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.