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A more recent version of this article appeared on July 25, 2006

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Submitted on March 23, 2006
Revised on April 29, 2006
Accepted on May 2, 2006

Clinical Relevance of C-Reactive Protein During Follow-Up of Patients With Acute Coronary Syndromes in the Aggrastat-to-Zocor Trial

David A. Morrow MD, MPH^*, James A. de Lemos MD, Marc S. Sabatine MD, MPH, Stephen D. Wiviott MD, Michael A. Blazing MD, Amy Shui BS, Nader Rifai PhD, Robert M. Califf MD, and Eugene Braunwald MD

From the TIMI Study Group, Cardiovascular Division, Brigham and Women’s Hospital, Boston, Mass (D.A.M., M.S.S., S.D.W., A.S., E.B.); Donald W. Reynolds Cardiovascular Clinical Research Center, University of Texas Southwestern Medical Center, Dallas, Tex (J.A.d.L.); Duke Clinical Research Institute, Durham, NC (M.A.B., R.M.C.); and Children’s Hospital, Boston, Mass (N.R.).

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

Background--Elevated levels of high-sensitivity C-reactive protein (hsCRP) are associated with higher risk of adverse outcomes in patients at risk for or with established coronary artery disease. Retrospective analyses suggest that this risk may be modified with statin therapy. However, a role for hsCRP in monitoring the success of therapy remains uncertain.

Methods and Results--We measured the serum concentration of hsCRP at 30 days (n=3813) and 4 months in patients with non-ST-elevation or ST-elevation acute coronary syndrome randomly assigned to an early intensive versus delayed conservative simvastatin strategy in the Aggrastat-to-Zocor Trial. Patients with hsCRP >3 mg/L at 30 days had significantly higher 2-year mortality rates than those with hsCRP 1 to 3 mg/L or hsCRP <1 mg/L (6.1% versus 3.7% versus 1.6%, P<0.0001). Results were similar with hsCRP measured at 4 months. After adjusting for age, gender, diabetes, smoking, cardiovascular history, index event, lipid levels, and randomly assigned treatment, patients with hsCRP >3 mg/L were at more than 3-fold higher risk of death (HR, 3.7; 95% CI, 1.9 to 7.2) compared with those with hsCRP <1 mg/L. "Average" levels of hsCRP (1 to 3 mg/L) were also associated with increased risk compared with those with hsCRP <1 mg/L (HR, 2.3; 95% CI, 1.2 to 4.6). Patients allocated to early intensive statin therapy were more likely to achieve hsCRP levels <1 mg/L at 30 days (P=0.028) and 4 months (P<0.0001).

Conclusions--Achieved levels of hsCRP at 30 days and 4 months after acute coronary syndrome are independently associated with long-term survival. Patients treated with more aggressive statin therapy are more likely to achieve lower levels of hsCRP.

Key words: coronary disease • prognosis • myocardial infarction • inflammation • C-reactive protein

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