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. 2025 Apr 23:12:1554429.
doi: 10.3389/fnut.2025.1554429. eCollection 2025.

Relationship between endothelial activation and stress index and all-cause mortality in rheumatoid arthritis patients: a moderating effect of gamma-glutamyl transferase

Wenjing Chang #  1 , Zhiming Zhao #  1 , Linlin Ma #  2 , Le Lu  1 , Chunli Liu  1 , Mengdi Hu  1 , Wei Shang  1
Affiliations

Relationship between endothelial activation and stress index and all-cause mortality in rheumatoid arthritis patients: a moderating effect of gamma-glutamyl transferase

Wenjing Chang et al. Front Nutr. .

Abstract

Aim: This study aimed to explore the relationship between endothelial activation and stress index (EASIX) and all-cause mortality in patients with rheumatoid arthritis (RA), and to further examine whether gamma-glutamyl transferase (GGT) influences this association.

Methods: We included 2,543 participants with RA from the National Health and Nutrition Examination Survey (NHANES) in this retrospective cohort study. The study outcome was considered to be all-cause mortality. EASIX and GGT levels were measured at baseline (study enrollment) using laboratory data from NHANES. EASIX was divided into two groups based on its median: ≥0.476 and <0.476, while GGT was divided into two groups based on its median: ≥23 U/L and <23 U/L. EASIX was calculated using the formula, lactate dehydrogenase (LDH, U/L) × creatinine (mg/dL)/platelet count (109/L), based on the baseline laboratory measurements. Weighted multivariate Cox regression models were used to assess the associations between EASIX and GGT with the risk of all-cause mortality. Importantly, a moderated analysis of GGT (moderator) was conducted to examine the relationship between EASIX and all-cause mortality among patients with RA. Additionally, subgroup analysis was performed based on age, duration of arthritis, diabetes, and hypertension.

Results: A total of 867 individuals developed all-cause mortality over a mean follow-up period of 122.86 ± 3.29 months. After fully adjusting for potential confounding factors, higher EASIX (≥0.476) was positively associated with all-cause mortality (hazard ratio [HR] = 1.42; 95% confidence interval [CI]: 1.18-1.73). However, the association between GGT and all-cause mortality was not significant (p > 0.05). Moderated analysis revealed that higher GGT levels strengthened the correlation between EASIX and all-cause mortality among patients with RA (p = 0.013). The association between EASIX and the risk of all-cause mortality varied depending on GGT levels. The subgroup analysis revealed that GGT moderated the relationship between EASIX and all-cause mortality among RA patients aged 60 years or older (p = 0.007), with a history of arthritis lasting more than 5 years (p = 0.040), or diagnosed with diabetes (p = 0.009) or hypertension (p = 0.016). Competing risks analysis accounting for cardiovascular mortality yielded consistent results (subdistribution hazard ratio [sHR] = 1.39; 95% CI: 1.15-1.69), further supporting the primary findings.

Conclusion: High EASIX was positively associated with all-cause mortality in patients with RA, and this association was significantly enhanced by higher GGT levels.

Keywords: all-cause mortality; endothelial activation and stress index; gamma-glutamyl transferase; moderating effect; rheumatoid arthritis.

PubMed Disclaimer

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Flowchart of participant inclusion.
Figure 2
Figure 2
Conditional effect of endothelial activation and stress index on all-cause mortality across different gamma-glutamyl transferase concentrations.
See this image and copyright information in PMC

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