Background
Stroke remains a leading cause of death and disability worldwide. Women face unique stroke risks due to a combination of well-established risk factors, under-recognized social-psychological influences, and female-specific reproductive factors. Understanding the relative impact of these categories is crucial to tailoring effective prevention strategies.
Aims
This prospective cohort study aimed to quantify the population attributable fractions (PAFs) for stroke associated with distinct risk factor profiles among women, and to investigate how these risks vary across different age strata.
Methods
The study analyzed data from 239,200 women enrolled in the UK Biobank. Following the framework established by the Lancet Women and Cardiovascular Disease Commission, stroke risk factors were categorized into three groups: eight well-established traditional risk factors (such as hypertension and smoking), four social-psychological risk factors (including low social support and high stress), and 11 reproductive factors (such as age at menarche and menopause, parity, and hormone therapy use).
A Cox proportional hazards regression model with multiple comparisons correction was employed to assess associations between these risk factors and incident stroke, including its subtypes (ischemic and hemorrhagic stroke). Population attributable fractions were calculated to estimate the proportion of stroke cases attributable to each individual risk factor, each risk factor category, and all risk factors combined. Analyses were stratified by age groups to explore age-related disparities.
Results
During a median follow-up period of 13.8 years, 4,580 women (1.9%) experienced a first-ever stroke. Hypertension emerged as the leading individual risk factor, with a PAF of 23.3% (95% confidence interval [CI]: 20.1% to 26.4%), meaning nearly one quarter of strokes could be attributed to high blood pressure in this cohort.
Assuming multiplicative effects, the eight well-established risk factors together explained 32.8% of stroke cases. Social-psychological factors accounted for 15.2%, and reproductive factors for 6.3%. The combined overall PAF for all risk factors was 47.6% (95% CI: 47.6% to 47.7%) under multiplicative assumptions and 40.2% (95% CI: 40.1% to 40.2%) under additive assumptions.
Age-stratified analyses revealed that women aged 60 to 65 years had the highest PAFs for overall risk factors (51.9%) and well-established risk factors (37.0%). For reproductive factors, the highest attributable fractions were observed among women aged 60-65 years (9.2%) and those aged 65 years or older (4.5%). This highlights the significant impact of reproductive history on stroke risk particularly in postmenopausal women.
Discussion
Conventional modifiable risk factors, especially hypertension, remain the most significant contributors to stroke risk among women. However, social-psychological factors — such as chronic stress, social isolation, and low socioeconomic status — show substantial influence and are often under-recognized in clinical practice. Additionally, reproductive factors unique to women, including hormonal changes and reproductive history, also contribute a meaningful portion of stroke risk.
These findings emphasize the importance of a comprehensive approach to stroke prevention that goes beyond traditional cardiovascular risk management. Addressing social determinants of health and incorporating women’s reproductive history into risk assessments can enhance identification of high-risk individuals.
Implications for Prevention
Effective stroke prevention in women requires integrated, targeted strategies tailored across the lifespan. This includes aggressive management of hypertension and other conventional risk factors, alongside interventions aimed at improving social-psychological well-being and addressing adverse reproductive health profiles.
Healthcare providers should consider screening for social stressors and reproductive risk factors during clinical evaluations. Public health policies aimed at reducing social disparities and supporting women’s reproductive health can further reduce stroke burden.
Conclusion
While well-established risk factors contribute the most to stroke burden in women, the significant roles of social-psychological and reproductive factors should not be overlooked. Integrated prevention strategies that holistically address these diverse risk factors are urgently needed to protect cardio-cerebrovascular health in women throughout their lives.
References
Sun W, Hou L, Wu J, Shan S, Song P. Population attributable fractions of established, social-psychological and reproductive risk factors for stroke among women: evidence from UK Biobank. Int J Stroke. 2025 Aug 2:17474930251365865. doi: 10.1177/17474930251365865. Epub ahead of print. PMID: 40751569.