Clinic of Internal Medicine II, Department of Cardiology, Paracelsus Medical University of Salzburg, Salzburg, Austria.
Universitätsherzzentrum Thüringen, Clinic of Internal Medicine I, Department of Cardiology, Friedrich Schiller University Jena, Jena, Germany.
Heart Lung Circ. 2020 Mar;29(3):337-344. doi: 10.1016/j.hlc.2019.03.004. Epub 2019 Apr 1.
Due to the non-specific clinical presentation of patients with pulmonary hypertension (PH), diagnosis is often delayed, consequently resulting in limited therapeutic success and an impaired prognosis. In this trial, we analysed the plasma concentrations of novel cardiovascular biomarkers that reflect different pathobiological pathways (sST2: soluble suppression of tumorigenicity 2, H-FABP: heart type fatty acid binding protein, suPAR: soluble urokinase plasminogen activator receptor and GDF-15: growth-differentiation factor-15) potentially involved in PH associated vascular and right ventricular remodelling. Thus, these markers could contribute to the development of a non-invasive approach for diagnosis and therapy surveillance of PH patients in the future.
In total, we enrolled 162 patients in this single-centre retrospective analysis consisting of 88 patients suffering from PH and 74 controls. The latter were admitted for elective coronary angiography and coronary artery disease was excluded. Plasma samples of all patients were obtained and analysed for sST2, H-FABP, GDF-15 and suPAR serum concentrations by means of enzyme-linked immunosorbent assay (ELISA) kits (DuoSet ELISA, DY523B, DY957, DY807, DGAL30, R&D Systems, Minneapolis, MN, USA) after obtaining informed consent.
Compared with controls, all of the investigated biomarkers were significantly elevated in patients with pulmonary hypertension (H-FABP median 3.5 ng/ml vs. median 0.0 ng/ml, p < 0.001; sST2 median 6364.6 pg/ml vs. median 5015.9 pg/ml, p = 0.004; GDF-15 median 1829.3 pg/ml vs. median 514.1 pg/ml, p < 0.001; suPAR median 4878.7 pg/ml vs. median 2227.0 pg/ml, p < 0.001). Interestingly, we found a significant difference in the biomarker concentrations of H-FABP, GDF-15 and suPAR between the five groups of pulmonary hypertension. In fact, we found that H-FABP levels were primarily elevated in group 2 and 3 PH, whereas the concentrations of GDF-15 and suPAR were primarily associated with pulmonary hypertension due to left sided heart disease (group 2).
While sST2 constitutes a general biomarker of pulmonary hypertension regardless of the subtype, H-FABP, GDF-15 and suPAR represent indicators of postcapillary PH. Thereby, they could constitute potential discriminators between pre- and postcapillary PH.
由于肺动脉高压（PH）患者的临床表现非特异性，诊断常常被延误，因此治疗效果有限，预后较差。在这项试验中，我们分析了可能参与 PH 相关血管和右心室重构的新型心血管生物标志物的血浆浓度，这些标志物反映了不同的病理生物学途径（sST2：可溶性肿瘤抑制物 2、H-FABP：心脏型脂肪酸结合蛋白、suPAR：可溶性尿激酶纤溶酶原激活物受体和 GDF-15：生长分化因子-15）。因此，这些标志物可能有助于未来开发用于 PH 患者诊断和治疗监测的非侵入性方法。
在这项单中心回顾性分析中，我们共纳入了 162 名患者，其中 88 名患有 PH，74 名作为对照。后者因择期冠状动脉造影而入院，排除了冠状动脉疾病。在获得知情同意后，通过酶联免疫吸附试验（ELISA）试剂盒（DuoSet ELISA、DY523B、DY957、DY807、DGAL30，R&D Systems，明尼苏达州明尼阿波利斯）获得所有患者的血浆样本，并分析 sST2、H-FABP、GDF-15 和 suPAR 的血清浓度。
与对照组相比，所有研究的生物标志物在肺动脉高压患者中均显著升高（H-FABP 中位数 3.5ng/ml 与中位数 0.0ng/ml，p<0.001；sST2 中位数 6364.6pg/ml 与中位数 5015.9pg/ml，p=0.004；GDF-15 中位数 1829.3pg/ml 与中位数 514.1pg/ml，p<0.001；suPAR 中位数 4878.7pg/ml 与中位数 2227.0pg/ml，p<0.001）。有趣的是，我们发现五个 PH 组之间 H-FABP、GDF-15 和 suPAR 的生物标志物浓度存在显著差异。事实上，我们发现 H-FABP 水平主要在 2 型和 3 型 PH 中升高，而 GDF-15 和 suPAR 浓度主要与左心疾病引起的肺动脉高压相关（2 型）。
虽然 sST2 是肺动脉高压的一般标志物，与亚型无关，但 H-FABP、GDF-15 和 suPAR 代表后毛细血管 PH 的指标。因此，它们可能构成毛细血管前和后毛细血管 PH 之间的潜在鉴别因素。
