High dose of simvastatin normalizes postprandial remnant-like particle response in patients with heterozygous familial hypercholesterolemia

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

doi:10.1161/01.ATV.20.11.2422

Title

High dose of simvastatin normalizes postprandial remnant-like particle response in patients with heterozygous familial hypercholesterolemia

Author

Twickler, T.B.

Dallinga-Thie, G.M.

de Valk, H.W.

Schreuder, P.C.N.J.

Jansen, H.

Cabezas, M.C.

Erkelens, D.W.

Abstract

Familial hypercholesterolemia (FH) and disturbances in postprandial lipoprotein metabolism are both associated with premature atherosclerosis. The effect of beta -hydroxy-beta -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.

Language

English

Source (journal)

Arteriosclerosis, thrombosis, and vascular biology / American Heart Association. - Dallas, Tex., 1995, currens

Publication

Dallas, Tex. : 2000

ISSN

1079-5642

1524-4636 [online]

DOI

10.1161/01.ATV.20.11.2422

Volume/pages