Higher remnant cholesterol inflammatory index is associated with increased frailty risk in the UK Biobank

Frailty is a major public health concern associated with adverse outcomes. The remnant cholesterol inflammatory index (RCII), a novel biomarker integrating lipid metabolism and systemic inflammation, has been proposed as an indicator of adverse health outcomes. However, little is known about its relationship with frailty. The study aimed to investigate the longitudinal association between RCII and frailty risk in the UK Biobank.

A total of 402,850 participants from the UK Biobank were included at baseline. RCII was calculated as remnant cholesterol (RC, mg/dL) × C-reactive protein (CRP, mg/L)/10, and frailty was assessed using the Fried frailty phenotype. Cox proportional hazards regression models were applied to evaluate the association between baseline RCII and incident frailty. Restricted cubic spline (RCS) analyses were used to explore potential nonlinear relationships. To capture cumulative exposure, we additionally analyzed 12,895 participants with the same measurements to examine the relationship between cumulative RCII and frailty risk.

During a median follow-up of 15.58 years, 2,327 participants (0.58%) developed frailty. Frailty incidence increased progressively across RCII quartiles, from 0.3% in Q1 to 0.9% in Q4 (P for trend <0.001). In the fully adjusted model, each standard deviation increase in RCII was associated with a 11% higher risk of frailty (HR = 1.11, 95% CI: 1.07-1.15). RCS analysis indicated a nonlinear positive relationship, with frailty risk rising more sharply at higher RCII levels. In the 11.68-year subset analysis, 497 participants (3.85%) suffered frailty. Participants in Q4 of cumulative RCII had a significantly higher risk of frailty compared with those in Q1 (HR = 2.34, 95% CI: 1.52-3.60). Subgroup analyses suggested that the association between RCII and frailty was generally consistent across subgroups (P for interaction > 0.05).

Higher RCII levels, both at baseline and cumulatively, are associated with an increased risk of frailty. RCII may be a promising biomarker for frailty risk stratification and a potential target for early prevention in aging populations.