title: Low-density lipoprotein cholesterol bulk is the pivotal determinant of atherosclerosis in familial hypercholesterolemia.
abstract: This study's aim was to determine whether biochemical risk factors such as lipoprotein(a), fibrinogen, homocysteine, and insulin, as well as low-density lipoprotein (LDL) particle size, were predictive of carotid intimamedia thickness (IMT), an early marker of atherosclerosis, in subjects with familial hypercholesterolemia (FH). We also determined whether plasma 8-isoprostane, as a marker of in vivo lipid oxidation, correlated with carotid IMT. Twenty-two homozygous and 20 heterozygous subjects with FH were compared with 20 normocholesterolemic controls. On univariate analysis, plasma total and LDL cholesterol, the cholesterol-years score (CYS), lipoprotein(a), and fibrinogen, but not homocysteine or insulin, were positively related, and high-density lipoprotein (HDL) cholesterol was negatively related to carotid IMT. However, on multivariate analysis, only LDL cholesterol and the CYS predicted carotid IMT (multiple r = 0.82; r2 = 0.68; p <0.0001). The subjects with FH had large rather than small dense LDL particles, and plasma 8-isoprostane levels were not increased. LDL cholesterol and the CYS, or "cholesterol bulk" are the pivotal determinants of atherosclerosis and are the strongest predictors of carotid IMT in FH.
authors.affiliation: Department of Medicine, University of the Witwatersrand, Johannesburg, South Africa. 014fred@chiron.wits.ac.za
authors.forename: F J
authors.initials: FJ
authors.lastname: Raal
authors.forename: G J
authors.initials: GJ
authors.lastname: Pilcher
authors.forename: R
authors.initials: R
authors.lastname: Waisberg
authors.forename: E P
authors.initials: EP
authors.lastname: Buthelezi
authors.forename: M G
authors.initials: MG
authors.lastname: Veller
authors.forename: B I
authors.initials: BI
authors.lastname: Joffe
mesh_terms: D000328:Adult; D001161:Arteriosclerosis / Q000097:blood* / Q000150:complications; D016893:Carotid Stenosis / Q000097:blood* / Q000209:etiology; D008078:Cholesterol, LDL / Q000097:blood*; D015237:Dinoprost / Q000031:analogs & derivatives / Q000097:blood; D028441:F2-Isoprostanes; D005260:Female; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000097:blood* / Q000235:genetics; D017270:Lipoprotein(a) / Q000097:blood; D008297:Male; D012307:Risk Factors
chemical_list: D008078:Cholesterol, LDL; D028441:F2-Isoprostanes; D017270:Lipoprotein(a); C075750:8-epi-prostaglandin F2alpha; D015237:Dinoprost