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Eur J Epidemiol. 2018 Jan;33(1):55-66. doi: 10.1007/s10654-017-0333-0. Epub 2017 Nov 27.

Serum metabolites and risk of myocardial infarction and ischemic stroke: a targeted metabolomic approach in two German prospective cohorts.

Author information

1
Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany. floegel@leibniz-bips.de.
2
Leibniz Institute for Prevention Research and Epidemiology - BIPS, Achterstraße 30, 28359, Bremen, Germany. floegel@leibniz-bips.de.
3
Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
4
Institute of Experimental Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.
5
Department of Molecular Systems Biology, Helmholtz Centre for Environmental Research (UFZ), Leipzig, Germany.
6
Department of Food Safety, Federal Institute for Risk Assessment, Berlin, Germany.
7
Institute for Social Medicine, Epidemiology and Health Economics, Charité University Medical Center, Berlin, Germany.
8
Hannover Unified Biobank, Hannover Medical School, Hannover, Germany.
9
Institute of Human Genetics, Hannover Medical School, Hannover, Germany.
10
University of Aalborg, Fredrik Bajers Vej 7H, 9220, Aalborg East, Denmark.
11
Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany.
12
Molecular Epidemiology Group, Max Delbrück Center for Molecular Medicine (MDC), Berlin, Germany.
13
Charité - Universitätsmedizin Berlin, Berlin, Germany.
14
German Center for Cardiovascular Research (DZHK), Partner Site Berlin, Berlin, Germany.

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.

KEYWORDS:

Biomarker; Metabolomics; Myocardial infarction; Prospective cohort study; Stroke

PMID:
29181692
PMCID:
PMC5803284
DOI:
10.1007/s10654-017-0333-0
[Indexed for MEDLINE]
Free PMC Article

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