Obstructive Sleep Apnea and the Risk of Gout

A Population-Based Case-Control Study

Caroline van Durme; Bart Spaetgens; Johanna Driessen; Johannes Nielen; Manuel Sastry; Annelies Boonen; Frank de Vries

Disclosures

Arthritis Res Ther. 2020;22(92) 

In This Article

Abstract and Introduction

Abstract

Background: Patients with obstructive sleep apnea (OSA) might be at risk of gout because of pathophysiological mechanisms that can lead to hyperuricemia and eventually gout or because of shared risk factors between both diseases. The objective of the present study was to investigate the risk of gout in patients with OSA.

Methods: A population-based case-control study using the UK Clinical Practice Research Datalink GOLD including all patients aged 40 years and older with a first diagnosis of gout between 1987 and 2014. Gout cases were matched by year of birth, sex, and practice to non-gout controls. Conditional logistic regression estimated the risk of gout with an earlier diagnosis of OSA. Analyses were adjusted for lifestyle factors, comorbidities, and recent drug use.

Results: One hundred eleven thousand five hundred nine cases were matched with 210,241 controls. Patients with OSA were at increased risk of gout (OR 1.86; 95%CI (1.71–2.02). However, this association disappeared (OR 1.05; 95% CI 0.96–1.16) after adjustment for smoking status, body mass index (BMI), alcohol use, a history of heart failure, diabetes mellitus, renal function, and recent use of diuretics and other medications. Among females with OSA and patients with OSA associated with heart failure, renal impairment, or higher BMI, the risk of gout was however still increased when compared to the total control population.

Conclusion: This study showed that the observed association between OSA and gout disappeared after adjustment.

Introduction

Gout is the most common inflammatory arthritis,[1] affecting up to 1–2% of adults, and leads to disability and reduced quality of life.[2] Gout is characterized by the deposition of monosodium urate (MSU) crystals in synovial fluids and other tissues. Individuals suffering from gout often have a complex profile of comorbidities, including cardiovascular disease, diabetes mellitus, and kidney disease.[3] One of the comorbidities in gout that has received more attention over the past years is obstructive sleep apnea (OSA).[4] Various underlying mechanisms may explain an association between gout and OSA. First, OSA-induced hypoxemia causes a rise in adenosine triphosphate (ATP) degradation which eventually increases purine concentrations and their end product uric acid.[5] Second, hypercapnia and acidosis caused by OSA could influence the likelihood of MSU precipitation.[6] Third, excretion of lactic acid, generated during the hypoxic episodes in OSA, could result in a higher renal reabsorption of uric acid.[7]

Alternatively, the relationship could also be explained by shared risk factors of gout and OSA, such as age, obesity, metabolic syndrome, renal impairment, and heart failure.[8]

Two prospective studies in large United Kingdom (UK) primary care databases have demonstrated a 1.5-fold increased risk of developing gout among patients with OSA[4,9] with the overall risk peaking 1 to 2 years after OSA diagnosis.[9] While both papers statistically adjusted their analyses for body mass index (BMI), type 2 diabetes mellitus, ischemic heart disease, hypertension, the use of diuretics of an unspecified class, and alcohol consumption, renal impairment was either ignored or considerably under-recorded.[4] Under-recording could be explained by selecting only medical diagnoses of chronic kidney disease (CKD), not taking > 30 million records of estimated glomerular filtration (eGFR) rates into consideration (that are available as of 2018).[4] As CKD is a well-known risk factor for gout,[10,11] adequate statistical adjustment for this risk factor is important. Furthermore, both studies ignored the presence of heart failure, which is associated with both gout[12] and with sleep disorders, especially OSA.[13]

The objective of the present study was to investigate the risk of gout in patients with OSA, while accounting for all relevant potential confounders, including CKD and heart failure.

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