Abstract 17945: Circulating Nucleoside and Bile Acid Intermediary Metabolites Are Associated With Recurrent Ischemic Events in Acute Coronary Syndrome
Introduction: Metabolomic profiling may identify altered metabolic pathways underlying atherosclerosis and myocardial ischemia. We hypothesized that organic acids, which report on mitochondrial respiratory chain perturbations, are associated with recurrent cardiovascular events and could therefore serve as prognostic biomarkers in acute coronary syndrome (ACS).
Methods: We studied 618 patients from the TRILOGY-ACS trial who presented with non-ST-elevation ACS. Sixty-one organic acids were quantified in plasma samples collected 30 days (n=495) or 6 months (n=421) after the index ACS event. Using Cox regression, we tested for association between organic acids and time to myocardial infarction (MI) after the index ACS, with metabolites considered both independently and as principal component analysis (PCA) factors. All models were adjusted for age, sex, race, diabetes, smoking, GFR, ACS event type and antiplatelet agent use. A false discovery q-value < 0.05 was used to adjust for multiple tests.
Results: Forty-two patients (6.8%) had an MI during follow-up (median time to MI: 7.5 months); the remaining subjects were censored after 6-38 months of follow-up. At 30 days, two nucleosides were associated with shorter time to MI: 2-deoxyuridine, a substrate of DNA synthesis (hazard ratio (HR) [95% CI]=16.9 [2.9 – 97.0], p=0.002), and inosine, an intermediate product of purine degradation (HR=1.5 [1.1-2.1], p=0.01). In contrast, 30-day levels of glycochenodeoxycholic acid (a bile acid) were associated with longer time to MI (HR=0.6 [0.4-0.9], p=0.006). PCA revealed 30-day levels of 2-deoxyuridine (HR=1.5, p=0.02) and inosine (HR=1.4, p=0.05) each as the single predominant metabolite in PCA factors nominally associated with time to MI, while glycochenodeoxycholic acid clustered in a factor with other bile acids, including glycocholic acid, taurocholic acid and taurochenodeoxycholic acid (HR=0.7, p=0.04). At 6 months, no metabolites were significantly associated with time to MI.
Conclusions: Circulating nucleosides are associated with shorter time to recurrent ischemic events while circulating bile acids are associated with a protective effect, suggesting their potential role as prognostic biomarkers and therapeutic targets in ACS.
Author Disclosures: L.C. Kwee: None. J. Morningstar: None. E. Grass: None. S. Gregory: Consultant/Advisory Board; Modest; Pfizer. M.L. Neely: None. K.A. Fox: Research Grant; Modest; Lilly, Bayer, Johnson-Johnson, AstraZeneca. Speakers Bureau; Modest; Bayer, Johnson-Johnson, AstraZeneca, Sanofi-Aventis. Consultant/Advisory Board; Modest; Lilly, Bayer, Johnson-Johnson, AstraZeneca, Sanofi-Aventis, Boehringer Ingelheim, Eli Lilly. H. White: Research Grant; Significant; Sanofi, Eli Lilly, MSD. Honoraria; Modest; Astra Zeneca. P. Armstrong: Research Grant; Significant; Merck, AstraZeneca. Consultant/Advisory Board; Modest; Merck. Other; Modest; Merck. E.M. Ohman: Research Grant; Significant; Daiichi Sankyo, Gilead Sciences, Janssen Pharmaceuticals. Consultant/Advisory Board; Modest; Abbott Vascular, Medscape, AstraZeneca, Biotie, Boehringer Ingelheim, Daiichi Sankyo, Merck, St. Jude Medical, Stealth Peptides, The Medidines Company. Consultant/Advisory Board; Significant; Faculty Connection, Abiomed. M. Roe: Research Grant; Significant; AstraZeneca, Eli Lilly & Co., Janssen Pharmaceuticals, Sanofi-Aventis, Daiichi-Sankyo, Familial Hypercholesterolemia Foundation, Ferring Pharmaceuticals. Consultant/Advisory Board; Modest; Eli Lilly & Co, Daiichi-Sankyo, Elsevier Publishers, Boehringer-Ingelheim, PriMed, Myokardia. Other; Modest; Amgen, Bristol-Myers Squibb. R.E. Gerszten: Research Grant; Significant; National Institutes of Health. M.Y. Chan: Research Grant; Significant; Eli-Lilly, Astra-Zeneca, Bayer Healthcare. Speakers Bureau; Modest; Astra Zeneca. S.H. Shah: None.
- © 2016 by American Heart Association, Inc.