Association of the Endothelial Activation and Stress Index with Mortality in Critically Ill Patients with Chronic Obstructive Pulmonary Disease: A Retrospective Cohort Study.
In view of the established role of endothelial dysfunction in the pathophysiology of chronic obstructive pulmonary disease (COPD), the Endothelial Activation and Stress Index (EASIX), a validated biomarker of endothelial injury, warrants investigation as a potential prognostic tool. We therefore investigated its association with outcomes in critically ill COPD patients.
This retrospective cohort study analyzed data from critically ill patients with COPD in the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. The exposure was log2(EASIX) (continuous or tertiles). The outcomes were 28‑, 60‑, and 90‑day all‑cause mortality. Cox regression was primarily used to assess the association, and multiple additional approaches were employed to verify its robustness.
A total of 1534 patients were included. Kaplan‑Meier survival curves showed significantly lower survival probabilities in higher EASIX tertiles (log‑rank p < 0.01 for all comparisons). Multivariable Cox regression confirmed that higher log2(EASIX) was independently associated with increased 28‑, 60‑, and 90‑day all‑cause mortality, with adjusted hazard ratios (HRs) of 1.87 (95% CI: 1.31-2.58), 1.83 (95% CI: 1.33-2.52), and 1.84 (95% CI: 1.36-2.50), respectively (all p < 0.01). Restricted cubic spline analysis indicated a linear relationship, and the association was robust across clinical subgroups. Sensitivity analyses in the fully imputed cohort confirmed linearity at 28 and 60 days but revealed a U‑shaped relationship at 90 days, with a nadir at log2(EASIX) = 0.56 (original EASIX = 1.47) and a HR of 0.74 (95% CI: 0.58-0.96). The E‑value of 2.96 (lower confidence bound 1.88) indicates robustness to unmeasured confounding.
Higher EASIX is independently associated with 28-day and 60-day mortality in critically ill COPD patients, whereas the 90-day relationship appears more complex. These findings suggest that EASIX may aid early risk assessment, pending external validation.
This retrospective cohort study analyzed data from critically ill patients with COPD in the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. The exposure was log2(EASIX) (continuous or tertiles). The outcomes were 28‑, 60‑, and 90‑day all‑cause mortality. Cox regression was primarily used to assess the association, and multiple additional approaches were employed to verify its robustness.
A total of 1534 patients were included. Kaplan‑Meier survival curves showed significantly lower survival probabilities in higher EASIX tertiles (log‑rank p < 0.01 for all comparisons). Multivariable Cox regression confirmed that higher log2(EASIX) was independently associated with increased 28‑, 60‑, and 90‑day all‑cause mortality, with adjusted hazard ratios (HRs) of 1.87 (95% CI: 1.31-2.58), 1.83 (95% CI: 1.33-2.52), and 1.84 (95% CI: 1.36-2.50), respectively (all p < 0.01). Restricted cubic spline analysis indicated a linear relationship, and the association was robust across clinical subgroups. Sensitivity analyses in the fully imputed cohort confirmed linearity at 28 and 60 days but revealed a U‑shaped relationship at 90 days, with a nadir at log2(EASIX) = 0.56 (original EASIX = 1.47) and a HR of 0.74 (95% CI: 0.58-0.96). The E‑value of 2.96 (lower confidence bound 1.88) indicates robustness to unmeasured confounding.
Higher EASIX is independently associated with 28-day and 60-day mortality in critically ill COPD patients, whereas the 90-day relationship appears more complex. These findings suggest that EASIX may aid early risk assessment, pending external validation.
Authors
Li Li, Li Li, Liang Liang, Zhang Zhang, Dai Dai, Yang Yang, Lyu Lyu, Wang Wang
View on Pubmed