Controlled Attenuation Parameter and Gallstone Disease Risk: A Retrospective Cohort Study with Mediation Analysis and Longitudinal Trajectory Modeling, Emphasizing Gender-Specific Effects

Background: The association between the controlled attenuation parameter (CAP)-a noninvasive marker for hepatic steatosis-and gallstone disease (GSD) remains poorly understood. This study aimed to investigate the impact of CAP levels and their longitudinal trajectories on GSD risk and explore potential mediating pathways. Methods: A dynamic cohort of 6,308 adults without baseline GSD underwent serial health examinations in Ya'an, China, from January 2020 to April 2025. The statistical methods included multivariate Cox regression analysis, restricted cubic spline (RCS) analysis, and mediation analysis. For sensitivity analyses, we performed gender-stratified analysis, trial sequential analysis (TSA), cumulative risk curve plotting, and re-analysis after excluding individuals with baseline diseases. Among 412 participants with ≥ 3 CAP measurements, group-based trajectory modelling (GBTM) identified CAP patterns and related them to GSD incidence. Results: < 0.01, proportion of mediation = 27.49%). Conclusion: CAP is positively and linearly associated with GSD risk, particularly in women. Persistently high CAP levels confer a significantly elevated GSD risk. HDL-C is a significant mediator.