Changes of lipoprotein profile in familial dysbetalipoproteinemia with gemfibrozil.
OBJECTIVE
This prospective study was undertaken to evaluate the effects of gemfibrozil on the lipoprotein profile of patients with familial dysbetalipoproteinemia (type III hyperlipoproteinemia).


METHODS
Eight patients with well-defined familial dysbetalipoproteinemia associated with the apolipoprotein (apo) E2/2 phenotype were treated with gemfibrozil (Lopid) at a dose of 600 mg twice daily for a period of 10 months. Blood samples were taken at baseline, after 4 and 5 weeks, after 3 months, and after 10 months. The separation of serum lipoprotein (sub)fractions was performed by a recently developed density gradient ultracentrifugation technique.


RESULTS
After 4 weeks of gemfibrozil therapy, the concentrations of serum total cholesterol and serum total triglyceride had decreased by 45% (from 11.87 to 6.51 mmol/L, p < 0.01) and by 63% (from 6.08 to 2.23 mmol/L, p < 0.001), respectively. The cholesterol concentrations of very-low-density lipoprotein-1 (VLDL1) (large VLDL), VLDL2 (small VLDL), and intermediate-density lipoprotein (IDL) had decreased significantly by 73%, 74%, and 34%, respectively. The low-density lipoprotein (LDL)-cholesterol level remained unchanged, whereas the particle size of LDL showed a small but significant increase (from 24.09 nm to 24.43 nm, p < 0.01). The concentrations of high-density lipoprotein (HDL)-cholesterol, apo A-I, and apo A-II had increased significantly by 23%, 13%, and 29%, respectively. Only minor changes in the composition of the lipoprotein (sub)fractions were observed. After 3 months of treatment with gemfibrozil, the concentrations of serum total cholesterol and serum total triglyceride were 5.95 mmol/L and 2.06 mmol/L, respectively, and after 10 months of treatment with gemfibrozil, the concentrations of serum total cholesterol and serum total triglyceride were 6.19 mmol/L and 2.27 mmol/L, respectively.


CONCLUSIONS
Gemfibrozil treatment in patients with familial dysbetalipoproteinemia resulted in a marked reduction of the concentrations of large VLDL, small VLDL, and IDL, and an increase in the levels of HDL, apo A-I, and apo A-II. These changes are considered to exert an antiatherosclerotic effect in these patients.
Zhao
S P
SP
Department of Cardiology, University Hospital, Leiden, The Netherlands.
Smelt
A H
AH
Leuven
J A
JA
Vroom
T F
TF
van der Laarse
A
A
van 't Hooft
F M
FM
D000328:Adult; D000368:Aged; D002499:Centrifugation, Density Gradient; D002784:Cholesterol / Q000097:blood; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D016521:Electrophoresis, Gel, Pulsed-Field; D005260:Female; D015248:Gemfibrozil / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D006952:Hyperlipoproteinemia Type III / Q000097:blood* / Q000188:drug therapy*; D008074:Lipoproteins / Q000097:blood*; D008079:Lipoproteins, VLDL / Q000097:blood; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D014280:Triglycerides / Q000097:blood
D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D008074:Lipoproteins; D008079:Lipoproteins, VLDL; D014280:Triglycerides; D002784:Cholesterol; D015248:Gemfibrozil