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Just a Drop of the Hard Stuff

Jennifer Cowger and Reema Hasan
University of Michigan Health Systems
Division of Cardiovascular Medicine
Ann Arbor, Michigan, USA

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March 17th is the feast day of the patron saint of Ireland, Patrick, who is known for (amongst other things) converting the Celtic pagans to Christianity. While St. Patrick's Day in Ireland is more of a religious celebration, Americans and other countries have assimilated the day for the purposes of merriment, inebriation, and enjoying all things "green" ... including their beverages. In fact, St. Patrick's Day was actually first "celebrated" in Boston, Massachusetts in 1737. According to folklore, St. Patrick was served an inadequate measure of whiskey at an inn. To teach the innkeeper about generosity, he told the innkeeper that a devil resided in the inn's basement, and was growing fat from the innkeeper's dishonesty. When St. Patrick revisited the inn months later, the innkeeper gave his patron an overflowing glass of liquor. St. Patrick then happily banished the emaciated demon from the inn and proclaimed that everyone should have a drop of the "hard stuff" on his feast day.

Perhaps folklore was on to something. Studies have shown that consumption of alcohol in moderate amounts (1-2 drinks/day) reduces all-cause mortality and cardiovascular disease (e.g. ischemic strokes, coronary heart disease). Scientific support for such outcomes includes a reduction in platelet aggregation and increased fibrinolysis and serum HDL. In red wines, flavonoids, resveratrol, and other polyphenols are believed to act as antioxidants and reduce adverse myocardial remodeling. However, Dr. Dipak Das, a scientist the University of Connecticut, was recently accused of falsifying data on resveratrol's benefits and some argue that red wine studies are confounded by healthier lifestyles undertaken by moderate wine drinkers.

If alcohol does possess beneficial effects, the impact on mortality is likely "J" shaped at best.1 According to the World Health Organization, alcohol is the third largest risk factor for disease burden in the world.2 In addition to its impact on the liver, alcohol and its metabolites can be toxic to cardiomyocytes. Alcoholic cardiomyopathy (ACM) is reported to affect 21-32% of long-term heavy alcohol consumers. The clinical phenotype of ACM is similar to other nonischemic cardiomyopathies with four chamber dilation and a reduced ejection fraction. Changes in myocardial structure are usually seen with >90 g/day (equivalent to ≥ 6 drinks/day) of alcohol for over 5 years, but ACM can develop in "binge drinkers" and consumers of smaller amounts of alcohol with genetic defects (including in the angiotensin converting enzyme DD genotype and defects in aldehyde dehydrogenase).3 More men develop ACM than women, largely because alcohol abuse is more prevalent in men and men tend to consume larger quantities of alcohol. However, women often develop ACM earlier and at a lower "lifetime alcohol dose" because they have fewer alcohol-metabolizing enzymes and a greater proportion of body fat, both leading to slower blood stream alcohol removal.

The pathophysiology for ACM development is likely multifactorial. Myocardial ultrastructure changes are similar to those seen in other cardiomyopathies and include an initial compensatory myocyte hypertrophy, followed by myocardial apoptosis, fragmentation of contractile proteins, expansion of intercalated discs, and diffuse fibrosis. Unfortunately, elucidating the mechanism underlying heart failure development in alcoholic abusers is compromised by an absence of good ACM animal models. While alcohol-induced cardiac dysfunction is seen in animals fed alcohol, some lack the myocardial fibrosis prominent in humans and all animal models show complete resolution of heart failure upon cessation of alcohol consumption, a finding not universal to humans who conquer alcohol addiction.

Several mechanisms for myocardial injury have been postulated, including increased oxidative stress, activation of the sympathetic nervous system, and damage to mitochondria energetics. During the metabolism of alcohol, alcohol dehydrogenase (present in the heart and liver) converts alcohol to acetaldehyde, a reactive organic compound. While acetaldehyde is normally converted to acetic acid by aldehyde dehydrogenase, free radicals are generated during acetaldehyde metabolism. Acetaldehyde and other free radicals can then interact with nucleophiles in myocardial proteins, nucleic acids, and lipids, forming adducts which stimulate apoptotic and fibrotic signaling pathways. In vivo studies have also shown acetaldehyde negatively impacts myocardial inotropy, lusotropy, and chronotropy through impairments in sarcoplasmic reticulum calcium handling. Finally, alcohol consumption stimulates the sympathetic nervous system, which leads to coronary vasospasm and augmentation of well-known cardiomyopathic signaling cascades (e.g. renin angiotensin system).

The most important determinants of survival with ACM appear to be alcohol abstinence and a shorter duration of symptoms prior to heart failure therapy initiation. In those who continue to abuse alcohol, survival is ~50% at 4 years.3 Up to 66% of patients who maintain alcohol abstinence and take evidence based heart failure medications can enjoy improvements (even normalization) in myocardial function, but this is likely contingent on the degree of myocardial damage the subject has sustained prior to achieving abstinence.

Thus, during this St. Patrick's Day, remember to screen your patients regularly for alcohol abuse and consume your own green beverages safely.

Disclosure Statement: The authors have no conflicts of interest to disclose.

References:

  1. di Castelnuovo A, Costananzo S, et al Arch Intern Med 2006;166:2437-45
  2. Source: WHO fact sheet 2011
  3. George A, Figueredo VM. J Cardiac Fail 2011;17:844-49