Coffee-Gene Interaction Raises Heart Attack Risk
By Michael Smith , MedPage Today Staff Writer
Reviewed by Zalman S. Agus, MD; Emeritus Professor at the University of Pennsylvania School of Medicine.
Source News Article: Boston Globe, Forbes, LA Times, USA Today
MedPage Today Action Points
Explain to interested patients that the relationship between coffee drinking and heart attack has been confusing and this study shows that a certain genetic make-up may increase the risk.
Caution that there is no commercially available test that can distinguish between the two genotypes studied.
Advise, however, that one implication of the study is that a single cup of coffee a day -- 250 mL -- is safe no matter what genotype is involved.
Review
TORONTO, March 7 - People with a gene variant that causes slow metabolism of caffeine have a sharply elevated risk of a non-fatal heart attack if they drink large amounts of coffee, according to researchers here.
In a large case-control study, only people who were slow to metabolize caffeine had an increased risk of non-fatal myocardial infarction when they drank large amounts of coffee, found Ahmed El-Sohemy, Ph.D., a professor of nutritional sciences at the University of Toronto here.
The finding begins to clarify the muddy picture of the coffee-heart risk interaction, Dr. El-Sohemy and colleagues at Harvard and the University of Costa Rica reported in the March 8 issue of the Journal of the American Medical Association.
"It reveals for the first time that we need to take into account not just how much caffeine you take in but how much stays in your system," Dr. El-Sohemy said in an interview.
Caffeine is "the most widely consumed stimulant in the world" and has been implicated in the development of such cardiovascular diseases as acute MI, the authors noted.
But coffee contains a range of other chemicals and is associated with other lifestyle factors that cloud the link between consumed caffeine and unwanted cardiovascular outcomes, the researchers wrote.
They noted also that 95% of consumed caffeine is metabolized in the liver by cytochrome P450 1A2 (CYP1A2), which varies greatly in terms of activity among individuals. Specifically, a substitution - dubbed CYP1A2*1F -- in the CYP1A2 gene decreases its activity, and carriers of the allele, whether homo- or heterozygous, are called "slow" metabolizers of caffeine.
By contrast, carriers of another variant -- CYP1A2*1A -- are called "fast" metabolizers of the stimulant, Dr. El-Sohemy and colleagues noted.
In that context, between 1994 and 2004, he and colleagues enrolled 2,014 people in Costa Rica who had survived a first MI and matched them for age, sex, and area of residence. They were genotyped to see which CYP1A2 allele they carried and a food frequency questionnaire was used to assess how much caffeinated coffee they drank.
A cup of coffee was defined as 250 mL. Most of the coffee drunk in Costa Rica is filtered, rather than espresso or other varieties of the drink.
Analysis of the study population showed that 55% of cases, or 1,114, and 54% of controls, or 1,082, carried the "slow" allele. Using people who drank less than a cup of coffee a day as a reference group (with an odds ratio of 1.00), the researchers found:
Overall, only drinking more than four cups of coffee a day increased the risk of MI -- by 40%, with a 95% confidence interval between 1.05 and 1.87. Other levels of intake were not significantly associated with increased risk.
But for those carrying the "slow" allele, drinking two to three cups a day increased the risk by 36% (OR: 1.36) and drinking four or more increased it by 64% (OR: 1.64). (The 95% confidence intervals were 1.01 to 1.83 and 1.14 to 2.34, respectively.)
Meanwhile, for those with the "fast" allele, there was no significant increase in risk even at or above the four-cup-a-day level, compared with those who drank less than a cup a day.
In other words, the researchers argue, "coffee consumption increases the risk of MI only among individuals with a slow metabolizer genotype."
The researchers also looked at the effects of cigarette smoking, which is associated with coffee drinking and also induces CYP1A2 activity. The effect of CYP1A2 genotype on the risk of MI was similar among smokers and nonsmokers.
Earlier studies have hinted that the risk of MI associated with caffeine is greater in younger people, Dr. El-Sohemy and colleagues noted. To look at that issue, they examined risk among participants above and below the median age of 59 and found a significant gene/coffee interaction only among those younger than 59.
A similar pattern was found when they looked at participants younger than 50. There were 448 cases and 478 controls. For carriers of the "slow" allele, the odds ratios of MI associated with consuming less than one, one, two to three, or four or more cups of coffee per day were 1.00, 2.12, 2.43, and 4.07. The latter two were significant, with 95% confidence intervals ranging from 1.89 to 8.74 and 1.22 to 4.82, respectively.
By contrast, fast metabolizers had corresponding odds ratios of 1.00, 0.39, 0.35 and 0.81, with 95% confidence intervals of 0.15 to 0.97, 0.17 to 0.76, and 0.32 to 2.05, respectively.
Dr. El-Sohemy said he and his colleagues can't explain yet why drinking coffee might have an apparent protective effect in young fast metabolizers. "We do know that coffee contains a number of different compounds, including anti-oxidants," he said, adding it might be that because the caffeine is removed relatively quickly beneficial compounds are "unmasked."
He said the finding has no immediate clinical application, since there is no commercially available test for the different CYP1A2 genes. But he added one conclusion that could be drawn from the study is that a single cup of coffee a day has no adverse effect -- no matter what the genotype.
Primary source: Journal of the American Medical Association
Source reference:
Cornelis MC et al. Coffee, CYP1A2 Genotype, and Risk of Myocardial Infarction. JAMA. 2006;295:1135-1141.
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