High-sensitivity C-reactive protein and cardiovascular risk in patients with coronary heart disease Robert S. Rosenson, MD,* and Wolfgang Koenig, MD † High-sensitivity C-reactive protein levels have received widespread attention because of a multitude of prospective studies that have shown that high levels of high-sensitivity C-reactive protein identify increased risk of initial cardiovascular events in coronary heart disease patients and increased risk of recurrent cardiac events in patients with stable and unstable angina, patients with acute myocardial infarction, and patients undergoing elective coronary revascularization procedures. In contrast to several other inflammatory markers, high-sensitivity C-reactive protein measurements are standardized and reproducible. The clinical significance of a reliable inflammatory marker includes identification of high-risk individuals, a gauge to monitor the activity of the disease, and a potential therapeutic target to alter the inflammatory component of the disease process. This review focuses on the importance of high-sensitivity C-reactive protein in cardiovascular risk stratification in coronary heart disease patients and discusses several preventive therapies that may reduce cardiovascular risk through reduction in high-sensitivity C-reactive protein. Curr Opin Cardiol 2002, 17:325–331 © 2002 Lippincott Williams & Wilkins, Inc. Prospective studies have identified many markers of sys- temic inflammation that are powerful predictors of future cardiovascular events in apparently healthy subjects and in patients with unstable angina and postmyocardial in- farction [1•,2,3]. In contrast to other inflammatory mark- ers, measurements of high-sensitivity C-reactive protein (hs-CRP) have received widespread attention because of the standardization of the methodology and commercial availability [4,5]. This article focuses specifically on the direct involvement of C-reactive protein (CRP) in ath- erothrombosis and the importance of hs-CRP measure- ments in coronary heart disease (CHD) patients, and reviews those secondary preventive therapies that may re- duce cardiovascular risk through, in part, reduction of CRP. Involvement of C-reactive protein in atherosclerosis Atherosclerosis is a chronic inflammatory disorder of the arterial intima that is related to abnormal regulation of oxidative stress [6]. Oxidative modifications of low- density lipoprotein (LDL) and other lipoproteins serve as signals that increase inflammation through regulation of monocyte adhesion, vascular gene expression of cel- lular adhesion molecules ICAM-1 and VCAM-1, and ac- tivation of the redox-sensitive transcription factors nuclear factor-B (NF-B) and activator protein 1 [6,7]. NF-B increases the expression of genes for many pro- inflammatory cytokines, chemokines, and enzymes whose products mediate inflammatory and immune re- sponses [6,8]. NF-B activates gene expression of TNF- and IL-1. TNF- and IL-1, in turn, increase transcrip- tion of IL-6, which regulates hepatic synthesis of CRP. Recent evidence suggests that CRP may be directly in- volved in atherothrombogenesis that extends beyond its previously accepted role as an inflammatory marker (Fig. 1). CRP is present in the vessel wall [9], where it induces expression of the adhesion molecules E-selection, VCAM-1, and ICAM-1 by endothelial cells [10] and serves as a chemoattractant for monocytes as mediated by induction of MCP-1 [11]. CRP opsonizes LDL and facilitates native LDL entry into macrophages [12••] primarily through the low-affinity immunoglobu- lin receptor CD32 [13,14]. CRP binds to plasma mem- branes of damaged cells and activates complement via the classical pathway [15]. This event may accentuate CRP accumulation in the plaque through binding of CRP to complement receptor on vascular smooth muscle cells [15]. In addition, CRP facilitates thrombogenesis *Preventive Cardiology Center, Departments of Medicine and Preventive Medicine, Northwestern University Medical School, Chicago, Illinois, USA; † Department of Internal Medicine II-Cardiology, University of Ulm Medical Center, Ulm, Germany. Correspondence to Robert S. Rosenson, MD, Preventive Cardiology Center, Northwestern University Medical School, 201 East Huron Street, Galter Pavilion, Suite 11-120, Chicago, IL 60611, USA; e-mail: r-rosenson@northwestern.edu Current Opinion in Cardiology 2002, 17:325–331 Abbreviations BMI body mass index CHD coronary heart disease CRP C-reactive protein HRT hormone replacement therapy hs-CRP high-sensitivity C-reactive protein LDL low-density lipoprotein MI myocardial infarction NF-B nuclear factor-B PCI percutaneous coronary intervention ISSN 0268–4705 © 2002 Lippincott Williams & Wilkins, Inc. 325 DOI: 10.1097/01.HCO.0000018146.37756.1D