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C-reactive protein (CRP) is a liver-derived protein whose concentration increases manyfold during inflammation or infection, making it a useful diagnostic and treatment measure in diseases such as rheumatoid arthritis. However, in the last decade, CRP has garnered interest as a biomarker of vascular risk that has stimulated more studies than perhaps any other “novel” biomarker. In these studies, the much lower CRP values seen in healthy individuals free from overt infection or inflammation, detected by a new generation of sensitive assays, have been associated in study after study with the risk of a first cardiovascular event (rev. in (1). Yet, despite the consistency of this association, whether CRP is causally involved in atherogenesis or whether it helps in prediction of cardiovascular disease (CVD) events remains intensely controversial (2,3).In light of this controversy, studies examining the association of CRP with vascular outcome and mortality in patient populations, such as those with diabetes, where prospective data remain relatively sparse are to be welcomed. In the current issue of Diabetes , Bruno et al. (4) report that although CRP was related to risk of all-cause and CVD mortality in their 5-year follow-up of the Casale Monferrato Study, the improvement in individual risk prediction beyond established risk markers, evaluated by a range of statistical tests, was marginal at best. The results from this helpful study, therefore, currently caution against routine measurement of CRP for risk prediction in diabetes patients.Why should CRP not better predict risk in individuals, given its consistent association with CVD and mortality? Several issues contribute. The association of CRP with incident events is linear when both CRP values and risk are plotted on …

C-Reactive Protein and Prognosis in Diabetes: Getting to the Heart of the Matter