Soluble neprilysin does not correlate with prognosis in pulmonary hypertension

Abstract

Aims: It has been reported that circulating soluble neprilysin (sNEP), which catalyses the degradation of several vasodilator peptides such as natriuretic peptides, predicts prognosis in heart failure patients with reduced ejection fraction. Hypoxia-induced decrease in NEP expression in lungs has been reported. However, the associations between sNEP and haemodynamic parameters, as well as the prognostic impact of sNEP in pulmonary hypertension (PH), remain unclear. We aimed to clarify the relationships between sNEP and natriuretic peptide, haemodynamics (e.g. parameters of echocardiography and right heart catheter) or prognosis in PH patients.

Methods and results: First, we examined the associations between sNEP levels and natriuretic peptide, echocardiography, or right heart catheter in PH patients (mean pulmonary artery pressure ≥ 25 mmHg and pulmonary artery wedge pressure ≤ 15 mm Hg on the basis of right heart catheterization, n = 79). Next, we followed up the patients for all-cause mortality. Laboratory data revealed no significant correlations between sNEP and B-type natriuretic peptide (R = 0.022, P = 0.872), N-terminal proBNP (R = -0.018, P = 0.872), and high-sensitivity troponin I (R = 0.206, P = 0.107). Regarding the parameters of echocardiography and right heart catheter, there were no significant correlations between sNEP and left ventricular ejection fraction (R = -0.036, P = 0.764), right ventricular fractional area change (R = -0.259, P = 0.064), tricuspid valve pressure gradient (R = -0.037, P = 0.767), and any of the right heart catheter parameters. In the Kaplan-Meier analysis (mean follow-up, 1284 days, log-rank P = 0.531), all-cause mortality rates were comparable between the higher NEP group (sNEP ≥ median levels of 1.45 ng/mL, n = 39) and the lower NEP group (sNEP < 1.45 ng/mL, n = 40). In the Cox proportional hazard analysis, sNEP was not a predictor of all-cause mortality (hazard ratio 0.902, 95% CI 0.674-1.207, P = 0.487) in PH patients.

Conclusions: Circulating sNEP does not correlate with natriuretic peptide, haemodynamic parameters, or prognosis in patients with PH.

Keywords: Echocardiography; Haemodynamics; Natriuretic peptide; Neprilysin; Prognosis; Pulmonary hypertension.