他汀类药物对代谢谱的影响：来自PREVEND IT（预防肾脏和血管终末期疾病干预试验）的数据。
Statin Effects on Metabolic Profiles: Data From the PREVEND IT (Prevention of Renal and Vascular End-stage Disease Intervention Trial).
作者信息
Kofink Daniel, Eppinga Ruben N, van Gilst Wiek H, Bakker Stephan J L, Dullaart Robin P F, van der Harst Pim, Asselbergs Folkert W
机构信息
From the Department of Cardiology, Division of Heart and Lungs, University Medical Center Utrecht, University of Utrecht, The Netherlands (D.K., F.W.A.); Department of Cardiology (R.N.E., W.H.v.G., P.v.d.H.), Department of Internal Medicine (S.J.L.B.), and Department of Endocrinology, University Medical Center Groningen (R.P.F.D.), University of Groningen, The Netherlands; Durrer Center for Cardiogenetic Research, ICIN-Netherlands Heart Institute, Utrecht (P.v.d.H., F.W.A.); and Institute of Cardiovascular Science, Faculty of Population Health Sciences, University College London, United Kingdom (F.W.A.).
出版信息
Circ Cardiovasc Genet. 2017 Dec;10(6). doi: 10.1161/CIRCGENETICS.117.001759.
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.
背景
他汀类药物通过抑制HMG-CoA还原酶来降低胆固醇，HMG-CoA还原酶是产生胆固醇和其他类异戊二烯的代谢途径中的限速酶。关于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，研究了与普伐他汀治疗相比，安慰剂给药相关的分子变化。
方法与结果
我们在PREVEND IT（预防肾和血管终末期疾病干预试验）研究中对231种脂蛋白和代谢物指标进行了代谢谱分析，这是一项安慰剂对照的随机临床试验，旨在测试普伐他汀（每日一次40毫克）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（标准差单位变化[95%置信区间]：-1.01[-1.14，-0.88]）、残留胆固醇（标准差单位变化[95%置信区间]：-1.03[-1.17，-0.89]）和载脂蛋白B（标准差单位变化[95%置信区间]：-0.98[-1.11，-0.86]），效应大小相似。此外，普伐他汀总体上降低了脂蛋白亚类的水平，但高密度脂蛋白亚类除外，其显示出更异质的反应模式。普伐他汀的降脂作用伴随着脂质组成的选择性变化，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证明了普伐他汀治疗对脂蛋白亚类谱和脂肪酸具有广泛影响。
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