Growth differentiation factor-15 in idiopathic pulmonary arterial hypertension.
BACKGROUND
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.


OBJECTIVE
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).


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.
Department of Respiratory Medicine, Hannover Medical School, Hannover, Germany.
Nils
N
Nickel
Tibor
T
Kempf
Heike
H
Tapken
Jörn
J
Tongers
Florian
F
Laenger
Ulrich
U
Lehmann
Heiko
H
Golpon
Karen
K
Olsson
Martin R
MR
Wilkins
J Simon R
JS
Gibbs
Marius M
MM
Hoeper
Kai C
KC
Wollert
D000328:Adult; D000368:Aged; D000959:Antihypertensive Agents / Q000494:pharmacology; D015415:Biomarkers / Q000097:blood; D016207:Cytokines / Q000097:blood*; D016903:Drug Monitoring; D005260:Female; D005500:Follow-Up Studies; D055436:Growth Differentiation Factor 15; D006801:Humans; D006976:Hypertension, Pulmonary / Q000175:diagnosis* / Q000188:drug therapy / Q000276:immunology; D053208:Kaplan-Meier Estimate; D016040:Lung Transplantation / Q000706:statistics & numerical data; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D016016:Proportional Hazards Models; D012372:ROC Curve; D018570:Risk Assessment; D012720:Severity of Illness Index
D000959:Antihypertensive Agents; D015415:Biomarkers; D016207:Cytokines; C526140:GDF15 protein, human; D055436:Growth Differentiation Factor 15