Cardiometabolic multimorbidity trajectories and incident non-steatotic chronic liver disease in middle-aged and older adults.

BACKGROUND AND AIMS: Cardiometabolic multimorbidity (CMM) may increase the risk of chronic liver disease, but evidence on non-steatotic chronic liver disease (NSCLD) remains limited. METHODS AND RESULTS: We used data from the China Health and Retirement Longitudinal Study and included adults aged 45 years or older. Participants were classified into 4 mutually exclusive CMM trajectory groups: H→M, H→C, H→M→CMM, and H→C→CMM. Cox proportional hazards models were used to examine the associations between CMM trajectories and incident NSCLD. Potential heterogeneity by percent predicted peak expiratory flow (PEF% predicted) and the potential mediating role of frailty were further assessed. Among 8310 participants, incident NSCLD increased across trajectory groups from 6.36% in H→M to 15.43% in H→C→CMM; frailty prevalence increased from 16.98% to 32.20% (both P < 0.001). Kaplan-Meier curves differed significantly across trajectories (log-rank P < 0.0001). Associations varied by PEF% predicted (adjusted P for interaction = 0.0025). In the low PEF% predicted stratum, adjusted HRs were 2.48 for H→C, 1.99 for H→M→CMM, and 2.34 for H→C→CMM versus H→M. Frailty mediated 4.82% of the observed association. CONCLUSIONS: CMM trajectories were associated with incident NSCLD in middle-aged and older adults. These associations varied by respiratory function and appeared stronger in participants with lower PEF% predicted. Frailty accounted for a modest proportion of the observed association.