Association between serum urate, gout and comorbidities: a case-control study using data from the UK Biobank.

Gabriela Sandoval-Plata,Kevin Morgan,Abhishek Abhishek,Mithun Chakravorty,Georgina Nakafero

doi:10.1093/rheumatology/keaa773

Abstract

To examine the association between comorbidities and serum urate (SU), gout and comorbidities, and to determine whether the association between gout and comorbidities is independent of SU. We performed a case-control study using UK Biobank data. Two separate analyses were conducted: one excluding participants with gout to investigate the association between comorbidities and SU and the other with participants with gout as the index condition to examine the association between gout and comorbidities. SU was measured at the baseline visit. Self-reported physician-diagnosed illnesses were used to define gout and comorbidities, except for chronic kidney disease (CKD), which was defined using an estimated glomerular filtration rate cut-off. Participants prescribed urate-lowering treatment were also classified as gout. Logistic regression was used to examine associations. Odds ratios (ORs) and 95% CIs were calculated and adjusted for covariates including comorbidities and SU. Data for 458781 UK Biobank participants were used to examine the association between comorbidities and SU. There was an association between hypertension, ischaemic heart disease (IHD), congestive cardiac failure (CCF), hyperlipidaemia, CKD and SU with and adjusted OR (aOR) of 1.10-3.14 for each 1 mg/dl SU increase. A total of 10265 gout cases and 458781 controls were included in the analysis of association between gout and comorbidities. Gout associated independently with hypertension, IHD, CCF, hyperlipidaemia and diabetes, with aORs of 1.21-4.15 after adjusting for covariates including SU. Comorbidities associate with increasing SU. The association between gout and cardiometabolic comorbidities was independent of SU, suggesting separate SU-independent mechanisms such as inflammation driven by crystal deposition, pro-inflammatory genotype or non-purine dietary factors.

Highlights

Gout is a common inflammatory arthritis with a prevalence of 2.5-3.9% in Europe and North America [1, 2]
This study reports that gout associates independently with comorbidities, and, that the association between gout and hypertension, ischaemic heart disease (IHD), cardiac failure (CCF), hypercholesterolemia and diabetes mellitus is independent of serum urate
This study reports that hypertension, IHD, CCF, chronic kidney disease (CKD), and hypercholesterolemia associate with serum urate, and that diabetes mellitus associates negatively with serum urate

Summary

Introduction

Gout is a common inflammatory arthritis with a prevalence of 2.5-3.9% in Europe and North America [1, 2]. Recent Mendelian randomisation studies have reported association between serum urate variants and IHD, hypertension, hypercholesterolemia, and CCF but not with CKD or diabetes [8,9,10,11]. It is unclear whether the association between gout and comorbidities is independent of serum urate. This is because most observational studies are conducted using data from electronic health records, and serum urate levels are rarely available for controls unless measured for clinical reasons such as suspected gout, pre-eclampsia, or CKD precluding valid attempts at association studies using these databases. The objectives of this study were to examine the association between [1] cardiovascular diseases, CKD, diabetes mellitus, hypercholesterolemia and serum urate level; [2] gout and cardiovascular diseases, CKD, diabetes mellitus, and hypercholesterolemia; and [3] to evaluate whether the association between gout and comorbidities is independent of serum urate

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