Association between blood caspase-8 levels and mortality of patients with malignant middle cerebral artery infarction

Abstract

Objective: High concentrations of caspase-8 (main initiator caspase of apoptosis extrinsic pathway) have been found in brain tissue from traumatic brain injury patients and in blood of patients with different diseases. However, there are not data on blood caspase-8 concentrations in ischemic stroke patients. Therefore, the objective of this study was to determine whether there is an association between blood caspase-8 concentrations and the probability and speed of mortality at 30 days in patients with malignant middle cerebral artery infarction (MMCAI).

Design: Observational prospective study.

Setting: Five Intensive Care Units (ICU).

Patients: Patients with severe malignant middle cerebral artery infarction (MMCAI) defined as acute infarction in more than of 50% of that territory and Glasgow Coma Scale (GCS)<9.

Interventions: Determination of serum caspase-8 levels when MMCAI was diagnosed.

Main variables of interest: Mortality at 30 days and time until this event.

Results: Severe MMCAI patients (n=28) compared to survivor patients (n=28) showed higher serum caspase-8 concentrations (p<0.001), lower platelet count (p=0.01) and lower GCS (p=0.002). We found an area under the curve for mortality prediction of 78% (95% CI=65%-91%; p<0.001) by serum caspase-8 levels. Kaplan-Meier analysis found higher mortality rate in patients with serum caspase-8 levels >62.8ng/mL (hazard ratio=11.2; 95% CI=4.4-28.4; p<0.001).

Conclusions: The association of high blood caspase-8 concentrations with the rate and the velocity of 30-day mortality in MMCAI patients is the main new finding of our study.

Keywords: Caspasa-8; Caspase-8; Infarto arteria cerebral media; Middle cerebral artery infarction; Mortalidad; Mortality; Pacientes; Patients.