 Herein, the investigators bring together previously unconnected data to propose a unifying hypothesis, centered on insufficient NO bioavailability INOBA, to explain the increased morbidity and mortality observed in some patients following RBC transfusion. In this model, variables associated with RBC units storage time; 2,3-diphosphoglycerate 2,3-DPG concentration and transfusion recipients endothelial dysfunction; hematocrit Hct collectively lead to changes in NO levels in vascular beds. Under certain circumstances, these variables are aligned such that NO concentrations are markedly reduced, leading to vasoconstriction, decreased local blood flow and insufficient O2 delivery to end organs. Under these circumstances, the likelihood of morbidity and mortality escalates. The INOBA hypothesis is attractive because of its explanatory power and because it leads to a number of readily testable predictions, which will be investigated t determine the effects of transfused RBCs in patients with endothelial dysfunction due to cardiovascular disease. A non-invasive ultrasound assay will be used to test whether patients with cardiovascular disease and endothelial dysfunction who have intrinsic defects in NO synthesis are more susceptible to adverse effects from storedprocessed RBCs impaired in NO bioavailability than fresh RBC units. Vasodilation and tissue oxygenation in response to transfusion will be monitored, and Framingham risk scores and cardiovascular disease biomarkers will be tested as potential predictive factors to identify patients most at risk from adverse effects of RBC transfusions. 