Effect of Plaque Burden on Coronary Vasoreactivity in Early Atherosclerosis

Coronary atherosclerosis, during its initial stages of development, may result in abnormal endothelium-dependent vasomotor responses. The relation between the degree of vasoreactivity and the amount of atheromatous plaque load has not been decisively determined. The aim of the present study was to investigate the effects of segmental plaque burden on endothelium-dependent and independent coronary stimulation. We studied 37 individual coronary segments along the course of coronary arteries that had angiographically either nonvisible or nonobstructive atheromatous lesions. Endothelium-dependent and independent stimulation of each segment from 10 patients with known significant coronary artery disease was examined with intracoronary administrations of normal saline, acetylcholine 10−6 M and 10−5 M, and nitroglycerin, respectively, using quantitative coronary angiography. Simultaneous vasomotor effects on the microcirculation were evaluated by a Doppler guidewire (Flowire). Subsequently, intracoronary ultrasound was used at each segment for detailed morphometric and composition analysis. By quantitative coronary angiography, when compared with normal saline, acetylcholine produced a reduction in minimal lumen diameter of 15.2 ± 25.6%, and nitroglycerin produced an increase of 18.0 ± 22.5%. The degree of vasoconstriction induced by acetylcholine correlated inversely (r = 0.51, p = 0.001) to the amount of segmental maximal plaque thickness. No relation between the response to nitroglycerin and the parameters obtained by intracoronary ultrasound was documented. Fibrous coronary plaques showed less vasomotor changes than plaques with mixed echogenicity, probably due to a significantly larger plaque burden. Acetylcholine produced overall a differential vasomotor response in the epicardial segments (vasoconstriction) compared with the microcirculation (vasodilation). These results indicate that in early atheromatous coronary lesions, the degree of endothelium-dependent vasoconstrictive response is inversely related to the amount of segmental plaque burden.