Simone J P M Eussen1, Per Magne Ueland2, Stein E Vollset3, Ottar Nygård4, Øivind Midttun5, Gerhard Sulo6, Arve Ulvik5, Klaus Meyer5, Eva Ringdal Pedersen7, Grethe S Tell6. 1. 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. 2. Department of Clinical Science, University of Bergen, Norway; Laboratory of Clinical Biochemistry, Haukeland University Hospital, Bergen, Norway. 3. Department of Global Public Health and Primary Care, University of Bergen, Bergen, Norway; Norwegian Institute of Public Health, Bergen, Norway. 4. 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. 5. Bevital AS, Bergen, Norway. 6. Department of Global Public Health and Primary Care, University of Bergen, Bergen, Norway. 7. Department of Clinical Science, University of Bergen, Norway.
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.
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: Vincent Chouraki; Sarah R Preis; Qiong Yang; Alexa Beiser; Shuo Li; Martin G Larson; Galit Weinstein; Thomas J Wang; Robert E Gerszten; Ramachandran S Vasan; Sudha Seshadri Journal: Alzheimers Dement Date: 2017-06-08 Impact factor: 21.566
Authors: María Isabel Cuartero; Juan de la Parra; Alicia García-Culebras; Iván Ballesteros; Ignacio Lizasoain; María Ángeles Moro Journal: Curr Pharm Des Date: 2016 Impact factor: 3.116
Authors: Qibin Qi; Simin Hua; Clary B Clish; Justin M Scott; David B Hanna; Tao Wang; Sabina A Haberlen; Sanjiv J Shah; Marshall J Glesby; Jason M Lazar; Robert D Burk; Howard N Hodis; Alan L Landay; Wendy S Post; Kathryn Anastos; Robert C Kaplan Journal: Clin Infect Dis Date: 2018-07-02 Impact factor: 9.079