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 K_(2) coefficient and apparent diffusion coefficient(ADC)values.Regression analyses for predictors of K_(2) 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 K_(2) coefficient(1027.4 vs 692.7×10^(-6)/s;p=0.006).In women,atrial fibrillation(β=583.6;p=0.04)and increasing NAWM ADC(β=4.4;p=0.02)were associated with increased NAWM K_(2) coefficient.In multivariable regression analysis,the K_(2) coefficient was an independent predictor of DWI volume in women(β=0.007;p=0.01)but not men.Conclusions In women with acute ischaemic stroke,increased NAWM K_(2) 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.