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

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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)

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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

♀

♂

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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