title: Growth-differentiation factor-15: a novel biomarker in patients with diastolic dysfunction?
abstract: BACKGROUND
  Growth differentiation factor-15 (GDF-15), a stress-responsive transforming growth factor-ß-related cytokine, is elevated and independently related to an adverse prognosis in systolic heart failure.
  
  
  OBJECTIVE
  This study aimed to investigate plasma levels of GDF-15 in patients with preclinical diastolic dysfunction or heart failure with normal ejection fraction (HFnEF).
  
  
  METHODS
  We evaluated 119 patients with normal ejection fraction referred for an elective coronary angiography, 75 (63%) of whom had coronary artery disease. Subjects were classified as having either mild left ventricular diastolic dysfunction (LVDD grade I, n = 61), HFnEF (LVDD grade II or III, n = 38) or normal diastolic function (controls, n = 20). In a subgroup of 20 subjects, changes in cardiac output (CO) were measured by inert gas rebreathing (InnocorTM) in response to an orthostatic hemodynamic test.
  
  
  RESULTS
  Growth differentiation factor-15 levels in HFnEF [median 1.08, interquartile range (0.88-1.30) ng/ml] were significantly higher than in controls [0.60 (0.50-0.71) ng/ml, p = 0.003] and in patients with LVDD grade I [0.78 (0.62-1.04) ng/ml, p < 0.001]. In addition, GDF-15 was significantly elevated in patients with LVDD grade I compared to controls (p = 0.003). Furthermore, GDF-15 was correlated with echocardiographic markers of diastolic dysfunction and was correlated with the magnitude of CO response to the change in body position from standing to supine (r = -0.67, p = 0.005).
  
  
  CONCLUSIONS
  Growth differentiation factor-15 levels are elevated in subjects with HFnEF and can differentiate normal diastolic function from asymptomatic LVDD. In addition, GDF-15 is associated with a reduced cardiac output response in the orthostatic hemodynamic test.
authors.affiliation: Institute for Heart and Circulation Research, University Witten/Herdecke, Germany. wilfried.dinh@googlemail.com
authors.forename: Wilfried
authors.initials: W
authors.lastname: Dinh
authors.forename: Reiner
authors.initials: R
authors.lastname: Füth
authors.forename: Mark
authors.initials: M
authors.lastname: Lankisch
authors.forename: Georg
authors.initials: G
authors.lastname: Hess
authors.forename: Dietmar
authors.initials: D
authors.lastname: Zdunek
authors.forename: Thomas
authors.initials: T
authors.lastname: Scheffold
authors.forename: Frank
authors.initials: F
authors.lastname: Kramer
authors.forename: Rolf Michael
authors.initials: RM
authors.lastname: Klein
authors.forename: Michael Coll
authors.initials: MC
authors.lastname: Barroso
authors.forename: Werner
authors.initials: W
authors.lastname: Nickl
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood; D004452:Echocardiography; D005260:Female; D005951:Glucose Tolerance Test; D055436:Growth Differentiation Factor 15 / Q000097:blood*; D054143:Heart Failure, Systolic / Q000175:diagnosis* / Q000503:physiopathology; D006439:Hemodynamics / Q000502:physiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D012016:Reference Values; D018709:Statistics, Nonparametric; D013318:Stroke Volume / Q000502:physiology*
chemical_list: D015415:Biomarkers; D055436:Growth Differentiation Factor 15