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.