Abstract 16917: Unique Small Molecule Metabolites Are Associated With Racial Differences In Heart Failure Death And Hospitalization
Introduction: Clinical outcomes for heart failure with reduced ejection fraction (HFrEF) are worse for Black Americans. We sought to determine if unique small molecule metabolites contribute to racial differences in HF outcomes.
Hypothesis: Small molecule metabolites will contribute to racial differences in HF death and hospitalization.
Methods: We performed a metabolome wide association study in 225 Blacks and Whites (46.5% Black) with HFrEF enrolled in the Atlanta Cardiomyopathy Consortium. Kaplan-Meier analysis and Cox proportional hazards regression were used to estimate the association of race and small molecule metabolites with a composite primary endpoint of death and HF hospitalization.
Results: During a median follow-up of 1114 (IQR 710 - 1422) days, the primary endpoint occurred in 176 (78.2%) patients, including 34 (15.1%) deaths and 174 (77.3%) hospitalizations. Black race was associated with a higher risk for the primary endpoint (adjusted HR 1.59, 95% CI 1.03 - 2.46; P=0.03). 86 metabolites were identified to be differentially expressed between Blacks and Whites at false discovery rate=0.2. The metabolite kynurenate (HR=1.03, 95% CI 1.00 - 1.06, P=0.04), and two metabolites tentatively identified as nitronaphthalene (HR=1.03, 95% CI 1.00 - 1.06, P=0.04) and salsolinol (HR=1.03, 95% CI 1.00 - 1.06, P=0.07) were associated with a higher risk of the primary endpoint in the entire cohort. There was a trend towards a race*salsolinol interaction (P=0.06), with Blacks in the highest salsolinol quartile having the highest risk for the primary endpoint, while Whites in the lowest salsolinol quartile had the lowest risk. Race-stratified Cox models confirmed elevated salsolinol levels were associated with increased risk for the primary endpoint in Whites (quartile 4 vs. 1: adjusted HR 3.07, 95% CI 1.18 - 7.96; P=0.02) and Blacks (quartile 4 vs. 1: adjusted HR 2.24, 95% CI 0.93 - 5.40; P=0.07).
Conclusions: In a HFrEF cohort, we found 86 metabolites differentially expressed between Blacks and Whites. Kynurenate, and metabolites tentatively identified as nitronaphthalene and salsolinol, were associated with a higher risk of death and HF hospitalization, while that identified as salsolinol was associated with differential risk in Blacks and Whites.
Author Disclosures: A.A. Morris: None. K. Uppal: None. E.Y. Chong: None. S. Hayek: None. A. Kalogeropoulos: None. V. Georgiopoulou: None. D.P. Jones: None. J. Butler: Consultant/Advisory Board; Modest; Amgen, Bayer. A. Quyyumi: None.
- © 2016 by American Heart Association, Inc.