Sakabe Koichi, Fukuda Nobuo, Wakayama Katsunori, Nada Teru, Shinohara Hisanori, Tamura Yoshiyuki
Department of Cardiology and Clinical Research, National Zentsuji Hospital, 2-1-1 Senyu-cho, Zentsuji, Kagawa 765-8507, Japan.
Int J Cardiol. 2004 Mar;94(1):111-7. doi: 10.1016/j.ijcard.2003.08.001.
It is unclear whether there are temporal differences for the pleiotropic effects for different members of the statin class. The present study investigated differences in the short- and intermediate-term pleiotropic effects of statins in hypercholesterolemic patients.
Thirty-five hypercholesterolemic patients were randomly treated with either atorvastatin or cerivastatin for 3 months. We measured fasting lipid concentrations, thiobarbituric acid reactive substances (TBARS), fibrinolytic parameters, and flow-mediated dilation of the brachial artery (FMD) at baseline and after 2 weeks and 3 months of therapy.
After 2 weeks of therapy, atorvastatin decreased the low density lipoprotein (LDL) cholesterol, small, dense LDL cholesterol (34+/-22 vs. 18+/-20%, P<0.01), remnant-like particles (RLP) cholesterol (8.8+/-6.0 vs. 5.1+/-2.6 mg/ml, P<0.01), and TBARS (3.3+/-1.0 vs. 3.1+/-0.9 nmol/ml, P<0.05), and cerivastatin decreased LDL cholesterol. After 3 months of therapy, atorvastatin decreased small dense LDL cholesterol (8+/-13%, P<0.0001) additionally, and cerivastatin decreased small, dense LDL cholesterol (51+/-11 vs. 12+/-22%, P<0.0001) and plasminogen activator inhibitor type 1 (68+/-32 vs. 51+/-21 ng/ml, P<0.05). FMD increased significantly in both groups after 2 weeks, although the relative change in FMD was greater with cerivastatin therapy after 2 weeks than atorvastatin therapy (60+/-78 vs. 23+/-26%, P<0.05). However, FMD was the same for both groups after 3 months (58+/-65 vs. 66+/-61%, NS), because atorvastatin additionally increased FMD. There was no correlation between these pleiotropic effects and the improvement in the lipid profile for either group.
These findings suggest that the degree of pleiotropic effect as well as the time course for the effect are different among members of the statin class of drugs.
尚不清楚他汀类药物不同成员的多效性作用是否存在时间差异。本研究调查了他汀类药物在高胆固醇血症患者中的短期和中期多效性作用差异。
35例高胆固醇血症患者被随机给予阿托伐他汀或西立伐他汀治疗3个月。我们在基线以及治疗2周和3个月后测量空腹血脂浓度、硫代巴比妥酸反应性物质（TBARS）、纤溶参数以及肱动脉血流介导的舒张功能（FMD）。
治疗2周后，阿托伐他汀降低了低密度脂蛋白（LDL）胆固醇、小而密LDL胆固醇（34±22% 对18±20%，P<0.01）、残粒样颗粒（RLP）胆固醇（8.8±6.0对5.1±2.6mg/ml，P<0.01）以及TBARS（3.3±1.0对3.1±0.9nmol/ml，P<0.05），西立伐他汀降低了LDL胆固醇。治疗3个月后，阿托伐他汀额外降低了小而密LDL胆固醇（8±13%，P<0.0001），西立伐他汀降低了小而密LDL胆固醇（51±11%对12±22%，P<0.0001）以及纤溶酶原激活物抑制剂1型（68±32对51±21ng/ml，P<0.05）。两组在治疗2周后FMD均显著增加，尽管治疗2周后西立伐他汀治疗组FMD的相对变化大于阿托伐他汀治疗组（60±78%对23±26%，P<><>然而，3个月后两组的FMD相同（58±65%对66±61%，无显著性差异），因为阿托伐他汀额外增加了FMD。这些多效性作用与两组中任何一组的血脂谱改善之间均无相关性。
这些发现表明，他汀类药物不同成员的多效性作用程度以及作用的时间进程存在差异。
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