Circulating microRNAs are potential predictors of cardiovascular events in patients presenting with ST-elevation myocardial infarction

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¹Department of Cardiology, Charité Berlin – University Medicine, Campus Benjamin Franklin and Berlin Institute of Health (BIH), Germany
²Department of Cardiology, Cardiovascular Center, University Hospital Zurich, Switzerland
³Department of Functional Genomics, Interfaculty Institute for Genetics and Functional Genomics, University Medicine and Ernst-Moritz-Arndt University Greifswald, Germany
⁴Institute of Social and Preventive Medicine (ISPM), and Clinical Trials Unit, Department of Clinical Research, University of Bern, Switzerland
⁵Department of General Internal Medicine, University Hospital Bern, Switzerland
⁶Institute of Primary Health Care (BIHAM), University of Bern, Switzerland
⁷Department of Ambulatory Care and Community Medicine, University of Lausanne, Switzerland
⁸Department of Cardiology, Cardiovascular Center, University Hospital Bern, Switzerland
⁹Department of Cardiology, Cardiovascular Center, University Hospital Lausanne, Switzerland
¹⁰Department of Cardiology, Cardiovascular Center, University Hospital Geneva, Switzerland

Aims: MicroRNAs are important non-coding intracellular modulators. However, profiling and validation of circulating miRNAs (miRNAs) that are associated with cardiovascular outcome in patients with ST-segment elevation myocardial infarction (STEMI) has not been performed.

Methods and Results: In a prospective acute coronary syndrome (ACS) cohort, 1002 out of 2138 patients presented with STEMI. 63 STEMI patients experienced a major cardiovascular event (MACE, defined as cardiac death or recurrent myocardial infarction) within 1 year follow-up. Profiling of 752 miRNAs in a matched derivation cohort resulted in 14 miRNAs that were validated in 63 cases and matched 126 controls. Comparing cases versus controls, miR-26b-5p, miR-320a and miR-660-5p showed differential abundances. These 3 miRNAs were good discriminators of cases and controls (area under the receiver-operating-characteristic curve (AUC) in age- and sex-adjusted Cox regression for miR-26b-5p = 0.707, miR-660-5p = 0.683 and miR-320a =0.672) and combination of the 3 miRNAs increased AUC to 0.718. Importantly, addition of the 3 miRNAs to both, the GRACE-score and a clinical model increased AUC from 0.679 to 0.720 and 0.722 to 0.732, respectively, with a net reclassification improvement (NRI) of 0.20 in both cases.

Conclusions: In this case-control study derived from a multicentre-prospective ACS cohort, we identified miR-26b-5p, miR-660-5p and miR-320a as potential predictors of MACE in STEMI patients. The 3 miRNAs were reliable discriminators of MACE and increased predictive value when added to a clinical model and the GRACE-score. These findings suggest that differential release of miRNAs into circulation may reflect pathophysiological alterations that impact on clinical outcome.