Changes in serum levels of angiopoietin-like protein-8 and glycosylphosphatidylinositol-anchored high-density lipoprotein binding protein 1 after ezetimibe therapy in patients with dyslipidemia.

Changes in serum levels of angiopoietin-like protein-8 (ANGPTL8) and glycosylphosphatidylinositol-anchored high-density lipoprotein binding protein 1 (GPIHBP1) in patients with dyslipidemia after ezetimibe therapy remain to be elucidated. Thirty-eight patients who initially received ezetimibe and were followed for 16 weeks were enrolled. Various parameters were investigated before and after 16 weeks of ezetimibe treatment in all patients. In addition, the patients were also divided into metabolic syndrome (MetS) (n = 22) and Non-MetS (n = 16) groups, and various parameters were compared between these groups. ANGPTL8 was significantly positively correlated with triglyceride (TG) and negatively correlated with high-density lipoprotein cholesterol (HDL-C) before treatment in all patients and in the MetS group. After treatment, TC and LDL-C were significantly decreased in all patients, and in both the MetS and Non-MetS groups, whereas there were no changes in TG or HDL-C. Serum levels of remnant-like particle cholesterol (RLP-C) significantly decreased in all patients and in the MetS group. The ANGPTL8 level before treatment was significantly positively associated with TG and negatively correlated with HDL-C in all patients and in the MetS group. ANGPTL8 and GPIHBP1were significantly decreased after treatment in all patients. GPIHBP1 was also significantly decreased after treatment in both groups. In conclusion, this is the first report to support the possibility of a new effect of ezetimibe therapy. Ezetimibe significantly decreased the serum level of LDL-C, but not TG or HDL-C, while reducing ANGPTL8 and GPIHBP1 in all patients with dyslipidemia. In addition, ezetimibe significantly decreased RLP-C levels in the MetS group.

Ezetimibe Monotherapy Reduces Serum Levels of Platelet-Activating Factor Acetylhydrolase in Patients With Dyslipidemia.

BACKGROUND: The combination of ezetimibe with statin therapy reduced cardiovascular events compared to statin monotherapy in IMPROVEIT study, and ezetimibe monotherapy attenuated atherosclerosis in basic study. We previously showed ezetimibe monotherapy was especially effective for metabolic syndrome (MetS) patients. We investigated the effects of ezetimibe monotherapy for high-density lipoprotein cholesterol (HDL-chol) function and platelet-activating factor acetylhydrolase (PAF-AH) activity. METHODS: Forty-two patients who initially received ezetimibe (10 mg/day) without statin treatment for 16 weeks from January 2009 to August 2011 were enrolled. Patients were divided into MetS and non-MetS groups, and serum levels of lipids, PAF-AH, and HDL-chol efflux capacity (HDL-CEC) at baseline and after 16 weeks of treatment were investigated. Serum PAF-AH, HDL-associated PAF-AH (HDL-PAF-AH), and LDL-associated PAF-AH (LDL-PAF-AH) were measured. RESULTS: In all patients, age, the percentages of males, and body mass index were 61.0 ± 8.8 years, 59.5% and 26.3 ± 3.4 kg/m2, respectively. Total cholesterol and low-density lipoprotein cholesterol (LDL-chol) were significantly decreased by ezetimibe monotherapy. Serum PAF-AH and LDL-PAF-AH were significantly decreased by ezetimibe monotherapy, whereas HDL-PAF-AH and HDL-CEC were not. There was no difference in the results of PAF-AH and HDL-CEC between MetS and non-MetS groups. CONCLUSIONS: Ezetimibe monotherapy might prevent coronary heart disease (CHD) regardless of the presence of MetS, because PAF-AH was independent risk factor for CHD.