Are Novel Biomarkers of Metabolomics and Oxidative Stress Associated with Racial Differences in Heart Failure Outcomes? Open Access

Morris, Alanna Amyre (2016)

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Background: Prior studies have shown clinical outcomes for heart failure with reduced ejection fraction (HFrEF) are worse for Black Americans, even after adjusting for confounders. We sought to determine if unique small molecule metabolites contribute to racial differences in HF outcomes. Methods: We performed a metabolome wide association study to identify metabolites differentially expressed between 225 Black and White patients (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: Compared to Whites, Blacks were younger, and were more likely to have nonischemic HF etiology, hypertension, and chronic kidney disease. During the study period, (median follow-up 1114 days, IQR 710 - 1422 days), the composite primary endpoint occurred in 176 (78.2%) patients, including 34 (15.1%) deaths and 174 (77.3%) hospitalizations. After adjustment for covariates, Black race was associated with a higher risk for the primary endpoint (HR 1.59, 95% CI 1.03 - 2.46; P=0.03). At false discovery rate=0.2, 86 metabolites were identified to be differentially expressed between Blacks and Whites after adjustment for the covariates. The highest risk for the primary endpoint was in Blacks in the highest salsolinol quartile, while the lowest risk for the primary endpoint was in Whites in the lowest salsolinol quartile (P=0.06 for race*salsolinol interaction). In race stratified Cox models, 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). Conclusion: In a cohort of patients with HFrEF, we have confirmed 86 metabolites differentially expressed between Blacks and Whites. Moreover, the metabolite salsolinol was associated with a higher risk for death and HF hospitalizations. Further investigations are warranted to confirm these findings in larger cohorts. Keywords: race/ethnicity, racial disparities, heart failure, metabolomics, oxidative stress

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INTRODUCTION__________________________1 BACKGROUND____________________________3 METHODS_______________________________6 RESULTS_______________________________11 DISCUSSION____________________________14 REFERENCES____________________________18 TABLES AND FIGURES____________________24

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