Influence of Simvastatin on apoB-100 Secretion in Non-Obese Subjects with Mild Hypercholesterolemia |
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Authors: | Heiner K Berthold Jessica Mertens Julia Birnbaum Susanne Brämswig Thomas Sudhop P Hugh R Barrett Klaus von Bergmann Ioanna Gouni-Berthold |
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Affiliation: | 1.Department of Clinical Pharmacology,University of Bonn,Bonn,Germany;2.Lipid Clinic, Interdisciplinary Metabolism Center,Charité University Medicine Berlin,Berlin,Germany;3.School of Medicine and Pharmacology,University of Western Australia,Perth,Australia;4.Department of Internal Medicine II,University of Cologne,Cologne,Germany |
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Abstract: | Statins decrease apoB-100-containing lipoproteins by increasing their fractional catabolic rates through LDL receptor-mediated
uptake. Their influence on hepatic secretion of these lipoproteins is controversial. The objective of the study was to examine
the influence of simvastatin on the secretion of apoB-100-containing lipoproteins in fasting non-obese subjects. Turnover
of apoB-100-containing lipoproteins was investigated using stable isotope-labeled tracers. Multicompartmental modeling was
used to derive kinetic parameters. Eight male subjects (BMI 25 ± 3 kg/m2) with mild hypercholesterolemia (LDL cholesterol 135 ± 30 mg/dL) and normal triglycerides (111 ± 44 mg/dL) were examined
under no treatment (A), under chronic treatment with simvastatin 40 mg/day (B) and after an acute-on-chronic dosage of 80 mg
simvastatin under chronic simvastatin treatment (C). Lipoprotein concentrations changed as expected under 40 mg/day simvastatin.
Fractional catabolic rates increased in IDL and LDL but not in VLDL fractions versus control VLDL +35% in B (n.s.) and +21%
in C (n.s.); IDL +169% in B (P = 0.08) and +187% in C (P = 0.032); LDL +87% in B (P = 0.025) and +133% in C (P = 0.025)]. Chronic (B) and acute-on-chronic simvastatin treatment (C) did not affect lipoprotein production rates VLDL −8
and −13%, IDL +47 and +38%, and LDL +19 and +30% in B and C, respectively (all comparisons n.s.)]. The data indicate that
simvastatin does not influence the secretion of apoB-100-containing lipoproteins in non-obese subjects with near-normal LDL
cholesterol concentrations. |
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