Abstract 14841: Whole-genome microRNA Sequencing Reveals Circulating microRNAs as High-Risk Markers in Non-ST-Elevation Acute Coronary Syndrome
Introduction: MicroRNAs (miRs) have emerged as promising circulating biomarkers in cardiovascular disease (CVD). Given the complex relationship between clinical risk factors and non-ST-elevation acute coronary syndrome (NSTE-ACS) outcomes, understanding the relationship of miRs and high-risk factors may help dissect independent versus mediating effects of miRs on NSTE-ACS outcomes.
Hypothesis: There are associations between specific circulating miRs and established clinical risk factors in patients with NSTE-ACS.
Methods: Whole-genome miR sequencing was performed on total RNA extracted from whole blood of 199 patients with NSTE-ACS from the TRILOGY-ACS trial with similar baseline characteristics. Generalized linear models were used to test associations between 247 identified miRs and 13 high-risk factors CVD risk factors including atrial fibrillation (AF), Global Registry of Acute Coronary Events (GRACE) score on presentation and chronic heart failure (HF). A false discovery rate of 0.05 was used to correct for multiple comparisons.
Results: Overall, 205 risk factor-miR associations were nominally significant (p<0.05) (Figure 1). Importantly, increasing GRACE score was inversely correlated with levels of miR 3135b (p<0.0001) and positively correlated with levels of miR 28-3p (p=0.0002). History of chronic HF, a potent predictor of poor outcomes in NSTE-ACS, was significantly associated with lower circulating levels of miR 126-5p (p<0.0001), miR 142-5p (p=0.0004), miR 144-5p (p=0.0007), and miR 3135b (p<0.0006).
Conclusions: We identified circulating miRs with expression patterns associated with high-risk factors in NSTE-ACS. MiRs 3135b, 126-5p, 142-5p, 144-5p and miR 28-3p are known mediators of CV development or disease, suggesting their potential role in modulating genomic risk in NSTE-ACS. These miRs may serve as prognostic biomarkers for risk stratification to better predict poor outcomes in patients with NSTE-ACS.
Author Disclosures: A. Wang: None. L. Coulter-Kwee: None. E. Grass: None. S.G. Gregory: Consultant/Advisory Board; Modest; Pfizer. P.W. Armstrong: 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. 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. 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. 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.