John Michelle E, Cockcroft John R, McKeever Tricia M, Coward William R, Shale Dennis J, Johnson Simon R, Thornton Jim G, Harrison Timothy W, Knox Alan J, Bolton Charlotte E
Nottingham Respiratory Research Unit, School of Medicine, University of Nottingham, Nottingham, UK.
Wales Heart Research Institute, Cardiff University, Cardiff, UK.
Int J Chron Obstruct Pulmon Dis. 2015 Jan 29;10:211-21. doi: 10.2147/COPD.S76061. eCollection 2015.
There is excess cardiovascular mortality in patients with chronic obstructive pulmonary disease. Aortic stiffness, an independent predictor of cardiovascular risk, and systemic and airway inflammation are increased in patients with the disease. Statins modulate aortic stiffness and have anti-inflammatory properties. A proof-of-principle, double-blind, randomized trial determined if 6 weeks of simvastatin 20 mg once daily reduced aortic stiffness and systemic and airway inflammation in patients with chronic obstructive pulmonary disease.
Stable patients (n=70) were randomized to simvastatin (active) or placebo. Pre-treatment and post-treatment aortic stiffness, blood pressure, spirometry, and circulating and airway inflammatory mediators and lipids were measured. A predefined subgroup analysis was performed where baseline aortic pulse wave velocity (PWV) was >10 m/sec.
Total cholesterol dropped in the active group. There was no significant change in aortic PWV between the active group and the placebo group (-0.7 m/sec, P=0.24). In those with aortic stiffness >10 m/sec (n=22), aortic PWV improved in the active group compared with the placebo group (-2.8 m/sec, P=0.03). Neither systemic nor airway inflammatory markers changed.
There was a nonsignificant improvement in aortic PWV in those taking simvastatin 20 mg compared with placebo, but in those with higher baseline aortic stiffness (a higher risk group) a significant and clinically relevant reduction in PWV was shown.
慢性阻塞性肺疾病患者存在心血管疾病死亡率过高的情况。主动脉僵硬度是心血管风险的独立预测指标,该疾病患者的主动脉僵硬度、全身及气道炎症均有所增加。他汀类药物可调节主动脉僵硬度并具有抗炎特性。一项原理验证性双盲随机试验确定,每日一次服用20 mg辛伐他汀6周是否能降低慢性阻塞性肺疾病患者的主动脉僵硬度、全身及气道炎症。
将病情稳定的患者(n = 70)随机分为辛伐他汀组(活性药物组)或安慰剂组。测量治疗前和治疗后主动脉僵硬度、血压、肺功能、循环及气道炎症介质和血脂。对基线主动脉脉搏波速度(PWV)>10 m/秒的患者进行预定义亚组分析。
活性药物组的总胆固醇下降。活性药物组与安慰剂组之间的主动脉PWV无显著变化(-0.7 m/秒,P = 0.24)。在主动脉僵硬度>10 m/秒的患者(n = 22)中,活性药物组的主动脉PWV较安慰剂组有所改善(-2.8 m/秒,P = 0.03)。全身及气道炎症标志物均未改变。
与安慰剂相比,服用20 mg辛伐他汀的患者主动脉PWV虽有改善但无统计学意义,但在基线主动脉僵硬度较高(风险较高组)的患者中,PWV出现了显著且具有临床意义的降低。