title: Associations between metabolomic compounds and incident heart failure among African Americans: the ARIC Study.
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.
authors.affiliation: Department of Epidemiology, Human Genetics, and Environmental Sciences, University of Texas Health Science Center at Houston, Houston, TX, USA.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zheng
authors.forename: Bing
authors.initials: B
authors.lastname: Yu
authors.forename: Danny
authors.initials: D
authors.lastname: Alexander
authors.forename: Teri A
authors.initials: TA
authors.lastname: Manolio
authors.forename: David
authors.initials: D
authors.lastname: Aguilar
authors.forename: Josef
authors.initials: J
authors.lastname: Coresh
authors.forename: Gerardo
authors.initials: G
authors.lastname: Heiss
authors.forename: Eric
authors.initials: E
authors.lastname: Boerwinkle
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Nettleton
mesh_terms: D001741:Black or African American / Q000706:statistics & numerical data*; D017677:Age Distribution; D050197:Atherosclerosis / Q000097:blood* / Q000453:epidemiology / Q000208:ethnology; D015415:Biomarkers / Q000097:blood; D015897:Comorbidity; D003920:Diabetes Mellitus / Q000453:epidemiology; D005260:Female; D005500:Follow-Up Studies; D006333:Heart Failure / Q000097:blood / Q000453:epidemiology / Q000208:ethnology*; D006801:Humans; D006973:Hypertension / Q000453:epidemiology; D007674:Kidney Diseases / Q000453:epidemiology; D008297:Male; D055432:Metabolomics / Q000379:methods / Q000706:statistics & numerical data*; D008875:Middle Aged; D008922:Mississippi / Q000453:epidemiology; D009765:Obesity / Q000453:epidemiology; D016016:Proportional Hazards Models; D057185:Sedentary Behavior
chemical_list: D015415:Biomarkers
keywords: heart failure; metabolomics; risk factors