Low density lipoproteins and atherosclerosis-quantity or quality?

Oxidative modification of low density lipoprotein (LDL) appears to be important in the pathogenesis of atherosclerosis. Inhibiting the oxidation of LDL may retard or prevent the atherogenic process. However, susceptibility of LDL to oxidation in vitro and its atherogenicity in vivo may not always correlate. Subjects with familial hypercholesterolaemia (FH) develop severe, premature atherosclerosis despite having large, bouyant LDL particles which are less susceptible to oxidation. High dose, long-term vitamin E increases the resistance of LDL to oxidation but, unlike probucol, has no effect on xanthoma regression in homozygous 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 particles are at increased risk for atherosclerosis despite desirable plasma LDL cholesterol levels. Small, dense LDL particles are more susceptible to oxidation and in these subjects antioxidant therapy may be of greater benefit. In subjects with atherosclerosis, current management should be aimed primarily at reducing the LDL cholesterol level. In the future antioxidant therapy may complement our management of hypercholesterolaemia.