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Inflammation in Atherosclerosis: From Vascular Biology to Biomarker Discovery and Risk Prediction

Leducq Center for Cardiovascular Research, Division of Cardiovascular Medicine, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA.

^aAddress correspondence to this author at: Leducq Center for Cardiovascular Research, Division of Cardiovascular Medicine, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, 77 Avenue Louis Pasteur, NRB 7, Boston, MA 02115. e-mail plibby{at}rics.bwh.harvard.edu.

Recent investigations of atherosclerosis have focused on inflammation, providing new insight into mechanisms of disease. Inflammatory cytokines involved in vascular inflammation stimulate the generation of endothelial adhesion molecules, proteases, and other mediators, which may enter the circulation in soluble form. These primary cytokines also induce production of the messenger cytokine interleukin-6, which stimulates the liver to increase production of acute-phase reactants such as C-reactive protein. In addition, platelets and adipose tissue can generate inflammatory mediators relevant to atherothrombosis. Despite the irreplaceable utility of plasma lipid profiles in assessment of atherosclerotic risk, these profiles provide an incomplete picture. Indeed, many cardiovascular events occur in individuals with plasma cholesterol concentrations below the National Cholesterol Education Program thresholds of 200 mg/dL for total cholesterol and 130 mg/dL for low-density lipoprotein (LDL) cholesterol. The concept of the involvement of inflammation in atherosclerosis has spurred the discovery and adoption of inflammatory biomarkers for cardiovascular risk prediction. C-reactive protein is currently the best validated inflammatory biomarker; in addition, soluble CD40 ligand, adiponectin, interleukin 18, and matrix metalloproteinase 9 may provide additional information for cardiovascular risk stratification and prediction. This review retraces the biology of atherothrombosis and the evidence supporting the role of inflammatory biomarkers in predicting primary cardiovascular events in this biologic context.

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