A previously reported increased risk of gout among patients with obstructive sleep apnea (OSA) was not confirmed in an extensively adjusted analysis, although the risk persisted among certain subgroups of OSA patients, a large population-based case-control study found.
In an unadjusted analysis, the risk for gout was almost doubled for patients with OSA (OR 1.86, 95% CI 1.71-2.02), but after adjustment for important confounders such as body mass index (BMI), smoking and alcohol use, medications, and comorbidities such as heart failure, diabetes, and kidney disease, the risk was no longer statistically significant (OR 1.05, 95% CI 0.96-1.16), according to Frank de Vries, PhD, of Utrecht University in the Netherlands, and colleagues.
Nonetheless, in a stratified analysis the risks remained significantly higher for women, patients with heart failure, renal impairment, or high BMI compared with controls, the researchers reported online in .
There are several possible explanations for why gout might be associated with OSA, the team noted.
"First, OSA-induced hypoxemia causes a rise in adenosine triphosphate degradation, which eventually increases purine concentrations and their end product, uric acid. Second, hypercapnia and acidosis caused by OSA could influence the likelihood of monosodium urate precipitation. Third, excretion of lactic acid, generated during the hypoxic episodes in OSA, could result in a higher renal reabsorption of uric acid," de Vries and co-authors explained.
Two prospective studies conducted in the U.K. found significantly elevated risks for incident gout in OSA patients. In , which included 9,865 patients with newly diagnosed OSA, the multivariable rate ratio for gout during the first year of follow-up was 1.5 (95% CI 1.1-2.1), while in , which included 15,879 patients with OSA, the adjusted hazard ratio for gout was 1.42 (95% CI 1.29-1.56).
However, both of those studies did not adjust for the presence of heart failure, which has been linked to both gout and OSA, and relied on medical diagnoses for chronic kidney disease rather than reports of estimated glomerular filtration rates (eGFR).
Therefore, to calculate the gout risks among OSA patients taking into account these factors, de Vries and colleagues analyzed data from the U.K. , which contains the medical records of 1.3 million individuals in primary care.
The analysis included all patients ages 40 and older with a first diagnosis of gout from 1987 to 2014 (total of 111,509) and up to two matched controls (210,241 patients). Their mean age was 62, and more than two-thirds were men. A total of 1,094 of the gout cases had OSA.
Because heart failure is typically under-reported in observational studies, the researchers also adjusted their model for the use of medications commonly given to patients with heart failure, including diuretics, beta-blockers, and angiotensin-converting enzyme inhibitors.
Despite the overall lack of association seen in this study for OSA and gout after adjustment for numerous potential confounders, further stratified analyses revealed that gout does develop more commonly among patients with comorbidities including obesity, heart failure, and renal impairment, the researchers reported.
Stratification of the fully adjusted model showed that patients with OSA whose BMI was 30-34 had an adjusted odds ratio for gout of 1.34 (95% CI 1.13-1.59), while those whose BMI was 35 or higher had an odds ratio of 1.56 (95% CI 1.33-1.83). In the most obese patients, OSA tends to be more severe, with worsening oxygen desaturation and hypoxemia, the team explained.
Other factors in OSA patients found to be associated with increased risk in the stratified adjusted analysis included the following:
- History of heart failure, OR 1.82 (95% CI 1.21-2.73)
- Recent use of loop diuretics, OR 1.73 (95% CI 1.33-2.26)
- Recent use of thiazide diuretics, OR 1.85 (95% CI 1.47-2.33)
Moreover, the risk of gout rose with worsening renal impairment among OSA patients. Those whose eGFR was 30-59 mL/min had an adjusted odds ratio of 2.22 (95% CI 1.70-2.91) and those whose eGFR was 15-29 mL/min had an adjusted odds ratio of 3.93 (95% CI 1.06-14.56). "When renal function declines, less uric acid is excreted, which leads to hyperuricemia and eventually gout," de Vries and colleagues explained.
Women with OSA also had a greater risk of gout then men did (OR 1.64, 95% CI 1.19-2.27). Factors contributing to this finding were differences in the anatomy of the upper airway and fat distribution, as well as the influence of sex hormones, de Vries and co-authors noted.
A limitation of the study, they said, was the likely under-reporting of gout and OSA in the database.
Disclosures
de Vries reported that he supervises two PhD students who are employed with F. Hoffmann La Roche, but does not receive any fees or reimbursements for this, and the topics of their PhD theses do not relate to the manuscript. Two co-authors reported financial relationships with the European Academy of Dental Sleep Medicine, AstraZeneca, and Amgen.
Primary Source
Arthritis Research & Therapy
Van Durme C, et al "Obstructive sleep apnea and the risk of gout: a population-based case-control study" Arthritis Res Ther 2020; DOI: 10.1186/s13075-020-02176-1.