Laboratory Medicine & Pathology, University of Minnesota, Minneapolis, MN 55455, United States.
Atherosclerosis. 2011 Feb;214(2):422-5. doi: 10.1016/j.atherosclerosis.2010.11.022. Epub 2010 Nov 26.
Fenofibrate significantly reduces circulating triglyceride (TG) concentrations, particularly in individuals with elevated levels. The purpose of the current study was to determine whether fenofibrate treatment reduces markers of oxidative stress, oxidized low density lipoprotein (ox-LDL) and 8-isoprostane (8-isoP), in a manner similar to TG where those with the highest levels show the greatest reductions.
MATERIALS/METHODS: The concentrations of TG, 8-isoP, and ox-LDL were measured in plasma before and after 3 weeks of fenofibrate treatment (160 mg/d) in a sub-cohort (n=187) of the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN) study.
Data were divided into tertiles as determined by pre-treatment values of the respective target. Fenofibrate treatment resulted in significant reductions in TG concentrations by 24.2% (p<0.0001), 41.9% (p < 0.0001), and 46.6% (p < 0.0001) in tertiles 1, 2, and 3, respectively. Significant reductions were also observed in ox-LDL of 7.2% (p=0.0096), 8.5% (p = 0.0019) and 12.1% (p < 0.0001) in tertiles 1, 2, and 3, respectively. Finally, fenofibrate treatment resulted in a 32.7% increase (p=0.0201) in 8-isoP levels in tertile 1, but a significant decrease of 34.4% (p < 0.0001) in tertile 3.
This study is the largest to date to demonstrate that fenofibrate reduces oxidative stress and the first to show a suppressive effect on 8-isoP levels in individuals with a high oxidative burden following short term (3 wk) drug therapy. Those with the highest baseline levels of ox-LDL and 8-isoP showed the greatest reductions following fenofibrate treatment. Given the role of oxidative stress in atherosclerosis and coronary heart disease, our observations may partially explain the efficacy of fenofibrate in reducing cardiovascular events in select patients.
非诺贝特可显著降低循环甘油三酯（TG）水平，尤其在TG 水平升高的患者中。本研究旨在确定非诺贝特治疗是否可降低氧化应激标志物氧化型低密度脂蛋白（ox-LDL）和 8-异前列腺素（8-isoP），其方式类似于 TG，即 TG 水平最高的患者降低幅度最大。
材料/方法：在遗传降脂药物和饮食网络（GOLDN）研究的一个亚组（n=187）中，在非诺贝特治疗（160 mg/d）前 3 周测量血浆中的 TG、8-isoP 和 ox-LDL 浓度。
根据各自靶标的治疗前值，将数据分为三分位数。非诺贝特治疗可使 TG 浓度分别降低 24.2%（p<0.0001）、41.9%（p<0.0001）和 46.6%（p<0.0001），分别在三分位数 1、2 和 3 中。ox-LDL 也分别显著降低 7.2%（p=0.0096）、8.5%（p=0.0019）和 12.1%（p<0.0001），分别在三分位数 1、2 和 3 中。最后，非诺贝特治疗使三分位数 1 中的 8-isoP 水平增加 32.7%（p=0.0201），而三分位数 3 中的 8-isoP 水平显著降低 34.4%（p<0.0001）。
本研究是迄今为止最大的研究，证明非诺贝特可降低氧化应激，也是首个证明在短期（3 周）药物治疗后，高氧化应激个体的 8-isoP 水平具有抑制作用的研究。ox-LDL 和 8-isoP 基线水平最高的患者，在接受非诺贝特治疗后降低幅度最大。鉴于氧化应激在动脉粥样硬化和冠心病中的作用，我们的观察结果可能部分解释了非诺贝特在降低特定患者心血管事件中的疗效。
