Endothelial function in human coronary arteries in vivo. Focus on hypercholesterolemia.

To examine whether and to what extent hypercholesterolemia may affect the vasoactive role of the endothelium before the onset of angiographically visible atherosclerosis in the coronary circulation, we studied normal subjects (group 1, n = 11), individuals with elevated low density lipoprotein plasma values but angiographically smooth coronary arteries (group 2, n = 8), and patients with hypercholesterolemia and minimal disease of the vessel under study (group 3, n = 8). Coronary vasomotor function was evaluated by three interventions: subselective intracoronary infusion of acetylcholine (0.036, 0.36, and 3.6 micrograms/min) with a 3F Doppler catheter in the left anterior descending artery, 0.3 mg intracoronary nitroglycerin ("endothelium-independent"), and increase in blood flow (assessment of flow-dependent, endothelium-mediated coronary dilation). In group 1, all interventions caused coronary dilation of the left anterior descending artery as assessed by automatic quantification of digitized cineframes. However, in group 2, acetylcholine elicited substantial coronary vasoconstriction, and the vasodilator response to nitroglycerin and to increases in flow (flow-dependent dilation) was preserved. In group 3, the acetylcholine-induced coronary vasoconstriction was even more pronounced, and the flow-dependent dilation was impaired (+5.1 +/- 1% versus +10.5 +/- 1.1% [group 1], p less than 0.05). The coronary flow reserve (derived from Doppler flow velocity measurements) in response to papaverine was not significantly different in normal and hypercholesterolemic individuals (groups 2 and 3). However, the increase in coronary flow exerted by acetylcholine was substantially depressed in patients with hypercholesterolemia (groups 2 and 3) as compared with normal individuals (+48 +/- 8.3% and +49 +/- 25% versus +220 +/- 28.5%, respectively, p less than 0.01). Thus, hypercholesterolemia elicits endothelial dysfunction in coronary conduit and resistance vessels in humans that precedes angiographically visible atherosclerotic lesions in large coronary arteries. Conceivably, these vascular alterations contribute to increased coronary vasomotor tone within the coronary circulation and may predispose these patients to myocardial ischemia.