Sex disparities in comorbidities, one-year functional outcome and mortality after ischemic stroke: a population-based...

Sex disparities in post-stroke prognosis have been reported, with women showing worse functional outcomes and higher mortality. However, whether these differences reflect a genuine biological disadvantage or are attributable to inadequate adjustment for comorbidities remains debated. We aimed to assess sex differences in one-year functional outcome and mortality after ischemic stroke by taking into consideration a broad set of comorbidities.

All cases of acute ischemic stroke were prospectively recorded using the population-based Dijon Stroke Registry, France (2017-2022). Demographics, vascular risk factors, stroke characteristics, and comorbidities across multiple domains were collected. Patients were follow-up at one-year. Sequential Cox and logistic regression models were constructed (unadjusted, age-adjusted, and fully adjusted) to assess the association between female sex and, respectively, all-cause mortality and poor functional outcome defined as a modified Rankin Scale (mRS) score of 3-6, or failure to return to the prestroke mRS score in patients with prestroke mRS >2.

1,361 patients were included of whom 718 were women (52.8%). Women were older (median age 83.4 vs. 75.0 years; p<0.001) and globally carried a lower burden of vascular risk factors and diseases, but a greater burden of other comorbidities. Stroke severity was also higher in women (median NIHSS score 5 vs. 3; p<0.001), whilst rates of acute revascularization therapy did not differ between sexes. In crude analyses, women had higher one-year mortality (32.3% vs. 27.2%; unadjusted HR=1.24, 95% CI 1.02-1.52; p=0.032) and worse functional outcome (59.8% vs. 48.3%; unadjusted OR=1.59; 95% CI 1.28-1.99, p<0.001). Adjustment for age alone abolished both associations (age-adjusted HR=0.90; 95% CI 0.73-1.10, p=0.29; age-adjusted OR=1.18, 95% CI 0.93-1.50, p=0.17). In fully adjusted models, no significant sex difference was observed for mortality (HR=0.78, 95% CI 0.60-1.03, p=0.08) or functional outcome (OR=1.15; 95% CI 0.93-1.59, p=0.38).

Sex differences in post-stroke outcomes were largely explained by confounding, with age as the primary driver. These findings suggest that female sex may not independently predict one-year mortality or functional outcome after ischemic stroke, and underline the need for identification and optimized management of age-related comorbidities in women as the key strategy to reduce disparities in post-stroke outcomes.