Background
Gout is caused by uric acid (UA) which is released into the blood when the body breaks down proteins from food. At high levels this UA forms tiny crystals which deposit in and around joints causing intense pain and swelling. The aim of long-term treatment for gout is therefore to reduce levels of UA using medication. However, UA is also thought to perform a useful function protecting nerve cells which are responsible for conducting messages around the body from damage.
Aims and Methods
This study will investigate whether patients with gout (and therefore higher levels of UA) are at lower risk of nerve cell damage which can cause Parkinson’s Disease (PD), Multiple Sclerosis (MS) and Alzheimer’s disease, than patients without gout using a large database of electronic general practice records. The effect of treating gout by lowering UA levels with medication on the risk of these conditions will also be tested.
PPIE:
This research question was informed by Keele’s gout Research User Group who highlighted the importance of identifying potentially avoidable complications of gout, but also the impact of concerns about side effects of medication when considering or taking urate-lowering gout treatments.
Objectives
This study aims to estimate the risk of neurodegenerative conditions (Parkinson’s Disease, dementia, and Multiple Sclerosis) in gout patients compared to those without gout and determine if this is affected by urate-lowering therapies (ULT).
Methods
We will identify incident gout cases between 1997 and 2016 from primary care using Read codes. All patients with a history of gout or evidence of ULT before the study start date will be excluded. Each gout case will be matched to 5 controls on age, gender, general practice and follow-up in CPRD. Among those with gout, we will assess the impact of ULT on fracture and utilise landmark analysis and propensity score matching to account for immortal time bias and confounding by indication.
Data analysis
The absolute rate of neurodegenerative disorders per 10,000 person-years will be calculated for cases and controls. Cox Proportional Hazards Regression will model time-to-event, and estimate the hazard ratio associated with exposure to gout. A multivariable regression model will be used to adjust for potential confounders. Subgroup analyses investigating the affect of ULT exposure (defined as a minimum of 6 months ULT) on neurodegenerative disorder risk in the gout cohort will be performed using landmark analysis.
We aim to quantify the risk neurodegenerative disorders (Parkinson’s disease, multiple sclerosis and Alzheimer’s disease) among patients with gout.
Lorna Clarson - Chief Investigator - Keele University
Lorna Clarson - Corresponding Applicant - Keele University
Alyshah Abdul Sultan - Collaborator - AstraZeneca Ltd - UK Headquarters
Christian Mallen - Collaborator - Keele University
Edward Roddy - Collaborator - Keele University
Louise Crowley - Collaborator - Keele University
Rebecca Whittle - Collaborator - Keele University
HES Admitted Patient Care;ONS Death Registration Data;Patient Level Index of Multiple Deprivation