title: Systemic markers of interferon-γ-mediated immune activation and long-term prognosis in patients with stable coronary artery disease.
abstract: OBJECTIVE
  Interferon γ (IFN-γ) is centrally involved in atherosclerosis-related inflammation, but its activity cannot be reliably assessed by systemic measurements. In activated macrophages, IFN-γ stimulates production of neopterin and conversion of tryptophan to kynurenine. We evaluated the relationships of plasma neopterin and plasma kynurenine:tryptophan ratio (KTR) to long-term prognosis in patients with stable angina pectoris and angiographically verified significant coronary artery disease.
  
  
  RESULTS
  Samples were obtained from 2380 patients with a mean age of 63.7 years; 77.3% were men. During a median follow-up of 56 months, 10.8% of patients experienced a major coronary event (MCE), and 9.5% died. For MCE, each SD increment of neopterin and KTR (logarithmically transformed) was associated with multivariable adjusted hazard ratios and 95% CIs of 1.28 (1.10 to 1.48) and 1.28 (1.12 to 1.48), respectively. The corresponding hazard ratios (95% CIs) for all-cause mortality were 1.40 (1.21 to 1.62) (neopterin) and 1.23 (1.06 to 1.43) (KTR).
  
  
  CONCLUSIONS
  In patients with stable angina pectoris, systemic markers of IFN-γ activity, plasma neopterin, and plasma KTR provide similar risk estimates for MCE and mortality. Our results support experimental data linking IFN-γ to acute atherosclerotic complications.
authors.affiliation: Section for Cardiology, Institute of Medicine, University of Bergen, 5021 Bergen, Norway. eva.pedersen@med.uib.no
authors.forename: Eva Ringdal
authors.initials: ER
authors.lastname: Pedersen
authors.forename: Øivind
authors.initials: Ø
authors.lastname: Midttun
authors.forename: Per Magne
authors.initials: PM
authors.lastname: Ueland
authors.forename: Hall
authors.initials: H
authors.lastname: Schartum-Hansen
authors.forename: Reinhard
authors.initials: R
authors.lastname: Seifert
authors.forename: Jannicke
authors.initials: J
authors.lastname: Igland
authors.forename: Jan Erik
authors.initials: JE
authors.lastname: Nordrehaug
authors.forename: Marta
authors.initials: M
authors.lastname: Ebbing
authors.forename: Gard
authors.initials: G
authors.lastname: Svingen
authors.forename: Øyvind
authors.initials: Ø
authors.lastname: Bleie
authors.forename: Rolf
authors.initials: R
authors.lastname: Berge
authors.forename: Ottar
authors.initials: O
authors.lastname: Nygård
mesh_terms: D000368:Aged; D000787:Angina Pectoris / Q000000981:diagnostic imaging / Q000209:etiology / Q000276:immunology* / Q000401:mortality; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000032:analysis; D017023:Coronary Angiography; D003324:Coronary Artery Disease / Q000150:complications / Q000000981:diagnostic imaging / Q000276:immunology* / Q000401:mortality; D005260:Female; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood*; D007371:Interferon-gamma / Q000276:immunology*; D053208:Kaplan-Meier Estimate; D007737:Kynurenine / Q000097:blood*; D008264:Macrophages / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D019798:Neopterin / Q000097:blood*; D009664:Norway; D016017:Odds Ratio; D016016:Proportional Hazards Models; D011446:Prospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D013997:Time Factors
chemical_list: D015415:Biomarkers; D018836:Inflammation Mediators; D007737:Kynurenine; D019798:Neopterin; D007371:Interferon-gamma; D002097:C-Reactive Protein