Associations between metabolomic compounds and incident heart failure among African Americans: the ARIC Study.

TitleAssociations between metabolomic compounds and incident heart failure among African Americans: the ARIC Study.
Publication TypeJournal Article
Year of Publication2013
AuthorsZheng, Y, Yu, B, Alexander, D, Manolio, TA, Aguilar, D, Coresh, J, Heiss, G, Boerwinkle, E, Nettleton, JA
JournalAm J Epidemiol
Volume178
Issue4
Pagination534-42
Date Published2013 Aug 15
ISSN1476-6256
KeywordsAge Distribution, Atherosclerosis, Biomarkers, Black or African American, Comorbidity, Diabetes Mellitus, Female, Follow-Up Studies, Heart Failure, Humans, Hypertension, Kidney Diseases, Male, Metabolomics, Middle Aged, Mississippi, Obesity, Proportional Hazards Models, Sedentary Behavior
Abstract

Heart failure is more prevalent among African Americans than in the general population. Metabolomic studies among African Americans may efficiently identify novel biomarkers of heart failure. We used untargeted methods to measure 204 stable serum metabolites and evaluated their associations with incident heart failure hospitalization (n = 276) after a median follow-up of 20 years (1987-2008) by using Cox regression in data from 1,744 African Americans aged 45-64 years without heart failure at baseline from the Jackson, Mississippi, field center of the Atherosclerosis Risk in Communities (ARIC) Study. After adjustment for established risk factors, we found that 16 metabolites (6 named with known structural identities and 10 unnamed with unknown structural identities, the latter denoted by using the format X-12345) were associated with incident heart failure (P < 0.0004 based on a modified Bonferroni procedure). Of the 6 named metabolites, 4 are involved in amino acid metabolism, 1 (prolylhydroxyproline) is a dipeptide, and 1 (erythritol) is a sugar alcohol. After additional adjustment for kidney function, 2 metabolites remained associated with incident heart failure (for metabolite X-11308, hazard ratio = 0.75, 95% confidence interval: 0.65, 0.86; for metabolite X-11787, hazard ratio = 1.23, 95% confidence interval: 1.10, 1.37). Further structural analysis revealed X-11308 to be a dihydroxy docosatrienoic acid and X-11787 to be an isoform of either hydroxyleucine or hydroxyisoleucine. Our metabolomic analysis revealed novel biomarkers associated with incident heart failure independent of traditional risk factors.

DOI10.1093/aje/kwt004
Alternate JournalAm J Epidemiol
PubMed ID23788672
PubMed Central IDPMC3736751
Grant ListHHSN268201100012C / HL / NHLBI NIH HHS / United States
HHSN268201100009I / HL / NHLBI NIH HHS / United States
HHSN268201100010C / HL / NHLBI NIH HHS / United States
HHSN268201100008C / HL / NHLBI NIH HHS / United States
HHSN268201100007C / HL / NHLBI NIH HHS / United States
U01 HG004402 / HG / NHGRI NIH HHS / United States
HHSN268201100006C / HL / NHLBI NIH HHS / United States
HHSN268201100005I / HL / NHLBI NIH HHS / United States
HHSN268201100007I / HL / NHLBI NIH HHS / United States
K01 DK082729 / DK / NIDDK NIH HHS / United States
HHSN268201100005G / HL / NHLBI NIH HHS / United States
HHSN268201100008I / HL / NHLBI NIH HHS / United States
3U01HG004402-02S1 / HG / NHGRI NIH HHS / United States
HHSN268201100011I / HL / NHLBI NIH HHS / United States
HHSN268201100011C / HL / NHLBI NIH HHS / United States
5K01DK082729-04 / DK / NIDDK NIH HHS / United States
HHSN268201100009C / HL / NHLBI NIH HHS / United States
HHSN268201100005C / HL / NHLBI NIH HHS / United States

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