Plasma Metalloproteinase-9 Concentration Predicts Hemorrhagic Transformation in Acute Ischemic Stroke

Background and Purpose—Matrix metalloproteinase-9 (MMP-9) activity has been associated with hemorrhagic transformation (HT) in experimental models of cerebral ischemia. Our aim was to investigate the relationship between MMP-9 concentrations in blood within 24 hours of stroke onset and subsequent HT of cerebral infarction. Methods—We studied 250 patients with a hemispheric ischemic stroke of 7.84.5 hours ’ duration. Early CT signs of cerebral infarction were evaluated on admission. The HT and infarct volume were analyzed from the CT performed on days 4 through 7. MMP-9 levels were determined by enzyme-linked immunosorbent assay in blood samples obtained on admission. Results—HT was observed in 38 patients (15.2%): 24 (63.2%) had a hemorrhagic infarction, and 14 (36.8%) had a parenchymal hematoma. A total of 108 patients (43%) received anticoagulants before the second CT scan. Systolic and diastolic blood pressures, body temperature, frequency of early CT signs of ischemia (92 % versus 22%), and treatment with anticoagulants (79 % versus 37%) were significantly higher in the group with HT (P0.001). Mean infarct volume was 12660 cm3 in the HT group and 9068 cm3 in the group without HT (P0.003). Median (quartiles) plasma MMP-9 concentrations were higher in the HT group (193 [163, 213] versus 62 [40, 93] ng/mL, P0.001), even in the 24 patients seen within 3 hours of symptom onset (P0.014). MMP-9 levels 140 ng/mL had a positive and negative predictive value of HT of 61 % and 97%, respectively. MMP-9 140 ng/mL was associated with HT (odds ratio, 12