Department of Cardiology and Vascular Medicine, Dr. Sardjito Hospital, Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada, Yogyakarta 55281, Indonesia.
SphingoTec GmbH, Hennigsdorf, 16761 Berlin, Germany.
Medicina (Kaunas). 2023 Apr 12;59(4):748. doi: 10.3390/medicina59040748.
The adrenomedullin level increases in pulmonary arterial hypertension (PAH, and correlates with a high mortality rate. Its active form, bioactive adrenomedullin (bio-ADM), has been recently developed and has significant prognostic applications in acute clinical settings. Aside from idiopathic/hereditary PAH (I/H-PAH), atrial septal defects-associated pulmonary artery hypertension (ASD-PAH) is still prevalent in developing countries and associated with increased mortality. This study aimed to investigate the mortality-wise prognostic value of the plasma bio-ADM level by comparing subjects with ASD-PAH and I/H-PAH with ASD patients without pulmonary hypertension (PH) as a control group. This was a retrospective, observational cohort study. The subjects were Indonesian adult patients who were recruited from the Congenital Heart Disease and Pulmonary Hypertension (COHARD-PH) registry and divided into three groups: (1) ASD without PH (control group), (2) ASD-PAH and (3) I/H-PAH. During right-heart catheterization at the time of diagnosis, a plasma sample was taken and assayed for bio-ADM using a chemiluminescence immunoassay. Follow-up was performed as a part of the COHARD-PH registry protocol in order to evaluate the mortality rate. Among the 120 subjects enrolled: 20 turned out to have ASD without PH, 85 had ASD-PAH and 15 had I/H-PAH. Compared to the control group (5.15 (3.0-7.95 pg/mL)) and ASD-PAH group (7.30 (4.10-13.50 pg/mL)), bio-ADM levels were significantly higher in the I/H-PAH group (median (interquartile range (IQR)): 15.50 (7.50-24.10 pg/mL)). Moreover, plasma bio-ADM levels were significantly higher in subjects who died (n = 21, 17.5%) compared to those who survived (median (IQR): 11.70 (7.20-16.40 pg/mL) vs. 6.90 (4.10-10.20 pg/mL), = 0.031). There was a tendency toward higher bio-ADM levels in those who died among the PAH subjects, in both ASD-PAH and I/H-PAH groups. In conclusion, the plasma bio-ADM level is elevated in subjects with PAH from both ASD-PAH and I/H-PAH origins, reaching the highest levels in subjects with the I/H-PAH form. A high bio-ADM level tended to be associated with a high mortality rate in all subjects with PAH, indicating a relevant prognostic value for this biomarker. In patients with I/H-PAH, monitoring bio-ADM could represent a valid tool for predicting outcomes, allowing more appropriate therapeutical choices.
在肺动脉高压（PAH）中，肾上腺髓质素水平升高，并与高死亡率相关。其活性形式，生物活性肾上腺髓质素（bio-ADM）最近已被开发出来，并在急性临床环境中有重要的预后应用。除特发性/遗传性 PAH（I/H-PAH）外，房间隔缺损相关肺动脉高压（ASD-PAH）在发展中国家仍然很普遍，并与死亡率增加有关。本研究旨在通过比较 ASD-PAH 和 I/H-PAH 患者与无肺动脉高压（PH）的 ASD 患者，探讨血浆生物活性 ADM 水平在死亡率方面的预后价值，以 ASD 患者作为对照组。这是一项回顾性、观察性队列研究。研究对象为来自先天性心脏病和肺动脉高压（COHARD-PH）登记处的印度尼西亚成年患者，并分为三组：（1）无 PH 的 ASD（对照组），（2）ASD-PAH 和（3）I/H-PAH。在诊断时进行右心导管检查时，采集血浆样本并使用化学发光免疫测定法测定生物活性 ADM。根据 COHARD-PH 登记处的协议进行随访，以评估死亡率。在纳入的 120 名受试者中：20 名被诊断为无 PH 的 ASD，85 名患有 ASD-PAH，15 名患有 I/H-PAH。与对照组（5.15（3.0-7.95 pg/mL））和 ASD-PAH 组（7.30（4.10-13.50 pg/mL））相比，I/H-PAH 组的生物活性 ADM 水平显着升高（中位数（四分位距（IQR））：15.50（7.50-24.10 pg/mL））。此外，死亡（n = 21，17.5%）的受试者的血浆生物活性 ADM 水平显着高于存活的受试者（中位数（IQR）：11.70（7.20-16.40 pg/mL）vs. 6.90（4.10-10.20 pg/mL），= 0.031）。在 ASD-PAH 和 I/H-PAH 组的 PAH 患者中，死亡患者的生物活性 ADM 水平均有升高的趋势。总之，来自 ASD-PAH 和 I/H-PAH 的 PAH 患者的血浆生物活性 ADM 水平升高，在 I/H-PAH 形式的患者中达到最高水平。高生物活性 ADM 水平在所有 PAH 患者中倾向于与高死亡率相关，表明该生物标志物具有相关的预后价值。在 I/H-PAH 患者中，监测生物活性 ADM 可能是预测结局的有效工具，从而可以做出更适当的治疗选择。
