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.

METHODS AND 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: Eva Ringdal Pedersen, Øivind Midttun, Per Magne Ueland, Hall Schartum-Hansen, Reinhard Seifert, Jannicke Igland, Jan Erik Nordrehaug, Marta Ebbing, Gard Svingen, Øyvind Bleie, Rolf Berge, Ottar Nygård
• Journal: Arteriosclerosis, thrombosis, and vascular biology (Arterioscler Thromb Vasc Biol) Vol. 31 Issue 3 Pg. 698-704 (Mar 2011) ISSN: 1524-4636 [Electronic] United States
• PMID: 21183733 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Biomarkers
• Inflammation Mediators
• Kynurenine
• Neopterin
• Interferon-gamma
• C-Reactive Protein

Topics

• Aged
• Angina Pectoris (diagnostic imaging, etiology, immunology, mortality)
• Biomarkers (blood)
• C-Reactive Protein (analysis)
• Coronary Angiography
• Coronary Artery Disease (complications, diagnostic imaging, immunology, mortality)
• Female
• Humans
• Inflammation Mediators (blood)
• Interferon-gamma (immunology)
• Kaplan-Meier Estimate
• Kynurenine (blood)
• Macrophages (immunology)
• Male
• Middle Aged
• Neopterin (blood)
• Norway
• Odds Ratio
• Proportional Hazards Models
• Prospective Studies
• Risk Assessment
• Risk Factors
• Time Factors