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

• Autor(a) principal: Barbosa, Simone Pinto de Melo [UNIFESP]
• Data de Publicação: 2013
• Outros Autores: Lins, Lívia Campos do Amaral Silva [UNIFESP], Fonseca, Francisco Antonio Helfenstein [UNIFESP], Matos, Lívia Nascimento de [UNIFESP], Aguirre, Ana Carolina Carneiro [UNIFESP], Bianco, Henrique Tria [UNIFESP], Amaral, Jônatas Bussador do [UNIFESP], Franca, Carolina Nunes [UNIFESP], Santana, José Marcos, Izar, Maria Cristina de Oliveira [UNIFESP]
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Repositório Institucional da UNIFESP
• Texto Completo: http://dx.doi.org/10.1016/j.lfs.2013.02.018; http://repositorio.unifesp.br/handle/11600/36330
• topic: Campesterol; beta-Sitosterol; Desmosterol; Inflammation; C-Reactive protein; Statins; Ezetimibe

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.