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C-reactive protein in atherosclerosis - A risk marker but not a causal factor? A 13-year population-based
Agnethe Eltoft1, Kjell Arne Arntzen1, John-Bjarne Hansen2
1Department of Clinical Medicine, The Arctic University of Norway, Tromsø, Norway; Department of Neurology, University Hospital of North Norway, Tromsø, Norway.
Insights
C-reactive protein (CRP) is linked to plaque presence but does not independently predict atherosclerosis progression. Further research is needed to understand CRP's role in cardiovascular disease mechanisms beyond plaque development.
Area of Science:
- Cardiovascular epidemiology
- Biomarkers in atherosclerosis
- Population-based studies
Background:
- C-reactive protein (CRP) is a known predictor of cardiovascular disease (CVD).
- The specific role of CRP in the development and advancement of atherosclerosis requires further investigation.
- Prospective population-based studies are crucial for understanding these relationships.
Purpose of the Study:
- To investigate the association between C-reactive protein (CRP) levels and subclinical atherosclerosis.
- To determine if baseline CRP predicts the formation and progression of atherosclerotic plaques over time.
- To elucidate the role of CRP in atherosclerosis within a population-based cohort.
Main Methods:
- Utilized data from The Tromsø Study, including 6503 middle-aged subjects with baseline assessments (1994) and follow-ups (2001, 2007).
- Collected serum CRP levels, carotid ultrasound data, and covariate information.
- Employed generalized estimating equations and linear mixed models, stratified by sex, to analyze cross-sectional and longitudinal associations between CRP and carotid atherosclerosis (plaque prevalence, novel plaque formation, plaque progression, total plaque area).
Main Results:
- CRP levels were associated with increased traditional risk factors and plaque prevalence at baseline across different CRP categories (<1 mg/L, 1-3 mg/L, >3 mg/L) in both sexes.
- Cross-sectional analyses revealed that multivariable-adjusted CRP was associated with plaque prevalence and total plaque area (TPA) in men and women.
- Age-adjusted baseline CRP >3 mg/L predicted novel plaque formation and TPA progression in men, but these associations were not significant when adjusted for traditional risk factors, and were not observed in women.
Conclusions:
- C-reactive protein (CRP) is associated with the presence of atherosclerotic plaques and total plaque area in cross-sectional analyses.
- Baseline CRP levels were not found to be an independent predictor of novel plaque formation or plaque progression after adjusting for traditional risk factors.
- These findings suggest that CRP may contribute to cardiovascular disease (CVD) through mechanisms other than the direct promotion of atherosclerotic plaque formation and progression.
Background And Aims:
CRP predicts cardiovascular disease (CVD) in large epidemiologic studies. The aim of the present study was to elucidate the role of CRP in atherosclerosis formation and progression in a prospective population-based study.
Methods:
6503 middle-aged subjects from The Tromsø study had serum CRP, carotid ultrasound and complete covariate data collected at baseline in 1994. Of these, 4730 and 2917 attended follow-up surveys with repeated assessments in 2001 and 2007, respectively. The cross-sectional associations between CRP and subclinical carotid atherosclerosis, and the longitudinal associations between baseline CRP and novel plaque formation and plaque progression were assessed in generalized estimating equations and linear mixed models stratified by sex.
Results:
At baseline, traditional risk factors and plaque prevalence increased by CRP risk categories (<1 mg/L, 1-3 mg/L, and >3 mg/L) in both sexes. In cross-sectional analyses, multivariable-adjusted CRP was associated with plaque prevalence and total plaque area (TPA) in men and women. Age-adjusted baseline CRP >3 mg/L compared to CRP <1 mg/L predicted novel plaque formation (OR 1.44, CI 1.08-1.92) and TPA progression (β = 0.0.029 (CI, 0.003-0.056)) in men, but not in women. In neither men nor women was baseline CRP a predictor of TPA-progression or novel plaque formation when adjusted for traditional risk factors.
Conclusions:
CRP was associated with plaque presence and TPA in cross-sectional analyses, but was not an independent predictor of novel plaque formation or plaque progression. Our findings suggest that CRP may link to CVD by other mechanisms than promoting formation and progression of atherosclerotic plaques.
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