Increased coffee intake is associated with an increased risk of nonfatal heart attacks among individuals with the gene variant for slow caffeine metabolism.

Caffeine, the most widely consumed stimulant in the world, has been implicated in the development of heart attacks and other cardiovascular diseases, and coffee is a major source of caffeine. However, coffee contains a number of other chemicals that affect the cardiovascular system in other ways.

It is not clear whether caffeine alone affects the risk of heart attack or whether other chemicals found in coffee may be responsible.

Genes Regulate Caffeine Metabolism

Caffeine is metabolized primarily by the enzyme cytochrome P450 1A2 (CYP1A2) in the liver. Variations of the gene for this enzyme can slow or quicken caffeine metabolism.

People who carry the gene variant CYP1A2*1F allele are "slow" caffeine metabolizers, while individuals with the gene variant CYP1A2*1A allele are "rapid" caffeine metabolizers.

Marilyn C. Cornelis, BSc, of the University of Toronto and colleagues conducted a study to determine whether gene variations of CYP1A2 modify the association between coffee consumption and risk of nonfatal heart attack.

The study, which was conducted among a population living in Costa Rica between 1994 and 2004, included 2,014 patients with a first acute nonfatal heart attack and 2,014 controls.

Researchers determined the genotypes of the participants and assessed their caffeinated coffee intake based on a food frequency questionnaire.

Greater Risk for Younger Individuals

Fifty-five percent of heart-attack cases and 54 percent of controls were carriers of the slow variant. Among those individuals, the ones who drank two to three cups of coffee a day had a 36 percent increased risk of heart attack. Those who drank four or more cups per day had a 64 percent increased chance of heart attack.

Corresponding consumption for individuals with the rapid gene variant resulted in a reduction of heart attack-risk by 22 percent among the heart-attack cases and 1 percent among the controls.

Younger individuals showed an increased risk. Among the slow metabolizers, the risk associated with drinking four cups or more per day compared with less than 1 cup per day increased from two-fold for individuals younger than 59 years to more than four-fold for those younger than 50 years.

Increased Nonfatal Heart Attacks

"In summary, consistent with most case-control studies, we found that increased coffee intake is associated with an increased risk of nonfatal MI," the authors say.

"The association between coffee and MI was found only among individuals with the slow CYP1A2*1F allele, which impairs caffeine metabolism, suggesting that caffeine plays a role in the association," they conclude.