Pentraxin3 in chronic thromboembolic pulmonary hypertension: a new biomarker for screening from remitted pulmonary thromboembolism

Abstract

Background: Pentraxin3 (PTX3) is a protein, which has multifaceted effects on innate immunity, angiogenesis, and vascular remodeling then could be a disease marker of acute myocardial infarction, heart failure, vasculitis. In addition, PTX3 has been recognized as a biomarker for pulmonary arterial hypertension, however whether it is the case in chronic thromboembolic pulmonary hypertension (CTEPH) remains unclear. Therefore, we investigated whether PTX3 would be a useful biomarker for detecting CTEPH with respect to differentiation from stable pulmonary thromboembolism (PTE), in comparison to other biomarkers.

Methods: Plasma PTX3 and brain natriuretic peptide (BNP) levels were measured in 70 patients with CTEPH at their first diagnostic right heart catheterization (CTEPH group) and in 20 patients with clinically stable PTE more than three months after the acute episode (control group). The levels of plasma C-reactive protein (CRP) and heart-type fatty acid-binding protein (H-FABP) were also analyzed to compare the diagnostic ability of these biomarkers.

Results: The mean level of PTX3 (ng/mL) was significantly higher in the CTEPH group than in the control group (5.51±4.53 versus 2.01±0.96, respectively), and PTX3 levels had mild negative correlation with cardiac output. BNP levels were also higher in the CTEPH group and better correlated with pulmonary hemodynamics than PTX3. However, a receiver operating characteristic (ROC) curve showed PTX3 levels were better for detecting CTEPH, and could detect CTEPH patients with less severe pulmonary hemodynamics and low plasma BNP levels. There was no significant increase in CRP and H-FABP levels in the CTEPH patients.

Conclusions: Plasma PTX3 level was the most sensitive biomarker of CTEPH. Although plasma PTX3 levels did not correlate with the severity of the pulmonary hemodynamics compared to BNP, high levels in clinically stable patients following PTE should prompt a further work-up for CTEPH, which may lead to an early diagnosis.

Figure 1. Plasma pentraxin3 (PTX3) and other biomarker's concentration in patients with CTEPH.

A) PTX3 (ng/mL), B) BNP (pg/mL), C) CRP (mg/L), and D) H-FABP. Plasma PTX3 and BNP levels were higher in patients with CTEPH than in controls. The CTEPH patients tended to have higher plasma CRP levels than the control patients, although this difference was not statistically significant. Both groups had a low plasma H-FABP level which is considered to be almost normal , although control patients had statistically higher H-FABP level than CTEPH patients.

Figure 2. Scatter diagram data on the correlation between PTX3 and pulmonary hemodynamic patameters.

A) Mean pulmonary arterial pressure (mmHg), B) Pulmonary vascular resistance (dynes.sec.cm⁻⁵), C) cardiac output (L/min), and D) cardiac index (L/min/m²). We found a mild negative correlation between PTX3 levels and cardiac output (CO) in patients with CTEPH. There was no significant correlation between PTX3 and other hemodynamic parameters.

Figure 3. AUC_ROC for PTX3, BNP, and CRP in patients with CTEPH.

Receiver operating characteristic (ROC) curves of PTX3, BNP, and CRP. The area under the ROC curve (AUC_ROC) is 0.913 [0.837–0.990] for PTX3, 0.863 [0.793–0.945] for BNP, and 0.644 [0.4714–0.81074] for CRP. A PTX3 threshold of 2.63 ng/mL maximizes the sensitivity and specificity of CTEPH diagnosis (sensitivity 88.5% and specificity 90.5%).