Serum Metabolomics and Incidence of Atrial Fibrillation (from the Atherosclerosis Risk in Communities Study)

Alvaro Alonso, Bing Yu, Yan V. Sun, Lin Y. Chen, Laura R. Loehr, Wesley T. O'Neal, Elsayed Z. Soliman, Eric Boerwinkle

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

Abstract

We have previously identified associations of 2 circulating secondary bile acids (glycocholenate and glycolithocolate sulfate) with atrial fibrillation (AF) risk in 1,919 blacks in the Atherosclerosis Risk in Communities cohort. We aimed to replicate these findings in an independent sample of 2,003 white and black Atherosclerosis Risk in Communities participants, and performed a new metabolomic analysis in the combined sample of 3,922 participants, followed between 1987 and 2013. Metabolomic profiling was done in baseline serum samples using gas and liquid chromatography mass spectrometry. AF was ascertained from electrocardiograms, hospitalizations, and death certificates. We used multivariable Cox regression to estimate hazard ratios (HR) and 95% confidence intervals (95%CI) of AF by 1 standard deviation difference of metabolite levels. Over a mean follow-up of 20 years, 608 participants developed AF. Glycocholenate sulfate was associated with AF in the replication and combined samples (HR 1.10, 95% CI 1.00, 1.21 and HR 1.13, 95% CI 1.04, 1.22, respectively). Glycolithocolate sulfate was not related to AF risk in the replication sample (HR 1.02, 95% CI 0.92, 1.13). An analysis of 245 metabolites in the combined cohort identified 3 additional metabolites associated with AF after multiple-comparison correction: pseudouridine (HR 1.18, 95% CI 1.10, 1.28), uridine (HR 0.86, 95% CI 0.79, 0.93) and acisoga (HR 1.17, 95% CI 1.09, 1.26). In conclusion, we replicated a prospective association among a previously identified secondary bile acid, glycocholenate sulfate, and AF incidence, and identified new metabolites involved in nucleoside and polyamine metabolism as markers of AF risk.

Original languageEnglish (US)
Pages (from-to)1955-1961
Number of pages7
JournalAmerican Journal of Cardiology
Volume123
Issue number12
DOIs
StatePublished - Jun 15 2019

Bibliographical note

Funding Information:
Sources of funding: The Atherosclerosis Risk in Communities study has been funded in whole or in part with Federal funds from the National Heart, Lung, and Blood Institute, National Institutes of Health, Department of Health and Human Services, under Contract nos. (HHSN268201700001I, HHSN268201700002I, HHSN268201700003I, HHSN268201700005I, HHSN268201700004I), Bethesda, MD. The metabolomics research was sponsored by the National Human Genome Research Institute (3U01HG004402-02S1) This work was additionally supported by American Heart Association grant 16EIA26410001 (Alonso), Dallas, TX. Dr. Yu is supported in part by American Heart Association (17SDG33661228) and the National Heart, Lung, and Blood Institute (HL141824 and HL142003). The authors thank the staff and participants of the ARIC study for their important contributions.

Funding Information:
Sources of funding: The Atherosclerosis Risk in Communities study has been funded in whole or in part with Federal funds from the National Heart, Lung, and Blood Institute, National Institutes of Health, Department of Health and Human Services, under Contract nos. (HHSN268201700001I, HHSN268201700002I, HHSN268201700003I, HHSN268201700005I, HHSN268201700004I), Bethesda, MD. The metabolomics research was sponsored by the National Human Genome Research Institute (3U01HG004402-02S1) This work was additionally supported by American Heart Association grant 16EIA26410001 (Alonso), Dallas, TX. Dr. Yu is supported in part by American Heart Association (17SDG33661228) and the National Heart, Lung, and Blood Institute (HL141824 and HL142003). Sources of funding: The Atherosclerosis Risk in Communities study has been funded in whole or in part with Federal funds from the National Heart, Lung, and Blood Institute, National Institutes of Health, Department of Health and Human Services, under Contract nos. ( HHSN268201700001I, HHSN268201700002I, HHSN268201700003I, HHSN268201700005I, HHSN268201700004I), Bethesda, MD. The metabolomics research was sponsored by the National Human Genome Research Institute ( 3U01HG004402-02S1) This work was additionally supported by American Heart Association grant 16EIA26410001 (Alonso), Dallas, TX. Dr. Yu is supported in part by American Heart Association ( 17SDG33661228) and the National Heart, Lung, and Blood Institute ( HL141824 and HL142003). The authors thank the staff and participants of the ARIC study for their important contributions. Sources of funding: The Atherosclerosis Risk in Communities study has been funded in whole or in part with Federal funds from the National Heart, Lung, and Blood Institute, National Institutes of Health, Department of Health and Human Services, under Contract nos. ( HHSN268201700001I, HHSN268201700002I, HHSN268201700003I, HHSN268201700005I, HHSN268201700004I), Bethesda, MD. The metabolomics research was sponsored by the National Human Genome Research Institute ( 3U01HG004402-02S1) This work was additionally supported by American Heart Association grant 16EIA26410001 (Alonso), Dallas, TX. Dr. Yu is supported in part by American Heart Association ( 17SDG33661228) and the National Heart, Lung, and Blood Institute ( HL141824 and HL142003).

Publisher Copyright:
© 2019 Elsevier Inc.

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