Low-density lipoprotein (LDL) oxidizability before and after LDL apheresis

Oxidation of low-density lipoprotein (LDL) plays a major role in the develo pment of atherosclerosis. Hypercholesterolemia has been associated with enh anced in vitro oxidation of LDL, and lipid-lowering therapy reduces LDL oxi dizability. In the present study, we investigated whether LDL apheresis per formed with different techniques affects in vitro diene formation (lag phas e) and modification of apolipoprotein B-100 (apoB). Baseline and posttreatm ent diene formation was correlated with the baseline pattern of plasma tota l fatty acids. We then performed a computer-simulation study to test the hy pothesis that LDL apheresis-induced changes in LDL oxidizability are relate d to changes in the mass ratio between freshly produced and older LDL. In 1 9 patients aged 49 +/- 7 years with heterozygous familial hypercholesterole mia (FH) regularly treated with either immunoadsorption, heparin-induced LD L precipitation (HELP), or dextran sulfate (DS) adsorption, we determined l ipoprotein levels, the lag phase, apoB modification, and the fatty acid pat tern in plasma samples drawn at the onset and termination of one LDL aphere sis. LDL apheresis significantly decreased total cholesterol, high-density lipoprotein (HDL) cholesterol, LDL cholesterol, and triglycerides by 50.4%, 14.9%, 62.6%, and 33.6%, respectively. The lag phase increased by a signif icant mean of 9.8%; the charge of apoB was not altered. The lag phase befor e treatment positively correlated with the baseline concentration of plasma total palmitic, myristic, and oleic acid. The increase in the lag phase du ring treatment correlated with a high pretreatment concentration of lauric, linoleic, and docosahexanoic acid. The simulation study indicates that a t emporary imbalance between two LDL compartments, one representing freshly s ecreted LDL and the other representing older LDL, could explain the observe d increase in the lag phase after LDL apheresis. In conclusion, in patients with heterozygous FH, LDL apheresis performed with different techniques de creases the susceptibility of LDL to oxidation. This decrease may be relate d to a temporary mass imbalance between freshly produced and order LDL part icles. Furthermore, the baseline fatty acid pattern influences pretreatment and posttreatment susceptibility to oxidation. Copyright (C) 1999 by W.B. Saunders Company.