Population Distributions of C-reactive Protein in Apparently Healthy Men and Women in the United States: Implication for Clinical Interpretation

Measurement of the acute-phase reactant C-reactive protein (CRP) has been used historically in the diagnosis and monitoring of active infection or inflammation. Recent prospective epidemiologic studies have demonstrated that CRP, at concentrations within the reference interval, is a strong predictor of myocardial infarction (1)(2)(3), stroke (1)(2)(4), sudden cardiac death (5), and peripheral arterial disease (6) in apparently healthy adults. High-sensitivity methods that are capable of reliably measuring CRP concentrations ≤0.15 mg/L (approximately the first and second percentiles of CRP distribution in healthy adults) have, therefore, been developed (7)(8). Furthermore, an algorithm for risk assessment of future coronary events that combines both CRP concentration and total cholesterol:HDL-cholesterol ratio has been proposed (9). According to this algorithm, an individual’s risk can be estimated with use of quintiles of CRP and lipids derived from ongoing population-based surveys. Because high-sensitivity methods have only recently become available, the frequency distributions of CRP in apparently healthy US adults have not been carefully examined. Such information is useful in determining the most appropriate CRP cutpoints for the risk assessment algorithm in men and women. In this report, we describe the frequency distribution of CRP in 22 403 US adults and propose new CRP cutpoints for clinical interpretation. CRP measurement was performed in 22 403 apparently healthy individuals participating in the Physicians’ Health Study (PHS), the Air Force/Texas Coronary Atherosclerosis Prevention Study (AFCAPS/TexCAPS), the Women’s Health Initiative (WHI), and the Women’s Health Study (WHS). Details of these studies have been published elsewhere (10)(11)(12)(13). To avoid the issue of confounding by disease outcome, we evaluated only those individuals who were free of cardiovascular disease at study entry and remained free from disease during follow-up. To avoid confounding by drugs, we eliminated those women …