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

Abstract

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. 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. 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). 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.