Elevated miRNA-499 Levels in Early Phase of Non-ST Elevation Acute Coronary Syndromes Predict Increased Long-Term Risk of Major Adverse Cardiac Events

<b>Background/Objectives</b>: Available data suggest the diagnostic potential of testing microRNAs (miRs) in myocardial infarction, but their prognostic value remains unclear. To evaluate the prognostic value of circulating miRs (miR-1, miR-21, miR-133a, miR-208 and miR-499) for predicting major adverse cardiac events (MACEs), including death, non-fatal myocardial infarction (MI) or cardiovascular rehospitalization, in patients with non-ST segment elevation acute coronary syndromes (NSTE-ACS). <b>Methods:</b> Our prospective, single-center, observational study included patients (pts) with NSTE-ACS admitted <24 h after symptoms onset and pts with confirmed stable coronary artery disease (SCAD) as controls. Relative expression of miRs was calculated, and subjects were categorized according to miRs expression on hospital admission into two groups (≤median and >median). <b>Results:</b> Overall, 103 NSTE-ACS (52 NSTEMI/51 UA) and 47 SCAD pts (median age 66 years, 67% male) were included. During the median 895 (581-1134) days of the follow-up, MACE occurred in 75 (50%) patients: 20 (13%) died, 28 (19%) presented with MI, and 65 (43%) were readmitted due to cardiovascular reasons. Incidence of MI, rehospitalization and MACE was significantly higher in pts with elevated (>median) miR-499 [MI: 34.3% vs. 7.3%; HR = 6.0 (2.8-12.7) for rehospitalization; 53.7% vs. 36.2%, HR = 2.3 (1.4-3.8) for MACE; 62.7% vs. 42%, HR = 2.4 (1.5-3.8)] for hospital readmission. In the Cox proportional hazards regression model, miR-499 expression above the median level [HR = 1.8 (1.1-3.1)], high-sensitivity cardiac troponin T [HR = 1.2 (1.02-1.5)], diabetes [HR = 1.7 (1.1-2.8)] and percutaneous intervention during hospital stay [HR = 2.1 (1.1-3.8)] were identified as independent predictors of MACE in long-term observation, even after adjustment for covariates. <b>Conclusions:</b> Elevated miR-499 level on hospital admission in NSTE-ACS is related to an increased rate of MACE in the 2.5-year follow-up.