Sex-specific differences in white matter microvascular integrity after ischaemic stroke.

Background and purpose: Functional outcomes after ischaemic stroke are worse in women, despite adjusting for differences in comorbidities and treatment approaches. White matter microvascular integrity represents one risk factor for poor long-term functional outcomes after ischaemic stroke. The aim of the study is to characterise sex-specific differences in microvascular integrity in individuals with acute ischaemic stroke. Methods: A retrospective analysis of subjects with acute ischaemic stroke and brain MRI with diffusion-weighted (DWI) and dynamic-susceptibility contrast-enhanced (DSC) perfusion-weighted imaging obtained within 9 hours of last known well was performed. In the hemisphere contralateral to the acute infarct, normal-appearing white matter (NAWM) microvascular integrity was measured using the K2 coefficient and apparent diffusion coefficient (ADC) values. Regression analyses for predictors of K2 coefficient, DWI volume and good outcome (90-day modified Rankin scale (mRS) score <2) were performed. Results: 105 men and 79 women met inclusion criteria for analysis. Despite no difference in age, women had increased NAWM K2 coefficient (1027.4 vs 692.7×10-6/s; p=0.006). In women, atrial fibrillation (ß=583.6; p=0.04) and increasing NAWM ADC (ß=4.4; p=0.02) were associated with increased NAWM K2 coefficient. In multivariable regression analysis, the K2 coefficient was an independent predictor of DWI volume in women (ß=0.007; p=0.01) but not men. Conclusions: In women with acute ischaemic stroke, increased NAWM K2 coefficient is associated with increased infarct volume and chronic white matter structural integrity. Prospective studies investigating sex-specific differences in white matter microvascular integrity are needed.

Diffuse microvascular dysfunction and loss of white matter integrity predict poor outcomes in patients with acute ischemic stroke.

We sought to investigate the relationship between blood-brain barrier (BBB) permeability and microstructural white matter integrity, and their potential impact on long-term functional outcomes in patients with acute ischemic stroke (AIS). We studied 184 AIS subjects with perfusion-weighted MRI (PWI) performed <9 h from last known well time. White matter hyperintensity (WMH), acute infarct, and PWI-derived mean transit time lesion volumes were calculated. Mean BBB leakage rates (K2 coefficient) and mean diffusivity values were measured in contralesional normal-appearing white matter (NAWM). Plasma matrix metalloproteinase-2 (MMP-2) levels were studied at baseline and 48 h. Admission stroke severity was evaluated using the NIH Stroke Scale (NIHSS). Modified Rankin Scale (mRS) was obtained at 90-days post-stroke. We found that higher mean K2 and diffusivity values correlated with age, elevated baseline MMP-2 levels, greater NIHSS and worse 90-day mRS (all p < 0.05). In multivariable analysis, WMH volume was associated with mean K2 ( p = 0.0007) and diffusivity ( p = 0.006) values in contralesional NAWM. In summary, WMH severity measured on brain MRI of AIS patients is associated with metrics of increased BBB permeability and abnormal white matter microstructural integrity. In future studies, these MRI markers of diffuse cerebral microvascular dysfunction may improve prediction of cerebral tissue infarction and functional post-stroke outcomes.

Elevated ischemic stroke risk among women living with HIV infection.

OBJECTIVE: To determine if the greater risk of ischemic stroke observed in women living with HIV infection (WLWH) compared with HIV-uninfected women persists after accounting for both traditional and sex-specific stroke risk factors. METHODS: We performed an observational cohort study of WLWH (n = 1214) and demographics-matched HIV-uninfected women (n = 12 041) seen between 1996 and 2011 at two tertiary care hospitals in Boston. We used Cox proportional hazards regression analyses to model time to ischemic stroke, adjusting first for demographics and traditional stroke risk factors and then for sex-specific stroke risk factors, including menopause and estrogen use. We also constructed demographics-adjusted Cox models to identify HIV-related risk factors associated with ischemic stroke among WLWH. RESULTS: The incidence of ischemic stroke was higher among WLWH compared with HIV-uninfected women [incidence rate ratio 2.39, 95% confidence interval (CI) 1.62-3.43]. After adjusting for demographics and traditional stroke risk factors, HIV infection was associated with almost twice the risk of ischemic stroke (hazard ratio 1.93, 95% CI 1.31-2.85). The association of HIV with ischemic stroke persisted after inclusion of sex-specific stroke risk factors in the model (hazard ratio 1.89, 95% CI 1.28-2.81). Among WLWH, longer duration of antiretroviral therapy was associated with lower ischemic stroke risk (hazard ratio 0.86 per year, 95% CI 0.76-0.96). CONCLUSION: The increased risk of ischemic stroke among WLWH compared with HIV-uninfected women persisted after adjusting for both traditional and sex-specific stroke risk factors. Further investigation into the mechanisms of elevated stroke risk among WLWH, including immunologic factors, will be key for developing targeted preventive strategies for this at-risk population.