GFAp and tau protein as predictors of neurological outcome after out-of-hospital cardiac arrest: A post hoc analysis of the COMACARE trial

Jaana Humaloja, Marika Lähde, Nicholas J Ashton, Matti Reinikainen, Johanna Hästbacka, Pekka Jakkula, Hans Friberg, Tobias Cronberg, Ville Pettilä, Kaj Blennow, Henrik Zetterberg, Markus B Skrifvars, COMACARE Study Groups, Jaana Humaloja, Marika Lähde, Nicholas J Ashton, Matti Reinikainen, Johanna Hästbacka, Pekka Jakkula, Hans Friberg, Tobias Cronberg, Ville Pettilä, Kaj Blennow, Henrik Zetterberg, Markus B Skrifvars, COMACARE Study Groups

Abstract

Aim: To determine the ability of serum glial fibrillary acidic protein (GFAp) and tau protein to predict neurological outcome after out-of-hospital cardiac arrest (OHCA).

Methods: We measured plasma concentrations of GFAp and tau of patients included in the previously published COMACARE trial (NCT02698917) on intensive care unit admission and at 24, 48, and 72 h after OHCA, and compared them to neuron specific enolase (NSE). NSE concentrations were determined already during the original trial. We defined unfavourable outcome as a cerebral performance category (CPC) score of 3-5 six months after OHCA. We determined the prognostic accuracy of GFAp and tau using the receiver operating characteristic curve and area under the curve (AUROC).

Results: Overall, 39/112 (35%) patients had unfavourable outcomes. Over time, both markers were evidently higher in the unfavourable outcome group (p < 0.001). At 48 h, the median (interquartile range) GFAp concentration was 1514 (886-4995) in the unfavourable versus 238 (135-463) pg/ml in the favourable outcome group (p < 0.001). The corresponding tau concentrations were 99.6 (14.5-352) and 3.0 (2.2-4.8) pg/ml (p < 0.001). AUROCs at 48 and 72 h were 0.91 (95% confidence interval 0.85-0.97) and 0.91 (0.85-0.96) for GFAp and 0.93 (0.86-0.99) and 0.95 (0.89-1.00) for tau. Corresponding AUROCs for NSE were 0.86 (0.79-0.94) and 0.90 (0.82-0.97). The difference between the prognostic accuracies of GFAp or tau and NSE were not statistically significant.

Conclusions: At 48 and 72 h, serum both GFAp and tau demonstrated excellent accuracy in predicting outcomes after OHCA but were not superior to NSE.

Clinical trial registration: NCT02698917 (https://www.clinicaltrials.gov/ct2/show/NCT02698917).

Keywords: Biomarkers; Glial fibrillary acidic protein; Neurological outcome prognostication; Out-of-hospital cardiac arrest; Tau protein.

Conflict of interest statement

Declaration of Competing Interest J. Humaloja, M.L., N.J.A, M.R., J. Hästbacka, P.J., H.F., T.C. and V.P. have nothing to disclose. M.B.S. has received a lecture fee and a travel grant from BARD Medical (Ireland and South Korea, not related to this study). H.Z. has served at scientific advisory boards and/or as a consultant for AbbVie, Alector, Eisai, Denali, Roche Diagnostics, Wave, Samumed, Siemens Healthineers, Pinteon Therapeutics, Nervgen, AZTherapies, CogRx and Red Abbey Labs; has given lectures in symposia sponsored by Cellectricon, Fujirebio, Alzecure and Biogen; and is a co-founder of Brain Biomarker Solutions in Gothenburg AB (BBS), which is a part of the GU Ventures Incubator Program (outside submitted work). KB has served as a consultant at advisory boards or at data-monitoring committees for Abcam, Axon, Biogen JOMDD/Shimadzu, Julius Clinical, Lilly, MagQu, Novartis, Prothena, Roche Diagnostics and Siemens Healthineers and is a co-founder of Brain Biomarker Solutions in Gothenburg AB (BBS), which is a part of the GU Ventures Incubator Program, all unrelated to the work presented in this paper.

Copyright © 2021 The Author(s). Published by Elsevier B.V. All rights reserved.

Figures

Fig. 1
Fig. 1
Flowchart of the study population and blood samples available for the analyses. Definitions of abbreviations: COMACARE trial: Carbon dioxide, Oxygen, and Mean Arterial pressure After Cardiac Arrest and Resuscitation trial ICU: intensive care unit GFAp: glial fibrillary acidic protein.
Fig. 2
Fig. 2
GFAp and tau concentrations between patients with favourable (CPC 1–2) and unfavourable (CPC 3–5) outcomes at six months presented on a logarithmic scale. The p-value indicates the difference of GFAp and tau concentrations over time between the outcome groups. Definitions of abbreviations: GFAp: glial fibrillary acidic protein CPC: cerebral performance category.
Fig. 3
Fig. 3
Receiver operating characteristic curves and areas under the curves (AUROC) for concentrations of GFAp and tau on ICU admission (0 h) and at 24, 48 and 72 h for prediction of favourable (CPC 1–2) vs unfavourable (CPC 3–5) outcomes six months after cardiac arrest. Definitions of abbreviations: 95% CI: 95% confidence interval ROC: receiver operating characteristic AUROC: area under the receiving operating characteristic curve GFAp: glial fibrillary acidic protein.

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