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

doi:10.1016/j.resuscitation.2021.11.033

Abstract

AimTo determine the ability of serum glial fibrillary acidic protein (GFAp) and tau protein to predict neurological outcome after out-of-hospital cardiac arrest (OHCA). MethodsWe 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). ResultsOverall, 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. ConclusionsAt 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 registrationNCT02698917 (https://www.clinicaltrials.gov/ct2/show/NCT02698917).

Highlights

MethodsHypoxic-ischemic brain injury is considered the major determinant of neurological outcome after cardiac arrest (CA).[1,2] The expected outcome should guide intensive care treatment efforts to those who are likely to benefit
Based on the measured concentrations of glial fibrillary acidic protein (GFAp) and tau at 48 and 72 h, we determined how the corresponding cutoff values predicting poor outcome with 95% specificity categorised the patients with favourable vs unfavourable outcomes in three scenarios: a) both GFAp and tau concentrations are below the cutoff, b) either GFAp or tau concentration is above the cutoff (“grey area”), and c) both GFAp and tau concentrations are above the cutoff
Median GFAp and tau concentrations were significantly higher in patients with unfavourable outcomes over time and individually at all timepoints except with tau upon ICU admission

Summary

Introduction

MethodsHypoxic-ischemic brain injury is considered the major determinant of neurological outcome after cardiac arrest (CA).[1,2] The expected outcome should guide intensive care treatment efforts to those who are likely to benefit. Resuscitation guidelines suggest a multimodal approach for outcome prediction utilising clinical examination, brain imaging, electroencephalography, and laboratory biomarkers.[3,4] Currently neuron specific enolase (NSE) is the only biomarker recommended by the guidelines. The serum level of glial fibrillary acidic protein (GFAp) has been recognised as predictor of neurological outcome after head trauma; elevated concentrations have been measured after stroke, subarachnoid haemorrhage, and CA.[6,7,8,9,10,11,12] GFAp is an intermediate-filament component of the astrocytic cytoskeleton highly specific to the central nervous system.[13] the tau protein forms microtubule-stabilising structures and is primarily found in axons in central nervous tissues.[14,15] Elevated tau concentrations in blood have been reported after ischemic stroke and CA. Tau concentrations increase in the cerebrospinal fluid of patients with traumatic brain injury or neurodegenerative diseases, Creutzfeldt – Jakob disease and Alzheimer’s disease.[16,17,18,19,20,21]

Objectives

Methods

Results

Discussion

Conclusion