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

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.

The association between plasma miR-122-5p release pattern at admission and all-cause mortality or shock after out-of-hospital cardiac arrest

“…Moreover, plasma levels of miR-122-5p during resuscitation for OHCA were higher among patients who died compared to survivors (Wander et al 2016). Plasma levels of miR-122-5p after OHCA seem to fall between 24 h and 72 h after OHCA but the timeframe between resuscitation and 24 h after OHCA has not been evaluated (Devaux et al 2017).…”

Characterization of Cellular Sources and Circulating Levels of Extracellular Vesicles in a Dietary Murine Model of Nonalcoholic Steatohepatitis

“…Similarly, biomarkers of liver disease may demonstrate sexual dimorphism . For example, plasma alanine aminotransferase (ALT) levels and microRNA‐122 levels are higher in men than women . The influence of biological sex on circulating EVs in NAFLD has not been carefully examined.…”

MicroRNAs as Potential Prognosticators of Neurological Outcome in Out-Of-Hospital Cardiac Arrest Patients

“…Only one study measured miRNA levels at time of arrest [47]. Other studies measured circulating miRNAs 24-48 h post-ROSC [43][44][45]48]. Table 1 summarizes miRNAs that have been identified as potential biomarkers predicting outcome in studies on patients with out-of-hospital-cardiac arrest.…”

“…The most recent study (2017) was another substudy of the Target Temperature Management After Cardiac Arrest trial [48]. A total of 590 patients who survived 24 h post-ROSC and had serum samples 48 h post-ROSC were included.…”