Associations of plasma kynurenines with risk of acute myocardial infarction in patients with stable angina pectoris.

Autor:	Pedersen ER; From the Department of Clinical Science (E.R.P., N.T., P.M.U., E.S., G.F.T.S., G.M., J.E.N., D.W.N., O.N.) and Department of Global Public Health and Primary Health Care (S.J.P.M.E.), University of Bergen, Bergen, Norway; Department of Heart Disease, Haukeland University Hospital, Bergen, Norway (N.T., O.N.); Department of Epidemiology, School for Public Health and Primary Care-CAPHRI, Maastricht University, Maastricht, The Netherlands (S.J.P.M.E.); Laboratory of Clinical Biochemistry (P.M.U.) and Hormone Laboratory (G.M.), Haukeland University Hospital, Bergen, Norway; Bevital AS, Bergen, Norway (P.M.U., Ø.M., K.M., A.U.); Department of Cardiology, Stavanger University Hospital, Stavanger, Norway (J.E.N., D.W.N.); and KG Jebsen Center for Diabetes Research, Bergen, Norway (G.M., O.N.). eva.pedersen@k2.uib.no., Tuseth N; From the Department of Clinical Science (E.R.P., N.T., P.M.U., E.S., G.F.T.S., G.M., J.E.N., D.W.N., O.N.) and Department of Global Public Health and Primary Health Care (S.J.P.M.E.), University of Bergen, Bergen, Norway; Department of Heart Disease, Haukeland University Hospital, Bergen, Norway (N.T., O.N.); Department of Epidemiology, School for Public Health and Primary Care-CAPHRI, Maastricht University, Maastricht, The Netherlands (S.J.P.M.E.); Laboratory of Clinical Biochemistry (P.M.U.) and Hormone Laboratory (G.M.), Haukeland University Hospital, Bergen, Norway; Bevital AS, Bergen, Norway (P.M.U., Ø.M., K.M., A.U.); Department of Cardiology, Stavanger University Hospital, Stavanger, Norway (J.E.N., D.W.N.); and KG Jebsen Center for Diabetes Research, Bergen, Norway (G.M., O.N.)., Eussen SJ; From the Department of Clinical Science (E.R.P., N.T., P.M.U., E.S., G.F.T.S., G.M., J.E.N., D.W.N., O.N.) and Department of Global Public Health and Primary Health Care (S.J.P.M.E.), University of Bergen, Bergen, Norway; Department of Heart Disease, Haukeland University Hospital, Bergen, Norway (N.T., O.N.); Department of Epidemiology, School for Public Health and Primary Care-CAPHRI, Maastricht University, Maastricht, The Netherlands (S.J.P.M.E.); Laboratory of Clinical Biochemistry (P.M.U.) and Hormone Laboratory (G.M.), Haukeland University Hospital, Bergen, Norway; Bevital AS, Bergen, Norway (P.M.U., Ø.M., K.M., A.U.); Department of Cardiology, Stavanger University Hospital, Stavanger, Norway (J.E.N., D.W.N.); and KG Jebsen Center for Diabetes Research, Bergen, Norway (G.M., O.N.)., Ueland PM; From the Department of Clinical Science (E.R.P., N.T., P.M.U., E.S., G.F.T.S., G.M., J.E.N., D.W.N., O.N.) and Department of Global Public Health and Primary Health Care (S.J.P.M.E.), University of Bergen, Bergen, Norway; Department of Heart Disease, Haukeland University Hospital, Bergen, Norway (N.T., O.N.); Department of Epidemiology, School for Public Health and Primary Care-CAPHRI, Maastricht University, Maastricht, The Netherlands (S.J.P.M.E.); Laboratory of Clinical Biochemistry (P.M.U.) and Hormone Laboratory (G.M.), Haukeland University Hospital, Bergen, Norway; Bevital AS, Bergen, Norway (P.M.U., Ø.M., K.M., A.U.); Department of Cardiology, Stavanger University Hospital, Stavanger, Norway (J.E.N., D.W.N.); and KG Jebsen Center for Diabetes Research, Bergen, Norway (G.M., O.N.)., Strand E; From the Department of Clinical Science (E.R.P., N.T., P.M.U., E.S., G.F.T.S., G.M., J.E.N., D.W.N., O.N.) and Department of Global Public Health and Primary Health Care (S.J.P.M.E.), University of Bergen, Bergen, Norway; Department of Heart Disease, Haukeland University Hospital, Bergen, Norway (N.T., O.N.); Department of Epidemiology, School for Public Health and Primary Care-CAPHRI, Maastricht University, Maastricht, The Netherlands (S.J.P.M.E.); Laboratory of Clinical Biochemistry (P.M.U.) and Hormone Laboratory (G.M.), Haukeland University Hospital, Bergen, Norway; Bevital AS, Bergen, Norway (P.M.U., Ø.M., K.M., A.U.); Department of Cardiology, Stavanger University Hospital, Stavanger, Norway (J.E.N., D.W.N.); and KG Jebsen Center for Diabetes Research, Bergen, Norway (G.M., O.N.)., Svingen GF; From the Department of Clinical Science (E.R.P., N.T., P.M.U., E.S., G.F.T.S., G.M., J.E.N., D.W.N., O.N.) and Department of Global Public Health and Primary Health Care (S.J.P.M.E.), University of Bergen, Bergen, Norway; Department of Heart Disease, Haukeland University Hospital, Bergen, Norway (N.T., O.N.); Department of Epidemiology, School for Public Health and Primary Care-CAPHRI, Maastricht University, Maastricht, The Netherlands (S.J.P.M.E.); Laboratory of Clinical Biochemistry (P.M.U.) and Hormone Laboratory (G.M.), Haukeland University Hospital, Bergen, Norway; Bevital AS, Bergen, Norway (P.M.U., Ø.M., K.M., A.U.); Department of Cardiology, Stavanger University Hospital, Stavanger, Norway (J.E.N., D.W.N.); and KG Jebsen Center for Diabetes Research, Bergen, Norway (G.M., O.N.)., Midttun Ø; From the Department of Clinical Science (E.R.P., N.T., P.M.U., E.S., G.F.T.S., G.M., J.E.N., D.W.N., O.N.) and Department of Global Public Health and Primary Health Care (S.J.P.M.E.), University of Bergen, Bergen, Norway; Department of Heart Disease, Haukeland University Hospital, Bergen, Norway (N.T., O.N.); Department of Epidemiology, School for Public Health and Primary Care-CAPHRI, Maastricht University, Maastricht, The Netherlands (S.J.P.M.E.); Laboratory of Clinical Biochemistry (P.M.U.) and Hormone Laboratory (G.M.), Haukeland University Hospital, Bergen, Norway; Bevital AS, Bergen, Norway (P.M.U., Ø.M., K.M., A.U.); Department of Cardiology, Stavanger University Hospital, Stavanger, Norway (J.E.N., D.W.N.); and KG Jebsen Center for Diabetes Research, Bergen, Norway (G.M., O.N.)., Meyer K; From the Department of Clinical Science (E.R.P., N.T., P.M.U., E.S., G.F.T.S., G.M., J.E.N., D.W.N., O.N.) and Department of Global Public Health and Primary Health Care (S.J.P.M.E.), University of Bergen, Bergen, Norway; Department of Heart Disease, Haukeland University Hospital, Bergen, Norway (N.T., O.N.); Department of Epidemiology, School for Public Health and Primary Care-CAPHRI, Maastricht University, Maastricht, The Netherlands (S.J.P.M.E.); Laboratory of Clinical Biochemistry (P.M.U.) and Hormone Laboratory (G.M.), Haukeland University Hospital, Bergen, Norway; Bevital AS, Bergen, Norway (P.M.U., Ø.M., K.M., A.U.); Department of Cardiology, Stavanger University Hospital, Stavanger, Norway (J.E.N., D.W.N.); and KG Jebsen Center for Diabetes Research, Bergen, Norway (G.M., O.N.)., Mellgren G; From the Department of Clinical Science (E.R.P., N.T., P.M.U., E.S., G.F.T.S., G.M., J.E.N., D.W.N., O.N.) and Department of Global Public Health and Primary Health Care (S.J.P.M.E.), University of Bergen, Bergen, Norway; Department of Heart Disease, Haukeland University Hospital, Bergen, Norway (N.T., O.N.); Department of Epidemiology, School for Public Health and Primary Care-CAPHRI, Maastricht University, Maastricht, The Netherlands (S.J.P.M.E.); Laboratory of Clinical Biochemistry (P.M.U.) and Hormone Laboratory (G.M.), Haukeland University Hospital, Bergen, Norway; Bevital AS, Bergen, Norway (P.M.U., Ø.M., K.M., A.U.); Department of Cardiology, Stavanger University Hospital, Stavanger, Norway (J.E.N., D.W.N.); and KG Jebsen Center for Diabetes Research, Bergen, Norway (G.M., O.N.)., Ulvik A; From the Department of Clinical Science (E.R.P., N.T., P.M.U., E.S., G.F.T.S., G.M., J.E.N., D.W.N., O.N.) and Department of Global Public Health and Primary Health Care (S.J.P.M.E.), University of Bergen, Bergen, Norway; Department of Heart Disease, Haukeland University Hospital, Bergen, Norway (N.T., O.N.); Department of Epidemiology, School for Public Health and Primary Care-CAPHRI, Maastricht University, Maastricht, The Netherlands (S.J.P.M.E.); Laboratory of Clinical Biochemistry (P.M.U.) and Hormone Laboratory (G.M.), Haukeland University Hospital, Bergen, Norway; Bevital AS, Bergen, Norway (P.M.U., Ø.M., K.M., A.U.); Department of Cardiology, Stavanger University Hospital, Stavanger, Norway (J.E.N., D.W.N.); and KG Jebsen Center for Diabetes Research, Bergen, Norway (G.M., O.N.)., Nordrehaug JE; From the Department of Clinical Science (E.R.P., N.T., P.M.U., E.S., G.F.T.S., G.M., J.E.N., D.W.N., O.N.) and Department of Global Public Health and Primary Health Care (S.J.P.M.E.), University of Bergen, Bergen, Norway; Department of Heart Disease, Haukeland University Hospital, Bergen, Norway (N.T., O.N.); Department of Epidemiology, School for Public Health and Primary Care-CAPHRI, Maastricht University, Maastricht, The Netherlands (S.J.P.M.E.); Laboratory of Clinical Biochemistry (P.M.U.) and Hormone Laboratory (G.M.), Haukeland University Hospital, Bergen, Norway; Bevital AS, Bergen, Norway (P.M.U., Ø.M., K.M., A.U.); Department of Cardiology, Stavanger University Hospital, Stavanger, Norway (J.E.N., D.W.N.); and KG Jebsen Center for Diabetes Research, Bergen, Norway (G.M., O.N.)., Nilsen DW; From the Department of Clinical Science (E.R.P., N.T., P.M.U., E.S., G.F.T.S., G.M., J.E.N., D.W.N., O.N.) and Department of Global Public Health and Primary Health Care (S.J.P.M.E.), University of Bergen, Bergen, Norway; Department of Heart Disease, Haukeland University Hospital, Bergen, Norway (N.T., O.N.); Department of Epidemiology, School for Public Health and Primary Care-CAPHRI, Maastricht University, Maastricht, The Netherlands (S.J.P.M.E.); Laboratory of Clinical Biochemistry (P.M.U.) and Hormone Laboratory (G.M.), Haukeland University Hospital, Bergen, Norway; Bevital AS, Bergen, Norway (P.M.U., Ø.M., K.M., A.U.); Department of Cardiology, Stavanger University Hospital, Stavanger, Norway (J.E.N., D.W.N.); and KG Jebsen Center for Diabetes Research, Bergen, Norway (G.M., O.N.)., Nygård O; From the Department of Clinical Science (E.R.P., N.T., P.M.U., E.S., G.F.T.S., G.M., J.E.N., D.W.N., O.N.) and Department of Global Public Health and Primary Health Care (S.J.P.M.E.), University of Bergen, Bergen, Norway; Department of Heart Disease, Haukeland University Hospital, Bergen, Norway (N.T., O.N.); Department of Epidemiology, School for Public Health and Primary Care-CAPHRI, Maastricht University, Maastricht, The Netherlands (S.J.P.M.E.); Laboratory of Clinical Biochemistry (P.M.U.) and Hormone Laboratory (G.M.), Haukeland University Hospital, Bergen, Norway; Bevital AS, Bergen, Norway (P.M.U., Ø.M., K.M., A.U.); Department of Cardiology, Stavanger University Hospital, Stavanger, Norway (J.E.N., D.W.N.); and KG Jebsen Center for Diabetes Research, Bergen, Norway (G.M., O.N.).
Jazyk:	angličtina
Zdroj:	Arteriosclerosis, thrombosis, and vascular biology [Arterioscler Thromb Vasc Biol] 2015 Feb; Vol. 35 (2), pp. 455-62. Date of Electronic Publication: 2014 Dec 18.
DOI:	10.1161/ATVBAHA.114.304674
Abstrakt:	Objective: Enhanced tryptophan degradation, induced by the proinflammatory cytokine interferon-γ, has been related to cardiovascular disease progression and insulin resistance. We assessed downstream tryptophan metabolites of the kynurenine pathway as predictors of acute myocardial infarction in patients with suspected stable angina pectoris. Furthermore, we evaluated potential effect modifications according to diagnoses of pre-diabetes mellitus or diabetes mellitus. Approach and Results: Blood samples were obtained from 4122 patients (median age, 62 years; 72% men) who underwent elective coronary angiography. During median follow-up of 56 months, 8.3% had acute myocardial infarction. Comparing the highest quartile to the lowest, for the total cohort, multivariable adjusted hazard ratios (95% confidence intervals) were 1.68 (1.21-2.34), 1.81 (1.33-2.48), 1.68 (1.21-2.32), and 1.48 (1.10-1.99) for kynurenic acid, hydroxykynurenine, anthranilic acid, and hydroxyanthranilic acid, respectively. The kynurenines correlated with phenotypes of the metabolic syndrome, and risk associations were generally stronger in subgroups classified with pre-diabetes mellitus or diabetes mellitus at inclusion (Pint≤0.05). Evaluated in the total population, hydroxykynurenine and anthranilic acid provided statistically significant net reclassification improvements (0.21 [0.08-0.35] and 0.21 [0.07-0.35], respectively). Conclusions: In patients with suspected stable angina pectoris, elevated levels of plasma kynurenines predicted increased risk of acute myocardial infarction, and risk estimates were generally stronger in subgroups with evidence of impaired glucose homeostasis. Future studies should aim to clarify roles of the kynurenine pathway in atherosclerosis and glucose metabolism. (© 2014 American Heart Association, Inc.)
Databáze:	MEDLINE
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