Abstract 29: A New Biomarker for Diagnosis of Ischemic Stroke: Plasma Glycogen Phosphorylase-BB

Abstract

Background: Glycogen phosphorylase-BB (GPBB) is the key enzyme that breaks down glycogen to yield glucose-1-phosphate in order to meet the emergent ATP need during cerebral ischemia. GPBB is one of the most sensitive and specific plasma markers for early detection of acute myocardial ischemia. GPBB concentration is about 100 times higher in brain than in heart. We hypothesized that plasma levels of GPBB might elevate following cerebral ischemia. Methods: We measured plasma GPBB levels in 172 patients with imaging-confirmed brain infarction at two time points (within 9 hours of symptom onset and at 48 hours). The control group consisted of 97 age-matched subjects without stroke. GPBB levels were determined blind to case/control assignment using a commercially available ELISA kit (Diagenics, Germany). Results: Baseline mean (±SD) GPBB level was 46.3 ng/ml (± 38.6 ng/ml) in cases and 4.8 ng/ml (±8.0 ng/ml) in controls (p < 0.001, Figure). GPBB levels slightly decreased from baseline to 48 hours in patients with stroke (38.7 ± 36.5 ng/ml, p = 0.02). The discriminative ability of GPBB between cases and controls as measured by the area under the Receiver Operating Characteristic (ROC) curve was high (0.95, 95% CI 0.93-0.98). GPBB level corresponding to optimal operating point on the ROC curve was 6 ng/ml. Based on the 6 ng/dl cut-off, baseline plasma GPBB showed 94% sensitivity and 90% specificity for diagnosis of ischemic stroke. Conclusion: Plasma GPBB appears to be a sensitive and specific marker for early diagnosis of brain ischemia. Its high proportional rise with respect to the discriminator value suggests that GPBB may find utility particularly in the diagnosis of mild ischemic syndromes associated with trace amounts of brain injury.