L-shaped association of plasma creatinine with frailty in oldest‑old: Evidence from a cross-sectional study of CLHLS

This study sought to identify key circulating hematological and biochemical indicators associated with frailty in the oldest-old and to investigate their interrelationships. Data from 2,434 participants aged ≥ 80 years (3,222 observations) were analyzed from the Chinese Longitudinal Healthy Longevity Survey (2008–2014). Frailty was assessed using a 50-item frailty index (FI). A panel of 14 hematological and biochemical markers was measured at each wave. Candidate markers were initially screened using univariate generalized linear mixed models (GLMMs), followed by further selection via a least absolute shrinkage and selection operator (LASSO) logistic regression model. The selected markers were then evaluated using multivariable GLMMs, adjusting for potential confounders. Nonlinear associations were assessed using restricted cubic splines (RCS). Of the 3,222 observations, 65.3% were classified as frail. LASSO identified albumin (ALB), creatinine (CREA) and malondialdehyde (MDA) emerged as the markers associated with frailty. RCS analyses indicated an L-shaped association between CREA and frailty with a statistical inflection point at 122 µmol/L, while ALB and MDA exhibited linear associations. In the adjusted GLMMs, lower CREA levels were associated with a higher likelihood of frailty when CREA levels were below 122 µmol/L (OR = 0.84, 95% CI: 0.76–0.91, P < 0.001), whereas CREA at or above 122 µmol/L showed no significant association with frailty (OR = 1.04, 95% CI: 0.95–1.14, P = 0.376). Meanwhile, lower ALB levels (OR = 0.90, 95% CI: 0.83–0.99, P = 0.015) and higher MDA levels (OR = 1.22, 95% CI: 1.11–1.34, P < 0.001) were associated with a higher likelihood of frailty. Circulating ALB, MDA and CREA levels were associated with frailty in Chinese adults aged ≥ 80 years. A nonlinear, L-shaped association was observed between CREA and frailty.