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

机译：依折麦布对高危C反应蛋白患者胆固醇合成和吸收标志物的影响

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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 β-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 β-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.
机译：目的：具有升高的C反应蛋白（CRP）的高风险受试者发生心血管事件的风险很高，并经常需要有效的他汀类药物或联合降脂治疗以达到脂质目标并减少炎症。我们的研究旨在评估三种脂质修饰疗法对LDL-胆固醇，CRP水平和胆固醇吸收与合成标志物的影响。主要方法前瞻性干预研究是在高心血管风险个体中接受每日10毫克阿托伐他汀治疗4周。 CRP≥2.0 mg / L的患者被随机分配到另外一个为期四周的治疗期，分别使用阿托伐他汀40 mg，依泽替米贝10 mg或阿托伐他汀40 mg /依泽替米贝10 mg的组合。在基线和研究结束时对脂质，胆固醇吸收的标志物（菜油甾醇和β-谷甾醇），合成物（去甾醇）以及CRP进行了定量。主要发现包括一百二十二人。单独使用阿托伐他汀或与依泽替米贝联用可降低LDL-胆固醇和CRP（相对于基线，P <0.002; Wilcoxon）;依泽替米贝未修改CRP。基于依泽替米贝的疗法可降低吸收标记物及其与胆固醇的比率（对于所有患者，P <0.0001，相对于基线; Wilcoxon），而单独使用阿托伐他汀可提高菜油甾醇/胆固醇和β-谷固醇/胆固醇的比例（相对于基线，P <0.05; Wilcoxon） 。此外，依泽替米贝还提高了去甾醇和去甾醇/胆固醇的比率（相对于基线，P <0.0001; Wilcoxon）。意义这些结果有助于理解细胞胆固醇动态平衡，炎症和脂质修饰疗法之间的联系。我们的发现凸显了与有效的他汀类药物和依泽替米贝联合治疗可降低炎症，防止胆固醇生物合成增加，这是单独使用依泽替米贝未见的效果。

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