title: Macrophage activation and coronary atherosclerosis in systemic lupus erythematosus and rheumatoid arthritis.
abstract: OBJECTIVE
  Activation of macrophages may contribute to increased atherosclerosis and coronary artery disease in systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). Neopterin, a pteridine derivative, is a novel marker of monocyte and macrophage activation that is associated with atherosclerosis and cardiovascular risk in the general population. We examined the hypothesis that macrophage activation is associated with accelerated atherosclerosis in SLE and RA.
  
  
  METHODS
  We compared serum neopterin concentrations, adjusted for age, race, sex, and serum creatinine concentration, in patients with SLE (n=148) or RA (n=166) and control subjects (n=177). In patients with SLE or RA, serum neopterin concentrations were then tested for association (adjusted for age, race, sex, serum creatinine, and medication use) with measures of disease activity or damage, inflammatory markers and mediators, and coronary artery calcium measured by electron beam computed tomography.
  
  
  RESULTS
  Neopterin concentrations were significantly higher in patients with SLE (median 8.0, interquartile range [IQR] 6.5-9.8 nmoles/liter) and RA (median 6.7, IQR 5.3-8.9 nmoles/liter) than controls (median 5.7, IQR 4.8-7.1 nmoles/liter), and were higher in SLE patients than in RA patients (all P<0.001). In SLE, neopterin was significantly correlated with higher erythrocyte sedimentation rate (ESR; P=0.001), tumor necrosis factor α (P<0.001), monocyte chemoattractant protein 1 (P=0.005), and homocysteine concentrations (P=0.01), but in RA, it was only associated with ESR (P=0.01). Neopterin was not associated with coronary calcium in either SLE (P=0.65) or RA (P=0.21).
  
  
  CONCLUSIONS
  Macrophage activation, reflected by increased serum neopterin concentrations, was increased in both SLE and RA. Neopterin was more robustly associated with atherogenic mediators of inflammation and homocysteine in SLE than in RA, but was not associated with coronary atherosclerosis in either disease.
authors.affiliation: Department of Clinical Pharmacology, School of Medicine, Vanderbilt University, 23rd Avenue South at Pierce Avenue, Nashville, TN 37232-6602, USA.
authors.forename: Young Hee
authors.initials: YH
authors.lastname: Rho
authors.forename: Joseph
authors.initials: J
authors.lastname: Solus
authors.forename: Paolo
authors.initials: P
authors.lastname: Raggi
authors.forename: Annette
authors.initials: A
authors.lastname: Oeser
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; D001172:Arthritis, Rheumatoid / Q000150:complications / Q000276:immunology* / Q000473:pathology*; D015415:Biomarkers / Q000097:blood; D015331:Cohort Studies; D003324:Coronary Artery Disease / Q000209:etiology / Q000276:immunology* / Q000473:pathology*; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000150:complications / Q000276:immunology* / Q000473:pathology*; D008262:Macrophage Activation / Q000502:physiology*; D008264:Macrophages / Q000473:pathology; D008297:Male; D008875:Middle Aged; D019798:Neopterin / Q000097:blood; D012307:Risk Factors
chemical_list: D015415:Biomarkers; D019798:Neopterin