Growth Differentiation Factor-15 Linked to Transplant-Free Survival in PH

pulmonary hypertension , pah, pulmonary arterial hypertension
Investigators sought to determine whether growth differentiation factor-15 is a significant prognostic biomarker in pulmonary hypertension.

Growth differentiation factor-15 (GDF-15) could be a promising biomarker to identify low-risk patients with normal GDF-15 levels, potentially serving as a predictor for mortality in adults with pulmonary hypertension (PH), according to study results published in Heart.

This single-center, prospective, observational cohort study included adults diagnosed with PH at their tertiary-care center between May 2012 and October 2016 (N=103). Researchers defined diagnostic right heart catheterization as the baseline and defined PH as a mean pulmonary artery pressure ≥25 mm Hg. To assess the biomarker, they sampled venous blood during the diagnostic right heart catheterization for study purposes only. Investigators used an electrochemiluminescence assay to directly measure N-terminal prohormone of brain natriuretic peptide (NT-proBNP) and GDF-15.

Growth differentiation factor-15 was elevated in 74% (n=76/103) of patients. It showed a significant moderate correlation with NT-proBNP (r =0.51, P <.001) and estimated glomerular filtration rate (r =−0.47, P <.001). Median follow-up was 3.4 years (interquartile range, 2.3-4.6). The primary endpoint of all-cause mortality or lung transplantation was reached in 31.1% of patients (n=32). The secondary endpoint, a composite that included the primary endpoint and heart failure, was reached in 39.8% (n=41) of patients. Causes of death in the 30 patients who died were end-stage heart failure (n=9), sudden death presumed cardiac (n=4), multiorgan failure (n=3), other diverse causes (n=13), and unknown cause (n=1).

Patients who had normal GDF-15 had a significantly higher transplant-free survival compared with patients with elevated GDF-15 (P =.007), which was specifically pronounced within the first 2 years of follow-up.

After adjusting for several clinical characteristics as well as age and NT-proBNP, GDF-15 was significantly associated with the primary endpoint.

The limitations of this study included the exclusion of patients with PH caused by left heart disease, which should be considered when extrapolating these results to other studies. This study consisted of a heterogeneous group of PH etiologies, so subgroup analysis could only be performed for pulmonary arterial hypertension. The clinical usefulness of GDF-15 might differ among PH etiologies. Because of limited statistical power, the additive value of GDF-15 could not be assessed.

Growth differentiation factor-15 was strongly associated with mortality in this study and specifically identified low-risk patients with PH at the time of diagnosis.

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Measuring GDF-15 could be considered as a means to identify and reassure newly diagnosed patients with PH. Follow-up frequency can probably be lowered in these patients compared with patients at high risk.

More research is needed to validate these findings before integrating them into clinical practice and to further explore the potential of GDF-15 as a biomarker for predicting mortality.


Geenen LW, Baggen VJM, Kauling RM, et al. Growth differentiation factor-15 as candidate predictor for mortality in adults with pulmonary hypertension [published online September 6, 2019]. Heart. doi:10.1136/heartjnl-2019-315111

This article originally appeared on The Cardiology Advisor