A once-daily pill of low-dose aspirin helps lower the
potential for clot-forming blood cells in both men and
women to stick together in narrow blood vessels, a study
from Johns Hopkins shows.
In what is believed to be the first direct comparison
of blood cell testing in both sexes of 81 milligrams of
acetyl salicylic acid a day, Hopkins researchers found
aspirin therapy prevents the clumping together of these
clot-forming cells, called platelets. Clots in blood
vessels of the heart and brain can cause heart attacks and
However, while the drug's overall effects on blood
cell function were the same for men and women, the
investigators found that women's platelets reacted somewhat
more strongly to aspirin before the start of therapy, and
remained so even after treatment.
The study findings, which appear in the Journal of
the American Medical Association online March 21,
challenge the conclusions from several other recent
studies, including the federal Women's Health Study, which
showed that low-dose aspirin had no effect in preventing
heart attacks in women, even though it worked in men.
Previous results, the researchers say, were not likely
caused by the failure of aspirin to prevent platelets from
clumping together and forming blood clots in women.
"Women are clearly benefiting from taking aspirin and
should continue to take it to improve their cardiovascular
health," said study senior investigator Diane Becker, a
professor at the schools of
Medicine and Public
Health. "Aspirin has been proven by all previous
studies to lower the risk of stroke and, as our latest
findings show, it also reduces platelet aggregation that
can lead to potentially fatal clots in blood vessels."
"Our results show that aspirin does what it is
supposed to do in both men and women," said platelet
biologist and study co-author Nauder Faraday, an associate
professor in the School of Medicine. "But women started at
a higher baseline level of platelet aggregation and
remained slightly higher even after taking aspirin. So, it
remains unclear if the residual differences in platelet
function impact the drug's overall beneficial effects, or
if the doses used in earlier studies were sufficient to
decisively prevent heart attacks in women.
"Further research is required to get a definitive
answer as to whom aspirin really benefits, under what
circumstances it does work and does not work, and just how
much is required in different people," he said.
Results in both men and women showed that aspirin,
taken daily for a two-week period, works by inhibiting key
biological pathways that lead to platelet clumping.
Using an electrical measure of how well platelets
stick together, researchers found that in aspirin-treated
men, clumping decreased by 15.1 ohms. The decrease was
statistically the same in aspirin-treated women, at 17.3
ohms. In this test, an ohm is the measure of electrical
resistance caused by platelets as they impede the flow of
electricity in a wire probe inside a test tube filled with
Moreover, platelet aggregation was largely suppressed
in at least three other key pathways related to their
function when platelets were stimulated with substances
that normally trigger clot formation. Each of these tests
involved mixing whole blood, or platelet-rich plasma, from
aspirin-treated men and women with various concentrations
of each of the main chemical compounds involved in the
pathways collagen, adenosine diphosphate and epinephrine to
see how platelets responded.
For example, in aspirin-treated men, platelet clumping
went down by 14.6 ohms when 1 microgram of collagen per
milliliter was added to whole blood, and decreased by 2.4
ohms when exposed to a higher dose of 5 micrograms per
milliliter. In treated women, reductions were the same, at
14.9 ohms and 2.42 ohms, respectively.
When 10 micromoles per liter of adenosine diphosphate
were added to whole blood, platelet aggregation decreased
the same amount, 0.19 ohms in men and 0.21 ohms in women.
Addition of 2 micromoles per liter of epinephrine to
platelet-rich plasma produced significantly greater
reductions in platelet clumping in treated women, a drop of
36.9 percent, while it was less of a reduction for men, at
31.5 percent. Again, the researchers say, these changes
would have been zero if aspirin had had no effect.
Further analysis of results highlighted mainly two
factors — platelet reactivity levels before therapy
starts and gender — as having played a significant
role in predicting the effects of aspirin therapy on
platelet clumping. Other factors such as age, race or known
risk factors for heart disease, including smoking, obesity
and high blood pressure, were not found to be good
predictors of aspirin's beneficial effects.
More than 500 men and 700 women participated in the
study, called the Genetic Study of Aspirin Responsiveness,
or GeneSTAR. Conducted solely at Hopkins from June 2004 to
November 2005, the study enrolled participants from across
the country who ranged in age from 21 to 80; 31 percent
were black, and the rest were white. None had previous
histories of heart problems, such as a heart attack, but
all were considered to be at slightly increased risk of
heart disease because of a family history. Fifty percent of
women participants were postmenopausal.
Blood testing was conducted both before and after
treatment. In total, more than 200 different tests of
platelet reactivity were performed and analyzed in the
study. Because whole blood contains other cells that affect
platelet aggregation, testing was repeated using a purified
version of test samples made up of strictly platelet-rich
At the start of the experiment, laboratory tests of
blood platelets in women were found four times more likely
than in men to aggregate when exposed to arachidonic acid,
a clot-inducing chemical in the pathway that is most
suppressed by aspirin.
While taking aspirin, participants maintained a strict
and consistent dietary and exercise regimen, with no
smoking or consumption of foods that by themselves affect
platelet activity, such as caffeine, chocolate, wine or
grapefruit juice. Physical examinations and pill counts
were conducted to ensure that all participants adhered to
the study protocol. Because aspirin reaches its maximal
effect in the body at five days, the researchers say a
longer study testing period was not required to determine
the drug's effects on platelet function.
Funding was provided by the National Heart, Lung and
Blood Institute, a member of the National Institutes of
Health; and the Johns Hopkins Clinical Research Center.
Besides Becker and Faraday, investigators in this
research were Jodi Segal, Dhananjay Vaidya, Lisa Yanek, J.
Enrique Herrera Galeano, Paul Bray, Taryn Moy and Lewis