ANGIOGRAPHICALLY SILENT ATHEROSCLEROSIS DETECTED BY INTRAVASCULAR ULTRASOUND IN PATIENTS WITH FAMILIAL HYPERCHOLESTEROLEMIA AND FAMILIAL COMBINED HYPERLIPIDEMIA - CORRELATION WITH HIGH-DENSITY-LIPOPROTEINS

Objectives. This study sought to evaluate the extent of atherosclerosi s in coronary and iliac arteries in patients with heterozygous familia l hypercholesterolemia or familial combined hyperlipidemia, using intr avascular ultrasound imaging. Background. Intravascular ultrasound ima ging provides cross-sectional tomographic views of the vessel wall and allows quantitative assessment of atherosclerosis. Methods. Forty-eig ht nonsmoking, asymptomatic patients with heterozygous familial hyperc holesterolemia or familial combined hyperlipidemia underwent intravasc ular ultrasound imaging of the left anterior descending coronary, left main coronary and common iliac arteries. Angiography showed only mini mal or no narrowing in these vessels. Intravascular ultrasound images obtained during catheter pullback underwent morphometric analysis. Pla que burden was expressed as the mean and maximal intimal index (ratio of plaque area and area within the internal elastic lamina) and as the percent of vessel surface covered by plaque. Results. Intravascular u ltrasound detected plaque more frequently than angiography in the left anterior descending (80% vs. 29%, respectively), left main (44% vs, 1 6%) and iliac arteries (33% vs, 27%). Plaque burden was higher in the left anterior descending (mean intimal index [+/-SD] 0.25 +/- 0.16) th an in the left main (0.11 +/- 0.16, p < 0.001) and iliac arteries (0.0 2 +/- 0.04, p < 0.001). Angiography detected lumen narrowing only in c oronary arteries with a maximal intimal index greater than or equal to 0.42 (left anterior descending artery) and greater than or equal to 0 .43 (left main artery), The area within the internal elastic lamina in creased with plaque area in the left anterior descending (r = 0.82, p < 0.001) and left main arteries (r = 0.53, p < 0.001). By step,vise mu ltiple regression analysis, the strongest predictor for plaque burden in the left anterior descending artery was the level of high density l ipoprotein (HDL) cholesterol and total/HDL cholesterol ratio for the l eft main artery. Conclusions. In patients with heterozygous familiar h ypercholesterolemia and familial combined hyperlipidemia, extensive co ronary plaque is present despite minimal or no angiographic changes. C ompensatory vessel enlargement and diffuse involvement with eccentric plaque may account for the lack of angiographic changes. Levels of HDL cholesterol and total/HDL cholesterol ratio are far more powerful pre dictors of coronary plaque burden than are low density lipoprotein cho lesterol levels in these patients with early, asymptomatic disease.