Mulder Han J G H, Schalij Martin J, van der Laarse Arnoud, Hollaar Leny, Zwinderman Aeilko H, Bruschke Albert V G
Department of Cardiology, Leiden University Medical Center, P.O. Box 9600, 2300RC Leiden, The Netherlands.
Atherosclerosis. 2003 Aug;169(2):309-15. doi: 10.1016/s0021-9150(03)00197-7.
Oxidation susceptibility of lipids in vitro is considered to reflect the exposure of lipids to oxidation stress in vivo which is related to cardiovascular morbidity. This study examined the effect of pravastatin therapy on serum oxidation susceptibility, particularly in relation to endothelial function of coronary arteries.
The participants were recruited from the Pravastatin-Related Effects Following Angioplasty on Coronary Endothelium trial, a double-blinded, placebo-controlled, randomized, multi-center study designed to analyze the effect of pravastatin treatment on endothelial function in previously dilated and normal coronary arteries. Serial, graded, intra-coronary acetylcholine infusions were used to assess endothelial function. In vitro, copper-induced, serum oxidation parameters were determined at randomization and at time of coronary endothelial function assessment.
Oxidation parameters were determined in 45 patients (pravastatin 23, placebo 22). Pravastatin therapy significantly improved serum oxidation lag time (+8%, P<0.05), maximal diene formation rate (-22%, P<0.01) and total amount of dienes formed after 5 h (-16%, P<0.01). These parameters remained essentially unchanged in the placebo group. Acetylcholine-evoked responses were positively correlated to therapy-induced change in serum oxidation susceptibility in the dilated segment group (r2=0.56, P=0.006).
Pravastatin's beneficial effect on endothelial dysfunction of dilated coronary segments may be secondary to pravastatin's improvement of oxidation susceptibility.
体外脂质的氧化易感性被认为反映了脂质在体内暴露于氧化应激的情况，而这与心血管疾病的发病率相关。本研究考察了普伐他汀治疗对血清氧化易感性的影响，特别是与冠状动脉内皮功能的关系。
参与者来自血管成形术后普伐他汀对冠状动脉内皮的相关影响试验，这是一项双盲、安慰剂对照、随机、多中心研究，旨在分析普伐他汀治疗对既往扩张和正常冠状动脉内皮功能的影响。采用冠状动脉内连续、分级注入乙酰胆碱来评估内皮功能。在体外，于随机分组时以及冠状动脉内皮功能评估时测定铜诱导的血清氧化参数。
对45例患者（普伐他汀组23例，安慰剂组22例）测定了氧化参数。普伐他汀治疗显著改善了血清氧化滞后时间（增加8%，P<0.05）、最大二烯生成速率（降低22%，P<0.01）以及5小时后生成的二烯总量（降低16%，P<0.01）。这些参数在安慰剂组基本保持不变。在扩张节段组，乙酰胆碱诱发的反应与治疗引起的血清氧化易感性变化呈正相关（r2=0.56，P=0.006）。
普伐他汀对扩张冠状动脉节段内皮功能障碍的有益作用可能继发于普伐他汀对氧化易感性的改善。
