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

Q: What are the key findings of this study?

Higher EASIX was independently associated with increased odds of elevated estimated 10-year ASCVD risk (OR 1.407), an association that was slightly attenuated in those with higher urinary genistein.

Q: What is the clinical evidence from this study?

Study design: Cross-Sectional. Population: Atherosclerotic cardiovascular disease (ASCVD) risk (n=4478). Intervention: Endothelial Activation and Stress Index (EASIX) vs. Lower EASIX. Primary outcome: Elevated estimated 10-year ASCVD risk classification (≥7.5%) (OR 1.407, 95% CI 1.208-1.640, p=<0.001).

Q: What does this research mean for the field?

Higher Endothelial Activation and Stress Index (EASIX) is associated with an elevated 10-year atherosclerotic cardiovascular disease risk, an effect that is slightly attenuated in individuals with higher urinary genistein levels. Novelty: ClaimNovelty.INCREMENTAL. Consensus alignment: ConsensusAlignment.NEUTRAL.

Q: What question did this study set out to answer?

To determine the association between the Endothelial Activation and Stress Index (EASIX) and estimated 10-year atherosclerotic cardiovascular disease (ASCVD) risk classification, and to evaluate potential effect modification by urinary genistein.

Xinru Guo; Yijie Lin; Shumei Mi; Yuqi Yin

doi:10.1371/journal.pone.0356477

August 19, 2026PLoS ONEOpen Access

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

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Key result

Higher EASIX links to ~41% greater odds of elevated 10-year ASCVD risk, attenuated by genistein.

OR 1.407
95% CI 1.208-1.640
P<0.001
n=4,478

Figures

Why the study?

EASIX has been proposed as a marker of endothelial stress and may be associated with ASCVD risk, but whether urinary genistein modifies this association remains unclear.

Does higher EASIX score associate with elevated estimated 10-year ASCVD risk classification in adults without prior CVD, and is this modified by urinary genistein?

Key Points

To determine the association between the Endothelial Activation and Stress Index (EASIX) and estimated 10-year atherosclerotic cardiovascular disease (ASCVD) risk classification, and to evaluate potential effect modification by urinary genistein.
Analyzed cross-sectional data from 4,478 participants classified into low (<7.5%, n = 2,157) and high (≥7.5%, n = 2,321) 10-year ASCVD risk categories.
Conducted multivariable logistic regression adjusting for age, educational level, marital status, poverty-to-income ratio, physical activity, BMI, hypolipidemic drugs, CRP, and uric acid.
Assessed effect modification and non-linear dose-response relationships using urinary genistein strata (<54.105 vs. ≥54.105 μg/g), interaction terms, and restricted cubic splines.
Higher continuous EASIX was independently associated with increased estimated 10-year ASCVD risk in the fully adjusted model (OR per unit increase = 1.407; 95% CI: 1.208–1.640; P < 0.001).
A significant multiplicative interaction occurred between EASIX and genistein (OR = 1.66; 95% CI: 1.17–2.35; P = 0.005), showing a slightly blunted effect 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).
Restricted cubic spline analyses demonstrated a non-linear S-shaped relationship in the lower-genistein group (P nonlinear = 0.020), but a predominantly linear relationship in the higher-genistein group (P nonlinear = 0.108).

Study Design

Type

Cross-Sectional (n=4,478)

Structured PICO

Does higher EASIX score associate with elevated estimated 10-year ASCVD risk classification in adults without prior CVD, and is this modified by urinary genistein?

P

Population

4,478 adults aged 40-79 years without a history of cardiovascular disease from the NHANES database, evaluated for estimated 10-year ASCVD risk.

E

Exposure

Endothelial Activation and Stress Index (EASIX) score and urinary genistein levels

O

Outcome

Estimated 10-year ASCVD risk classification (<7.5% vs ≥7.5%) calculated using the 2013 ACC/AHA pooled cohort equationsurrogate

Main Result

Odds Ratio: 1.407 (95% CI 1.208–1.64)

p-value: p=<0.001

Higher EASIX scores are associated with an elevated estimated 10-year ASCVD risk, an association that is slightly attenuated in individuals with higher urinary genistein levels.

Limitations

Cross-sectional design precludes the establishment of temporal relationships or causal inferences.
Urinary genistein was measured at a single time point and may primarily reflect recent dietary exposure.
The primary outcome was an estimated 10-year ASCVD risk classification rather than observed cardiovascular events.
Residual confounding from unmeasured or incompletely measured dietary and lifestyle factors cannot be completely excluded.
Subgroup analyses were exploratory, and no correction for multiple testing was performed.
Exclusion of nearly 60% of otherwise eligible participants because of unavailable urinary genistein measurements may have introduced selection bias.
The clinical utility and incremental predictive value of EASIX beyond established ASCVD risk factors were not assessed.

Implication

Hypothesis-generating for EASIX-ASCVD link with genistein modification; prospective studies needed before clinical consideration.

Abstract

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.

Discussion

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Cite This Study

Guo et al. (2026) conducted a cross-sectional in Atherosclerotic cardiovascular disease (ASCVD) risk (n=4,478). Endothelial Activation and Stress Index (EASIX) vs. Lower EASIX was evaluated on Elevated estimated 10-year ASCVD risk classification (≥7.5%) (OR 1.407, 95% CI 1.208-1.640, p=<0.001). Higher EASIX was independently associated with increased odds of elevated estimated 10-year ASCVD risk (OR 1.407), an association that was slightly attenuated in those with higher urinary genistein.

synapsesocial.com/papers/6a895f41ca7ade938187dc34 https://doi.org/10.1371/journal.pone.0356477

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

Figures

Key Points

Study Design

Structured PICO

Main Result

Limitations

Implication

Abstract

Discussion

Cite This Study

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

Figures

Key Points

Study Design

Structured PICO

Main Result

Limitations

Implication

Abstract

Discussion

Cite This Study

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