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A prospective study of serum metabolites and risk of ischemic stroke.

TitleA prospective study of serum metabolites and risk of ischemic stroke.
Publication TypeJournal Article
Year of Publication2019
AuthorsSun D, Tiedt S, Yu B, Jian X, Gottesman RF, Mosley TH, Boerwinkle E, Dichgans M
Secondary AuthorsFornage M
JournalNeurology
Volume92
Issue16
Paginatione1890-e1898
Date Published2019 04 16
ISSN1526-632X
KeywordsBiomarkers, Brain Ischemia, Female, Follow-Up Studies, Genetic Association Studies, Humans, Incidence, Male, Metabolome, Metabolomics, Middle Aged, Polymorphism, Single Nucleotide, Prospective Studies, Risk Factors, Stroke
Abstract

OBJECTIVE: To identify promising blood-based biomarkers and novel etiologic pathways of disease risk, we applied an untargeted serum metabolomics profiling in a community-based prospective study of ischemic stroke (IS).

METHODS: In 3,904 men and women from the Atherosclerosis Risk In Communities study, Cox proportional hazard models were used to estimate the association of incident IS with the standardized level of 245 fasting serum metabolites individually, adjusting for age, sex, race, field center, batch, diabetes, hypertension, current smoking status, body mass index, and estimated glomerular filtration rate. Validation of results was carried out in an independent sample of 114 IS cases and 112 healthy controls.

RESULTS: Serum levels of 2 long-chain dicarboxylic acids, tetradecanedioate and hexadecanedioate, were strongly correlated ( = 0.88) and were associated with incident IS after adjusting for covariates (hazard ratio [95% confidence interval (CI)] 1.11 [1.06-1.16] and 1.12 [1.07-1.17], respectively;

CONCLUSION: Two serum long-chain dicarboxylic acids, metabolic products of ω-oxidation of fatty acids, were associated with IS and CES independently of known risk factors. Pathways related to intracellular hexadecanedioate synthesis or those involved in its clearance from the circulation may mediate IS risk. These results highlight the potential of metabolomics to discover novel circulating biomarkers for stroke and to unravel novel pathways for IS and its subtypes.

DOI10.1212/WNL.0000000000007279
Alternate JournalNeurology
PubMed ID30867269
PubMed Central IDPMC6550501
Grant ListR01 NS087541 / NS / NINDS NIH HHS / United States
U01 AG052409 / AG / NIA NIH HHS / United States