title: Inflammatory markers and extent and progression of early atherosclerosis: Meta-analysis of individual-participant-data from 20 prospective studies of the PROG-IMT collaboration.
abstract: BACKGROUND
  Large-scale epidemiological evidence on the role of inflammation in early atherosclerosis, assessed by carotid ultrasound, is lacking. We aimed to quantify cross-sectional and longitudinal associations of inflammatory markers with common-carotid-artery intima-media thickness (CCA-IMT) in the general population.
  
  
  METHODS
  Information on high-sensitivity C-reactive protein, fibrinogen, leucocyte count and CCA-IMT was available in 20 prospective cohort studies of the PROG-IMT collaboration involving 49,097 participants free of pre-existing cardiovascular disease. Estimates of associations were calculated within each study and then combined using random-effects meta-analyses.
  
  
  RESULTS
  Mean baseline CCA-IMT amounted to 0.74 mm (SD = 0.18) and mean CCA-IMT progression over a mean of 3.9 years to 0.011 mm/year (SD = 0.039). Cross-sectional analyses showed positive linear associations between inflammatory markers and baseline CCA-IMT. After adjustment for traditional cardiovascular risk factors, mean differences in baseline CCA-IMT per one-SD higher inflammatory marker were: 0.0082 mm for high-sensitivity C-reactive protein (p < 0.001); 0.0072 mm for fibrinogen (p < 0.001); and 0.0025 mm for leucocyte count (p = 0.033). 'Inflammatory load', defined as the number of elevated inflammatory markers (i.e. in upper two quintiles), showed a positive linear association with baseline CCA-IMT (p < 0.001). Longitudinal associations of baseline inflammatory markers and changes therein with CCA-IMT progression were null or at most weak. Participants with the highest 'inflammatory load' had a greater CCA-IMT progression (p = 0.015).
  
  
  CONCLUSIONS
  Inflammation was independently associated with CCA-IMT cross-sectionally. The lack of clear associations with CCA-IMT progression may be explained by imprecision in its assessment within a limited time period. Our findings for 'inflammatory load' suggest important combined effects of the three inflammatory markers on early atherosclerosis.
authors.affiliation: The Department of Public Health and Primary Care, University of Cambridge, UK Department of Neurology, Medical University Innsbruck, Austria.
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authors.affiliation: Department of Neurology, Benedictus Krankenhaus Tutzing and Feldafing, Tutzing, Germany and Technische Universität München, Germany D.Sander@mac.com.
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mesh_terms: D050197:Atherosclerosis / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000032:analysis*; D059168:Carotid Intima-Media Thickness; D018450:Disease Progression; D005340:Fibrinogen / Q000032:analysis*; D006801:Humans; D007249:Inflammation / Q000097:blood; D007958:Leukocyte Count
chemical_list: D015415:Biomarkers; D005340:Fibrinogen; D002097:C-Reactive Protein
keywords: Inflammation; atherosclerosis; meta-analysis