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C-reactive protein and other inflammatory risk markers in acute coronary syndromes

^* Center for Cardiovascular Disease Prevention, the Leducq Center for Cardiovascular Research, and the Cardiovascular Division, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts, UK

Manuscript received May 7, 2002; revised manuscript received October 11, 2002, accepted November 27, 2002.

^* Reprint requests and correspondence: Dr. Paul M. Ridker, Center for Cardiovascular Disease Prevention, Brigham and Women’s Hospital, 900 Commonwealth Avenue East, Boston, Massachusetts 02215, UK.
pridker{at}partners.org

Markers of myocyte necrosis such as cardiac troponin or creatine kinase-myocardial band are invaluable tools for risk stratification among patients presenting with acute coronary syndromes (ACS). Nonetheless, many patients without any evidence of myocyte necrosis may be at high risk for recurrent ischemic events. In consideration of the important role that inflammatory processes play in determining plaque stability, recent work has focused on whether plasma markers of inflammation may help improve risk stratification. Of these markers, C-reactive protein (CRP) has been the most widely studied, and there is now robust evidence that CRP is a strong predictor of cardiovascular risk among apparently healthy individuals, patients undergoing elective revascularization procedures, and patients presenting with ACS. Moreover, even among patients with troponin-negative ACS, elevated levels of CRP are predictive of future risk. Other, more upstream markers of the inflammatory cascade, such as interleukin (IL)-6, have also been found to be predictive of recurrent vascular instability. A recent report from the second FRagmin during InStability in Coronary artery disease trial investigators suggests that elevated levels of an inflammatory marker such as IL-6 may indicate which patients may benefit most from an early invasive strategy. Other inflammatory markers currently under investigation include lipoprotein-associated phospholipase A₂, myeloperoxidase, and pregnancy-associated plasma protein A. Of all these novel markers, CRP appears to meet most of the criteria required for potential clinical application. Furthermore, the benefits of lifestyle modification and drug therapy with aspirin or statins may be most marked among those with elevated CRP levels.

Abbreviations and Acronyms   ACS = acute coronary syndrome(s)   BNP = B-type natriuretic peptide   CAD = coronary artery disease   CK-MB = creatine kinase-myocardial band   CRP = C-reactive protein   IL = interleukin   LDL = low-density lipoprotein   Lp-PLA2 = lipoprotein-associated phospholipase A2   MI = myocardial infarction   MPO = myeloperoxidase   PAPP-A = pregnancy-associated plasma protein A

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