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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2004;24:744.)
© 2004 American Heart Association, Inc.

Atherosclerosis and Lipoproteins

Subclasses of Low-Density Lipoprotein and Very Low-Density Lipoprotein in Familial Combined Hyperlipidemia: Relationship to Multiple Lipoprotein Phenotype

A.M. Georgieva; M.M.J. van Greevenbroek; R.M. Krauss; M.C.G.J. Brouwers; V.M.M.-J. Vermeulen; M.G. Robertus-Teunissen; C.J.H. van der Kallen; T.W.A. de Bruin

From the Cardiovascular Research Institute Maastricht, Laboratory of Molecular Metabolism and Endocrinology, Department of Medicine, University of Maastricht, The Netherlands; and Donner Laboratory (R.M.K.), Lawrence Berkeley National Laboratory, University of California, Berkeley.

Correspondence to Dr Tjerk W. A. de Bruin, Department of Internal Medicine and Endocrinology, Academic Hospital Maastricht, PO Box 5800, 6202 AZ Maastricht, The Netherlands. E-mail tdb{at}sint.azm.nl

Objective— The present study addresses the presence of distinct metabolic phenotypes in familial combined hyperlipidemia (FCHL) in relation to small dense low-density lipoprotein (sd LDL) and very low-density lipoprotein (VLDL) subclasses.

Methods and Results— Hyperlipidemic FCHL relatives (n=72) were analyzed for LDL size by gradient gel electrophoresis. Pattern B LDL (sd LDL, particle size <258 Å) and pattern A LDL (buoyant LDL, particle size 258 Å) were defined. Analyses showed bimodal distribution of LDL size associated with distinct phenotypes. Subjects with predominantly large, buoyant LDL showed a hypercholesterolemic phenotype and the highest apo B levels. Subjects with predominantly sd LDL showed a hypertriglyceridemic, low high-density lipoprotein (HDL) cholesterol phenotype, with moderately elevated apoB, total cholesterol level, and LDL cholesterol level. Subjects with both buoyant LDL and sd LDL (pattern AB, n=7) showed an intermediate phenotype, with high normal plasma triglycerides. VLDL subfraction analysis showed that the sd LDL phenotype was associated with a 10-times higher number of VLDL1 particles of relatively lower apo AI and apo E content, as well as smaller VLDL2 particles, in combination with increased plasma insulin concentration in comparison to pattern A.

Conclusions— The present observations underscore the importance of the VLDL triglyceride metabolic pathway in FCHL as an important determinant of the phenotypic heterogeneity of the disorder.

Key Words: sd LDL • apolipoprotein B • triglycerides • insulin resistance • VLDL

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