Low-density lipoprotein cholesterol bulk is the pivotal determinant of atherosclerosis in familial hypercholesterolemia

This study's aim was to determine whether biochemical risk factors such as lipoprotein(a), fibrinogen, homocysteine, and insulin, as well as low-densi ty lipoprotein (LDL) particle size, were predictive of carotid intimamedia thickness (IMT), an early marker of atherosclerosis, in subjects with famil ial hypercholesterolemia (FH). We also determined whether plasma 8-isoprost ane, as a marker of in vivo lipid oxidation, correlated with carotid IMT. T wenty-two homozygous and 20 heterozygous subjects with FH were compared wit h 20 normocholesterolemic controls. On univariate analysis, plasma total an d LDL cholesterol, the cholesterol-years score (CYS), lipoprotein(a), and f ibrinogen, but not homocysteine or insulin, were positively related, and hi gh-density lipoprotein (HDL) cholesterol was negatively related to carotid IMT. However, on multivariate analysis, only LDL cholesterol and the CYS pr edicted carotid IMT (multiple r = 0.82; r(2) = 0.68; p < 0.0001). The subje cts with FH had large rather than small dense LDL particles, and plasma 8-i soprostone levels were not increased. LDL cholesterol and the CYS, or "chol esterol bulk" are the pivotal determinants of atherosclerosis and are the s trongest predictors of carotid IMT in FH. (C) 1999 by Excerpta Medica, Inc.