Subacute Elevation of Plasma Level of Caspase-Cleaved Cytokeratin-18 is Associated with Hemorrhagic Transformation and Functional Outcome in Ischemic Stroke

J Stroke Cerebrovasc Dis. 2019 Mar;28(3):719-727. doi: 10.1016/j.jstrokecerebrovasdis.2018.11.015. Epub 2018 Dec 5.

Abstract

Background: Caspase-cleaved cytokeratin-18 (CCCK-18) is an apoptosis marker. Here, we analyzed the relationship between plasma level of CCCK-18 in the acute and subacute stage of ischemic stroke and early and late functional outcome. Besides, correlation among CCCK-18 and complications, such as hemorrhagic transformation (HT) were also explored.

Methods: Plasma concentration of CCCK-18 was investigated in 54 patients at admission and poststroke 72 hours. HT was evaluated by CT scans on 24 poststroke hours. Outcome measures were assessed by modified Rankin scale at hospital discharge and 6-month later. Receiver operating characteristics (ROC) analysis was used to determine the best cut-off values of CCCK-18 as a predictor of unfavorable functional outcome.

Results: Significantly elevated CCCK-18 level was observed at 72 hours after onset of stroke, in nonsurviving compared to surviving patients (331 ± 191 ng/L versus 251 ± 164 ng/L, P = .01). Based on ROC analysis, the cut-off value of plasma CCCK-18 levels >223 ng/L at 72 poststroke hours predicted 6-month unfavorable stroke outcome with a sensitivity of 84.4% and a specificity of 77.3% (area under the curve: .851, 95% confidence interval = .745-.955, P < .001). The rate of complications such as HT and in-hospital infection was significantly higher in patients presented with a plasma CCCK-18 level above the cut-off value.

Conclusions: The association between high serum CCCK-18 levels and unfavorable early and late stroke outcome in an unselected study population was first described here. Besides, the apoptosis marker CCCK-18 might be a predictor of further complication such as HT and in-hospital infection.

Keywords: Caspase-cleaved cytokeratin-18; hemorrhagic transformation; ischemic stroke; outcome.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Biomarkers / blood
  • Brain Ischemia / blood*
  • Brain Ischemia / diagnosis
  • Brain Ischemia / physiopathology
  • Brain Ischemia / therapy
  • Caspases / metabolism*
  • Cross Infection / etiology
  • Disability Evaluation
  • Female
  • Humans
  • Intracranial Hemorrhages / blood*
  • Intracranial Hemorrhages / diagnosis
  • Intracranial Hemorrhages / physiopathology
  • Intracranial Hemorrhages / therapy
  • Keratin-18 / blood*
  • Male
  • Middle Aged
  • Multidetector Computed Tomography
  • Patient Admission
  • Peptide Fragments / blood*
  • Prognosis
  • Prospective Studies
  • Recovery of Function
  • Risk Factors
  • Stroke / blood*
  • Stroke / diagnosis
  • Stroke / physiopathology
  • Stroke / therapy
  • Time Factors
  • Up-Regulation

Substances

  • Biomarkers
  • KRT18 protein, human
  • Keratin-18
  • Peptide Fragments
  • Caspases