Altered heart rate variability is associated with all-cause mortality in patients with co-morbid insomnia and obstructive sleep apnea.

STUDY

OBJECTIVES

Data regarding the additive effect of co-morbid insomnia and obstructive sleep apnea (COMISA) on autonomic modulation is lacking, and an association between cardiac autonomic burden and all-cause mortality in COMISA remains underexplored.

METHODS

In total, 5225 participants from the Sleep Heart Health Study (SHHS) were included. COMISA was diagnosed if the criteria for insomnia (difficulties initiating sleep, maintaining sleep, and/or early morning awakenings 16-30 times/month and daytime impairment) and obstructive sleep apnea (OSA) (apnea-hypopnea index [AHI] ≥ 15 events/h) were met. Heart rate variability (HRV) measures were computed from electrocardiogram during wakefulness before sleep onset and sleep using linear and non-linear analysis. Analysis of covariance was used to compare HRV among groups. Cox regression analysis was performed to examine associations between HRV and all-cause mortality in COMISA.

RESULTS

Of the 5225 participants, 2697 were controls without insomnia or OSA, 170 had only insomnia, 2221 had only OSA, and 137 had COMISA. Of 42 deaths occurred in COMISA (30.6%). By comparisons of HRV among these 4 groups, COMISA were associated with elevated autonomic burdens, showing decreased parasympathetic activity. In multivariable Cox models, higher deceleration capacity (DC) of heart rate per 1-SD increase was independently associated with a lower risk of all-cause mortality in COMISA during wakefulness (hazard ratio [HR], 0.75; 95% confidence interval [CI], 0.57-0.98; p = 0.037) and sleep (HR, 0.68; 95% CI, 0.49-0.95; p = 0.024).

CONCLUSIONS

Autonomic dysfunction is highly burdensome with COMISA through decreased parasympathetic function, leading to increased mortality. Among HRV measures, DC demonstrated the strongest predictive value, indicating its potential utility for improving mortality risk identification and stratification of all-causal mortality in COMISA.

CLINICAL TRIAL INFORMATION: Data were derived from the SHHS, available at: https://clinicaltrials.gov/study/NCT00005275. Clinical trial identifier: NCT00005275. Statement of Significance Co-morbid insomnia and sleep apnea (COMISA) is increasingly recognized as an independent factor for the development of mortality. The associated autonomic burden, reflecting the cumulative impact of chronic autonomic stressors over time, represents a modifiable risk variant for mortality. This study provided a novel insight into the associations between autonomic abnormalities and COMISA. Our findings highlighted that deceleration capacity of heart rate can be a robust biomarker of autonomic burden to predict all-cause mortality risk in COMISA. Early detection on autonomic impairment in these patients is critical to prevent adverse clinical events (e.g. cardiovascular morbidity and mortality). COMISA-predisposed autonomic abnormalities are related to increased all-cause mortality through burdensome autonomic responses during wakefulness and sleep. Further studies are warranted to investigate the role of autonomic burden in clinical outcomes of COMISA.