One-Year Effects of High-Intensity Statin on Bioactive Lipids: Findings From the JUPITER Trial.

IF 7.4 1区 医学 Q1 HEMATOLOGY Arteriosclerosis, Thrombosis, and Vascular Biology Pub Date : 2024-07-01 Epub Date: 2024-06-06 DOI:10.1161/ATVBAHA.124.321058
Rosangela Akemi Hoshi, Mona Alotaibi, Yanyan Liu, Jeramie D Watrous, Paul M Ridker, Robert J Glynn, Charles N Serhan, Heike Luttmann-Gibson, M Vinayaga Moorthy, Mohit Jain, Olga V Demler, Samia Mora
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Abstract

Background: Statin effects extend beyond low-density lipoprotein cholesterol reduction, potentially modulating the metabolism of bioactive lipids (BALs), crucial for biological signaling and inflammation. These bioactive metabolites may serve as metabolic footprints, helping uncover underlying processes linked to pleiotropic effects of statins and yielding a better understanding of their cardioprotective properties. This study aimed to investigate the impact of high-intensity statin therapy versus placebo on plasma BALs in the JUPITER trial (Justification for the Use of Statins in Prevention: an Intervention Trial Evaluating Rosuvastatin; NCT00239681), a randomized primary prevention trial involving individuals with low-density lipoprotein cholesterol <130 mg/dL and high-sensitivity C-reactive protein ≥2 mg/L.

Methods: Using a nontargeted mass spectrometry approach, over 11 000 lipid features were assayed from baseline and 1-year plasma samples from cardiovascular disease noncases from 2 nonoverlapping nested substudies: JUPITERdiscovery (n=589) and JUPITERvalidation (n=409). The effect of randomized allocation of rosuvastatin 20 mg versus placebo on BALs was examined by fitting a linear regression with delta values (∆=year 1-baseline) adjusted for age and baseline levels of each feature. Significant associations in discovery were analyzed in the validation cohort. Multiple comparisons were adjusted using 2-stage overall false discovery rate.

Results: We identified 610 lipid features associated with statin randomization with significant replication (overall false discovery rate, <0.05), including 26 with annotations. Statin therapy significantly increased levels of 276 features, including BALs with anti-inflammatory activity and arterial vasodilation properties. Concurrently, 334 features were significantly lowered by statin therapy, including arachidonic acid and proinflammatory and proplatelet aggregation BALs. By contrast, statin therapy reduced an eicosapentaenoic acid-derived hydroxyeicosapentaenoic acid metabolite, which may be related to impaired glucose metabolism. Additionally, we observed sex-related differences in 6 lipid metabolites and 6 unknown features.

Conclusions: Statin allocation was significantly associated with upregulation of BALs with anti-inflammatory, antiplatelet aggregation and antioxidant properties and downregulation of BALs with proinflammatory and proplatelet aggregation activity, supporting the pleiotropic effects of statins beyond low-density lipoprotein cholesterol reduction.

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高强度他汀对生物活性脂质的一年期影响:JUPITER试验结果
背景:他汀类药物的作用不仅限于降低低密度脂蛋白胆固醇,还可能调节生物活性脂质(BALs)的代谢,而生物活性脂质对生物信号转导和炎症反应至关重要。目的:在JUPITER试验(在预防中使用他汀类药物的理由:评价瑞舒伐他汀的干预试验;NCT00239681)中,研究高强度他汀类药物治疗与安慰剂相比对血浆BALs的影响:采用非靶向质谱方法,从两个非重叠嵌套子研究中的心血管疾病非病例的基线和 1 年血浆样本中测定了超过 11000 个脂质特征:JUPITERdiscovery (n=589) 和 JUPITERvalidation (n=409)。罗伐他汀 20 毫克与安慰剂的随机分配对 BALs 的影响通过拟合线性回归进行检验,delta 值(Δ=第 1 年-基线)根据年龄和各项特征的基线水平进行调整。在验证队列中分析了发现中的显著关联。多重比较采用两阶段总体错误发现率进行调整:结果:我们发现了 610 个与他汀类药物随机分配相关的血脂特征,这些特征具有显著的重复性(总体误发现率,结论:他汀类药物分配与血脂升高显著相关):他汀类药物的分配与具有抗炎、抗血小板聚集和抗氧化特性的 BALs 的上调以及具有促炎和促血小板聚集活性的 BALs 的下调明显相关,支持他汀类药物在降低低密度脂蛋白胆固醇之外的多生物效应。
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来源期刊
CiteScore
15.60
自引率
2.30%
发文量
337
审稿时长
2-4 weeks
期刊介绍: The journal "Arteriosclerosis, Thrombosis, and Vascular Biology" (ATVB) is a scientific publication that focuses on the fields of vascular biology, atherosclerosis, and thrombosis. It is a peer-reviewed journal that publishes original research articles, reviews, and other scholarly content related to these areas. The journal is published by the American Heart Association (AHA) and the American Stroke Association (ASA). The journal was published bi-monthly until January 1992, after which it transitioned to a monthly publication schedule. The journal is aimed at a professional audience, including academic cardiologists, vascular biologists, physiologists, pharmacologists and hematologists.
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