Bergheanu Sandrin C, Reijmers Theo, Zwinderman Aeilko H, Bobeldijk Ivana, Ramaker Raymond, Liem An-Ho, van der Greef Jan, Hankemeier Thomas, Jukema J Wouter
Leiden University Medical Center, Leiden, The Netherlands.
Curr Med Res Opin. 2008 Sep;24(9):2477-87. doi: 10.1185/03007990802321709. Epub 2008 Jul 24.
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.
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.
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 dose/timepoint (p<0.05), a ratio reported to be of clinical importance in coronary artery disease.
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.
脂质谱分析（脂质组学）可能有助于揭示有关脂质代谢影响、心血管风险以及区分不同治疗方法的详细信息。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脂质变化；（2）比较两种药物在脂质谱变化方面的差异；（3）将研究结果与冠状动脉疾病有意义的病理机制联系起来。
应用液相色谱 - 质谱法获取来自RADAR研究中一个前瞻性定义的亚组（n = 80）参与者的血浆样本代谢物谱，在为期18周的时间内对这些参与者随机给予递增剂量的瑞舒伐他汀或阿托伐他汀治疗。
多种鞘磷脂（SPM）和磷脂酰胆碱（PC）与两种他汀类药物对低密度脂蛋白胆固醇/高密度脂蛋白胆固醇（LDL - C/HDL - C）比值的不同影响相关。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（治疗组间比较p<0.01）。阿托伐他汀和瑞舒伐他汀均降低了血浆SPM浓度，但阿托伐他汀在最高剂量时表现出更显著的效果（p = 0.03）。在任何剂量/时间点，瑞舒伐他汀导致[SPM/(SPM + PC)]比值的降低比阿托伐他汀更有效（p<0.05），据报道该比值在冠状动脉疾病中具有临床重要性。
脂质组学技术表明，他汀类药物在对详细脂质谱的影响方面存在差异。如[SPM/(SPM + PC)]比值所示，观察到的脂质差异可能与不同的临床结果相关。
