C-reactive protein and cardiovascular disease: a critical appraisal.
OBJECTIVE
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.


RESULTS
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.


CONCLUSIONS
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.
Sepulveda
Jorge L
JL
Department of Pathology, University of Pittsburgh, Pittsburgh, Pennsylvania 15213, USA. sepulvedajl@upmc.edu
Mehta
Jawahar L
JL
D002097:C-Reactive Protein / Q000378:metabolism* / Q000502:physiology; D002318:Cardiovascular Diseases / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D016207:Cytokines / Q000378:metabolism; D004730:Endothelium, Vascular / Q000503:physiopathology; D006801:Humans; D008074:Lipoproteins / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism
D016207:Cytokines; D008074:Lipoproteins; D009569:Nitric Oxide; D002097:C-Reactive Protein