Novel biomarkers for risk stratification in pulmonary arterial hypertension

Thomas Zelniker, Lorenz Uhlmann, Sebastian Spaich, Jörg Friedrich, Michael R Preusch, Franz J Meyer, Hugo A Katus, Evangelos Giannitsis, Thomas Zelniker, Lorenz Uhlmann, Sebastian Spaich, Jörg Friedrich, Michael R Preusch, Franz J Meyer, Hugo A Katus, Evangelos Giannitsis

Abstract

Risk stratification in pulmonary arterial hypertension (PAH) is paramount to identifying individuals at highest risk of death. So far, there are only limited parameters for prognostication in patients with PAH. 95 patients with confirmed PAH were included in the present analysis and followed for a total of 4 years. Blood samples were analysed for serum levels of N-terminal pro-brain natriuretic peptide, high-sensitivity troponin T (hsTnT), pro-atrial natriuretic peptide (proANP), growth differentiation factor 15, soluble fms-like tyrosine kinase 1 and placental growth factor. 27 (28.4%) patients died during a follow-up of 4 years. Levels of all tested biomarkers, except for placental growth factor, were significantly elevated in nonsurvivors compared with survivors. Receiver operating characteristic analyses demonstrated that cardiac biomarkers had the highest power in predicting mortality. In particular, proANP exhibited the highest area under the curve, followed by N-terminal pro-brain natriuretic peptide and hsTnT. Furthermore, proANP and hsTnT added significant additive prognostic value to the established markers in categorical and continuous net reclassification index. Moreover, after Cox regression, proANP (hazard ratio (HR) 1.91), hsTnT (HR 1.41), echocardiographic right ventricular impairment (HR 1.30) and 6-min walk test (HR 0.97 per 10 m) remained the only significant parameters in prognostication of mortality. Our data suggest benefits of the implementation of proANP and hsTnT as additive biomarkers for risk stratification in patients with PAH.

Conflict of interest statement

can be found alongside this article at openres.ersjournals.com

Figures

FIGURE 1
FIGURE 1
Receiver operating curves assessing the prognostic accuracy of a) N-terminal pro-brain natriuretic peptide, b) pro-atrial natriuretic peptide, c) high-sensitivity troponin T, d) soluble fms-like tyrosine kinase 1, e) growth differentiation factor 15 and f) placental growth factor for prediction of 4-year mortality.
FIGURE 2
FIGURE 2
Kaplan–Meier survival curves according to receiver operative characteristic-optimised cut-off values for a) N-terminal pro-brain natriuretic peptide, b) pro-atrial natriuretic peptide and c) high-sensitivity troponin T.
FIGURE 3
FIGURE 3
Forest plots of a) categorical and b) continuous net reclassification index (NRI) and c) integrated discrimination index (IDI) from biomarkers related to pulmonary arterial hypertension. Error bars represent 95% confidence intervals. ProANP: pro-atrial natriuretic peptide; hsTnT: high-sensitivity troponin T; GDF-15: growth differentiation factor 15; sFlt-1: soluble fms-like tyrosine kinase 1; PlGF: placental growth factor.

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Source: PubMed

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