The rebound of lipoproteins after LDL-apheresis. Effects on chemical composition and LDL-oxidizability

The changes in low density lipoprotein (LDL) composition and oxidizability after LDL-apheresis (LA) using dextran sulfate cellulose columns were evaluated in 12 hypercholesterolemic men (mean +/- S.D. total cholesterol (TC) 9.7 +/- 1.8 mmol/l). After 10-20 months on biweekly LA combined with simvastatin 40 mg per day immediate pre-apheresis levels of TC, LDL-cholesterol, and apolipoprotein B were decreased to 5.3 +/- 1.3 mmol/l, 3.3 +/- 1.2 mmol/l, and 1.6 +/- 0.4 g/l, respectively, whereas apheresis induced mean acute reductions of 61, 78, and 76%, respectively. Measurements of copper-induced LDL-oxidizability in vitro showed an increased resistance against oxidation after LA until day 3 post-treatment: lag time (min) (day 0 (before LA) versus day 1 (post-LA)) 112 +/- 27 versus 130 +/- 26 (P = 0.001), maximal rate of diene production (nmol/min per mg LDL) 11.1 +/- 2.7 versus 9.1 +/- 2.1 (P = 0.001), and time to maximal diene production (min) 186 +/- 39 versus 209 +/- 35 (P = 0.001). Analysis of the chemical composition of LDL revealed a 25% (P < 0.001) reduced content of cholesteryl esters and a decrease of the cholesterol to protein ratio of 1.20 +/- 0.25 to 0.70 +/- 0.22 (P < 0.001) through the 3rd day post-LA. Linoleic acid and arachidonic acid content of LDL decreased 11 and 18%, respectively, at the expense of palmitic acid. Vitamin E levels (mg/l) were significantly lowered due to reduction of the lipoprotein pool by apheresis; however, vitamin E content of LDL did not change in the days after apheresis when expressed per g protein or per mu mol linoleic acid. The changes in fatty acid pattern were strongly associated with changes in LDL-oxidizability indices (P < 0.01). Thus, LA effectively decreased LDL pool size, inducing the presence of less buoyant lipoproteins, which were less susceptible to in vitro oxidation. This was not explained by changes in vitamin E levels, but by short-term changes in the fatty acids composition. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved.