title: Impairment of endothelium-dependent dilation is an early event in children with familial hypercholesterolemia and is related to the lipoprotein(a) level.
abstract: Familial hypercholesterolemia is associated with premature atherosclerosis. Since endothelial dysfunction is an early event in atherogenesis, we used a noninvasive method to assess endothelial function in the systemic arteries of 30 children aged 7-17 yr (median 11) with familial hypercholesterolemia (2 homozygotes, 28 heterozygotes, total cholesterol 240-696 mg/dl) and 30 healthy age- and sex-matched controls. Using high resolution ultrasound, the diameter of the superficial femoral artery was measured at rest, in response to reactive hyperemia (with increased flow causing endothelium-dependent dilation), and after sublingual 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-mediated dilation (r = -0.61, P < 0.0001). In the hypercholesterolemic children, flow-mediated dilation was inversely related to the lipoprotein(a) level (r = -0.61, P = 0.027) but not to other lipid fractions. Glyceryltrinitrate-induced dilation was present in all subjects but was 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.
authors.affiliation: Cardiothoracic Unit, Hospital for Sick Children, London, United Kingdom.
authors.forename: K E
authors.initials: KE
authors.lastname: Sorensen
authors.forename: D S
authors.initials: DS
authors.lastname: Celermajer
authors.forename: D
authors.initials: D
authors.lastname: Georgakopoulos
authors.forename: G
authors.initials: G
authors.lastname: Hatcher
authors.forename: D J
authors.initials: DJ
authors.lastname: Betteridge
authors.forename: J E
authors.initials: JE
authors.lastname: Deanfield
mesh_terms: D000293:Adolescent; D000367:Age Factors; D002648:Child; D002675:Child, Preschool; D002784:Cholesterol / Q000097:blood; D004730:Endothelium, Vascular / Q000000981:diagnostic imaging / Q000502:physiology / Q000503:physiopathology*; D005260:Female; D005263:Femoral Artery / Q000000981:diagnostic imaging / Q000502:physiology / Q000503:physiopathology*; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000097:blood / Q000000981:diagnostic imaging / Q000503:physiopathology*; D017270:Lipoprotein(a) / Q000097:blood*; D008075:Lipoproteins, HDL / Q000097:blood; D008077:Lipoproteins, LDL / Q000097:blood; D008297:Male; D015999:Multivariate Analysis; D005996:Nitroglycerin; D012016:Reference Values; D012044:Regression Analysis; D012737:Sex Factors; D014280:Triglycerides / Q000097:blood; D014463:Ultrasonography; D014664:Vasodilation / Q000187:drug effects
chemical_list: D017270:Lipoprotein(a); D008075:Lipoproteins, HDL; D008077:Lipoproteins, LDL; D014280:Triglycerides; D002784:Cholesterol; D005996:Nitroglycerin