Longitudinal trajectories of the C-reactive protein-triglyceride-glucose index and frailty progression in two nationwide prospective cohorts.
Abstract
Background
The C-reactive protein-triglyceride-glucose index is a novel biomarker reflecting combined cardiometabolic and inflammatory burdens. This dual-cohort study investigated relationships between longitudinal trajectories of this index and multidimensional frailty progression.
Methods
We analyzed data from the China Health and Retirement Longitudinal Study and the English Longitudinal Study of Aging. K-means clustering partitioned continuous longitudinal index measurements into distinct developmental trajectories. Frailty was evaluated using a 31-item index. After adjusting for covariates, multivariable linear regression, Cox proportional hazards, and linear mixed-effects models evaluated cross-sectional associations, incident risk, and dynamic accumulation velocity of frailty, respectively.
Results
The analysis included 3947 Chinese and 1431 English participants. Clustering identified consistently low, moderate, and high trajectories. Compared with the low trajectory, the high group exhibited a more severe baseline frailty score (Chinese cohort: β = 1.96, 95% confidence interval 1.03-2.91; English cohort: β = 2.42, 95% confidence interval 1.04-3.80). During follow-up, the high trajectory was independently associated with augmented incident frailty risk (Chinese cohort: hazard ratio 1.24, 95% confidence interval 1.03-1.49; English cohort: hazard ratio 1.42, 95% confidence interval 1.06-1.90). Furthermore, linear mixed-effects modeling revealed accelerated deficit accumulation over time in this high-risk group (Chinese cohort: β = 0.263, 95% confidence interval 0.074-0.451; English cohort: β = 0.330, 95% confidence interval 0.214-0.445). These effects remained robust across body mass index classifications.
Conclusions
Consistently high longitudinal trajectories of the C-reactive protein-triglyceride-glucose index serve as powerful, dynamic indicators of incident frailty and accelerated biological aging. Tracking this cumulative metabolic and inflammatory burden provides an accessible clinical strategy for early risk identification.