COLUMBUS, Ohio -- Researchers who were looking for the reason why simple aspirin use protects some people from developing heart attacks have traced the mechanism back to a specific genetic factor present on the surface of clotting cells called platelets.
The discovery could be used to determine which people at risk for heart attacks and heart disease might benefit mostly from daily doses of aspirin and which people might need other non-aspirin drugs to gain the same effect.
The study by Ohio State University researchers was published in the latest issue of the British medical journal The Lancet.
Earlier studies have shown that about 25 to 50 percent of a normal population can reduce their risk of a heart attack if they take daily doses of aspirin. But until now, researchers didn't understand why this beneficial effect occurred, and why aspirin's benefit was limited to such a small group of patients.
The new research suggests that aspirin may specifically target patients who display an altered gene, called the PlA2 polymorphism, which impacts upon the protective action of aspirin.
Generally speaking, genes are changed by one of two mechanisms -- mutations and polymorphisms. Mutations tend to occur in a small portion of the population and are the genetic changes most often closely linked to diseases because they alter the function of the protein product, the blueprint of which has been disrupted by the mutation.
Polymorphisms, on the other hand, are gene changes that do not grossly alter the function of the gene product but, instead, provide alternative templates for the making of certain proteins. These polymorphisms are much more common in the population and can represent improvements in the genetic makeup of species over time.
Glen Cooke, a post-doctoral researcher in the laboratory of Pascal Goldschmidt, chief of the division of cardiology and director of the Heart and Lung Institute at Ohio State, linked the existence of the PlA2 polymorphism to aspirin's beneficial effects on the heart.
"We know that aspirin is a very efficient drug in the prevention of heart attacks," said Goldschmidt. "It reduces the risk of heart attacks by 25 to 50 percent, which happens to be, perhaps coincidentally, almost exactly the frequency of this polymorphism in Western society."
Goldschmidt said that the effect of the polymorphism on heart attacks is linked to the clotting of blood in the vessels of the heart. In blood, cells called platelets play the primary role in initiating blood clots when receptors on their surfaces bind to fibrinogen, making the cells "sticky." If the platelets don't become sticky, clots won't form and heart attacks won't occur, he said.
"However, our research showed that platelets in people who had the PlA2 polymorphism were 10 times more sensitive to the effect of aspirin than were the platelets of individuals who do not have the polymorphism," he said. Therefore, aspirin might be particularly indicated for patients with the PlA2 polymorphism.
Goldschmidt said that within a couple of years, doctors will start to genotype their patients to determine if they have polymorphisms. This information might help with the decision-making process related to the choice of therapies.
For example, if they don't have the PlA2 polymorphism but still have problems with heart attacks, patients might be given one of several other antithrombotic medications, such as daily warfarin of clopidogrel, for example -- to get the same beneficial effect that aspirin provides individuals with the PlA2 polymorphism.
The work was supported through grants from the American Heart Association and the Bremmer Foundation.
Written by Earle Holland
(614) 292-8384
Holland.8@osu.edu
Journal
The Lancet