Stroke risk associated with the interaction between composite dietary antioxidant index and heavy metals: A...

PurposeStroke remains the second leading global cause of death. Traditional risk factors and statistical models fail to fully clarify its pathogenesis or quantify the interactive effects of dietary antioxidants and heavy metals.MethodsBased on the data of 35,171 subjects from the National Health and Nutrition Examination Survey (NHANES) conducted in the United States between 2005 and 2018, this Cross-Sectional study constructed a Composite Dietary Antioxidant Index (CDAI) calibrated for the study population. By incorporating blood lead, blood cadmium, manganese elements, antioxidant nutrients and traditional stroke risk factors, five tree-based machine learning models were trained and validated. Meanwhile, with the application of the SHapley Additive exPlanations (SHAP), Restricted Cubic Spline (RCS) and piecewise regression analysis, this research analyzed the mechanism of the models, verified the non-linear correlations, and defined the protective threshold of the Composite Dietary Antioxidant Index as well as the recommendations for dietary protection.ResultsThe HistGradientBoosting model achieved the best performance (AUC=0.7771, 95%CI: 0.765-0.791). CDAI showed a non-linear protective effect against stroke, with an optimal threshold of 1.67 (95%CI: 1.45-1.89), above which stroke risk decreased by 40.2% (OR=0.60, 95%CI: 0.48-0.75, P<0.001). High blood lead (≥2.2 μg/dL) and cadmium (≥0.5 μg/L) significantly attenuated CDAI's protective effect by 146%-167%, while high CDAI may account for mitigated heavy metal-related stroke risk. The model showed stable performance in gender subgroups and adults aged <65 years.ConclusionThis cross-sectional study constructed an interpretable machine learning framework for stroke risk using NHANES data. The HistGradientBoosting model performed best. We identified a nonlinear protective threshold of CDAI at 1.67, above which stroke risk decreased by 40.2%. High blood lead and cadmium significantly attenuated the protective effect of CDAI, while manganese showed synergistic antioxidant protection. SHAP and RCS analyses confirmed robust interactions between CDAI and heavy metals. These findings provide evidence for personalized dietary antioxidant interventions in stroke prevention, especially for individuals with heavy metal exposure.