Section for Cardiology, Institute of Medicine, Section for Pharmacology, Institute of Medicine, Institute of Public Health and Primary Health Care, and Nordic Centre of Excellence in Human Nutrition-MitoHealth, University of Bergen, Bergen, Norway; Bevital A/S, Bergen, Norway (.M.); Laboratory of Clinical Biochemistry and Department of Heart Disease (R.S., J.E.N., M.E., G.S., .B., R.B., O.N.), Haukeland University Hospital, Bergen, Norway.
OBJECTIVE: Interferon ? (IFN-?) is centrally involved in atherosclerosis-related inflammation, but its activity cannot be reliably assessed by systemic measurements. In activated macrophages, IFN-? 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-? activity, plasma neopterin, and plasma KTR provide similar risk estimates for MCE and mortality. Our results support experimental data linking IFN-? to acute atherosclerotic complications.