Confounded by obesity and modulated by urinary uric acid excretion, sleep-disordered breathing indirectly relates to hyperuricaemia in males: A structural equation model.

Sleep-disordered breathing (SDB) causes hypoxic stress and can trigger uric acid (UA) overproduction. We comprehensively investigated whether SDB, interacting with components of metabolic syndrome, hepatic and renal dysfunctions, low physical fitness, sedentary lifestyle, disrupted sleep, and chronic systemic inflammation (CSI), is directly associated with hyperuricaemia. In 528 community-based males (mean [SD] age 46.2 [7.4] years), we cross-sectionally analysed measures of anthropometry; self-reported lifestyle habits; overnight sleep polysomnography data; cardiopulmonary exercise tests; and biomarkers of cardiometabolic, hepatic, and renal functions; and CSI, using structural equation modelling. Objective disrupted sleep, C-reactive protein, low physical fitness, and sedentary lifestyle were not related to UA levels in univariate analysis and were excluded. The latent variables (with corresponding manifest variables) obesity (body mass index, waist-hip ratio), hypertension (post-sleep systolic, diastolic blood pressure), dyslipidaemia (total cholesterol, triglyceride/high-density lipoprotein cholesterol), hepatic dysfunction (alanine aminotransferase, aspartate transaminase), and renal dysfunction (blood urea nitrogen, serum creatinine) were positively; and hyperglycaemia (fasting glucose, glycated haemoglobin) was negatively associated with hyperuricaemia (serum UA), except for SDB (Apnea-Hypopnea Index, percentage of oxygen saturation <90% period against total sleep time, oxygen desaturation index) in the one-stage influence model. In the two-stage model, SDB, closely interacting with obesity, was positively indirectly associated with hyperuricaemia through directly linked renal dysfunction and obesity-linked hypertension, inverse hyperglycaemia, dyslipidaemia, and hepatic dysfunction. In conclusion, structural equation modelling reveals that SDB closely interacts with obesity and is positively but indirectly related to hyperuricaemia in males. This suggests that urinary UA excretion modulates and obesity confounds the SDB-hyperuricaemia relationship.