A mediation analysis of metabolic and inflammatory factors in the severe sleep apnea–coronary heart disease association

Abstract

Background: It is unclear whether metabolic and inf lammatory factors mediate the association between severe sleep apnea and coronary heart disease (CHD) in observational studies based on the large-scale population. This study aims to assess the association between severe sleep apnea and CHD and to explore the extent to which this association is mediated by metabolic factors and C-reactive protein (CRP). Methods: In UK Biobank, 213 442 CHD-free (mean age: 55.00) adults were followed up for 15 years to detect incident CHD. Metabolic factors included hyperglycemia, hypertension, dyslipidemia, hypertriglyceridemia, and hyperuricemia. A higher CRP concentration level was defined as a cutoff point of >3.0 mg/l. Data were analyzed using Cox proportional hazards models and the generalized structural equation model. Results: During follow-up, 9278 participants developed incident CHD (4.3%). The multi-adjusted hazard ratio and 95% confidence interval of CHD related to severe sleep apnea were 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 severe sleep apnea and CHD (β = 0.22, 95% confidence interval = 0.16–0.28), followed by hypertriglyceridemia (12.3%). The proportion of mediation increased to 29.1% when CRP was added to the metabolic mediators. Conclusions: Severe sleep apnea was associated with an increased risk of CHD. Lipid factors might play an essential role in the severe sleep apnea–CHD relationship. CRP increased the magnitude of mediation effects of overall metabolic factors.