Regulating effect of genistein on the association of endothelial activation and stress index with atherosclerotic cardiovascular disease risk: a cross-sectional study of the NHANES database

The aim of this study is to assess the associations of urinary genistein and endothelial activation and stress index (EASIX) with 10-year atherosclerotic cardiovascular disease (ASCVD) risk. This cross-sectional analysis employed data obtained from the National Health and Nutrition Examination Survey (NHANES). Weighted univariable and multivariable logistic regression models examined EASIX-ASCVD risk correlations, with odds ratio and 95% confidence interval [OR (95%CI)] as effect measures. The potential interactions were explored between EASIX and genistein on 10-year ASCVD risk using additive and multiplicative interaction analyses. The relationships of EASIX and 10-year ASCVD risk were further assessed at different genistein levels. Subgroup analyses examined age, BMI, diabetes, hypertension, and dyslipidemia categories. Totally, 4478 eligible participants were stratified into low-risk (n = 2157) and high-risk (n = 2321) ASCVD groups. Elevated levels of EASIX (OR = 1.35, 95% CI 1.18-1.54), EASIX_median ≥ 0.427 (OR = 1.40, 95% CI 1.14-1.73), EASIX_RCS ≥ 0.434 (OR = 1.45, 95% CI 1.18-1.77), EASIX_quartile (0.325-0.427, OR = 1.48, 95% CI 1.05-2.07; 0.427-0.567, OR = 1.51, 95% CI 1.08-2.10; ≥ 0.567, OR = 2.08, 95% CI 1.57-2.77), and log2(EASIX) (OR = 1.32, 95% CI 1.19-1.46) were associated with higher odds of 10-year ASCVD. Low genistein levels presented no significant correlation with 10-year ASCVD risk. The multiplicative interaction between EASIX and genistein levels was significant. When genistein levels < 54.105 µg/g, the connections between elevated EASIX levels and higher 10-year ASCVD risk were established in subgroups of age < 60 years, BMI ≥ 25 kg/m², non-diabetes, hypertension, and dyslipidemia. Elevated EASIX levels correlated with a higher 10-year ASCVD risk. Whether genistein modulates this association requires further validation, which may have potential implications for ASCVD prevention strategies in the general population.