Abstract
Cardiometabolic Syndrome (CMS) is associated with increased risks of cardiovascular disease, type 2 diabetes mellitus, and all-cause mortality. The Weight-Adjusted Waist Circumference Index (WWI) has emerged as a novel metric for assessing obesity and its health implications. To investigate the relationship between WWI and mortality in CMS patients, considering the mediating role of inflammatory markers. The study analyzed the National Health and Nutrition Examination Survey (NHANES) data from 2003 to 2018 and identified 6506 patients with CMS. WWI was calculated as the square root of waist circumference (cm) divided by weight (kg). Mortality data were correlated with the National Death Index (NDI). Cox regression models, adjusted for demographic and clinical covariates, assessed the effect of WWI on all-cause and cause-specific mortality. Finally, the role of inflammatory markers in the relationship between WWI and mortality was explored using mediation analysis. The study observed a positive linear association between WWI and all-cause, cardiovascular, and diabetes-related mortalities among CMS patients. After adjusting for demographic and clinical confounders, WWI remained a significant predictor of mortality. Mediation analysis revealed that inflammatory markers, particularly the neutrophil and systemic immune-inflammation index (SII), significantly mediated the relationship between WWI and all-cause mortality. WWI is an independent predictor of mortality in CMS patients, with inflammation potentially linking obesity to mortality risk. These findings may inform clinical risk assessment and management strategies for CMS.