High-sensitive C-reactive protein: universal prognostic and causative biomarker in heart disease?

C-reactive protein (CRP), a pentraxin protein, is an established marker of acute phase reactions. There is some experimental evidence that the CRP molecule could be causative in all stages of atherosclerotic disease starting from endothelial dysfunction, continuing to plaque formation and destabilization, and to atherothrombotic complications. However, each claim of causality has elicited a counterpoint argument, and Mendelian randomization studies have confidently shown that the concentration of CRP is unlikely to be causative. Meta-analyses have attributed a 1.5-1.7-fold risk to one standard deviation increase of high-sensitive CRP (a high-sensitivity CRP assay) for major cardiovascular events after adjustments for classical risk factors. Additional adjustments for metabolic factors reduced the risk to approximately 1.2-1.4-fold, which is still significant. Of interest, high-sensitive CRP also predicted all-cause and cancer mortality. Driven by the JUPITER trial that showed a benefit on outcome for treatment with rosuvastatin in primary prevention, treatment has been recommended in patients with a moderate Framingham Risk Score with a high-sensitive CRP of >2 mg/l. However, adding CRP to risk charts and biomarker panels mostly yielded small and inconsistent improvements.