Growth differentiation factor-15 in children and adolescents with thalassemia intermedia: Relation to subclinical atherosclerosis and pulmonary vasculopathy

Blood Cells Mol Dis. 2015 Aug;55(2):144-50. doi: 10.1016/j.bcmd.2015.06.001. Epub 2015 Jun 6.

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.

Aim: 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.

Conclusion: GDF-15 would identify TI patients at increased risk of pulmonary and cardiovascular complications as well as subclinical atherosclerosis.

Keywords: Atherosclerosis; Carotid intima media thickness; Growth differentiation factor-15; Iron overload; Pulmonary hypertension; Thalassemia intermedia.

MeSH terms

  • Adolescent
  • Atherosclerosis / diagnosis
  • Atherosclerosis / etiology
  • Biomarkers
  • Carotid Intima-Media Thickness
  • Case-Control Studies
  • Child
  • Echocardiography
  • Female
  • Growth Differentiation Factor 15 / blood*
  • Humans
  • Hypertension, Pulmonary / diagnosis
  • Hypertension, Pulmonary / etiology
  • Male
  • ROC Curve
  • beta-Thalassemia / blood*
  • beta-Thalassemia / complications
  • beta-Thalassemia / diagnosis

Substances

  • Biomarkers
  • Growth Differentiation Factor 15