Ky Bonnie, Burke Anne, Tsimikas Sotirios, Wolfe Megan L, Tadesse Mahlet G, Szapary Philippe O, Witztum Joseph L, FitzGerald Garret A, Rader Daniel J
Institute for Translational Medicine and Therapeutics, University of Pennsylvania, Philadelphia, Pennsylvania 19104-6160, USA.
J Am Coll Cardiol. 2008 Apr 29;51(17):1653-62. doi: 10.1016/j.jacc.2008.01.026.
The aim of this study was to determine the effects of pravastatin and atorvastatin on markers of oxidative stress in plasma.
Hydroxymethylglutaryl coenzyme A reductase inhibitors reduce low-density lipoprotein cholesterol (LDL-C) and cardiovascular risk, but their effects on circulating biomarkers of oxidative stress are not well-defined.
Hypercholesterolemic subjects (n = 120, ages 21 to 80 years with LDL-C 130 to 220 mg/dl) were randomized in a double-blind, parallel design to pravastatin 40 mg/day (prava40), atorvastatin 10 mg/day (atorva10), atorvastatin 80 mg/day (atorva80), or placebo. At baseline and 16 weeks, urinary isoprostanes (8, 12-iso-iPF(2 alpha)-VI isoform), plasma lipoprotein-associated phospholipase A2 (Lp-PLA2), Mercodia oxidized LDL (OxLDL) with antibody 4E6, oxidized phospholipids/apolipoprotein B-100 particle (OxPL/apoB) with antibody E06, immunoglobulin (Ig)G/IgM autoantibodies to malondialdehyde (MDA)-LDL, and apolipoprotein B (apoB)-immune complexes (IC) were measured.
After 16 weeks, there were no significant changes in urinary 8, 12-iso-iPF(2 alpha)-VI. The Lp-PLA2 and OxLDL were reduced in statin-treated groups, but after adjusting for apoB, only prava40 led to a reduction in Lp-PLA2 (-15%, p = 0.008) and atorva10 to a decrease in OxLDL (-12.9%, p = 0.01). The OxPL/apoB increased 25.8% (p < 0.01) with prava40 and 20.2% (p < 0.05) with atorva80. There were no changes in MDA-LDL autoantibodies, but significant decreases in IC were noted.
This study suggests that statin therapy results in variable effects on oxidative stress markers in hypercholesterolemic subjects. Future outcome studies should collectively assess various oxidative markers to define clinical utility.
本研究旨在确定普伐他汀和阿托伐他汀对血浆氧化应激标志物的影响。
羟甲基戊二酰辅酶A还原酶抑制剂可降低低密度脂蛋白胆固醇（LDL-C）并降低心血管风险，但其对循环氧化应激生物标志物的影响尚不明确。
将高胆固醇血症患者（n = 120，年龄21至80岁，LDL-C为130至220mg/dl）采用双盲、平行设计随机分为普伐他汀40mg/天（prava40）组、阿托伐他汀10mg/天（atorva10）组、阿托伐他汀80mg/天（atorva80）组或安慰剂组。在基线和16周时，检测尿中异前列腺素（8,12-异-iPF(2α)-VI异构体）、血浆脂蛋白相关磷脂酶A2（Lp-PLA2）、用抗体4E6检测的美迪科氧化低密度脂蛋白（OxLDL）、用抗体E06检测的氧化磷脂/载脂蛋白B-100颗粒（OxPL/apoB）、抗丙二醛（MDA）-LDL的免疫球蛋白（Ig）G/IgM自身抗体以及载脂蛋白B（apoB）免疫复合物（IC）。
16周后，尿中8,12-异-iPF(2α)-VI无显著变化。他汀类药物治疗组的Lp-PLA2和OxLDL降低，但在调整apoB后，只有prava40导致Lp-PLA2降低（-15%，p = 0.008），atorva10导致OxLDL降低（-12.9%，p = 0.01）。prava40使OxPL/apoB升高25.8%（p < 0.01），atorva80使OxPL/apoB升高20.2%（p < 0.05）。MDA-LDL自身抗体无变化，但IC显著降低。
本研究表明他汀类药物治疗对高胆固醇血症患者的氧化应激标志物有不同影响。未来的结局研究应综合评估各种氧化标志物以确定其临床应用价值。
