Sex Differences in Early Functional Outcomes After Acute Stroke: A Retrospective Cohort Study at a United Kingdom Tertiary Stroke Centre

Abstract

Background Women are frequently reported to have poorer functional outcomes after stroke than men, but women with stroke are also often older and may have greater functional impairment before the index event. We examined sex differences in early functional outcomes after acute stroke and assessed whether any observed association persisted after accounting for age, pre-stroke disability, stroke severity, stroke subtype, and relevant comorbidities. Materials and methods We conducted a retrospective cohort study of 1,252 consecutive adults admitted with acute ischaemic stroke or primary intracerebral haemorrhage to a tertiary stroke centre in the United Kingdom between June and December 2023. The primary outcome was functional status at hospital discharge across the full modified Rankin Scale (mRS; 0-6). Cumulative-link ordinal logistic regression was used to examine the association between female sex and worse discharge mRS. Sequential models adjusted for age, pre-stroke mRS, admission National Institutes of Health Stroke Scale (NIHSS) score, stroke subtype, and prespecified comorbidities. Sensitivity analyses included patients with ischaemic stroke only, patients with pre-stroke mRS 0-2, dichotomised functional outcomes, and in-hospital mortality. Results The cohort comprised 601 women (48.0%) and 651 men (52.0%). Women were older than men (median 77 years (interquartile range (IQR) 66-85) vs 72 years (IQR 62-81), p<0.001) and had greater pre-stroke functional impairment (median pre-stroke mRS 2 (IQR 1-3) vs 1 (IQR 0-2), p<0.001). Discharge mRS of 3-6 occurred in 405 women (67.4%) and 391 men (60.1%; unadjusted odds ratio (OR) 1.37, 95% confidence interval (CI) 1.09-1.73; p=0.008). In the primary ordinal analysis, female sex was associated with worse discharge mRS before adjustment (common OR 1.34, 95% CI 1.10-1.64; p=0.003). The association attenuated after adjustment for age (OR 1.13, 95% CI 0.92-1.37; p=0.247) and moved close to the null after additional adjustment for pre-stroke mRS (OR 0.95, 95% CI 0.77-1.16; p=0.604). The fully adjusted common OR was 0.94 (95% CI 0.76-1.16; p=0.568). Sensitivity analyses produced similar findings. Conclusions Women had poorer unadjusted functional status at discharge after acute stroke, but this association was substantially attenuated after accounting for age and pre-stroke functional status. Female sex was not independently associated with worse early functional outcome after multivariable adjustment. These findings emphasise the importance of premorbid disability and baseline case mix when interpreting apparent sex differences in early stroke outcomes.