Growth differentiation factor-15 in idiopathic pulmonary arterial hypertension

Am J Respir Crit Care Med. 2008 Sep 1;178(5):534-41. doi: 10.1164/rccm.200802-235OC. Epub 2008 Jun 19.


Rationale: Growth-differentiation factor (GDF)-15 is a stress-responsive, transforming growth factor-beta-related cytokine. Circulating levels of GDF-15 provide independent prognostic information in patients with acute pulmonary embolism and chronic left-sided heart failure.

Objectives: To assess the prognostic value of GDF-15 in idiopathic pulmonary arterial hypertension.

Methods: GDF-15 levels were determined in 76 treatment-naive patients at the time of baseline right heart catheterization. Patients were monitored for a median (range) of 48 (0-101) months (first cohort). Twenty-two additional patients were studied at baseline and 3 to 6 months after initiation of therapy (second cohort).

Measurements and main results: Fifty-five percent of the patients in the first cohort presented with GDF-15 levels above 1,200 ng/L, the previously defined upper reference limit. The risk of death or transplantation at 3 years was 15 and 44% in patients with GDF-15 levels below or above 1,200 ng/L, respectively (P = 0.006). Elevated levels of GDF-15 were associated with increased mean right atrial and pulmonary capillary wedge pressures, a lower mixed venous oxygen saturation (Sv(O(2))), and higher levels of uric acid and N-terminal pro-brain natriuretic peptide (NT-proBNP). After adjustment for hemodynamic and biochemical variables, GDF-15 remained an independent predictor of adverse outcomes (P = 0.002). GDF-15 provided prognostic information in clinically relevant patient subgroups, and added prognostic information to hemodynamic variables and NT-proBNP. Changes in GDF-15 over time in the second cohort were related to changes in NT-proBNP (P = 0.031) and inversely related to changes in Sv(O(2)) (P < 0.001).

Conclusions: GDF-15 is a promising new biomarker in idiopathic pulmonary arterial hypertension.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antihypertensive Agents / pharmacology
  • Biomarkers / blood
  • Cytokines / blood*
  • Drug Monitoring
  • Female
  • Follow-Up Studies
  • Growth Differentiation Factor 15
  • Humans
  • Hypertension, Pulmonary / diagnosis*
  • Hypertension, Pulmonary / drug therapy
  • Hypertension, Pulmonary / immunology
  • Kaplan-Meier Estimate
  • Lung Transplantation / statistics & numerical data
  • Male
  • Middle Aged
  • Prognosis
  • Proportional Hazards Models
  • ROC Curve
  • Risk Assessment
  • Severity of Illness Index


  • Antihypertensive Agents
  • Biomarkers
  • Cytokines
  • GDF15 protein, human
  • Growth Differentiation Factor 15