Abstract 19024: Regulation of Platelet Reactivity Identified Through MicroRNA Profiling in Acute Coronary Syndrome
Introduction: Recent studies suggest an association between changes in platelet-specific microRNAs (miRs) and changes in platelet reactivity. However, molecular pathways that govern platelet reactivity are incompletely characterized. We hypothesize that miRs expressed in plasma are associated with measured platelet reactivity in the TRILOGY-ACS cohort and highlight the genomic regulatory architecture of platelet reactivity.
Methods: The study included 712 patients with non-ST elevation acute coronary syndrome (NSTEACS) enrolled in the TRILOGY-ACS trial. Plasma samples collected prior to anti-platelet therapy randomization were used to determine P2Y12 Reaction Units (PRU) measured on the VerifyNow system as well as the concentration of 35 miR species known to be involved in cardiovascular development and disease. We tested for association between PRU and miR expression using multivariable linear regression, adjusting for age, sex, race, prior clopidogrel and aspirin status, diabetes and cytochrome 2C19 genotype. P-values are nominal values representing discovery analysis and have not been corrected for multiple comparisons.
Results: Clinical characteristics of the study sample were similar to the overall TRILOGY-ACS cohort for all covariates used in the linear regression analysis. MiR-18a, a known regulator of angiogenesis, demonstrated a 7.0 PRU increase per 1 SD increase in miR concentration (p=0.04). MiR-30a, a known contributor to cardiac ECM remodeling, demonstrated a 6.8 PRU increase per 1 SD change in miR concentration (p=0.04). Previously identified platelet-specific miRs, including miR-21, 20b, 24, 126, 191 and 223 did not correlate with PRU.
Conclusions: Plasma miR-18a and 30a but not platelet-specific miRs showed modest association with increased platelet reactivity in patients with NSTEACS. These results suggest that the relationship between circulating miRs and platelet reactivity extends beyond known platelet-specific miRs.
Author Disclosures: K.C. Becker: Research Grant; Modest; Duke University. L. Coulter: None. M.L. Neely: None. E. Grass: None. J.A. Jakubowski: Employment; Significant; Eli Lilly and Company. Ownership Interest; Modest; Minor shareholder of Eli Lilly and Company. K.A. Fox: Research Grant; Modest; Eli Lilly, Bayer, Johnson & Johnson, AstraZeneca. Speakers Bureau; Modest; Bayer, Johnson & Johnson, AstraZeneca, Sanofi-Aventis. Consultant/Advisory Board; Modest; Eli Lilly, Johnson & Johnson, Bayer, Sanofi-Aventis, AstraZeneca, Boehringer Ingelheim. P.W. Armstrong: None. H. White: Research Grant; Modest; Sanofi Aventis, Eli Lilly, Merck Sharpe & Dohme, NIH, Glaxo-Smith-Kline, Daiichi Sankyo. Consultant/Advisory Board; Modest; AstraZeneca. 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. Consultant/Advisory Board; Significant; AstraZeneca, Merck & Co, Amgen. Other; Modest; Amgen, Bristol-Myers Squibb. E. 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. S.G. Gregory: Consultant/Advisory Board; Modest; Pfizer. S.H. Shah: None. M.Y. Chan: Research Grant; Significant; Eli-Lilly, Astra-Zeneca, Bayer Healthcare. Speakers Bureau; Modest; Astra Zeneca.
- © 2016 by American Heart Association, Inc.