High-sensitivity C-reactive protein is not associated with carotid intima-media progression: the carotid atherosclerosis progression study.

BACKGROUND AND PURPOSE It is unclear whether elevated serum C-reactive protein (CRP) is causal to the initiation and progression of atherosclerosis. We undertook a prospective longitudinal cohort study to address this question. METHODS In a population-based sample of 3122 subjects, we measured carotid intima media thickness (IMT) at baseline and after 3 years and surveyed clinical events. Associations between baseline high-sensitivity CRP (hs-CRP) and baseline IMT, and IMT progression were determined before and after controlling for vascular risk factors. The relationship between baseline IMT and clinical events during follow up was determined. RESULTS All vascular risk factors were significantly associated with hs-CRP (P<0.001). Hs-CRP was significantly associated with baseline IMT in all carotid segments (P<0.001), but this association was no longer significant after controlling for age, gender, and cardiovascular risk factors. Hs-CRP was not related to individual IMT progression. Interactions between hs-CRP and body mass index, HbA1c, or blood pressure showed no association with IMT progression. Baseline hs-CRP was related to the risk of clinical events (myocardial infarction or stroke or death, hazard ratio of 1.22 per mg/L hs-CRP increase, 95% CI: 1.07 to 1.39, P=0.004, adjusted for age and gender), but this association was not significant after controlling for age, gender, and cardiovascular risk factors (1.59, 95% CI: 0.96 to 2.64, P=0.072). CONCLUSIONS Our results suggest that hs-CRP is not an independent causal factor for the initiation and progression of early atherosclerotic changes of the carotid arteries. Univariate associations between hs-CRP and IMT were largely explained by confounding by age, gender, and cardiovascular risk factors.