Original artcile
Inflammation and atherosclerosis: role of C-Reactive protein in risk assessment

https://doi.org/10.1016/j.amjmed.2004.02.006Get rights and content

Abstract

Inflammation participates critically in atherosclerosis. Circulating levels of several inflammatory markers rise in individuals at risk for atherosclerotic events. In particular, elevation of plasma C-reactive protein (CRP), a nonspecific acute-phase reactant that is easily and reliably measured, has strong predictive power for cardiovascular events. Indeed, measurements of high-sensitivity CRP (hs-CRP) plasma levels add to both the prognostic information gleaned from assay of plasma lipid risk factors and the risk levels estimated by means of Framingham study–based criteria. Retrospective data suggest the hypothesis that hs-CRP plasma levels may be useful for guiding use of lipid-lowering therapy in individuals who appear to be at low risk according to traditional risk assessment. A large-scale, randomized clinical trial—Justification for the Use of Statins in Primary Prevention: an Intervention Trial Evaluating Rosuvastatin (JUPITER)—will test whether rosuvastatin therapy will reduce incident cardiovascular disease in subjects with elevated plasma hs-CRP concentrations who do not meet current criteria for initiation of lipid-lowering drug therapy. Such clinical trial data may provide an evidence base for the use of plasma CRP assay as an adjuvant guide to therapy to complement the established traditional risk factors such as plasma lipid levels. Thus, medical practitioners are ushering in an era in which the biology of inflammation in atherosclerosis will find its way into clinical application.

Section snippets

Overview of atherosclerosis: an inflammatory disease

Atherosclerotic plaque development begins with endothelial cell activation, including overexpression of leukocyte adhesion proteins (Figure 1). 1, 2 Triggers of this inflammatory response may include oxidized lipoproteins, hypertension, diabetes mellitus, and conditions such as obesity. The healthy endothelium resists prolonged leukocyte attachment. Expression of adhesion molecules, such as vascular cell adhesion molecule–1 (VCAM-1), enhances the recruitment of inflammatory cells from the

Role of inflammatory markers in risk assessment: C-reactive protein and cardiovascular disease

One of the great success stories of modern medicine is the ability to harness the basic knowledge of cholesterol and its metabolism, with clinical use of this knowledge allowing the modification of plasma cholesterol levels in a way that uniformly improves clinical outcomes. Although determination of plasma lipid profiles constitutes an important component of risk assessment for atherosclerosis, the picture provided by lipid profiles alone is incomplete. Castelli3 demonstrated that plasma total

Potential clinical utility of C-reactive protein measurement

The suitability of plasma CRP assay for clinical application compares favorably with determination of other inflammatory markers.11 For example, there is no standard assay for measuring lipoprotein(a), and circadian variations in fibrinogen make its measurement difficult. Although measurement of homocysteine is reliable, prospective data on its predictive utility are inconsistent, as are prospective data on utility of the lipoprotein(a).4 The predictive abilities of both plasma hs-CRP and

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