Ž . Clinica Chimica Acta 314 2001 167–173 www.elsevier.comrlocaterclinchim Quantity versus quality of LDL cholesterol in patients with familial hypercholesterolemia—which is more important? Janice E. Paiker a, ) , Frederick J. Raal b , Rita Waisberg a , E. Pilani Buthelezi a a Department of Chemical Pathology, South African Institute for Medical Research, UniÕersity of the Witwatersrand, 7 York Rd., Parktown, 2193, Johannesburg, South Africa b Lipid Metabolism Research Group, UniÕersity of the Witwatersrand, Johannesburg, South Africa Received 19 January 2001; received in revised form 9 August 2001; accepted 16 August 2001 Abstract Ž . Background: The aim of this study was to determine the effects of low-density lipoprotein LDL particle size and Ž . composition on the susceptibility of LDL to oxidation in subjects with Familial Hypercholesterolemia FH . Methods: LDL was isolated from 20 FH homozygotes, 20 FH heterozygotes and 20 normal controls. Susceptibility of LDL to ex vivo copper-mediated oxidation was assessed by measuring conjugated diene production at 234 nm. Other factors known to influence LDL oxidation, namely particle size, vitamin E levels, and fatty acid composition of the LDL particles were also measured. Results: The mean duration of the lag phase was 1.42-fold longer in the FH homozygotes, and 1.21-fold longer in the FH heterozygotes than in the normal controls. LDL particle size was significantly larger in the FH homozygotes Ž . Ž . Ž . 26.45 "0.37 nm and FH heterozygotes 26.01 "0.40 nm compared to the normal control group 25.17 "0.39 nm . LDL vitamin E concentrations, when expressed relative to LDL cholesterol concentrations, were similar in all the groups. In addition, no significant differences were observed in the total saturated, monounsaturated or polyunsaturated fatty acid content of LDL in the three groups of subjects. Conclusion: These results suggest that it is the great excess in LDL quantity, rather than LDL ‘quality’, that is responsible for the severe and premature atherosclerosis in patients with FH. q 2001 Elsevier Science B.V. All rights reserved. Keywords: Atherosclerosis; Familial Hypercholesterolemia; Lipid oxidation; LDL particle size; Vitamin E; Fatty acids 1. Introduction Oxidative modification of low-density lipoprotein Ž . LDL cholesterol has been reported to play a pivotal w x role in the pathogenesis of atherosclerosis 1–3 . Ž . Oxidized LDL ox-LDL is thought to exert its atherogenic effect at several levels of the athero- sclerotic process, including direct cytotoxicity of en- ) Corresponding author. Tel.: q 27-11-489-8500; fax: q 27-11- 647-2521. Ž . E-mail address: janicep@mail.saimr.wits.ac.za J.E. Paiker . dothelial cells, stimulation of the immune system, altered gene expression, enhanced coagulation, and w x promotion of endothelial dysfunction 4–6 . Partly oxidized LDL and antibodies, which recognize epi- topes on ox-LDL, have been demonstrated in athero- w x sclerotic lesions supporting this theory 7,8 . Further- more, there have been reports showing a correlation between the susceptibility of LDL to oxidation and w x the severity of atherosclerosis 9,10 . LDL particle size, composition, and density are thought to influ- ence the susceptibility of LDL to oxidation. Smaller, denser LDL particles have been shown to display 0009-8981r01r$ - see front matter q 2001 Elsevier Science B.V. All rights reserved. Ž . PII: S0009-8981 01 00688-X