Lipoprotein and apolipoprotein abnormalities in familial combined hyperlipidemia: a 20-year prospective study.
In order to characterize the lipoprotein abnormalities in familial combined hyperlipidemia (FCHL) and to describe factors associated with the stability of the FCHL phenotype during 20-year follow-up, 287 individuals from 48 families with FCHL originally identified in the early 1970s (baseline) were studied. Hyperlipidemia was defined as lipid-lowering medication use, or > or =age- and sex-specific 90th percentile for triglycerides or cholesterol. Triglyceride, cholesterol and medical history data were obtained at baseline and 20-year follow-up. Additional follow-up measures included HDL-C, LDL-C, LDL particle size, lipoprotein(a), apolipoprotein (apo) A-I, apoB, and apoE polymorphism. Longitudinally, two-thirds of relatives were consistently normolipidemic or hyperlipidemic, and one third were discordant for hyperlipidemic status at baseline and 20-year follow-up. Individuals with hyperlipidemia at baseline and/or follow-up had higher apoB levels than those with consistently normal lipids (P<0.05), whereas small LDL size was associated with concurrent hyperlipidemia. Among individuals who were normolipidemic at baseline, the following variables were independently associated with development of hyperlipidemia over 20 years: older age at baseline, male sex, greater increase in BMI during follow-up, and apoE alleles epsilon 2 or epsilon 4. In conclusion, apoB is associated with hyperlipidemia and apoE polymorphism is associated with later onset of hyperlipidemia in FCHL.
McNeely
M J
MJ
Department of Medicine, School of Medicine, University of Washington, Box 356429, Seattle, WA 98195, USA. mcneely@u.washington.edu
Edwards
K L
KL
Marcovina
S M
SM
Brunzell
J D
JD
Motulsky
A G
AG
Austin
M A
MA
D000328:Adult; D017677:Age Distribution; D016632:Apolipoprotein A-I / Q000032:analysis / Q000235:genetics; D001053:Apolipoproteins / Q000097:blood / Q000235:genetics*; D002648:Child; D008076:Cholesterol, HDL / Q000097:blood / Q000235:genetics; D008078:Cholesterol, LDL / Q000097:blood / Q000235:genetics; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D006950:Hyperlipidemia, Familial Combined / Q000453:epidemiology / Q000235:genetics*; D015994:Incidence; D008074:Lipoproteins / Q000097:blood / Q000235:genetics*; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D011110:Polymorphism, Genetic; D011336:Probability; D011446:Prospective Studies; D012016:Reference Values; D012307:Risk Factors; D017678:Sex Distribution
D016632:Apolipoprotein A-I; D001053:Apolipoproteins; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D008074:Lipoproteins