Prevalent patients were over-represented in many pulmonary hypertension registries and clinical trials. These patients have better survival compared with incident patients. As pulmonary hypertension (PH) is diagnosed and managed in designated pulmonary hypertension centres only in the United Kingdom (UK) and Ireland, this provides a unique opportunity to define the demographics, epidemiology and outcomes of a large cohort of purely incident, treatment-naive idiopathic, heritable and anorexigen-associated pulmonary arterial hypertension (PAH) patients. We included all newly diagnosed, treatment naive patients diagnosed in all eight PH centres in the UK and Ireland between January 2001 and December 2009 in our study. We used the same inclusion criteria used in the French and Scottish registries to define our idiopathic, heritable and anorexigen-associated PAH patients. We further refined our criteria for idiopathic, heritable and anorexigen-associated PAH by excluding patients with evidence of parenchymal lung disease on thoracic CT. These excluded patients (refer as Pre-capillary pulmonary hypertension co-existing lung disease in this thesis) were managed as idiopathic PAH by their PH physicians and otherwise satisfied the usual haemodynamic and pulmonary function criteria used to define idiopathic PAH in many PH registries and clinical trials. We divided our idiopathic, heritable and anorexigen-associated PAH patients into two age subgroups according to their median age to study the effect of age on their phenotypes and survival. We also divided our idiopathic, heritable and anorexigen-associated PAH patients into three subgroups according to their year of diagnosis to study the changing epidemiology of the disease over the past decade. We also compared the baseline characteristics and outcomes of our idiopathic, heritable and anorexigen-associated PAH patients with PAH with ‘co-existing lung disease’ patients. Firstly, we confirmed that the demographics, epidemiology and survival of incident idiopathic, heritable and anorexigen-associated PAH has changed compared with patients from the pre-disease targeted therapy era of the 1980s, and continued to evolve in the UK and Ireland over the past decade. The incidence of idiopathic PAH continued to increase over the past decade in the UK and Ireland, most likely reflecting increased referral to the pulmonary hypertension centres. Patients were still referred late with severe functional and haemodynamic impairment. Greater education is needed to raise awareness amongst the non-pulmonary hypertension community of the changing epidemiology of the disease. We have used our incident study cohort of idiopathic, heritable and anorexigen-associated PAH to validate currently available survival prediction models in PAH. Our results suggested that some survival prediction models performed better than others. We observed different phenotypic characteristics and survival between younger and older idiopathic, heritable and anorexigen-associated PAH patients. Baseline variables with prognostic significance were also different between younger and older idiopathic, heritable and anorexigen-associated PAH patients. Interestingly, obesity was associated with better survival in older patients but the contrary in younger patients. We also explored the prognostic significance of short term improvement in six minute walk distance and functional class in response to treatment in incident idiopathic, heritable and anorexigen-associated PAH. Change in six minute walk distance after three months of pulmonary hypertension treatment was associated with improved survival in patients with low baseline six minute walk distance. Change in functional class at six months was also predictive of survival in our idiopathic, heritable and anorexigen-associated PAH patients. Finally, we observed that pre-capillary pulmonary hypertension with co-existing lung disease patients who otherwise satisfied the usual haemodynamic and pulmonary function criteria for idiopathic PAH had significantly different demographics and worse survival compared with idiopathic PAH patients. Better characterisation of this subgroup of PH patients will avoid bias from inclusion of these patients as idiopathic PAH in future clinical trials.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:622025 |
| Date | January 2014 |
| Creators | Ling, Yi |
| Publisher | University of Glasgow |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://theses.gla.ac.uk/5462/ |
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