A study of cardiovscular mortality and morbidity of patients with adrenal insufficiency

Date of ISAC Approval: 
Lay Summary: 
Adrenal insufficiency is the state where there is inadequate production of cortisol, a vital hormone regulating the chemical processes in living individuals and the circulatory system. Cortisol is one of a group of substances called glucocorticoids and without glucocorticoid replacement, adrenal insufficiency leads to premature death. However, with conventional treatment, adrenal insufficiency continues to be associated with reduced life expectancy often due to circulatory problems (cardiovascular disease). Unintended glucocorticoid overdose may be a factor. In the past, glucocorticoids have traditionally been prescribed in high doses because normal amounts of glucocorticoid production were not known. In modern treatment regimens, lower glucocorticoid dosages are employed. Also, statins and blood pressure lowering drugs are increasingly being used. All could help reduce cardiovascular disease. Therefore, death and disability from cardiovascular disease may now be lower than observed with previous treatment regimens. This observational study will examine the overall death and disability rates from cardiovascular disease in people with adrenal insufficiency. We hypothesise that the life expectancy and general health of these patients are now similar to that of the general population.
Technical Summary: 
A retrospective cohort study is planned. The study population comprises patients diagnosed with Addison's disease, hypopituitarism, and/or adrenal insufficiency - as per the Clinical Practice Research Datalink record - between 1st January 1987 and 31st December 2017. Outcomes of interest are risks of cardiovascular mortality, all-cause mortality, cardiovascular morbidity (myocardial infarction, ischaemic heart disease, congestive heart failure, atrial fibrillation, cerebrovascular disease, and peripheral arterial diseases), and adrenal crisis, all of which will be derived from primary care code lists, Hospital Episode Statistics and Office for National Statistics mortality information. The primary aim is to compare the cardiovascular event rate in adrenal insufficiency patients with that in a background population. A further aim is to compare the all-cause mortality rate in adrenal insufficiency patients with that in the general population and to describe other causes of deaths in adrenal insufficiency patients. The observed rate of cardiovascular events in adrenal insufficiency patients will be compared with the expected rate, as observed in the CPRD general population, with age and sex standardization, and derivation of the standardised incidence ratio (SIR). Factors associated with cardiovascular mortality and morbidity will be evaluated using a multivariate Cox regression model. The hazard ratio with 95% confidence interval will be adjusted by age of onset, sex, and period of follow-up.
Health Outcomes to be Measured: 
- cardiovascular mortality - Prevalence of congestive heart failure - Prevalence of asdrenal Crisis - Overall mortality - Prevalence of cerebrovascular disease including transient Cerebral ischaemia and intracranial hemorrhage - Number of hospital admission - Prevalence of myocardial infarction and Ischaemic heart disease - other causes of Death - Prevalence of diabetes, hypertension, and dyslipidaemia

Professor Desmond Johnston - Chief Investigator - Imperial College London
Dr Ailsa McKay - Collaborator - Imperial College London
Professor Azeem Majeed - Collaborator - Imperial College London
Dr Kanchana Ngaosuwan - Corresponding Applicant - Imperial College London
Professor Stephen Robinson - Collaborator - Imperial College London

HES Admitted;ONS