Bouzina Habib, Rådegran Göran
Section of Cardiology, Faculty of Medicine, Lund University, Lund, Sweden; The Hemodynamic Lab, Skåne University Hospital, Lund, Sweden.
Pulm Circ. 2020 Jun 15;10(3):2045894020931317. doi: 10.1177/2045894020931317. eCollection 2020 Jul-Sep.
Adrenomedullin is a potent vasodilatory peptide, linked to pulmonary arterial hypertension pathology. Proximity extension assays were utilized to study plasma biomarkers related to vasoregulation, with focus on adrenomedullin peptides and precursor levels, collectively referred to as ADM. ADM was measured in 48 treatment-naïve pulmonary arterial hypertension patients at diagnosis, and in 31 of them at an early treatment follow-up. Plasma ADM was additionally assessed in patients with chronic thromboembolic pulmonary hypertension ( = 20) and pulmonary hypertension due to heart failure with preserved (HFpEF) ( = 33) or reduced (HFrEF) ( = 36) ejection fraction, as well as healthy controls ( = 16). ADM was studied in relation to pulmonary arterial hypertension hemodynamics, risk assessment, prognosis, treatment response, and differentiation. Plasma ADM levels in pulmonary arterial hypertension patients at diagnosis were higher than in healthy controls ( < 0.001), similar as in chronic thromboembolic pulmonary hypertension patients ( = ns), but lower compared to HFpEF ( < 0.03) and HFrEF ( < 0.001). In pulmonary arterial hypertension, specifically, plasma ADM at diagnosis correlated mainly to mean right atrial pressure ( = 0.73, < 0.001), N-terminal prohormone of brain natriuretic peptide ( = 0.75, < 0.001), six-minute walking distance ( = -0.57, < 0.001), and venous oxygen saturation ( = -0.57, < 0.001). ADM also correlated to the ECS/ERS- ( = 0.74, < 0.001) and REVEAL risk scores ( = 0.54, < 0.001) at pulmonary arterial hypertension diagnosis. Plasma ADM in pulmonary arterial hypertension patients was unaltered at early treatment follow-up compared to baseline ( = ns). Pulmonary arterial hypertension patients with supra-median ADM at diagnosis showed worse overall survival than those with infra-median levels (median survival 34 versus 66 months, = 0.0077). In conclusion, the present results suggest that baseline plasma ADM levels mirror disease severity, correlating to both ECS/ERS- and the REVEAL risk scores.
肾上腺髓质素是一种强效血管舒张肽，与肺动脉高压病理相关。采用邻近延伸分析来研究与血管调节相关的血浆生物标志物，重点关注肾上腺髓质素肽及其前体水平，统称为ADM。对48例初治肺动脉高压患者在诊断时进行ADM检测，其中31例在早期治疗随访时再次检测。另外，对20例慢性血栓栓塞性肺动脉高压患者、33例射血分数保留的心力衰竭（HFpEF）所致肺动脉高压患者、36例射血分数降低的心力衰竭（HFrEF）所致肺动脉高压患者以及16例健康对照者进行血浆ADM评估。研究了ADM与肺动脉高压血流动力学、风险评估、预后、治疗反应及鉴别诊断的关系。肺动脉高压患者诊断时的血浆ADM水平高于健康对照者（P<0.001），与慢性血栓栓塞性肺动脉高压患者相似（P=无显著差异），但低于HFpEF患者（P<0.03）和HFrEF患者（P<于0.001）。具体而言，在肺动脉高压中，诊断时的血浆ADM主要与平均右心房压相关（r=0.73，P<0.001）、与脑钠肽N末端前体相关（r=0.75，P<0.001）、与6分钟步行距离相关（r=-0.57，P<0.001）以及与静脉血氧饱和度相关（r=-0.57，P<0.001）。ADM还与肺动脉高压诊断时的ECS/ERS-风险评分（r=0.74，P<0.001）和REVEAL风险评分相关（r=0.54，P<0.001）。与基线相比，肺动脉高压患者早期治疗随访时的血浆ADM未发生改变（P=无显著差异）。诊断时ADM高于中位数的肺动脉高压患者总体生存率低于ADM低于中位数的患者（中位生存期分别为34个月和66个月，P=0.0077）。总之，目前的结果表明，基线血浆ADM水平反映疾病严重程度，与ECS/ERS-风险评分和REVEAL风险评分均相关。
