Effects of gemfibrozil on plasma lipoprotein-apolipoprotein distribution and platelet reactivity in patients with hypertriglyceridemia

The effects of gemfibrozil on plasma lipoprotein distribution and composition and on platelet function were investigated in 11 patients with stable hypertriglyceridemia, six belonging to Fredrickson type IIb and five to type IV. Gemfibrozil (600 mg twice a day) significantly reduced total and very low density lipoprotein (VLDL)-associated triglyceridemia (respectively -32.4% and -40.4%, after 6 weeks of treatment). No significant variations were noted in the lipid components of low-density lipoproteins; by contrast, a marked increase (18%) was detected in high-density lipoprotein (HDL)-associated cholesterol. Comparison of the two patient groups (type IIb and type IV) showed that those with type IIb had both a more significant reduction of triglyceridemia and a more marked increase of HDL-cholesterol. Apolipoprotein B levels were reduced in both groups (-12%) with no change in apolipoprotein AI. The cholesterol content in the HDL subfractions, separated by rate zonal ultracentrifugation, was raised in HDL₃ (18%) and in HDL₂ (14%). Both particles also showed significant increases of the cholesterol/protein and the cholesterol/phospholipid ratios. A non-statistically significant decrease in collagen-induced aggregation and in the release of thromboxane B₂ was noted after treatment. These findings suggest that, similar to what was recently reported in normal individuals and in laboratory animals, the probable mode of action of gemfibrozil is in reducing the secretion of atherogenic lipoproteins, particularly VLDL, while stimulating the production of small HDL particles.