Arvidsson Mattias, Ahmed Abdulla, Säleby Joanna, Ahmed Salaheldin, Hesselstrand Roger, Rådegran Göran
Department of Clinical Sciences Lund, Cardiology Faculty of Medicine, Lund University Lund Sweden.
The Hemodynamic Lab, The Section for Heart Failure and Valvular Disease VO Heart and Lung Medicine, Skåne University Hospital Lund Sweden.
Pulm Circ. 2023 Jul 25;13(3):e12269. doi: 10.1002/pul2.12269. eCollection 2023 Jul.
Pulmonary arterial hypertension (PAH) is a rare vasculopathy, with high morbidity and mortality. The sensitivity of the current european society of cardiology/european respiratory society (ESC/ERS) risk assessment strategy may be improved by the addition of biomarkers related to PAH pathophysiology. Such plasma-borne biomarkers may also reduce time to diagnosis, if used as diagnostic tools in patients with unclear dyspnea, and in guiding treatment decisions. Plasma levels of proteins related to tumor necrosis factor (TNF), inflammation, and immunomodulation were analyzed with proximity extension assays in patients with PAH ( = 48), chronic thromboembolic pulmonary hypertension (PH; CTEPH, = 20), PH due to left heart failure (HF) with preserved (HFpEF-PH, = 33), or reduced (HFrEF-PH, = 36) ejection fraction, HF without PH ( = 15), and healthy controls ( = 20). TNF-related apoptosis-inducing ligand (TRAIL) were lower in PAH versus the other disease groups and controls ( < 0.0082). In receiver operating characteristics analysis, TRAIL levels identified PAH from the other disease groups with a sensitivity of 0.81 and a specificity of 0.53 [area under the curve: 0.70; (95% confidence interval, CI: 0.61-0.79; < 0.0001)]. In both single ( < 0.05) and multivariable Cox regression models Annexin A1 (ANXA1) [hazard ratio, HR: 1.0367; (95% CI: 1.0059-1.0684; = 0.044)] and carcinoembryonic antigen-related cell adhesion molecule 8 [HR: 1.0603; (95% CI: 1.0004-1.1237; = 0.0483)] were significant predictors of survival, adjusted for age, female sex and ESC/ERS-initial risk score. Low plasma TRAIL predicted PAH among patients with dyspnea and differentiated PAH from those with CTEPH, HF with and without PH; and healthy controls. Higher plasma ANXA1 was associated with worse survival in PAH. Larger multicenter studies are encouraged to validate our findings.
肺动脉高压（PAH）是一种罕见的血管病变，发病率和死亡率都很高。通过添加与PAH病理生理学相关的生物标志物，当前欧洲心脏病学会/欧洲呼吸学会（ESC/ERS）风险评估策略的敏感性可能会得到提高。如果将这些血浆生物标志物用作呼吸困难原因不明患者的诊断工具，并指导治疗决策，还可能缩短诊断时间。我们采用邻位延伸分析方法，对PAH患者（n = 48）、慢性血栓栓塞性肺动脉高压（PH；CTEPH，n = 20）、射血分数保留的左心衰竭（HF）所致PH（HFpEF-PH，n = 33）或射血分数降低的左心衰竭（HFrEF-PH，n = 36）、无PH的HF患者（n = 15）以及健康对照者（n = 20）的血浆中与肿瘤坏死因子（TNF）、炎症和免疫调节相关的蛋白质水平进行了分析。与其他疾病组和对照组相比，PAH患者的肿瘤坏死因子相关凋亡诱导配体（TRAIL）水平较低（P < 0.0082）。在受试者工作特征分析中，TRAIL水平鉴别PAH与其他疾病组的敏感性为0.81，特异性为0.53 [曲线下面积：0.70；（95%置信区间，CI：0.61 - 0.79；P < 0.0001）]。在单变量（P < 0.05）和多变量Cox回归模型中，膜联蛋白A1（ANXA1）[风险比，HR：1.0367；（95% CI：1.0059 - 1.0684；P = 0.044）]和癌胚抗原相关细胞黏附分子8 [HR：1.0603；（95% CI：1.0004 - 1.1237；P = 0.0483）]是生存的显著预测因子，校正了年龄、性别和ESC/ERS初始风险评分。血浆TRAIL水平低可预测呼吸困难患者中的PAH，并将PAH与CTEPH、有或无PH的HF患者以及健康对照者区分开来。PAH患者血浆ANXA1水平较高与较差的生存率相关。鼓励开展更大规模的多中心研究来验证我们的研究结果。
