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Influence of Simvastatin on apoB‐100 Secretion in Non‐Obese Subjects with Mild Hypercholesterolemia
Author(s) -
Berthold Heiner K.,
Mertens Jessica,
Birnbaum Julia,
Brämswig Susanne,
Sudhop Thomas,
Barrett P. Hugh R.,
Bergmann Klaus,
GouniBerthold Ioanna
Publication year - 2010
Publication title -
lipids
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.601
H-Index - 120
eISSN - 1558-9307
pISSN - 0024-4201
DOI - 10.1007/s11745-010-3420-5
Subject(s) - simvastatin , apolipoprotein b , medicine , endocrinology , lipidology , very low density lipoprotein , chemistry , clinical chemistry , catabolism , lipoprotein , cholesterol , secretion , metabolism
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/m 2 ) 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.