Sex-Specific Patterns Of The Influence Of Age On Functional Outcome After Acute Ischemic Stroke.

Background: Age is a major determinant of stroke outcome, but few studies have investigated whether the effect of age differs between men and women. Methods: Analysis of all patients enrolled in a multicenter acute stroke trial (FAST-MAG) presenting with acute cerebral ischemia and treated without intravenous thrombolysis. Effects of age and sex were evaluated for: 1) disability or death (modified Rankin Scale, mRS, 2-6); 2) reduced stroke-related quality of life (Stroke Impact Scale, SIS < 80); and 3) mortality, unadjusted and adjusted for baseline NIHSS, ASPECTS, and 7 additional prognostic variables. Results: Among the 772 patients meeting entry criteria, age was 71.2, 44.0% were women, and presenting NIHSS 6.8. Overall, men were slightly younger than women (69.9 vs 73.0), without difference in initial NIHSS (6.4 vs 7.2), nor in 3m outcomes: mRS 2-6, 44.7% vs 50.2%, p=0.13; SIS<80, 44.6% vs 44.1%, p=0.90; mortality 9.5% vs 9.7%, p=0.92. However, the sexes differed in age-functional outcome patterns. Among women, there were U-shaped relationships between age and rates of both mRS 2-6 (Figure) and SIS <80. In contrast, among men, a much more attenuated U-shaped relationship was visualized, did not reach statistical significance. For both sexes, mortality showed a generally linear increase with age. Compared to those aged 40-64, mortality rates in the oldest old (age ≥85) were: women - HR 4.81 (95CI 0.98-23.39); men - HR 4.06 (95CI 1.17-14.14). Conclusions: The relationship between age and functional outcome in supportively treated acute cerebral ischemia patients differs between the sexes, with women but not men showing better outcomes in early senescence than either midlife or very late-life. This contrasting outcome profile may reflect sex-specific biological differences in ischemic stroke mechanism and neuroplasticity, cultural differences in social roles and support, or additional factors that merit further study.