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

Abstract

Abstract 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 Higher HB quartiles were progressively associated with increased risk of elevated LDL-C (OR, 2.372; p < 0.001), hypercholesterolemia (OR, 2.518; p < 0.001), and hypertriglyceridemia (OR, 1.933; p = 0.021). These associations were robust among younger (<45 years), female, and normal-weight (BMI < 24 kg/m2) 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.