Quantity versus quality of LDL cholesterol in patients with familial hypercholesterolemia--which is more important?

The aim of this study was to determine the effects of low-density lipoprotein (LDL) particle size and composition on the susceptibility of LDL to oxidation in subjects with Familial Hypercholesterolemia (FH).

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.

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 (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.

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.