Inflammatory mediators and premature coronary atherosclerosis in rheumatoid arthritis

Arthritis Rheum. 2009 Nov 15;61(11):1580-5. doi: 10.1002/art.25009.


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).

Conclusion: TNFalpha and IL-6 are significantly associated with the severity of subclinical atherosclerosis, independent of Framingham risk score, in RA.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Age of Onset
  • Aged
  • Arthritis, Rheumatoid / blood
  • Arthritis, Rheumatoid / epidemiology*
  • Arthritis, Rheumatoid / immunology
  • Biomarkers / blood*
  • Coronary Artery Disease / blood
  • Coronary Artery Disease / epidemiology*
  • Coronary Artery Disease / immunology
  • E-Selectin / blood
  • Female
  • Humans
  • Inflammation Mediators / blood*
  • Intercellular Adhesion Molecule-1 / blood
  • Interleukin-1alpha / blood
  • Interleukin-6 / blood
  • Logistic Models
  • Male
  • Matrix Metalloproteinase 9 / blood
  • Middle Aged
  • Neutrophils
  • Peroxidase / metabolism
  • Risk Factors
  • Serum Amyloid A Protein / metabolism
  • Tumor Necrosis Factor-alpha / blood
  • Vascular Endothelial Growth Factor A / blood


  • Biomarkers
  • E-Selectin
  • IL6 protein, human
  • Inflammation Mediators
  • Interleukin-1alpha
  • Interleukin-6
  • Serum Amyloid A Protein
  • Tumor Necrosis Factor-alpha
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • Intercellular Adhesion Molecule-1
  • Peroxidase
  • Matrix Metalloproteinase 9