The mediating role of cardiac autonomic imbalance in the association between hypoxic burden and dyslipidemia in obstructive sleep apnea

BACKGROUND: Obstructive sleep apnea (OSA) is associated with cardiac autonomic dysfunction and impaired lipid homeostasis. We investigated whether cardiac autonomic imbalance mediates the association between hypoxic burden (HB) and dyslipidemia. METHODS: Between January 2022 and March 2026, we consecutively enrolled 2,580 patients with suspected OSA for cross-sectional evaluation. All underwent overnight polysomnography and fasting lipid profiling. HB served as the exposure, heart rate variability (HRV) indices (pNN50 and LF/HF ratio) as mediators, and lipid parameters (LDL-C, total cholesterol, triglycerides) as outcomes. Multivariable logistic regression estimated odds ratios (ORs) for dyslipidemia across HB quartiles, and mediation analysis quantified indirect effects transmitted through HRV. RESULTS: ) individuals but were attenuated in older (>60 years) and obese individuals. Mediation analysis indicated that the HRV indices statistically accounted for part of these associations, consistent with a potential mediating role. The indirect effects (bootstrap 95% CI) of pNN50 on LDL-C, total cholesterol, and triglycerides were 0.004, 0.010, and 0.007, accounting for approximately 4.3%, 8.4%, and 3.8% of the total effect; the corresponding indirect effects of the LF/HF ratio were 0.004, 0.006, and 0.007, accounting for approximately 4.3%, 5.1%, and 3.8% of the total effect. CONCLUSIONS: HB is independently associated with dyslipidemia, an association that is partially mediated by cardiac autonomic imbalance, particularly in younger, female, and non-obese populations.