Ezetimibe decreases serum amyloid A levels in HDL3 in hemodialysis patients

Abstract

The aim of this study was to investigate the effects of ezetimibe on high-density lipoprotein (HDL) subspecies and serum amyloid A (SAA), an apolipoprotein mainly bound and transported by HDL particles, in patients with end-stage renal disease (ERSD), a condition typically characterized by high SAA- and low HDL-cholesterol (C ) levels. 26 ERSD patients receiving hemodialysis (HD) were given ezetimibe (10 mg/d) for 6 - 8 weeks. HDL3 was separated from serum by a single precipitation method established by our group. HDL2 was estimated by subtracting HDL3 from total HDL. Serum amyloid A (SAA) was measured by the ELISA method. Ezetimibe significantly reduced remnant-like particle (RLP)-C, low-density lipoprotein (LDL)-C, and apolipoprotein (apo) B without affecting triglyceride, HDL-C and LCAT activities. HDL2-C levels were lower and HDL3-C was substantially lower in the HD patients than in the controls. Ezetimibe increased HDL2-apoAI but decreased HDL3-apoAI without affecting serum apoAI or AII. HDL-SAA was 5-fold higher in the HD patients than in the controls (56 ± 49 vs. 12 ± 9 µg/ml). Ezetimibe decreased HDL-SAA by 43 % (to 32 ± 36 µg/ml), and this inhibitory effect was exclusively attributable to a 72% reduction in HDL3-SAA in response to the ezetimibe treatment. The reduction of HDL3-SAA was significantly associated with increased HDL2-apo AI and reduced HDL3-apo AI. Ezetimibe treatment decreased "inflammatory" (SAA-containing) HDL3, and may thus have restored the anti-atherogenic function of HDL particles in ESRD patients.