Post-mortem
study finds that sudden death is associated with higher C-reactive
protein levels in blood and coronary plaques
In a post-mortem study, people who had sudden cardiac death had higher
levels of C-reactive protein in blood and in coronary plaques than
people who died from non-cardiac causes, according to an article in
the April 16th rapid access issue of Circulation.
"Our research provides
the first indication that C-reactive protein is a risk factor for
atherosclerotic vascular disease and sudden death," says lead
investigator Renu Virmani, M.D.
In the American study, researchers
autopsied 302 men and women lacking any inflammatory conditions
other than atherosclerosis. These included 73 bodies with arterial
blockages caused by plaque rupture or erosion, 71 bodies with stable
arterial plaque, and 158 controls - the last group made up of people
who died from non-cardiac sudden death and without any condition
associated with elevated C-reactive protein level.
During the autopsy, researchers
determined C-reactive protein levels from post-mortem blood samples
and used a special staining technique to look at C-reactive protein
in the plaque itself. They found that people who had sudden cardiac
death had higher levels of C-reactive protein in their blood and
their coronary plaque than those who died from non-cardiac causes.
Scientists have known for some
time that elevated blood levels of C-reactive protein indicate damage
to arterial walls. However, until now it has not been known that
blood levels also correlate to levels within atherosclerotic plaque
and plaque vulnerability to rupture, says Virmani.
"This is the first time
it has been linked to sudden death from cardiovascular disease,"
she says. "If circulating C-reactive protein levels are elevated,
there are more vulnerable plaques. It is that simple. It is very
important to identify vulnerable plaques in order to begin treatment."
C-reactive protein can increase
1,000-fold in the bloodstream in response to acute infection, trauma,
burns, and other inflammatory conditions. It is also released into
the bloodstream when coronary arteries are constricted or damaged.
Along with C-reactive protein
levels in plaque and in blood serum, the overall plaque burden on
the heart, total cholesterol, diabetes, smoking history, and body
mass index were determined for each subject. The number of thin-cap
plaques, also called atheroma, per heart was also determined. Plaques
with thin caps are the least stable and most likely to rupture unexpectedly.
C-reactive protein levels were compared and subjects were stratified
into highest and lowest quintiles.
"It's exciting to think
we may be able to detect the culprit lesion that might kill a patient,"
explains Virmani. "There are people walking around with high
C-reactive protein levels who have no idea they are at risk because
all the other signs appear normal. C-reactive protein is the only
abnormality that gives rise to heightened risk of sudden death once
factors such as pneumonia and other conditions that raise C-reactive
protein levels are factored out."
The researchers found the median
C-reactive protein level was 3.2 micrograms per milliliter (ug/mL)
in cases with acute plaque rupture, 2.9 ug/mL in cases with plaque
erosion, 2.5 ug/mL in cases with stable plaque, and 1.4 ug/mL in
the control group.
In the study, 52.8 percent
of people whose plaque had ruptured had serum levels above 3 ug/mL
compared with only 20 percent of controls. About 39 percent of people
with eroded plaques and 35 percent of people with stable plaque
had levels above 3 ug/mL.
Previous studies have shown
that baseline plasma levels of circulating C-reactive protein can
predict risk of future stroke and myocardial infarction. In unstable
angina, elevated levels are associated with poorer disease prognosis.
This study shows C-reactive protein is also significantly elevated
in patients with coronary artery disease, both with and without
acute coronary thrombosis.
The only other predictor of
sudden cardiac death determined in the study was cigarette smoking.
About 70 to 80 percent of people with eroded plaques were smokers
compared with 40 percent of people with stable plaque.
"In the future,
all patients should have their C-reactive protein levels checked.
That way we can intervene with lifestyle counseling and drugs like
statins and aspirin," Virmani says.
|