Mediation analysis of metabolic and inflammatory factors on the association between sleep apnoea and coronary heart disease in the large population–based cohort

Background Previous research has linked a history of sleep apnoea with coronary heart disease (CHD). This study is aimed to assess the association between sleep apnoea and CHD and to explore the extent to which this association is mediated by metabolic factors and C–reactive protein (CRP). Methods In this large population–based cohort study based on the UK Biobank, 213,442 CHD–free (mean age: 55.00) adults were followed up for 15 years to detect incident CHD. Sleep apnoea and CHD were ascertained from self–report and hospital records. Metabolic factors were included hyperglycemia, hypertension, dyslipidemia, hypertriglyceridemia and hyperuricemia. Higher CRP concentration level was defined as a cut–off point of > 3.0 mg/L. Data were analyzed using Cox proportional hazards models and generalized structural equation model (GSEM). Results During follow–up (median: 11.74 years, interquartile range: 10.97 to 12.48 years), 9,278 participants developed incident CHD (4.3%). The multi–adjusted hazard ratio (HR) and 95% confidence interval (CI) of CHD related to sleep apnoea was 1.76 (1.44–2.15). In the mediation analysis, the strongest indirect association was for dyslipidemia, accounting for 20.8% of the association between sleep apnoea and CHD ( β = 0.22, 95% CI = 0.16–0.28), followed by hypertriglyceridemia (12.3%) and hyperglycemia mediated (8.5%). The proportion of mediation increased to 29.1% when CRP was added to the metabolic mediators. Conclusions Sleep apnoea was associated with an increased risk of CHD. 20.8% and 12.3% of the association of sleep apnoea with CHD may be accounted respectively for by dyslipidemia and hypertriglyceridemia. CRP increased the magnitude of every metabolic factors–mediated association to 29.1%.