C-reactive protein and cardiovascular disease: a critical appraisal

C-reactive protein, a nonspecific marker of inflammation, has recently been proposed both as a marker of low-grade inflammation involved in atherogenesis and as a predictor of disease progression.

The physiologic functions of C-reactive protein as an anti-inflammatory scavenger molecule have begun to emerge. For example, C-reactive protein binds to damaged lipoproteins and facilitates their removal by phagocytes without full complement activation. Increased levels of C-reactive protein may result in direct effects on vascular cells, including induction of cytokines and prothrombotic factors. Several sources of biologic variation in the levels of C-reactive protein have been identified, chief among which are abdominal obesity and the metabolic syndrome. Although previous studies showed a potent independent association of C-reactive protein levels with cardiac events, the strength of association was shown to be much weaker than previously reported in recent large meta-analyses. Therapy with nonspecific anti-inflammatory agents such as statins in patients with coronary artery disease has been found to reduce adverse outcomes in association with reductions in C-reactive protein, on the basis of retrospective analysis of stored blood specimens.

Despite a relatively strong epidemiologic association with future adverse cardiovascular events, the great majority of apparently healthy individuals with elevated C-reactive protein will not experience cardiovascular disease. Even though more than 15 000 articles in PubMed mention C-reactive protein, current knowledge is insufficient to implicate C-reactive protein as a causative factor in atherothrombosis or to enable the recommendation of C-reactive protein testing to guide preventive or therapeutic interventions in cardiovascular diseases.