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Sex Differences in Microvascular Integrity Tied to Different Outcomes After Ischemic Stroke

Key findings

  • Functional outcomes after acute ischemic stroke are worse in women than in men
  • In previous studies, Massachusetts General Hospital researchers identified an association between women's worse outcomes and K2, an MRI biomarker of blood–brain barrier permeability
  • In this new analysis, the K2 coefficient of white matter was independently associated with increased microstructural white matter integrity and predicted infarct volume in women
  • These observations suggest sex-specific differences in microvascular integrity may contribute to the sex disparity in poststroke outcomes

Functional outcomes after acute ischemic stroke are worse in women than in men even after adjustment for age, antecedent disability, history of atrial fibrillation and rates of treatment with thrombolytic therapy. Two factors known to influence outcomes are the structural integrity of cerebral white matter and the permeability of the blood–brain barrier (BBB).

In previous research published in the Journal of Cerebral Blood Flow & Metabolism, Massachusetts General Hospital clinicians identified a novel association between worse functional outcomes after ischemic stroke and an MRI biomarker—the average BBB leakage rate in contralesional normal-appearing white matter (NAWM Κ2 coefficient). In addition, NAWM Κ2 was greater in women than in men.

In new research, Natalia S. Rost, MD, chief of the Stroke Division at Mass General and principal investigator of the Determinants of Incident Stroke Cognitive Outcomes and Vascular Effects on Recovery (DISCOVERY) study, and Mark R. Etherton, MD, PhD, assistant in the Department of Neurology, and colleagues used NAWM Κ2 to explore the etiology of the sex differences in stroke outcomes. In Stroke and Vascular Neurology, they report that in women with acute ischemic stroke (AIS), increased NAWM K2 was associated with increased infarct volume.

Study Details

The researchers retrospectively analyzed data on 105 men and 79 women who had participated in a prospective biomarker study after suffering ischemic stroke. The subjects presented within 9 hours of last known well and underwent brain MRI within the same timeframe.


  • As in the earlier study, NAWM Κ2 was significantly higher in women than men, despite no significant differences in age or stroke severity
  • In women, increased NAWM Κ2 was independently associated with increased NAWM apparent diffusion coefficient (ADC), a measure of microstructural white matter integrity
  • NAWM Κ2 predicted infarct volume in women
  • In both sexes, increased NAWM ADC independently predicted a decreased likelihood of a good functional outcome (modified Rankin scale score <2) at 90 days

Continued Scrutiny Needed

These findings suggest that increased NAWM K2 in women, a surrogate measure of BBB dysfunction, is associated with increased infarct size, which predisposes to worse long-term outcomes after stroke. Prospective trials are needed to further investigate the basis of sex-specific differences in white matter microvascular integrity.

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