The objectives are to determine candidate sex differences in cerebrovascular and hemodynamic predictors of stroke outcome for hypothesis generation from a retrospective database and prospectively test the hypothesis that sex differences in cerebrovascular and hemodynamic factors predict sex differences in stroke outcome.
Women have worse clinical outcomes from ischemic stroke than men. There is also evidence that women have a differential response to stroke reperfusion therapies, thrombolysis and thrombectomy. It is also recognized that age and race interact with sex in predicting outcome and these factors may explain some of the variance and inconsistency in the published clinical data on the sex differences in treatment response. There are also well known cerebral vascular measurements on imaging that predict outcome from stroke.
However, there have been no systematic studies in clinical populations to directly relate cerebrovascular factors known to predict stroke outcome to the observed sex differences in outcomes. Within the territory of the middle cerebral artery, several cerebrovascular factors are known to predict the outcomes of final infarct volume and functional independence in the laboratory as well as the clinic. The factors include the volume of the acutely hypoperfused brain region (the ischemic region), the core volume of irreversibly injured brain with that region, the volume of at-risk but salvageable brain (the ischemic penumbra), the presence of cerebral collateral circulation, and the time to reperfusion (duration of ischemia). These biological predictors are measurable by modern clinical imaging methods.
Data from the PIs previous work at NIH demonstrated that women were significantly more likely than men to have evidence of middle cerebral artery occlusion and ischemic penumbra on MRI at the time of presentation, after adjustment for age, time from stroke onset and NIH Stroke Scale severity. Furthermore, preliminary analysis of pooled data from endovascular thrombectomy trials suggests a higher rate of recanalization in women than in men. Taken with the literature of higher recanalization rates in women after iv thrombolysis, these cerebrovascular measurements predict the known clinical observation that the untreated stroke in women would have worse outcome than in men (more likely to have a large artery occlusion), but when treated, women would have a greater opportunity for brain salvage (higher recanalization rates and more likely to have penumbra). These preliminary imaging biomarker observations predict the known sex differences that have been clinically observed: worse stroke outcomes in woman but the differences are not apparent after recanalization treatments are given. This project will seek to confirm and expand on these preliminary observations.