title: A metabolomic profile is associated with the risk of incident coronary heart disease.
abstract: BACKGROUND
  Metabolomics, defined as the comprehensive identification and quantification of low-molecular-weight metabolites to be found in a biological sample, has been put forward as a potential tool for classifying individuals according to their risk of coronary heart disease (CHD). Here, we investigated whether a single-point blood measurement of the metabolome is associated with and predictive for the risk of CHD.
  
  
  RESULTS
  We obtained proton nuclear magnetic resonance spectra in 79 cases who developed CHD during follow-up (median 8.1 years) and in 565 randomly selected individuals. In these spectra, 100 signals representing 36 metabolites were identified. Applying least absolute shrinkage and selection operator regression, we defined a weighted metabolite score consisting of 13 proton nuclear magnetic resonance signals that optimally predicted CHD. This metabolite score, including signals representing a lipid fraction, glucose, valine, ornithine, glutamate, creatinine, glycoproteins, citrate, and 1.5-anhydrosorbitol, was associated with the incidence of CHD independent of traditional risk factors (TRFs) (hazard ratio 1.50, 95% CI 1.12-2.01). Predictive performance of this metabolite score on its own was moderate (C-index 0.75, 95% CI 0.70-0.80), but after adding age and sex, the C-index was only modestly lower than that of TRFs (C-index 0.81, 95% CI 0.77-0.85 and C-index 0.82, 95% CI 0.78-0.87, respectively). The metabolite score was also associated with prevalent CHD independent of TRFs (odds ratio 1.59, 95% CI 1.19-2.13).
  
  
  CONCLUSIONS
  A metabolite score derived from a single-point metabolome measurement is associated with CHD, and metabolomics may be a promising tool for refining and improving the prediction of CHD.
authors: Department of Molecular Epidemiology, Leiden University Medical Center, Leiden, The Netherlands. Electronic address: a.a.m.vaarhorst@lumc.nl.
authors: Anika A M
authors: AA
authors: Vaarhorst
authors: Department of Parasitology, Leiden University Medical Center, Leiden, The Netherlands.
authors: Aswin
authors: A
authors: Verhoeven
authors: Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands.
authors: Claudia M
authors: CM
authors: Weller
authors: Department of Medical Statistics, Leiden University Medical Center, Leiden, The Netherlands.
authors: Stefan
authors: S
authors: Böhringer
authors: Department of Parasitology, Leiden University Medical Center, Leiden, The Netherlands.
authors: Sibel
authors: S
authors: Göraler
authors: Department of Parasitology, Leiden University Medical Center, Leiden, The Netherlands.
authors: Axel
authors: A
authors: Meissner
authors: Department of Parasitology, Leiden University Medical Center, Leiden, The Netherlands.
authors: André M
authors: AM
authors: Deelder
authors: Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands.
authors: Peter
authors: P
authors: Henneman
authors: Department of Cardiology, Maastricht University Medical Centre, Maastricht, The Netherlands.
authors: Anton P M
authors: AP
authors: Gorgels
authors: Department of Epidemiology (CAPHRI School for Public Health and Primary Care), Maastricht University, Maastricht, The Netherlands; Department of Epidemiology (GROW School of Oncology and Developmental Biology), Maastricht University, Maastricht, The Netherlands.
authors: Piet A
authors: PA
authors: van den Brandt
authors: Department of Epidemiology (GROW School of Oncology and Developmental Biology), Maastricht University, Maastricht, The Netherlands.
authors: Leo J
authors: LJ
authors: Schouten
authors: Department of Internal Medicine (CARIM School for Cardiovascular diseases), Maastricht University Medical Centre, Maastricht, The Netherlands.
authors: Marleen M
authors: MM
authors: van Greevenbroek
authors: Department of Epidemiology (CAPHRI School for Public Health and Primary Care), Maastricht University, Maastricht, The Netherlands.
authors: Audrey H H
authors: AH
authors: Merry
authors: National Institute for Public Health and the Environment, Bilthoven, The Netherlands.
authors: W M Monique
authors: WM
authors: Verschuren
authors: Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands; Department of Neurology, Leiden University Medical Center, Leiden, The Netherlands.
authors: Arn M J M
authors: AM
authors: van den Maagdenberg
authors: Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands; Department of Endocrinology, Leiden University Medical Center, Leiden, The Netherlands.
authors: Ko Willems
authors: KW
authors: van Dijk
authors: Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands.
authors: Aaron
authors: A
authors: Isaacs
authors: Biological Psychology, VU University, Amsterdam, The Netherlands.
authors: Dorret
authors: D
authors: Boomsma
authors: Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands.
authors: Ben A
authors: BA
authors: Oostra
authors: Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands.
authors: Cornelia M
authors: CM
authors: van Duijn
authors: Department of Cardiology, Leiden University Medical Center, Leiden, The Netherlands; The Durrer Center for Cardiogenetic Research, Amsterdam, The Netherlands; Interuniversity Cardiology Institute of the Netherlands (ICIN), Utrecht, The Netherlands.
authors: J Wouter
authors: JW
authors: Jukema
authors: National Institute for Public Health and the Environment, Bilthoven, The Netherlands.
authors: Jolanda M A
authors: JM
authors: Boer
authors: Division of Human Nutrition, Wageningen University and Research Center, Wageningen, The Netherlands.
authors: Edith
authors: E
authors: Feskens
authors: Department of Molecular Epidemiology, Leiden University Medical Center, Leiden, The Netherlands.
authors: Bastiaan T
authors: BT
authors: Heijmans
authors: Department of Molecular Epidemiology, Leiden University Medical Center, Leiden, The Netherlands; Netherlands Consortium for Healthy Ageing, Leiden, The Netherlands. Electronic address: P.Slagboom@lumc.nl.
authors: P Eline
authors: PE
authors: Slagboom
mesh_terms: D000328:Adult; D003327:Coronary Disease / Q000097:blood* / Q000453:epidemiology*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D015994:Incidence; D008055:Lipids / Q000097:blood*; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D008297:Male; D055432:Metabolomics / Q000379:methods*; D008875:Middle Aged; D009426:Netherlands / Q000453:epidemiology; D016017:Odds Ratio; D011237:Predictive Value of Tests; D011379:Prognosis; D011446:Prospective Studies; D012307:Risk Factors; D013997:Time Factors; D055815:Young Adult
chemical_list: D008055:Lipids