Abstract / Summary
Cardiovascular-kidney-metabolic (CKM) syndrome is a complex multisystem disorder driven by the interlinked pathophysiological processes of metabolic dysregulation and chronic inflammation, yet lacks reliable clinical biomarkers. The ratio of red blood cell distribution width to albumin concentration (RAR) is an integrative biomarker, reflecting inflammatory and nutritional pathways, with validated predictive capacity for diverse cardiovascular outcomes. However, the association between RAR and the stages of CKM syndrome has not been well characterized. This study aimed to evaluate this association. This study included participants from two observational studies: the National Health and Nutrition Examination Survey (NHANES, 1999–2018) and the UK Biobank (UKB, 2006–2010). We assessed the associations between RAR and CKM syndrome stages using multinomial logistic regression models, multivariate logistic regression models, multivariate Cox proportional hazards regression models, and restricted cubic splines. The restricted cubic spline analysis was specifically employed to investigate the linear and nonlinear relationships between RAR and CKM syndrome stages. A total of 142,191 participants from NHANES ( n = 32,068) and the UK Biobank ( n = 110,123) cohorts were included in this study. Elevated RAR levels were significantly associated with increased CKM syndrome stages and incident CVDs. Cross-sectional analyses showed that each standard deviation increase in RAR was associated with a 47% and 23% greater risk of advanced CKM stages in NHANES (OR = 1.47, 95% CI: 1.42–1.54) and the UK Biobank (OR = 1.23, 95% CI: 1.21–1.25), respectively (all p < 0.001). Longitudinal analyses revealed elevated RAR predicted increased risks of incident CVDs (per 1-SD increase: HR = 1.12, 95% CI: 1.10–1.14), AF, CHD, HF, PAD, and STROKE (all p < 0.001). The RAR index serves as a robust, stage-dependent biomarker for higher CKM stages and CVD incidence. Its strong association with advanced CKM stages and incident cardiovascular events, particularly in stages 2–3, suggests potential utility for risk stratification of CKM stage severity and for guiding early cardiovascular intervention strategies. Not applicable.