01-genest-acc-ll-200
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Jacques Genest, Jr., MD FRCPC FACCJacques Genest, Jr., MD FRCPC FACC
Professor and Novartis Chair in Medicine, McGill UniversityDirector of the Division of Cardiology, McGill University Health Centre/Royal Victoria HospitalMontréal, Québec, Canada
Professor and Novartis Chair in Medicine, McGill UniversityDirector of the Division of Cardiology, McGill University Health Centre/Royal Victoria HospitalMontréal, Québec, Canada
In Vino Veritas: Are You MADD?
Jacques Genest
From the Cardiovascular Research LaboratoriesMcGill University Health Centre, Montreal
McGill University Health CenterDivision of CardiologyRoyal Victoria Hospital
Advisory Board, Speaker’s Bureau, Consultant, Grants
sanofi-aventis
AstraZeneca
Merck Frosst
Schering Plough
Pfizer (CV Research Award)
Novartis
Biotech: Resverlogix (Research Grant)
I attend ACC Lake Louise and drink wine in fair moderation
Disclosure J. Genest MD
Alcohol and Heart Disease
Questions Epidemiology of alcohol drinking and
mortality Insights into possible mechanisms
Flip side of the coin
(Who cares?)
The Preparation of Beers
Saccharomyces cerevisiae Hordeum vulgare (Barley)
Beer preparation inAncient Egypt
+ =
Fermentation of Grapes
C
+ =
Yeast
GrapeWine
Ethanol
Epidemiology of Alcohol Drinking and
All-Cause Mortality
► Individual studies suggest benefit of alcohol drinking on specific causes of death
► Meta-analysis of 34 large-scale studies (predominantly Europe and US) Di Castelnuovo, A. et al. Arch Intern Med 2006;166:2437-2445.
► Evidence of overall benefit with moderate drinking
► Rapid increase in morbidity and mortality with increase drinking
Alcohol Dosing and Total Mortality in
Men and in Women
► Studies (n=34); 1,015,835 subjects and 94,533 deaths.►Pooled data, adjusted for age, gender, social status, dietary factors, geographic origin►Adjustment for size of study, country, year of publication
Di Castelnuovo, A. et al. Arch Intern Med 2006;166:2437-2445.
Risk Factors and Risk of MI
Smoking
Diabetes
Hypertension
Abd. Obesity
Psychol index
Fruits/Veg
Exercise (-)
Alcohol (-)
Apo B / Apo AI
WomenMen
Yusuf S et al. INTERHEART Lancet 2004;364:937-952
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 mortality (95% confidence interval) and alcohol intake extracted from 56 curves using fixed- and random-effects models
What is a drink?
10 g Ethanol = 1 drink
►Wine (12.5% EtOH): 80 mL (!) one glass 125-200 mL
►Beer (5% EtOH): 200 mL (!) 1 bttle is 341 mL
►Scotch whisky (40% EtOH): 25 mL <1 ounce
So… ½ bottle of wine is 47 g Ethanol (roughly)
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”
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.
Fermentation and Distillation
Cereal Name of fermented beverage Name of distilled beverage
barley beer, ale, barley wineScotch whisky, Irish whiskey,
shōchū
rye rye beer, kvass rye whiskey
corn chicha, corn beer bourbon whiskey, vodka
sorghumBurukutu, pito, merisa,
bilibilimaotai, gaoliang, baijiu
wheat wheat beer vodka, whisky,
ricehuangjiu, choujiu, sake,
sonti, makgeolli, tuak, thwon
rice baijiu, shōchū, soju
millet millet beer, tongba
buckwheat shōchū (sobajōchū)
FruitName of fermented
beverageName of distilled beverage
grapes wine
brandy, Cognac, Vermouth, Armagnac, Branntwein, pisco, Rakia also Rakiya, Rakija, Rakı, singani, pálinka
apples hard cider, apfelwein applejack, calvados, cider,
pears perry, poiré pear brandy, Eau-de-Vie
sugarcane basi, betsa-betsa rum, pinga, aguardiente, guaro
agave pulque tequila, mezcal
plums plum wineslivovitz, tzuica, palinca,
umeshu
pineapples Tepache,
bananasUrgwagwa, mbege,
kasikisi
gouqi gouqi jiu gouqi jiu
Myrica rubra yangmei jiu yangmei jiu
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
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
♀
♂
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
Geographic Differences?
►The available data does not allow to resolve the debate concerning the type of alcohol and health benefits
►Mediterranean style diet (wine with meals) differs markedly from beer drinkers or binge drinkers, more often encountered in the US
►Possibility of “healthy” ingredients in specific types of alcohol
►Value of social drinking on stress remains unexplored.
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)
Alcohol and Heart Disease
Epidemiology of alcohol drinking and
mortality Insights into possible mechanisms
Flip side of the coin
(Who cares?)
Alcohol and Risk Factors
(potential) Mechanisms of Action
Increase in HDL-C Reduction in plasma viscosity Fibrinogen concentration Increase in fibrinolysis Decrease in platelet aggregation Improvement in endothelial function Reduction of inflammation Antioxidant effects
Resveratrol
Olas B, Wachowicz B. Resveratrol, a phenolic antioxidant with effects on blood platelet functions. Platelets. 2005;16(5):251-60.
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
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 (!)
Physiological Effects of Resveratrol
Life extension Cancer Prevention Athletic performance Antiviral effects Neuroprotective
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 from animal trials, apparently not in sufficient amounts to have a physiologically significant role in man.
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 FoundIs the French Paradox Still Alive?
Is the French Paradox Still Alive?
BMJ 1999;318:1471
Alcohol and Heart Disease
Epidemiology of alcohol drinking and
mortality Insights into possible mechanisms
Flip side of the coin
The Flip Side of the Coin
The dark side… Alcohol-related morbidity Alcohol-related mortality
Road-traffic accidents Hepatic cirrhosis Cancer
The Flip Side of the Coin
The dark side… Alcohol-related mortality
2006:17,602 people died in alcohol-related crashes (1/30 min), representing 41% of total traffic fatalities.
Alcohol and the Heart
Excessive Alcohol:
↑ Mortality
►Hypertension
►Alcoholic cardiomyopathy
►Cancer
►Cerebrovascular events
Alcohol and Arrhythmias
↑ PAC, PCV
↑ SVT
↑ Atrial flutter
↑ Atrial Fibrillation (most common)►Holiday Heart
↑ VT/VF
Alcohol and Electrophysiologists
Alcoholic Cardiomyopathy
Features similar to DCM Dose-dependent exposure and host susceptibility Pathological examination: indistinguishable from DCM
► Interstitial fibrosis►Myocyte dropout►Myocyte hypertrophy►Small vessel CAD►EM: disorganized mitochondria and glycogen vacuoles
Treatment is abstinence from alcohol Adverse prognosis linked to continued alcohol intake
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
Andreev E, et al. Eur J Public Health. 2007 Dec 26• An investigation of the growing number of deaths of
unidentified people in Russia. “ unidentified men were at a higher risk of death from
exposure to natural cold, violence, alcoholic cardiomyopathy, acute respiratory infections and poisonings”
“The increase in deaths among unidentified men of working-age indicates the emergence of a health threat associated with homelessness and social marginalization.”
Conclusions
Alcohol intake has a small, but apparently beneficial effect on all-cause mortality (predominantly cardiovascular)
This benefit is partly offset by an increase in violent deaths, toxic cardiovascular effects and alcoholic liver disease
Recommendations
The drinking of fermented beverages is part of most cultures.
Prohibition attempts have failed to curb teenage drinking
Road-traffic accidents have decreased somewhat but still remain a major cause of death in teenage years and early adulthood
Moderate drinking appears to have no ill health effects
Recommendations
Avoid ACC Lake Louise