Low-risk obstructive sleep apnoea, insomnia, and continuous positive airway pressure: implications for cardiovascular outcomes in clinical trials

This commentary refers to ‘Cardiovascular benefit of continuous positive airway pressure according to high-risk obstructive sleep apnoea: a multi-trial analysis’, by A. Azarbarzin et al., https://doi.org/10.1093/eurheartj/ehaf447 and the discussion piece ‘The overlooked role of insomnia and comorbid insomnia and sleep apnoea in continuous positive airway pressure cardiovascular outcome trials’, by M. Meira e Cruz, https://doi.org/10.1093/eurheartj/ehag032. We thank the correspondents for their thoughtful engagement with our work. We agree that co-morbid insomnia and sleep apnea (COMISA) represents an important and often underappreciated phenotypic aspect of obstructive sleep apnea (OSA) in cardiovascular outcome trials, and that its systematic assessment could provide valuable insights in future studies. Notably, insomnia was not an exclusion criterion in the randomized trials studied. As the correspondents suggest, ‘Low Risk OSA’—characterized by neither increased hypoxic burden nor high heart rate responses to events, and signals suggesting cardiovascular harm among those randomized to continuous positive airway pressure (CPAP) vs usual care1—may represent a subpopulation enriched for COMISA. Indeed, an analysis of clinical cohorts have suggested that individuals with OSA and insomnia-related symptoms exhibit a lower hypoxic burden compared with others with OSA.2 Likewise, a low arousal threshold, potentially a physiological correlate of insomnia, is associated with reduced sleepiness, and lower levels of hypoxia.3