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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.
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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