Title: Improving long term outcome in giant cell arteritis: evaluating the risk of aortic aneurysm
Funder: Department of Health (England)

Abstract: Background Giant cell arteritis (GCA) is the most common form of systemic vasculitis, especially in the elderly, usually presenting with new onset of headache and scalp tenderness; it is treated urgently with high doses of steroids. Although overall mortality is not increased, cardiovascular risk is increased, reflecting extensive involvement of large blood vessels. There is a possible increased risk of aortic aneurysm development (as high as 22% of a small series of patients) compared to people without GCA. We propose to examine the evidence for aneurysm development in a retrospective study using a large primary care records resource (General Practice Research Database, GPRD). These findings should provide evidence that will be used to improve current guidance on the treatment of patients with GCA. Aims The aim of this retrospective study is to assess the risk of aneurysms of the ascending thoracic or abdominal aorta in patients with established giant cell arteritis compared to the general, age and gender matched population. We will assess whether different features of GCA are associated with a higher or lower risk of aneurysm development, including complications such as visual loss. We will look at other outcomes in GCA, including: myocardial infarction, stroke, cancer and death (all causes and aneurysm related). A key aim is to produce evidence on aneurysm risk to inform the next revision of national and international guidelines for management of GCA and large vessel vasculitis, to incorporate the need for an aneurysm screening programme if necessary. Plan of Investigation In this retrospective study we will make use of the General Practice Research Database to identify new cases of giant cell arteritis diagnosed from 1990. We will track the records to look for subsequent development of aortic aneurysms Severity of aneurysms will be defined by the need for surgery, using the GPRD link to Hospital Episode Statistics. Other outcomes, including death, cancer, stroke, visual loss and heart attacks will be assessed using the GPRD and linked Cancer Registries. For each patient, we will identify 4 age, gender and practice matched controls selected from the GPRD, which contains records of 7,128 patients with GCA and 16,719 patients with aortic aneurysm (from 1987 to 2009). Statistical methods will include Kaplan Meier survival curves and Cox proportional hazards. Potential Impact The proposal is designed to address the question of long term risk of aortic aneurysm, as potentially fatal complication affecting a substantial number of patients with GCA. Current practice in the UK is based on British Society for Rheumatology guidelines for managing GCA where there is only weak evidence regarding aneurysm risk and advice on screening is limited. If the risk of future aortic aneurysm in GCA is substantiated, this will have a significant impact on clinical practice. We will need to introduce a comprehensive screening programme to detect and manage aortic aneurysms in this group of patients. Several applicants are on guideline committees for the British Society for Rheumatology and could directly translate the findings into practice via changes to the guidelines.


Research activity codes: 2.4 SURVEILLANCE AND DISTRIBUTION
Health categories: CARDIOVASCULAR