Early overexpression of miR-499 in non-ST elevation acute coronary syndromes predicts long-term risk of major adverse cardiac events. (25th November 2020)

• Record Type: Journal Article
• Authors: Miskowiec, D; Kupczynska, K; Simiera, M; Michalski, B; Filipiak-Strzecka, D; Wejner-Mik, P; Wierzbowska-Drabik, K; Szymczyk, E; Lipiec, P; Kasprzak, J.D
• Is Part Of: European heart journal. Volume 41:(2020)Supplement 2
• Publication Date: 2020-11-25
• Subjects: Acute Coronary Syndromes - Clinical; Cardiology -- Periodicals; Heart -- Diseases -- Periodicals; 616.12005
• DOI: 10.1093/ehjci/ehaa946.1756
• Languages: English
• ISSNs: 0195-668X

Abstract

Abstract: Background: Some studies reported utility of microRNAs in myocardial infarction diagnostic process, whereas their prognostic remains unclear. Aim: To evaluate the prognostic value of five circulating miRs (miR-1, miR-21, miR-133a, miR-208, miR-499) levels for predicting major adverse cardiac events (MACE), including death, nonfatal myocardial infarction (MI) or cardiovascular rehospitalization (reh.) in patients with NSTE-ACS. Material and methods: In our prospective, single-center observational study we recruited patients (pts) with NSTE-ACS with symptoms onset <24 hours before the hospital admission and age, gender-matched patients with stable coronary artery disease (SCAD) as controls. Blood was sampled twice (at admission and 4h after in NSTE-ACS and once in SCAD). Relative expression of miRs were calculated using the ΔΔCt method after normalization to the cel-miR-39 spiked-in control. The mean value of miRs relative expression from two time samples in NSTE-ACS pts were used for further analysis. Subjects were categorized according to mean miRs expression at hospital admission into two group (≤ or > median level of miRs). Results: 103 NSTE-ACS pts (median age 67 years, 68% male) were included in this study. During median 1569 (IQR 935–1842) days of follow-up the primary endpoint (MACE) occurred in 66 (64.1%) pts: 18 pts (18.7%) died, 30 pts (20%) presented with MI and 85 pts (56.7%) were readmitted. In a Cox proportional-hazards regression model miR-499 expression > median level (HR=1.82, 95% CI 1.07–3.09) and high-sensitivity troponin T level (HR=1.24, 95% CI 1.05–1.46) were independent predictors of MACE in long term observation, even after adjustment for other covariates (including other miRNAs). Incidence of MI [34% vs 10%, HR=4.1 (2.0–8.5)], rehospitalization for cardiovascular reasons [67% vs 49%, HR=2.1 (1.3–3.3)] and MACE [76% vs 55%, HR=2.2 (1.5–3.5)] was significantly higher in pts with elevated (> median) miR-499 levels at hospital admission. None of analyzed miRNAs was related to long-term mortality, whereas the left ventricular ejection fraction (EF) has been identified as the only one survival predictor (HR=0.95, 95% CI 0.92–0.98). Conclusions: Elevated miR-499 levels independently of high sensitivity troponin T levels in early phase of NSTE-ACS are related to increased rate of MACE in 4-year follow-up. Funding Acknowledgement: Type of funding source: Public grant(s) – National budget only. Main funding source(s): This study was supported by the Polish Ministry of Science and Higher Education "Diamond Grant" program.