A la Votre

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A la Votre
Rami Khouzam, MD
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Alcohol(Pros Cons)
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• The word "toast" meaning a wish of good health,
  started in ancient Rome, where a piece of toasted
  bread was dropped into wine

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• In Vino veritas In wine is truth, old latin
  saying
• "In water you see your own face, but in wine the
  heart of its garden,
• ancient Egyptian proverb

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• Hippocrates illustrated the value of wine as a
  medicine. Wine is vital to a healthy diet
• Paracelsus a German physician of the 16th
  century Whether wine is a nourishment, medicine
  or poison is a matter of dosage

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Beyond the French Paradox The Impact of Moderate
Beverage Alcohol Wine Consumption in the
Prevention of Cardiovascular DiseaseCardiology
Clinics, Volume 21. Number 3. August 2003Tedd M.
Goldfinger, DO, FACC

• Telling people to avoid any alcohol consumption
  , because of the potential dangers of heavy use
  may not be in the best health interest of the
  public

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• In our society, CVD is the leading cause of death
  and prevention is vital to longer life and better
  health
• Many epidemiologic and observational studies
  indicate that a healthy lifestyle including
  cigarette avoidance, low fat high fiber diet,
  lean body weight, regular exercise and small
  amounts of daily beverage alcohol, is protective
  against CHD

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History of Alcohol Health

• Through the ages, alcohol, particularly wine
  elixir for better health
• Ancient societies
• Evidence of wine consumption in moderation.
• Earliest wine consumers better nourished and
  less prone to sickness
• Judaic records Wine is at the head of all
  medicines Where wine is lacking, drugs are
  necessary

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Wine in Ancient Egypt

• According to William Younger in his book, Gods,
  Men and Wine
• It is in Egypt where we must go for our fullest
  knowledge of man's early and deliberate growing
  of wine

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• In Ancient Egypt wine was regarded as a gift from
  the gods. This belief may have come from the fact
  that Egyptian wine was only available to the
  socially elite classes
• Wine was used in funeral rites as well. The
  higher the social status of the deceased, the
  greater quantity of wine was used to anoint his
  body and belongings before entombment

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• Some Pharaohs, such as King Tutankhamen, were
  given jars of wine in their tombs in order to
  accompany the royal spirit on its journey to the
  underworld
• 36 Jars were found!

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• 20th century epidemiologic reports an inverse
  relationship between alcohol consumption and
  atherosclerotic disease
• Heavy drinkers highest mortality
• Abstainers prone to a higher mortality
• Moderate drinkers lowest mortality
• Cirrhosis sparing of vascular intima from
  atherosclerosis particularly in the coronary
  circulation ? anti-atherosclerosic effect of
  alcohol a salutary effect on the endothelium

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Studies facts

• Copenhagen Center for Population Studies
• At all levels of alcohol intake, wine drinkers
  were at significantly lower risk than non-wine
  drinkers for all cause mortality (plt0.001)

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• Non-drinkers Relative risk for death from CHD of
  0.76, and wine drinkers had a risk of 0.58
• 6051 men and 7234 women aged 30 to 70 of the
  Copenhagen City Heart Study the risk for dying
  steadily decreased with an increasing intake of
  wine
• Neither beer nor spirits was associated with a
  reduced risk

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• The association between alcohol intake and CHD
  was studied prospectively among 51,529 male
  health professionals
• Alcohol consumption was consistently associated
  with a reduced risk for a fatal and non-fatal
  myocardial infarction and the need for (CABG) or
  (PCI)

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• A meta-analysis of studies involving 209,413
  persons relationship between wine beer
  consumption and risk for fatal and non-fatal
  vascular events
• The relative risk for vascular endpoints among
  wine drinkers was 0.68 (CI, 0.59-0.77) relative
  to non-drinkers

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How Much Is Too Much?

• A significant inverse relationship was found at a
  daily intake of 150 ml of wine a maximum risk
  reduction was predicted at 750 mL/day
• A risk reduction in favor of beer drinkers was
  also noted with a RR of 0.78 (CI, 0.70-0.86).
  There was no observed dose relationship

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• Thomas Jefferson Wine of long habit has become
  indispensable to my health, I think it is a
  great error to consider a heavy tax on wine as a
  tax on luxury. On the contrary, it is a tax on
  the health of our citizens

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Biology of Alcohol Wine

• Mechanism of CVD risk reduction for alcohol
  drinkers caused by significant rise in HDL-C
• At least 50 of the benefit has been attributed
  to HDL-C rise

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• Alcohol intake may be the strongest positive
  predictor for an increased HDL-C in men and women
  
• (at present, lifestyle factors, such as aerobic
  exercise, and lipid lowering drugs, produce only
  small increases in HDL-C)

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• In 1992, Renauld and DeLongeril the French
  Paradox, enhancing an interset in wine worldwide
• Mortality rate for CHD in France was paradoxical
  and unexpectedly lower than other industrialized
  countries such as the USA and the UK, despite
  similarly high dietary intake of saturated fat

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• The ontoward effects of saturated fats are
  counteracted by the intake of wine
• Serum concentrations of HDL-C were seen, however,
  to be no higher in France than other European
  countries

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• A critical effect on hemostasis at levels of
  moderate alcohol intake
• Decrease in platelet reactivity and aggregability
  in humans
• Dramatic and significant decrease in
  intravascular platelet deposition in a normal
  laminar flow state and high shear flow states
  across a stenotic atherosclerotic lesion

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• Effect of a single alcohol beverage on the
  bleeding time, a sensitive measure of platelet
  function, is increased and lengthened, when
  consumed with aspirin or within thirty six hours
  after aspirin ingestion

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• Louis Pasteur, French biologist Wine is the
  most healthful and hygienic of beverages
• William Heberdens classic description of angina
  pectoris in 1786 included the statementWine and
  spiritious liquors afford considerable relief
  and postulated that alcohol was a coronary
  vasodilator

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Alcohol Wine in Vascular Biology

• Wine is a rich source of flavonoid phenolics such
  as resveratrol
• Substances giving wine its astringency and
  bitterness and are the foundation of long aging
  since they are effective antioxidants

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• Red wines, unlike white wines, are high in
  concentrations of these substances and age
  gracefully
• Derived from the skins and seeds of red wine
  grapes
• Moderate wine consumption increases measurable
  plasma antioxidant activity, and inhibits the
  oxidation of LDL-C

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• Whitehead 18 increase in serum antioxidant
  capacity in subjects who drank 300 mL of red
  wine, compared with a 4 increase for the same
  amount of white wine

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• Anderson addition of a potent antioxidant to a
  regimen of aggressive lipid lowering produced
  enhanced endothelial-dependent vasodilatation
• (Red wine, de-alcoholized red wine, purple grape
  juice)

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• Resveratrol (a red wine polyphenol)
• Inhibits a number of (PMN) functions considered
  to contribute to the pathogenesis and evolution
  of acute and chronic CHD
• ? Inhibiting toxic reactive oxygen species
  
• produced by activated PMNs, B-glucuronidase
• and elastase release, proteolytic enzymes
• responsible for acute vascular damage

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• Resveratrol also inhibits the production of
  5-lipooxygenase derived metabolites which are
  chemotactic for neutrophils, esinophils and
  monocytes
• ? Blunting the inflammatory response
• of neurophil aggregation,
• degranulation and superoxide
• production

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• Leikert colleagues increase in endothelial
  nitric oxide synthase (eNOS) enhanced
  transcription of the eNOS gene in human
  endothelial cells exposed to alcohol-free red
  wine polyphenol extract
• This effect may not be common to all red wines
• French red wines, not German red wines increase
  endothelial nitric oxide mRNA protein

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• Endothelin-1 (ET-1) a potent vasoconstrictor
• Khan associates a concentration dependent
  inhibition of ET-1 from a cabernet sauvignon wine

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• One investigator suggested
• Differences in grape variety
• Regions of production
• Cultivation
• Method of post fermentation processing
• may be important variables for health benefits

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• Flesch colleagues Red wines produced en
  barique that is small barrels, typical of French
  Bordeaux produced a particularly pronounced
  vasodilatory effect compared with other red wines
• Châteauneuf du Pape and Bordeaux

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The Heart in Ancient Egypt

• The heart was considered the most important of
  the body's organs
• The Egyptians believed that the heart, rather
  then the brain, was the source of the human
  wisdom, the emotions, the memory, the soul and
  the personality itself
• Notions of physiology and disease were all
  connected in concept to the heart, and it was
  through the heart that god spoke, giving ancient
  Egyptians knowledge

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Inflammation Vascular Remodeling

• C-reactive protein is an emerging marker for
  acute CHD
• Associated with a significantly higher mortality
  in patients presenting with ACS

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• Moderate red wine consumption has
  anti-inflammatory properties and is associated
  with a lowered level of CRP
• In a study of 2008 men women, ages 18-88 years,
  alcohol consumption showed a U-shaped association
  with mean values of CRP

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• Effect of red wine on vessel wall remodeling
  including
• Neointimal hyperplasia
• Monocyte recruitment adhesion to the
  endothelium
• Inhibition of intracellular adhesion molecules
• Foam cell accumulation
• Smooth muscle cell (SMC) proliferation and
  migration
• Abnormal expression of intracellular tissue factor

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• Feng colleagues a significant reduction in
  Monocyte Chemotactic Protein (MCP-1) expression
  and reduced neointimal thickening in rabbits fed
  a high cholesterol diet with red wine after
  balloon injury

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• In a study of 247 patients undergoing PCI,
  nondrinkers compared with alcohol drinkers had a
  5-fold increase in risk of cardiac death,
  non-fatal MI, and other adverse end points

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• Despite the ancient Egyptians seemingly advanced
  medical and surgical knowledge, the heart's role
  in blood circulation was not precisely understood
• It was felt that the heart channels (metu) linked
  all parts of the body together
• These channels delivered not only blood, but also
  air, tears, saliva, mucus, sperm, nutriment and
  even bodily waste
• The only real function of the brain was thought
  to be to pass mucus to the nose, so it was one of
  the organs that were discarded during
  mummification

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Amount Type of Alcohol and Risk of Dementia
The Copenhagen City Heart StudyNeurology- 12
NOV-2002 59 (9) 1313-9 TruelsenT

• Objective
• To assess whether amount or type of alcohol is
  associated with risk of dementia

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• Methods subjects
• Case-control, a cohort study among participants
  in the third Copenhagen City Heart Study
  (1991-1994), aged 65 years and more. Mini-Mental
  State Examination

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• Results
• Monthly and weekly intake of wine was
  significantly associated with a lower risk of
  dementia
• The effect of alcohol on risk of dementia did not
  differ between men women

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• Conclusions
• Monthly and weekly intake of wine is associated
  with a lower risk of dementia

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Alcohol is not associated with increased risk of
heart failureWalsh C, Larson M, Evans J.
Alcohol consumption risk for CHF in the
Framingham Heart StudyAnn Intern Med 2002
136(3) 181-191
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• Background
• Excessive alcohol consumption can be harmful,
  little is known about whether alcohol increases
  the risk of CHF
• Some studies have suggested that moderate alcohol
  intake has a protective effect

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• Objective
• Examine the relationship between alcohol
  consumption and risk of CHF
• Setting
• United states recruitment from 1948, data
  collected 1971-1995

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• Method
• Community-based prospective observational study
• Participants
• 6289 in the Framingham Heart Study without CHF or
  coronary heart disease at baseline

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• Main Results
• Heart failure risk was lower among men who
  consumed any level of alcohol compared to
  non-drinkers
• After adjusting for confounders, there was no
  association between alcohol intake and heart
  failure in women

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• Authors Conclusions
• Even among heavy drinkers (gt15 drinks/wk in men
  gt8 drinks/wk in women) , alcohol consumption is
  not linked with increased risk of CHF
• When consumed in moderation ( 8-14 drinks/wk in
  men 3-7 drinks/wk in women), alcohol may have a
  protective effect a lower hazard ratio compared
  to less than one drink/wk

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• How might alcohol benefit the heart?
• Alcohol may impact on other cardiac risk factors
• Improvements in lipid profile and anti-oxidant
  effect, among others...
• Alcohol in moderation may therefore have
  beneficial cardiovascular effects, however, high
  intake and binge drinking are not supported by
  this study

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• In the Final Judgment portrayed by the Book of
  the Dead, the heart of the deceased was shown
  being weighed against the feather of Maat, a
  symbol of universal truth, harmony and balance
• For this reason, the heart was one of the only
  organs not removed from the body during
  mummification

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Summary

• Alcohol beverages, particularly red wine, when
  consumed in moderation reduce the risk of acute
  CVD and death
• The mechanism for alcohol beverage benefit is
  complex includes an independent benefit of ethyl
  alcohol

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• The multiplicity of effects identified for the
  non-alcohol components of red wine play a role in
  improved endothelial physiology and enhance
  vascular homeostasis
• CAD begins early in life, and it progresses over
  decades
• Prospective studies of alcohol or wine
  consumption in the young, middle and older aged
  persons would be interesting

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• It is prudent for physicians to discuss the
  harmful effects of alcohol with their patients
  while at the same time, not discourage a
  potentially healthy practice of wine in
  moderation (eg, with meals)

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Thank you