In Australian adults, gout was more prevalent in those with diagnosed or probable sleep apnoea, after adjustment for relevant confounders. Of the 1948 participants, 126 (6.5%) had gout, and 124 (6.4%) had sleep apnoea diagnosed by polysomnography. A further 190 participants (9.8%) had symptoms suggestive of sleep apnoea without a formal diagnosis. Even after accounting for age, BMI, sex, alcohol intake and the presence of arthritis, diagnosis of gout was 2.8 times more likely in respondents with possible OSA. A participant with diagnosed OSA was 2.6 times more likely to have gout. Our results are in keeping with two large primary care matched retrospective cohort studies, in which patients with sleep apnoea were almost twice as likely to have gout [11, 12]. It is known than sleep apnea is under diagnosed in the community [13].
Our study was novel in that we found the association also emerged in those with suspected, but undiagnosed, sleep apnea. Our study design does not allow for consideration of the directionality of these relationships. However, a recent study by Singh and Cleveland showed a higher risk for OSA in patients with gout in the 5% United States Medicare beneficiary sample. They propose that two mechanisms are consistent between gout and OSA – specifically, inflammation and oxidative stress [4]. Prospective studies with gold-standard measurement of OSA, and inclusion of serum urate measures over time, will be required to further examine these relationships.
Our second aim was to explore the relationship between gout and patient reported sleep problems. Interestingly, participants with gout were twice as likely to have restless legs symptoms or periodic leg movements of sleep. Restless legs syndrome has been has reported associations with gout as well as many other comorbidities including obesity, diabetes, hypertension, thyroid disease and iron deficiency [14]. However, the mechanism behind the association between gout and restless legs syndrome is unclear. In fact, a 2019 study of 281 patients with restless legs syndrome showed reduced urate levels compared to controls matched by age and gender. It is worth noting however, that lower urate levels were also associated by increasing age, disease duration and haemoglobin level [15].
Given the prevalence of gout and the substantive financial burden of sleep-related conditions and flow on effects including productivity, employment, accidents and well-being, our findings highlight the importance of identifying and managing sleep problems in patients with gout [16]. Those with gout were also twice as likely to worry about sleep and 1.5 times as likely to have discussed sleep with a health professional. However, in those with gout, while there were trends towards issues with perceived adequacy of sleep and disruption of sleep secondary to pain, these effects were not significant. This result was surprising and not in keeping with our proposed hypothesis.
While gout is implicated in sleep related issues, this appear to be distinct from pain. One possible interpretation is that current pain may not be a primary contributor to sleep disruption in gout. Importantly, these findings highlight that simply reinforcing the need for regular, good quality sleep will not be sufficient in this patient group, as the majority have routines which allow for adequate sleep. Instead, it will be important to identify patient-specific sleep complaints and concerns and manage these on a case-by-case basis. Our findings are unique in linking gout with a diverse range of sleep outcomes beyond self reported duration and quality from a patient perspective, which provides important insight into the sleep health messaging and advice likely to benefit patients living with gout. Specifically, patients with gout differ from the general population, with reports of feeling they receive adequate opportunity to sleep. Given the relationship identified between OSA and gout, this patient group are more likely to benefit from messaging about assessment for sleep disorders rather than sleep hygiene (e.g. habitual routines, and allowing adequate opportunities to sleep).
One of the strengths of our study was the large sample that closely matched the general Australian population. It should be noted however, that while the sample was representative in regards to age, gender and geographical location across metropolitan and rural locations, there was a higher proportion of post-school qualifications, particularly Bachelor degrees or higher, than population estimates. We used self-reported doctor diagnosed gout, which has been shown to be reliable in epidemiologic studies [17]. Findings should be interpreted in the context of the study limitations. A key limitation is the cross-sectional nature of our study, so we were unable to comment on causation. An unmeasured shared risk factor for both gout and sleep apnea, is an important consideration, and a source of potential bias in our study. It is important to note that a large case control study using primary care data, published earlier this year, has shown that after adjustment for renal function, recent use of diuretics and heart failure, the association between gout and sleep apnea was no longer seen in males [18]. We were unable to correct for renal function as were limited to information collected via an existing patient questionnaire and did not have specifics related to treatments used.
Our study has highlighted that sleep disorders and gout are common and frequently comorbid in the Australian population. Sleep apnoea and gout are both associated with significant cardiovascular morbidity and mortality, but are also treatable. An awareness of the co-existence of both conditions should lead to increased screening and appropriate treatment tailored to patient needs. Further research is required to delineate the nature of the relationship between conditions, and also to establish if treatment of one condition may influence the trajectory of the other condition.
