Paragh G, Törocsik D, Seres I, Harangi M, Illyés L, Balogh Z, Kovács P
Department of Metabolic Diseases, University of Debrecen, Medical and Health Science Center, Debrecen, Hungary.
Curr Med Res Opin. 2004 Aug;20(8):1321-7. doi: 10.1185/030079904125004394.
High-density lipoprotein (HDL)-associated paraoxonase (PON) activity may play an important role in the inhibition of low-density lipoprotein (LDL) oxidation. Previous studies have demonstrated that serum PON activity is decreased in patients with hyperlipoproteinaemia and coronary heart disease. The study presented here examined the effect of short-term treatment with simvastatin and atorvastatin on lipids and PON activity in patients with hyperlipoproteinaemia.
A prospective, non-blinded, single-group, cross-over, comparative trial was performed. Following an 8-week dietary run-in period, 49 patients (23 men and 26 women, mean age: 59.8 +/- 7.9 years) with Fredrickson type IIa. and IIb. hyperlipoproteinaemias were randomized to receive either simvastatin 20 mg/day or atorvastatin 10 mg/day for 3 months. Following an 8-week washout period, patients were crossed-over to receive the other drug for a further 3 months. Serum lipids were measured and serum PON activity was determined spectrophotometrically using paraoxon as a substrate.
Simvastatin treatment significantly reduced serum cholesterol, LDL-cholesterol (LDL-C) and apolipoprotein (apo) B levels (p < 0.001). Atorvastatin had a more pronounced cholesterol, LDL-C- and apo B-lowering effect (p < 0.001) compared with simvastatin. Both statins also significantly reduced serum triglyceride levels (p < 0.01). Simvastatin and atorvastatin caused no significant change in the levels of HDL-cholesterol (HDL-C) and apo A1. HDL-associated PON activity did not change significantly after simvastatin therapy, but significantly increased after atorvastatin treatment (p < 0.05).
Short-term administration of simvastatin did not increase PON activity. Atorvastatin treatment had a favourable effect on lipid profile and increased the activity of HDL-associated PON.
高密度脂蛋白（HDL）相关的对氧磷酶（PON）活性可能在抑制低密度脂蛋白（LDL）氧化中起重要作用。既往研究表明，高脂血症和冠心病患者的血清PON活性降低。本研究探讨了辛伐他汀和阿托伐他汀短期治疗对高脂血症患者血脂及PON活性的影响。
进行了一项前瞻性、非盲、单组、交叉、对照试验。在为期8周的饮食导入期后，49例（23例男性和26例女性，平均年龄：59.8±7.9岁）弗雷德里克森IIa型和IIb型高脂血症患者被随机分为接受辛伐他汀20mg/天或阿托伐他汀10mg/天治疗3个月。在为期8周的洗脱期后，患者交叉接受另一种药物治疗3个月。测定血清脂质，并以对氧磷为底物，采用分光光度法测定血清PON活性。
辛伐他汀治疗显著降低血清胆固醇、低密度脂蛋白胆固醇（LDL-C）和载脂蛋白（apo）B水平（p<0.001）。与辛伐他汀相比，阿托伐他汀对胆固醇、LDL-C和apo B的降低作用更显著（p<0.001）。两种他汀类药物也显著降低血清甘油三酯水平（p<0.01）。辛伐他汀和阿托伐他汀对高密度脂蛋白胆固醇（HDL-C）和apo A1水平无显著影响。辛伐他汀治疗后HDL相关的PON活性无显著变化，但阿托伐他汀治疗后显著增加（p<0.05）。
短期服用辛伐他汀不会增加PON活性。阿托伐他汀治疗对血脂谱有良好影响，并增加了HDL相关PON的活性。
