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Cardiac risk factors and prevention
Original research article
Subclinical sleep apnoea and plasma levels of endothelin-1 among young and healthy adults
  1. Tobias Schoen1,2,3,
  2. Stefanie Aeschbacher2,3,
  3. Joerg D Leuppi4,
  4. David Miedinger4,
  5. Ursina Werthmüller5,
  6. Joel Estis6,
  7. John Todd6,
  8. Martin Risch7,8,
  9. Lorenz Risch7,9,10 and
  10. David Conen2,3,11,12
  1. 1Division of Cardiology, University Hospital Basel, Basel, Switzerland
  2. 2Cardiovascular Research Institute Basel, Basel, Switzerland
  3. 3Division of Internal Medicine, University Hospital Basel, Basel, Switzerland
  4. 4Medical University Clinic of Baselland and Medical Faculty of Basel, Liestal/Basel, Switzerland
  5. 5Faculty of Medicine, University of Basel, Basel, Switzerland
  6. 6Singulex, Inc, Alameda, California, USA
  7. 7Labormedizinisches Zentrum Dr. Risch, Schaan, Liechtenstein
  8. 8Division of Laboratory Medicine, Kantonspital Graubünden, Chur, Switzerland
  9. 9Division of Clinical Biochemistry, Medical University Innsbruck, Austria
  10. 10Private University, Triesen, Liechtenstein
  11. 11Cardiology Division, St. Joseph's Healthcare, Hamilton, Ontario, Canada
  12. 12Population Health Research Institute, Vascular and Stroke Research Institute, Hamilton, Ontario, Canada
  1. Correspondence to Dr David Conen; david.conen{at}usb.ch

Abstract

Objective Obstructive sleep apnoea (OSA) is a risk factor for vascular disease and other adverse outcomes. These associations may be at least partly due to early endothelin-1 (ET-1)-mediated endothelial dysfunction (ED). Therefore, we assessed the relationships between subclinical sleep apnoea and plasma levels of ET-1.

Methods We performed a population-based study among 1255 young and healthy adults aged 25–41 years. Cardiovascular disease, diabetes or a body mass index >35 kg/m2 were exclusion criteria. Plasma levels of ET-1 were measured using a high-sensitivity, single-molecule counting technology. The relationships between subclinical sleep apnoea (OSA indices: respiratory event index (REI), oxygen desaturation index (ODI), mean night-time blood oxygen saturation (SpO2)) and ET-1 levels were assessed by multivariable linear regression analysis.

Results Median age of the cohort was 35 years. Median ET-1 levels were 2.9 (IQR 2.4–3.6) and 2.5 pg/mL (IQR 2.1–3.0) among patients with (n=105; 8%) and without subclinical sleep apnoea (REI 5–14), respectively. After multivariable adjustment, subclinical sleep apnoea remained significantly associated with plasma levels of ET-1 (β=0.13 (95% CI 0.06 to 0.20) p=0.0002 for a REI 5–14; β=0.10 (95% CI 0.03 to 0.16) p=0.003 for an ODI≥5). Every 1% decrease in mean night-time SpO2 increased ET-1 levels by 0.1 pg/mL, an association that remained significant after multivariable adjustment (β=0.02 (95% CI 0.003 to 0.033) p=0.02).

Conclusions In this study of young and healthy adults, we found that participants with subclinical sleep apnoea had elevated plasma ET-1 levels, an association that was due to night-time hypoxaemia. Our results suggest that ED may already be an important consequence of subclinical sleep apnoea.

  • SLEEP APNEA
  • ENDOTHELIN-1
  • HYPOXEMIA

This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/

https://doi.org/10.1136/openhrt-2016-000523

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    Footnotes

    • Contributors TS and DC were involved in all parts of the conduct of this study: design of the study (TS, DC), acquisition of data (TS, DC), analysis and/or interpretation (TS, DC), drafting of the manuscript (TS), revising the manuscript (TS, DC). All other authors were involved in the conduct of this study and approved the revised version of the manuscript.

    • Funding The Liechtenstein Government, the Swiss Heart Foundation, the Swiss Society of Hypertension, the University of Basel, the University Hospital Basel, the Hanela Foundation, Schiller AG and Novartis supported the GAPP study. DC was supported by a grant of the Swiss National Science Foundation (PP00P3_133681 and PP00P3_159322). Endothelin-1 was measured free of charge by Singulex, Alameda, CA 94502, USA. The ApneaLink devices were provided by ResMed Schweiz AG (Basel, Switzerland).

    • Competing interests JT and JE are employees of Singulex and hold stock options in Singulex. They are also co-inventors on patents filed in regard to assay methods for measuring endothelin-1 levels.

    • Patient consent Obtained.

    • Ethics approval The local ethics committee approved the study protocol.

    • Provenance and peer review Not commissioned; externally peer reviewed.

    • Data sharing statement No additional data are available.