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Research sheds light on aspirin therapy resistance


Published:   |   Updated: July 11, 2013 at 07:54 AM

sing a powerful genetic analysis technique, Duke Medicine researchers have come up with what they think are some answers to the question of why aspirin is effective in protecting some people from heart attacks and strokes but does little for others.

They also believe they have a tool that will allow doctors to predict who is at risk of dying from both disorders.

Writing in the July 3 issue of the Journal of the American College of Cardiology, Duke Medicine researchers report they used the technique known as RNA microarray profiling to discover 60 genes that act in concert and play a role in rendering some people unable to benefit from low-dose aspirin therapy against heart attack and strokes.

These genes produce what the researchers call a genomic "aspirin response signature."

In aspirin resistance, aspirin appears to have an insufficient impact on blood cells known as platelets in both healthy people and those with cardiovascular disease.

Also known as thrombocytes, platelets are small disk-shaped cells that play a role in blood clotting and the repair of blood vessels and connective tissues. Sometimes, they also help to produce blood clots in response to artery-clogging plaque.

Scientists believe one of the many things aspirin does is keep platelets from clumping together, known as platelet aggregation.

The Duke researchers conducted the RNA microarray testing on healthy volunteers who were given 325 milligrams of aspirin a day for up to a month and heart disease patients who were being treated with low-dose aspirin.

In both healthy people and heart disease patients, the response signature associated with aspirin resistance was the same.

"The aspirin response signature can determine who is at risk for heart attack and death," said Deepak Voora, a Duke assistant professor of medicine and lead author of the study.

"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."

Geoffrey S. Ginsburg, director of genomic medicine at Duke's Institute for Genome Sciences & Policy and executive director of the Center for Personalized Medicine and the study's senior author, said he and his colleagues are now working to develop a standardized testing system that could one day move the use of the RNA microarray analysis to detect the resistance signature into daily practice.

According to Rochelle Long, chief of the Pharmacological and Physiological Sciences Branch of the National Institute of General Medical Sciences, the Duke research "may eventually lead to a simple blood test to identify those who do not benefit from aspirin, enabling them to seek other therapeutic options."

In addition to the National Institute of General Medical Sciences, funding for the Duke study came from the Duke Institute for Genome Sciences & Policy; the National Institutes of Health; the National Center for Research Resources; the Centers for Disease Control and Prevention; and the David H. Murdock Research Institute.

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