Sex-difference in stroke outcome in young people in relation to haemoglobin level

Introduction: Worse stroke outcome in women than men is partly explained by differences in age, aetiology and pre-morbid disability, but lower haemoglobin (Hb) could also contribute, particularly at younger ages. We therefore aimed to explore whether lower Hb levels might correlate with stroke outcome in younger women. Methods: In a population-based cohort (Oxford Vascular study) we studied all patients aged ≤55 years with a stroke between 1st April 2002 and 31st March 2023 and face-to-face follow up at one-month. We used ordinal multi-regression models to assess one-month post-stroke modified Rankin Scale score (mRS), and the change from pre-morbid status (ΔmRS), in relation to Hb levels (continuous and by WHO definition of anaemia) and sex, with adjustment for age, vascular comorbidities, pre-morbid mRS and medications. Results: Among 348 patients (mean/SD age = 45.4/8.01; 149 female, 42.8%) anaemia was associated with a higher post-stroke mRS (adjusted OR=3.18, 95%CI =1.66-6.06, p<0.001) and greater ΔmRS (adjusted OR=2.72, 1.39-5.30, p=0.003). These trends were consistent in both women and men analysed separately and in those with ischaemic stroke only. Women had higher one-month mRS compared with men (adjusted OR=1.58,1.05-2.38, p=0.03), but further adjustment for the sex difference in Hb (mean/SD Hb: 13.12/1.64 g/dl in women vs 15.13/1.36 in men, p<0.001) removed the effect of sex (fully adjusted OR=1.07, 0.65-1.74, p=0.80). The higher ΔmRS in women (adjusted OR=1.57, 1.04-2.38, p=0.03) also diminished after adjustment for Hb (fully adjusted OR=1.04; 0.64-1.70, p=0.87). Conclusion: Low Hb levels are associated with a poor outcome after stroke and could be a clinically important determinant of the sex-difference in stroke outcome at younger ages. If confirmed, these findings further justify correction of iron-deficient anaemia at the population level and in situations where stroke risk is increased.