Associations between the triglyceride glucose-body roundness index and frailty trajectory in populations with Cardiovascular–Kidney–Metabolic syndrome: A nationwide prospective cohort study

Abstract Background Frailty is a key intervention target for older adults with cardiovascular-kidney-metabolic (CKM) syndrome. Evidence suggests that the triglyceride glucose (TyG) index and body roundness index (BRI) are associated with frailty; however, the predictive value of their combination (TyG-BRI) remains unclear. Methods We analyzed data from 3,687 middle-aged and older adults with CKM syndrome in the China Health and Retirement Longitudinal Study (CHARLS, 2011 to 2020). The frailty index serving as the outcome variable was constructed based on 30 multidimensional health deficit items. The primary exposure, the TyG-BRI index, was calculated as the product of the TyG index and the BRI. Latent growth mixture modeling (LGMM) was employed to identify frailty trajectories. Multivariable adjusted logistic regression was conducted to explore the association between TyG-BRI and frailty trajectories. Subgroup analyses were performed to elucidate the interactions among these factors further. Results Three distinct frailty trajectories emerged: pre-frailty to frailty deterioration (18.8%), persistent frailty (53.7%), and pre-frailty transition to health (27.4%). The highest TyG-BRI quartile was associated with a higher risk of pre-frailty to frailty deterioration than the lowest quartile (OR = 2.229, 95% CI: 1.137–4.367). Subgroup analysis indicated a significant interaction between age and the association of TyG-BRI with frailty trajectories (P = 0.041), suggesting the need for age-specific intervention strategies. Conclusion The TyG-BRI may be an early metabolic biomarker for pre-frailty to frailty deterioration in individuals with CKM syndrome, particularly in older adults. These findings suggest a critical intervention window targeting metabolic dysregulation during the pre-frailty stage.