Abstract
“The pawn has been promoted to queen.”1 C-reactive protein (CRP), formerly considered solely as a biomarker for inflammation, is now viewed as a prominent partaker in endothelial dysfunction and atherosclerosis.2,3 Serving clinically for several years as a nonspecific marker for inflammatory processes, CRP, with the advent of high-sensitivity assays, has emerged as one of the most powerful independent predictors of cardiovascular disease.4,5 The Centers for Disease Control and Prevention and the American Heart Association issued a Class IIa recommendation for the screening of high-sensitivity (hs) CRP as a routine part of global cardiovascular risk assessment.6 However, several questions about CRP’s mechanism of action remain. In the present issue of Circulation , Khreiss et al7 provide evidence suggesting that native, pentameric CRP must undergo structural modification, forming monomeric subunits, before promoting a proinflammatory phenotype. This molecular finding may not only serve to influence basic molecular research examining CRP’s detrimental effect, but may also influence the clinical use of CRP as a prognostic marker. See p 2016 Compelling evidence exists to support CRP’s designation as a powerful independent predictor of future cardiovascular risk. CRP predicts cardiovascular risk in a wide variety of clinical settings, including men and women without overt cardiovascular disease,8,9 patients with stable angina or presenting with acute coronary syndromes,10,11 postmyocardial infarction patients, and those with the metabolic syndrome.12 Furthermore, CRP predicts not only incident myocardial infarction and cardiovascular death, but also the risk of ischemic stroke,13 sudden cardiac death,14 incident peripheral artery disease,15 and restenosis after percutaneous coronary intervention.16 In primary prevention, CRP confers additional prognostic value at all levels of Framingham risk and at all levels of the metabolic syndrome and blood pressure.17–19 In head-to-head comparisons with LDL cholesterol, CRP was found to be the …
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