Obstructive sleep apnoea heterogeneity and cardiovascular disease

Obstructive sleep apnoea (OSA), characterized by recurrent periods of upper airway obstruction and intermittent hypoxaemia, is prevalent in patients with cardiovascular disease (CVD), and is therefore important to consider in the prevention and management of CVD. Observational studies indicate that OSA is a risk factor for incident hypertension, poorly controlled blood pressure, stroke, myocardial infarction, heart failure, cardiac arrhythmias, sudden cardiac death and all-cause death. However, clinical trials have not provided consistent evidence that treatment with continuous positive airway pressure (CPAP) improves cardiovascular outcomes. These overall null findings might be explained by limitations in trial design and low levels of adherence to CPAP. Studies have also been limited by the failure to consider OSA as a heterogeneous disorder that consists of multiple subtypes resulting from variable contributions from anatomical, physiological, inflammatory and obesity-related risk factors, and resulting in different physiological disturbances. Novel markers of sleep apnoea-associated hypoxic burden and cardiac autonomic response have emerged as predictors of OSA-related susceptibility to adverse health outcomes and treatment response. In this Review, we summarize our understanding of the shared risk factors and causal links between OSA and CVD and emerging knowledge on the heterogeneity of OSA. We discuss the varied mechanistic pathways that result in CVD that also vary across subgroups of OSA, as well as the potential role of new biomarkers for CVD risk stratification.