Two landmark studies offer the best evidence yet that inflammation plays a key role in heart disease and could immediately change the way doctors monitor and treat patients at risk for heart attacks and strokes.

If the changes are adopted, researchers say that thousands of deaths from heart disease could be prevented in the United States each year.

Prevention of heart disease currently focuses on lowering levels of "bad" LDL cholesterol (search) through diet, exercise, and medication. But these studies suggest that reducing inflammation, which is thought to play a role in heart disease, may be just as important. Doctors can gauge inflammation in the body through a blood test that measures the amount of C-reactive protein (search) (CRP) in the blood.

Study participants taking cholesterol-lowering statin drugs (search) showed reductions in CRP levels. Lowering CRP, like lowering cholesterol, was found to be an important, independent predictor of heart attack and stroke risk. Lowering CRP levels with statin drugs also slowed or reversed atherosclerosis (search), a buildup of plaque in blood vessel (search) walls also known as hardening of the arteries.

“We now know that it is not just cholesterol that drives the plaque buildup in the arteries. It is also C-reactive protein,” Cleveland Clinic cardiovascular researcher Steve Nissen, MD, tells WebMD. Nissen led one of the two studies.

“These days, avant-garde physicians may measure CRP levels once to help determine underlying risk for cardiovascular disease. But that is not enough. CRP is not a risk factor anymore. It is a player. It’s a part of the disease process.”

The Payoff

Longtime C-reactive protein researcher Paul M. Ridker, MD, led the second study, which was conducted at Harvard University’s Brigham and Women’s Hospital. Both studies are published in the Jan. 6 issue of The New England Journal of Medicine.

Ridker tells WebMD that while the new findings have important implications for the development of new drugs to prevent heart disease, there is also “an immediate clinical payoff.”

“We believe we can save tens of thousands of lives immediately simply by making physicians understand that they need to monitor CRP levels in the same manner that they now monitor cholesterol levels,” he says.

Ridker and colleagues examined the impact on heart disease of lowering LDL cholesterol and CRP levels with statin therapy. The study involved just over 3,700 patients with heart disease.

Lowering CRP levels with statin therapy was found to reduce the risk of heart attack and death from heart disease among patients who did not lower their cholesterol to recommended levels.

Patients with the lowest levels of both LDL cholesterol and CRP after 30 days of statin therapy had the lowest overall risk of heart attack and death from heart disease.

“There are now over 30 major studies that have shown that CRP levels independently predict heart attack risk,” Ridker says. “What has been missing is direct evidence that if you lower CRP you could lower cardiac risk. Now we have two independent papers coming out simultaneously that show this.”

The Cleveland Clinic (search) researchers measured arterial plaque buildup along with LDL and CRP levels in 502 patients with heart disease being treated with statin drugs. They found that cholesterol and inflammation levels independently predicted the progression of atherosclerosis.

“The striking thing was that about half the benefit of these drugs came not from lowering cholesterol but from lowering CRP levels,” Nissen says. “This means that if a patient has achieved target cholesterol levels on statin therapy but still has elevated CRP, then more aggressive treatment is called for. If you don’t work to get CRP levels down you are only getting half the benefits of statin therapy.”

The Challenge

The target LDL cholesterol level for very high risk patients on statin drugs was recently lowered from 100 mg/dL to 70 mg/dL.

There are no uniform guidelines for optimal CRP, but Ridker says the goal for heart disease patients should be to lower CRP levels to below 2 mg/dL.

American Heart Association spokesperson Sidney Smith Jr., MD, says it is clear from the two studies that some patients could benefit from more aggressive statin treatment. But the optimal treatment strategy for patients who have elevated CRP levels despite aggressive statin treatment is not yet clear, he says.

“We need a better understanding of which therapeutic strategies work best in people whose CRP levels aren’t lowered with statins,” he says.

Smith says the studies do argue in favor of including CRP in the tests used to monitor patients with cardiovascular disease. Ridker says the next step is to get that message to doctors and their patients.

“The challenge is to educate physicians and patients about the importance of CRP measurement and CRP reduction, just as we did a decade ago when we taught them about LDL measurement and reduction,” he says.

By Salynn Boyles, reviewed by Brunilda Nazario, MD

SOURCES: The New England Journal of Medicine, Jan. 6, 2005; vol 352: pp 20-39. Paul M. Ridker, MD, Center for Cardiovascular Disease Prevention, Brigham and Women’s Hospital and Harvard Medical School, Boston. Steven E. Nissen, MD, department of cardiovascular medicine, The Cleveland Clinic, Ohio. Michael R. Ehrenstein, PhD, FRCP, Center for Rheumatology, University College, London. Sidney Smith Jr., MD, director, Center for Cardiovascular Science and Medicine, University of North Carolina at Chapel Hill; spokesman, American Heart Association.