Confounding by Pre-Morbid Functional Status in Studies of Apparent Sex Differences in Severity and Outcome of Stroke

Background and purpose: Several studies have reported unexplained worse outcomes after stroke in women but none included the full spectrum of symptomatic ischemic cerebrovascular events while adjusting for prior handicap.

Methods: Using a prospective population-based incident cohort of all transient ischemic attack/stroke (OXVASC [Oxford Vascular Study]) recruited between April 2002 and March 2014, we compared pre-morbid and post-event modified Rankin Scale score (mRS) in women and men and change in mRS score 1 month, 6 months, 1 year, and 5 years after stroke. Baseline stroke-related neurological impairment was measured with the National Institutes of Health Stroke Scale.

Results: Among 2553 patients (50.6% women) with a first transient ischemic attack/ischemic stroke, women had a worse handicap 1 month after ischemic stroke (age-adjusted odds ratio for mRS score, 1.35; 95% confidence interval, 1.12-1.63). However, women also had a higher pre-morbid mRS score compared with men (age-adjusted odds ratio, 1.58; 95% confidence interval, 1.36-1.84). There was no difference in stroke severity when adjusting for age and pre-morbid mRS (odds ratio, 1.10; 95% confidence interval, 0.90-1.35) and no difference in the pre-/poststroke change in mRS at 1 month (age-adjusted odds ratio, 1.00; 95% confidence interval, 0.82-1.21), 6 months, 1 year, and 5 years. Women had a lower mortality rate, and there was no sex difference in risk of recurrent stroke.

Conclusions: We found no evidence of a worse outcome of stroke in women when adjusting for age and pre-morbid mRS. Failure to account for sex differences in pre-morbid handicap could explain contradictory findings in previous studies. Properties of the mRS may also contribute to these inconsistencies.