The Hypoxic Burden of Sleep Apnea Predicts Cardiovascular Disease-related Mortality: the Osteoporotic Fractures in Men Study and the Sleep Heart Health Study

Apnea-hypopnea index (AHI), the universal clinical metric of sleep apnea severity, poorly predicts the adverse outcomes of sleep apnea, potentially because the AHI, a frequency measure, does not adequately capture disease burden. Therefore, we sought to evaluate whether quantifying the severity of sleep apnea by the ‘hypoxic burden’ would predict mortality among adults aged 40 and older. 

The samples were derived from two cohort studies: The Outcomes of Sleep Disorders in Older Men (MrOS), which included 2743 men, age 76.3 ± 5.5 years; and the Sleep Heart Health Study (SHHS), which included 5111 middle-aged and older adults (52.8% women), age: 63.7 ± 10.9 years. The outcomes were all-cause and Cardiovascular disease (CVD)-related mortality. The hypoxic burden was determined by measuring the respiratory event-associated area under the desaturation curve from pre-event baseline. Cox models were used to calculate the adjusted hazard ratios for hypoxic burden. Unlike the AHI, the hypoxic burden strongly predicted CVD mortality but not all-cause mortality. Individuals in the MrOS study with hypoxic burden in the highest two quintiles had hazard ratios of 1.60 [95% confidence interval (CI) 1.13-2.28] and 2.04 (95% CI 1.34-3.09), respectively. Similarly, the group in the SHHS with hypoxic burden in the highest quintile had a hazard ratio of 1.96 (95% CI 1.11-3.43). 

The ‘hypoxic burden’, an easily derived signal from overnight sleep study, predicts CVD mortality across populations. The findings suggest that not only the frequency but the depth and duration of sleep related upper airway obstructions, are important disease characterizing features.