Effects of ezetimibe on markers of synthesis and absorption of cholesterol in high-risk patients with elevated C-reactive protein

Author(s)

Barbosa, Simone P. ^[1] ; Lins, Livia C. ^[1] ; Fonseca, Francisco A. ^[1] ; Matos, Livia N. ^[1] ; Aguirre, Ana C. ^[1] ; Bianco, Henrique T. ^[1] ; Amaral, Jonatas B. ^[1] ; Franca, Carolina N. ^[1] ; Santana, Jose M. ^[2] ; Izar, Maria C. ^[1]

Affiliation

^[1] Univ Fed Sao Paulo, Lipids Atherosclerosis & Vasc Biol Sect, Div Cardiol, Dept Med, BR-04039030 Sao Paulo - Brazil

^[2] Tasqa, Campinas, SP - Brazil

• Document type: Journal article
• Source: Life Sciences; v. 92, n. 14-16, p. 845-851, MAY 2 2013.
• Web of Science Citations: 10

Abstract

Aims: High-risk subjects with elevated C-reactive protein (CRP) are at high risk for cardiovascular events and frequently require potent statins or combined lipid-lowering therapy to achieve lipid targets and decrease inflammation. Our study aimed at evaluating the effects of three lipid-modifying therapies on LDL-cholesterol, CRP levels and markers of cholesterol absorption and synthesis. Main methods: A prospective intervention study was performed in high cardiovascular risk individuals receiving atorvastatin 10 mg daily for four weeks. Those with CRP >= 2.0 mg/L were randomized to another four-week treatment period with atorvastatin 40 mg, ezetimibe 10 mg or the combination of atorvastatin 40 mg/ezetimibe 10 mg. Lipids, markers of cholesterol absorption (campesterol and p-sitosterol), and synthesis (desmosterol), as well as CRP were quantified at baseline and end of study. Key findings: One hundred and twenty two individuals were included. Atorvastatin alone or combined with ezetimibe reduced both LDL-cholesterol and CRP (P < 0.002 vs. baseline; Wilcoxon); ezetimibe did not modify CRP. Ezetimibe-based therapies reduced absorption markers and their ratios to cholesterol (P < 0.0001 vs. baseline, for all; Wilcoxon), whereas atorvastatin alone increased campesterol/cholesterol and beta-sitosterol/cholesterol ratios (P < 0.05 vs. baseline; Wilcoxon). In addition, ezetimibe also increased desmosterol and desmosterol/cholesterol ratio (P < 0.0001 vs. baseline; Wilcoxon). Significance: These results contribute to understanding the link between cellular cholesterol homeostasis, inflammation and lipid-modifying therapies. Our findings highlight the broader benefit of combined therapy with a potent statin and ezetimibe decreasing inflammation, and preventing increase in cholesterol biosynthesis, an effect not observed with ezetimibe alone. (C) 2013 Elsevier Inc. All rights reserved. (AU)