The role of iron in pulmonary hypertension
File(s)
Author(s)
Watson, Geoffrey
Type
Thesis
Abstract
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.
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.
Version
Open Access
Date Issued
2018-02
Date Awarded
2019-01
Copyright Statement
Creative Commons Attribution-Non Commercial 4.0 International Licence (CC BY-NC).
Advisor
Howard, Luke
Zhao, Lan
Wilkins, Martin
Publisher Department
Department of Medicine
Publisher Institution
Imperial College London
Qualification Level
Doctoral
Qualification Name
Doctor of Medicine (Research) MD (Res)