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EXPEDITED REVIEW: VIEWPOINT

C-Reactive Protein and the Prediction of Cardiovascular Events Among Those at Intermediate Risk

Moving an Inflammatory Hypothesis Toward Consensus

Center for Cardiovascular Disease Prevention, the Divisions of Preventive Medicine and Cardiovascular Diseases, Brigham and Women's Hospital, the Harvard Medical School, and the Harvard School of Public Health, Boston, Massachusetts

Manuscript received January 31, 2007; revised manuscript received February 13, 2007, accepted February 13, 2007.

^_* Reprint requests and correspondence: Dr. Paul M Ridker, Center for Cardiovascular Disease Prevention, Brigham and Women's Hospital, 900 Commonwealth Avenue East, Boston, Massachusetts 02215. (Email: pridker{at}partners.org).

Over 20 large-scale prospective studies show that the inflammatory biomarker high-sensitivity C-reactive protein (hsCRP) is an independent predictor of future cardiovascular events that additionally predicts risk of incident hypertension and diabetes. In many studies, the relative impact of hsCRP is at least as large as that individually of low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, blood pressure, or smoking, and knowledge of hsCRP correctly reclassifies a substantial proportion of "intermediate-risk" individuals into clinically relevant higher- or lower-risk categories. Other studies show the relative benefit of statins to be greater among those with increased hsCRP and that achieved hsCRP levels after statin therapy predict recurrent event rates as much as achieved levels of low-density lipoprotein cholesterol. Nonetheless, it remains controversial whether the time has come to modify traditional algorithms used for global risk detection. As described here, 6 areas of controversy regarding hsCRP are resolvable with a consensus position that focuses in primary prevention on selective use among individuals with 5% to 20% 10-year risk as estimated by Adult Treatment Panel III, and focuses in secondary prevention on high-risk patients being treated with statin therapy. Forthcoming trial data could expand or contract this "screen selectively" policy, and investigators should be open to the possibility that second-generation inflammatory biomarkers may be developed that supplant hsCRP altogether. In the meantime, however, this consensus position on hsCRP should be one to which both advocates and critics of the inflammatory hypothesis of atherosclerosis can adhere because it is one that can immediately improve patient care.

Abbreviations and Acronyms   ATP = Adult Treatment Panel III   HDL = high-density lipoprotein   hsCRP = high-sensitivity C-reactive protein   LDL = low-density lipoprotein   ROC = receiver-operator characteristic

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