Differential effects of fenofibrate and extended-release niacin on high-density lipoprotein particle size distribution and cholesterol efflux capacity in dyslipidemic patients

Effects of Established Hypolipidemic Drugs on HDL Concentration, Subclass Distribution, and Function

“…These observed results might be explained by a shift of HDL from large to small particles, the preferential cholesterol acceptors for ABCA1 (Adorni et al 2007). This result was not confirmed in a more recent paper by the same group (Franceschini et al 2013), likely because of the different HDL particle profile in the two investigated populations of patients. In the first study (Guerin et al 2002), patients displayed a greater content of large HDL particles, whereas in patients with dyslipidemia of the last study (Franceschini et al 2013), the small, ABCA1-interacting HDL was the predominant fraction, and no further increase in this HDL population was observed after fenofibrate therapy, consistent with the lack of changes in ABCA1-mediated CEC.…”

“…This result was not confirmed in a more recent paper by the same group (Franceschini et al 2013), likely because of the different HDL particle profile in the two investigated populations of patients. In the first study (Guerin et al 2002), patients displayed a greater content of large HDL particles, whereas in patients with dyslipidemia of the last study (Franceschini et al 2013), the small, ABCA1-interacting HDL was the predominant fraction, and no further increase in this HDL population was observed after fenofibrate therapy, consistent with the lack of changes in ABCA1-mediated CEC. Whether fenofibrate therapy modulate the ability of plasma or HDL to facilitate cholesterol efflux from macrophages has been investigated also in a subset of the FIELD study showing that cholesterol efflux values from macrophage foam cells to HDL and plasma in the fenofibrate group (200 mg/day for 5 years) were comparable to those of the placebo group .…”

“…Several studies have confirmed this observation in patients with different types of dyslipidemia treated with 2, 3, or 4 g/day of regular or ER niacin (Johansson and Carlson 1990;Knopp et al 1998;Morgan et al 2003;Wahlberg et al 1990) and in patients with coronary artery disease (Kuvin et al 2006). A very recent study showed that also 1 g/day of ER niacin increases large HDL particles in dyslipidemic patients, with a concomitant significant increase in mean HDL size (Franceschini et al 2013). The analysis of HDL subclasses by 2-D gel electrophoresis recently confirmed the observation that niacin promotes the maturation of HDL into large particles (Lamon-Fava et al 2008), likely explained by a reduction in CETP activity.…”

Dysfunctional high-density lipoproteins in coronary heart disease: implications for diagnostics and therapy

“…165 An intervention study in patients with dyslipidemia found no significant change in serum cholesterol efflux capacity after 6 weeks of extended-release niacin therapy (titrated up to 1 g/day). 170 Similarly, adding niacin (2 g daily) to simvastatin therapy provided no additional benefit with regard to cholesterol efflux capacity and HDL inflammatory index in patients with carotid atherosclerosis, despite increasing HDL-cholesterol by 29%. 171 A placebo-controlled clinical trial by Taylor et al examined whether extended-release niacin slows the progression and/or causes regression of angiographically assessed coronary atherosclerosis.…”

“…178 Treatment of patients with fenofibrate, bezafibrate, ciprofibrate, or the potent and selective PPAR-α agonist LY518674 increased the capacity of total or apoB-free plasma to release cholesterol from macrophages in some studies, [179][180][181][182][183] but not in others. 170,184 Potential reasons are differences in patient populations and cholesterol efflux assays. Notably, ABCA1-mediated cholesterol efflux capacity appears to be improved upon fibrate treatment.…”