Prognostic value of Endothelial Activation and Stress Index (EASIX) in moderate-to-severe aortic stenosis patients: the ARISTOTLE cohort study

Q: What does this research mean for the field?

Higher Endothelial Activation and Stress Index (EASIX) is independently associated with an increased risk of all-cause mortality in patients with moderate-to-severe aortic stenosis. Novelty: ClaimNovelty.INCREMENTAL. Consensus alignment: ConsensusAlignment.NEUTRAL.

Zhenxia Zhang; Yiqi Zheng; Miaohong Li; Ziwei Zhou; Zhen Guo; Jiayuan Zhang; Xinyuan Chen; Han Wen; Zhenyu Xiong; Menghui Liu; Shaozhao Zhang; Yue Guo; Xinghao Xu; Li Ruijie; Xiaodong Zhuang; Xinxue Liao

doi:10.1186/s12872-026-06561-7

October 26, 2026BMC Cardiovascular DisordersOpen Access

Prognostic value of Endothelial Activation and Stress Index (EASIX) in moderate-to-severe aortic stenosis patients: the ARISTOTLE cohort study

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Why the study?

The Endothelial Activation and Stress Index (EASIX) is a validated marker of endothelial dysfunction, but its prognostic value in patients with aortic stenosis required further investigation.

Does an elevated Endothelial Activation and Stress Index (EASIX) predict all-cause and cardiovascular mortality in patients with moderate-to-severe aortic stenosis?

Key Points

To investigate the prognostic value of the Endothelial Activation and Stress Index (EASIX) for predicting mortality in patients with moderate-to-severe aortic stenosis.
Clinical study evaluating 817 patients with moderate-to-severe aortic stenosis (registered under NCT06069232) followed for a median duration of 31.17 months (IQR: 10.40–75.50 months).
Patients were stratified by an optimal EASIX cut-off value of 1.39 derived from the Youden index into low (< 1.39, N=461) and high (≥ 1.39, N=356) groups.
Associations between EASIX and mortality were analyzed using Kaplan–Meier curves, multivariable Cox regression models, and restricted cubic spline analyses.
Patients in the high EASIX group exhibited higher all-cause mortality (30.90% vs. 21.26%, p for log-rank = 0.039) and cardiovascular mortality (19.38% vs. 11.50%, p for log-rank = 0.022) compared to the low EASIX group.
Multivariable Cox regression demonstrated that high EASIX was associated with a 1.66-fold increased risk of all-cause mortality (HR 1.66, 95% CI 1.25–2.20, p = 0.001) and each log2 increase corresponded to a 24% increase in risk (HR 1.24, 95% CI 1.07–1.43, p = 0.004).
High EASIX was also linked to increased cardiovascular mortality (HR 2.06, 95% CI 1.41–3.01, p < 0.001), showing a linear dose-response relationship across all-cause mortality (p for nonlinear = 0.068).

Structured PICO

Does an elevated Endothelial Activation and Stress Index (EASIX) predict all-cause and cardiovascular mortality in patients with moderate-to-severe aortic stenosis?

P

Population

817 hospitalized adults (>18 years) with moderate-to-severe aortic stenosis (29.99% moderate, 70.01% severe) from the ARISTOTLE study across three academic medical centers in South China (October 2013 to March 2026), mean age 67.94 ± 13.08 years (median 69.00, IQR 61.00-77.00), 58.02% male. Key inclusion: echocardiographic evidence of moderate AS (3 m/s ≤ Vmax < 4 m/s, 20 mmHg ≤ MG < 40 mmHg, or 1.0 cm² < AVA ≤ 1.5 cm²) or severe AS (Vmax ≥ 4 m/s, MG ≥ 40 mmHg, or AVA ≤ 1.0 cm²), without prior history of aortic valve replacement (AVR) before enrollment. Key exclusions: missing baseline EASIX parameters, baseline platelet count >500 × 10⁹/L or <50 × 10⁹/L, eGFR < 15 ml/min/1.73 m², missing key covariates, or loss to follow-up.

I

Intervention

High Endothelial Activation and Stress Index (EASIX ≥ 1.39, n=356) or continuous log2-transformed EASIX, calculated at baseline after overnight fasting as: LDH (U/L) × creatinine (mg/dL) / platelet count (×10⁹/L).

C

Comparator

Low Endothelial Activation and Stress Index (EASIX < 1.39, n=461).

O

Outcome

All-cause mortality over a median follow-up of 31.17 months (IQR 10.40–75.50 months), assessed via death certificates, hospital records, or phone calls to patients or families.hard clinical

The Endothelial Activation and Stress Index (EASIX), calculated from routine laboratory parameters (LDH, creatinine, and platelets), independently predicts all-cause and cardiovascular mortality and provides incremental prognostic value in patients with moderate-to-severe aortic stenosis.

Limitations

Conventional methods for endothelial function assessment are limited by technical complexity, high cost, and suboptimal reproducibility
Potential immortal time bias due to the heterogeneous timing of AVR intervention during follow-up

Implication

High EASIX may stratify mortality risk in aortic stenosis; leaves open its incremental value for clinical decisions pending prospective validation.

Abstract

Endothelial dysfunction is a pivotal pathophysiological change in aortic stenosis (AS). The Endothelial Activation and Stress Index (EASIX) is a validated marker associated with endothelial dysfunction, with predictive value in prognosis of several diseases. However, the prognostic value of EASIX in AS patients requires further investigation. The study cohort comprised 817 moderate-to-severe AS patients. The optimal EASIX cut-off value was obtained by the Youden index, and patients were subsequently stratified accordingly. The correlation between EASIX and mortality was assessed by Kaplan–Meier curves, Cox regression and restricted cubic spline analyses. The incremental predictive value of EASIX was evaluated. Kaplan-Meier curves revealed higher all-cause mortality ( p for log-rank < 0.039) in high EASIX group. In multivariate Cox analysis, the high EASIX group exhibited a 1.66-fold greater all-cause mortality risk compared to the low EASIX group (HR 1.66, 95% CI 1.25–2.20, p = 0.001) and per log2 increase in EASIX was corresponding to a 24% elevated all-cause mortality risk (HR 1.24, 95% CI 1.07–1.43, p = 0.004). A significant linear correlation was observed between log2(EASIX) and all-cause mortality risk in the restricted cubic spline analysis ( p for nonlinear = 0.068). EASIX conferred additional prognostic information beyond the baseline risk model for predicting all-cause mortality. For patients with moderate to severe AS, increased EASIX is linked to an adverse prognosis. This study was registered in the Chinese Clinical Trials Registry. Registration Number: NCT06069232. Prognostic value of Endothelial Activation and Stress Index (EASIX) in moderate to severe aortic stenosis. The figure was created with BioGDP.com [1].

Discussion

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Cite This Study

Zhang et al. (2026) studied this question.

synapsesocial.com/papers/6ae13cba043bfbd63533255d https://doi.org/10.1186/s12872-026-06561-7

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Prognostic value of Endothelial Activation and Stress Index (EASIX) in moderate-to-severe aortic stenosis patients: the ARISTOTLE cohort study

Key Points

Structured PICO

Limitations

Implication

Abstract

Discussion

Cite This Study

Prognostic value of Endothelial Activation and Stress Index (EASIX) in moderate-to-severe aortic stenosis patients: the ARISTOTLE cohort study

Key Points

Structured PICO

Limitations

Implication

Abstract

Discussion

Cite This Study

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