C-reactive protein as a cardiovascular risk factor: more than an epiphenomenon?
BACKGROUND
Circulating levels of C-reactive protein (CRP) may constitute an independent risk factor for cardiovascular disease. How CRP as a risk factor is involved in cardiovascular disease is still unclear.


RESULTS
By reviewing available studies, we discuss explanations for the associations between CRP and cardiovascular disease. CRP levels within the upper quartile/quintile of the normal range constitute an increased risk for cardiovascular events, both in apparently healthy persons and in persons with preexisting angina pectoris. High CRP responses after acute myocardial infarction indicate an unfavorable outcome, even after correction for other risk factors. This link between CRP and cardiovascular disease has been considered to reflect the response of the body to the inflammatory reactions in the atherosclerotic (coronary) vessels and adjacent myocardium. However, because CRP localizes in infarcted myocardium (with colocalization of activated complement), we hypothesize that CRP may directly interact with atherosclerotic vessels or ischemic myocardium by activation of the complement system, thereby promoting inflammation and thrombosis.


CONCLUSIONS
CRP constitutes an independent cardiovascular risk factor. Unraveling the molecular background of this association may provide new directions for prevention of cardiovascular events.
Departments of Cardiology, Pathology and Internal Medicine, Free University Hospital, Amsterdam, The Netherlands.
W K
WK
Lagrand
C A
CA
Visser
W T
WT
Hermens
H W
HW
Niessen
F W
FW
Verheugt
G J
GJ
Wolbink
C E
CE
Hack
D000328:Adult; D000368:Aged; D015415:Biomarkers; D002097:C-Reactive Protein / Q000032:analysis*; D002318:Cardiovascular Diseases / Q000097:blood / Q000453:epidemiology* / Q000209:etiology; D016022:Case-Control Studies; D015897:Comorbidity; D003167:Complement Activation; D003324:Coronary Artery Disease / Q000097:blood / Q000453:epidemiology / Q000473:pathology; D016207:Cytokines / Q000097:blood; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007239:Infections / Q000097:blood / Q000150:complications / Q000453:epidemiology; D007249:Inflammation; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D009203:Myocardial Infarction / Q000097:blood / Q000453:epidemiology; D009206:Myocardium / Q000473:pathology; D009336:Necrosis; D011379:Prognosis; D011446:Prospective Studies; D012189:Retrospective Studies; D012307:Risk Factors; D019851:Thrombophilia / Q000209:etiology / Q000503:physiopathology
D015415:Biomarkers; D016207:Cytokines; D002097:C-Reactive Protein