CRP Levels as Important as Cholesterol as Indicator of Cardiac Health, Studies Find
Lowering levels of C-reactive protein, which causes arterial inflammation, in the blood is as important as lowering LDL, or bad, cholesterol levels in preventing heart attacks and strokes, according to two studies published Thursday in the New England Journal of Medicine, USA Today reports (Sternberg, USA Today, 1/6). According to the Wall Street Journal, "the results also amount to the strongest evidence yet that CRP ... is a cause of heart disease" (Winslow, Wall Street Journal, 1/6).
One of the studies, led by Dr. Paul Ridker of Boston's Brigham and Women's Hospital, tracked 3,745 patients who had been hospitalized with heart attacks or severe coronary artery blockage.
The study originally sought to determine whether a moderate statin therapy -- 40 milligrams per day of Bristol-Myers Squibb's Pravachol -- was as effective in the prevention of heart attacks as a higher dose, 80 milligrams per day of Pfizer's Lipitor. Ridker amended the study to include questions about CRP to determine whether there would be fewer heart attacks and deaths in patients with lower amounts of the protein.
The second study, led by Dr. Steven Nissen of the Cleveland Clinic and sponsored by Pfizer, involved 502 patients with heart disease. Nissen treated participants with the same medication regimen as Ridker's study. Nissen's study aimed to determine whether CRP alone predicted heart disease progression. Statins reduce both cholesterol and CRP levels (Kolata, New York Times, 1/6).
According to Ridker's study, reducing levels of CRP was as important as reducing LDL cholesterol levels in preventing heart attacks. In addition, those with low CRP levels had a lower risk of heart attack regardless of whether LDL levels were high or low, the study found (Stein, Washington Post, 1/6).
Ridker's study found the following:
- Patients whose LDL levels were above 70 milligrams per deciliter and whose CRP was higher than two milligrams per liter had a 9.9% risk of heart attack recurrence.
- Patients who lowered CRP levels to below 2 mg/l, even when cholesterol levels stayed high, reduced the risk of heart attack to 7%, and lowering cholesterol but not CRP showed the same decline in risk.
- Lowering levels of both CRP and LDL resulted in a risk reduction of 4.9%, and lowering CRP levels below 1mg/l reduced risk to 4%, the study found (Maugh, Los Angeles Times, 1/6).
- Nearly 10% of participants whose CRP and cholesterol levels remained high had a heart attack or died by the end of the study (Allen, Boston Globe, 1/6).
In Nissen's study, patients' arteries were examined to measure CRP levels. Patients with low CRP levels had the least progression of heart disease, independent of cholesterol levels, according to the study (Washington Post, 1/6). In patients who lowered their CRP and cholesterol levels, researchers found a regression of plaque in the coronary arteries. "I'm looking right at the plaque, and when your CRP level is reduced, you are stopping the disease," Nissen said (New York Times, 1/6).
According to the Globe, "The new research is expected to accelerate the trend toward prescribing statins to treat cardiovascular disease" (Boston Globe, 1/6). The New York Times reports that if the research "is correct, a huge new market for the already popular statins could be opened among people whose cholesterol levels are normal but who have high levels of CRP."
Scientists speculate that high CRP levels could produce plaque build-up on artery walls, which could the lead to blood clots that block arteries. In healthy people, CRP levels usually are less than one mg/l, but the level increases with age as well as with obesity, diabetes, smoking and lack of exercise.
However, levels drop with certain behaviors, such as with exercise and weight loss, leading some scientists to say CRP is a marker -- rather than a cause -- of heart disease. Ridker said about one-third of the population has CRP levels in excess of three mg/l (New York Times, 1/6).
Researchers said the studies' findings might prompt physicians to routinely test for inflammation and treat it to lower the risk of heart disease (Ryerson-Cruz, Bloomberg/Hartford Courant, 1/6). Nissen said the results of the studies are "really going to change [the] practice" of treating heart disease patients (Ricks, Long Island Newsday, 1/6).
Although the prolonged use of statins has been associated with the risk of developing liver and muscle damage that increase with dose, researchers "indicated that a first step was to increase the dosage of a patient's statin when possible," the Los Angeles Times reports. The studies found a small increase in such risk, but the risk itself was small compared to the lowered risk of heart attack.
According to Nissen, "There is a very powerful benefit-to-risk ratio." Ridker said trying different brands of statins also could be effective if a higher dose doesn't lower CRP levels. "All statin drugs lower CRP," but some patients respond better to one brand than another, Ridker said (Los Angeles Times, 1/6). He added that "physicians can do a better job immediately. That translates into tens of thousand of lives right away just by doing better management of statin therapy" (Wall Street Journal, 1/6).
Ridker said, "This is the first hard evidence that lowering CRP can reduce events. You need to monitor both. It's simply not adequate (to treat) cholesterol alone" (Fauber, Milwaukee Journal Sentinel, 1/5).
Eugene Braunwald, chair of the CRP study group at Brigham and Women's, said, "The emerging CRP data represents a paradigm shift that has the potential to save thousands of lives. Our challenge now is to educate physicians and patients about the importance of CRP management" (Boston Globe, 1/6).
James Cleeman, coordinator of the National Cholesterol Education Program at the National Heart, Lung and Blood Institute, said, "These are very important papers. They are provocative. But we need to recognize that the relationship between CRP and heart disease is a developing story. This adds to the evidence, but I'm not sure it settles the issue" (New York Times, 1/6).
Scott Grundy of the University of Texas Southwestern Medical Center and author of the current treatment guidelines for lowering LDL said, "I agree lowering LDL only reduces heart attack risk by one-third. You've got two-thirds of the risk remaining. CRP is responsible for some of that risk but there are other factors involved, too" (USA Today, 1/6).
Mark Pepys of the United Kingdom's Royal & Free University College Medical School said, "There's no good evidence that lowering CRP will lower the risk. The evidence is not there that you must measure CRP in everybody and give statins to people with normal cholesterol. There's just no evidence for that" (Washington Post, 1/6).
Ridker's and Nissen's studies are available online.
ABCNews' "World News Tonight" on Wednesday reported on the study. The segment includes comments from Nissen and Ridker (McKenzie, "World News Tonight," ABCNews, 1/5).
In addition, NPR's "All Things Considered" on Wednesday reported on the study. The segment includes comments from Lori Mosca, director of preventive cardiology at New York-Presbyterian Hospital; Nissen; and Ridker (Knox, "All Things Considered," NPR, 1/5). The complete segment is available online in RealPlayer.