Department of Cardiology, Campus Kerckhoff of the University of Giessen, Kerckhoff Heart and Thorax Center, Benekestrasse 2-8, 61231, Bad Nauheim, Germany.
German Center for Cardiovascular Research (DZHK), Partner Site Rhine-Main, Frankfurt am Main, Germany.
Respir Res. 2020 Aug 3;21(1):204. doi: 10.1186/s12931-020-01472-3.
In chronic thromboembolic pulmonary hypertension (CTEPH) impaired pulmonary hemodynamics lead to right heart failure. Natriuretic peptides reflect hemodynamic disease severity. Pregnancy-associated plasma protein-A (PAPP-A) might address another aspect of CTEPH - chronic tissue injury and inflammation. This study assessed dynamics of PAPP-A in CTEPH patients who undergo therapy with pulmonary endarterectomy (PEA) or balloon pulmonary angioplasty (BPA).
The study included a total of 125 CTEPH patients scheduled for treatment (55 PEA/ 70 BPA) and a control group of 58 patients with pulmonary hypertension other than CTEPH. Biomarker measurement was performed at baseline and follow-up in the CTEPH cohort, prior to each BPA in the BPA cohort and once in the control group.
The median PAPP-A level was slightly higher (p = 0.05) in CTEPH patients [13.8 (11.0-18.6) mU/L], than in the control group [12.6 (8.6-16.5) mU/L], without a difference between the BPA and PEA group (p = 0.437) and without a correlation to mean pulmonary artery pressure (p = 0.188), pulmonary vascular resistance (p = 0.893), cardiac index (p = 0.821) and right atrial pressure (p = 0.596). PEA and BPA therapy decreased the mean pulmonary artery pressure (p < 0.001) and pulmonary vascular resistance (p < 0.001) and improved the WHO-functional-class (baseline: I:0/II:25/III:80/IV:20 vs. follow-up: I:55/II:58/III:10/IV:2). PAPP-A levels decreased after PEA [13.5 (9.5-17.5) vs. 11.3 (9.8-13.6) mU/L; p = 0.003) and BPA treatment [14.3 (11.2-18.9) vs. 11.1 (9.7-13.3) mU/L; p < 0.001). The decrease of PAPP-A levels is delayed in comparison to N-terminal pro-B-type natriuretic peptide.
PAPP-A is overexpressed in CTEPH and decrease significantly after surgical or interventional therapy, however without association to hemodynamics. Further investigation is needed to define the underlying mechanism of PAPP-A expression and changes after therapy in CTEPH.
在慢性血栓栓塞性肺动脉高压（CTEPH）中，肺血流动力学受损导致右心衰竭。利钠肽反映血流动力学疾病的严重程度。妊娠相关血浆蛋白-A（PAPP-A）可能反映 CTEPH 的另一个方面——慢性组织损伤和炎症。本研究评估了接受肺动脉内膜切除术（PEA）或球囊肺动脉成形术（BPA）治疗的 CTEPH 患者中 PAPP-A 的动态变化。
本研究共纳入 125 例计划接受治疗的 CTEPH 患者（55 例 PEA/70 例 BPA）和 58 例非 CTEPH 性肺动脉高压患者作为对照组。在 CTEPH 组中，在治疗前和随访时进行生物标志物检测，在 BPA 组中，在每次 BPA 前进行检测，在对照组中仅进行一次检测。
与对照组[12.6（8.6-16.5）mU/L]相比，CTEPH 患者的 PAPP-A 水平略高（p=0.05）[13.8（11.0-18.6）mU/L]，但 PAPP-A 水平在 BPA 和 PEA 组之间无差异（p=0.437），与平均肺动脉压（p=0.188）、肺血管阻力（p=0.893）、心指数（p=0.821）和右心房压（p=0.596）也无相关性。PEA 和 BPA 治疗降低了平均肺动脉压（p<0.001）和肺血管阻力（p<0.001），并改善了 WHO 功能分级（基线：I：0/II：25/III：80/IV：20 vs. 随访：I：55/II：58/III：10/IV：2）。PEA 后 PAPP-A 水平降低[13.5（9.5-17.5）比 11.3（9.8-13.6）mU/L；p=0.003]，BPA 治疗后 PAPP-A 水平降低[14.3（11.2-18.9）比 11.1（9.7-13.3）mU/L；p<0.001]。与 N 末端脑利钠肽前体相比，PAPP-A 水平的降低滞后。
PAPP-A 在 CTEPH 中过度表达，在手术或介入治疗后显著降低，但与血流动力学无关。需要进一步研究以确定 CTEPH 中 PAPP-A 表达和治疗后变化的潜在机制。
