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@ARTICLE{Floegel:132469,
      author       = {A. Floegel and T. Kühn$^*$ and D. Sookthai$^*$ and T. S.
                      Johnson$^*$ and C. Prehn and U. Rolle-Kampczyk and W. Otto
                      and C. Weikert and T. Illig and M. von Bergen and J. Adamski
                      and H. Boeing and R. Kaaks$^*$ and T. Pischon},
      title        = {{S}erum metabolites and risk of myocardial infarction and
                      ischemic stroke: a targeted metabolomic approach in two
                      {G}erman prospective cohorts.},
      journal      = {European journal of epidemiology},
      volume       = {33},
      number       = {1},
      issn         = {1573-7284},
      address      = {Dordrecht [u.a.]},
      publisher    = {Springer Science + Business Media B.V.},
      reportid     = {DKFZ-2018-00157},
      pages        = {55 - 66},
      year         = {2018},
      abstract     = {Metabolomic approaches in prospective cohorts may offer a
                      unique snapshot into early metabolic perturbations that are
                      associated with a higher risk of cardiovascular diseases
                      (CVD) in healthy people. We investigated the association of
                      105 serum metabolites, including acylcarnitines, amino
                      acids, phospholipids and hexose, with risk of myocardial
                      infarction (MI) and ischemic stroke in the European
                      Prospective Investigation into Cancer and Nutrition
                      (EPIC)-Potsdam (27,548 adults) and Heidelberg (25,540
                      adults) cohorts. Using case-cohort designs, we measured
                      metabolites among individuals who were free of CVD and
                      diabetes at blood draw but developed MI (n = 204 and
                      n = 228) or stroke (n = 147 and n = 121) during
                      follow-up (mean, 7.8 and 7.3 years) and among randomly
                      drawn subcohorts (n = 2214 and n = 770). We used Cox
                      regression analysis and combined results using
                      meta-analysis. Independent of classical CVD risk factors,
                      ten metabolites were associated with risk of MI in both
                      cohorts, including sphingomyelins,
                      diacyl-phosphatidylcholines and
                      acyl-alkyl-phosphatidylcholines with pooled relative risks
                      in the range of 1.21-1.40 per one standard deviation
                      increase in metabolite concentrations. The metabolites
                      showed positive correlations with total- and LDL-cholesterol
                      (r ranged from 0.13 to 0.57). When additionally adjusting
                      for total-, LDL- and HDL-cholesterol, triglycerides and
                      C-reactive protein, acyl-alkyl-phosphatidylcholine C36:3 and
                      diacyl-phosphatidylcholines C38:3 and C40:4 remained
                      associated with risk of MI. When added to classical CVD risk
                      models these metabolites further improved CVD prediction
                      (c-statistics increased from 0.8365 to 0.8384 in
                      EPIC-Potsdam and from 0.8344 to 0.8378 in EPIC-Heidelberg).
                      None of the metabolites was consistently associated with
                      stroke risk. Alterations in sphingomyelin and
                      phosphatidylcholine metabolism, and particularly metabolites
                      of the arachidonic acid pathway are independently associated
                      with risk of MI in healthy adults.},
      cin          = {C020},
      ddc          = {610},
      cid          = {I:(DE-He78)C020-20160331},
      pnm          = {323 - Metabolic Dysfunction as Risk Factor (POF3-323)},
      pid          = {G:(DE-HGF)POF3-323},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:29181692},
      pmc          = {pmc:PMC5803284},
      doi          = {10.1007/s10654-017-0333-0},
      url          = {https://inrepo02.dkfz.de/record/132469},
}