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J. Am. Coll. Cardiol. · Jul 2011
Iron deficiency and raised hepcidin in idiopathic pulmonary arterial hypertension: clinical prevalence, outcomes, and mechanistic insights.
- Christopher J Rhodes, Luke S Howard, Mark Busbridge, Damien Ashby, Eumorfia Kondili, J Simon R Gibbs, John Wharton, and Martin R Wilkins.
- Centre for Pharmacology and Therapeutics, Experimental Medicine, Imperial College London, London, UK.
- J. Am. Coll. Cardiol. 2011 Jul 12; 58 (3): 300-9.
ObjectivesThis study sought to understand the prevalence and clinical relevance of iron deficiency in patients with idiopathic pulmonary arterial hypertension (IPAH).BackgroundIron availability influences the pulmonary vascular response to hypoxia in humans and may be significant in the pathogenesis of IPAH.MethodsIron deficiency, defined by raised levels of soluble transferrin receptor (sTfR), was investigated in 98 patients with IPAH. Hepcidin and erythropoietin (EPO) levels were also measured. The effect of bone morphogenetic protein (BMP) receptor knockdown on BMP-6-stimulated hepcidin production was assessed in human hepatoma HepG2 cells. Relationships between sTfR and exercise capacity, functional class, and all-cause mortality were analyzed.ResultsCirculating sTfR levels were raised in 63% of IPAH patients, indicating significant iron deficiency. Consistent with this, iron, ferritin, and transferrin saturation levels were reduced and red cell distribution width increased, without overt anemia. Hepcidin correlated inversely with sTfR and positively with increasing ferritin. Hepcidin was inappropriately raised in IPAH independent of the inflammatory marker interleukin-6. EPO levels were also raised and correlated inversely with hepcidin. BMP receptor-type 2 (BMPR2) knockdown in HepG2 cells increased BMP-6-stimulated hepcidin expression. sTfR increased with World Health Organization functional class (p < 0.05), correlated negatively with exercise capacity (p = 0.027), and values >28.1 nmol/l independently predicted survival (p = 0.011).ConclusionsIron deficiency is common in IPAH patients and associated with disease severity and poor clinical outcome. Inappropriately raised hepcidin levels, which impair iron absorption from the gut, may be a factor.Copyright © 2011 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.
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