Endothelial function and clinical outcome

Under pro-atherosclerotic conditions, endothelial cells lose the ability to produce bioactive nitric oxide and demonstrate increased expression of vasoconstrictor, pro-inflammatory, and pro-thrombotic factors. The available evidence suggests that these alterations in endothelial phenotype contribute to the formation, progression, and rupture of atherosclerotic lesions. There currently is great interest in understanding the mechanisms and clinical relevance of these changes in endothelial cell biology, because they could lead to new approaches for the management of patients with atherosclerosis. While it is clear that the endothelium regulates many aspects of vascular homeostasis, current approaches to evaluate local “endothelial function” in humans have been limited to assessment of endothelium dependent vasodilation. In addition, investigators have the ability to measure blood concentrations of various endothelium derived thrombotic and inflammatory factors and, most recently, numbers of endothelial progenitor cells. The clinical relevance of endothelial dysfunction for cardiovascular disease events is strongly supported by studies in the human coronary circulation showing that impaired endothelium dependent vasodilation in response to acetylcholine or shear stress predicts clinical outcome. For example, more severe impairment of the vasomotor response to intracoronary acetylcholine infusion identifies individuals with increased risk for acute coronary syndromes, cardiovascular death, and stroke.1–4 Impaired flow mediated dilation2 and a more severe constrictor response to the cold pressor test2,5 also predict future cardiovascular events. These findings apply to patients with advanced coronary artery disease2,3 and to individuals with angiographically normal or nearly normal coronary arteries.1,3,5 Although studies in the coronary circulation have the greatest clinical relevance, it is interesting that measures of endothelial function in peripheral arteries also have predictive value for coronary heart disease. For example, impaired endothelium dependent …