Prognostic Significance of the Centers for Disease Control/American Heart Association High-Sensitivity C-Reactive Protein Cut Points for Cardiovascular and Other Outcomes in Patients With Stable Coronary Artery Disease

Abstract

MD; for the PEACE InvestigatorsBackground-Data supporting the prognostic significance of high-sensitivity C-reactive protein (hs-CRP) are derived largely from individuals with no overt coronary artery disease or from patients with acute coronary syndromes. In contrast, the ability of hs-CRP to predict outcomes in patients with stable coronary artery disease and the prognostic significance of the Centers for Disease Control/American Heart Association hs-CRP cut points in such a population remain relatively unexplored. Methods and Results-We measured hs-CRP in 3771 patients with stable coronary artery disease from the Prevention of Events With Angiotensin-Converting Enzyme Inhibition (PEACE) trial, a randomized placebo-controlled trial of the angiotensin-converting enzyme inhibitor trandolapril. Patients were followed up for a median of 4.8 years for cardiovascular death, myocardial infarction, or stroke, as well as new heart failure and diabetes. After adjustment for baseline characteristics and treatments, higher hs-CRP levels, even Ͼ1 mg/L, were associated with a significantly greater risk of cardiovascular death, myocardial infarction, or stroke (hs-CRP 1 to 3 mg/L: adjusted hazard ratio, 1.39; 95% CI, 1.06 to 1.81; Pϭ0.016; hs-CRP Ͼ3 mg/L: adjusted hazard ratio, 1.52; 95% CI, 1.15 to 2.02; Pϭ0.003).Similarly, elevated hs-CRP levels were an independent predictor of new heart failure (adjusted PϽ0.001 for trend) and new diabetes (adjusted PϽ0.001 for trend). There were no significant interactions between hs-CRP levels and the effects of trandolapril on any of the above outcomes. Conclusions-In stable coronary artery disease, an elevated hs-CRP level, even Ͼ1 mg/L, is a significant predictor of adverse cardiovascular events independently of baseline characteristics and treatments. An elevated hs-CRP does not appear to identify patients with stable coronary artery disease and preserved ejection fraction who derive particular benefit from angiotensin-converting enzyme inhibition.

Effect of atorvastatin on circulating hsCRP concentrations: A sub-study of the Achieve Cholesterol Targets Fast with Atorvastatin Stratified Titration (ACTFAST) study

“…HsCRP is an independent risk factor for atherosclerotic disease [1,2,[10][11][12]. Large randomized trials have demonstrated that statins significantly reduce the risk of MI and cardiovascular mortality [27][28][29][30][31], with a magnitude that is greater than expected based on LDL-C reduction alone.…”

“…Although its role as a biomarker or a mediator of atherosclerosis is still debated, CRP actively contributes to all stages of atherogenesis, including endothelial dysfunction, atherosclerotic-plaque formation, maturation, destabilization and eventual rupture [1,[7][8][9]. A high concentration of hsCRP has been shown to be a strong independent risk factor for cardiovascular events [1,2,[10][11][12], thus, adding prognostic information to traditional risk factors.…”

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