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Stroke. 2003;34:40-46
Published online before print December 5, 2002, doi: 10.1161/01.STR.0000046764.57344.31
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(Stroke. 2003;34:40.)
© 2003 American Heart Association, Inc.


Original Contributions

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

Mar Castellanos, MD; Rogelio Leira, MD, PhD; Joaquín Serena, MD, PhD; José M. Pumar, MD, PhD; Ignacio Lizasoain, MD, PhD; José Castillo, MD, PhD Antoni Dávalos, MD, PhD

From Hospital Universitari Doctor Josep Trueta, Girona (M.C., J.S., A.D.); Departamento de Farmacología, Facultad de Medicina, Universidad Complutense, Madrid (I.L.); and Hospital Clínico Universitario, Santiago de Compostela (R.L., J.M.P., J.C.), Spain.

Correspondence to Dr Antoni Dávalos, Section of Neurology, Hospital Universitari Doctor Josep Trueta, E-17007 Girona, Spain. E-mail min.adavalos{at}htrueta.scs.es

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 7.8±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 cm3 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 >=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; 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.

Editorial Comment

Gerhard F. Hamann, MD



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