Influence of simvastatin on apoB-100 secretion in non-obese subjects with mild hypercholesterolemia

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.