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Original research
Growth differentiation factor-15 as candidate predictor for mortality in adults with pulmonary hypertension
  1. Laurie W Geenen1,
  2. Vivan J M Baggen1,
  3. Robert M Kauling1,
  4. Thomas Koudstaal2,
  5. Karin A Boomars2,
  6. Eric Boersma1,3,
  7. Jolien W Roos-Hesselink1,
  8. Annemien E van den Bosch1
  1. 1 Department of Cardiology, Erasmus University Medical Centre, Rotterdam, The Netherlands
  2. 2 Department of Pulmonary Diseases, Erasmus University Medical Centre, Rotterdam, The Netherlands
  3. 3 Department of Clinical Epidemiology, Erasmus University Medical Centre, Rotterdam, The Netherlands
  1. Correspondence to Dr Annemien E van den Bosch, Department of Cardiology, Erasmus University Medical Centre, Rotterdam 3000 CA, The Netherlands; a.e.vandenbosch{at}


Objective Despite its predictive value for mortality in various diseases, the relevance of growth differentiation factor-15 (GDF-15) as prognostic biomarker in pulmonary hypertension (PH) remains unclear. This study investigated the association between GDF-15 and outcomes in adults with PH.

Methods This is a single-centre prospective observational cohort study. All adults with PH were included at the day of their diagnostic right heart catheterisation between 2012 and 2016. PH due to left heart disease was excluded. Venous blood sampling was performed and included GDF-15 and N-terminal pro-B-type natriuretic peptide (NT-proBNP) measurements. Kaplan-Meier curves and Cox regression analysis were used to investigate the association between GDF-15 and a composite endpoint of death or lung transplantation. We adjusted for age and NT-proBNP in multivariable analysis. Reference values were established by GDF-15 measurements in healthy controls.

Results GDF-15 was measured in 103 patients (median age 59.2 years, 65% women, 51% pulmonary arterial hypertension). GDF-15 was elevated in 76 patients (74%). After a median follow-up of 3.4 (IQR 2.3–4.6) years, 32 patients (31.1%) reached the primary endpoint. Event-free survival 2 years after diagnosis was 100% in patients with normal GDF-15 versus 72.4% in patients with elevated GDF-15 (p=0.007). A significant association was found between GDF-15 and the primary endpoint (HR per twofold higher value 1.77, 95% CI 1.39 to 2.27, p<0.001), also after adjustment for age and NT-proBNP (HR 1.41, 95% CI 1.02 to 1.94, p=0.038).

Conclusions High GDF-15 levels are associated with an increased risk of death or transplant in adults with PH, independent of age and NT-proBNP. As non-specific biomarker, GDF-15 could particularly be useful to detect low-risk patients.

  • Primary pulmonary hypertension
  • Biostatistics

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  • Correction notice Since this article was first published online, figure 3 has been replaced with a higher resolution image.

  • Contributors All the authors contributed to one or more of the following: conception of design of the work (VJMB, KAB, EB, JWR-H, AEvdB), data collection (LWG, VJMB, RMK, TK, KAB, JWR-H, AEvdB), data analysis and interpretation (LWG, VJMB, EB, JWR-H and AEvdB), drafting the manuscript (LWG, JWR-H and AEvdB) and critical revision of the manuscript for important intellectual content (all authors).

  • Funding Roche provided GDF-15 assays free of charge for the support of this investigator-initiated study.

  • Competing interests None declared.

  • Patient consent for publication Not required.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement Data are available on reasonable request.