Abstract
Cardiovascular-kidney-metabolic (CKM) syndrome is a systemic condition driven by inflammation. The red blood cell distribution width-to-albumin ratio (RAR) has emerged as a novel marker of systemic inflammation, but its prognostic value in CKM remains unclear. We analyzed 9135 participants from National Health and Nutrition Examination Survey 2007 to 2016 with mortality data obtained from the National Death Index. Weighted Cox proportional hazards models assessed the association between RAR and mortality. Generalized additive models, time-dependent receiver operating characteristic curves, and Fine-Gray competing risk models were used for further evaluation. Over a median follow-up of 91.95 months, 987 deaths occurred, including 241 cardiovascular deaths. Based on an optimal cutoff (RAR = 3.33), participants were stratified into higher and lower RAR groups. The weighted Cox proportional hazards model revealed that individuals with higher RAR had significantly increased risks of all-cause mortality (hazard ratio 2.30, 95% confidence interval [CI] 1.95-2.70) and cardiovascular mortality (hazard ratio 3.26, 95% CI 2.40-4.42). Generalized additive models demonstrated a positive association between RAR and mortality. The main findings remained consistent in the sensitivity analyses. The area under the curve values for predicting all-cause mortality at 1, 3, 5, and 10 years were 0.756, 0.717, 0.708, and 0.695, respectively; the corresponding area under the curves for cardiovascular mortality were 0.708, 0.729, 0.737, and 0.714, respectively. Furthermore, even after accounting for noncardiovascular deaths as competing risk factors, The Fine-Gray model revealed that RAR was an independent predictor of cardiovascular mortality (subdistribution hazard ratio 1.68, 95% CI 1.38-2.04). Elevated RAR independently increases the risk of all-cause and cardiovascular mortality in patients with CKM stages 1 to 4.