IMPAIRMENT OF ENDOTHELIUM-DEPENDENT DILATION IS AN EARLY EVENT IN CHILDREN WITH FAMILIAL HYPERCHOLESTEROLEMIA AND IS RELATED TO THE LIPOPROTEIN(A) LEVEL

Familial hypercholesterolemia is associated with premature atheroscler osis. Since endothelial dysfunction is an early event in atherogenesis , we used a noninvasive method to assess endothelial function in the s ystemic arteries of 30 children aged 7-17 yr (median 11) with familial hypercholesterolemia (2 homozygotes, 28 heterozygotes, total choleste rol 240-696 mg/dl) and 30 healthy age- and sex-matched controls. Using high resolution ultrasound, the diameter of the superficial femoral a rtery was measured at rest, in response to reactive hyperemia (with in creased flow causing endothelium-dependent dilation), and after sublin gual glyceryltrinitrate( causing endothelium-independent vasodilation) . Flow-mediated dilation was present in the controls (7.5+/-0.7%) but was impaired or absent in the hypercholesterolemic children (1.2+/-0.4 %, P < 0.0001). Total cholesterol was inversely correlated with flow-m ediated dilation (r = -0.61, P < 0.0001). In the hypercholesterolemic children, flow-mediated dilation was inversely related to the lipoprot ein(a) level (v = -0.61, P = 0.027) but not to other lipid fractions. Glyceryltrinitrate-induced dilation was present in all subjects but wa s lower in the hypercholesterolemia group (10.0+/-0.6% vs 12.4+/-0.8%, P = 0.023). Thus, impaired endothelium-dependent dilation is present in children with familial hypercholesterolemia as young as 7 yr of age and the degree of impairment is related to the lipoprotein(a) level.