Oxidative modification of low density lipoprotein (LDL) appears to be
important in the pathogenesis of atherosclerosis. Inhibiting the oxida
tion of LDL may retard or prevent the atherogenic process. However, su
sceptibility of LDL to oxidation in vitro and its atherogenicity in vi
vo may not always correlate. Subjects with familial hypercholesterolae
mia (FH) develop severe, premature atherosclerosis despite having larg
e, bouyant LDL particles which are less susceptible to oxidation. High
dose, long-term vitamin E increases the resistance of LDL to oxidatio
n but, unlike probucol, has no effect on xanthoma regression in homozy
gous FH, In FH, the quantity of LDL takes priority and the main aim of
therapy is reduction of LDL bulk. Individuals with small, dense LDL p
articles are at increased risk for atherosclerosis despite desirable p
lasma LDL cholesterol levels. Small, dense LDL particles are more susc
eptible to oxidation and in these subjects antioxidant therapy may be
of greater benefit, In subjects with atherosclerosis, current manageme
nt should be aimed primarily at reducing the LDL cholesterol level. In
the future antioxidant therapy may complement our management of hyper
cholesterolaemia.