Short and long term anti-inflammatory effects of bosentan therapy in patients with pulmonary arterial hypertension: relation to clinical and hemodynamic responses
Short and long term anti-inflammatory effects of bosentan therapy in patients with pulmonary arterial hypertension: relation to clinical and hemodynamic responses
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DOI：
10.1517/14728222.2010.523421
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发表时间：
2010-12-01
影响因子：
5.8
通讯作者：
Voudris, Vassilis
中科院分区：
文献类型：
--
作者：
Karavolias, George K.;Georgiadou, Panagiota;Voudris, Vassilis
目的：我们试图研究波生坦治疗对肺动脉高压（PAH）患者的内皮、炎症和纤维化标志物的短期和长期影响，以及与临床和血流动力学反应的关系。方法：我们研究了16例中重度特发性PAH患者，WHO功能分级II-IV，尽管接受常规治疗。患者接受波生坦额外治疗，62.5 mg每日两次，持续1个月，随后125 mg每日两次，持续11个月。研究终点包括6分钟步行距离（6 MWD）、平均肺动脉压（mPAP）、肺血管阻力（PVR）和血浆细胞内细胞粘附分子-1（ICAM-1）、血管细胞粘附分子-1（VCAM-1）、IL-6和脑钠肽（BNP）水平。结果：治疗2个月后，6 MWD（p < 0.001）和功能分级（p <0.001）均有改善，PVR（p <0.001）、ICAM-1（p <0.001）、IL-6（p <0.001）和BNP（p = 0.001）明显下降。12个月时，6 MWD进一步改善（p < 0.001），PVR仍显著改善（p < 0.001），mPAP显著降低（p < 0.001），ICAM-1、IL-6和BNP仍显著降低（p < 0.001）。ICAM-1的变化与心脏指数之间存在显著相关性（r = 0.59，p = 0.01），IL-6和PVR（r = 0.51，p = 0.04），BNP和6MWD BNP与PAP之间有显著相关性（r =-0.53，p = 0.03）（r = 0.51，p = 0.04）。结论：在中重度PAH患者中，治疗中添加波生坦可发挥有利的抗炎作用，与临床和血流动力学改善相关。
Objective: We sought to investigate the short-and long-term effects of bosentan therapy on endothelial, inflammatory and fibrotic markers in patients with pulmonary arterial hypertension (PAH) and the relation to clinical and hemodynamic responses.Methods: We studied 16 patients with moderate-severe idiopathic PAH, in WHO functional class II-IV, despite conventional treatment. Patients received additional treatment with bosentan, 62.5 mg twice daily for 1 month, followed by 125 mg twice daily for 11 months. Study endpoints included 6-min walking distance (6MWD), mean pulmonary artery pressure (mPAP), pulmonary vascular resistance (PVR) and plasma levels of intracellular cell adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1), IL-6 and brain natriuretic peptide (BNP). Patients were assessed at baseline, 2 months and 12 months after initiation of bosentan.Results: At 2 months there was an improvement in 6MWD (p < 0.001) and functional class (p < 0.001) and a marked fall in PVR (p < 0.001), ICAM-1 (p < 0.001), IL-6 (p < 0.001) and BNP (p = 0.001). At 12 months, 6MWD was further improved (p < 0.001), PVR remained significantly improved (p < 0.001), mPAP was significantly decreased (p < 0.001) and ICAM-1, IL-6 and BNP remained significantly lower (p < 0.001). Significant correlations were found between changes in ICAM-1 and cardiac index (r = 0.59, p = 0.01), IL-6 and PVR (r = 0.51, p = 0.04), BNP and 6MWD (r = -0.53, p = 0.03) and BNP and PAP (r = 0.51, p = 0.04) between 2- and 12-months treatment.Conclusions: In patients with moderate-severe PAH, the addition of bosentan to therapy, exerts favorable anti-inflammatory effects, which are associated with clinical and hemodynamic improvement.