title: Changes of lipoprotein profile in familial dysbetalipoproteinemia with gemfibrozil.
abstract: 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.
authors.affiliation: Department of Cardiology, University Hospital, Leiden, The Netherlands.
authors.forename: S P
authors.initials: SP
authors.lastname: Zhao
authors.forename: A H
authors.initials: AH
authors.lastname: Smelt
authors.forename: J A
authors.initials: JA
authors.lastname: Leuven
authors.forename: T F
authors.initials: TF
authors.lastname: Vroom
authors.forename: A
authors.initials: A
authors.lastname: van der Laarse
authors.forename: F M
authors.initials: FM
authors.lastname: van 't Hooft
mesh_terms: 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
chemical_list: D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D008074:Lipoproteins; D008079:Lipoproteins, VLDL; D014280:Triglycerides; D002784:Cholesterol; D015248:Gemfibrozil