Objective: Cell apoptosis is involved in acute brain injury after aneurysmal subarachnoid hemorrhage (aSAH). The protein cytokeratin-18 (CK-18) is cleaved by the action of caspases during apoptosis, and the resulting fragments are released into the blood as caspase-cleaved CK (CCCK)-18. Our study examined the relationship between circulating CCCK-18 levels and long-term clinical outcomes among aSAH patients.
Methods: We recruited 128 aSAH patients and 128 controls (matched on age and sex). Serum was collected at admission to the emergency department. Unfavorable outcome was defined as the Glasgow Outcome Score scores of 1-3. After a 6-month follow-up period, outcomes were assessed using a logistic regression analyses. The prognostic predictive values were evaluated according to receiver operating curves analysis.
Results: aSAH patients had higher plasma CCCK-18 levels compared to controls (235.1 ± 86.8 U/L vs. 25.6 ± 23.4 U/L, P<0.001). CCCK-18 was independently associated with World Federation of Neurological Surgeons (WFNS) scores (t=4.460, P<0.001) and modified Fisher scores (t=3.781, P<0.001). Furthermore, CCCK-18 levels were markedly higher among patients with an unfavorable outcome and among non-survivors. CCCK-18 was yet identified as an independent prognostic predictor for mortality (odds ratio, 5.769; 95% confidence interval, 1.196-27.832; P=0.029) and unfavorable outcome (odds ratio, 4.909; 95% confidence interval, 1.521-15.838; P=0.008), as well as had similar predictive values for them compared with WFNS scores and modified Fisher scores.
Conclusions: High circulating CCCK-18 levels were associated with injury severity and a poor clinical outcome after aSAH and CCCK-18 had the potential to be a good prognostic biomarker for aSAH.
Keywords: Aneurysm; Biomarker; Caspase-cleaved cytokeratin-18; Functional outcome; Mortality; Prognosis; Subarachnoid hemorrhage.
Copyright © 2015 Elsevier B.V. All rights reserved.