Biomarkers of Cardiovascular Disorders - Applications of Biotechnology in Cardiovascular Therapeutics - page 124

C-Reactive Protein as Biomarker of Response to Statin Therapy
CRP levels are low in healthy young people - usually less than 1 mg/L of blood -
but they rise with age, obesity, diabetes, smoking, and a sedentary life. If people
lose weight, stop smoking, exercise, or take oral diabetes drugs, their CRP levels
fall. But a third of the population has levels greater than 3 mg/L, and levels that
high have been associated with heart disease risk. Questions remain as to the CRP's
normal role in the body. It was discovered about 70 years ago by scientists who
were trying to understand why some streptococci caused disease and others did not.
It is so named because it was found in the third band, called Band C, in a gel used
to separate proteins. Then, about half a century ago, physicians noticed that CRP
flooded the patient's blood after a heart attack, and for several years, the protein
was used to help diagnose heart attacks.
Two studies have shown that reducing the levels of CRP, which plays a role in
heart disease, may be as powerful a tool in slowing heart disease and preventing
heart attacks and cardiac-related death as lowering cholesterol (Ridker et al. 2005 ;
Nissen et al. 2005 ). The participants were patients with severe heart disease who
were taking high doses of statin drugs, which reduce both cholesterol and CRP. In
both studies, CRP independently predicted heart disease progression. Lower CRP
levels were linked to a slower progression of atherosclerosis and fewer heart attacks
and deaths. And this effect was independent of the effect of lowering cholesterol.
This is hard clinical evidence that reducing CRP is at least as important as lowering
cholesterol. These findings indicate that physicians should monitor CRP levels in
patients with severe heart disease and do whatever it takes, including giving high
doses of the most powerful statins, to get levels below 2 mg/L blood.
However, more work is needed to prove that CRP directly causes heart disease.
The studies involved only people with severe heart disease; therefore, it remained
unknown whether healthy people would benefit from reducing their CRP levels.
It is also possible that CRP is a biomarker for some other abnormality that is
corrected by statin drugs to reduce heart disease risk. Even before these studies,
evidence had been accumulating that CRP and heart disease were somehow linked.
There were hypotheses to explain why the protein could cause plaque to develop in
coronary arteries, lead plaque to burst open or bring on the formation of blood clots,
which block arteries and cause heart attacks. Some pharmaceutical companies have
started programs to develop drugs that make a specific target of CRP and prevent
its synthesis. That CRP levels drop with exercise and weight loss has led some to
argue that the protein is a biomarker of heart disease risk, not a cause. CRP is made
in the liver and also in the walls of coronary arteries and possibly elsewhere in the
body. Its levels, which can be measured with a simple blood test, often rise and
remain high in patients who have chronic inflammation from conditions like rheu-
matoid arthritis, for example, or periodontal disease. Patients with chronic inflam-
mation also have an increased risk of heart disease. The next step is to see if
reducing CRP levels can prevent heart attacks in healthy people. A new study will
enroll 15,000 people with normal cholesterol levels but higher-than-average levels
of CRP, >2 mg/L blood. The participants will be randomly assigned to take either
a statin or a placebo.