Pii: S0021-9150(00)00371-3

We studied the rebound of lipoproteins in 20 hypercholesterolemic men [mean total cholesterol (TC) levels 9.691.8 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 (9SD) measured by integration of the area under the curve were as follows: TC 4.491.0 mmol/l, LDL cholesterol (LDL-C) 2.591.0 mmol/l, apolipoprotein B (apo B) 1.390.3 g/l, triglycerides (TG) 1.790.7 mmol/l, HDL-C 1.190.2 mmol/l, and lipoprotein(a) [Lp(a)] 53.7949.4 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 (CAVG) could be estimated uniformly for the four latter parameters with the formula: CAVG=CMIN+0.73(CMAX−CMIN), where CMAX and CMIN are the immediate preand post-treatment levels. During long-term treatment the whole-body cholesterol synthesis was increased as measured by the ratio lathosterol to cholesterol of 3.2491.49 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 preand post-treatment levels only. © 2000 Elsevier Science Ireland Ltd. All rights reserved.