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

doi:10.7150/thno.19851

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

Department of Clinical Medicine

19 Citations (Scopus)

43 Downloads (Pure)

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.

Original language	English
Journal	Theranostics
Volume	7
Issue number	10
Pages (from-to)	2555-2564
Number of pages	10
ISSN	1838-7640
DOIs	https://doi.org/10.7150/thno.19851
Publication status	Published - 2017

Keywords

Adult
Aged
Aged, 80 and over
Biomarkers/blood
Brain Diseases/epidemiology
Female
Humans
Male
MicroRNAs/blood
Middle Aged
Out-of-Hospital Cardiac Arrest/diagnosis
Prognosis
Serum/chemistry
Survival Analysis
Treatment Outcome
Young Adult

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10.7150/thno.19851Licence: CC BY-NC

Incremental Value of Circulating MiR-122-5p to Predict Outcome after Out of Hospital Cardiac ArrestFinal published version, 655 KBLicence: CC BY-NC

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Devaux, Y., Salgado-Somoza, A., Dankiewicz, J., Boileau, A., Stammet, P., Schritz, A., Zhang, L., Vausort, M., Gilje, P., Erlinge, D., Hassager, C., Wise, M. P., Kuiper, M., Friberg, H., Nielsen, N., & TTM-Trial Investigators (2017). Incremental Value of Circulating MiR-122-5p to Predict Outcome after Out of Hospital Cardiac Arrest. Theranostics, 7(10), 2555-2564. https://doi.org/10.7150/thno.19851

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 & TTM-Trial Investigators 2017, 'Incremental Value of Circulating MiR-122-5p to Predict Outcome after Out of Hospital Cardiac Arrest', Theranostics, vol. 7, no. 10, pp. 2555-2564. https://doi.org/10.7150/thno.19851

@article{c07c5531873a4460a8c2fdc6ac615ab8,

title = "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.",

keywords = "Adult, Aged, Aged, 80 and over, Biomarkers/blood, Brain Diseases/epidemiology, Female, Humans, Male, MicroRNAs/blood, Middle Aged, Out-of-Hospital Cardiac Arrest/diagnosis, Prognosis, Serum/chemistry, Survival Analysis, Treatment Outcome, Young Adult",

author = "Yvan Devaux and Antonio Salgado-Somoza and Josef Dankiewicz and Adeline Boileau and Pascal Stammet and Anna Schritz and Lu Zhang and M{\'e}lanie Vausort and Patrik Gilje and David Erlinge and Christian Hassager and Wise, {Matthew P} and Michael Kuiper and Hans Friberg and Niklas Nielsen and {TTM-Trial Investigators}",

year = "2017",

doi = "10.7150/thno.19851",

language = "English",

volume = "7",

pages = "2555--2564",

journal = "Theranostics",

issn = "1838-7640",

publisher = "Ivyspring International Publisher",

number = "10",

}

TY - JOUR

T1 - Incremental Value of Circulating MiR-122-5p to Predict Outcome after Out of Hospital Cardiac Arrest

AU - Devaux, Yvan

AU - Salgado-Somoza, Antonio

AU - Dankiewicz, Josef

AU - Boileau, Adeline

AU - Stammet, Pascal

AU - Schritz, Anna

AU - Zhang, Lu

AU - Vausort, Mélanie

AU - Gilje, Patrik

AU - Erlinge, David

AU - Hassager, Christian

AU - Wise, Matthew P

AU - Kuiper, Michael

AU - Friberg, Hans

AU - Nielsen, Niklas

AU - TTM-Trial Investigators

PY - 2017

Y1 - 2017

N2 - 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.

AB - 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.

KW - Adult

KW - Aged

KW - Aged, 80 and over

KW - Biomarkers/blood

KW - Brain Diseases/epidemiology

KW - Female

KW - Humans

KW - Male

KW - MicroRNAs/blood

KW - Middle Aged

KW - Out-of-Hospital Cardiac Arrest/diagnosis

KW - Prognosis

KW - Serum/chemistry

KW - Survival Analysis

KW - Treatment Outcome

KW - Young Adult

U2 - 10.7150/thno.19851

DO - 10.7150/thno.19851

M3 - Journal article

C2 - 28819446

SN - 1838-7640

VL - 7

SP - 2555

EP - 2564

JO - Theranostics

JF - Theranostics

IS - 10

ER -

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

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Keywords

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