van Himbergen Thomas M, Matthan Nirupa R, Resteghini Nancy A, Otokozawa Seiko, Ai Masumi, Stein Evan A, Jones Peter H, Schaefer Ernst J
Lipid Metabolism Laboratory, Human Nutrition Research Center on Aging at Tufts University, Boston, MA, USA.
J Lipid Res. 2009 Apr;50(4):730-9. doi: 10.1194/jlr.P800042-JLR200. Epub 2008 Nov 30.
We measured plasma markers of cholesterol synthesis (lathosterol) and absorption (campesterol, sitosterol, and cholestanol) in order to compare the effects of maximal doses of rosuvastatin with atorvastatin and investigate the basis for the significant individual variation in lipid lowering response to statin therapy. Measurements were performed in participants (n = 135) at baseline and after 6 weeks on either rosuvastatin (40 mg/day) or atorvastatin (80 mg/day) therapy. Plasma sterols were measured using gas-liquid chromatography. Rosuvastatin and atorvastatin significantly (P < 0.001) altered plasma total cholesterol (C) levels by -40%, and the ratios of lathosterol/C by -64% and -68%, and campesterol/C by +52% and +72%, respectively, with significant differences (P < 0.001) between the treatment groups for the latter parameter. When using absolute values of these markers, subjects with the greatest reductions in both synthesis (lathosterol) and absorption (campesterol) had significantly greater reductions in total C than subjects in whom the converse was true (-46% versus -34%, P = 0.001), with similar effects for LDL-C. Rosuvastatin and atorvastatin decreased markers of cholesterol synthesis and increased markers of fractional cholesterol absorption, with rosuvastatin having significantly less effect on the latter parameter than atorvastatin. In addition, alterations in absolute values of plasma sterols correlated with the cholesterol lowering response.
我们测量了胆固醇合成（羊毛甾醇）和吸收（菜油甾醇、谷甾醇和胆甾烷醇）的血浆标志物，以比较瑞舒伐他汀最大剂量与阿托伐他汀的效果，并研究他汀类药物治疗后血脂降低反应中显著个体差异的基础。在参与者（n = 135）基线时以及接受瑞舒伐他汀（40毫克/天）或阿托伐他汀（80毫克/天）治疗6周后进行测量。使用气液色谱法测量血浆甾醇。瑞舒伐他汀和阿托伐他汀分别使血浆总胆固醇（C）水平显著降低（P < 0.001）40%，羊毛甾醇/C比值分别降低64%和68%，菜油甾醇/C比值分别升高52%和72%，后一参数在治疗组之间存在显著差异（P < 0.001）。当使用这些标志物的绝对值时，合成（羊毛甾醇）和吸收（菜油甾醇）降低幅度最大的受试者，其总C降低幅度显著大于相反情况的受试者（-46%对-34%，P = 0.001），对低密度脂蛋白胆固醇（LDL-C）有类似影响。瑞舒伐他汀和阿托伐他汀降低了胆固醇合成标志物，增加了胆固醇分数吸收标志物，瑞舒伐他汀对后一参数的影响显著小于阿托伐他汀。此外，血浆甾醇绝对值的变化与胆固醇降低反应相关。
