title: Growth differentiation factor-15 in children and adolescents with thalassemia intermedia: Relation to subclinical atherosclerosis and pulmonary vasculopathy.
abstract: BACKGROUND
  Heart disease is the leading cause of mortality and one of the main causes of morbidity in β-thalassemia. Growth differentiation factor-15 (GDF-15), a member of the transforming growth factor-β superfamily, is a marker of ineffective erythropoiesis in several anemias.
  
  
  OBJECTIVE
  To determine GDF-15 levels in children and adolescents with TI and the relation to hemolysis, iron overload and cardiovascular complications.
  
  
  METHODS
  GDF-15 was measured in 35 TI patients without symptoms for heart disease and correlated to echocardiographic parameters and carotid intima media thickness (CIMT).
  
  
  RESULTS
  GDF-15 levels were significantly higher in TI patients compared with controls (p < 0.001). Transfusion dependent patients had higher GDF-15 than non-transfusion dependent patients. TI patients with splenectomy, pulmonary hypertension risk, and heart disease had higher GDF-15 levels than those without. GDF-15 was lower among hydroxyurea-treated patients. Multiple linear regression analysis revealed that transfusion index (p=0.012), serum ferritin (p < 0.001), tricuspid regurgitant jet velocity (p < 0.001), ejection fraction (p=0.01) and CIMT (p=0.007) were independently related to GDF-15. According to ROC curve analysis, the cutoff value of GDF-15 at 1500 pg/mL could differentiate patients with and without heart disease.
  
  
  CONCLUSIONS
  GDF-15 would identify TI patients at increased risk of pulmonary and cardiovascular complications as well as subclinical atherosclerosis.
authors.affiliation: Pediatrics Department, Faculty of Medicine, Ain Shams University, Cairo, Egypt. Electronic address: azatantawy@hotmail.com.
authors.forename: Azza Abdel Gawad
authors.initials: AA
authors.lastname: Tantawy
authors.affiliation: Pediatrics Department, Faculty of Medicine, Ain Shams University, Cairo, Egypt.
authors.forename: Amira Abdel Moneam
authors.initials: AA
authors.lastname: Adly
authors.affiliation: Clinical Pathology Department, Faculty of Medicine, Ain Shams University, Cairo, Egypt.
authors.forename: Eman Abdel Rahman
authors.initials: EA
authors.lastname: Ismail
authors.affiliation: Pediatrics Department, Faculty of Medicine, Ain Shams University, Cairo, Egypt.
authors.forename: Omneya Ibrahim
authors.initials: OI
authors.lastname: Youssef
authors.affiliation: Pediatrics Department, Faculty of Medicine, Ain Shams University, Cairo, Egypt.
authors.forename: Mohamed ElSayed
authors.initials: ME
authors.lastname: Ali
mesh_terms: D000293:Adolescent; D050197:Atherosclerosis / Q000175:diagnosis / Q000209:etiology; D015415:Biomarkers; D059168:Carotid Intima-Media Thickness; D016022:Case-Control Studies; D002648:Child; D004452:Echocardiography; D005260:Female; D055436:Growth Differentiation Factor 15 / Q000097:blood*; D006801:Humans; D006976:Hypertension, Pulmonary / Q000175:diagnosis / Q000209:etiology; D008297:Male; D012372:ROC Curve; D017086:beta-Thalassemia / Q000097:blood* / Q000150:complications / Q000175:diagnosis
chemical_list: D015415:Biomarkers; D055436:Growth Differentiation Factor 15
keywords: Atherosclerosis; Carotid intima media thickness; Growth differentiation factor-15; Iron overload; Pulmonary hypertension; Thalassemia intermedia