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 Montral, Qubec, Canada

In Vino Veritas: Are You MADD?

Jacques Genest

From the Cardiovascular Research Laboratories McGill University Health Centre, Montreal

McGill University Health Center

Division of Cardiology Royal Victoria Hospital

Disclosure J. Genest MD
Advisory Board, Speakers 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

Alcohol and Heart Disease

Questions
Epidemiology of alcohol drinking and mortality Insights into possible mechanisms
(Who cares?)

Flip side of the coin

The Preparation of Beers

+
Hordeum vulgare (Barley)
Saccharomyces cerevisiae

Beer preparation in Ancient Egypt

Fermentation of Grapes

+
Yeast

=
Wine

Grape

C
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
Women Men

Yusuf S et al. INTERHEART Lancet 2004;364:937-952

Alcohol and the Heart

Alcohol and the Heart

Relative risk of total mortality (95% confidence interval) and alcohol intake extracted from 56 curves using fixed- and random-effects models

Di Castelnuovo, A. et al. Arch Intern Med 2006;166:2437-2445.

Copyright restrictions may apply.

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 bottle of wine is 47 g Ethanol (roughly)

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

Di Castelnuovo, A. et al. Arch Intern Med 2006;166:2437-2445.

Copyright restrictions may apply.

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
barley rye corn sorghum wheat rice millet buckwheat

Name of fermented beverage Name of distilled beverage

beer, ale, barley wine rye beer, kvass chicha, corn beer Burukutu, pito, merisa, bilibili wheat beer huangjiu, choujiu, sake, sonti, makgeolli, tuak, thwon millet beer, tongba shch (sobajch) Scotch whisky, Irish whiskey, shch rye whiskey bourbon whiskey, vodka maotai, gaoliang, baijiu vodka, whisky, rice baijiu, shch, soju

Fruit

Name of fermented beverage

Name of distilled beverage brandy, Cognac, Vermouth, Armagnac, Branntwein, pisco, Rakia also Rakiya, Rakija, Rak, singani, plinka applejack, calvados, cider, pear brandy, Eau-de-Vie

grapes

wine

apples pears

hard cider, apfelwein perry, poir

sugarcane
agave plums

basi, betsa-betsa
pulque plum wine

rum, pinga, aguardiente, guaro

tequila, mezcal slivovitz, tzuica, palinca, umeshu

pineapples
bananas gouqi

Tepache,
Urgwagwa, mbege, kasikisi gouqi jiu gouqi jiu yangmei jiu

Myrica rubra yangmei jiu

Relative risk of total mortality and alcohol intake curves

Di Castelnuovo, A. et al. Arch Intern Med 2006;166:2437-2445.

Copyright restrictions may apply.

Relative risk of total mortality (99% confidence interval) and alcohol intake in men and women

Di Castelnuovo, A. et al. Arch Intern Med 2006;166:2437-2445.

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

Europe US Women

US Europe

Men

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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
(Who cares?)

Flip side of the coin

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
Howitz KT, Small molecule activators of sirtuins extend Saccharomyces cerevisiae lifespan. Nature. 2003;425(6954):191-6. 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. 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?

1977 Data

SCD not counted

Is the French Paradox Still Alive?

No Caption Found

Law, M. et al. BMJ 1999;318:1471-1480

Copyright 1999 BMJ Publishing Group Ltd.

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 alcoholrelated 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

Cardiac deaths in men with ACM and IDCM

ACM no R:OH

IDCM

ACM + R:OH

Piano, M. R. Chest 2002;121:1638-1650

Proposed hypothetical schema for the pathogenesis of ACM

~ 1 bttle wine/day

Piano, M. R. Chest 2002;121:1638-1650

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