title: Circulating angiopopietin-1 correlates with the clinical course of multiple organ dysfunction syndrome and mortality in patients with severe sepsis.
abstract: 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.
authors.affiliation: From the Department of Thoracic Medicine, Chang Gung Memorial Hospital, Chang Gung University, School of Medicine, Taipei, Taiwan.
authors.forename: Shu-Min
authors.initials: SM
authors.lastname: Lin
authors.forename: Fu-Tsai
authors.initials: FT
authors.lastname: Chung
authors.forename: Chih-Hsi
authors.initials: CH
authors.lastname: Kuo
authors.forename: Pai-Chien
authors.initials: PC
authors.lastname: Chou
authors.forename: Tsai-Yu
authors.initials: TY
authors.lastname: Wang
authors.forename: Po-Jui
authors.initials: PJ
authors.lastname: Chang
authors.forename: Yu-Lun
authors.initials: YL
authors.lastname: Lo
authors.forename: Chien-Da
authors.initials: CD
authors.lastname: Huang
authors.forename: Horng-Chyuan
authors.initials: HC
authors.lastname: Lin
authors.forename: Chun-Hua
authors.initials: CH
authors.lastname: Wang
authors.forename: Han-Pin
authors.initials: HP
authors.lastname: Kuo
mesh_terms: D018806:APACHE; D000368:Aged; D042683:Angiopoietin-1 / Q000097:blood*; D042702:Angiopoietin-2 / Q000097:blood; D005260:Female; D006801:Humans; D008297:Male; D009102:Multiple Organ Failure / Q000097:blood* / Q000209:etiology / Q000401:mortality; D016016:Proportional Hazards Models; D011446:Prospective Studies; D042787:Receptor, TIE-2 / Q000097:blood; D018805:Sepsis / Q000097:blood* / Q000150:complications / Q000401:mortality; D012720:Severity of Illness Index; D042461:Vascular Endothelial Growth Factor A / Q000097:blood
chemical_list: C467630:ANGPT1 protein, human; C586513:ANGPT2 protein, human; D042683:Angiopoietin-1; D042702:Angiopoietin-2; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D042787:Receptor, TIE-2