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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2003;23:1289.)
© 2003 American Heart Association, Inc.

Atherosclerosis and Lipoproteins

Small, Dense LDL and Elevated Apolipoprotein B Are the Common Characteristics for the Three Major Lipid Phenotypes of Familial Combined Hyperlipidemia

Amir F. Ayyobi; Sandra H. McGladdery; Marguerite J. McNeely; Melissa A. Austin; Arno G. Motulsky; John D. Brunzell

From the Division of Metabolism, Endocrinology, and Nutrition, Department of Medicine (A.F.A., S.H.M., J.D.B.); Division of General Internal Medicine, Department of Medicine (M.J.M); Department of Epidemiology and Institute for Public Health Genetics, School of Public Health and Community Medicine (M.A.A.); and Division of Medical Genetics, Department of Medicine, and Department of Genome Sciences (A.G.M.), University of Washington, Seattle, Wash.

Correspondence to Dr John D. Brunzell, University of Washington Medical Center, Department of Medicine, Division of Metabolism, Endocrinology, and Nutrition, Box 356426, Seattle, WA 98195-6426. E-mail brunzell{at}u.washington.edu

Objective— Familial combined hyperlipidemia (FCHL) is associated with variable lipid and lipoprotein phenotypes arbitrarily defined as type IIa, IIb, and IV based on plasma total cholesterol and triglyceride levels. This study sought to characterize consistent lipoprotein and lipid abnormalities across the 3 lipoprotein phenotypes in 62 patients with documented FCHL (IIa [n=14], IIb [n=19], and IV [n=29]) and 44 healthy individuals.

Methods and Results— The lipoprotein cholesterol distribution was determined over 38 fractions obtained by density gradient ultracentrifugation. As expected, FCHL patients with hypertriglyceridemia (IIb and IV) had higher cholesterol levels in VLDL than IIa, whereas IIa showed higher cholesterol in the big, buoyant LDL and in HDL. LDL cholesterol was higher in IIb than IV; most of the increase in LDL cholesterol was associated with big, buoyant LDL rather than small, dense LDL (sdLDL). The differences in lipoproteins between phenotypes were attributable to changes in VLDL and big, buoyant LDL levels. Comparison of the FCHL patients with healthy individuals showed a significant elevation in plasma apolipoprotein B levels and sdLDL in all 3 FCHL phenotypes.

Conclusions— Although triglyceride and cholesterol levels are variable by lipoprotein phenotype, sdLDL and elevated plasma apolipoprotein B levels are consistent characteristics of FCHL shared by the 3 different lipoprotein phenotypes.

Key Words: cholesterol • triglyceride • Fredrickson’s lipoprotein phenotype

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