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普伐他汀对慢性阻塞性肺疾病合并肺动脉高压患者功能能力的影响。

Effects of pravastatin on functional capacity in patients with chronic obstructive pulmonary disease and pulmonary hypertension.

作者信息

Lee Tsung-Ming, Chen Chien-Chang, Shen Hsiu-Nien, Chang Nen-Chung

机构信息

Cardiology Section, Department of Medicine, Taipei Medical University and Chi-Mei Medical Center, Tainan, Taiwan.

出版信息

Clin Sci (Lond). 2009 Mar;116(6):497-505. doi: 10.1042/CS20080241.

Abstract

PH (pulmonary hypertension) often complicates the disease course of patients with COPD (chronic obstructive pulmonary disease) and is an indication of a worse prognosis. In the present study, we assessed whether pravastatin administration was effective in improving PH and exercise capacity in COPD patients with PH, and whether the pulmonary protection was mediated by inhibiting ET-1 (endothelin-1) production. In a double-blind parallel design, 53 COPD patients with PH were randomly assigned to receive either placebo or pravastatin (40 mg/day) over a period of 6 months at a medical centre. Baseline characteristics were similar in both groups. The exercise time remained stable throughout the study in the placebo group. After 6 months, the exercise time significantly increased 52% from 660+/-352 to 1006+/-316 s (P<0.0001) in pravastatin-treated patients. With pravastatin, echocardiographically derived systolic PAP (pulmonary artery pressure) decreased significantly from 47+/-8 to 40+/-6 mmHg. There was significant improvement in the Borg dyspnoea score after administering pravastatin. Despite unchanged plasma ET-1 levels throughout the study, urinary excretion of the peptide was decreased and significantly correlated with an improvement in exercise time in pravastatin-treated patients (r=-0.47, P=0.01). In conclusion, pravastatin significantly improved exercise tolerance, and decreased PH and dyspnoea during exercise in COPD patients with PH, probably by inhibiting ET-1 synthesis.

摘要

肺动脉高压(PH)常使慢性阻塞性肺疾病(COPD)患者的病程复杂化,是预后较差的一个指标。在本研究中,我们评估了给予普伐他汀是否能有效改善合并PH的COPD患者的PH及运动能力,以及肺保护作用是否通过抑制内皮素-1(ET-1)生成来介导。在一项双盲平行设计中,53例合并PH的COPD患者在一家医疗中心被随机分配接受安慰剂或普伐他汀(40毫克/天)治疗,为期6个月。两组的基线特征相似。在整个研究过程中,安慰剂组的运动时间保持稳定。6个月后,接受普伐他汀治疗的患者运动时间从660±352秒显著增加52%至1006±316秒(P<0.0001)。使用普伐他汀后,超声心动图测得的收缩期肺动脉压(PAP)从47±8毫米汞柱显著降至40±6毫米汞柱。给予普伐他汀后,Borg呼吸困难评分有显著改善。尽管在整个研究过程中血浆ET-1水平未变,但肽的尿排泄量减少,且与接受普伐他汀治疗患者的运动时间改善显著相关(r=-0.47,P=0.01)。总之,普伐他汀可能通过抑制ET-1合成,显著改善了合并PH的COPD患者的运动耐量,降低了PH及运动时的呼吸困难。

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