18 March 2019

The mysterious connection between sleep apnoea and gout

Clinical Conditions Gout

Does sleep apnoea cause gout – or is it the other way around? Or, is obesity really to blame for both conditions?

Two new studies have recently shed some light on this conundrum.

The first, an online survey of around 300 patients with gout, showed that it’s not all that uncommon for patients with gout to be bleary-eyed, foggy-headed and stifling a yawn.

Sleep problems affect around one in every four patients with gout, and around 17% of patients have sleep apnoea, according to the survey.

Even those without a diagnosed sleep problem were unsettled at night; on average, respondents reported sleeping 6.7 hours per night with sleep quality of 5.5 on a scale of 0-10.

The majority of patients (86%) said they snored, and about half reported snorting, gasping or stopping breathing while asleep.

“Frequent daytime sleepiness was reported by two thirds of people with gout, which is quite concerning,” the authors wrote.

Given the growing evidence that gout and sleep problems are linked, it might be worth  screening gout patients for sleep disorders in the clinic, the authors said.

The second study, which was also published earlier this year, teased out some of the variables through a stronger study design – a retrospective matched cohort analysis.

The researchers followed around 15,800 patients in UK general practices with (and 63,000 without) obstructive sleep apnoea for about six years to see which group was more likely to develop gout.

After adjusting for age, sex and co-morbidities (including obesity), the patients who had sleep apnoea were about 40% more likely to be diagnosed with gout – which mirrored previous studies.

Interestingly, the connection between sleep apnoea and gout was strong in patients with normal BMI not just in patients who were overweight or obese.

The risk of developing gout was highest 1-2 years after sleep apnoea diagnosis, the study found.

Associate Professor Neil McGill, a rheumatologist at the Royal Prince Alfred Hospital, Sydney, said the novelty of this study was that it showed an association between sleep apnoea and gout that was independent from other risk factors, including obesity.

However, obesity is known to be strongly associated with both gout and sleep apnoea, he said.

So, this one study shouldn’t be enough to convince doctors that the relationship between sleep apnoea and gout had nothing to do obesity at all. “We need to be cautious,” he said.

Observational studies like these couldn’t show cause and effect. But there was a plausible mechanism presented in the study.

“The intermittent hypoxia present in OSA enhances nucleotide turnover, generating purines which are metabolized to uric acid, providing a biologically plausible mechanism by which OSA predisposes patients to hyperuricemia and gout,” the authors said.

Curiously, it could actually be the other way around (that is gout causes sleep apnoea), the authors of the other study suggested.

“Gout-associated oxidative stress and acute and chronic inflammation through NALP3 (NACHT, LRR and PYD domains-containing protein 3) inflammasome activation and cytokine activation can put an individual at risk for developing obstructive sleep apnoea, since these pathways are activated in both these conditions,” the authors said.

“The exact mechanisms for association either way have not been defined and will need careful examination with basic, clinical and translational research.”

Arthritis Research & Therapy 2019

Arthritis & Rheumatology 2019