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Effects of increasing doses of simvastatin on fasting lipoprotein subfractions, and the effect of high-dose simvastatin on postprandial chylomicron remnant clearance in normotriglyceridemic patients with premature coronary sclerosis.
van Wijk, J P H; Buirma, R; van Tol, A; Halkes, C J M; De Jaegere, P P Th; Plokker, H W M; van der Helm, Y J M; Castro Cabezas, M.
Afiliação
  • van Wijk JP; Department of Vascular Medicine, University Medical Center Utrecht, The Netherlands.
Atherosclerosis ; 178(1): 147-55, 2005 Jan.
Article em En | MEDLINE | ID: mdl-15585212
ABSTRACT
Postprandial hyperlipidemia has been linked to premature coronary artery disease (CAD) in fasting normotriglyceridemic patients. We investigated the effects of increasing doses of simvastatin up to 80 mg/day on fasting and postprandial lipoprotein metabolism in 18 normotriglyceridemic patients with premature CAD. Fasting lipoprotein subfractions and cholesteryl ester transfer protein (CETP) activity were determined after each 5-week dose titration (0, 20, 40 and 80 mg/day). At baseline and after treatment with simvastatin 80 mg/day, standardised Vitamin A oral fat loading tests (50 g/m2; 10 h) were carried out. Ten normolipidemic healthy control subjects matched for gender, age and BMI underwent tests without medication. Treatment with simvastatin resulted in dose-dependent reductions of fasting LDL-cholesterol, without changing cholesterol levels in the VLDL-1, VLDL-2 and IDL fractions. In addition, simvastatin decreased CETP activity dose-dependently, although HDL-cholesterol remained unchanged. Simvastatin 80 mg/day decreased fasting plasma triglycerides (TG) by 26% (P < 0.05), but did not decrease significantly TG levels in any of the subfractions. The TG/cholesterol ratio increased in all subfractions. The plasma TG response to the oral fat loading test, estimated as area under the curve (TG-AUC), improved by 30% (from 21.5 +/- 2.5 to 15.1 +/- 1.9 mmol h/L; P < 0.01). Treatment with simvastatin 80 mg/day improved chylomicron remnant clearance (RE-AUC) by 36% from 30.0 +/- 2.6 to 19.2 +/- 3.3 mg h/L (P < 0.01). After therapy, remnant clearance in patients was similar to controls (19.2 +/- 3.3 and 20.3 +/- 2.7 mg h/L, respectively), suggesting a normalization of this potentially atherogenic process. In conclusion, high-dose simvastatin has beneficial effects in normotriglyceridemic patients with premature CAD, due to improved chylomicron remnant clearance, besides effective lowering of LDL-cholesterol. In addition, the lipoprotein subfractions became more cholesterol-poor, as reflected by the increased TG/cholesterol ratio, which potentially makes them less atherogenic.
Assuntos
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Base de dados: MEDLINE Assunto principal: Triglicerídeos / Doença da Artéria Coronariana / Quilomícrons / Jejum / Inibidores de Hidroximetilglutaril-CoA Redutases / Período Pós-Prandial / Sinvastatina / Lipoproteínas Tipo de estudo: Prognostic_studies Limite: Female / Humans / Male / Middle aged Idioma: En Ano de publicação: 2005 Tipo de documento: Article
Buscar no Google
Base de dados: MEDLINE Assunto principal: Triglicerídeos / Doença da Artéria Coronariana / Quilomícrons / Jejum / Inibidores de Hidroximetilglutaril-CoA Redutases / Período Pós-Prandial / Sinvastatina / Lipoproteínas Tipo de estudo: Prognostic_studies Limite: Female / Humans / Male / Middle aged Idioma: En Ano de publicação: 2005 Tipo de documento: Article