Effects of fenofibrate on atherogenic dyslipidemia in hypertriglyceridemic subjects

Background: The metabolic syndrome (MS) is often accompanied by atherogenic dyslipidemia, which is characterized by elevated triglycerides (TG), reduced high-density lipoprotein cholesterol (HDL-C), and elevated numbers of small, dense low-density lipoprotein (LDL) particles. Hypothesis: It was hypothesized that a threshold exists for the circulating TG level needed to produce changes in LDL subclass distribution. Methods: Hypertriglyceridemic (TG >= 300 and < 1000 mg/dl) subjects with the MS were randomly assigned to placebo (n = 50) or 130 mg/day of micronized fenofibrate-coated microgranules (n = 96) for 8 weeks. Results: In the overall analysis, fenofibrate treatment resulted in significant (p < 0.05) changes versus placebo in TG (-36.6%), non-HDL-C (-7.5%), very low-density lipoprotein-C (-32.7%), LDL-C (15.0%), HDL-C (14.0%), remnant hpoprotein-C (-35.1%), apolipoprotein B (-6.0%), apolipoprotein A-I (5.3%), and apolipoprotein C-III -29.7%). Changes in LDL particle diameter in the fenofibrate group were significantly inversely associated with the TG level achieved on treatment (p = 0.019). When individually matched for percent change in TG, subjects with on-treatment TG < 200 mg/dl, in contrast to those with on-treatment values >= 200 mg/dl, had significantly different median responses (p < 0.05) in LDL size (0.79 vs. -0.06 m) and cholesterol carried by small (-35 vs. 21 mg/dl) and large (31 vs. 11 mg/dl) particles. Conclusion: These data support the view that a threshold exists below which the TG level must be lowered to produce shifts in LDL particle size.