By William J. Cromie
For about $20 you can determine your risk of a future heart attack, according
to a new study from Harvard Medical School.
The test measures levels of a protein that increase with the amount of
inflammation in coronary arteries. The study showed that healthy women
with the highest levels of this substance, known as high-sensitivity C-reactive
protein, have more than four times the risk of suffering a heart or blood-vessel
problem than women with lower levels of the marker. Previous research
revealed that men with the highest levels of this protein in their blood
have three times the risk of heart attack and two times the risk of stroke
compared to men with the lowest levels.
"Cholesterol screening is currently the gold standard for predicting
heart-attack risk, but nearly half of all heart attacks occur among men
and women with normal cholesterol levels," notes Paul Ridker, a cardiologist
at Harvard-affiliated Brigham and Womens Hospital in Boston. "In
fact, the amount of risk associated with high-sensitivity C-reactive protein
is almost twice that associated with high levels of low density cholesterol."
The Food and Drug Administration approved the first test for this protein
last November. "Its now available to all doctors and costs
about $15-$20," says Ridker, who is also an associate professor of
medicine at Harvard Medical School.
An improved ability to predict risk of heart attack can reveal who will
benefit most from preventive strategies, such as increased exercise, a
healthier diet, and quitting smoking. Also, it pinpoints the best candidates
for so-called statin drugs, such as pravastatin, which lower levels of
both high-sensitivity C-reactive protein and low-density, or harmful,
"These drugs can prevent first heart attacks," Ridker points
out, "but they are too expensive to prescribe for everyone. The new
test, along with cholesterol screening, should enable doctors to better
determine who is most likely to benefit from their use."
Not all tests for the protein are equal, however. "Doctors who use
this new approach must use an accurate high-sensitivity test for C-reactive
protein, not one of the older tests, which are far less reliable,"
cautions Nader Rifai, a Harvard associate professor of pathology who participated
in this research.
Healing Begets Harm
Exactly how the protein is linked to heart disease and stroke remains
unclear. Its known to help white blood cells destroy invading bacteria
and viruses, a process accompanied by inflammation. But theres a
harmful side to such healing. Inflammation sometimes leads to vulnerable
plaques, or raised clumps of cholesterol in the lining of blood vessels.
The plaques are vulnerable because they are likely to rupture, and the
fragments can block narrower arteries downstream, leading to a heart attack
"Inflammation is now understood to play a critical role in the conversion
of a stable cholesterol plaque into a worrisome, unstable lesion (injury),"
Ridker points out.
To clarify the relationship between various markers involved in this
process, including C-reactive protein, total cholesterol, low density
cholesterol, and other compounds, Ridker and his colleagues checked blood
samples from 28,263 healthy, middle-aged women. The women were followed
for three years, and levels of 12 different markers were compared with
incidences of death from heart disease, heart attacks, stroke, and need
for procedures to unblock their coronary arteries.
High-sensitivity C-reactive protein levels turned out to be the strongest
and most significant predictor of who would suffer these cardiovascular
problems. The relationship held true even among people with cholesterol
levels considered safe by national guidelines.
"Heart disease is the number one killer of men and women in the
United States," Ridker says. "Any improvement we can make in
a doctors ability to predict heart attacks will increase the number
of lives we can save through targeted use of drugs like the statins and
more aggressive changes in lifestyles."
A report on this research was published today in the March 23 2000 issue
of the New England Journal of Medicine.