title: Urinary excretion of kynurenine and tryptophan, cardiovascular events, and mortality after elective coronary angiography.
abstract: OBJECTIVE
  Kynurenine is a potent endothelium-derived vasodilator. Its synthesis from tryptophan is stimulated by interferon γ and may represent an important compensatory pathway for the regulation of vascular function in inflammatory conditions. We assessed associations of urine kynurenine to tryptophan ratio (KTR) levels to incident major coronary events (MCEs), acute myocardial infarction (AMI), and ischaemic stroke and mortality in patients with suspected stable coronary artery disease (CAD).
  
  
  RESULTS
  A total of 3224 patients (mean age 62 years, 69% men) underwent urine and blood sampling prior to elective coronary angiography and were subsequently followed up for median 55 months. A total of 8.4% experienced an MCE, 7.8% suffered an AMI, and 7.6% died. In age- and gender-adjusted analyses, the hazard ratios [HRs; 95% confidence intervals (CI)] of MCE, AMI, and all-cause mortality were 1.43 (1.29-1.59), 1.44 (1.29-1.59), and 1.38 (1.23-1.54) per standard deviation increment of the (log-transformed) urinary KTR, respectively. These estimates were only minimally attenuated after adjustment for potential confounders. The addition of the urine KTR to a model of conventional risk factors significantly improved goodness of fit, discrimination, and risk classification for these clinical endpoints. No association was seen between the urine KTR and the risk of incident ischaemic stroke.
  
  
  CONCLUSIONS
  A novel urinary inflammation marker, KTR, is strongly associated with adverse prognosis in patients with suspected stable CAD. Underlying pathomechanisms should be further elucidated.
authors.affiliation: Department of Clinical Science, University of Bergen, Laboratory Building, Bergen N-5021, Norway.
authors.forename: Eva Ringdal
authors.initials: ER
authors.lastname: Pedersen
authors.forename: Gard Frodahl Tveitevåg
authors.initials: GF
authors.lastname: Svingen
authors.forename: Hall
authors.initials: H
authors.lastname: Schartum-Hansen
authors.forename: Per Magne
authors.initials: PM
authors.lastname: Ueland
authors.forename: Marta
authors.initials: M
authors.lastname: Ebbing
authors.forename: Jan Erik
authors.initials: JE
authors.lastname: Nordrehaug
authors.forename: Jannicke
authors.initials: J
authors.lastname: Igland
authors.forename: Reinhard
authors.initials: R
authors.lastname: Seifert
authors.forename: Roy Miodini
authors.initials: RM
authors.lastname: Nilsen
authors.forename: Ottar
authors.initials: O
authors.lastname: Nygård
mesh_terms: D017023:Coronary Angiography; D003324:Coronary Artery Disease / Q000000981:diagnostic imaging / Q000401:mortality / Q000652:urine*; D005260:Female; D006801:Humans; D007737:Kynurenine / Q000652:urine*; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000000981:diagnostic imaging / Q000401:mortality / Q000652:urine*; D012307:Risk Factors; D020521:Stroke / Q000000981:diagnostic imaging / Q000401:mortality / Q000652:urine*; D014364:Tryptophan / Q000652:urine*
chemical_list: D007737:Kynurenine; D014364:Tryptophan
keywords: Coronary artery disease; Inflammation; Kynurenine; Risk prediction; Tryptophan; Urinary biomarker