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Background: High plasma C-reactive protein (CRP) levels have been associated with an unfavorable outcome in patients with coronary artery disease (CAD), and a direct participation of CRP in the atherosclerotic process has been postulated., Hypothesis: The aim of this study was to evaluate the possible relationship of high plasma CRP levels with the rapid progression of coronary atherosclerosis (RPCAD)., Methods: In all, 194 patients who were readmitted and underwent repeat coronary angiography because of recurrence of symptoms following successful percutaneous coronary intervention were studied. Median angiographic follow-up time was 6 months. Rapid progression CAD was defined as the presence of a new lesion, > 25% in luminal diameter stenosis, in a previously nondiseased vessel, or deterioration of a known, nontreated lesion by at least 25%., Results: By multivariate analysis, patients with high plasma CRP levels upon first admission were at higher risk of RPCAD. In particular, odds ration (OR) = 1.8; 95% confidence interval (CI) = 1.3-3.6; p value = 0.02 in patients with CRP = 0.5-2 mg/dl versus patients with CRP < 0.5 mg/dl, and OR = 7.1; 95% CI = 3.8-9.5; p value < 0.001 in patients with CRP > 2 mg/dl versus patients with CRP < 0.5 mg/dl., Conclusion: Increased plasma CRP levels could possibly identify patients at high risk for the development of RPCAD.