Heterogeneous postprandial lipoprotein responses in the metabolic syndrome, and response to fenofibrate therapy

Background: Hypertriglyceridemia subjects with metabolic syndrome exhibit variable postprandial triglyceride responses. We investigate the effects of fenofibrate therapy on postprandial triglyceride-containing lipoproteins in subjects with early (3.5 h) versus late (8 h) postprandial triglyceride responses. Methods: Fifty-five subjects with fasting hypertriglyceridemia (≥1.7 mmol/L (150 mg/ dL) and <5.8 mmol/L (500 mg/dL)) and ≥2 Adult Treatment Panel III criteria of the metabolic syndrome were randomized to daily fenofibrate (160 mg/d) or placebo for 12 weeks in a double-blind controlled clinical trial. A standardized fat load (50 g/m²) was given orally after a 12 h fast. Blood specimens were obtained at 0 h (fasting), 3.5 h, and 8 h after the test meal. Analysis is confined to the 53 subjects with clearly identifiable early or late triglyceride peaks prior to therapy. Results: Fenofibrate was more effective in late peakers (n= 8) when compared to early peakers (n=15) with respect to reducing postprandial triglyceride concentrations (-67% vs. -34%, p=0.0024) and large VLDL (-76% vs. -31%, p= 0.0016), and increasing total HDL particles (20% vs. 11%, p=0.008) and large HDL particles (185% vs. 88%, p=0.003). On fenofibrate therapy, 100% of those initially designated as late peakers were reclassified as early peakers; 47% of late peakers assigned to placebo were reclassified as early peakers. Conclusions: Late postprandial triglyceride responders have attenuated clearance of large VLDL particles, but they were more responsive to fenofibrate.