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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2000;20:2422.)
© 2000 American Heart Association, Inc.

Atherosclerosis and Lipoproteins

High Dose of Simvastatin Normalizes Postprandial Remnant-Like Particle Response in Patients With Heterozygous Familial Hypercholesterolemia

Th. B. Twickler; G. M. Dallinga-Thie; H. W. de Valk; P. C. N. J. Schreuder; H. Jansen; M. Castro Cabezas; D. W. Erkelens

From the Department of Cardiovascular Medicine, University Medical Center Utrecht, Utrecht, the Netherlands, and the Departments of Internal Medicine, Biochemistry, and Clinical Chemistry (H.J.), Erasmus University, Rotterdam, the Netherlands.

Correspondence to Dr Th.B. Twickler, Department of Cardiovascular Medicine, G02.228, University Medical Center Utrecht, PO Box 85500, 3508 GA Utrecht, Netherlands.

Abstract—Familial hypercholesterolemia (FH) and disturbances in postprandial lipoprotein metabolism are both associated with premature atherosclerosis. The effect of ß-hydroxy-ß-methylglutaryl coenzyme A reductase inhibitors on plasma cholesterol levels in patients with FH is well established; however, it is not known whether postprandial lipoproteins are also influenced. In this case-controlled intervention study, we investigated the effects of high-dose simvastatin on postprandial lipoproteins. We used a new method to analyze remnant lipoproteins based on the immunoseparation principle (remnant-like particle cholesterol [RLP-C] assay) and the well-established measurement of retinyl ester (RE) analysis in plasma and in the Svedberg flotation unit (Sf)<1000 fraction. Seven heterozygous FH patients and 7 control subjects matched for sex, age, body mass index, triglycerides, and apolipoprotein E genotype were enrolled in the study. An oral vitamin A (RE) fat-loading test was performed at baseline in both groups and after 3 months of high-dose simvastatin (80 mg/d) treatment in the FH patients. Before treatment, FH patients had significantly higher fasting and postprandial concentrations of lipoprotein remnants (plasma RLP-C 42±19 mg/dL and area under the RLP-C curve 415±82 mg · L^-1 · h^-1, respectively) than did control subjects (7±3 mg/dL and 101±35 mg · L ^-1 · h^-1, respectively; P<0.05), suggesting a delayed clearance of chylomicron remnant particles in the FH patients. Treatment with simvastatin significantly reduced fasting and postprandial remnant lipoprotein cholesterol concentrations (13±3 mg/dL and 136±53 mg · L^-1 · h^-1, respectively; P<0.05 for both). Postprandial RE in the Sf<1000 fraction, not total RE in plasma, was also significantly higher in FH patients than in control subjects (24±10 versus 6.3±5.9 mg · L ^-1 · h^-1, P<0.05), but treatment with simvastatin did not result in improvement of the postprandial RE response, either in the Sf<1000 fraction or in plasma. It is concluded that heterozygous FH patients have increased fasting and postprandial remnant lipoprotein concentrations. Treatment with simvastatin significantly reduced the fasting and postprandial RLP-C concentrations but did not result in improved postprandial RE response.

Key Words: heterozygous familial hypercholesterolemia • remnant lipoproteins • simvastatin

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