Bidirectional association between non-steatotic chronic liver disease and heart disease: the potential link of insulin resistance

Abstract Background Chronic liver disease (CLD) and heart disease (HD) are major contributors to global morbidity and mortality. Although increasing evidence supports close interactions between the liver and heart, population-based longitudinal data evaluating their bidirectional temporal relationship remain limited, particularly beyond metabolic dysfunction–associated steatotic liver disease (MASLD). This study aimed to investigate the bidirectional association between CLD, excluding steatotic liver disease, and HD, and to explore the potential mediating role of insulin resistance (IR) in a nationally representative cohort. Methods This longitudinal cohort study utilized data from five waves of the China Health and Retirement Longitudinal Study conducted between 2011 and 2020. Cox proportional hazards models were applied to examine the bidirectional associations between HD and CLD. Mediation analyses were performed to assess whether IR, measured by the triglyceride–glucose (TyG) index and the metabolic score for IR (METS-IR), mediated these associations. Multiple sensitivity and subgroup analyses were conducted to evaluate robustness. Results Among 6,230 participants free of HD at baseline, CLD was associated with a significantly increased risk of incident HD (HR:1.803, 95% CI 1.376–2.362). Conversely, among 6,917 participants without baseline CLD, HD was associated with a higher risk of developing CLD (HR: 2.303, 95% CI 1.813–2.924). These associations were consistent across predefined subgroups and sensitivity analyses. Mediation analyses indicated that the TyG index and the METS-IR partially mediated the association between HD and incident CLD but not the association between CLD and incident HD. Conclusion In this nationally representative longitudinal study, CLD and HD were bidirectionally associated among middle-aged and older adults. IR partially mediated the pathway from HD to CLD, suggesting asymmetric mechanisms underlying liver–heart interactions. These findings underscore the clinical relevance of the liver–heart axis and highlight the need for integrated strategies to prevent and manage liver and cardiovascular diseases in aging populations. Graphical Abstract