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

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Original abstract

<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Results</h4>Higher HB quartiles were progressively associated with increased risk of elevated LDL-C (OR, 2.372; <i>p</i> < 0.001), hypercholesterolemia (OR, 2.518; <i>p</i> < 0.001), and hypertriglyceridemia (OR, 1.933; <i>p</i> = 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.<h4>Conclusions</h4>HB is independently associated with dyslipidemia, an association that is partially mediated by cardiac autonomic imbalance, particularly in younger, female, and non-obese populations.

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