BACKGROUND: The effectiveness of therapies that raise high-density lipoprotein cholesterol (HDL-C) to lower cardiovascular disease risk is currently under debate, and further research into the relationship between HDL-C and function is required. OBJECTIVE: o investigate whether 2 established HDL-C-raising therapies had differential effects on parameters of high-density lipoprotein (HDL) quality and function, such as HDL particle profile and cholesterol efflux capacity (CEC), in patients with dyslipidemia. METHODS AND RESULTS: Sixty-six patients with dyslipidemia, 24 with low HDL-C levels (<40 mg/dL) and 42 with normal HDL-C levels (40-59 mg/dL), were treated for 6 weeks with fenofibrate (160 mg/d) or extended-release (ER) niacin (0.5 g/d for 3 weeks, then 1 g/d) with 4 weeks of washout between treatments. Lipoprotein particle size distribution was determined using nuclear magnetic resonance, and pathway-specific serum CECs were assessed in J774 macrophages, hepatoma, and Chinese hamster ovary-human adenosine triphosphate-binding cassette transporter G1 cells. Comparable increases in HDL-C and apolipoprotein A-I levels were seen with fenofibrate and ER niacin. There was a shift toward larger HDL, predominantly to medium-size HDL particles for fenofibrate (+209%) and to large HDL particles for ER niacin (+221%). Minor changes in serum CECs were observed with fenofibrate and ER niacin for all the efflux pathways measured. Small increases in plasma cholesteryl ester transfer protein and lecithin: cholesterol acyltransferase concentrations, and decreases in cholesteryl ester transfer protein activity were seen with both drugs. CONCLUSIONS: Fenofibrate and ER niacin increased plasma HDL-C level similarly, but modulated HDL particle size distribution differently; however, these changes did not result in differential effects on serum CECs.
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