Plasma metalloproteinase-9 concentration predicts hemorrhagic transformation in acute ischemic stroke.
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.
Castellanos
Mar
M
Hospital Universitari Doctor Josep Trueta, Girona, Spain.
Leira
Rogelio
R
Serena
Joaquín
J
Pumar
José M
JM
Lizasoain
Ignacio
I
Castillo
José
J
Dávalos
Antoni
A
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
D015415:Biomarkers; D020780:Matrix Metalloproteinase 9