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High-sensitivity C-reactive protein is not associated with carotid intima-media progression: the carotid
Matthias W Lorenz1, Peter Karbstein, Hugh S Markus
1Department of Neurology, J.W. Goethe-University, Frankfurt am Main, Germany. matthias.lorenz@em.uni-frankfurt.de
Insights
Elevated high-sensitivity C-reactive protein (hs-CRP) is not an independent cause of atherosclerosis initiation or progression. Associations between hs-CRP and early atherosclerotic changes are explained by other cardiovascular risk factors.
Area of Science:
- Cardiovascular Medicine
- Biomarkers
- Atherosclerosis Research
Background:
- The role of C-reactive protein (CRP) in atherosclerosis is debated.
- High-sensitivity CRP (hs-CRP) is a marker of inflammation.
- Causality between hs-CRP and atherosclerosis requires investigation.
Purpose of the Study:
- To determine if elevated hs-CRP causally influences atherosclerosis initiation and progression.
- To investigate the association between hs-CRP and carotid intima-media thickness (IMT).
- To assess the relationship between hs-CRP and clinical cardiovascular events.
Main Methods:
- Prospective longitudinal cohort study of 3122 subjects.
- Measurement of carotid IMT at baseline and 3-year follow-up.
- Analysis of associations between hs-CRP, IMT, and clinical events, controlling for risk factors.
Main Results:
- Hs-CRP associated with baseline IMT, but this was confounded by age, gender, and risk factors.
- No significant association found between hs-CRP and IMT progression.
- Initial association between hs-CRP and clinical events lost significance after adjustment for confounders.
Conclusions:
- Hs-CRP is not an independent causal factor for early carotid atherosclerosis.
- Observed associations between hs-CRP and IMT are explained by confounding factors.
- Inflammation markers like hs-CRP should be interpreted alongside traditional cardiovascular risk factors.
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.
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