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  • Review Article
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Obstructive sleep apnoea heterogeneity and cardiovascular disease

Nature Reviews Cardiology volume 20, pages 560–573 (2023)Cite this article

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Abstract

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.

Key points

  • Obstructive sleep apnoea (OSA) is a heterogeneous disorder that consists of multiple subtypes that result from variable contributions from anatomical, physiological, inflammatory and obesity-related risk factors.

  • OSA-related risk of cardiovascular disease (CVD) varies with age, sex, symptom profile and severity of OSA-related physiological disturbance.

  • OSA results in a range of physiological disturbances that are not well characterized by the apnoea–hypopnoea index and which are associated with increased risk of CVD.

  • Existing clinical trials have not enriched enrolment to target subgroups of patients who are most at risk of CVD or most likely to respond to intervention.

  • Quantitative measures of apnoea-related hypoxic burden, cardiac autonomic response and respiratory arousal intensity are emerging markers of increased risk of CVD and are potential targets for risk stratification and intervention.

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Fig. 1: Heterogeneity of OSA, leading to various pathways that increase the risk of cardiovascular disease.
Fig. 2: Polysomnographic features of severe obstructive sleep apnoea.
Fig. 3: AHI and endotypic features of obstructive sleep apnoea vary according to BMI, age, sex and race/ethnicity.

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Acknowledgements

S.R. acknowledges support from the National Institutes of Health (grant HL135818). A.A. reports grant support from the National Institutes of Health and the American Academy of Sleep Medicine Foundation. Y.P. acknowledges institutional grants from the ResMed Foundation.

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Authors and Affiliations

  1. Division of Sleep and Circadian Disorders, Brigham and Women’s Hospital, Boston, MA, USA

    Susan Redline, Ali Azarbarzin & Yüksel Peker

  2. Harvard Medical School, Boston, MA, USA

    Susan Redline & Ali Azarbarzin

  3. Koc University School of Medicine, Istanbul, Turkey

    Yüksel Peker

  4. University of Gothenburg, Gothenburg, Sweden

    Yüksel Peker

  5. University of Pittsburgh School of Medicine, Pittsburgh, PA, USA

    Yüksel Peker

  6. Lund University School of Medicine, Lund, Sweden

    Yüksel Peker

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The authors contributed substantially to all aspects of the article.

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Correspondence to Susan Redline.

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Competing interests

S.R. reports receipt of consulting funds from Apnimed, Eli Lilly and Jazz Pharm. A.A. receives grant support from Somnifix and serves as a consultant for Apnimed, Eli Lilly, Respicardia and Somnifix. A.A.’s interests were reviewed by Brigham and Women’s Hospital and Mass General Brigham in accordance with their institutional policies. Y.P. receives grant support from ResMed Foundation. Apnimed and Eli Lilly are developing pharmacological treatments for obstructive sleep apnoea, and ResMed produces devices for the treatment of sleep apnoea.

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Redline, S., Azarbarzin, A. & Peker, Y. Obstructive sleep apnoea heterogeneity and cardiovascular disease. Nat Rev Cardiol 20, 560–573 (2023). https://doi.org/10.1038/s41569-023-00846-6

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