Elevated plasma YKL-40 as a prognostic indicator in patients with idiopathic pulmonary arterial hypertension

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Abstract

Background and objective:

Pulmonary vascular remodelling and inflammation have been implicated in pulmonary arterial hypertension (PAH). YKL-40, a marker of tissue remodelling and inflammation, has recently been recognized as a risk predictor of cardiovascular and inflammatory diseases. The study aimed to investigate a potential role of YKL-40 in predicting prognosis in idiopathic PAH (IPAH).

Methods:

Plasma YKL-40 levels were measured in 82 IPAH patients without current or previous PAH-specific treatment during right heart catheterization and in 54 healthy volunteers. Concurrent data included clinical, haemodynamic and biochemical variables.

Results:

Plasma YKL-40 levels were increased in IPAH patients compared with control subjects (median, interquartile range: IPAH: 24.90, 17.68–39.78 ng/mL; controls: 16.58, 14.20–19.64 ng/mL;P< 0.001). YKL-40 levels correlated with cardiac index (r= −0.244,P= 0.027) and N-terminal pro-brain natriuretic peptide (NT-proBNP,r= 0.263,P= 0.017). After a median follow-up of 578 days, YKL-40 outperformed NT-proBNP, uric acid, and 6-min walk distance in receiver operating characteristic (ROC) analyses in predicting both clinical worsening (area under the curve (AUC) 0.681) and death (AUC 0.717). Compared with patients with YKL-40 below the ROC-derived cut-off point (24.5 ng/mL), the high YKL-40 group showed higher pulmonary vascular resistance and serum uric acid levels, and showed more clinical worsening events and deaths in Kaplan–Meier analyses. Plasma YKL-40 was independently associated with clinical worsening in univariate and multivariate Cox analyses (allP< 0.05).

Conclusions:

Plasma YKL-40 might serve as a promising indicator of disease severity and prognosis in patients with IPAH.

Conclusions:

The ability of YKL-40, an inflammation and remodelling marker, to predict prognosis of IPAH was explored. Plasma YKL-40 was significantly elevated in IPAH patients compared with healthy controls. Patients with higher YKL-40 had increased hemodynamic severity and right heart dysfunction. After follow-up, YKL-40 independently predicted clinical worsening in IPAH.

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