Dietary inflammatory potential and dietary quality in relation to advanced cardiovascular-kidney-metabolic syndrome and mortality risk: traditional and machine learning-based analysis

BACKGROUND: Cardiovascular-kidney-metabolic (CKM) syndrome, recently defined by the American Heart Association, represents a complex interplay of cardiovascular, renal, and metabolic disorders linked by shared inflammatory pathways. This study investigates Dietary Inflammatory Index (DII) and Healthy Eating Index (HEI) influence CKM progression and mortality, while exploring the mediating role of inflammatory markers and identifying key dietary predictors. METHODS: We analyzed 19,742 National Health and Nutrition Examination Survey participants (1999–2020) with complete dietary and clinical data. DII and HEI were calculated from 24-hour dietary recalls. Advanced CKM syndrome (stages 3–4) and all-cause mortality were primary outcomes. We employed (1) multivariable logistic/cox regression to assess DII/HEI-outcomes associations; (2) mediation analysis for inflammatory markers; (3) machine learning with SHAP analysis to identify critical dietary components. RESULTS: Higher DII was associated with advanced CKM syndrome (OR = 1.046, 95%CI: 1.001–1.092) and mortality (HR = 1.096, 95%CI: 1.046–1.149), while HEI showed protective effects (OR = 0.993, 95%CI: 0.988–0.999; HR = 0.993, 95%CI: 0.987–0.999). Cluster analysis revealed the pro-inflammatory low-quality diet (Pattern D) had 35% higher CKM risk (OR = 1.351) and 41% greater mortality risk (HR = 1.411) versus anti-inflammatory high-quality diet. Neutrophils mediated 26.50% (DII) and 24.48% (HEI) of advanced CKM syndrome, 11.16% (DII) and 14.72% (HEI) of mortality risk. Machine learning identified vitamin B6, vitamin D, niacin, monounsaturated fatty acids (MUFA), polyunsaturated fatty acids (PUFA) emerged as critical predictors for CKM staging and mortality risk. CONCLUSION: Higher DII scores are associated with increased risks of advanced CKM syndrome and all-cause mortality, while higher HEI scores are associated with reduced risks. Neutrophils were identified as a key inflammatory mediator in these associations. Vitamin B6, vitamin D, niacin, MUFA, PUFA emerged as key dietary factors, suggesting precision nutrition strategies for CKM management.