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Men who consumed at least one drink per day and were homozygous for the [{gamma}] 2 allele had the greatest reduction in risk (relative risk, 0.14; 95 percent confidence interval, 0.04 to 0.45)

http://heartdisease.about.com/library/weekly/aa022201a.htm?once=true&PM=59_0104_T

Uh, oh. A little alcohol really is good for the heart

A new study shows that it's the alcohol itself - not lifestyle, socioeconomic status, or flavenoids - that protects against coronary artery disease. This information greatly intensifies the doctors' dilemma.

By DrRich

Dateline: 02/22/2001

Doctors, alcohol, and the heart

Doctors have struggled for several years now over whether to tell their patients about the potential cardiac benefits of alcohol. Over 60 clinical studies have suggested that light to moderate alcohol consumption (the equivalent of one 1 � oz. of alcohol per day) can increase HDL cholesterol levels (the “good” cholesterol) by approximately 12%, and can reduce the incidence of myocardial infarction.

However, excessive alcohol consumption reliably causes a number of severe medical problems including auto accidents, cardiomyopathy and heart failure, liver failure, stroke, and cancer, not to mention the destructive social pathologies associated with alcoholism itself. Some people are extremely sensitive to alcohol, and can develop some of these alcohol-associated conditions with what most would consider only moderate consumption. And others seem to have a definite predilection for alcohol addiction, and find it difficult if not impossible to limit themselves to, say, one drink per day.
In addition, many have argued that it may not be the alcohol itself that provides the benefit, but the “company” alcohol keeps. It has been postulated, for instance, that people who enjoy a glass of fine red wine with dinner may just have a relatively healthy lifestyle, or may belong to a relatively favorable socioeconomic class. Some studies have even suggested that substances in beer and wine other than the alcohol (such as flavenoids) might actually be the beneficial agent
The dilemma:
Should doctors tell patients of the cardiac protective effects of alcohol, when the potential hazards of alcohol are so great?

For all these reasons, a special advisory panel of the American Heart Association issued a formal statement, published last month in Circulation, urging doctors not to recommend alcohol to their patients as a means of reducing the risk of heart disease.

Don't tell

But the real dilemma faced by doctors isn't whether to recommend drinking alcohol (most have not been doing that anyway.) The dilemma is whether to even tell patients about the potential cardiac benefits of alcohol. If doctors were seen to be encouraging alcohol, that would not only be politically incorrect, but might also lead to a significant increase in alcohol-related medical and social problems. The recent statement from the American Heart Association, while it does not explicitly advise doctors to keep quiet about the potential cardiac benefits of alcohol, nonetheless lends tacit support to this “don’t tell” position.

A new study complicates the doctor's dilemma

A new report in the February 22, 2001 New England Journal of Medicine has just made the doctors’ dilemma more difficult. This study strongly indicates that the cardiac benefits of alcohol are not only real, but also that they are not due to lifestyle, socioeconomic class or flavenoids – instead, they are due to the alcohol itself:

The study takes advantage of the fact that a substantial minority of individuals are born with a genetic variation in an enzyme called alcohol dehydrogenase (ADH). ADH helps to metabolize (break down) alcohol in the liver. People with the genetic variation of ADH do not metabolize alcohol as efficiently as people with normal ADH, so that alcohol stays in their system longer.

In this study, a large number of subjects with no history of heart disease were followed for several years. Among those who drank a moderate amount of alcohol (about one drink per day), HDL levels were significantly higher and the incidence of heart attacks was significantly lower than for subjects who did not drink alcohol. This result, of course, is nothing new. It merely confirms the findings of many other studies.

But there was a major new finding in this study. Among the patients who drank moderate amounts of alcohol (all of whom received some degree of cardiac protection), those with the variant ADH had significantly higher HDL levels and significantly fewer heart attacks than those with the normal form of ADH. In other words, when the variant form of ADH made alcohol remain in the system longer, the degree of cardiac protection increased.

Since ADH acts only on alcohol, this study essentially proves that it is the alcohol itself, and not some other substance associated with alcoholic beverages, that confers the cardiac protection.

This new information intensifies the dilemma faced by doctors. Now that it seems quite certain that it’s the alcohol itself that is helping to prevent heart disease, can doctors still intentionally withhold this information from their patients?

Can doctors still withhold information about the possible benefits of alcohol?

Many will argue that this study doesn’t really change anything at all. After all, they might say, we strongly suspected all along that alcohol confers cardiac benefits. But to society at large, alcohol remains a major health hazard. For instance, despite its ability to reduce coronary artery disease, alcohol remains one of the major causes of cardiomyopathy and heart failure. The line between drinking "just enough" alcohol and "too much" alcohol is hard to define - and is probably different for everybody. So until it is demonstrated that encouraging drinking saves more lives than it costs (a dubious proposition at best) doctors should keep quiet. For an organization like the American Heart Association, one that aims to improve overall public health, such arguments are both reasonable and compelling.

Yet, at the same time several arguments can be made against withholding this information from patients. For one thing, to withhold information from patients is paternalistic. For another, in the Internet era, trying to hide scientific information from patients is ultimately doomed to failure (this very article being an example of this phenomenon.)

But the most compelling argument against withholding this information from patients is that to do so will often violate the doctor-patient compact. It is the doctor’s duty – according to tradition, to medical ethics, and to the law – to act in the best interests of their individual patients. This is true even when those interests are contrary to the interests of society at large. Thus, if a particular patient needs a referral to a cardiologist but the HMO (society’s surrogate) discourages such referrals because of cost, the doctor is nonetheless obligated – morally and legally – to make the referral. (Click here for a more detailed commentary on the importance of the doctor-patient relationship - and why we can't have it anymore.)

In the case of alcohol as a cardiac preventative, it is clearly in society’s best interest for the medical profession to avoid a wholesale recommendation that everyone consume a drink a day. To embrace such a recommendation might well cause net harm to society.

However, doctors commonly see individual patients whose HDL levels remain too low and whose risk for cardiac disease remains too high, despite taking all standard measures to increase those levels and reduce that risk. To withhold from such an individual the scientific information about the potential cardiac benefits of alcohol would be unethical, immoral and illegal. Taking this argument a step further, one might argue that even if other, more routine, risk reduction measures are available, it might often be in the patient’s own best interests to be fully apprised of all their options.

As usual, it will be difficult to articulate a policy on the use of alcohol for cardiac prevention that meets both the needs of society and the needs of all individuals that comprise society. The policy that is in wide use now, however – to simply avoid discussing the issue with patients – has just become a bit less tenable.

Here is the abstract of the new study on alcohol from the New England.

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http://heartdisease.about.com/gi/dynamic/offsite.htm?site=http://www.nejm.org/content/2001/0344/0008/0549.asp

Lisa M. Hines, S.M., Meir J. Stampfer, M.D., Dr.P.H., Jing Ma, M.D., Ph.D., J. Michael Gaziano, M.D., Paul M. Ridker, M.D., Susan E. Hankinson, Sc.D., Frank Sacks, M.D., Eric B. Rimm, Sc.D., and David J. Hunter, M.B., B.S., Sc.D.

ABSTRACT

Background A polymorphism in the gene for alcohol dehydrogenase type 3 (ADH3 ) alters the rate of alcohol metabolism. We investigated the relation among the ADH3 polymorphism, the level of alcohol consumption, and the risk of myocardial infarction in a nested case–control study based on data from the prospective Physicians' Health Study.

Methods We identified 396 patients with eligible newly diagnosed cases of myocardial infarction among men in the Physicians' Health Study. Of these patients, 374 were matched with 2 randomly selected control subjects each and the remaining 22 with 1 control each (total, 770 controls). The ADH3 genotype ( [{gamma}] 1 [{gamma}] 1, [{gamma}] 1 [{gamma}] 2, or [{gamma}] 2 [{gamma}] 2) was determined in all subjects. We examined the relations among the level of alcohol intake, the ADH3 genotype, and plasma high-density lipoprotein (HDL) levels in this study population and in a similar cohort of women.

Results As compared with homozygosity for the allele associated with a fast rate of ethanol oxidation ( [{gamma}] 1), homozygosity for the allele associated with a slow rate of ethanol oxidation ( [{gamma}] 2) was associated with a reduced risk of myocardial infarction (relative risk, 0.65; 95 percent confidence interval, 0.43 to 0.99). Moderate alcohol consumption was associated with a decreased risk of myocardial infarction in all three genotype groups ( [{gamma}] 1 [{gamma}] 1, [{gamma}] 1 [{gamma}] 2, and [{gamma}] 2 [{gamma}] 2); however, the ADH3 genotype significantly modified this association (P=0.01 for the interaction). Among men who were homozygous for the [{gamma}] 1 allele, those who consumed at least one drink per day had a relative risk of myocardial infarction of 0.62 (95 percent confidence interval, 0.34 to 1.13), as compared with the risk among men who consumed less than one drink per week. Men who consumed at least one drink per day and were homozygous for the [{gamma}] 2 allele had the greatest reduction in risk (relative risk, 0.14; 95 percent confidence interval, 0.04 to 0.45). Such men also had the highest plasma HDL levels (P for interaction = 0.05). We confirmed the interaction among the ADH3 genotype, the level of alcohol consumption, and the HDL level in an independent study of postmenopausal women (P=0.02).

Conclusions Moderate drinkers who are homozygous for the slow-oxidizing ADH3 allele have higher HDL levels and a substantially decreased risk of myocardial infarction.


Source Information

From the Departments of Epidemiology (L.M.H., M.J.S., S.E.H., E.B.R., D.J.H.) and Nutrition (M.J.S., F.S., E.B.R., D.J.H.), Harvard School of Public Health; the Channing Laboratory, Department of Medicine, Harvard Medical School and Brigham and Women's Hospital (M.J.S., J.M., S.E.H., F.S., E.B.R., D.J.H.); the Divisions of Preventive Medicine and Cardiology, Harvard Medical School (J.M.G, P.M.R.); and the Massachusetts Veterans Epidemiologic Research and Information Center, Department of Veterans Affairs Boston Healthcare System (J.M.G.) — all in Boston.

Address reprint requests to Ms. Hines at the Channing Laboratory, 181 Longwood Ave., Boston, MA 02115, or at lhines@hsph.harvard.edu.

 

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