Circulating Angiopopietin-1 Correlates with the Clinical Course of Multiple Organ Dysfunction Syndrome and Mortality in Patients with Severe Sepsis

To determine plasma concentrations of angiopoietin (Ang)- 1, Ang-2, Tie-2, and vascular endothelial growth factor (VEGF) in patients with sepsis-induced multiple organ dysfunction syndrome (MODS) and determine their association with mortality. The study prospectively recruited 96 consecutive patients with severe sepsis in a l intensive care unit of a tertiary hospital. Plasma Ang-1, Ang-2, Tie-2, and VEGF levels and MODS were determined in patients on days 1, 3, and 7 of sepsis. Univariate and Cox proportional hazards analysis were performed to develop a prognostic model. Days 1, 3, and 7 plasma Ang-1 concentrations were persistently decreased in MODS patients than in non-MODS patients (day1: 4.0±0.5 vs 8.0±0.5 ng/mL, P<0.0001; day 3, 3.2±0.6 vs 7.3±0.5 ng/mL, P<0.0001, day 7, 2.8±0.6 vs 10.4±0.7 ng/mL, P<0.0001). In patients with resolved MODS on day 7 of sepsis, Ang-1 levels were increased from day 1 (4.7±0.6 ng/mL vs 9.1±1.4 ng/mL, n=43, P=0.004). Plasma Ang-1 levels were lower in nonsurvivors than in survivors on days 1 (4.0±0.5 vs 7.1±0.5 ng/ mL, P<0.0001), 3 (3.8±0.6 vs 7.1±0.5 ng/mL, P<0.0001), and 7 (4.7±0.7 vs 11.0±0.8 ng/mL, P<0.0001) of severe sepsis. In contrast, plasma Ang-2 levels were higher in nonsurvivors than in survivors only on day 1 (15.8±2.0 vs 9.5±1.2 ng/mL, P=0.035). VEGF and Tie-2 levels were not associated with MODS and mortality. Ang-1 level less than the median value was the only independent predictor of mortality (hazard ratio, 2.57; 95% CI 1.12-5.90, P=0.025). Persistently decreased Ang-1 levels are associated with MODS and subsequently, mortality in patients with sepsis.