CHANGES OF LIPOPROTEIN PROFILE IN FAMILIAL DYSBETALIPOPROTEINEMIA WITH GEMFIBROZIL

PURPOSE: This prospective study was undertaken to evaluate the effects of gemfibrozil on the lipoprotein profile of patients with familial d ysbetalipoproteinemia (type III hyperlipoproteinemia). PATIENTS AND ME THODS: Eight patients with well-defined familial dysbetalipoproteinemi a associated, sociated with the apolipoprotein (ape) E2/2 phenotype we re treated with gemfibrozil (Lopid) at a dose of 600 mg twice daily fo r 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 s erum 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), res pectively. The cholesterol concentrations of very-low-density lipoprot ein-1 (VLDL(1)) (large VLDL), VLDL(2) (small VLDL), and intermediate-d ensity 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 b ut significant increase (from 24.09 nn to 24.43 nm, p <0.01). The conc entrations of high-density lipoprotein (HDL)cholesterol, ape A-I, and ape A-II had increased significantly by 23%, 13%, and 29%, respectivel y. Only minor changes in the composition of the lipoprotein (sub)fract ions 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 o f treatment with gemfibrozil, the concentrations of serum total choles terol and serum total triglyceride were 6.19 mmol/L and 2.27 mmol/L, r espectively. CONCLUSION: Gemfibrozil treatment in patients with famili al dysbetalipoproteinemia resulted in a marked reduction of the concen trations of large VLDL, small VLDL, and IDL, and an increase in the le vels of HDL, ape A-I, and ape A-II. These changes are considered to ex ert an antiatherosclerotic effect in these patients.