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(Circulation. 2002;106:788.)
© 2002 American Heart Association, Inc.

Clinical Investigation and Reports

Elevated Remnant-Like Particles in Heterozygous Familial Hypercholesterolemia and Response to Statin Therapy

Pernette R. W. de Sauvage Nolting, MD; Marcel B. Twickler, MD; Geesje M. Dallinga-Thie, PhD; Rudolf J.A. Buirma, MD; Barbara A. Hutten, PhD; John J.P. Kastelein, MD, PhD, for the Examination of Probands and Relatives in Statin Studies with Familial Hypercholesterolemia (ExPRESS) Study Group

From the Department of Vascular Medicine, Academic Medical Center (P.R.W.d.S.N., B.A.H., J.J.P.K.), Amsterdam, the Netherlands; Department of Vascular Medicine, University Medical Center (M.B.T., G.M.D.-T.), Utrecht, the Netherlands; and Merck, Sharp and Dohme (R.J.A.B.), Clinical Research, Haarlem, the Netherlands.

Correspondence to P.R.W. de Sauvage Nolting, MD, Academic Medical Center, G1-114. Meibergdreef 9, 1105AZ Amsterdam, Netherlands. E-mail p.desauvagenolting{at}amc.uva.nl

Background— Remnant lipoproteins (RLP-C) are considered important in atherogenesis. Hence, this study was designed to assess RLP-C levels and the effect of statin therapy in patients with familial hypercholesterolemia (FH). Elevated RLP-C levels have been associated with the presence and progression of atherosclerotic disease, and their presence in FH patients has been proposed but never established in a large cohort, nor has their response to statin therapy been confirmed.

Methods and Results— FH patients were recruited from 36 lipid clinics. After a washout period of 6 weeks, all patients were started on monotherapy with 80 mg of simvastatin for 2 years. RLP-C levels were assessed by an immune-separation assay. In 327 FH patients, RLP-C measurements could be performed before and after treatment. Mean total cholesterol (10.55±2.17 mmol/L), mean LDL cholesterol (8.40±2.13 mmol/L), and median RLP-C (0.47 mmol/L) levels were all severely elevated at baseline. After treatment, RLP-C levels were reduced by 49% (0.24 mmol/L; P<0.0001). Even patients with normal triglyceride levels had elevated RLP-C levels at baseline, and those with high RLP-C levels were generally characterized by a very atherogenic lipoprotein profile.

Conclusions— Baseline RLP-C levels are severely elevated in FH patients and are reduced by simvastatin but do not return to normal. These elevated RLP-C levels could be the consequence of impaired function of the LDL receptor in FH. RLP-C levels in FH contribute to an atherogenic lipoprotein profile and could identify patients who require additional treatment.

Key Words: hypercholesterolemia • lipids • lipoproteins • atherosclerosis

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