van den Akker Judith M, Bredie Sebastian J H, Diepenveen Sabine H A, van Tits Lambertus J H, Stalenhoef Anton F H, van Leusen Rob
Department of Internal Medicine, Rijnstate Hospital of Arnhem, Arnhem, The Netherlands.
J Nephrol. 2003 Mar-Apr;16(2):238-44.
Cardiovascular disease as a result of accelerated atherogenesis is common in patients with end-stage renal disease (ESRD). Dyslipidemia may be a major contributor in this process and can be influenced by lipid-lowering drugs (statins). Moreover, statins may exhibit additional inhibitory effects on the atherogenesis, such as a modulation of the immune system as triggered by oxidatively modified LDL and a reduction of the inflammatory marker C-reactive protein (CRP).
We evaluated in a single-blind randomized trial of 28 ESRD patients on hemodialysis, the dose-depending effects of both atorvastatin and simvastatin on lipids, lipoproteins, LDL particle heterogeneity, high sensitive-CRP, and markers of in vivo LDL oxidation.
Both statin therapies significantly lowered total plasma cholesterol and LDL-cholesterol concentrations to the same extent, whereas reduction in the concentrations of triglyceride-rich particles was less pronounced. Furthermore, statin therapy reduced LDL cholesterol in all LDL subfractions, without altering the overall LDL particle density. After both statins plasma hs-CRP concentrations were not significantly reduced; parameters of in vivo LDL oxidation (plasma ox-LDL concentration and the oxidation level of isolated LDL), were significantly decreased. Autoantibodies against ox-LDL, however, did not change during this trial period.
These results show that atorvastatin and simvastatin exhibit comparable favourable effects on lipid profiles in ESRD. Moreover, the reduction of in vivo oxidatively modified LDL as shown in this ESRD population, may indicate that these statins exhibit favourable effects on oxidative stress in vivo.
在终末期肾病(ESRD)患者中,由于动脉粥样硬化加速导致的心血管疾病很常见。血脂异常可能是这一过程的主要促成因素,并且可能受到降脂药物(他汀类药物)的影响。此外,他汀类药物可能对动脉粥样硬化表现出额外的抑制作用,例如对氧化修饰低密度脂蛋白(LDL)引发的免疫系统的调节以及炎症标志物C反应蛋白(CRP)的降低。
我们在一项针对28例接受血液透析的ESRD患者的单盲随机试验中,评估了阿托伐他汀和辛伐他汀对血脂、脂蛋白、LDL颗粒异质性、高敏CRP以及体内LDL氧化标志物的剂量依赖性影响。
两种他汀类药物治疗均能在相同程度上显著降低总血浆胆固醇和LDL胆固醇浓度,而富含甘油三酯颗粒浓度的降低则不太明显。此外,他汀类药物治疗降低了所有LDL亚组分中的LDL胆固醇,而未改变整体LDL颗粒密度。两种他汀类药物治疗后,血浆hs-CRP浓度均未显著降低;体内LDL氧化参数(血浆氧化型LDL浓度和分离出的LDL的氧化水平)显著降低。然而,在该试验期间,抗氧化型LDL自身抗体并未改变。
这些结果表明,阿托伐他汀和辛伐他汀对ESRD患者的血脂谱表现出相当的有利影响。此外,在该ESRD人群中所显示的体内氧化修饰LDL的降低,可能表明这些他汀类药物对体内氧化应激具有有利影响。