Aspirin's Ability to Protect Against Heart Attacks and Stroke Depends on Genomic Signature

Researchers at Duke Medicine have developed a blood-based test of gene activity capable of predicting whether or not taking aspirin will help a patient protect against heart disease and stroke.

Aspirin has been used for more than 50 years as a common, inexpensive blood thinner. However, despite this long precedence, doctors have little understanding of how it works and why some people benefit and others don't.

To help solve this mystery, scientists enlisted two groups of healthy volunteers and one comprised of patients with heart disease seen in outpatient cardiology practices.

The healthy volunteers were given a dosage of 325 milligrams of aspirin daily for up to a month while the heart disease patients had been prescribed a low dose of aspirin as part of their treatment. The researchers then analyzed the participants' blood for the impact of aspirin on RNA expression and the function of platelets, blood cells involved in clotting.

The RNA microarray profiling after aspirin showed a set of 60 co-expressed genes the study calls the "aspirin response signature" because they consistently correlated with an insufficient platelet response to aspirin therapy among the healthy subjects as well as the heart disease patients.

The researchers also examined the aspirin response signature in another group of patients who had undergone cardiac catheterizations and found the signature was effective in identifying those patients who eventually suffered a heart attack or died as well.

"There is something about the biology of platelets that determines how well we respond to aspirin and we can now capture that with a genomic signature in blood," Dr. Deepak Voora, assistant professor of medicine at Duke and one of the study's authors, said in a press release regarding the study's results.

Researcher Dr. Geoffrey S. Ginsburg is the director of genomic medicine at Duke's Institute for Genome Sciences and Policy and executive director of the Center for Personalized Medicine.

Based on the results of the study, Ginsburg believes that more specific tailoring is clearly needed in order to improve care for each patient.

"We give the same dose to all patients, but maybe some patients need a larger dose of aspirin, or maybe they need to try a different therapy entirely," he said.

To solve this problem, he argues that better tools are needed in order to monitor patients and adjust their care based on their needs.

Fortunately, the study shows that such tools may not be very long off.

"Nearly 60 million people take aspirin regularly to reduce their chances of heart attack and death, but it doesn't work for everyone," said Rochelle Long of the National Institutes of Health's National Institute of General Medical Sciences, which partly supported the study. "By monitoring gene activity patterns these investigators uncovered a 'signature' linked to inadequate responsiveness. This work may eventually lead to a simple blood test to identify those who do not benefit from aspirin, enabling them to seek other therapeutic options."