Abstract: Objective To identify distinct frailty trajectories among middle-aged and older adults and to examine their association with the subsequent risk of incident cardiometabolic multimorbidity (CMM), utilizing data from the China Health and Retirement Longitudinal Study (CHARLS) prospective cohort. Methods This study included 7 523 participants aged ≥45 years who were free of CMM at the 2011 baseline. Frailty was assessed using the Fried phenotype across three waves (2011, 2013, and 2015). Latent class growth curve modeling was employed to identify distinct frailty trajectories. The primary outcome was incident CMM, ascertained in 2018 and 2020. The association between frailty trajectories and incident CMM was analyzed using Kaplan-Meier curves and Cox proportional hazards regression models. Results Three distinct frailty trajectories were identified: low-stable (n=4 550, 60.48%), moderate-slowly increasing (n=2 241, 29.79%), and high-rapidly increasing (n=732, 9.73%). During follow-up, 1,728 (22.97%) participants developed incident CMM, with the highest incidence rate observed in the high-rapidly increasing group (P<0.05). The Kaplan-Meier cumulative incidence curves diverged significantly among the three groups starting from the second year of follow-up (log-rank χ²=714.698, P<0.01). Compared to the low-stable trajectory group, the multivariable-adjusted hazard ratios (HRs) for incident CMM were 1.871 (95% CI: 1.675-2.090) for the moderate-slowly increasing group and 4.718 (95% CI: 4.121-5.401) for the high-rapidly increasing group. Subgroup analyses indicated that this association was more pronounced among females and individuals aged ≥60 years. Conclusion Individuals exhibiting a trajectory of persistently worsening or rapidly progressing frailty face a significantly elevated risk of developing CMM. Consequently, dynamic monitoring of frailty trajectories may be a valuable strategy for mitigating the burden of CMM in middle-aged and older populations.

Key words: Frailty, Cardiometabolic multimorbidity, Cohort studies, Latent class analysis, Risk factors, Fried frailty phenotype