Analysis of Novel Cardiovascular Biomarkers in Patients With Pulmonary Hypertension (PH)

Abstract

Background: 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.

Methods: 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.

Results: 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).

Conclusions: 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.

Keywords: BNP; Biomarkers; GDF-15; H-FABP; Pulmonary hypertension; sST2; suPAR.