Serum tau and neurological outcome in cardiac arrest

Niklas Mattsson; Henrik Zetterberg; Niklas Nielsen; Kaj Blennow; Josef Dankiewicz; Hans Friberg; Gisela Lilja; Philip S Insel; Christian Rylander; Pascal Stammet; Anders Aneman; Christian Hassager; Jesper Kjaergaard; Michael Kuiper; Tommaso Pellis; Jørn Wetterslev; Matthew Wise; Tobias Cronberg

doi:10.1002/ana.25067

Serum tau and neurological outcome in cardiac arrest

Niklas Mattsson, Henrik Zetterberg, Niklas Nielsen, Kaj Blennow, Josef Dankiewicz, Hans Friberg, Gisela Lilja, Philip S Insel, Christian Rylander, Pascal Stammet, Anders Aneman, Christian Hassager, Jesper Kjaergaard, Michael Kuiper, Tommaso Pellis, Jørn Wetterslev, Matthew Wise, Tobias Cronberg

Institut for Klinisk Medicin

39 Citationer (Scopus)

54 Downloads (Pure)

Abstract

Objective: To test serum tau as a predictor of neurological outcome after cardiac arrest. Methods: We measured the neuronal protein tau in serum at 24, 48, and 72 hours after cardiac arrest in 689 patients in the prospective international Target Temperature Management trial. The main outcome was poor neurological outcome, defined as Cerebral Performance Categories 3–5 at 6 months. Results: Increased tau was associated with poor outcome at 6 months after cardiac arrest (median = 38.5, interquartile range [IQR] = 5.7–245ng/l in poor vs median = 1.5, IQR = 0.7–2.4ng/l in good outcome, for tau at 72 hours, p < 0.0001). Tau improved prediction of poor outcome compared to using clinical information (p < 0.0001). Tau cutoffs had low false-positive rates (FPRs) for good outcome while retaining high sensitivity for poor outcome. For example, tau at 72 hours had FPR = 2% (95% CI = 1–4%) with sensitivity = 66% (95% CI = 61–70%). Tau had higher accuracy than serum neuron-specific enolase (NSE; the area under the receiver operating characteristic curve was 0.91 for tau vs 0.86 for NSE at 72 hours, p = 0.00024). During follow-up (up to 956 days), tau was significantly associated with overall survival. The accuracy in predicting outcome by serum tau was equally high for patients randomized to 33 °C and 36 °C targeted temperature after cardiac arrest. Interpretation: Serum tau is a promising novel biomarker for prediction of neurological outcome in patients with cardiac arrest. It may be significantly better than serum NSE, which is recommended in guidelines and currently used in clinical practice in several countries to predict outcome after cardiac arrest. Ann Neurol 2017;82:665–675.

Originalsprog	Engelsk
Tidsskrift	Annals of Neurology
Vol/bind	82
Udgave nummer	5
Sider (fra-til)	665-675
Antal sider	11
ISSN	0364-5134
DOI	https://doi.org/10.1002/ana.25067
Status	Udgivet - nov. 2017

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10.1002/ana.25067Licens: CC BY-NC-ND

RESEARCH ARTICLESerum Tau and Neurological Outcome inCardiac ArrestForlagets udgivne version, 912 KBLicens: CC BY-NC-ND

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Mattsson, N., Zetterberg, H., Nielsen, N., Blennow, K., Dankiewicz, J., Friberg, H., Lilja, G., Insel, P. S., Rylander, C., Stammet, P., Aneman, A., Hassager, C., Kjaergaard, J., Kuiper, M., Pellis, T., Wetterslev, J., Wise, M., & Cronberg, T. (2017). Serum tau and neurological outcome in cardiac arrest. Annals of Neurology, 82(5), 665-675. https://doi.org/10.1002/ana.25067

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abstract = "Objective: To test serum tau as a predictor of neurological outcome after cardiac arrest. Methods: We measured the neuronal protein tau in serum at 24, 48, and 72 hours after cardiac arrest in 689 patients in the prospective international Target Temperature Management trial. The main outcome was poor neurological outcome, defined as Cerebral Performance Categories 3–5 at 6 months. Results: Increased tau was associated with poor outcome at 6 months after cardiac arrest (median = 38.5, interquartile range [IQR] = 5.7–245ng/l in poor vs median = 1.5, IQR = 0.7–2.4ng/l in good outcome, for tau at 72 hours, p < 0.0001). Tau improved prediction of poor outcome compared to using clinical information (p < 0.0001). Tau cutoffs had low false-positive rates (FPRs) for good outcome while retaining high sensitivity for poor outcome. For example, tau at 72 hours had FPR = 2% (95% CI = 1–4%) with sensitivity = 66% (95% CI = 61–70%). Tau had higher accuracy than serum neuron-specific enolase (NSE; the area under the receiver operating characteristic curve was 0.91 for tau vs 0.86 for NSE at 72 hours, p = 0.00024). During follow-up (up to 956 days), tau was significantly associated with overall survival. The accuracy in predicting outcome by serum tau was equally high for patients randomized to 33 °C and 36 °C targeted temperature after cardiac arrest. Interpretation: Serum tau is a promising novel biomarker for prediction of neurological outcome in patients with cardiac arrest. It may be significantly better than serum NSE, which is recommended in guidelines and currently used in clinical practice in several countries to predict outcome after cardiac arrest. Ann Neurol 2017;82:665–675.",

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author = "Niklas Mattsson and Henrik Zetterberg and Niklas Nielsen and Kaj Blennow and Josef Dankiewicz and Hans Friberg and Gisela Lilja and Insel, {Philip S} and Christian Rylander and Pascal Stammet and Anders Aneman and Christian Hassager and Jesper Kjaergaard and Michael Kuiper and Tommaso Pellis and J{\o}rn Wetterslev and Matthew Wise and Tobias Cronberg",

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year = "2017",

month = nov,

doi = "10.1002/ana.25067",

language = "English",

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pages = "665--675",

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TY - JOUR

T1 - Serum tau and neurological outcome in cardiac arrest

AU - Mattsson, Niklas

AU - Zetterberg, Henrik

AU - Nielsen, Niklas

AU - Blennow, Kaj

AU - Dankiewicz, Josef

AU - Friberg, Hans

AU - Lilja, Gisela

AU - Insel, Philip S

AU - Rylander, Christian

AU - Stammet, Pascal

AU - Aneman, Anders

AU - Hassager, Christian

AU - Kjaergaard, Jesper

AU - Kuiper, Michael

AU - Pellis, Tommaso

AU - Wetterslev, Jørn

AU - Wise, Matthew

AU - Cronberg, Tobias

PY - 2017/11

Y1 - 2017/11

N2 - Objective: To test serum tau as a predictor of neurological outcome after cardiac arrest. Methods: We measured the neuronal protein tau in serum at 24, 48, and 72 hours after cardiac arrest in 689 patients in the prospective international Target Temperature Management trial. The main outcome was poor neurological outcome, defined as Cerebral Performance Categories 3–5 at 6 months. Results: Increased tau was associated with poor outcome at 6 months after cardiac arrest (median = 38.5, interquartile range [IQR] = 5.7–245ng/l in poor vs median = 1.5, IQR = 0.7–2.4ng/l in good outcome, for tau at 72 hours, p < 0.0001). Tau improved prediction of poor outcome compared to using clinical information (p < 0.0001). Tau cutoffs had low false-positive rates (FPRs) for good outcome while retaining high sensitivity for poor outcome. For example, tau at 72 hours had FPR = 2% (95% CI = 1–4%) with sensitivity = 66% (95% CI = 61–70%). Tau had higher accuracy than serum neuron-specific enolase (NSE; the area under the receiver operating characteristic curve was 0.91 for tau vs 0.86 for NSE at 72 hours, p = 0.00024). During follow-up (up to 956 days), tau was significantly associated with overall survival. The accuracy in predicting outcome by serum tau was equally high for patients randomized to 33 °C and 36 °C targeted temperature after cardiac arrest. Interpretation: Serum tau is a promising novel biomarker for prediction of neurological outcome in patients with cardiac arrest. It may be significantly better than serum NSE, which is recommended in guidelines and currently used in clinical practice in several countries to predict outcome after cardiac arrest. Ann Neurol 2017;82:665–675.

AB - Objective: To test serum tau as a predictor of neurological outcome after cardiac arrest. Methods: We measured the neuronal protein tau in serum at 24, 48, and 72 hours after cardiac arrest in 689 patients in the prospective international Target Temperature Management trial. The main outcome was poor neurological outcome, defined as Cerebral Performance Categories 3–5 at 6 months. Results: Increased tau was associated with poor outcome at 6 months after cardiac arrest (median = 38.5, interquartile range [IQR] = 5.7–245ng/l in poor vs median = 1.5, IQR = 0.7–2.4ng/l in good outcome, for tau at 72 hours, p < 0.0001). Tau improved prediction of poor outcome compared to using clinical information (p < 0.0001). Tau cutoffs had low false-positive rates (FPRs) for good outcome while retaining high sensitivity for poor outcome. For example, tau at 72 hours had FPR = 2% (95% CI = 1–4%) with sensitivity = 66% (95% CI = 61–70%). Tau had higher accuracy than serum neuron-specific enolase (NSE; the area under the receiver operating characteristic curve was 0.91 for tau vs 0.86 for NSE at 72 hours, p = 0.00024). During follow-up (up to 956 days), tau was significantly associated with overall survival. The accuracy in predicting outcome by serum tau was equally high for patients randomized to 33 °C and 36 °C targeted temperature after cardiac arrest. Interpretation: Serum tau is a promising novel biomarker for prediction of neurological outcome in patients with cardiac arrest. It may be significantly better than serum NSE, which is recommended in guidelines and currently used in clinical practice in several countries to predict outcome after cardiac arrest. Ann Neurol 2017;82:665–675.

KW - Journal Article

U2 - 10.1002/ana.25067

DO - 10.1002/ana.25067

M3 - Journal article

C2 - 28981963

SN - 0364-5134

VL - 82

SP - 665

EP - 675

JO - Annals of Neurology

JF - Annals of Neurology

IS - 5

ER -

Serum tau and neurological outcome in cardiac arrest

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