Chronic liver disease and stroke risk in middle-aged women: Evidence from a retrospective analysis of a prospective cohort study

BACKGROUND: The association between chronic liver disease and stroke risk remains inconclusive, particularly in prospective, community-based settings. Individuals aged 45-59 years represent a critical window of cardiometabolic transition that coincides with female perimenopause. Prospective evidence is limited regarding whether liver disease independently contributes to stroke risk during this vulnerable period. METHODS: We conducted a retrospective analysis of data from the China Health and Retirement Longitudinal Study (CHARLS), a nationally representative prospective cohort. Using 2011 baseline data, we included 14,662 participants aged ≥45 years after excluding individuals with a history of stroke at baseline or missing key variables. Guided by a priori hypotheses regarding cardiometabolic changes during perimenopause, we performed age- and sex-stratified analyses to assess the association between chronic liver disease and incident stroke. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). We additionally developed a stroke risk prediction model incorporating liver disease status and internally validated it using bootstrap resampling with 1,000 iterations. RESULTS: Among women aged 45-59 years, chronic liver disease was associated with an 81% higher risk of stroke (HR 1.81, 95% CI 1.05-3.13). This association was not observed in men of the same age (HR 1.15, 95% CI 0.63-2.08) or in women aged ≥60 years. The effect magnitude remained after stepwise adjustment for hypertension, diabetes, the activity of daily living (ADL) score, and other cardiovascular risk factors. In the female subgroup aged 45-59 years, a prediction model incorporating liver disease showed an area under the receiver operating characteristic curve (AUC) of 0.717 (95% CI 0.706-0.830) after bias correction using bootstrap resampling. CONCLUSION: Chronic liver disease is associated with an increased risk of stroke in women aged 45-59 years, and this association persisted after adjustment for traditional cardiovascular risk factors. Although interaction tests were not statistically significant, multidimensional sensitivity analyses supported the robustness of the association. These findings suggest that liver disease status may warrant consideration in cardiovascular risk assessment for middle-aged women.