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.
Kroon
A A
AA
Division of General Internal Medicine, Department of Medicine, 541 AIG, University Hospital Nijmegen, PO Box 9101, 6500 HB, Nijmegen, The Netherlands.
van't Hof
M A
MA
Demacker
P N
PN
Stalenhoef
A F
AF
D000328:Adult; D000368:Aged; D000924:Anticholesteremic Agents / Q000627:therapeutic use; D001055:Apolipoproteins B / Q000097:blood; D001781:Blood Component Removal; D002784:Cholesterol / Q000097:blood; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use; D006937:Hypercholesterolemia / Q000097:blood / Q000628:therapy*; D017270:Lipoprotein(a) / Q000097:blood; D008077:Lipoproteins, LDL / Q000097:blood*; D008297:Male; D008875:Middle Aged; D019821:Simvastatin / Q000627:therapeutic use; D012855:Sitosterols / Q000097:blood; D014280:Triglycerides / Q000097:blood
D000924:Anticholesteremic Agents; D001055:Apolipoproteins B; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D017270:Lipoprotein(a); D008077:Lipoproteins, LDL; D012855:Sitosterols; D014280:Triglycerides; C025473:gamma-sitosterol; C001521:lathosterol; D002784:Cholesterol; D019821:Simvastatin