Abstract 11931: Plasma Metabolite Profiling in Heart Failure Patients: Risk Association and Heritability
Background: Metabolite profiling can unveil biomarker signatures for health and disease. We tested whether the plasma metabolite profile in heart failure (HF) patients could predict survival independent of established factors, and whether the metabolite levels are heritable.
Methods: Patients (n=400) who met Framingham criteria for HF were included. Fasting blood samples were obtained, and DNA and plasma isolated and stored at -70oC. Amino acids, organic acids, and acyl carnitines were quantified using mass spectrometry. Genome wide genotyping was also performed. Association of metabolites with survival was tested using lasso penalized Cox regression; a resulting multi-metabolite risk score (MRS) was tested in 10-fold cross validation using time-dependent ROC curves. We retested the MRS in Cox models adjusted for conventional covariates (age, gender, race, ejection fraction (EF), CAD, COPD, creatinine, atrial fibrillation, stroke, NTproBNP). We estimated heritability of the MRS components using genome-wide data, calculated separately in African Americans and whites.
Results: The cohort was 50% African American, 50% female, 67% low EF, and mean age 70 y. In cross-validation the MRS had AUC of 0.705 and 0.658 at 1 and 5 years, respectively. Dichotomized MRS was associated with a 4.5 fold risk of death (FDR=1.49x10-8, Figure). When added to a conventional risk model, the MRS still carried a HR of 2.6 (p=2.38 x 10-4). Among 14 MRS analytes, 4 had heritability estimates >20% in each race group (Table).
Conclusion: Plasma metabolite profile is an independent predictor of survival among HF patients, and risk-associated metabolite levels may be heritable. Validation is needed.
Author Disclosures: D. Lanfear: Research Grant; Significant; Janssen. A. Levin: None. J. Li: None. R. She: None. Y. Wang: None. L. Williams: None. S. Gardell: None. H. Sabbah: Research Grant; Significant; Stealth Biotherapeutics, Inc., Mast Therapeutics, Inc.. Consultant/Advisory Board; Modest; Stealth Biotherapeutics, Inc., Mast Therapeutics, Inc..
- © 2015 by American Heart Association, Inc.