Arvidsson Mattias, Ahmed Abdulla, Bouzina Habib, 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.
ESC Heart Fail. 2021 Apr;8(2):1230-1243. doi: 10.1002/ehf2.13184. Epub 2021 Jan 5.
Right ventricular dysfunction may arise because of pulmonary arterial hypertension (PAH). Development of new diagnostic methods able to identify PAH and allow for earlier treatment initiation, before the development of vascular remodelling and manifest right heart failure (HF), could potentially improve prognosis. Proteoglycans and inflammatory proteins are involved in vascular remodelling. We aimed to investigate their potential as biomarkers to differentiate PAH in a dyspnoeic population.
Plasma from 152 patients with PAH (n = 48), chronic thrombo-embolic pulmonary hypertension (n = 20), pulmonary hypertension due to HF with reduced (n = 36) or preserved (n = 33) ejection fraction, and HF without pulmonary hypertension (n = 15) and 20 healthy controls were analysed with proximity extension assays. Haemodynamics were assessed in the patients with right heart catheterization. Plasma prolargin levels in PAH were lower compared with all the other studied disease groups (P < 0.001) but higher than the controls' levels (P = 0.003). Receiver operating characteristic curve of prolargin as a PAH-differentiating marker in a pooled population, encompassing all the other studied disease groups, had a sensitivity of 74% and a specificity of 83.3% (area under the curve = 0.84, P < 0.001). Prolargin correlated with the mean right atrial pressure (r = 0.65, P < 0.001), N-terminal pro-brain natriuretic peptide (r = 0.64, P < 0.001), cardiac index (r = -0.31, P = 0.029), stroke volume index (r = -0.41, P = 0.004), right ventricular stroke work index (r = -0.31, P = 0.032), six-minute walking distance (r = -0.41, P = 0.005), and mixed venous blood oxygen saturation (r = -0.42, P = 0.003).
Plasma prolargin levels differentiate PAH patients from controls and the other investigated dyspnoea groups including HF. Its potential in PAH differentiation may be enhanced by inclusion in a multi-marker panel. Larger studies are needed to evaluate its discriminative ability of PAH in relation to other dyspnoea aetiologies and its potential role in PAH risk stratification and pathobiology.
右心室功能障碍可能由肺动脉高压（PAH）引起。开发能够识别PAH并在血管重塑和明显的右心衰竭（HF）发生之前允许更早开始治疗的新诊断方法，可能会改善预后。蛋白聚糖和炎症蛋白参与血管重塑。我们旨在研究它们作为生物标志物在鉴别呼吸困难人群中PAH的潜力。
采用邻位延伸分析对152例PAH患者（n = 48）、慢性血栓栓塞性肺动脉高压患者（n = 20）、射血分数降低（n = 36）或保留（n = 33）的HF所致肺动脉高压患者以及无肺动脉高压的HF患者（n = 15）和20名健康对照者的血浆进行分析。通过右心导管检查评估患者的血流动力学。与所有其他研究的疾病组相比，PAH患者的血浆脯氨酸水平较低（P < 0.001），但高于对照组水平（P = 0.003）。在包括所有其他研究疾病组的汇总人群中，脯氨酸作为PAH鉴别标志物的受试者工作特征曲线的敏感性为74%，特异性为83.3%（曲线下面积 = 0.84，P < 0.001）。脯氨酸与平均右心房压（r = 0.65，P < 0.001）、N末端脑钠肽前体（r = 0.64，P < 0.001）、心脏指数（r = -0.31，P = 0.029）、每搏量指数（r = -0.41，P = 0.004）、右心室每搏功指数（r = -0.31，P = 0.032）、6分钟步行距离（r = -0.41，P = 0.005）和混合静脉血氧饱和度（r = -0.42，P = 0.003）相关。
血浆脯氨酸水平可将PAH患者与对照组以及包括HF在内的其他所研究的呼吸困难组区分开来。将其纳入多标志物组合可能会增强其在鉴别PAH方面的潜力。需要进行更大规模的研究来评估其相对于其他呼吸困难病因鉴别PAH的能力及其在PAH风险分层和病理生物学中的潜在作用。
