Abstract
BackgroundCirculating angiopoietin-1 (Ang-1) has been linked to pulmonary hypertension (PH) in experimental studies. However, the clinical relevance of Ang-1 as a biomarker in PH remains unknown. We aimed to investigate the prognostic and clinical significance of Ang-1 in PH using data from the prospectively recruiting Giessen PH Registry.MethodsPatients with suspected PH (without previous specific pulmonary arterial hypertension [PAH] therapy) who underwent initial right heart catheterization (RHC) in our national referral center between July 2003 and May 2012 and who agreed to optional biomarker analysis were included if they were diagnosed with idiopathic PAH, connective tissue disease-associated PAH (CTD-PAH), PH due to left heart disease (PH-LHD), or chronic thromboembolic PH (CTEPH), or if PH was excluded by RHC (non-PH controls). The association of Ang-1 levels with disease severity (6-minute walk distance and pulmonary hemodynamics) was assessed using linear regression, and the impact of Ang-1 levels on transplant-free survival (primary endpoint) and clinical worsening was assessed using Kaplan—Meier curves, receiver operating characteristic (ROC) analyses, and Cox regression.Results151 patients (39, 39, 32, and 41 with idiopathic PAH, CTD-PAH, PH-LHD, and CTEPH, respectively) and 41 non-PH controls were included. Ang-1 levels showed no significant difference between groups (p = 0.8), and no significant associations with disease severity in PH subgroups (p ≥ 0.07). In Kaplan—Meier analyses, Ang-1 levels (stratified by quartile) had no significant impact on transplant-free survival (p ≥ 0.27) or clinical worsening (p ≥ 0.51) in PH subgroups. Regression models found no significant association between Ang-1 levels and outcomes (p ≥ 0.31). ROC analyses found no significant cut-off that would maximize sensitivity and specificity.ConclusionsDespite a strong pathophysiological association in experimental studies, this first comprehensive analysis of Ang-1 in PH subgroups suggests that Ang-1 is not a predictive and clinically relevant biomarker in PH.
Highlights
Pulmonary hypertension (PH) is characterized by elevated pulmonary vascular resistance (PVR), reduced cardiac output (CO), and increased pulmonary arterial pressure, due to progressive remodeling of the pulmonary arteries caused by multiple pathophysiological mechanisms [1]
Patients with suspected PH who underwent initial right heart catheterization (RHC) in our national referral center between July 2003 and May 2012 and who agreed to optional biomarker analysis were included if they were diagnosed with idiopathic pulmonary arterial hypertension (PAH), connective tissue disease-associated PAH (CTD-PAH), PH due to left heart disease (PH-LHD), or chronic thromboembolic PH (CTEPH), or if PH was excluded by RHC
Patients with PH are classified into five major clinical groups according to current guidelines: pulmonary arterial hypertension (PAH; group 1); pulmonary veno-occlusive disease and/or pulmonary capillary hemangiomatosis; persistent PH of the newborn; PH due to left heart disease (PH-LHD; group 2); PH due to lung diseases and/or hypoxia; chronic thromboembolic PH (CTEPH; group 4); and PH with unclear and/or multifactorial mechanisms [1]
Summary
Pulmonary hypertension (PH) is characterized by elevated pulmonary vascular resistance (PVR), reduced cardiac output (CO), and increased pulmonary arterial pressure, due to progressive remodeling of the pulmonary arteries caused by multiple pathophysiological mechanisms [1]. In the routine treatment and follow-up of patients with PH, a key role has been attributed to parameters and biomarkers associated with long-term survival, time to clinical worsening (TTCW), or disease severity [2, 3]. Numerous important biomarkers such as N-terminal fragment of pro-B-type natriuretic peptide [4], red cell distribution [5], endothelin-1 [6], troponin [7], serum creatinine [8], and glycosylated hemoglobin A1c [9] have been described previously, and N-terminal fragment of pro-B-type natriuretic peptide is recommended as a prognostic biomarker in current guidelines [1].
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