Association of Inflammatory Burden Index with All-Cause and Cardiovascular Mortality Among Individuals with Cardiovascular-Kidney-Metabolic Syndrome

BackgroundCardiovascular-Kidney-Metabolic (CKM) syndrome, as defined by the American Heart Ass ociation (AHA) in 2023, encompasses pathophysiological interconnections among the cardiovascular, rena l, and metabolic systems, which collectively lead to multi-organ dysfunction. The Inflammatory Burden In dex (IBI), a newly developed inflammatory marker, has an unclarified association with mortality in the con text of CKM syndrome. Our study aimed to explore the relationships between IBI and mortality in this pop ulation, with the goal of facilitating early clinical intervention. Methods6,091 NHANES (1999-2018) participants with CKM syndrome were analyzed. Weighted Cox models and Restricted cubic spline (RCS) analysis assessed IBIs association with all-cause and cardiovasc ular mortality. We tested proportional hazards (Schoenfeld residuals), model performance (ROC curves), a nd confounding (subgroup/stratified analyses). ResultsIBI independently predicted mortality after full adjustment: All-cause mortality: HR=1.13, 95% C I:1.05-1.21, *p*=0.002;Cardiovascular mortality: HR=1.35, 95% CI:1.21-1.51, *p*<0.001.The fully ad justed model (AUC>0.8) showed optimal predictive performance. IBI exhibited non-linear ("U-shaped" all-cause, "J-shaped" cardiovascular) mortality relationships. The highest IBI quartile (Q4) robustly predicted cardiovascular death (HR=1.77, 95% CI:1.18-2.67).Subgroup and stratified analyses revealed that male s ex, advanced age, smoking, and high-risk chronic kidney disease (CKD) were synergistic factors exacerbating the association between IBI and all-cause mortality risk, while female sex, smoking, diabetes, and meta bolic abnormalities were synergistic factors exacerbating the association with cardiovascular mortality risk. ConclusionOur study is the first to demonstrate that IBI exhibits significant non-linear associations with both all-cause and cardiovascular mortality in patients with CKM syndrome and serves as a risk factor for t hese patients. Monitoring the Inflammatory Burden Index holds important clinical significance for assessin g mortality risk in individuals with CKM syndrome.