Lai Jiangtao, Wu Bifeng, Sun Jian, Shang Yunpeng, Zhu Jianhua
Department of Cardiology, the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China.
Coron Artery Dis. 2013 Nov;24(7):566-71. doi: 10.1097/MCA.0000000000000029.
Sustained use of nitrates is associated with adverse effects on vascular function by increasing oxidative stress. It remains unclear whether oxidative stress impairs endothelial function in patients with coronary artery disease (CAD) during long-term oral use of nitrates. The purpose of this study was to evaluate the effects of long-term isosorbide mononitrate (ISMN) treatment on oxidative stress and endothelial function in patients with CAD.
In this prospective, double-blinded, placebo-controlled, randomized, single-center study, 60 patients were assigned to treatment with ISMN 20 mg retarded release orally twice per day (ISMN group, n=30) or placebo (control group, n=30) for 1 year. The primary endpoint was the change in brachial artery endothelium-dependent dilation [flow-mediated dilation (FMD)] from baseline to follow-up. Furthermore, serum superoxide dismutase, malondialdehyde, and hypersensitive C-reactive protein levels were also measured at baseline and follow-up.
The FMD decreased significantly (from 5.97±2.88 to 5.33±2.56%) in the ISMN group, whereas it increased from 6.27±3.23 to 6.96±2.84% in the control group after treatment for 1 year. There was a significant difference in the changes in FMD when the two groups were compared (-0.64±1.83 vs. 0.69±1.77%, P=0.006). There were no significant changes in serum superoxide dismutase, malondialdehyde, and hypersensitive C-reactive protein levels in the two groups.
Long-term ISMN treatment may impair endothelial function in patients with CAD.
持续使用硝酸盐会通过增加氧化应激对血管功能产生不利影响。长期口服硝酸盐期间，氧化应激是否会损害冠状动脉疾病（CAD）患者的内皮功能仍不清楚。本研究的目的是评估长期单硝酸异山梨酯（ISMN）治疗对CAD患者氧化应激和内皮功能的影响。
在这项前瞻性、双盲、安慰剂对照、随机、单中心研究中，60例患者被分配接受每日两次口服20mg缓释ISMN治疗（ISMN组，n = 30）或安慰剂治疗（对照组，n = 30），为期1年。主要终点是从基线到随访时肱动脉内皮依赖性扩张[血流介导的扩张（FMD）]的变化。此外，还在基线和随访时测量了血清超氧化物歧化酶、丙二醛和超敏C反应蛋白水平。
治疗1年后，ISMN组的FMD显著降低（从5.97±2.88降至5.33±2.56%），而对照组的FMD从6.27±3.23增加至6.96±2.84%。两组比较时，FMD变化有显著差异（-0.64±1.83 vs. 0.69±1.77%，P = 0.006）。两组血清超氧化物歧化酶、丙二醛和超敏C反应蛋白水平均无显著变化。
长期ISMN治疗可能损害CAD患者的内皮功能。
