Interaction between genistein and the endothelial activation and stress index in relation to estimated 10-year atherosclerotic cardiovascular disease risk classification.

BACKGROUND: The Endothelial Activation and Stress Index (EASIX) has been proposed as a marker of endothelial stress and may be associated with atherosclerotic cardiovascular disease (ASCVD) risk. Whether urinary genistein modifies this association remains unclear. METHODS: Multivariable logistic regression examined the association between EASIX and estimated 10-year ASCVD risk classification. Effect modification by urinary genistein (<54.105 vs. ≥ 54.105 μg/g) was assessed using interaction terms and stratified analyses. Restricted cubic splines (RCS) evaluated dose-response relationships. RESULTS: In the fully adjusted model, higher EASIX was independently associated with increased ASCVD risk (OR per unit increase = 1.407; 95% CI: 1.208-1.640; P < 0.001). A significant multiplicative interaction between EASIX and genistein was observed (OR = 1.66; 95% CI: 1.17-2.35; P = 0.005). Stratified analysis showed that this adverse association was slightly attenuated in the higher genistein group (OR = 1.360; 95% CI: 1.066-1.736; P = 0.015) compared to the lower group (OR = 1.397; 95% CI: 1.202-1.624; P < 0.001). RCS analyses showed a non-linear S-shaped association in the lower-genistein group (P nonlinear = 0.020), whereas a predominantly linear relationship was observed in the higher-genistein group (P nonlinear = 0.108). CONCLUSIONS: Higher EASIX was associated with elevated estimated 10-year ASCVD risk classification, and this association differed across urinary genistein strata. These findings should be interpreted as hypothesis-generating.