Pathogenesis of vascular complications in Cushing's syndrome

Chronic exposure to high glucocorticoid levels in Cushing's syndrome (CS) is often associated with alterations in the hemostatic system and the expression of prothrombotic phenotypes. Increased frequency of both atherothrombotic and venous thromboembolic events (VTE) has been reported in patients with CS. In general, cardiovascular complications in these patients cause a five-fold increase in mortality compared to the normal population. Although numerous abnormalities in the hemostatic system have been detected in patients with CS, the underlying mechanisms of the prothrombotic state are not fully elucidated. High levels of factor VIII and von Willebrand factor, with evidence of enhanced thrombin generation and decreased fibrinolytic activity, have been documented in several studies. However, it is not clear to what extent these changes contribute to the shift of hemostatic balance towards the hypercoagulable state and expression of thrombophilic phenotypes. Thrombosis is usually a multicausal disease, and all three components of the so-called Virchow triad, namely 1) vascular abnormalities and endothelial dysfunction, 2) hypercoagulability and 3) stasis, may play a variable role in the pathogenesis of the prothrombotic state in CS patients. Larger studies are needed to establish strategies for prevention of cardiovascular complications in patients with Cushing's syndrome.