Effects of ezetimibe on markers of synthesis and absorption of cholesterol in high-risk patients with elevated C-reactive protein
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 t...
| Autores: | , , , , , , , , , |
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| Tipo de recurso: | artículo |
| Estado: | Versión publicada |
| Fecha de publicación: | 2013 |
| País: | Brasil |
| Institución: | Universidade Federal de São Paulo (UNIFESP) |
| Repositorio: | Repositório Institucional da UNIFESP |
| Idioma: | inglés |
| OAI Identifier: | oai:repositorio.unifesp.br:11600/36330 |
| Acceso en línea: | http://dx.doi.org/10.1016/j.lfs.2013.02.018 http://repositorio.unifesp.br/handle/11600/36330 |
| Access Level: | acceso abierto |
| Palabra clave: | Campesterol beta-Sitosterol Desmosterol Inflammation C-Reactive protein Statins Ezetimibe |
| Sumario: | 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. |
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