The significance of hypertriglyceridemia as a cardiovascular risk factor is further highlighted by its inclusion as a component of the metabolic syndrome, a cluster of metabolic abnormalities, related to insulin resistance. The other criteria for metabolic syndrome include low HDL cholesterol, central obesity, elevated blood pressure, and abnormal fasting glucose. People with metabolic syndrome are at increased risk of cardiovascular disease and type 2 diabetes.

We have found evidence that fenofibrate lowers TG levels and produces improvements in several lipid markers for cardiovascular disease risk in subjects with hypertriglyceridemia and the metabolic syndrome.¹ Fenofibrate treatment resulted in significant changes versus placebo in TG,VLDL cholesterol, LDL cholesterol,HDL cholesterol, remnant lipoprotein-C, apolipoprotein B, apolipoprotein A-I, and apolipoprotein C-III.

Several previous studies have shown that fibrate therapy has the beneficial effect of increasing LDL particle size.^2–4 It has been hypothesized that changes in LDL particle size do not occur uniformly, but rather follow a pattern where larger, more buoyant LDL particles predominate (LDL subclass pattern A) when the circulating TG concentration is low, but that a shift occurs to a predominance of small, dense LDL particles (LDL subclass pattern B) when the TG level increases above a threshold value.⁵ The threshold at which this shift in LDL subclass pattern occurs may be largely hereditary and, in the majority of individuals, appears to occur in the range of 100–200mg/dl.^6-8

In our investigations with hypertriglyceridemic subjects, changes in LDL particle diameter with fenofibrate treatment were shown to be significantly inversely associated with the TG level achieved on treatment.When individually matched for per cent change in TG, subjects with on-treatment TG <200mg/dl, in contrast to those with on-treatment values ≥200mg/dl, had significantly different responses with regard to changes in LDL size. In the Diabetes Atherosclerosis Intervention Study (DAIS), fenofibrate reduced the rate of coronary artery disease progression in subjects with type 2 diabetes.¹⁹ The change in LDL particle size also correlated inversely with the plasma TG level achieved.5 Subjects in the lowest tertile of on-treatment TG concentration (<113mg/dl) had a mean increase of 1.19nm in LDL particle diameter, whereas those in the highest tertile (>160mg/dl) had a mean increase of 0.69nm.