Published Online
on March 19, 2007

A more recent version of this article appeared on March 27, 2007

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Submitted on July 6, 2006
Accepted on January 5, 2007

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

Marc S. Sabatine MD, MPH^*, David A. Morrow MD, MPH, Kathleen A. Jablonski PhD, Madeline Murguia Rice PhD, J. Wayne Warnica MD, Michael J. Domanski MD, Judith Hsia MD, Bernard J. Gersh MD, Nader Rifai PhD, Paul M Ridker MD, Marc A. Pfeffer MD, PhD, Eugene Braunwald MD, for the PEACE Investigators

From the Cardiovascular Division, Brigham and Women’s Hospital and Department of Medicine, Harvard Medical School, Boston, Mass (M.S.S., D.A.M., P.M.R., M.A.P., E.B.); George Washington University, Rockville, Md, and Washington, DC (K.A.J., M.M.R., J.H.); Department of Cardiac Sciences, University of Calgary, Calgary, Alberta, Canada (J.W.W.); National Heart, Lung, and Blood Institute, Bethesda, Md (M.J.D.); Mayo Clinic Foundation, Rochester, Minn (B.J.G.); and Department of Laboratory Medicine and Pathology, Children’s Hospital, Boston, Mass (N.R.).

^* To whom correspondence should be addressed. E-mail: msabatine{at}partners.org.

Background--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 >1 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; P=0.016; hs-CRP >3 mg/L: adjusted hazard ratio, 1.52; 95% CI, 1.15 to 2.02; P=0.003). Similarly, elevated hs-CRP levels were an independent predictor of new heart failure (adjusted P<0.001 for trend) and new diabetes (adjusted P<0.001 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 >1 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.

Key words: coronary disease • C-reactive protein • inflammation • risk factors

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