></ul><ul>...
Resveratrol <ul><ul><li>Olas B, Wachowicz B. Resveratrol, a phenolic antioxidant with effects on blood platelet functions....
Resveratrol Lagouge M,  et al . Resveratrol improves mitochondrial function and protects against metabolic disease by acti...
Physiological Effects of Resveratrol <ul><li>Life extension </li></ul><ul><li>Cancer Prevention </li></ul><ul><li>Athletic...
Of Mice and Wine: Resveratrol
Resveratrol Resveratrol is found in the skin of red grapes and is a constituent of red wine but, based on extrapolation fr...
Is the French Paradox Still Alive? SCD not counted 1977 Data
Copyright ©1999 BMJ Publishing Group Ltd. Law, M. et al. BMJ 1999;318:1471-1480 No Caption Found Is the French Paradox Sti...
Is the French Paradox Still Alive? BMJ 1999;318:1471
Alcohol and Heart Disease <ul><li>Epidemiology of alcohol drinking and mortality </li></ul><ul><li>Insights into possible ...
The Flip Side of the Coin <ul><li>The dark side… </li></ul><ul><li>Alcohol-related morbidity </li></ul><ul><li>Alcohol-rel...
The Flip Side of the Coin <ul><li>The dark side…  </li></ul><ul><li>Alcohol-related mortality </li></ul><ul><ul><li>2006:1...
Alcohol and the Heart
Excessive Alcohol:  <ul><li>Mortality </li></ul><ul><li>Hypertension </li></ul><ul><li>Alcoholic cardiomyopathy </li></ul>...
Alcohol and Arrhythmias <ul><li>PAC, PCV </li></ul><ul><li>SVT </li></ul><ul><li>Atrial flutter </li></ul><ul><li>Atrial F...
Alcohol and Electrophysiologists
Alcoholic Cardiomyopathy <ul><li>Features similar to DCM </li></ul><ul><li>Dose-dependent exposure and host susceptibility...
Piano, M. R. Chest 2002;121:1638-1650 Cardiac deaths in men with ACM and IDCM ACM no R:OH ACM + R:OH IDCM
Piano, M. R. Chest 2002;121:1638-1650 Proposed hypothetical schema for the pathogenesis of ACM ~ 1 bttle wine/day
Alcoholic Liver Disease
Alcoholic Liver Disease
Caput Medusae Esophageal varices Splenomegaly
Hepatocellular cancer
Alcohol and Social Isolation <ul><li>Andreev E ,  et al.  Eur J Public Health. 2007 Dec 26 </li></ul><ul><li>An investigat...
Conclusions <ul><li>Alcohol intake has a small, but apparently beneficial effect on all-cause mortality (predominantly car...
Recommendations <ul><li>The drinking of fermented beverages is part of most cultures.  </li></ul><ul><li>Prohibition attem...
Recommendations <ul><li>Avoid ACC Lake Louise </li></ul>
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Transcript of "01-genest-acc-ll-200.."

  1. 1. Jacques Genest, Jr., MD FRCPC FACC Professor and Novartis Chair in Medicine, McGill University Director of the Division of Cardiology, McGill University Health Centre/Royal Victoria Hospital Montréal, Québec, Canada
  2. 2. In Vino Veritas: Are You MADD? Jacques Genest From the Cardiovascular Research Laboratories McGill University Health Centre, Montr e al McGill University Health Center Division of Cardiology Royal Victoria Hospital
  3. 3. <ul><li>Advisory Board, Speaker’s Bureau, Consultant, Grants </li></ul><ul><ul><li>sanofi-aventis </li></ul></ul><ul><ul><li>AstraZeneca </li></ul></ul><ul><ul><li>Merck Frosst </li></ul></ul><ul><ul><li>Schering Plough </li></ul></ul><ul><ul><li>Pfizer (CV Research Award) </li></ul></ul><ul><ul><li>Novartis </li></ul></ul><ul><ul><li>Biotech: Resverlogix (Research Grant) </li></ul></ul><ul><li>I attend ACC Lake Louise and drink wine in fair moderation </li></ul>Disclosure J. Genest MD
  4. 4. Alcohol and Heart Disease <ul><li>Questions </li></ul><ul><li>Epidemiology of alcohol drinking and mortality </li></ul><ul><li>Insights into possible mechanisms </li></ul><ul><li>Flip side of the coin </li></ul>(Who cares?)
  5. 5. The Preparation of Beers Saccharomyces cerevisiae Hordeum vulgare (Barley) Beer preparation in Ancient Egypt + =
  6. 6. Fermentation of Grapes + = Yeast Grape Wine Ethanol C
  7. 7. Epidemiology of Alcohol Drinking and All-Cause Mortality <ul><li>Individual studies suggest benefit of alcohol drinking on specific causes of death </li></ul><ul><li>Meta-analysis of 34 large-scale studies (predominantly Europe and US) Di Castelnuovo, A. et al. Arch Intern Med 2006;166:2437-2445. </li></ul><ul><li>Evidence of overall benefit with moderate drinking </li></ul><ul><li>Rapid increase in morbidity and mortality with increase drinking </li></ul>
  8. 8. Alcohol Dosing and Total Mortality in Men and in Women <ul><li>Studies (n=34); 1,015,835 subjects and 94,533 deaths. </li></ul><ul><li>Pooled data, adjusted for age, gender, social status, dietary factors, geographic origin </li></ul><ul><li>Adjustment for size of study, country, year of publication </li></ul>Di Castelnuovo, A. et al. Arch Intern Med 2006;166:2437-2445.
  9. 9. Risk Factors and Risk of MI Smoking Diabetes Hypertension Abd. Obesity Psychol index Fruits/Veg Exercise (-) Alcohol (-) Apo B / Apo AI Women Men Yusuf S et al. INTERHEART Lancet 2004;364:937-952
  10. 10. Alcohol and the Heart
  11. 11. Alcohol and the Heart
  12. 12. Copyright restrictions may apply. Di Castelnuovo, A. et al. Arch Intern Med 2006;166:2437-2445. Relative risk of total mortality (95% confidence interval) and alcohol intake extracted from 56 curves using fixed- and random-effects models
  13. 13. What is a drink? <ul><li>10 g Ethanol = 1 drink </li></ul><ul><li>Wine (12.5% EtOH): 80 mL (!)  one glass 125-200 mL </li></ul><ul><li>Beer (5% EtOH): 200 mL (!)  1 bttle is 341 mL </li></ul><ul><li>Scotch whisky (40% EtOH): 25 mL  <1 ounce </li></ul><ul><li>So… ½ bottle of wine is 47 g Ethanol (roughly) </li></ul>
  14. 14. Copyright restrictions may apply. Di Castelnuovo, A. et al. Arch Intern Med 2006;166:2437-2445. Relative risk of total mortality (95% confidence interval) and alcohol intake extracted from 56 curves using fixed- and random-effects models “ My wife and I share a bottle of wine in the evening”
  15. 15. In Bottle Sizes...Bigger is Better HALF-BOTTLE - 375 ml. BOTTLE - Standard sized bottle. 750 ml. MAGNUM - 1.5 L. JEROBOAM (DOUBLE MAGNUM) - 4 bottles. 3 L REHOBOAM - 6 standard bottles. METHUSALEM (IMPERIAL) - 8 bottles. 6 L SALMANAZER - 12 bottles 9 L. BALTHAZAR - 16 bottles. 12 L. NEBUCHADNEZZAR - 16 to 20 bottles. 12 to 16 L SOVERIGN - 67 bottles or 50 L.
  16. 16. Fermentation and Distillation shōchū (sobajōchū) buckwheat millet beer, tongba millet rice baijiu, shōchū, soju huangjiu, choujiu, sake, sonti, makgeolli, tuak, thwon rice vodka, whisky, wheat beer wheat maotai, gaoliang, baijiu Burukutu, pito, merisa, bilibili sorghum bourbon whiskey, vodka chicha, corn beer corn rye whiskey rye beer, kvass rye Scotch whisky, Irish whiskey, shōchū beer, ale, barley wine barley Name of distilled beverage Name of fermented beverage Cereal
  17. 17. yangmei jiu yangmei jiu Myrica rubra gouqi jiu gouqi jiu gouqi Urgwagwa, mbege, kasikisi bananas Tepache, pineapples slivovitz, tzuica, palinca, umeshu plum wine plums tequila, mezcal pulque agave rum, pinga, aguardiente, guaro basi, betsa-betsa sugarcane pear brandy, Eau-de-Vie perry, poiré pears applejack, calvados, cider, hard cider, apfelwein apples brandy, Cognac, Vermouth, Armagnac, Branntwein, pisco, Rakia also Rakiya, Rakija, Rakı, singani, pálinka wine grapes Name of distilled beverage Name of fermented beverage Fruit
  18. 18. Copyright restrictions may apply. Di Castelnuovo, A. et al. Arch Intern Med 2006;166:2437-2445. Relative risk of total mortality and alcohol intake curves
  19. 19. Copyright restrictions may apply. Di Castelnuovo, A. et al. Arch Intern Med 2006;166:2437-2445. Relative risk of total mortality (99% confidence interval) and alcohol intake in men and women ♀ ♂
  20. 20. Copyright restrictions may apply. Relative risk of total mortality (99% confidence interval) and alcohol intake in men and women (A) and in women (B) and men (C) in the United States, Europe, and other countries (Australia, Japan, and/or China), extracted from adjusted curves Women Men US Europe US Europe
  21. 21. Geographic Differences? <ul><li>The available data does not allow to resolve the debate concerning the type of alcohol and health benefits </li></ul><ul><li>Mediterranean style diet (wine with meals) differs markedly from beer drinkers or binge drinkers, more often encountered in the US </li></ul><ul><li>Possibility of “healthy” ingredients in specific types of alcohol </li></ul><ul><li>Value of social drinking on stress remains unexplored. </li></ul>
  22. 22. Relative risk of total mortality (99% confidence interval) and alcohol intake stratified according to type of reference category (A), sample size at baseline (B), year of publication (C), and follow-up duration (D)
  23. 23. Alcohol and Heart Disease <ul><li>Epidemiology of alcohol drinking and mortality </li></ul><ul><li>Insights into possible mechanisms </li></ul><ul><li>Flip side of the coin </li></ul>(Who cares?)
  24. 24. Alcohol and Risk Factors
  25. 25. (potential) Mechanisms of Action <ul><li>Increase in HDL-C </li></ul><ul><li>Reduction in plasma viscosity </li></ul><ul><li>Fibrinogen concentration </li></ul><ul><li>Increase in fibrinolysis </li></ul><ul><li>Decrease in platelet aggregation </li></ul><ul><li>Improvement in endothelial function </li></ul><ul><li>Reduction of inflammation </li></ul><ul><li>Antioxidant effects </li></ul>
  26. 26. Resveratrol <ul><ul><li>Olas B, Wachowicz B. Resveratrol, a phenolic antioxidant with effects on blood platelet functions. Platelets. 2005;16(5):251-60. </li></ul></ul><ul><ul><li>de la Lastra CA, Villegas I. Resveratrol as an antioxidant and pro-oxidant agent: mechanisms and clinical implications. Biochem Soc Trans. 2007;5:1156-60 </li></ul></ul>
  27. 27. Resveratrol Lagouge M, et al . Resveratrol improves mitochondrial function and protects against metabolic disease by activating SIRT1 and PGC-1alpha. Cell. 2006;127(6):1109-22. Howitz KT, Small molecule activators of sirtuins extend Saccharomyces cerevisiae lifespan. Nature. 2003;425(6954):191-6. Alvira D et al . Comparative analysis of the effects of resveratrol in two apoptotic models: inhibition of complex I and potassium deprivation in cerebellar neurons. Neuroscience. 2007;147(3):746-56 resveratrol, a natural antioxidant, as a potential drug for the treatment of neurodegenerative diseases (!)
  28. 28. Physiological Effects of Resveratrol <ul><li>Life extension </li></ul><ul><li>Cancer Prevention </li></ul><ul><li>Athletic performance </li></ul><ul><li>Antiviral effects </li></ul><ul><li>Neuroprotective </li></ul>
  29. 29. Of Mice and Wine: Resveratrol
  30. 30. Resveratrol Resveratrol is found in the skin of red grapes and is a constituent of red wine but, based on extrapolation from animal trials, apparently not in sufficient amounts to have a physiologically significant role in man.
  31. 31. Is the French Paradox Still Alive? SCD not counted 1977 Data
  32. 32. Copyright ©1999 BMJ Publishing Group Ltd. Law, M. et al. BMJ 1999;318:1471-1480 No Caption Found Is the French Paradox Still Alive?
  33. 33. Is the French Paradox Still Alive? BMJ 1999;318:1471
  34. 34. Alcohol and Heart Disease <ul><li>Epidemiology of alcohol drinking and mortality </li></ul><ul><li>Insights into possible mechanisms </li></ul><ul><li>Flip side of the coin </li></ul>
  35. 35. The Flip Side of the Coin <ul><li>The dark side… </li></ul><ul><li>Alcohol-related morbidity </li></ul><ul><li>Alcohol-related mortality </li></ul><ul><ul><li>Road-traffic accidents </li></ul></ul><ul><ul><li>Hepatic cirrhosis </li></ul></ul><ul><ul><li>Cancer </li></ul></ul>
  36. 36. The Flip Side of the Coin <ul><li>The dark side… </li></ul><ul><li>Alcohol-related mortality </li></ul><ul><ul><li>2006:17,602 people died in alcohol-related crashes (1/30 min), representing 41% of total traffic fatalities. </li></ul></ul>
  37. 37. Alcohol and the Heart
  38. 38. Excessive Alcohol: <ul><li>Mortality </li></ul><ul><li>Hypertension </li></ul><ul><li>Alcoholic cardiomyopathy </li></ul><ul><li>Cancer </li></ul><ul><li>Cerebrovascular events </li></ul>
  39. 39. Alcohol and Arrhythmias <ul><li>PAC, PCV </li></ul><ul><li>SVT </li></ul><ul><li>Atrial flutter </li></ul><ul><li>Atrial Fibrillation (most common) </li></ul><ul><ul><li>Holiday Heart </li></ul></ul><ul><li>VT/VF </li></ul>
  40. 40. Alcohol and Electrophysiologists
  41. 41. Alcoholic Cardiomyopathy <ul><li>Features similar to DCM </li></ul><ul><li>Dose-dependent exposure and host susceptibility </li></ul><ul><li>Pathological examination: indistinguishable from DCM </li></ul><ul><ul><li>Interstitial fibrosis </li></ul></ul><ul><ul><li>Myocyte dropout </li></ul></ul><ul><ul><li>Myocyte hypertrophy </li></ul></ul><ul><ul><li>Small vessel CAD </li></ul></ul><ul><ul><li>EM: disorganized mitochondria and glycogen vacuoles </li></ul></ul><ul><li>Treatment is abstinence from alcohol </li></ul><ul><li>Adverse prognosis linked to continued alcohol intake </li></ul>
  42. 42. Piano, M. R. Chest 2002;121:1638-1650 Cardiac deaths in men with ACM and IDCM ACM no R:OH ACM + R:OH IDCM
  43. 43. Piano, M. R. Chest 2002;121:1638-1650 Proposed hypothetical schema for the pathogenesis of ACM ~ 1 bttle wine/day
  44. 44. Alcoholic Liver Disease
  45. 45. Alcoholic Liver Disease
  46. 46. Caput Medusae Esophageal varices Splenomegaly
  47. 47. Hepatocellular cancer
  48. 48. Alcohol and Social Isolation <ul><li>Andreev E , et al. Eur J Public Health. 2007 Dec 26 </li></ul><ul><li>An investigation of the growing number of deaths of unidentified people in Russia. </li></ul><ul><li>“ unidentified men were at a higher risk of death from exposure to natural cold, violence, alcoholic cardiomyopathy, acute respiratory infections and poisonings” </li></ul><ul><li>“ The increase in deaths among unidentified men of working-age indicates the emergence of a health threat associated with homelessness and social marginalization.” </li></ul>
  49. 49. Conclusions <ul><li>Alcohol intake has a small, but apparently beneficial effect on all-cause mortality (predominantly cardiovascular) </li></ul><ul><li>This benefit is partly offset by an increase in violent deaths, toxic cardiovascular effects and alcoholic liver disease </li></ul>
  50. 50. Recommendations <ul><li>The drinking of fermented beverages is part of most cultures. </li></ul><ul><li>Prohibition attempts have failed to curb teenage drinking </li></ul><ul><li>Road-traffic accidents have decreased somewhat but still remain a major cause of death in teenage years and early adulthood </li></ul><ul><li>Moderate drinking appears to have no ill health effects </li></ul>
  51. 51. Recommendations <ul><li>Avoid ACC Lake Louise </li></ul>
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