A prospective evaluation of C-reactive protein in the progression of carotid artery stenosis

Objective: Our institution previously reported an association between elevated C-reactive protein (CRP) and carotid artery stenosis. Based on this finding, we sought to further evaluate the association of CRP levels with ultrasound progression of carotid artery stenosis, and/or clinical events. Methods: A prospective observational study of patients evaluated for carotid artery stenosis was performed at a tertiary medical center from 2003-2007. Patients underwent serial lab draws for serum CRP, as well as serial duplex ultrasounds of their carotid bifurcations. Examinations were performed at 6-month intervals. Initial risk factors and CRP levels were evaluated with univariate statistics. Ultrasound progression of disease was evaluated with Kaplan-Meier curves and Cox regression analysis. Results: During the study period, 271 patients completed study requirements with a mean follow-up of 37 (±6) months. Initial duplex examination revealed 114 (41%) of patients had 0% to 15%, 94 (35%) had 16% to 49%, and 63 (23%) had 50% to 79% stenosis of the carotid bifurcation. Sixty-three patients (23%) demonstrated progression of disease by ultrasound examination, 27 (10%) progressed to carotid endarterectomy, and three (1%) experienced a stroke during follow-up. Mean CRP levels were higher among patients that progressed on duplex examination (6.7 ± 1.28 vs 4.6 ± 0.4 mg/dl, P < .05). Kaplan-Meier analysis revealed a significant difference in freedom from progression of carotid artery disease for patients with 1^st and 3^rd quartile CRP levels (log-rank test P < .05). Adjusting for diabetes, hyperlipidemia, hypertension, coronary artery disease, aspirin or other anti-inflammatory uses, and statin therapy, 4^th quartile CRP was independently associated with disease progression (OR 1.8, 95% CI; 1.03-2.99, P < .05). Conclusions: High CRP levels predict ultrasound progression of disease in patients with carotid artery stenosis. In addition, CRP levels may provide additional information to help guide ultimate therapy for evaluation and follow-up of patients with borderline lesions identified by duplex exam.