Early Dysregulation of Angiopoietin-1 and -2 as a Predictor of Mortality in Critically Ill Burn Patients.

Abstract

Shock-induced endothelial dysfunction plays a critical role in burn pathophysiology, with endothelial glycocalyx layer (EGL) degradation promoting systemic inflammation, vascular instability, and multi-organ failure. The Angiopoietin-TIE2 axis, particularly the Angiopoietin-1 (Ang-1) and Angiopoietin-2 (Ang-2) balance, regulates endothelial function; elevated Ang-2 and a high Ang-2/1 ratio are linked to worse outcomes in critical illness. While well-documented in sepsis and trauma, effects of burn-induced Angiopoietin dysregulation remains unclear. This study evaluates Ang-1, Ang-2, and the Ang-2/1 ratio as biomarkers of endothelial dysfunction and predictors of 30-day mortality in burn patients. In this prospective study, 62 adult burn patients were enrolled (January 2021-November 2024), with serum Ang-1 and Ang-2 measured via ELISA on post-burn day 1 (PBD1). Of 62 patients, 52 were analyzed; 78.05% of survivors and 90.91% of non-survivors were male. Median age was 45 (survivors) vs. 54 years (non-survivors, p = 0.139). Non-survivors trended toward burns >20% TBSA (72.73% vs. 41.46%, p = 0.093). Ang-1 was lower in non-survivors (3.96 vs. 7.97 ng/mL, p<0.001), predicting early mortality (AUROC 0.82) with a cut-off of 4.825 ng/mL and decreased mortality risk (OR 0.63, 95% CI 0.40-0.87, p = 0.017). Ang-2 was higher (6.07 vs. 1.99 ng/mL, p<0.001; AUROC 0.95), with a cut-off of 3.554 ng/mL. The Ang-2/1 ratio was elevated (1.59 vs. 0.23, p<0.001; AUROC 0.93), with a cut-off of 0.504 and increased mortality risk (OR 2.17, 95% CI 1.10-5.12, p = 0.038). Early Ang-1, Ang-2, and Ang-2/1 ratio levels correlate with 30-day mortality and may guide early prognostication.