Associations of the Endothelial Activation and Stress Index with breast cancer prevalence and mortality based on NHANES 2001 to 2018

This study investigated the association between the Endothelial Activation and Stress Index (EASIX) and both the prevalence and mortality of breast cancer (BC). Further, it explored the potential mediating role of the Systemic Inflammation Response Index (SIRI). Data were obtained from the National Health and Nutrition Examination Survey 2001 to 2018. Weighted logistic regression models were used to examine the association between EASIX and BC prevalence, while mediation analysis evaluated the contribution of SIRI. Weighted Cox proportional hazards models estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for BC mortality, and Kaplan–Meier curves compared survival across EASIX levels. Restricted cubic spline regression assessed linearity, and subgroup analyses tested consistency across covariates. Among 21,329 participants, 593 BC cases were identified. Each 1-unit increase in EASIX was associated with a 39% higher BC risk (odds ratios [ORs] = 1.39, 95% CI: 1.07–1.82, P = .016). Compared with the lowest tertile (T1), the risk was elevated in T2 (OR = 1.61, 95% CI: 1.15–2.26, P = .006) and markedly higher in T3 (OR = 3.07, 95% CI: 2.28–4.14, P < .001). SIRI showed a modest but significant mediating effect, explaining 2.26% of the association ( P = .034). No significant interactions were detected. In Cox models, each 1-standard deviation increase in EASIX was associated with a 56% higher risk of all-cause mortality (HR = 1.56, 95% CI: 1.47–1.65, P < .001) and a 104% higher risk among BC patients (HR = 2.04, 95% CI: 1.40–2.98, P < .001). Compared with T1, all-cause mortality increased by 59% in T2 (HR = 1.59) and more than 3-fold in T3 (HR = 3.11). BC-specific mortality was also higher in T3 (HR = 1.16, 95% CI: 1.05–1.27, P = .012). Restricted cubic spline analyses confirmed a linear positive association between EASIX and both BC prevalence and mortality. Elevated EASIX was significantly associated with higher BC prevalence and mortality, partly mediated by systemic inflammation. EASIX may serve as a valuable biomarker for risk assessment and prognosis in BC.