Associations of longitudinal C-reactive protein-triglyceride-glucose and its adiposity-related derivatives with frailty onset and progression in cardiovascular-kidney-metabolic syndrome stages 0-3: a national prospective cohort study.

BACKGROUND

Frailty is a pivotal geriatric syndrome within the cardiovascular-kidney-metabolic (CKM) spectrum. This study systematically evaluated the association of longitudinal C-reactive protein-triglyceride-glucose index (CTI) combined with diverse adiposity markers-including body mass index (BMI), waist circumference (WC), waist-to-height ratio (WHtR), weight-adjusted-waist index (WWI), body roundness index (BRI), conicity index (CI), and relative fat mass (RFM)-with frailty incidence and progression in CKM stages 0-3.

METHODS

Using the China Health and Retirement Longitudinal Study (2011-2018) data, we established a baseline cohort (n = 4950) and a landmark cohort (n = 3596) to evaluate baseline and cumulative CTI-adiposity effects, respectively. Outcomes included incident frailty and frailty index (FI) progression. Logistic regression, mixed-effects, and weighted quantile sum (WQS) models quantified associations.

RESULTS

In the landmark cohort, 670 frailty cases occurred. Longitudinal CTI-adiposity indices significantly outperformed baseline assessments. Participants in the highest cumulative exposure or trajectory categories exhibited markedly elevated risks, with CTI-RFM emerging as the strongest predictor (Incident OR: 2.34 and 1.89, respectively). High-exposure groups also showed accelerated annual FI progression (CTI-RFM β: 0.29/0.35) and a greater likelihood of following a high-risk FI trajectory (CTI-RFM OR: 3.54/2.53). WQS analysis identified adiposity as the predominant driver of frailty, followed by glycemia and inflammation. Crucially, CTI-RFM consistently provided superior risk reclassification across both internal and external comparisons.

CONCLUSION

Dynamic monitoring of CTI-adiposity derivatives, particularly CTI-RFM, provides refined frailty risk stratification in CKM stages 0-3. This underscores the necessity of integrating metabolic-inflammatory-adiposity control for preventive interventions in the CKM spectrum.