C-Reactive Protein: A New Risk Factor for Heart Attack
A recent study shows that high levels of this protein may be
a better predictor of heart attacks than high cholesterol levels.
Should you be tested for it?
One of the key markers for measuring
heart attack risk has been a high level of low density lipoprotein
(LDL, or “bad”)
cholesterol. Yet about half of the people who develop coronary
heart disease (CHD) have normal or even low LDL levels. In the
search for additional ways to predict the risk of CHD, considerable
evidence indicates that a molecule called C-reactive protein
(CRP)—a blood marker for excessive inflammation of the
artery walls—tends to be elevated in people who go on to
develop CHD and have a heart attack. While lowering cholesterol
remains a primary goal in preventing heart attacks, it is possible
that CRP may be slightly better than cholesterol (or at least
comparable with cholesterol) at predicting a person’s risk
for heart attack.
At first, researchers thought that CRP might
just be associated with other risk factors for CHD, like smoking,
high blood pressure,
or high LDL cholesterol levels, rather than a causative factor.
But a study published in January 2003 in Circulation shows that
elevated CRP in the blood may directly contribute to the formation
of blood clots that can cause heart attacks. Based on this and
other studies, CRP appears to have a predictive value that is
independent of other risk factors for CHD.
We do not know whether
treatment to lower high CRP levels decreases the risk of heart
attacks. But if future randomized trials show
that this is the case, then measuring CRP—in addition to
cholesterol levels and blood pressure—may become an established
protocol of primary heart attack prevention.
What Is CRP?
The liver produces CRP when inflammation occurs
anywhere in the body. Such inflammation can stem from a number
of sources, not
just within the walls of arteries, including gingivitis (gum
disease), metabolic syndrome, high blood pressure, obesity, diabetes,
and smoking. Inflammation is also a component of infections (such
as the influenza virus or Helicobacter pylori—the bacterium
that causes peptic ulcers) and of rheumatoid arthritis.
above 3 mg/L (milligrams per liter) are considered elevated.
Up to 50% of heart attack patients have elevated CRP
levels, as do over 65% of unstable angina patients and over 90%
of patients with unstable angina who’ve also had a heart
attack. In people without CHD, high CRP levels are rare, occurring
in less than 10%.
Some of the strongest evidence showing that CRP
levels are independently related to the risk of heart attacks
was published in November
2002 in The New England Journal of Medicine. Researchers measured
LDL cholesterol and CRP levels in nearly 28,000 healthy women
and followed them for an average of about 8 years, looking for
evidence of cardiovascular disease.
Women with the highest CRP
levels (over 4.2 mg/L) at the beginning of the study were 2.3
times more likely to develop cardiovascular
disease than those with
the lowest CRP levels (below 0.5 mg/L). Those with the highest LDL cholesterol
levels (over 154 mg/dL), on the other hand, were only 1.5 times more likely to
develop cardiovascular disease than those with the lowest LDL levels (below 98
mg/dL). Among women not using hormone replacement therapy at the study’s
start, those with low LDL cholesterol but high CRP levels were slightly more
likely to have cardiovascular disease by the end of the study than did women
with low CRP but high LDL cholesterol levels. These data led the researchers
to conclude that CRP “is a stronger predictor of future cardiovascular
events than LDL cholesterol.”
Who Should Be Tested?
The test for CRP is easy for doctors to
perform (it involves drawing blood from a vein in the arm) and
costs only about
$15 to $20. Does this mean everyone should
get the test? According to guidelines jointly published by the American Heart
Association (AHA) and Centers for Disease Control and Prevention (CDC) in January
2003 in Circulation, the people who will likely benefit from CRP testing
those with an intermediate risk of CHD—that is, a 10% to 20% risk of a
heart attack in the next 10 years. (To determine your risk level, talk to your
doctor or assess your risk at a Web
site sponsored by the National Institutes
If you are found to be at intermediate risk for a heart attack,
establishing that you have a high CRP level may indicate the need to begin a
CHD prevention program. You may also be more motivated to improve prevention
efforts such as exercising more and eating a healthier diet.
People already at
high risk for CHD and those receiving medication to prevent or treat CHD do
not need or benefit from a CRP test, according to the AHA and
CDC. Such people should already be aware of their overall elevated risk for
and finding an elevated CRP level will not provide any additional information.
If you are at intermediate risk for CHD and decide
to have a CRP test, the AHA and CDC suggest you average the results
two tests taken at least two
apart. Don’t begin treatment to lower CRP levels on the basis of one
test, since test results can be affected by a flare-up of inflammation from
or an infection. If you know you have an infection, postpone the test. Several
versions of the test are available. Be sure to use the high sensitivity CRP
(hs-CRP) version; this is the only one that can detect small differences in
CRP that may
translate into large differences in CHD risk.
The AHA/CDC report states that
people who have a CRP level below 1 mg/L are at a low risk for cardiovascular
events, while those with a CRP level from
3 mg/L are at intermediate risk.
The two organizations emphasize that the
CRP test cannot replace an evaluation of other risk factors,
and that an elevated CRP alone does not provide sufficient
evidence to warrant starting drug therapy.
Treating High CRP Levels
Currently, no drug is specifically designed
to lower elevated CRP levels, and no clinical trial has yet been
show that lowering CRP directly
causes a reduction in heart attacks. However, if you have a high CRP level,
the measures that play a role in reducing other risk factors for CHD appear
to also lower elevated CHD levels—and so could potentially decrease
risk of heart attack even further.
Physical activity. A correlational
study of 722 men published in the November 2002 issue of Arteriosclerosis,
Thrombosis, and Vascular Biology found that
the more men exercised, the lower their CRP levels were. While some preliminary
suggest that initiating a regular exercise program may cut CRP levels up
to 35%, the type and intensity of exercise that may be necessary to reduce
Weight control. If you are overweight, losing weight may
also lower CRP levels. A February 2002 Circulation report found
that, among 25 obese postmenopausal women who lost an average of 32 lbs.,
CRP levels also fell by 32%.
Aspirin. Aspirin not only
reduces the likelihood of a blood clot, but also decreases inflammation.
Talk to your doctor before taking aspirin for this
Statin drugs. Prescribed for lowering
LDL cholesterol levels, statin drugs also lower CRP levels. In
a 2001 New England
Journal of Medicine study
of 5,742 people
with elevated CRP but normal LDL cholesterol levels, those who received
lovastatin (Mevacor) reduced their CRP levels by 15%. They also experienced
of heart attacks and other CHD events than participants who took a
placebo. However, more definitive data are needed before physicians
to lower CRP in people with normal LDL cholesterol levels.
ACE inhibitors. Some research indicates that a group of blood pressure-lowering
drugs called ACE inhibitors can also decrease CRP levels. More research
is needed, however, before doctors begin to prescribe ACE inhibitors