Angiopoietin-2, a Regulator of Vascular Permeability in Inflammation Is Elevated in Severe Acute Pancreatitis and Is Associated With Systemic Organ Failure

Background: A major complication of severe acute pancreatitis is the vascular leak syndrome, which can result in intravascular volume depletion and adult respiratory distress syndrome. Angiopoietin-2 is an endothelial cell autocrine peptide, released by local injury and leading to destabilization of endothelial cells with increased vascular permeability. Aim: To assess serum levels of Angiopoietin-2 in patients with AP and their role as predictor of disease severity. Methods: A cohort of 185 patients with acute pancreatitis was prospectively enrolled between June 2003 and September 2007. Demographic information, clinical features, DNA and daily serum samples were collected. Patients were classified into mild (79%) and severe acute pancreatitis (21%) based on the presence of organ failure. Angiopoietin-2 levels were measured in previously frozen serum samples from patients on days 2-7 from onset of pain and controls. Angiopoietin-2 levels were compared with clinical outcomes using Naïve Bayes and logistic ridge regression to generate statistical models predicting disease severity. Results: Angiopoietin-2 levels were measured in 93 patient serum samples on Days 2-7 and 58 controls. Angiopoietin-2 levels were significantly higher in patients with severe acute pancreatitis compared to mild acute pancreatitis and control subjects on all days. Using logistic ridge regression the highest accuracy was on day 2 (84%) with an area under the curve of 0.76 as a predictive statistical model for disease severity. Conclusions: In AP significantly elevated angiopoietin-2 levels are strongly associated with organ failure and disease severity. Angiopoietin-2 levels early in the course of the disease appear to accurately predict a severe course.