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Journal of Lipid Research, Vol. 44, 1536-1544, August 2003
Copyright © 2003 by American Society for Biochemistry and Molecular Biology

Determinants of low HDL levels in familial combined hyperlipidemia

Aino Soro^*, Matti Jauhiainen, Christian Ehnholm and Marja-Riitta Taskinen^1,*

^* Division of Cardiology, Department of Medicine, University of Helsinki, Finland
Department of Molecular Medicine, Biomedicum, National Public Health Institute, Helsinki, Finland

¹ To whom correspondence should be addressed. e-mail: mataskin{at}cc.helsinki.fi

In familial combined hyperlipidemia (FCHL), affected family members frequently have reduced levels of HDL cholesterol, in addition to elevated levels of total cholesterol and/or triglycerides (TGs). In the present study, we focused on those determinants that are important regulators of HDL cholesterol levels in FCHL, and measured postheparin plasma activities of hepatic lipase (HL), lipoprotein lipase, cholesterol ester transfer protein, and phospholipid transfer protein (PLTP) in 228 subjects from 49 FCHL families. In affected family members (n = 88), the levels of HDL cholesterol, HDL₂ cholesterol, HDL₃ cholesterol, and apolipoprotein A-I were lower than in unaffected family members (n = 88) or spouses (n = 52). The main change was the reduction of HDL₂ cholesterol by 25.4% in affected family members (P < 0.001 vs. unaffected family members; P = 0.003 vs. spouses). Affected family members had higher HL activity than unaffected family members (P = 0.001) or spouses (P = 0.013). PLTP activity was higher in affected than unaffected family members (P = 0.025). In univariate correlation analysis, a strong negative correlation was observed between HL activity and HDL₂ cholesterol (r = -0.339, P < 0.001). Multivariate regression analysis demonstrated that gender, HL activity, TG, and body mass index have independent contributions to HDL₂ cholesterol levels.

We suggest that in FCHL, TG enrichment of HDL particles and enhanced HL activity lead to the reduction of HDL cholesterol and HDL₂ cholesterol.

Supplementary key words HDL₂ cholesterol • hepatic lipase • triglycerides • phospholipid transfer protein • cholesteryl ester transfer protein • lipoprotein lipase • insulin resistance

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