Red Blood Cell-Derived Inflammatory Markers and Frailty Risk: Evidence from Two Observational Studies

Background Red blood cell distribution width (RDW), hemoglobin-to-RDW ratio (HRR) and RDW-to-albumin ratio (RAR) are three red blood cell–derived inflammatory markers. Inflammation plays a critical role in frailty, but the association between RDW, RAR, and HAR and frailty is unclear. Methods This cross-sectional study incorporated datasets from the Affiliated Hospital of Qingdao University and the National Health and Nutrition Examination Survey (NHANES, 2003–2018). In the NHANES dataset, weighted multivariable logistic regression models were employed to examine the relationship between RDW, HRR, RAR, and frailty. Restricted cubic spline analysis was employed to assess the nonlinear trend. Subgroup analyses, interaction and sensitivity analysis were also conducted. In the cohort study, the association was validated using multivariate logistic regression models. Results In the NHANES dataset, 11,016 participants were included. Higher RDW, higher RAR, and lower HRR were significantly associated with increased frailty risk [adjusted odds ratio (aOR) 1.52, 95% CI 1.42–1.62; aOR 4.12, 95% CI 3.51–4.84; aOR 0.62, 95% CI 0.59–0.65; all p  < 0.001]. Linear associations were observed between RDW, RAR and frailty, whereas HRR demonstrated a nonlinear relationship, with a turning point at 11.475. In the cohort study, higher HRR had a significantly lower frailty risk (aOR 0.71, 95% CI 0.54–0.93, p  = 0.012), whereas higher RAR was associated with increased frailty risk (aOR 2.57, 95% CI 1.08–6.15, p  = 0.034). Conclusions A significant association exists between RDW, HRR, RAR, and frailty risk. RDW, HRR, and RAR may aid in the early identification of frailty.