Article Text

Original research
Does intermittent exposure to high altitude increase the risk of cardiovascular disease in workers? A systematic narrative review
  1. Jerónimo Aragón-Vela1,
  2. Jacob Bejder1,
  3. Jesús R Huertas2,3,
  4. Julio Plaza-Diaz4,5,6,
  5. Nikolai B Nordsborg1
  1. 1Department of Nutrition, Exercise, and Sports (NEXS), University of Copenhagen, Copenhagen, Denmark
  2. 2Department of Physiology, School of Sport Sciences, University of Granada, Granada, Spain
  3. 3Institute of Nutrition and Food Technology “José Mataix”, Biomedical Research Centre, University of Granada, Granada, Spain
  4. 4Children’s Hospital of Eastern Ontario Research Institute, Ottawa, Ontario, Canada
  5. 5Department of Biochemistry & MolecularBiology II, School of Pharmacy, University of Granada, Granada, Spain
  6. 6Instituto de Investigación Biosanitaria IBS Granada, Complejo Hospitalario Universitario de Granada, Granada, Spain
  1. Correspondence to Dr Nikolai B Nordsborg; nbn{at}


Objective Several working groups (eg, miners, flight crews and soldiers) are subjected to chronic intermittent hypoxic exposure. The cardiovascular implications have been studied but not systematically reviewed with focus on possible negative health implications. The aim of the present review was to systematically evaluate the hypothesis that intermittent hypoxic exposure causes cardiovascular stress detrimental to health in workers.

Design Systematic review.

Data sources Electronic database search of PubMed, Scopus and Web of Science up to April 2020.

Eligibility criteria Studies of workers ≥18 years repeatedly subjected to months to years of irregular intermittent hypoxia, lasting from a few hours (eg, flight crews), one or a few days (eg, soldiers), or several days to weeks (eg, miners working at high altitude), written in English and evaluating the effect of intermittent hypoxia on cardiovascular disease were included. Animal studies, books, book chapters, personal communication and abstracts were excluded. The primary outcome measure was changes in standardised mortality ratio.

Data extraction and synthesis Two independent reviewers extracted data and assessed risk of bias using the Cochrane Collaboration’s tool.

Results 119 articles were identified initially, 31 of which met the inclusion criteria. Of these, 17 were retrospective cohort mortality studies (irregular short-term intermittent hypoxia), and 14 studies were observational (long-term intermittent hypoxia). The population of irregular short-term intermittent hypoxia users (flight crew) showed a lower mortality by cardiovascular disease. Long-term intermittent hypoxia over several years such as in miners or soldiers may produce increased levels of cardiac disorders (12 studies), though this is probably confounded by factors such as obesity and socioeconomic status.

Conclusion This systematic narrative review found that cardiovascular disease mortality in flight crews is lower than average, whereas miners and soldiers exposed to intermittent hypoxia experience increased risks of cardiovascular diseases. The impact of socioeconomic status and lifestyle appears of importance.

PROSPERO registry number CRD42020171301.

  • physiology
  • coronary heart disease
  • occupational & industrial medicine
  • public health

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, appropriate credit is given, any changes made indicated, and the use is non-commercial. See:

View Full Text

Statistics from

Supplementary materials

  • Supplementary Data

    This web only file has been produced by the BMJ Publishing Group from an electronic file supplied by the author(s) and has not been edited for content.


  • Contributors NN and JRH designed research (project conception, development of overall research plan and study oversight); JA, JB and JP-D conducted research (hands-on conduct of the experiments and data collection); NN and JRH provided essential reagents or provided essential materials; JP-D and JA analysed data or performed statistical analysis; JA, JB, JP-D and NN wrote the paper.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests None declared.

  • Patient consent for publication Not required.

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

  • Data availability statement Data sharing not applicable as no datasets generated and/or analysed for this study.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.