Lipidomic approach to evaluate rosuvastatin and atorvastatin at various dosages: investigating differential effects among statins
Lipidomic approach to evaluate rosuvastatin and atorvastatin at various dosages: investigating differential effects among statins
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DOI：
10.1185/03007990802321709
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发表时间：
2008-09-01
影响因子：
2.3
通讯作者：
Jukema, J. Wouter
中科院分区：
文献类型：
--
作者：
Bergheanu, Sandrin C.;Reijmers, Theo;Jukema, J. Wouter
目的：脂质分析（脂质组学）可能有助于揭示有关脂质代谢影响、心血管风险的详细信息以及区分治疗方法。本研究的目的是：（1）深入分析不同剂量瑞舒伐他汀和阿托伐他汀引起的血脂变化； (2)比较两种药物在血脂变化方面的差异； (3) 将研究结果与冠状动脉疾病的有意义的病理机制联系起来。研究设计和方法：采用液相色谱-质谱法来获取从 RADAR 研究中前瞻性定义的参与者子集 (n = 80) 中采集的血浆样本的代谢物谱，其中在 18 周期间随机分配瑞舒伐他汀或阿托伐他汀，并增加剂量。结果：许多鞘磷脂 (SPM) 和磷脂酰胆碱 (PC) 与两种他汀类药物对 LDL-C/HDL-C 比率的不同影响相关。瑞舒伐他汀在 6 周和 18 周后增加了 PC 的血浆浓度，而阿托伐他汀在两个时间点和剂量下均降低了 PC 的血浆浓度（治疗间比较 p < 0.01）。阿托伐他汀和瑞舒伐他汀均可降低血浆 SPM 浓度，但阿托伐他汀在最高剂量下表现出更明显的效果 (p = 0.03)。在任何关闭/时间点，瑞舒伐他汀都能比阿托伐他汀更有效地降低 [SPMs/(SPMs + PCs)] 比率 (p < 0.05)，据报道，该比率在冠状动脉疾病中具有临床重要性。 结论：脂质组学技术表明，他汀类药物在对详细血脂谱的影响方面是不同的。正如 [SPMs/(SPMs + PCs)] 比率所示，观察到的血脂差异可能与不同的临床结果有关。
Objective: Lipid profiling (lipidomics) may be useful in revealing detailed information with regard to the effects on lipid metabolism, the cardiovascular risk and to differentiate between therapies. The aims of the present study were to: (1) analyze in depth the lipid changes induced by rosuvastatin and atorvastatin at different dosages; (2) compare differences between the two drugs with respect to the lipid profile change; (3) relate the findings with meaningful pathological mechanisms of coronary artery disease.Research design and methods: Liquid chromatography-mass spectrometry was applied to obtain the metabolite profiles of plasma samples taken from a prospectively defined subset (n = 80) of participants in the RADAR study where a randomly assigned treatment with rosuvastatin or atorvastatin in increasing dosages was administered during an 18-week period.Results: A number of sphingomyelins (SPMs) and phosphatidylcholines (PCs) correlate with the different effects of the two statins on the LDL-C/HDL-C ratio. Rosuvastatin increased the plasma concentration of PCs after 6 and 18 weeks, while atorvastatin reduced the plasma concentrations of PCs at both timepoints and dosages (p < 0.01 for between-treatment comparison). Both atorvastatin and rosuvastatin lowered plasma SPMs concentrations, but atorvastatin demonstrated a more pronounced effect with the highest dose (p = 0.03). Rosuvastatin resulted in a significantly more effective lowering of the [SPMs/(SPMs + PCs)] ratio than atorvastatin at any close/timepoint (p < 0.05), a ratio reported to be of clinical importance in coronary artery disease.Conclusions: The lipidomic technique has revealed that statins are different with regards to the effect on detailed lipid profile. The observed difference in lipids may be connected with different clinical outcomes as suggested by the [SPMs/(SPMs + PCs)] ratio.