Polysomnographic phenotypes and their cardiovascular implications in obstructive sleep apnoea

Abstract

Background: Obstructive sleep apnoea (OSA) is a heterogeneous disorder, and improved understanding of physiologic phenotypes and their clinical implications is needed. We aimed to determine whether routine polysomnographic data can be used to identify OSA phenotypes (clusters) and to assess the associations between the phenotypes and cardiovascular outcomes.

Methods: Cross-sectional and longitudinal analyses of a multisite, observational US Veteran (n=1247) cohort were performed. Principal components-based clustering was used to identify polysomnographic features in OSA's four pathophysiological domains (sleep architecture disturbance, autonomic dysregulation, breathing disturbance and hypoxia). Using these features, OSA phenotypes were identified by cluster analysis (K-means). Cox survival analysis was used to evaluate longitudinal relationships between clusters and the combined outcome of incident transient ischaemic attack, stroke, acute coronary syndrome or death.

Results: Seven patient clusters were identified based on distinguishing polysomnographic features: 'mild', 'periodic limb movements of sleep (PLMS)', 'NREM and arousal', 'REM and hypoxia', 'hypopnoea and hypoxia', 'arousal and poor sleep' and 'combined severe'. In adjusted analyses, the risk (compared with 'mild') of the combined outcome (HR (95% CI)) was significantly increased for 'PLMS', (2.02 (1.32 to 3.08)), 'hypopnoea and hypoxia' (1.74 (1.02 to 2.99)) and 'combined severe' (1.69 (1.09 to 2.62)). Conventional apnoea-hypopnoea index (AHI) severity categories of moderate (15≤AHI<30) and severe (AHI ≥30), compared with mild/none category (AHI <15), were not associated with increased risk.

Conclusions: Among patients referred for OSA evaluation, routine polysomnographic data can identify physiological phenotypes that capture risk of adverse cardiovascular outcomes otherwise missed by conventional OSA severity classification.

Keywords: cardiovascular diseases; cluster analysis; heterogeneity; mortality; obstructive sleep apnea (OSA); phenotype.

Figure 1

Kaplan-Meier survival probability curves for risk of acute coronary syndrome, transient ischaemic attack, stroke or death for seven polysomnographic clusters. NREM, non-rapid eye movement; PLMS, periodic limb movements of sleep; REM, rapid eye movement.

Figure 2

Risk (odds ratio, OR) of ACS, TIA, stroke or death for those with regular versus not regular CPAP use for each cluster. ACS, acute coronary syndrome; CPAP, continuous positive airway pressure; NREM, non-rapid eye movement; PLMS, periodic limb movements of sleep; REM, rapid eye movement; TIA, transient ischaemic attack. p value is for Breslow-Day homogeneity of ORs test. OR and 95% CI reported for those with regular CPAP use versus not regular CPAP use.