Holzhauser Luise, Hovnanians Ninel, Eshtehardi Parham, Mojadidi M Khalid, Deng Yi, Goodman-Meza David, Msaouel Pavlos, Ko Yi-An, Zolty Ronald
Department of Medicine, Jacobi Medical Center, Albert Einstein College of Medicine, Bronx, NY, USA.
Department of Biostatistics and Bioinformatics, Rollins School of Public Health, Emory University, Atlanta, GA, USA.
Heart Vessels. 2017 Aug;32(8):969-976. doi: 10.1007/s00380-017-0957-8. Epub 2017 Mar 16.
Inflammation is an increasingly recognized hallmark of pulmonary hypertension (PH). Statins have been shown to attenuate key pathologic mechanisms via pleiotropic effects in animal models. However, clinical benefit of statins in patients with PH is unknown and their effect on mortality has not been studied. We performed a retrospective analysis of patients between January 2002 to January 2012, with severe PH (pulmonary artery systolic pressure ≥60 mmHg) and preserved left ventricular function (ejection fraction ≥50%), defined by transthoracic echocardiograms. Patients were divided into two groups based on statin therapy for 12 consecutive months after diagnosis of PH. Propensity score matching was performed. Subgroup analysis was done based on COPD status. Study endpoint was 1-year all-cause mortality and hospitalization. 2363 patients (age 71 ± 16; 31% male) were included; 140 (6%) were on statin therapy. Overall 1-year mortality was 34%. Following propensity score matching, 138 patients were included in the statin group and 624 patients in the no-statin group; all-cause mortality was significantly lower in the statin group compared with the no-statin group [15.2 vs. 33.8%, HR 0.42 (95% CI 0.27, 0.66), p < 0.001], but hospitalization was comparable between two groups. After stratifying patients based on COPD status, patients with COPD showed a marginally significant survival benefit from statins [HR 0.53 (95% CI 0.26, 1.10), p = 0.09]; and statins significantly reduced 1-year all-cause mortality in patients without COPD [HR 0.36 (95% CI 0.19, 0.67), p = 0.001]. We found no significant difference in the effect of statins on patients with COPD compared to those without (p = 0.16). Statin therapy is associated with reduced mortality risk in patients with severe PH and preserved left ventricular function. This beneficial effect was not found to be dependent on COPD status. These novel findings should be confirmed in large randomized trials.
炎症是肺动脉高压(PH)中一个日益被认识到的特征。在动物模型中,他汀类药物已被证明可通过多效性作用减轻关键病理机制。然而,他汀类药物对PH患者的临床益处尚不清楚,且其对死亡率的影响尚未得到研究。我们对2002年1月至2012年1月期间经胸超声心动图定义为患有严重PH(肺动脉收缩压≥60 mmHg)且左心室功能保留(射血分数≥50%)的患者进行了回顾性分析。根据PH诊断后连续12个月的他汀类药物治疗情况将患者分为两组。进行了倾向评分匹配。根据慢性阻塞性肺疾病(COPD)状态进行亚组分析。研究终点为1年全因死亡率和住院率。纳入了2363例患者(年龄71±16岁;31%为男性);140例(6%)接受他汀类药物治疗。总体1年死亡率为34%。经过倾向评分匹配后,他汀类药物组纳入138例患者,非他汀类药物组纳入624例患者;与非他汀类药物组相比,他汀类药物组的全因死亡率显著更低[15.2%对33.8%,风险比(HR)0.42(95%置信区间0.27,0.66),p<0.001],但两组间住院率相当。根据COPD状态对患者进行分层后,COPD患者从他汀类药物中获得的生存益处略有显著差异[HR 0.53(95%置信区间0.26,1.10),p = 0.09];他汀类药物显著降低了无COPD患者的1年全因死亡率[HR 0.36(95%置信区间0.19,0.67),p = 0.001]。我们发现他汀类药物对COPD患者和非COPD患者的影响无显著差异(p = 0.16)。他汀类药物治疗与严重PH且左心室功能保留患者的死亡风险降低相关。未发现这种有益作用依赖于COPD状态。这些新发现应在大型随机试验中得到证实。