Associations of dietary inflammatory and antioxidant indices with mortality in adults with cardiovascular–kidney–metabolic syndrome: A mediation analysis

Cardiovascular–kidney–metabolic (CKM) syndrome carries high mortality risk. Whether A Body Shape Index (ABSI), Weight-Adjusted Waist Index (WWI), Systemic Inflammation Response Index (SIRI), and Systemic Immune-Inflammation Index (SII) mediate the associations of Dietary Inflammatory Index (DII) and Composite Dietary Antioxidant Index (CDAI) with mortality in this population remains unknown. We included 21,420 adults with CKM from National Health and Nutrition Examination Survey 1999 to 2018 with mortality follow-up through December 31, 2019. DII and CDAI were calculated from 24-hour dietary recalls. Survey-weighted Cox proportional hazards regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for all-cause and cardiovascular mortality, modeling DII and CDAI as continuous variables and tertiles. Restricted cubic splines and 2-piecewise Cox models assessed nonlinearity. Mediation analyses evaluated indirect effects through ABSI, WWI, SIRI, and SII. During follow-up, 3532 all-cause and 1103 cardiovascular deaths occurred. In fully adjusted models, higher DII was associated with increased all-cause mortality (HR per 1-unit increase: 1.06, 95% CI: 1.04–1.09) and cardiovascular mortality (HR: 1.06, 95% CI: 1.02–1.10); the highest versus lowest tertile was associated with HRs of 1.27 (95% CI: 1.16–1.39) and 1.27 (95% CI: 1.08–1.49), respectively. Higher CDAI was associated with lower all-cause and cardiovascular mortality; the highest versus lowest tertile showed HRs of 0.84 (95% CI: 0.77–0.93) and 0.78 (95% CI: 0.65–0.93), respectively. Nonlinearity was observed between CDAI and all-cause mortality ( P  = .017). The percentage mediated by ABSI, WWI, SIRI, and SII ranged from approximately 4% to 9% for the association with all-cause mortality. In adults with CKM, DII and CDAI were independently associated with mortality outcomes, and ABSI, WWI, SIRI, and SII mediated a modest proportion of the association with all-cause mortality. Further studies are needed to confirm these findings.