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
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
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
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."