Abstract
BACKGROUND: Life's Essential 8 (LE8) is a comprehensive cardiovascular health (CVH) metric that is associated with chronic diseases. This study aimed to investigate the association between LE8 and diabetic retinopathy (DR) and the mediating role of depression in this association. METHODS: We analyzed cross-sectional data from 3,815 adults with diabetes mellitus from the National Health and Nutrition Examination Survey (NHANES) (1999-2020). LE8 scores (0-100) were calculated based on diet, physical activity, nicotine exposure, sleep health, body mass index (BMI), blood lipid levels, blood glucose levels, and blood pressure. DR was diagnosed using retinal imaging or self-reports. Depression was assessed using the Patient Health Questionnaire-9 (PHQ-9). Weighted logistic regression and mediation analysis were performed. In addition, machine learning (Shapley additive explanation [SHAP]) was used to explain the importance ranking of variables. RESULTS: Weighted logistic regression models revealed a significant negative association between LE8 scores and the risk of DR. The LE8 score had strong, dose-dependent protective effects against DR, with each 10-point increase in the score being associated with a 2% reduction in the risk of DR (odds ratio [OR] = 0.98, P < 0.0001) across adjusted models. A threshold effect was observed at the LE8 score of 73.12. The protective effect of the LE8 score was significant below this threshold (OR1 = 0.98, P < 0.0001), whereas it was diminished above this threshold (OR2 = 1.06, P = 0.097). Mediation analysis indicated that PHQ-9 scores mediated 13.66% of the total effect of LE8 (P < 0.0001). SHAP analysis showed that blood glucose levels (35.5% importance) had the greatest impact on risk prediction, followed by modifiable behaviors such as physical activity (18.0%) and sleep health (13.5%). CONCLUSIONS: LE8 scores are negatively associated with the risk of DR in US adults with diabetes mellitus, and this association is partially mediated by depressive symptoms. Longitudinal studies are warranted to validate causality and elucidate the underlying mechanisms. Interventions targeting both metabolic and mental health may reduce the disease burden of DR.