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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2003;23:2078.)
© 2003 American Heart Association, Inc.

Atherosclerosis and Lipoproteins

Magnitude of HDL Cholesterol Variation After High-Dose Atorvastatin Is Genetically Determined at the LDL Receptor Locus in Patients With Homozygous Familial Hypercholesterolemia

Andrei C. Sposito; Sophie Gonbert; Eric Bruckert; Marielle Atassi; Isabel Beucler; Sabine Amsellem; Oumayma Khallouf; Pascale Benlian; Gerard Turpin

From the Dyslipoproteinemia and Atherosclerosis Research Unit (U.551) (A.C.S., S.G.), National Institute for Health and Medical Research (INSERM), Paris; Department of Endocrinology and Metabolism (S.G., E.B., M.A., G.T.) and Laboratory of Lipids, Department of Medical Biochemistry (I.B.), APHP Hôpital de La Pitié-Salpetrière; and Department of Biochemistry and Molecular Biology (O.K., S.A., P.B.), APHP Saint Antoine Hospital, Paris, France; and Heart Institute (InCor) (A.C.S.), Zerbini Foundation, Brasilia, Brazil.

Correspondence to Dr Andrei C. Sposito, Instituto do Coração (InCor), Fundação Zerbini, Estrada do Contorno do Bosque–Cruzeiro Novo, Brasilia, DF, Brazil, 70685.700. E-mail sposito{at}zerbini.org.br

Objective— The combination of LDL apheresis with high doses of a potent hepatic hydroxymethylglutaryl coenzyme A reductase inhibitor, such as atorvastatin, has been the best therapy available for the prevention of cardiovascular disease in patients with homozygous familial hypercholesterolemia (HFH). However, some concerns have been made about the effect of atorvastatin on HDL cholesterol levels in these patients.

Methods and Results— HDL cholesterol levels were determined bimonthly over the course of 2 years of treatment with high-dose atorvastatin in genotypically defined HFH patients either receptor-defective (n=6) or receptor-negative (n=6) under long-term treatment with LDL apheresis. We additionally stratified the atorvastatin effect on HDL cholesterol according to the genotype as an indicator of residual in vivo LDL receptor activity. Our findings indicate that (1) an early and transitory reduction of plasma HDL cholesterol levels occurs during the first 4 weeks of atorvastatin treatment; (2) the degree of the transient HDL reduction is higher in receptor-negative than in receptor-defective patients (-21±11 versus -10±4%; P=0.01); and (3) after long-term treatment, HDL cholesterol concentration remains higher in receptor-defective than receptor-negative patients (P=0.026).

Conclusions— The present study reveals that HDL cholesterol reduction after high-dose atorvastatin is an early and transient event in HFH patients which magnitude depends on the presence of a residual LDL-R activity.

Key Words: hypercholesterolemia • prevention • follow-up studies

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