CORONARY ATHEROSCLEROTIC WALL THICKENING AND VASCULAR REACTIVITY IN HUMANS - ELEVATED HIGH-DENSITY-LIPOPROTEIN LEVELS AMELIORATE ABNORMAL VASOCONSTRICTION IN EARLY ATHEROSCLEROSIS

Background Abnormal vascular reactivity represents a fundamental distu rbance in vascular biology with the development of atherosclerosis. Be cause endothelial vasodilator function plays a pivotal role in control ling vasomotor tone, we hypothesized that atherosclerotic wall thicken ing might directly interfere with deficient endothelium-mediated dilat ion and thereby contribute to the abnormal reactivity of atherosclerot ic arteries in vivo. Methods and Results In 26 patients without focal stenoses in the left anterior descending coronary artery, acetylcholin e (0.036 to 3.6 mu g/mL) was infused into the artery to evaluate endot helium-mediated vasodilation. Segmental vasomotor responses to acetylc holine were correlated with the local extent of atherosclerotic wall t hickening quantitated by intracoronary ultrasound examination. Sevente en of the patients also underwent cold presser testing to assess the v asoreactivity to sympathetic activation. The response of coronary arte ry segments to acetylcholine varied from 35% dilation to 52% constrict ion and demonstrated a segmental pattern, with dilation and constricti on observed in different segments of the same artery. The vasomotor re sponse to acetylcholine was closely correlated with the extent of loca l atherosclerotic wall thickening (r=-.82, P<.0001). Over the entire r ange of atherosclerotic wall thickening, segments from patients with e levated high-density lipoprotein (HDL) cholesterol serum levels (>75th percentile) demonstrated a significantly blunted constrictor response to acetylcholine (P<.01 at the maximal acetylcholine concentration) c ompared with segments from patients with HDL cholesterol <75th percent ile. The degree of constriction or dilation in response to the acetylc holine infusion correlated with the response to cold presser testing ( r=.75, P<.0001). Again, the cold presser test-induced constrictor resp onse was significantly (P<.05) blunted in segments from patients with elevated HDL cholesterol serum levels compared with those from patient s with HDL cholesterol <75th percentile despite equal degrees of ather osclerotic wall thickening. Conclusions Coronary vasomotor responses t o the endothelium-dependent dilator acetylcholine and to sympathetic s timulation by cold presser test correlate with local atherosclerotic w all thickening. Thus, the degree of abnormal local vascular reactivity is closely related to the extent of atherosclerotic ''plaque load'' i n human epicardial arteries in vivo. Elevated HDL cholesterol serum le vels ameliorate abnormal vasoconstriction at any given extent of ather osclerotic wall thickening, suggesting that HDL cholesterol exerts a b eneficial effect on abnormal vascular reactivity, a fundamental functi onal disturbance associated with coronary atherosclerosis.