Molcányiová Angela, Stancáková Alena, Javorský Martin, Tkác Ivan
Department of Clinical Biochemistry, LABMED, Kosice, Slovakia.
Pharmacol Res. 2006 Sep;54(3):203-7. doi: 10.1016/j.phrs.2006.04.009. Epub 2006 May 4.
Beneficial effects of statin treatment on cardiovascular morbidity and mortality has been not entirely explained by the reduction in LDL-cholesterol level. We hypothesised that antioxidant activity of statins may contribute to their salutary cardiovascular effects. The aim of the present study was to examine effect of simvastatin treatment on some parameters of LDL oxidation and antioxidant protection in patients with hypercholesterolemia and combined hyperlipidemia. Furthermore, we were interested, whether the effect of treatment is related to the type of hyperlipidemia.
Fourty-two patients (12 males, 30 females, mean age 60+/-10 years) were included in the present study. Fourteen patients had hypercholesterolemia defined as total cholesterol>5.0 mmol/l. Twenty-eight patients had combined hyperlipidemia defined by total cholesterol>5.0 mmol/l and triglycerides>1.7 mmol/l. Simvastatin was administered to patients during 8-week period in a daily dose of 20mg. Oxidation of LDL was measured by assessment of circulating conjugated diene (CD) and malondialdehyde (MDA) level. Antioxidant properties of blood were assessed based on measurement of total antioxidant status (TAS) and glutathione peroxidase (GPx) activity.
Besides expected significant decrease in total cholesterol, LDL-cholesterol, apolipoprotein B and triglyceride levels, simvastatin treatment also reduced significantly circulating CD by 41% (p<0.0001) and MDA level non-significantly by 6% (p=0.078). Simvastatin treatment resulted in an increase of GPx activity by 38% (p<0.0001), but did not have a significant effect on TAS. Patients with combined hyperlipidemia had significantly higher baseline CD (p<0.01) and consequently significantly greater absolute and relative decrease (46% versus 23%) in circulating CD (DeltaCD), when compared with patients with hypercholesterolemia. The increase in GPx activity was significant only in patients with combined hyperlipidemia (p<0.0001). In the multiple stepwise linear regression analysis, both baseline triglyceride (r(2)=0.32; p=0.004) and LDL cholesterol (r(2)=0.08; p=0.05) levels were significant independent predictors of DeltaCD after simvastatin treatment.
Simvastatin treatment significantly reduced circulating conjugated diene level and led to an increase in glutathione peroxidase activity. These effects were more pronounced in patients with combined hyperlipidemia than in hypercholesterolemia. The results suggest that simvastatin possesses certain antioxidant properties, which may contribute to its beneficial cardiovascular effect.
他汀类药物治疗对心血管疾病发病率和死亡率的有益影响尚未完全由低密度脂蛋白胆固醇水平的降低来解释。我们推测他汀类药物的抗氧化活性可能有助于其有益的心血管作用。本研究的目的是检查辛伐他汀治疗对高胆固醇血症和混合性高脂血症患者低密度脂蛋白氧化和抗氧化保护的一些参数的影响。此外，我们还关注治疗效果是否与高脂血症的类型有关。
本研究纳入了42例患者（12例男性，30例女性，平均年龄60±10岁）。14例患者患有高胆固醇血症，定义为总胆固醇>5.0 mmol/L。28例患者患有混合性高脂血症，定义为总胆固醇>5.0 mmol/L且甘油三酯>1.7 mmol/L。辛伐他汀以每日20mg的剂量给予患者，持续8周。通过评估循环共轭二烯（CD）和丙二醛（MDA）水平来测量低密度脂蛋白的氧化。基于总抗氧化状态（TAS）和谷胱甘肽过氧化物酶（GPx）活性的测量来评估血液的抗氧化特性。
除了预期的总胆固醇、低密度脂蛋白胆固醇、载脂蛋白B和甘油三酯水平显著降低外，辛伐他汀治疗还使循环CD显著降低41%（p<0.0001），MDA水平非显著降低6%（p=0.078）。辛伐他汀治疗使GPx活性增加38%（p<0.0001），但对TAS没有显著影响。与高胆固醇血症患者相比，混合性高脂血症患者的基线CD显著更高（p<0.01），因此循环CD（ΔCD）的绝对和相对降低幅度显著更大（46%对23%）。GPx活性的增加仅在混合性高脂血症患者中显著（p<0.0001）。在多元逐步线性回归分析中，基线甘油三酯（r²=0.32；p=0.004）和低密度脂蛋白胆固醇（r²=0.08；p=0.05）水平都是辛伐他汀治疗后ΔCD的显著独立预测因素。
辛伐他汀治疗显著降低了循环共轭二烯水平，并导致谷胱甘肽过氧化物酶活性增加。这些作用在混合性高脂血症患者中比在高胆固醇血症患者中更明显。结果表明辛伐他汀具有一定抗氧化特性，这可能有助于其有益的心血管作用。
