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C-Reactive Protein and Other Emerging Blood Biomarkers to Optimize Risk Stratification of Vulnerable Patients

Sotirios Tsimikas, MD, FACC^_*,_*, James T. Willerson, MD, FACC and Paul M. Ridker, MD, FACC

^_* Department of Medicine, Division of Cardiology, University of California, San Diego, San Diego, California
St. Luke’s Episcopal Hospital/Texas Heart Institute, Houston, Texas
Center for Cardiovascular Disease Prevention, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts

Manuscript received June 16, 2005; revised manuscript received October 21, 2005, accepted October 25, 2005.

^_* Reprint requests and correspondence: Dr. Sotirios Tsimikas, Vascular Medicine Program, University of California, San Diego, 9500 Gilman Drive, BSB 1080, La Jolla, California 92093-0682. (Email: stsimikas{at}ucsd.edu).

Several emerging plasma biomarkers may ultimately prove useful in risk stratification and prognosis of cardiovascular disease. The clinical utility of these biomarkers will depend on their ability to provide a reflection of the underlying atherosclerotic burden or activity; the ability to provide reliable, accurate, and cost-effective information; and the ability to predict future events. High-sensitivity C-reactive protein (hs-CRP) fulfills many, if not all, of these criteria, and blood levels of hs-CRP are now commonly used in clinical practice to improve vascular risk prediction in primary and secondary prevention across all levels of low-density lipoprotein-cholesterol (LDL-C), all levels of the Framingham Risk Score, and all levels of metabolic syndrome. High-sensitivity C-reactive protein may also have clinical relevance as an adjunct to LDL-C for both the targeting and monitoring of statin therapy. Accumulating evidence suggests that several other selected emerging biomarkers may also potentially prove useful in the diagnosis and prognosis of cardiovascular disease. Specifically, data are accumulating on the potential clinical utility of lipoprotein-associated lipoprotein-associated phospholipase A₂, myeloperoxidase, oxidized LDL, lipoprotein (a), isoprostanes, and small, dense LDL. This review focuses on hs-CRP and these emerging plasma biomarkers, and their potential diagnostic and prognostic utility in cardiovascular disease. Plasma biomarkers that reflect the clinical potential of atherothrombotic disease may allow more precise risk stratification and prognostication in high-risk populations, and perhaps earlier diagnosis and intervention in patients at risk for or with occult cardiovascular disease.

Abbreviations and Acronyms   ACS = acute coronary syndrome   apo = apolipoprotein   CAD = coronary artery disease   CETP = cholesterol ester transfer protein   ELISA = enzyme-linked immunoabsorbent assay   HDL-C = high-density lipoprotein cholesterol   HOCl = hypochlorous acid   hs-CRP = high-sensitivity C-reactive protein   LDL-C = low-density lipoprotein cholesterol   Lp(a) = lipoprotein (a)   Lp-PLA2 = lipoprotein-associated phospholipase A2   MPO = myeloperoxidase   OR = odds ratio   OxLDL = oxidized LDL   OxPLs = oxidized phospholipids   PAF-AH = platelet-activating factor acetylhydrolase   PCI = percutaneous coronary intervention

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