Theranostics 2017; 7(10):2555-2564. doi:10.7150/thno.19851
Incremental Value of Circulating MiR-122-5p to Predict Outcome after Out of Hospital Cardiac Arrest
1. Cardiovascular Research Unit, Luxembourg Institute of Health, Luxembourg;
2. Department of Cardiology, Clinical Sciences, Lund University and Skane University Hospital, Lund, Sweden;
3. Department of Anaesthesia and Intensive Care Medicine, Centre Hospitalier de Luxembourg, Luxembourg;
4. Competence Centre for Methodology and Statistics, Luxembourg Institute of Health, Luxembourg;
5. Department of Cardiology B, The Heart Centre, Rigshospitalet University Hospital, Copenhagen, Denmark;
6. Department of Intensive Care, University Hospital of Wales, Cardiff, United Kingdom;
7. Department of Intensive Care, Leeuwarden Medical Centrum, Leeuwarden, The Netherlands;
8. Department of Anesthesia and Intensive Care, Clinical Sciences, Lund University and Skane University Hospital, Lund, Sweden;
9. Department of Anesthesia and Intensive Care, Clinical Sciences, Lund University and Helsingborg Hospital, Helsingborg, Sweden.
Rationale. The value of microRNAs (miRNAs) as biomarkers has been addressed in various clinical contexts. Initial studies suggested that miRNAs, such as the brain-enriched miR-124-3p, might improve outcome prediction after out-of-hospital cardiac arrest. The aim of this study is to determine the prognostic value of miR-122-5p in a large cohort of comatose survivors of out-of-hospital cardiac arrest.
Methods. We analyzed 590 patients from the Targeted Temperature Management trial (TTM-trial). Circulating levels of miR-122-5p were measured in serum samples obtained 48 hours after return of spontaneous circulation. The primary end-point was poor neurological outcome at 6 months evaluated by the cerebral performance category score. The secondary end-point was survival at the end of the trial.
Results. Forty-eight percent of patients had a poor neurological outcome at 6 months and 43% were dead at the end of the trial. Levels of miR-122-5p were lower in patients with poor neurological outcome compared to patients with good neurological outcome (p<0.001), independently of targeted temperature management regimen. Levels of miR-122-5p were significant univariate predictors of neurological outcome (odds ratios (OR), 95% confidence intervals (CI): 0.71 [0.57-0.88]). In multivariable analyses, miR-122-5p was an independent predictor of neurological outcome and improved the predictive value of a clinical model including miR-124-3p (integrated discrimination improvement of 0.03 [0.02-0.04]). In Cox proportional hazards models, miR-122-5p was a significant predictor of survival at the end of the trial.
Conclusion. Circulating levels of miR-122-5p improve the prediction of outcome after out-of-hospital cardiac arrest.
Keywords: microRNAs, biomarker, prognostic, cardiac arrest, neurological function.
Devaux Y, Salgado-Somoza A, Dankiewicz J, Boileau A, Stammet P, Schritz A, Zhang L, Vausort M, Gilje P, Erlinge D, Hassager C, Wise MP, Kuiper M, Friberg H, Nielsen N,