Statin Effects on Metabolic Profiles: Data From the PREVEND IT (Prevention of Renal and Vascular End-stage Disease Intervention Trial).

Circulation: Cardiovascular Genetics Pub Date : 2017-12-01 DOI:10.1161/CIRCGENETICS.117.001759

Daniel Kofink, Ruben N Eppinga, Wiek H van Gilst, Stephan J L Bakker, Robin P F Dullaart, Pim van der Harst, Folkert W Asselbergs

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引用次数: 17

Abstract

Background: Statins lower cholesterol by inhibiting HMG-CoA reductase, the rate-limiting enzyme of the metabolic pathway that produces cholesterol and other isoprenoids. Little is known about their effects on metabolite and lipoprotein subclass profiles. We, therefore, investigated the molecular changes associated with pravastatin treatment compared with placebo administration using a nuclear magnetic resonance-based metabolomics platform.

Methods and results: We performed metabolic profiling of 231 lipoprotein and metabolite measures in the PREVEND IT (Prevention of Renal and Vascular End-stage Disease Intervention Trial) study, a placebo-controlled randomized clinical trial designed to test the effects of pravastatin (40 mg once daily) on cardiovascular risk. Metabolic profiles were assessed at baseline and after 3 months of treatment. Pravastatin lowered low-density lipoprotein cholesterol (change in SD units [95% confidence interval]: -1.01 [-1.14, -0.88]), remnant cholesterol (change in SD units [95% confidence interval]: -1.03 [-1.17, -0.89]), and apolipoprotein B (change in SD units [95% confidence interval]: -0.98 [-1.11, -0.86]) with similar effect magnitudes. In addition, pravastatin globally lowered levels of lipoprotein subclasses, with the exception of high-density lipoprotein subclasses, which displayed a more heterogeneous response pattern. The lipid-lowering effect of pravastatin was accompanied by selective changes in lipid composition, particularly in the cholesterol content of very-low-density lipoproteinparticles. In addition, pravastatin reduced levels of several fatty acids but had limited effects on fatty acid ratios.

Conclusions: These randomized clinical trial data demonstrate the widespread effects of pravastatin treatment on lipoprotein subclass profiles and fatty acids.

Clinical trial registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT03073018.

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他汀类药物对代谢谱的影响:来自preventit(预防肾脏和血管终末期疾病干预试验)的数据。

背景:他汀类药物通过抑制HMG-CoA还原酶降低胆固醇，HMG-CoA还原酶是产生胆固醇和其他类异戊二烯的代谢途径的限速酶。它们对代谢物和脂蛋白亚类谱的影响知之甚少。因此，我们使用基于核磁共振的代谢组学平台研究了普伐他汀治疗与安慰剂治疗相关的分子变化。方法和结果:我们在预防肾脏和血管终末期疾病干预试验(Prevention of Renal and Vascular终末期疾病干预试验)研究中对231种脂蛋白和代谢物进行了代谢分析，这是一项安慰剂对照随机临床试验，旨在测试普伐他汀(40mg，每日一次)对心血管风险的影响。在基线和治疗3个月后评估代谢谱。普伐他汀降低了低密度脂蛋白胆固醇(SD单位变化[95%置信区间]:-1.01[-1.14，-0.88])、残余胆固醇(SD单位变化[95%置信区间]:-1.03[-1.17，-0.89])和载脂蛋白B (SD单位变化[95%置信区间]:-0.98[-1.11，-0.86])，效果幅度相似。此外，普伐他汀在全球范围内降低了脂蛋白亚类的水平，但高密度脂蛋白亚类除外，高密度脂蛋白亚类表现出更异质性的反应模式。普伐他汀的降脂作用伴随着脂质组成的选择性改变，特别是极低密度脂蛋白颗粒的胆固醇含量。此外，普伐他汀降低了几种脂肪酸的水平，但对脂肪酸比例的影响有限。结论:这些随机临床试验数据表明普伐他汀治疗对脂蛋白亚类和脂肪酸的广泛影响。临床试验注册:网址:http://www.clinicaltrials.gov。唯一标识符:NCT03073018。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Circulation: Cardiovascular Genetics CARDIAC & CARDIOVASCULAR SYSTEMS-GENETICS & HEREDITY

自引率

0.00%

发文量

审稿时长

6-12 weeks

期刊介绍： Circulation: Genomic and Precision Medicine considers all types of original research articles, including studies conducted in human subjects, laboratory animals, in vitro, and in silico. Articles may include investigations of: clinical genetics as applied to the diagnosis and management of monogenic or oligogenic cardiovascular disorders; the molecular basis of complex cardiovascular disorders, including genome-wide association studies, exome and genome sequencing-based association studies, coding variant association studies, genetic linkage studies, epigenomics, transcriptomics, proteomics, metabolomics, and metagenomics; integration of electronic health record data or patient-generated data with any of the aforementioned approaches, including phenome-wide association studies, or with environmental or lifestyle factors; pharmacogenomics; regulation of gene expression; gene therapy and therapeutic genomic editing; systems biology approaches to the diagnosis and management of cardiovascular disorders; novel methods to perform any of the aforementioned studies; and novel applications of precision medicine. Above all, we seek studies with relevance to human cardiovascular biology and disease.