A daily low-dose aspirin is widely prescribed to prevent cardiovascular disease. Now, a new study claims that gene variations in some individuals may modify the cardiovascular benefits of aspirin, leading to slightly harmful effects.
According to researchers, a common genetic variation in the gene for catechol-O-methyltransferase (COMT) may alter aspirin's benefit.
COMT is a key enzyme in the metabolism of catecholamines, a group of hormones that include epinephrine, norepinephrine and dopamine.
"This is one of the few cases where you can identify a single genetic polymorphism which has a significant interaction with aspirin, such that it affects, whether or not it protects against cardiovascular disease," informed Kathryn Hall, an investigator at Harvard Medical School.
To answer this question, researchers used data from a cohort of over 23,000 women who were followed for 10 years in a placebo-controlled trial of low-dose aspirin or vitamin E for the primary prevention of incident cardiovascular disease.
Their analysis focused on "val158met", a common variant in the COMT gene.
Individuals who are homozygous for the enzyme's high-activity valine form, the "val/vals," have been shown to have lower levels of catecholamines.
"When we examined women in the placebo trial, we found that 23 percent of women who were 'val/vals' were naturally protected against incident cardiovascular disease," explained Daniel I Chasman, a genetic epidemiologist at Brigham and Women's Hospital (BWH).
Further investigation revealed the surprising discovery that when the women with the "val/val" polymorphism were allocated to aspirin, this natural protection was eliminated.
"We can be smarter about the groups of patients that would most likely benefit from aspirin," said Joseph Loscalzo, chairman of the department of medicine at BWH.
Rather than give aspirin to all patients with risk factors for heart disease, we need to identify those individuals for whom aspirin has the greatest benefit and the lowest risk of adverse effects, Loscalzo advised.
The study appeared online in the American Heart Association's journal Arteriosclerosis, Thrombosis, and Vascular Biology.
