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Abstract

Rationale: Obstructive sleep apnea (OSA) is a common sleep disorder that affects approximately a billion adults worldwide. OSA is associated with an increased risk of cardio/cerebrovascular disease and cognitive impairment. The apnea-hypopnea index (AHI) (the key clinical OSA severity index) is defined as the frequency of respiratory events per hour of sleep; however, the relationship between AHI and OSA-associated outcomes is weak and inconsistent. One potential explanation is that AHI does not assess the physiologic responses to respiratory events. We hypothesized that there is variability in the physiologic responses to respiratory events. Furthermore, measuring these physiologic biomarkers from polysomnography could provide nuanced information regarding the link between OSA and related outcomes. Objectives: 1)To systematically review studies that investigated novel metrics of OSA severity. 2)To determine whether the magnitude of the physiologic responses to events are correlated with the degree of event hypoxemia and other factors. 3)To assess whether physiologic responses are associated with a variety of OSA-related adverse outcomes (chronic kidney disease (CKD), cognitive impairment and MRI evidence of brain damage). Methods: For objectives 2 and 3, we used data from the Canadian Sleep and Circadian Network cohort. Event-related hypoxemia severity was assessed by OSA-specific hypoxic burden (HB). Physiologic responses to events were assessed by processing polysomnograms. The outcomes ofinterest were a validated risk score for CKD and objective cognitive performance. Finally, the association between HB and MRI indicators of brain damage was investigated using data from the Multi-Ethnic Study of Atherosclerosis. Results: We found that HB was associated with an increase in a wide range of physiological responses. In terms of outcomes, greater HB and blunted mean autonomic responses conferred a higher risk of CKD progression. Furthermore, we identified a negative association between electroencephalogram (EEG) response and the risk of cognitive impairment. Finally, we found that an increased HB was associated with greater levels of white matter damage. Conclusion: All respiratory events are not equal, and there is variability in physiologic response to such events. These physiologic measurements may provide more nuanced information to better understand the mechanisms that link OSA to health outcomes.