title: Plasma Biomarkers of Inflammation, the Kynurenine Pathway, and Risks of All-Cause, Cancer, and Cardiovascular Disease Mortality: The Hordaland Health Study.
abstract: We aimed to evaluate 10 biomarkers related to inflammation and the kynurenine pathway, including neopterin, kynurenine:tryptophan ratio, C-reactive protein, tryptophan, and 6 kynurenines, as potential predictors of all-cause and cause-specific mortality in a general population sample. The study cohort was participants involved in a community-based Norwegian study, the Hordaland Health Study (HUSK). We used Cox proportional hazards models to assess associations of the biomarkers with all-cause mortality and competing-risk models for cause-specific mortality. Of the 7,015 participants, 1,496 deaths were recorded after a median follow-up time of 14 years (1998-2012). Plasma levels of inflammatory markers (neopterin, kynurenine:tryptophan ratio, and C-reactive protein), anthranilic acid, and 3-hydroxykynurenine were positively associated with all-cause mortality, and tryptophan and xanthurenic acid were inversely associated. Multivariate-adjusted hazard ratios for the highest (versus lowest) quartiles of the biomarkers were 1.19-1.60 for positive associations and 0.73-0.87 for negative associations. All of the inflammatory markers and most kynurenines, except kynurenic acid and 3-hydroxyanthranilic acid, were associated with cardiovascular disease (CVD) mortality. In this general population, plasma biomarkers of inflammation and kynurenines were associated with risk of all-cause, cancer, and CVD mortality. Associations were stronger for CVD mortality than for mortality due to cancer or other causes.
authors.forename: Hui
authors.initials: H
authors.lastname: Zuo
authors.forename: Per M
authors.initials: PM
authors.lastname: Ueland
authors.forename: Arve
authors.initials: A
authors.lastname: Ulvik
authors.forename: Simone J P M
authors.initials: SJ
authors.lastname: Eussen
authors.forename: Stein E
authors.initials: SE
authors.lastname: Vollset
authors.forename: Ottar
authors.initials: O
authors.lastname: Nygård
authors.forename: Øivind
authors.initials: Ø
authors.lastname: Midttun
authors.forename: Despoina
authors.initials: D
authors.lastname: Theofylaktopoulou
authors.forename: Klaus
authors.initials: K
authors.lastname: Meyer
authors.forename: Grethe S
authors.initials: GS
authors.lastname: Tell
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000378:metabolism; D005260:Female; D006801:Humans; D007249:Inflammation / Q000097:blood; D007737:Kynurenine / Q000097:blood*; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D009026:Mortality; D019798:Neopterin / Q000097:blood*; D009664:Norway; D014364:Tryptophan / Q000097:blood*
chemical_list: D015415:Biomarkers; D007737:Kynurenine; D019798:Neopterin; D014364:Tryptophan; D002097:C-Reactive Protein
keywords: cancer; cardiovascular disease; inflammation; mortality; tryptophan
references.citation: J Nutr. 2006 Jun;136(6 Suppl):1731S-1740S
references.pmid: 16702348
references.citation: Eur Heart J. 2012 Aug;33(16):2025-34
references.pmid: 22711758
references.citation: FEBS J. 2012 Apr;279(8):1386-97
references.pmid: 22248239
references.citation: Nat Rev Drug Discov. 2013 Jan;12(1):64-82
references.pmid: 23237916
references.citation: Stat Med. 1995 Aug 15;14(15):1707-23
references.pmid: 7481205
references.citation: J Bone Miner Res. 2013 Jul;28(7):1688-98
references.pmid: 23456822
references.citation: Int J Tryptophan Res. 2009;2:1-19
references.pmid: 22084578
references.citation: J Nutr. 2014 May;144(5):784-90
references.pmid: 24647388
references.citation: Diabetes Care. 2014 Jan;37 Suppl 1:S14-80
references.pmid: 24357209
references.citation: Cell. 2010 Mar 19;140(6):883-99
references.pmid: 20303878
references.citation: Cancer. 2014 Nov 1;120(21):3370-7
references.pmid: 24948355
references.citation: Eur Heart J. 2013 Sep;34(34):2689-96
references.pmid: 23886918
references.citation: Nutr Rev. 2013 Apr;71(4):239-44
references.pmid: 23550784
references.citation: BMC Med. 2013;11:117
references.pmid: 23635324
references.citation: Ann Intern Med. 2009 May 5;150(9):604-12
references.pmid: 19414839
references.citation: J Nutr. 2011 Apr 1;141(4):611-7
references.pmid: 21310866
references.citation: Cancer Epidemiol Biomarkers Prev. 2012 Nov;21(11):2076-86
references.pmid: 23136255
references.citation: J Infect Dis. 2014 Aug 1;210(3):383-91
references.pmid: 24585899
references.citation: Am J Clin Nutr. 2006 Feb;83(2):456S-460S
references.pmid: 16470012
references.citation: Nat Rev Cancer. 2013 Nov;13(11):759-71
references.pmid: 24154716
references.citation: Int J Cardiol. 2013 Sep 30;168(2):1435-40
references.pmid: 23336953
references.citation: Clin Chim Acta. 2006 Feb;364(1-2):82-90
references.pmid: 16139256
references.citation: J Bone Miner Res. 2014 Feb;29(2):418-23
references.pmid: 23857741
references.citation: Clin Transplant. 2014 Jan;28(1):111-9
references.pmid: 24372612
references.citation: Neurochem Int. 2007 Jan;50(1):83-94
references.pmid: 16959377
references.citation: Asian Pac J Cancer Prev. 2013;14(1):243-8
references.pmid: 23534731
references.citation: Parkinsons Dis. 2011;2011:716859
references.pmid: 21687761
references.citation: Oxid Med Cell Longev. 2014;2014:646909
references.pmid: 24693337
references.citation: Lancet. 2010 Jan 9;375(9709):132-40
references.pmid: 20031199
references.citation: N Engl J Med. 2005 Apr 21;352(16):1685-95
references.pmid: 15843671
references.citation: Br J Cancer. 2004 Oct 4;91(7):1229-35
references.pmid: 15305188
references.citation: Scand J Clin Lab Invest. 2004;64(8):709-22
references.pmid: 15719889
references.citation: Clin Exp Immunol. 2013 Jul;173(1):121-30
references.pmid: 23607723
references.citation: Rapid Commun Mass Spectrom. 2009 May;23(9):1371-9
references.pmid: 19337982
references.citation: Diabetes Care. 2013 Jan;36(1):166-75
references.pmid: 23264288
references.citation: J Neurol Sci. 2007 Jun 15;257(1-2):221-39
references.pmid: 17462670
references.citation: Science. 2013 Jan 11;339(6116):166-72
references.pmid: 23307734
references.citation: Diabetologia. 2009 Jun;52(6):1040-7
references.pmid: 19326095
references.citation: Arterioscler Thromb Vasc Biol. 2011 Mar;31(3):698-704
references.pmid: 21183733
references.citation: Int J Epidemiol. 2012 Jun;41(3):861-70
references.pmid: 22253319
references.citation: Eur Heart J. 2010 Jul;31(13):1624-32
references.pmid: 20423919
references.citation: J Interferon Cytokine Res. 2005 Jan;25(1):20-30
references.pmid: 15684619
references.citation: Anal Chem. 2014 Jun 17;86(12):5807-14
references.pmid: 24848523
references.citation: Diabetes Care. 2012 Feb;35(2):396-403
references.pmid: 22210562
references.citation: Thorax. 2006 Oct;61(10):849-53
references.pmid: 16738034
references.citation: Am J Pathol. 2011 Sep;179(3):1360-72
references.pmid: 21855684