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Plasma metalloproteinase-9 concentration predicts hemorrhagic transformation in acute ischemic stroke
Mar Castellanos1, Rogelio Leira, Joaquín Serena
1Hospital Universitari Doctor Josep Trueta, Girona, Spain.
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 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.
Insights
High matrix metalloproteinase-9 (MMP-9) levels in acute ischemic stroke patients predict hemorrhagic transformation (HT). This finding aids in identifying stroke patients at risk for HT, improving patient outcomes.
Area of Science:
- Neurology
- Biochemistry
- Medical Imaging
Background:
- Matrix metalloproteinase-9 (MMP-9) activity is linked to hemorrhagic transformation (HT) in experimental cerebral ischemia models.
- Investigating MMP-9's role in human stroke is crucial for understanding HT development.
Purpose of the Study:
- To determine the association between blood MMP-9 concentrations within 24 hours of stroke onset and subsequent HT in cerebral infarction.
- To evaluate MMP-9 as a potential biomarker for predicting HT after ischemic stroke.
Main Methods:
- A cohort of 250 patients with hemispheric ischemic stroke was studied.
- MMP-9 levels were measured using enzyme-linked immunosorbent assay in blood samples obtained on admission.
- Early CT signs, HT, and infarct volume were assessed via CT scans performed at different time points.
Main Results:
- Hemorrhagic transformation (HT) occurred in 15.2% of patients.
- Median plasma MMP-9 concentrations were significantly higher in patients with HT (193 ng/mL) compared to those without (62 ng/mL).
- MMP-9 levels ≥140 ng/mL were independently associated with HT (OR, 12; P<0.001) and had a high negative predictive value (97%).
Conclusions:
- Elevated plasma MMP-9 levels in the acute phase of cerebral infarction serve as an independent biochemical predictor of HT.
- MMP-9 is a valuable biomarker for predicting HT across all ischemic stroke subtypes.
- These findings can inform clinical management and risk stratification for stroke patients.