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Title: The role of iron in pulmonary hypertension
Author: Watson, Geoffrey
ISNI:       0000 0004 7658 8170
Awarding Body: Imperial College London
Current Institution: Imperial College London
Date of Award: 2019
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Introduction: Iron is a critical ion in the regulation of many cellular processes and iron deficiency (ID) has been shown to be a powerful predictor of survival in many diseases. It has been shown that ID, defined by increased soluble transferrin receptor (sTfR) levels impacts on outcomes in idiopathic pulmonary arterial hypertension (IPAH). sTfR is not widely available as an assay. It is also not known how common ID is in other forms of pulmonary hypertension (PH) and whether it impacts on function and survival. Aims: 1) To identify the best routinely-available biomarker of ID in patients with IPAH; 2) Assess the prevalence of ID in common forms of PH; 3) Explore the relationship between ID and function and survival in PH; 4) Run a double-blind, randomised, placebo-controlled trial of iv iron in IPAH. Methods: Data were collected historically from patients in the PH service at Hammersmith Hospital and analysed to provide the best clinical criteria to identify patients with ID. Subsequently, a larger cohort of patients with IPAH as well as other forms of PH was analysed to assess the prevalence of ID at diagnosis and the impact on functional status and survival. A crossover trial was run to assess the impact of iv iron on haemodynamics and exercise in IPAH. Results: ID can be best identified by using red cell distribution width (RDW) in IPAH. RDW is associated with exercise capacity in IPAH, but more so, is associated with functional changes in chronic thromboembolic PH. RDW was a strong marker of survival across all groups but independence could not be established from other markers. The clinical trial did not complete in time, but unblinded data suggest improvements in aerobic exercise, but no change in haemodynamics. Conclusion: ID is common in all forms of PH, and has functional and survival implications. Iron replacement in IPAH may improve exercise function but complete results from the trial are awaited.
Supervisor: Howard, Luke ; Zhao, Lan ; Wilkins, Martin Sponsor: Not available
Qualification Name: Thesis (M.D.) Qualification Level: Doctoral