Polysomnographic phenotypes and their cardiovascular implications in obstructive sleep apnoea

Thorax. 2018 May;73(5):472-480. doi: 10.1136/thoraxjnl-2017-210431. Epub 2017 Sep 21.

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.

Publication types

  • Multicenter Study
  • Observational Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Acute Coronary Syndrome / epidemiology
  • Aged
  • Cardiovascular Diseases / epidemiology*
  • Cluster Analysis
  • Cross-Sectional Studies
  • Female
  • Humans
  • Ischemic Attack, Transient / epidemiology
  • Longitudinal Studies
  • Male
  • Middle Aged
  • Mortality
  • Phenotype
  • Polysomnography*
  • Proportional Hazards Models
  • Risk Assessment
  • Severity of Illness Index
  • Sleep Apnea, Obstructive / classification*
  • Sleep Apnea, Obstructive / complications
  • Sleep Apnea, Obstructive / physiopathology*
  • Stroke / epidemiology