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目的研究他汀类药物在慢性阻塞性肺疾病(COPD)合并肺动脉高压(PH)患者中疗效和机制以及对预后的影响。方法选择2007年1月至2011年1月诊治的COPD合并PH患者156例,随机分为治疗组和对照组各78例。对照组给予常规治疗;治疗组在常规治疗基础上加用阿托伐他汀,首剂10～20 mg/d,qd,若无不良反应,则维持剂量,10 mg/d。疗程1个月、6个月、12个月,观察高敏感性C-反应蛋白(hs-CRP)、D-二聚体、一氧化氮(NO)、内皮素-1(ET-1)、Tei指数、肺动脉收缩压(PAPs)、1 s用力呼气容积占预计值百分比(FEV1%)及6 min步行距离(6MWD)。治疗后1年随访患者的再入院人数及死亡人数。结果治疗1个月后,两组CRP、D-二聚体、ET-1显著下降(P均<0.01),NO明显升高(P均<0.01);但治疗组较对照组更明显,差异有统计学意义,继续服药6个月、12个月时,治疗组CRP、D-二聚体、ET-1持续下降,NO持续升高,6个月与1个月(P<0.01,P<0.05)、12个月与6个月(P<0.01,P<0.05)比较差异有统计学意义。而对照组CRP、D-二聚体、ET-1、NO无明显变化(P>0.05)。Spearman相关分析显示,血hs-CRP、ET-1、D二聚体水平与PAPs呈正相关(r=0.478,-0.564,0.562,0.716,P<0.05),NO数值与PAPs呈负相关(r=-0.564)。应用阿托伐他汀治疗1个月后,两组PAPa、Tei指数显著下降(P均<0.01),FEV1%、6MWD明显升高(P均<0.01);治疗组FEV1%、6MWD、PAPa较对照组明显好转(P<0.01),Tei指数变化无明显差异(P>0.05)。继续用药治疗,FEV1%、6MWD、PAPa进一步改善,6个月与1个月,12个月与6个月变化均有统计学意义;而Tei指数的改善较缓慢,6个月时治疗组与对照组出现统计学差异;同组比较,治疗组6个月与1个月,12个月与6个月无统计学意义,12个月与1个月比较差异有统计学意义(P<0.01);而对照组FEV1%、6MWD、PAPa、Tei指数均无明显变化(P>0.05)。随访1年的再入院人数及死亡人数,治疗组较对照组明显减少,差异有统计学意义(P均<0.05)。结论阿托伐他汀能降低COPD合并PH患者肺动脉压,改善患者心肺功能及运动耐量,具时间依赖性,其机制与阿托伐他汀能抑制炎性反应,改善高凝状态和血管内皮功能有关。
Objective To investigate the effects and mechanisms of statins in patients with chronic obstructive pulmonary disease (COPD) complicated with pulmonary hypertension (PH) and their effects on prognosis. Methods 156 patients with COPD complicated with PH who were diagnosed and treated from January 2007 to January 2011 were randomly divided into treatment group (78 cases) and control group (78 cases). The control group was given routine treatment. The treatment group was given atorvastatin on the basis of conventional treatment. The first dose of 10 ~ 20 mg / d, qd, if no adverse reaction, the maintenance dose, 10 mg / d. The duration of treatment was 1 month, 6 months and 12 months respectively. High sensitivity C-reactive protein (hs-CRP), D-dimer, nitric oxide (NO), endothelin- Tei index, pulmonary artery systolic pressure (PAPs), forced expiratory volume 1% of predicted value (FEV1%) and 6 min walking distance (6MWD). The number of hospital admissions and the number of deaths were followed up for 1 year after treatment. Results After treatment for one month, the levels of CRP, D-dimer and ET-1 decreased significantly in both groups (all P <0.01) and NO increased (all P <0.01), but the treatment group was more obvious than the control group (P <0.01, P <0.01), and the levels of CRP, D-dimer and ET-1 in treatment group continued to decrease, while NO continued to increase at 6 and 12 months <0.05). There was significant difference between 12 months and 6 months (P <0.01, P <0.05). The control group CRP, D-dimer, ET-1, NO no significant change (P> 0.05). Spearman correlation analysis showed that there was a positive correlation between serum hs-CRP, ET-1 and D dimers and PAPs (r = 0.478, -0.564, 0.562, 0.716, -0.564). After 1 month of atorvastatin treatment, PAPa and Tei index decreased significantly in both groups (all P <0.01), FEV1% and 6MWD increased significantly (all P <0.01), and FEV1%, 6MWD and PAPa Group improved significantly (P <0.01), Tei index no significant difference (P> 0.05). The continued improvement of FEV1%, 6MWD, PAPa, 6 months and 1 month, 12 months and 6 months showed statistically significant changes, while the Tei index improved more slowly. At 6 months, There was statistical difference in the control group. Compared with the same group, the treatment group had no significant difference between 6 months and 1 month, 12 months and 6 months, and there was significant difference between 12 months and 1 month (P <0.01) ), While FEV1%, 6MWD, PAPa and Tei index in the control group showed no significant change (P> 0.05). Follow-up of 1 year of the number of hospitalizations and deaths, the treatment group was significantly reduced compared with the control group, the difference was statistically significant (P all <0.05). Conclusions Atorvastatin can reduce pulmonary arterial pressure and improve cardiopulmonary function and exercise tolerance in COPD patients with PH. It is related to that atorvastatin can inhibit inflammatory reaction, improve hypercoagulable state and vascular endothelial function.