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 (10(9)/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.