Population attributable fractions of established, social-psychological and reproductive risk factors for stroke among women: evidence from UK Biobank

Stroke is a leading cause of death and disability worldwide, with women facing unique risks due to a combination of well-established, under-recognized, and female-specific factors. This prospective cohort study aimed to quantify the population attributable fractions (PAFs) of stroke with distinct risk factor profiles, and to explore disparities across age stratas. Data were from 239,200 women recruited in the UK Biobank. Following the framework established by the Lancet women and cardiovascular disease Commission, stroke risk factors were sorted into three categories, including eight well-established risk factors, four social-psychological risk factors, and 11 reproductive factors. Cox regression model with correction of multiple comparisons was used to assess their associations with incident stroke and its subtypes. PAFs were calculated to estimate the attributable stroke burden for individual risk factors, each risk factor category, and all risk factors combined. Age-stratified analyses were further conducted. During a median follow-up of 13.8 years, 4580 (1.9%) women developed incident stroke. Hypertension served as the leading individual risk factor (PAF 23.3%, 95% confidence interval [CI] 20.1%, 26.4%). Under the assumption of multiplicative effect, well-established risk factors accounted for 32.8% of stroke cases, followed by social-psychological factors (15.2%) and reproductive factors (6.3%). The overall PAF (95% CI) of total stroke with all risk factors combined was 47.6% (47.6%, 47.7%) or 40.2% (40.1%, 40.2%) with multiplicative or additive effect. Across the age groups, the highest total stroke PAFs for overall risk factors (51.9%) and well-established risk factors (37.0%) were observed among women aged 60-65 years. For reproductive factors, the highest PAFs were observed among women aged 60-65 (9.2%) and ≥65 years (4.5%). While the conventional risk factors contributed to the greatest stroke burden, the potential benefit of addressing issues related to unfavorable social-psychological conditions and adverse reproductive profiles should not be neglected. Integrated and targeted prevention strategies are in urgent need to protect women's cardio-cerebrovascular health throughout the lifespan.