Incremental Value of Circulating MiR-122-5p to Predict Outcome after Out of Hospital Cardiac Arrest

Yvan Devaux, Antonio Salgado-Somoza, Josef Dankiewicz, Adeline Boileau, Pascal Stammet, Anna Schritz, Lu Zhang, Mélanie Vausort, Patrik Gilje, David Erlinge, Christian Hassager, Matthew P Wise, Michael Kuiper, Hans Friberg, Niklas Nielsen, TTM-Trial Investigators

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Abstract

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.

OriginalsprogEngelsk
TidsskriftTheranostics
Vol/bind7
Udgave nummer10
Sider (fra-til)2555-2564
Antal sider10
ISSN1838-7640
DOI
StatusUdgivet - 2017

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