Composite dietary antioxidant index with hepatic indices for predicting mortality in cardiovascular-kidney-metabolic syndrome: Integrated analysis of a nationwide cohort study using machine learning approaches.
Higher Composite Dietary Antioxidant Index is associated with reduced all-cause and CVD mortality in CKM patients, while elevated hepatic indices correlate significantly with increased mortality risk, and both serve as effective predictors for CKM risk stratification.
Key Findings
Results
Participants in the highest CDAI quartile had a significantly lower risk of all-cause mortality compared to the lowest quartile in CKM patients.
Hazard ratio of 0.717 (95% CI: 0.611–0.841; P < .0001) in the fully adjusted model
Data derived from the US National Health and Nutrition Examination Survey (NHANES) 2001–2018
Analysis used multivariate Cox regression with full covariate adjustment
Restricted cubic spline analysis confirmed a significant inverse association between CDAI and all-cause mortality
Results
Participants in the highest CDAI quartile had a significantly lower risk of CVD mortality compared to the lowest quartile.
The highest CDAI quartile was associated with a 23.1% reduction in CVD mortality risk
Restricted cubic spline analysis confirmed a significant inverse association between CDAI and CVD mortality
Kaplan-Meier curve analysis also showed an inverse association between higher CDAI and CVD mortality
Results
Elevated hepatic indices were associated with increased all-cause and CVD mortality risk in CKM patients.
Hepatic indices examined included Fatty Liver Index, NAFLD Fibrosis Score (NFS), AST to Platelet Ratio Index, and Fibrosis-4 Index (FIB-4)
Kaplan-Meier curve analysis showed hepatic fibrosis indices (FIB-4, NFS, and AST to Platelet Ratio Index) were positively associated with mortality
Both all-cause and CVD mortality risk increased with elevated hepatic index levels
Results
The protective effect of CDAI on mortality was partially mediated through reduced hepatic steatosis but was independent of the liver fibrosis pathway.
Mediation analysis was used to assess pathways linking CDAI to mortality outcomes
CDAI's protective effect was independent of the liver fibrosis pathway
Hepatic steatosis (as reflected by the Fatty Liver Index) partially mediated the association between CDAI and mortality
Results
The Light Gradient Boosting Machine algorithm demonstrated optimal performance among machine learning approaches for predicting advanced CKM stages.
Multiple machine learning approaches were compared for predicting advanced CKM staging
Light Gradient Boosting Machine outperformed other tested models
Key predictors of advanced CKM staging included advanced age, hepatic indices (NFS, FIB-4, and Fatty Liver Index), and vitamin E levels
Results
Both CDAI and hepatic indices were identified as effective predictors for CKM risk stratification.
CDAI serves as a comprehensive measure of overall antioxidant capacity of the diet
Hepatic indices reflect steatosis and fibrosis burden relevant to metabolic dysfunction-associated steatotic liver disease
The study integrated Cox regression, survival analysis, mediation analysis, and machine learning to assess predictive value
Data spanned NHANES survey cycles from 2001 to 2018
What This Means
This research suggests that eating a diet rich in antioxidants—measured by a scoring tool called the Composite Dietary Antioxidant Index (CDAI)—is linked to lower risks of death from all causes and from heart disease among people with cardiovascular-kidney-metabolic (CKM) syndrome, a cluster of conditions involving heart disease, kidney disease, and metabolic disorders like obesity and diabetes. Using data from a large, nationally representative US health survey collected between 2001 and 2018, researchers found that people with the highest antioxidant diet scores had about a 28% lower risk of dying from any cause and roughly a 23% lower risk of dying from cardiovascular disease compared to those with the lowest scores.
The study also found that liver health markers—specifically indices that reflect liver fat accumulation and scarring (fibrosis)—are strongly linked to mortality risk in CKM patients. Higher levels of liver fat and fibrosis scores were associated with greater risk of death. Importantly, the protective effect of a high-antioxidant diet appeared to work partly by reducing liver fat, but not through the liver fibrosis pathway, suggesting these are distinct biological mechanisms. Using machine learning, the researchers also identified that age, liver health scores, and vitamin E levels were among the most important factors for predicting who has advanced CKM disease.
This research suggests that dietary antioxidant intake and liver health markers could be useful tools for identifying CKM patients at higher risk of death and for monitoring disease progression. The findings highlight the potential importance of diet quality—particularly antioxidant-rich foods—in managing CKM syndrome, and point to liver health as a key factor in understanding how these conditions lead to serious outcomes.
Yang Z, Song S, Li Y. (2026). Composite dietary antioxidant index with hepatic indices for predicting mortality in cardiovascular-kidney-metabolic syndrome: Integrated analysis of a nationwide cohort study using machine learning approaches.. Medicine. https://doi.org/10.1097/MD.0000000000050319