title: Kynurenines as predictors of acute coronary events in the Hordaland Health Study.
abstract: BACKGROUND
  The kynurenine pathway, the main metabolic route of tryptophan degradation, has been related to inflammatory responses. Some of its metabolites, referred to as kynurenines, have been associated with prevalence of coronary heart disease (CHD) in cross-sectional studies. This prospective study aims to investigate whether increased concentrations of kynurenines are associated with risk of acute coronary events, defined as unstable angina pectoris, acute myocardial infarction, and/or sudden death in community-dwelling elderly.
  
  
  METHODS
  The baseline examinations included 2819 individuals aged 71-74 years recruited into the Hordaland Health Study. Participants with known CHD at baseline were excluded from analyses. Baseline plasma concentrations of tryptophan, kynurenine, kynurenic acid, anthranilic acid, 3-hydroxykynurenine, xanthurenic acid, and 3-hydroxyanthranilic acid were measured by LC-MS/MS. During a median follow-up period of 10.8 years, with linkage to acute coronary event endpoints through the CVDNOR project, hazard ratios (HRs) for acute coronary events (n = 376) were estimated using Cox proportional hazard analyses.
  
  
  RESULTS
  After adjustment for established cardiovascular risk factors, HRs (95% CI) comparing the 4th vs 1st quartile were 1.86 (1.19-2.92) for kynurenine and 1.72 (1.19-2.49) for 3-hydroxykynurenine. Tryptophan, kynurenic acid, anthranilic acid, xanthurenic acid and 3-hydroxyanthranilic acid were not associated with acute coronary events.
  
  
  CONCLUSIONS
  Kynurenine and 3-hydroxykynurenine were associated with increased risk of acute coronary events in community-dwelling elderly without a known history of CHD. These results suggest the involvement of the kynurenine pathway in the early development of CHD, and their potential usefulness to estimate CHD risk.
authors.affiliation: Department of Global Public Health and Primary Care, University of Bergen, Bergen, Norway; Department of Clinical Science, University of Bergen, Norway; Department of Epidemiology, School for Cardiovascular Diseases (CARIM) and School for Public Health and Primary Care (CAPHRI), Maastricht University, The Netherlands. Electronic address: Simone.Eussen@farm.uib.no.
authors.forename: Simone J P M
authors.initials: SJ
authors.lastname: Eussen
authors.affiliation: Department of Clinical Science, University of Bergen, Norway; Laboratory of Clinical Biochemistry, Haukeland University Hospital, Bergen, Norway.
authors.forename: Per Magne
authors.initials: PM
authors.lastname: Ueland
authors.affiliation: Department of Global Public Health and Primary Care, University of Bergen, Bergen, Norway; Norwegian Institute of Public Health, Bergen, Norway.
authors.forename: Stein E
authors.initials: SE
authors.lastname: Vollset
authors.affiliation: Department of Clinical Science, University of Bergen, Norway; Department of Heart Disease, Haukeland University Hospital, Bergen, Norway; KG Jebsen Centre for Diabetes Research, University of Bergen, Norway.
authors.forename: Ottar
authors.initials: O
authors.lastname: Nygård
authors.affiliation: Bevital AS, Bergen, Norway.
authors.forename: Øivind
authors.initials: Ø
authors.lastname: Midttun
authors.affiliation: Department of Global Public Health and Primary Care, University of Bergen, Bergen, Norway.
authors.forename: Gerhard
authors.initials: G
authors.lastname: Sulo
authors.affiliation: Bevital AS, Bergen, Norway.
authors.forename: Arve
authors.initials: A
authors.lastname: Ulvik
authors.affiliation: Bevital AS, Bergen, Norway.
authors.forename: Klaus
authors.initials: K
authors.lastname: Meyer
authors.affiliation: Department of Clinical Science, University of Bergen, Norway.
authors.forename: Eva Ringdal
authors.initials: ER
authors.lastname: Pedersen
authors.affiliation: Department of Global Public Health and Primary Care, University of Bergen, Bergen, Norway.
authors.forename: Grethe S
authors.initials: GS
authors.lastname: Tell
mesh_terms: D054058:Acute Coronary Syndrome / Q000097:blood* / Q000401:mortality* / Q000503:physiopathology; D000367:Age Factors; D000368:Aged; D000787:Angina Pectoris / Q000097:blood / Q000401:mortality / Q000503:physiopathology; D015415:Biomarkers / Q000378:metabolism; D015331:Cohort Studies; D016001:Confidence Intervals; D005260:Female; D015577:Geriatric Assessment / Q000379:methods; D006306:Health Surveys; D006801:Humans; D057187:Independent Living; D007737:Kynurenine / Q000378:metabolism*; D008297:Male; D009203:Myocardial Infarction / Q000097:blood / Q000401:mortality / Q000503:physiopathology; D009664:Norway; D011237:Predictive Value of Tests; D011379:Prognosis; D016016:Proportional Hazards Models; D011446:Prospective Studies; D018570:Risk Assessment; D012720:Severity of Illness Index; D012737:Sex Factors; D018709:Statistics, Nonparametric; D016019:Survival Analysis
chemical_list: D015415:Biomarkers; D007737:Kynurenine
keywords: Acute coronary events; Inflammation; Kynurenines; Prospective cohort study