The rebound of lipoproteins after LDL-apheresis. Kinetics and estimation of mean lipoprotein levels

We studied the rebound of lipoproteins in 20 hypercholesterolemic men [mean total cholesterol (TC) levels 9.6 +/- 1.8 mmol/l] after LDL-apheresis (LA) to determine the rate of recovery and the change in cholesterol synthesis, and to find a uniform estimation for time-averaged levels. After 10-20 months on biweekly LA using dextran sulfate cellulose columns and concomitant simvastatin administration, time-averaged levels (+/- SD) measured by integration of the area under the curve were as follows: TC 4.4 +/- 1.0 mmol/l, LDL cholesterol (LDL-C) 2.5 +/- 1.0 mmol/l, apolipoprotein B (apo B) 1.3 +/- 0.3 g/l, triglycerides (TG) 1.7 +/- 0.7 mmol/l, HDL-C 1.1 +/- 0.2 mmol/l, and lipoprotein(a) [Lp(a)] 53.7 +/- 49.4 mg/dl. Mean acute reductions in TC, LDL-C, apo B, Lp(a), and TG were 61, 77, 75, 76, and 62%, respectively. HDL-C levels were not influenced. Median recovery half times for TC, LDL-C, apo B, and Lp(a) were 3.0, 4.0, 2.3, and 3.5 days, respectively. The rebound of Lp(a) was identical to LDL-C, in 12 and 13 days post-treatment, respectively, whereas apo B and TC returned to pre-treatment levels in 7.5 and 10 days, respectively, due to the fast rebound of VLDL particles. Notwithstanding these differences, time-averaged levels (C-AVG) could be estimated uniformly for the four latter parameters with the formula: C-AVG = C-MIN + 0.73(C-MAX - C-MIN), where C-MAX and C-MIN are the immediate pre- and post-treatment levels. During long-term treatment the whole-body cholesterol synthesis was increased as measured by the ratio lathosterol to cholesterol of 3.24 +/- 1.49 mmol/mmol, whereas no further transient increase in the recovery period after LA was found. In conclusion, long-term LA and simvastatin therapy induced acute and chronic changes in lipids and lipoproteins showing the feasibility of biweekly treatment. It was shown that time-averaged levels, as a measure for the effective plasma levels, can be accurately estimated from pre- and post-treatment levels only. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.