Sen Nihat, Tavil Yusuf, Erdamar Hüsamettin, Yazici Hüseyin Uğur, Cakir Erdinç, Akgül Emin Ozgür, Bilgi Cumhur, Erbil Mehmet Kemal, Poyraz Fatih, Okyay Kaan, Turfan Murat, Cemri Mustafa
Department of Cardiology, Faculty of Medicine, Gazi University, Ankara, Turkey.
Anadolu Kardiyol Derg. 2009 Oct;9(5):371-9.
We sought to determine whether nebivolol affects coronary endothelial function and exercise induced ischemia in patients with cardiac syndrome X (CSX).
The study protocol undertaken was based on a single-blind randomized controlled prospective study. After a 2-week washout period, 38 patients with cardiac syndrome X were randomized to receive either nebivolol 5 mg daily (n=19) or metoprolol 50 mg daily (n=19) in a single- blind design for 12 weeks. The control group under study was consisted of 16 age- and gender-matched subjects with negative treadmill exercise tests. Plasma endothelial nitric oxide (NOx), L-arginine, and asymmetric dimethylarginine (ADMA) were measured in all patients at baseline and after 12 weeks of treatment. Statistical differences among groups were tested by one-way analysis of variance and unpaired samples t test for parametric; Kruskal-Wallis and Mann-Whitney U tests for non-parametric variables, respectively. A paired samples t test was used to compare continuous variables before and after drug therapy.
At baseline, plasma level of NOx, L-arginine, and L-arginine/ADMA ratio were lower (p<0.001 for all) in patients with CSX than in the control patients. Whereas, the plasma ADMA levels were increased in the patient group (p<0.001). After 12 weeks of drug therapy, the patients taking nebivolol had increased levels of plasma NOx , plasma L-arginine, the L-arginine/ADMA ratio and decreased levels of plasma ADMA compared to those of the patients taking metoprolol (p<0.001). In addition, exercise duration to 1-mm ST depression and total exercise duration significantly increased after treatment in the nebivolol group compared to the metoprolol group (p<0.01). In the nebivolol group, Canadian Cardiovascular Society (CCS) angina classification improved by one or more categories in 12 (70%) patients, whereas it deteriorated or remained in the same category in 5 (30%) patients. Meanwhile, in the metoprolol group, the CCS angina classification improved by one or more categories in 7 (41%), whereas it deteriorated or remained in the same category in 10 (59%) patients.
Circulating endothelial function parameters (plasma ADMA, L-arginine, NOx levels) were impaired in patients with CSX. Nebivolol treatment was associated with better improvements in both circulating endothelial function and exercise stress test parameters than metoprolol. We believe that further studies are needed to evaluate the effects of nebivolol treatment on long-term clinical outcomes in patients with CSX.
我们试图确定奈必洛尔是否会影响心脏X综合征（CSX）患者的冠状动脉内皮功能和运动诱发的缺血。
所采用的研究方案基于一项单盲随机对照前瞻性研究。在为期2周的洗脱期后，38例心脏X综合征患者被随机分为两组，采用单盲设计，一组每日服用5mg奈必洛尔（n = 19），另一组每日服用50mg美托洛尔（n = 19），为期12周。研究中的对照组由16名年龄和性别匹配且平板运动试验阴性的受试者组成。在所有患者的基线期和治疗12周后，测量血浆内皮一氧化氮（NOx）、L-精氨酸和不对称二甲基精氨酸（ADMA）。组间的统计学差异分别通过单因素方差分析和非参数变量的Kruskal-Wallis检验以及参数变量的不成对样本t检验和Mann-Whitney U检验进行检验。采用配对样本t检验比较药物治疗前后的连续变量。
在基线期，CSX患者的血浆NOx、L-精氨酸水平以及L-精氨酸/ADMA比值均低于对照组患者（均p < 0.001）。然而，患者组的血浆ADMA水平升高（p < 0.001）。药物治疗12周后，与服用美托洛尔的患者相比，服用奈必洛尔的患者血浆NOx、血浆L-精氨酸水平、L-精氨酸/ADMA比值升高，血浆ADMA水平降低（p < 0.001）。此外，与美托洛尔组相比，奈必洛尔组治疗后出现1mm ST段压低的运动持续时间和总运动持续时间显著增加（p < 0.01）。在奈必洛尔组中，12例（70%）患者的加拿大心血管学会（CCS）心绞痛分级改善了一级或更多级别，而5例（30%）患者的分级恶化或维持在同一级别。同时，在美托洛尔组中，7例（41%）患者的CCS心绞痛分级改善了一级或更多级别，而10例（59%）患者的分级恶化或维持在同一级别。
CSX患者的循环内皮功能参数（血浆ADMA、L-精氨酸、NOx水平）受损。与美托洛尔相比，奈必洛尔治疗在循环内皮功能和运动应激试验参数方面的改善更好。我们认为，需要进一步研究来评估奈必洛尔治疗对CSX患者长期临床结局的影响。
