Associations Between Metabolomic Compounds and Incident Heart Failure Among African Americans: The ARIC Study

American journal of epidemiology (Impact Factor: 5.23). 06/2013; 178(4). DOI: 10.1093/aje/kwt004
Source: PubMed


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.

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    • "Luan et al. [63] 2013 Case–control (23 HF and 23 CAD patients) Free fatty acids, sphingolipids and amino acid derivatives OPLS-DA model analyzed by LC–MS Lipid molecules associated with energy metabolism and signaling pathways significantly differed between the two groups (free fatty acids, sphingolipids and amino acid derivatives). Zheng et al. [64] 2013 Prospective observational (1744 African Americans from the ARIC study) 204 stable serum metabolites Not specified MS After a median follow-up of 20 years, incident heart failure was strong associated with amino acid isoform: dihydroxy docosatrienoic acid (HR 0.75 [CI 95% 0.65–0.86]; p b 0.05) and an isoform of either hydroxyleucine or hydroxyisoleucine (HR 1.23 [CI 95% 1.10–1.37]; "
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