High-Sensitivity C-Reactive Protein As a Predictor of All-Cause Mortality: Implications for Research and Patient Care (Editorial‪)‬

Based on more than a decade of evidence, high-sensitivity C-reactive protein (hsCRP) [1] is in clinical use as an inexpensive adjunct to global cardiovascular risk prediction, as a tool to determine risk of future diabetes and metabolic syndrome, and as a method for monitoring efficacy of statin therapy. In the last decade, more than 20 prospective cohort studies have indicated that hsCRP concentrations independently associate with future risk of myocardial infarction, stroke, metabolic syndrome, and type 2 diabetes, and most studies of adequate sample size have found that hsCRP adds prognostic information to global risk prediction scores. On this basis, guidelines for use of hsCRP in clinical practice have been issued by the Centers for Disease Control and Prevention (1), and novel algorithms for risk prediction that incorporate hsCRP, such as the Reynolds Risk Score (www.reynoldsriskscore.com), have been shown to improve risk classification, particularly for "intermediate risk" patients who account for more than 70% of all vascular events (2). Further, as statins lower hsCRP in an LDL cholesterol-independent manner and as best clinical outcomes occur among statin-treated patients who not only reduce LDL cholesterol below 700 mg/L (70 mg/ dL) but also reduce hsCRP below 2 mg/L, the concept of "dual goals" has been introduced into cardiovascular clinical practice (3, 4). Because of its relationships with insulin resistance, leptin, and cytokine function (5), as well as its role in endothelial dysfunction and inhibition of fibrinolysis (6, 7), CRP has also been of pathophysiologic interest as an intellectual bridge linking low-grade systemic inflammation to both diabetogenesis and atherogenesis. Given the consistency and generalizability of these data, it is not surprising that clinical investigators might also seek evidence regarding CRP as a potential determinant of all-cause mortality. After all, coronary heart disease, cerebrovascular disease, and diabetes together account for 60% of adult deaths in the United States and Europe. In this issue of Clinical Chemistry, two reports address this research question from different perspectives, one evaluating CRP measurement among hospitalized patients and one evaluating hsCRP in a general outpatient community.