title: Improvement of myocardial infarction risk prediction via inflammation-associated metabolite biomarkers.
abstract: The comprehensive assaying of low-molecular-weight compounds, for example, metabolomics, provides a unique tool to uncover novel biomarkers and understand pathways underlying myocardial infarction (MI). We used a targeted metabolomics approach to identify biomarkers for MI and evaluate their involvement in the pathogenesis of MI.
  
  
  
  Using three independent, prospective cohorts (KORA S4, KORA S2 and AGES-REFINE), totalling 2257 participants without a history of MI at baseline, we identified metabolites associated with incident MI (266 cases). We also investigated the association between the metabolites and high-sensitivity C reactive protein (hsCRP) to understand the relation between these metabolites and systemic inflammation. Out of 140 metabolites, 16 were nominally associated (p<0.05) with incident MI in KORA S4. Three metabolites, arginine and two lysophosphatidylcholines (LPC 17:0 and LPC 18:2), were selected as biomarkers via a backward stepwise selection procedure in the KORA S4 and were significant (p<0.0003) in a meta-analysis comprising all three studies including KORA S2 and AGES-REFINE. Furthermore, these three metabolites increased the predictive value of the Framingham risk score, increasing the area under the receiver operating characteristic score in KORA S4 (from 0.70 to 0.78, p=0.001) and AGES-REFINE study (from 0.70 to 0.76, p=0.02), but was not observed in KORA S2. The metabolite biomarkers attenuated the association between hsCRP and MI, indicating a potential link to systemic inflammatory processes.
  
  
  
  We identified three metabolite biomarkers, which in combination increase the predictive value of the Framingham risk score. The attenuation of the hsCRP-MI association by these three metabolites indicates a potential link to systemic inflammation.
authors.affiliation: Institute of Epidemiology II, Helmholtz Zentrum München, Neuherberg, Germany.
authors.forename: Cavin K
authors.initials: CK
authors.lastname: Ward-Caviness
authors.affiliation: Institute of Epidemiology II, Helmholtz Zentrum München, Neuherberg, Germany.|Research Unit of Molecular Epidemiology, Helmholtz Zentrum München, Neuherberg, Germany.
authors.forename: Tao
authors.initials: T
authors.lastname: Xu
authors.affiliation: Icelandic Heart Association, Kopavogur, Iceland.|Centre for Public Health, University of Iceland, Reykjavik, Iceland.
authors.forename: Thor
authors.initials: T
authors.lastname: Aspelund
authors.affiliation: Institute of Epidemiology II, Helmholtz Zentrum München, Neuherberg, Germany.
authors.forename: Barbara
authors.initials: B
authors.lastname: Thorand
authors.affiliation: Institute of Bioinformatics and Systems Biology, Helmholtz Zentrum München, Neuherberg, Germany.
authors.forename: Corinna
authors.initials: C
authors.lastname: Montrone
authors.affiliation: Institute of Epidemiology II, Helmholtz Zentrum München, Neuherberg, Germany.
authors.forename: Christa
authors.initials: C
authors.lastname: Meisinger
authors.affiliation: Institute of Bioinformatics and Systems Biology, Helmholtz Zentrum München, Neuherberg, Germany.
authors.forename: Irmtraud
authors.initials: I
authors.lastname: Dunger-Kaltenbach
authors.affiliation: Institute of Epidemiology II, Helmholtz Zentrum München, Neuherberg, Germany.
authors.forename: Astrid
authors.initials: A
authors.lastname: Zierer
authors.affiliation: Institute of Epidemiology II, Helmholtz Zentrum München, Neuherberg, Germany.|Research Unit of Molecular Epidemiology, Helmholtz Zentrum München, Neuherberg, Germany.
authors.forename: Zhonghao
authors.initials: Z
authors.lastname: Yu
authors.affiliation: Icelandic Heart Association, Kopavogur, Iceland.
authors.forename: Inga R
authors.initials: IR
authors.lastname: Helgadottir
authors.affiliation: National Institute on Aging, Bethesda, Maryland, USA.
authors.forename: Tamara B
authors.initials: TB
authors.lastname: Harris
authors.affiliation: National Institute on Aging, Bethesda, Maryland, USA.
authors.forename: Lenore J
authors.initials: LJ
authors.lastname: Launer
authors.affiliation: Molecular Epidemiology and Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
authors.forename: Andrea
authors.initials: A
authors.lastname: Ganna
authors.affiliation: Department of Medical Sciences and Cardiovascular Epidemiology, Uppsala University, Uppsala, Sweden.
authors.forename: Lars
authors.initials: L
authors.lastname: Lind
authors.affiliation: Icelandic Heart Association, Kopavogur, Iceland.
authors.forename: Gudny
authors.initials: G
authors.lastname: Eiriksdottir
authors.affiliation: Institute of Epidemiology II, Helmholtz Zentrum München, Neuherberg, Germany.|Research Unit of Molecular Epidemiology, Helmholtz Zentrum München, Neuherberg, Germany.
authors.forename: Melanie
authors.initials: M
authors.lastname: Waldenberger
authors.affiliation: Institute of Experimental Genetics, Genome Analysis Center, Helmholtz Zentrum München, Neuherberg, Germany.
authors.forename: Cornelia
authors.initials: C
authors.lastname: Prehn
authors.affiliation: Institute of Bioinformatics and Systems Biology, Helmholtz Zentrum München, Neuherberg, Germany.
authors.forename: Karsten
authors.initials: K
authors.lastname: Suhre
authors.affiliation: Hannover Unified Biobank, Hannover Medical School, Hannover, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Illig
authors.affiliation: Institute of Experimental Genetics, Genome Analysis Center, Helmholtz Zentrum München, Neuherberg, Germany.|Chair of Experimental Genetics, Technische Universität München, München, Germany.
authors.forename: Jerzy
authors.initials: J
authors.lastname: Adamski
authors.affiliation: Institute of Bioinformatics and Systems Biology, Helmholtz Zentrum München, Neuherberg, Germany.|Chair of Experimental Genetics, Technische Universität München, München, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Ruepp
authors.affiliation: Department of Internal Medicine II, University of Ulm Medical Center, Ulm, Germany.|Deutsches Herzzentrum, Technische Universität München, München, Germany.|DZHK (German Centre for Cardiovascular Research), Partner site Munich Heart Alliance, Munchen, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Koenig
authors.affiliation: Icelandic Heart Association, Kopavogur, Iceland.|Faculty of Medicine, University of Iceland, Reykjavik, Iceland.
authors.forename: Vilmundur
authors.initials: V
authors.lastname: Gudnason
authors.affiliation: Icelandic Heart Association, Kopavogur, Iceland.|Faculty of Pharmaceutical Sciences, University of Iceland, Reykjavik, Iceland.
authors.forename: Valur
authors.initials: V
authors.lastname: Emilsson
authors.affiliation: Institute of Epidemiology II, Helmholtz Zentrum München, Neuherberg, Germany.|Research Unit of Molecular Epidemiology, Helmholtz Zentrum München, Neuherberg, Germany.
authors.forename: Rui
authors.initials: R
authors.lastname: Wang-Sattler
authors.affiliation: Institute of Epidemiology II, Helmholtz Zentrum München, Neuherberg, Germany.|DZHK (German Centre for Cardiovascular Research), Partner site Munich Heart Alliance, Munchen, Germany.|Department of Environmental Health, Harvard School of Public Health, Boston, Massachusetts, USA.
authors.forename: Annette
authors.initials: A
authors.lastname: Peters
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000378:metabolism*; D018450:Disease Progression; D005260:Female; D005858:Germany / Q000453:epidemiology; D006801:Humans; D015994:Incidence; D007249:Inflammation / Q000378:metabolism*; D008297:Male; D013058:Mass Spectrometry; D008875:Middle Aged; D009203:Myocardial Infarction / Q000175:diagnosis / Q000453:epidemiology / Q000378:metabolism*; D011237:Predictive Value of Tests; D011446:Prospective Studies; D018570:Risk Assessment / Q000379:methods*; D011795:Surveys and Questionnaires
chemical_list: D015415:Biomarkers
keywords: Myocardial infarction; biomarkers; inflammation; metabolomics