Inflammation and abnormal glucose-lipid metabolism are critical for population stratification toward progressive frailty in Cardiovascular-Kidney-Metabolic syndrome

Abstract

Background: Chronic inflammation and dysregulated glucose-lipid metabolism are key contributors to frailty progression, though their combined impact remains unclear. This study investigates the association between the remnant cholesterol inflammatory index (RCII) and the triglyceride-glucose (TyG) index with frailty progression across different stages of Cardiovascular-Kidney-Metabolic (CKM) syndrome.

Methods: Data from the China Health and Retirement Longitudinal Study were analyzed, with frailty status assessed using the frailty index.

Results: A total of 5,790 participants were included, with 2,012 developing frailty over 7 years of follow-up. Both higher TyG index (adjusted hazard ratio [HR] 1.18, 95 % confidence interval [CI] 1.08 to 1.29) and RCII (aHR 1.24, 95 % CI 1.13 to 1.35) were independently associated with increased frailty progression risk, particularly in the early stages of CKM. Notably, cumulative RCII and TyG index values were linked to frailty risk in individuals with persistently advanced CKM stages and those progressing to advanced CKM stages.

Conclusions: RCII, TyG, and their cumulative values are independent risk factors for frailty progression, with a synergistic effect on risk stratification, especially in the early stages of CKM. Cumulative biomarker monitoring in early CKM stages, coupled with proactive, multi-modal interventions, may enable precise population stratification and prevent frailty progression.

Keywords: Cardiovascular-Kidney-Metabolic; Frailty; Inflammation; Population stratification; Remnant cholesterol inflammatory index; Triglyceride-glucose.