Abstract
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 lipoprotein‐C (−35.1%), apolipoprotein B (−6.0%), apoli‐poprotein 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 nm) 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.
Keywords: triglycerides, hypertriglyceridemia, low‐density lipoprotein, particle size, fenofibrate
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