Expression Patterns of MiR-125a and MiR-223 and Their Association with Diabetes Mellitus and Survival in Patients with Non-ST-Segment Elevation Acute Coronary Syndrome

Abstract

Background: MicroRNAs (miRNA, miR) are small, non-coding RNAs which have become increasingly relevant as diagnostic and prognostic biomarkers. The objective of this study was the investigation of blood-derived miRNAs and their link to long-term all-cause mortality in patients who suffered from non-ST-segment elevation acute coronary syndrome (NSTE-ACS). Methods: This study was an observational prospective study, which included 109 patients with NSTE-ACS. Analysis of the expression of miR-125a and miR-223 was conducted by polymerase chain reaction (PCR). The follow-up period comprised a median of 7.5 years. Long-term all-cause mortality was considered as the primary endpoint. Adjusted Cox-regression analysis was performed for prediction of events. Results: Increased expression of miR-223 (>7.1) at the time point of the event was related to improved long-term all-cause survival (adjusted (adj.) hazard ratio (HR) = 0.09, 95% confidence interval (95%CI): 0.01–0.75; p = 0.026). The receiver operating characteristic (ROC) analysis provided sufficient c-statistics (area under the curve (AUC) = 0.73, 95%CI: 0.58–0.86; p = 0.034; negative predictive value of 98%) for miR-223 to predict long-term all-cause survival. The Kaplan–Meier time to event analysis showed a separation of the survival curves between the groups at an early stage (log rank p = 0.015). Higher plasma miR-125a levels were found in patients with diabetes mellitus vs. in those without (p = 0.010). Furthermore, increased miR-125a expression was associated with an elevated HbA1c concentration. Conclusions: In this hypothesis-generating study, higher values of miR-223 were related to improved long-term survival in patients after NSTE-ACS. Larger studies are required in order to evaluate whether miR-223 can be used as a suitable predictor for long-term all-cause mortality.