Published Online
on April 19, 2007

A more recent version of this article appeared on June 1, 2007

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Submitted on October 20, 2006
Revised on December 27, 2006
Accepted on January 5, 2007

High-Sensitivity C-reactive Protein Is Not Associated With Carotid Intima-Media Progression. The Carotid Atherosclerosis Progression Study

Matthias W. Lorenz MD^*; Peter Karbstein; Hugh S. Markus FRCP, MD; and Matthias Sitzer MD

From the Department of Neurology (M.W.L., P.K., M.S.), Johann Wolfgang Goethe-University, Frankfurt am Main, Germany; and Clinical Neuroscience (H.S.M.), St. Georges University of London, London, UK.

^* To whom correspondence should be addressed. E-mail: matthias.lorenz{at}em.uni-frankfurt.de.

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.

Key words: atherosclerosis • carotid artery • C-reactive protein • inflammation • intima media thickness

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