Effect of fenofibrate treatment on plasma lipoprotein lipids, high-density lipoprotein cholesterol subfractions, and apolipoproteins B, AI, AII, and E

Abstract

In this segment of a multicenter study, 36 hypercholesterolemic patients were randomly assigned to fenofibrate or placebo treatment to assess effects on plasma concentrations of lipoprotein cholesterol and triglyceride, high-density lipoprotein-cholesterol subfractions, and apolipoproteins E, B, AI, and AII. All of these factors are of known or potential value in determining the patient's risk of arteriosclerosis. Observations were made during initial screening and placebo phases, a 24-week, double-blind treatment phase, and a subsequent 24-week, open-label fenofibrate phase. There were three possible expressions of fenofibrate efficacy. Changes in lipoprotein cholesterol and total triglyceride concentrations observed in these patients were very similar to those seen with the larger multicenter cohort: total triglyceride levels decreased 38 to 46 percent, low-density lipoprotein cholesterol levels decreased 13 to 20 percent, and high-density lipoprotein cholesterol levels increased 4 to 13 percent. Triglyceride concentrations were significantly reduced (p <0.01) in very low-density lipoprotein (50 to 56 percent, similar to those of total triglyceride and very low-density lipoprotein cholesterol), and in low-density lipoprotein cholesterol levels (17 to 21 percent). A slight but statistically insignificant decrease in high-density lipoprotein triglyceride was observed (9 to 15 percent). High-density lipoprotein 2 cholesterol levels did not change significantly, whereas high-density lipoprotein 3 cholesterol levels increased 8 to 16 percent, accounting for all of the increase in high-density lipoprotein cholesterol. Apoprotein AII levels increased significantly (13 to 20 percent) whereas those of apolipoprotein AI did not, consistent with an increase in high-density lipoprotein 3 levels, where apolipoprotein AII is more abundant relative to apolipoprotein AI than in high-density lipoprotein 2. Apolipoprotein B levels decreased 20 to 26 percent and those of apolipoprotein E went from 29 to 34 percent, relative to the 16 to 20 percent decreases in very low-density lipoprotein and low-density lipoprotein triglyceride and cholesterol levels. Five patients with combined elevations of triglyceride and low-density lipoprotein cholesterol treated with fenofibrate, had reductions primarily in triglyceride, total apolipoprotein E (50 percent reduction), and apolipoprotein B (18 percent) levels. High-density lipoprotein 3 cholesterol levels increased 19 percent and high-density lipoprotein 2 cholesterol levels were unchanged. Low-density lipoprotein cholesterol levels declined slightly in four patients and a slight rise was observed in a fifth patient. We conclude that fenofibrate lowers levels of apolipoproteins E and B, with reductions in total triglyceride and cholesterol levels of very low-density lipoprotein and low-density lipoprotein in type II A patients, and very low-density lipoprotein in type II B patients. All of these changes are potentially beneficial in reducing the risk of cardiovascular disease. The mechanism and significance for atherosclerosis prevention of selective increases in high-density lipoprotein 3 and apolipoprotein AII in both types II A and II B hypercholesterolemic patients treated with fenofibrate remains to be determined.