title: Plasma metalloproteinase-9 concentration predicts hemorrhagic transformation in acute ischemic stroke.
abstract: OBJECTIVE
  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 7.8+/-4.5 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 (P<0.001). Mean infarct volume was 126+/-60 cm(3) in the HT group and 90+/-68 cm3 in the group without HT (P=0.003). Median (quartiles) plasma MMP-9 concentrations were higher in the HT group (193 [163, 213] versus 62 [40, 93] ng/mL, P<0.001), even in the 24 patients seen within 3 hours of symptom onset (P=0.014). MMP-9 levels > or =140 ng/mL had a positive and negative predictive value of HT of 61% and 97%, respectively. MMP-9 > or =140 ng/mL was associated with HT (odds ratio, 12; 95% confidence interval, 3 to 51; P<0.001) after adjustment for potential confounders and final infarct volume.
  
  
  CONCLUSIONS
  High plasma MMP-9 concentration in the acute phase of a cerebral infarct is an independent biochemical predictor of HT in all stroke subtypes.
authors.affiliation: Hospital Universitari Doctor Josep Trueta, Girona, Spain.
authors.forename: Mar
authors.initials: M
authors.lastname: Castellanos
authors.forename: Rogelio
authors.initials: R
authors.lastname: Leira
authors.forename: Joaquín
authors.initials: J
authors.lastname: Serena
authors.forename: José M
authors.initials: JM
authors.lastname: Pumar
authors.forename: Ignacio
authors.initials: I
authors.lastname: Lizasoain
authors.forename: José
authors.initials: J
authors.lastname: Castillo
authors.forename: Antoni
authors.initials: A
authors.lastname: Dávalos
mesh_terms: D015415:Biomarkers / Q000097:blood; D002545:Brain Ischemia / Q000150:complications; D002543:Cerebral Hemorrhage / Q000145:classification / Q000201:enzymology* / Q000209:etiology; D002544:Cerebral Infarction / Q000150:complications*; D005260:Female; D006801:Humans; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000097:blood*; D008875:Middle Aged; D011446:Prospective Studies; D012307:Risk Factors; D020521:Stroke / Q000145:classification / Q000150:complications
chemical_list: D015415:Biomarkers; D020780:Matrix Metalloproteinase 9