Circulating angiopoietins and cardiovascular mortality in cardiogenic shock

Vascular integrity is disturbed in shock contributing to clinical appearance and serious outcomes. While angiopoietin (Ang)-1 protects from vascular inflammation and leakage, Ang-2 disrupts endothelial barrier function. The imbalance of Ang-1 and Ang-2, their association to haemodynamic deterioration, and their prognostic relevance are not known and, thus, were prospectively evaluated in patients with cardiogenic shock (CS) in this study.

Plasma Ang-1 and Ang-2 were determined by the enzyme immunoassay in patients with CS (n = 96), uncomplicated acute myocardial infarction (AMI, n = 20) and age-matched healthy controls (HC, n = 20). Angiopoietin-2 was three-fold elevated in CS compared with HC (P < 0.001), remained elevated in non-survivors, and decreased in survivors (P < 0.001). In contrast, Ang-1 decreased up to 35-fold in CS (P < 0.001). Angiopoietin-1 was correlated and Ang-2 was inversely related to a cardiac power index and mixed venous oxygen saturation, respectively (P < 0.001 for all). To assess the prognostic relevance, two outcome variables were considered: the 28-day mortality and the survival time (follow-up time 1 year). For Ang-2 at admission a cut-off point of 2500 pg/mL had a sensitivity of 61% and a specificity of 80% to determine 28-day mortality in CS (confirmed by receiver operating characteristic analysis, area under the curve = 0.71 ± 0.06, P < 0.001). Angiopoietin-2 levels >2500 pg/mL at admission were observed to be an independent predictor for 1-year mortality in CS confirmed by Cox proportional hazard analysis [hazard ratio (HR) 2.11; 95% confidence interval (CI) 1.03-4.36; P = 0.042].

Circulating Angs are closely related to outcome and severity in CS. Angiopoietin-2 emerged as an independent predictor of 28-day and 1-year mortality in CS. Larger studies are required to define the cut-off and predictive values for Ang-2. Angiopoietins may be prognostic biomarkers for survival in CS and might represent a novel therapeutic target.