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

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

Author Barbosa, Simone Pinto de Melo Autor UNIFESP Google Scholar
Lins, Lívia Campos do Amaral Silva Autor UNIFESP Google Scholar
Fonseca, Francisco Antonio Helfenstein Autor UNIFESP Google Scholar
Matos, Lívia Nascimento de Autor UNIFESP Google Scholar
Aguirre, Ana Carolina Carneiro Autor UNIFESP Google Scholar
Bianco, Henrique Tria Autor UNIFESP Google Scholar
Amaral, Jônatas Bussador do Autor UNIFESP Google Scholar
Franca, Carolina Nunes Autor UNIFESP Google Scholar
Santana, José Marcos Google Scholar
Izar, Maria Cristina de Oliveira Autor UNIFESP Google Scholar
Institution Universidade Federal de São Paulo (UNIFESP)
Tasqa
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.
Keywords Campesterol
beta-Sitosterol
Desmosterol
Inflammation
C-Reactive protein
Statins
Ezetimibe
Language English
Sponsor Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
Grant number FAPESP: 2009/50052-1
Date 2013-05-02
Published in Life Sciences. Oxford: Pergamon-Elsevier B.V., v. 92, n. 14-16, p. 845-851, 2013.
ISSN 0024-3205 (Sherpa/Romeo, impact factor)
Publisher Elsevier B.V.
Extent 845-851
Origin http://dx.doi.org/10.1016/j.lfs.2013.02.018
Access rights Open access Open Access
Type Article
Web of Science ID WOS:000318190900005
URI http://repositorio.unifesp.br/handle/11600/36330

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