HEALTHCRP gains notice as key marker of cardiovascular healthResearch on C-reactive protein has some experts saying cholesterol guidelines should be rewritten. Others caution it's too soon for routine CRP testing.By Victoria Stagg Elliott, amednews staff. Dec. 16, 2002. Levels of C-reactive protein may be a stronger predictor of potential heart attack or stroke than cholesterol, according to a study published in the Nov. 14 New England Journal of Medicine. The study, which involved more than 27,000 people, is by far the largest to date. It echoes what experts have suspected and smaller studies have been implying for years: Cholesterol is not the be-all and end-all in predicting cardiovascular health. About half of people who have heart attacks have normal levels of cholesterol. CRP may be one of the missing links behind cardiovascular events for these people.
Among heart attack patients, about half have normal cholesterol levels.
"CRP has arrived," said Ishwarlal Jialal, MD, PhD, professor of internal medicine and pathology at the University of California, Davis. "It is time for CRP testing to be used in primary prevention." Researchers at Harvard Medical School and Brigham and Women's Hospital in Boston, led by Paul M. Ridker, MD, MPH, director of the hospital's Center for Cardiovascular Disease Prevention, analyzed blood samples taken from thousands of participants in the Women's Health Initiative. They also gathered information from autopsy reports, death certificates, medical records and family members about any cardiovascular events. The investigators found that levels of both cholesterol and C-reactive protein were indicative of potential heart attacks and strokes, although the latter was more so. Also, women with high levels of one didn't necessarily have high levels of the other. Waiting in the wingsCRP has long been considered to have the most potential as a possible screen for cardiovascular risk, particularly for those who have normal cholesterol levels. Testing is relatively simple. Levels can be determined by a blood test that could be done at the same time that cholesterol is measured, although few labs are set up to do it. This situation, however, is expected to change as demand for CRP testing grows. Treatment to lower the CRP is also readily available because the same therapies that lower cholesterol -- exercise, aspirin and statins -- also lower CRP. Experts say the study is large enough and compelling enough to take very seriously. The first recommendations on the use of CRP testing are expected from the American Heart Assn. and the Centers for Disease Control and Prevention within the next few months.
The same treatments that lower cholesterol also work for C-reactive protein levels.
"It really is entering the mainstream," said Robert Bonow, MD, president of AHA. "There is a growing body of evidence here that this is an important marker of risk." Many also say it may even be time for the inclusion of CPR testing in more established heart health guidelines. For instance, some say last year's "Third Report of the Expert Panel on the Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults," by the National Heart, Lung and Blood Institute, should be rewritten. Those guidelines do not recommend routine testing of CRP, although the document does suggest that people with elevated levels may be candidates for more aggressive cholesterol-lowering treatment. "They have to go back to the drawing board," said Dr. Jialal, who also researches CRP. But although the NEJM study was compelling, few believe CRP testing should be as routine as cholesterol testing -- at least not yet. More research is needed to determine if reducing CRP actually reduces heart attacks. And, at the American Heart Assn.'s scientific sessions in Chicago last month, the team that published the NEJM study announced plans to do just that with a 15,000-subject study. "A large-scale clinical trial should be able to determine if individuals with low LDL but elevated CRP may ultimately be good candidates for medical therapy with statin drugs," said Dr. Bonow, who is also chief of cardiology at Northwestern University in Chicago. And CRP will certainly not replace cholesterol. Critics charge that CRP is not specific enough by itself. It can be elevated by many factors, such as physical trauma or cancer, that may not contribute to heart disease. Behaviors such as smoking that are already known as heart health risk factors can also up the numbers. But in that situation, many doctors are hoping that the test will provide another concrete number that may be able to scare patients into taking action to reduce their heart attack risk.
CRP levels are measured by a simple blood test.
"I wouldn't say CRP testing is better. I'd say it's additive to cholesterol testing," said Dr. Bonow. "But it could be a wake-up call to exercise more, stop smoking, lose weight, etc." Experts also feel the confirmation of CRP as a heart risk factor may lead to more therapies that specifically target inflammation. A greater understanding of CRP is also broadening the understanding of heart disease and the factors that play a part in it. "This is an advance in medicine that will further reduce the burden of heart disease in our population," said Dr. Jialal. "We are trying to find out now why, with the statins, we're only reducing heart disease 40%. What's happening to the other 60%? For them, is lowering CRP important? Are there other modalities that will emerge in the future? What about designer drugs that will specifically lower inflammation that we are going to be adding on to what we already have?" But there are additional concerns that, because CRP testing may mark more people for primary prevention, many more patients could end up on statin drugs, possibly unnecessarily and at great cost. "Are we going to be treating everyone with statin drugs?" said Dr. Bonow. "We're still not sure what to do with the CRP regarding treatment. Even if we identify people at risk, what do we recommend they do?" ADDITIONAL INFORMATION:Predicting strokes and heart attacksA Boston study is prompting experts to examine the role of C-reactive protein testing. Objective: To determine how well levels of cholesterol or C-reactive protein predict cardiovascular events.
Source: New England Journal of Medicine, Nov. 14 WeblinkAbstract, "Comparison of C-Reactive Protein and Low-Density Lipoprotein Cholesterol Levels in the Prediction of First Cardiovascular Events," abstract, New England Journal of Medicine, Nov. 14 (vol. 347, issue 20) (http://content.nejm.org/cgi/content/full/347/20/1557) Article, "C-Reactive Protein: To Screen or Not to Screen?" New England Journal of Medicine, Nov. 14 (vol. 347, issue 20) (http://content.nejm.org/cgi/content/full/347/20/1615) AHA 2003 Scientific Sessions (http://www.scientificsessions.org/) Copyright 2002 American Medical Association. All rights reserved.
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