title: Cardiovascular Risk Factors Associated With Blood Metabolite Concentrations and Their Alterations During a 4-Year Period in a Population-Based Cohort.
abstract: BACKGROUND
  The effects of lifestyle risk factors considered collectively on the human metabolism are to date unknown. We aim to investigate the association of these risk factors with metabolites and their changes during 4 years.
  
  
  RESULTS
  One hundred and sixty-three metabolites were measured in serum samples with the AbsoluteIDQ kit p150 (Biocrates) following a targeted metabolomics approach, in a population-based cohort of 1030 individuals, aged 45 to 83 years at baseline. We evaluated associations between metabolite concentrations (28 acylcarnitines, 14 amino acids, 9 lysophosphocholines, 72 phosphocholines, 10 sphingomyelins and sum of hexoses) and 5 lifestyle risk factors (body mass index [BMI], alcohol consumption, smoking, diet, and exercise). Multilevel or simple linear regression modeling adjusted for relevant covariates was used for the evaluation of cross-sectional or longitudinal associations, respectively; multiple testing correction was based on false discovery rate. BMI, alcohol consumption, and smoking were associated with lipid metabolism (reduced lyso- and acyl-alkyl-phosphatidylcholines and increased diacylphosphatidylcholines concentrations). Smoking showed positive associations with acylcarnitines, and BMI correlated inversely with nonessential amino acids. Fewer metabolites showed relative changes that were associated with baseline risk factors: increases in 5 different acyl-alkyl phosphatidylcholines were associated with lower alcohol consumption and BMI and with a healthier diet. Increased levels of tyrosine were associated with BMI. Sex-specific effects of smoking and BMI were found specifically related to acylcarnitine metabolism: in women higher BMI and in men more pack-years were associated with increases in acylcarnitines.
  
  
  CONCLUSIONS
  This study showed sex-specific effects of lifestyle risks factors on human metabolism and highlighted their long-term metabolic consequences.
authors: From the Institute of Medical Epidemiology, Biostatistics and Informatics (M.E.L., A.K., D.T., D.M., J.H.), Clinic of Psychiatry, Psychotherapy, and Psychosomatics (I.G., D.R.), and Department of Medicine III, Martin-Luther University Halle-Wittenberg, Halle Saale, Germany (S.F.); Institute of Experimental Genetics, Genome Analysis Center, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg (C.P., J.A.); Lehrstuhl für Experimentelle Genetik, Technische Universität München, Freising-Weihenstephan, Germany (J.A.); German Center for Diabetes Research (DZD), Neuherberg (J.A.); Division of Cancer Epidemiology, German Cancer Research Centre, Heidelberg (K.H.G.); Laboratory of Immunology, Wadsworth Center, New York State Department of Health, Albany (R.T.E.); and Institute of Bioinformatics and Systems Biology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg (G.K.). elena.lacruz@uk-halle.de.
authors: Maria Elena
authors: ME
authors: Lacruz
authors: From the Institute of Medical Epidemiology, Biostatistics and Informatics (M.E.L., A.K., D.T., D.M., J.H.), Clinic of Psychiatry, Psychotherapy, and Psychosomatics (I.G., D.R.), and Department of Medicine III, Martin-Luther University Halle-Wittenberg, Halle Saale, Germany (S.F.); Institute of Experimental Genetics, Genome Analysis Center, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg (C.P., J.A.); Lehrstuhl für Experimentelle Genetik, Technische Universität München, Freising-Weihenstephan, Germany (J.A.); German Center for Diabetes Research (DZD), Neuherberg (J.A.); Division of Cancer Epidemiology, German Cancer Research Centre, Heidelberg (K.H.G.); Laboratory of Immunology, Wadsworth Center, New York State Department of Health, Albany (R.T.E.); and Institute of Bioinformatics and Systems Biology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg (G.K.).
authors: Alexander
authors: A
authors: Kluttig
authors: From the Institute of Medical Epidemiology, Biostatistics and Informatics (M.E.L., A.K., D.T., D.M., J.H.), Clinic of Psychiatry, Psychotherapy, and Psychosomatics (I.G., D.R.), and Department of Medicine III, Martin-Luther University Halle-Wittenberg, Halle Saale, Germany (S.F.); Institute of Experimental Genetics, Genome Analysis Center, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg (C.P., J.A.); Lehrstuhl für Experimentelle Genetik, Technische Universität München, Freising-Weihenstephan, Germany (J.A.); German Center for Diabetes Research (DZD), Neuherberg (J.A.); Division of Cancer Epidemiology, German Cancer Research Centre, Heidelberg (K.H.G.); Laboratory of Immunology, Wadsworth Center, New York State Department of Health, Albany (R.T.E.); and Institute of Bioinformatics and Systems Biology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg (G.K.).
authors: Daniel
authors: D
authors: Tiller
authors: From the Institute of Medical Epidemiology, Biostatistics and Informatics (M.E.L., A.K., D.T., D.M., J.H.), Clinic of Psychiatry, Psychotherapy, and Psychosomatics (I.G., D.R.), and Department of Medicine III, Martin-Luther University Halle-Wittenberg, Halle Saale, Germany (S.F.); Institute of Experimental Genetics, Genome Analysis Center, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg (C.P., J.A.); Lehrstuhl für Experimentelle Genetik, Technische Universität München, Freising-Weihenstephan, Germany (J.A.); German Center for Diabetes Research (DZD), Neuherberg (J.A.); Division of Cancer Epidemiology, German Cancer Research Centre, Heidelberg (K.H.G.); Laboratory of Immunology, Wadsworth Center, New York State Department of Health, Albany (R.T.E.); and Institute of Bioinformatics and Systems Biology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg (G.K.).
authors: Daniel
authors: D
authors: Medenwald
authors: From the Institute of Medical Epidemiology, Biostatistics and Informatics (M.E.L., A.K., D.T., D.M., J.H.), Clinic of Psychiatry, Psychotherapy, and Psychosomatics (I.G., D.R.), and Department of Medicine III, Martin-Luther University Halle-Wittenberg, Halle Saale, Germany (S.F.); Institute of Experimental Genetics, Genome Analysis Center, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg (C.P., J.A.); Lehrstuhl für Experimentelle Genetik, Technische Universität München, Freising-Weihenstephan, Germany (J.A.); German Center for Diabetes Research (DZD), Neuherberg (J.A.); Division of Cancer Epidemiology, German Cancer Research Centre, Heidelberg (K.H.G.); Laboratory of Immunology, Wadsworth Center, New York State Department of Health, Albany (R.T.E.); and Institute of Bioinformatics and Systems Biology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg (G.K.).
authors: Ina
authors: I
authors: Giegling
authors: From the Institute of Medical Epidemiology, Biostatistics and Informatics (M.E.L., A.K., D.T., D.M., J.H.), Clinic of Psychiatry, Psychotherapy, and Psychosomatics (I.G., D.R.), and Department of Medicine III, Martin-Luther University Halle-Wittenberg, Halle Saale, Germany (S.F.); Institute of Experimental Genetics, Genome Analysis Center, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg (C.P., J.A.); Lehrstuhl für Experimentelle Genetik, Technische Universität München, Freising-Weihenstephan, Germany (J.A.); German Center for Diabetes Research (DZD), Neuherberg (J.A.); Division of Cancer Epidemiology, German Cancer Research Centre, Heidelberg (K.H.G.); Laboratory of Immunology, Wadsworth Center, New York State Department of Health, Albany (R.T.E.); and Institute of Bioinformatics and Systems Biology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg (G.K.).
authors: Dan
authors: D
authors: Rujescu
authors: From the Institute of Medical Epidemiology, Biostatistics and Informatics (M.E.L., A.K., D.T., D.M., J.H.), Clinic of Psychiatry, Psychotherapy, and Psychosomatics (I.G., D.R.), and Department of Medicine III, Martin-Luther University Halle-Wittenberg, Halle Saale, Germany (S.F.); Institute of Experimental Genetics, Genome Analysis Center, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg (C.P., J.A.); Lehrstuhl für Experimentelle Genetik, Technische Universität München, Freising-Weihenstephan, Germany (J.A.); German Center for Diabetes Research (DZD), Neuherberg (J.A.); Division of Cancer Epidemiology, German Cancer Research Centre, Heidelberg (K.H.G.); Laboratory of Immunology, Wadsworth Center, New York State Department of Health, Albany (R.T.E.); and Institute of Bioinformatics and Systems Biology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg (G.K.).
authors: Cornelia
authors: C
authors: Prehn
authors: From the Institute of Medical Epidemiology, Biostatistics and Informatics (M.E.L., A.K., D.T., D.M., J.H.), Clinic of Psychiatry, Psychotherapy, and Psychosomatics (I.G., D.R.), and Department of Medicine III, Martin-Luther University Halle-Wittenberg, Halle Saale, Germany (S.F.); Institute of Experimental Genetics, Genome Analysis Center, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg (C.P., J.A.); Lehrstuhl für Experimentelle Genetik, Technische Universität München, Freising-Weihenstephan, Germany (J.A.); German Center for Diabetes Research (DZD), Neuherberg (J.A.); Division of Cancer Epidemiology, German Cancer Research Centre, Heidelberg (K.H.G.); Laboratory of Immunology, Wadsworth Center, New York State Department of Health, Albany (R.T.E.); and Institute of Bioinformatics and Systems Biology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg (G.K.).
authors: Jerzy
authors: J
authors: Adamski
authors: From the Institute of Medical Epidemiology, Biostatistics and Informatics (M.E.L., A.K., D.T., D.M., J.H.), Clinic of Psychiatry, Psychotherapy, and Psychosomatics (I.G., D.R.), and Department of Medicine III, Martin-Luther University Halle-Wittenberg, Halle Saale, Germany (S.F.); Institute of Experimental Genetics, Genome Analysis Center, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg (C.P., J.A.); Lehrstuhl für Experimentelle Genetik, Technische Universität München, Freising-Weihenstephan, Germany (J.A.); German Center for Diabetes Research (DZD), Neuherberg (J.A.); Division of Cancer Epidemiology, German Cancer Research Centre, Heidelberg (K.H.G.); Laboratory of Immunology, Wadsworth Center, New York State Department of Health, Albany (R.T.E.); and Institute of Bioinformatics and Systems Biology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg (G.K.).
authors: Stefan
authors: S
authors: Frantz
authors: From the Institute of Medical Epidemiology, Biostatistics and Informatics (M.E.L., A.K., D.T., D.M., J.H.), Clinic of Psychiatry, Psychotherapy, and Psychosomatics (I.G., D.R.), and Department of Medicine III, Martin-Luther University Halle-Wittenberg, Halle Saale, Germany (S.F.); Institute of Experimental Genetics, Genome Analysis Center, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg (C.P., J.A.); Lehrstuhl für Experimentelle Genetik, Technische Universität München, Freising-Weihenstephan, Germany (J.A.); German Center for Diabetes Research (DZD), Neuherberg (J.A.); Division of Cancer Epidemiology, German Cancer Research Centre, Heidelberg (K.H.G.); Laboratory of Immunology, Wadsworth Center, New York State Department of Health, Albany (R.T.E.); and Institute of Bioinformatics and Systems Biology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg (G.K.).
authors: Karin Halina
authors: KH
authors: Greiser
authors: From the Institute of Medical Epidemiology, Biostatistics and Informatics (M.E.L., A.K., D.T., D.M., J.H.), Clinic of Psychiatry, Psychotherapy, and Psychosomatics (I.G., D.R.), and Department of Medicine III, Martin-Luther University Halle-Wittenberg, Halle Saale, Germany (S.F.); Institute of Experimental Genetics, Genome Analysis Center, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg (C.P., J.A.); Lehrstuhl für Experimentelle Genetik, Technische Universität München, Freising-Weihenstephan, Germany (J.A.); German Center for Diabetes Research (DZD), Neuherberg (J.A.); Division of Cancer Epidemiology, German Cancer Research Centre, Heidelberg (K.H.G.); Laboratory of Immunology, Wadsworth Center, New York State Department of Health, Albany (R.T.E.); and Institute of Bioinformatics and Systems Biology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg (G.K.).
authors: Rebecca Thwing
authors: RT
authors: Emeny
authors: From the Institute of Medical Epidemiology, Biostatistics and Informatics (M.E.L., A.K., D.T., D.M., J.H.), Clinic of Psychiatry, Psychotherapy, and Psychosomatics (I.G., D.R.), and Department of Medicine III, Martin-Luther University Halle-Wittenberg, Halle Saale, Germany (S.F.); Institute of Experimental Genetics, Genome Analysis Center, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg (C.P., J.A.); Lehrstuhl für Experimentelle Genetik, Technische Universität München, Freising-Weihenstephan, Germany (J.A.); German Center for Diabetes Research (DZD), Neuherberg (J.A.); Division of Cancer Epidemiology, German Cancer Research Centre, Heidelberg (K.H.G.); Laboratory of Immunology, Wadsworth Center, New York State Department of Health, Albany (R.T.E.); and Institute of Bioinformatics and Systems Biology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg (G.K.).
authors: Gabi
authors: G
authors: Kastenmüller
authors: From the Institute of Medical Epidemiology, Biostatistics and Informatics (M.E.L., A.K., D.T., D.M., J.H.), Clinic of Psychiatry, Psychotherapy, and Psychosomatics (I.G., D.R.), and Department of Medicine III, Martin-Luther University Halle-Wittenberg, Halle Saale, Germany (S.F.); Institute of Experimental Genetics, Genome Analysis Center, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg (C.P., J.A.); Lehrstuhl für Experimentelle Genetik, Technische Universität München, Freising-Weihenstephan, Germany (J.A.); German Center for Diabetes Research (DZD), Neuherberg (J.A.); Division of Cancer Epidemiology, German Cancer Research Centre, Heidelberg (K.H.G.); Laboratory of Immunology, Wadsworth Center, New York State Department of Health, Albany (R.T.E.); and Institute of Bioinformatics and Systems Biology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg (G.K.).
authors: Johannes
authors: J
authors: Haerting
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000428:Alcohol Drinking / Q000009:adverse effects / Q000097:blood; D000596:Amino Acids / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D015992:Body Mass Index; D002318:Cardiovascular Diseases / Q000097:blood* / Q000175:diagnosis / Q000453:epidemiology; D002331:Carnitine / Q000031:analogs & derivatives* / Q000097:blood; D003430:Cross-Sectional Studies; D005260:Female; D005858:Germany / Q000453:epidemiology; D006601:Hexoses / Q000097:blood*; D006801:Humans; D016014:Linear Models; D008055:Lipids / Q000097:blood*; D008137:Longitudinal Studies; D008297:Male; D055432:Metabolomics / Q000379:methods; D008875:Middle Aged; D015999:Multivariate Analysis; D009765:Obesity / Q000097:blood / Q000453:epidemiology; D018570:Risk Assessment; D012307:Risk Factors; D012737:Sex Factors; D012907:Smoking / Q000009:adverse effects / Q000097:blood; D013997:Time Factors
chemical_list: D000596:Amino Acids; D015415:Biomarkers; D006601:Hexoses; D008055:Lipids; C116917:acylcarnitine; D002331:Carnitine
keywords: acylcarnitines; amino acids; cardiovascular disease; lifestyle; lipids; metabolomics