Bidirectional association between MASLD and cardiovascular disease mediated by insulin resistance in middle-aged and older Chinese adults

Metabolic dysfunction-associated steatotic liver disease (MASLD) and cardiovascular disease (CVD) frequently coexist and share common pathophysiological mechanisms, but whether their association is bidirectional and whether insulin resistance mediates this link remain poorly defined. We conducted two complementary longitudinal analyses using data from five waves of the China Health and Retirement Longitudinal Study (2011–2020), a nationally representative cohort of Chinese adults aged 45 years and older. The analytic cohorts comprised 5,193 participants for the MASLD-to-CVD analysis and 3,342 participants for the CVD-to-MASLD analysis after exclusions. MASLD was defined using the lipid accumulation product index combined with cardiometabolic risk factors, and CVD was ascertained via self-reported physician diagnosis. Multivariable logistic regression models with three sequential adjustments were employed to evaluate the bidirectional associations. Mediation analyses were performed to quantify the mediating role of the triglyceride-glucose-waist circumference (TyG-WC) index and the triglyceride-glucose-waist-to-height ratio (TyG-WHtR) index, two composite surrogate markers of insulin resistance. Subgroup and sensitivity analyses were conducted to test the robustness of the findings. Over a median follow-up of 9 years, baseline MASLD was associated with an increased risk of incident CVD after full adjustment (OR: 1.53, 95% CI: 1.32–1.78). Conversely, over a median follow-up of 4 years, baseline CVD was associated with an increased risk of incident MASLD (OR: 1.40, 95% CI: 1.09–1.79). TyG-WC and TyG-WHtR partially mediated the MASLD-to-CVD association, accounting for 46.15% and 42.16% of the total effect, respectively, whereas no significant mediation was observed in the reverse direction. Subgroup analyses revealed that marital status significantly modified the MASLD-to-CVD association (P for interaction = 0.040), while diabetes significantly modified the CVD-to-MASLD association (P for interaction = 0.025). Sensitivity analyses using alternative MASLD definitions and excluding events from different follow-up waves confirmed the robustness of the primary findings. MASLD and CVD exhibit a significant bidirectional association in middle-aged and older Chinese adults. TyG-WC and TyG-WHtR asymmetrically mediate only the MASLD-to-CVD direction, suggesting distinct pathophysiological mechanisms underlie each pathway. These findings highlight the importance of the cardiohepatic axis and support bidirectional screening and integrated management of both conditions, with particular attention to diabetic patients.