title: Inflammatory mediators and premature coronary atherosclerosis in rheumatoid arthritis.
abstract: OBJECTIVE
  Rheumatoid arthritis (RA) is an inflammatory disease associated with premature atherosclerosis. We hypothesized that mediators of inflammation associated with atherosclerosis in other populations (interleukin-6 [IL-6], tumor necrosis factor alpha [TNFalpha], serum amyloid A [SAA], vascular endothelial growth factor, neutrophil count, IL-1alpha, E-selectin, intercellular adhesion molecule 1 [ICAM-1], myeloperoxidase [MPO], matrix metalloproteinase 9, and vascular cell adhesion molecule 1) would be increased and associated with the severity of coronary atherosclerosis in patients with RA.
  
  
  METHODS
  Clinical variables, concentrations of inflammatory mediators, and coronary artery calcification were measured in 169 patients with RA and 92 control subjects. Differences in concentrations of inflammatory mediators were compared using median quantile regression. The relationship of inflammatory mediators with the severity of coronary calcification in RA and control subjects was examined using proportional odds logistic regression, allowing for interaction with disease status. Models were adjusted for traditional cardiovascular risk factors.
  
  
  RESULTS
  Median serum concentrations of IL-6, SAA, ICAM-1, E-selectin, TNFalpha, and MPO and peripheral blood neutrophil count were higher in patients with RA than controls (all P < 0.05), independent of Framingham risk score and diabetes mellitus (DM). IL-6 (main effect odds ratio [OR] 1.72; 95% confidence interval [95% CI] 1.12, 2.66) and TNFalpha (main effect OR 1.49; 95% CI 1.16, 1.90) concentrations were significantly associated with higher amounts of coronary calcium, independent of Framingham risk score and DM, and such main effects significantly differed from controls (P = 0.001 and 0.03 for interaction, respectively).
  
  
  CONCLUSIONS
  TNFalpha and IL-6 are significantly associated with the severity of subclinical atherosclerosis, independent of Framingham risk score, in RA.
authors.affiliation: Vanderbilt University, Nashville, Tennessee 37232-6602, USA.
authors.forename: Young Hee
authors.initials: YH
authors.lastname: Rho
authors.forename: Cecilia P
authors.initials: CP
authors.lastname: Chung
authors.forename: Annette
authors.initials: A
authors.lastname: Oeser
authors.forename: Joseph
authors.initials: J
authors.lastname: Solus
authors.forename: Yu
authors.initials: Y
authors.lastname: Asanuma
authors.forename: Tuulikki
authors.initials: T
authors.lastname: Sokka
authors.forename: Theodore
authors.initials: T
authors.lastname: Pincus
authors.forename: Paolo
authors.initials: P
authors.lastname: Raggi
authors.forename: Tebeb
authors.initials: T
authors.lastname: Gebretsadik
authors.forename: Ayumi
authors.initials: A
authors.lastname: Shintani
authors.forename: C Michael
authors.initials: CM
authors.lastname: Stein
mesh_terms: D000328:Adult; D017668:Age of Onset; D000368:Aged; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000453:epidemiology* / Q000276:immunology; D015415:Biomarkers / Q000097:blood*; D003324:Coronary Artery Disease / Q000097:blood / Q000453:epidemiology* / Q000276:immunology; D019040:E-Selectin / Q000097:blood; D005260:Female; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood*; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood; D053582:Interleukin-1alpha / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D016015:Logistic Models; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000097:blood; D008875:Middle Aged; D009504:Neutrophils; D009195:Peroxidase / Q000378:metabolism; D012307:Risk Factors; D000685:Serum Amyloid A Protein / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D042461:Vascular Endothelial Growth Factor A / Q000097:blood
chemical_list: D015415:Biomarkers; D019040:E-Selectin; C508600:IL6 protein, human; D018836:Inflammation Mediators; D053582:Interleukin-1alpha; D015850:Interleukin-6; D000685:Serum Amyloid A Protein; D014409:Tumor Necrosis Factor-alpha; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D018799:Intercellular Adhesion Molecule-1; D009195:Peroxidase; D020780:Matrix Metalloproteinase 9