Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

Transportation noise pollution and cardiovascular disease

Nature Reviews Cardiology volume 18, pages 619–636 (2021)Cite this article

Subjects

Abstract

Epidemiological studies have found that transportation noise increases the risk of cardiovascular morbidity and mortality, with high-quality evidence for ischaemic heart disease. According to the WHO, ≥1.6 million healthy life-years are lost annually from traffic-related noise in Western Europe. Traffic noise at night causes fragmentation and shortening of sleep, elevation of stress hormone levels, and increased oxidative stress in the vasculature and the brain. These factors can promote vascular dysfunction, inflammation and hypertension, thereby elevating the risk of cardiovascular disease. In this Review, we focus on the indirect, non-auditory cardiovascular health effects of transportation noise. We provide an updated overview of epidemiological research on the effects of transportation noise on cardiovascular risk factors and disease, discuss the mechanistic insights from the latest clinical and experimental studies, and propose new risk markers to address noise-induced cardiovascular effects in the general population. We also explain, in detail, the potential effects of noise on alterations of gene networks, epigenetic pathways, gut microbiota, circadian rhythm, signal transduction along the neuronal–cardiovascular axis, oxidative stress, inflammation and metabolism. Lastly, we describe current and future noise-mitigation strategies and evaluate the status of the existing evidence on noise as a cardiovascular risk factor.

Key points

  • Noise is associated with cardiovascular diseases, such as arterial hypertension, coronary artery disease, heart failure and arrhythmia, and should therefore be considered a cardiovascular risk factor.

  • Noise-induced stress increases blood pressure, stress hormone levels, endothelial dysfunction, oxidative stress, NADPH oxidase 2 (NOX2) activity, nitric oxide synthase uncoupling and vascular inflammation in mice, all of which are prevented by NOX2 deficiency.

  • Translational field studies in healthy individuals and patients with heart disease established that short-term simulated aircraft and railway noise impairs sleep quality and increases stress hormone levels, blood pressure, endothelial dysfunction and oxidative stress.

  • The quality of evidence on the adverse cardiovascular effects of noise exposure has increased for several cardiometabolic risk factors since the WHO evaluation in 2018, especially for obesity and diabetes mellitus.

  • Noise-induced stress increases cerebral oxidative stress and downregulates and uncouples neuronal nitric oxide synthase, providing a potential explanation for the observed retardation in the development of cognitive function (memory and learning) in children exposed to aircraft noise.

  • Mitigation strategies to reduce population exposure to transportation noise are available and need to be implemented.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: Timeline of research on adverse health effects of noise.
Fig. 2: Noise sources and levels and their adverse health effects based on epidemiological data.
Fig. 3: Noise–stress concept and the adverse health consequences in humans.
Fig. 4: Adverse health effects of night-time noise in humans.
Fig. 5: Adverse health effects of aircraft noise exposure in mice.

Similar content being viewed by others

References

  1. Cohen, A. J. et al. Estimates and 25-year trends of the global burden of disease attributable to ambient air pollution: an analysis of data from the Global Burden of Diseases Study 2015. Lancet 389, 1907–1918 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  2. World Health Organization. Environmental Noise Guidelines for the European Region http://www.euro.who.int/en/publications/abstracts/environmental-noise-guidelines-for-the-european-region-2018 (2018).

  3. GBD 2016 Risk Factors Collaborators. Global, regional, and national comparative risk assessment of 84 behavioural, environmental and occupational, and metabolic risks or clusters of risks, 1990-2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet 390, 1345–1422 (2017).

  4. OECD/EU. Health at a Glance: Europe 2018: State of Health in the EU Cycle (OECD Publishing, 2018).

  5. Piepoli, M. F. et al. 2016 European Guidelines on Cardiovascular Disease Prevention in Clinical Practice: The Sixth Joint Task Force of the European Society of Cardiology and Other Societies on Cardiovascular Disease Prevention in Clinical Practice (constituted by representatives of 10 societies and by invited experts) developed with the special contribution of the European Association for Cardiovascular Prevention & Rehabilitation (EACPR). Eur. Heart J. 37, 2315–2381 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  6. Arnett, D. K. et al. 2019 ACC/AHA guideline on the primary prevention of cardiovascular disease: a report of the American College of Cardiology/American Heart association task force on clinical practice guidelines. Circulation 140, e596–e646 (2019).

    PubMed  PubMed Central  Google Scholar 

  7. Lim, S. S. et al. A comparative risk assessment of burden of disease and injury attributable to 67 risk factors and risk factor clusters in 21 regions, 1990-2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet 380, 2224–2260 (2012).

    Article  PubMed  PubMed Central  Google Scholar 

  8. WHO. Projections of mortality and causes of death, 2016 to 2060 https://www.who.int/healthinfo/global_burden_disease/projections/en/ (2021).

  9. WHO. The Global Health Observatory https://www.who.int/data/gho/data/themes/noncommunicable-diseases (2021).

  10. Landrigan, P. J. et al. The lancet commission on pollution and health. Lancet 391, 462–512 (2018).

    Article  PubMed  Google Scholar 

  11. Lelieveld, J. et al. Cardiovascular disease burden from ambient air pollution in Europe reassessed using novel hazard ratio functions. Eur. Heart J. 40, 1590–1596 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Burnett, R. et al. Global estimates of mortality associated with long-term exposure to outdoor fine particulate matter. Proc. Natl Acad. Sci. USA 115, 9592–9597 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Wild, C. P. Complementing the genome with an “exposome”: the outstanding challenge of environmental exposure measurement in molecular epidemiology. Cancer Epidemiol. Biomarkers Prev. 14, 1847–1850 (2005).

    Article  CAS  PubMed  Google Scholar 

  14. Münzel, T. et al. The adverse effects of environmental noise exposure on oxidative stress and cardiovascular risk. Antioxid. Redox Signal. 28, 873–908 (2018).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  15. Kryter, K. D. Effects of Noise on Man. 1st edn (Academic Press, 1970).

  16. Peterson, E. A., Augenstein, J. S., Tanis, D. C. & Augenstein, D. G. Noise raises blood pressure without impairing auditory sensitivity. Science 211, 1450–1452 (1981).

    Article  CAS  PubMed  Google Scholar 

  17. European Environment Agency. Environmental noise in Europe https://www.eea.europa.eu/publications/environmental-noise-in-europe (2020).

  18. Babisch, W., Gallacher, J. E., Elwood, P. C. & Ising, H. Traffic noise and cardiovascular risk. The Caerphilly study, first phase. Outdoor noise levels and risk factors. Arch. Env. Health 43, 407–414 (1988).

    Article  CAS  Google Scholar 

  19. Babisch, W. Updated exposure-response relationship between road traffic noise and coronary heart diseases: a meta-analysis. Noise Health 16, 1–9 (2014).

    Article  PubMed  Google Scholar 

  20. Vienneau, D., Schindler, C., Perez, L., Probst-Hensch, N. & Röösli, M. The relationship between transportation noise exposure and ischemic heart disease: a meta-analysis. Environ. Res. 138, 372–380 (2015).

    Article  CAS  PubMed  Google Scholar 

  21. Kempen, E. V., Casas, M., Pershagen, G. & Foraster, M. WHO environmental noise guidelines for the European region: a systematic review on environmental noise and cardiovascular and metabolic effects: a summary. Int. J. Environ. Res. Public Health 15, 379 (2018).

    Article  PubMed Central  Google Scholar 

  22. Monrad, M. et al. Residential exposure to traffic noise and risk of incident atrial fibrillation: A cohort study. Env. Int. 92-93, 457–463 (2016).

    Article  CAS  Google Scholar 

  23. Héritier, H. et al. Transportation noise exposure and cardiovascular mortality: a nationwide cohort study from Switzerland. Eur. J. Epidemiol. 32, 307–315 (2017).

    Article  PubMed  CAS  Google Scholar 

  24. Seidler, A. et al. Myocardial infarction risk due to aircraft, road, and rail traffic noise. Dtsch. Arztebl Int. 113, 407–414 (2016).

    PubMed  PubMed Central  Google Scholar 

  25. van Kamp, I., Simon, S., Notley, H., Baliatsas, C. & van Kempen, E. Evidence relating to environmental noise exposure and annoyance, sleep disturbance, cardio-vascular and metabolic health outcomes in the context of IGCB (N): a scoping review of new evidence. Int. J. Environ. Res. Public Health https://doi.org/10.3390/ijerph17093016 (2020).

    Article  PubMed  PubMed Central  Google Scholar 

  26. Sorensen, M. et al. Road traffic noise and stroke: a prospective cohort study. Eur. Heart J. 32, 737–744 (2011).

    Article  PubMed  Google Scholar 

  27. Beelen, R. et al. The joint association of air pollution and noise from road traffic with cardiovascular mortality in a cohort study. Occup. Env. Med. 66, 243–250 (2009).

    Article  CAS  Google Scholar 

  28. Huss, A., Spoerri, A., Egger, M. & Röösli, M. Aircraft noise, air pollution, and mortality from myocardial infarction. Epidemiology 21, 829–836 (2010).

    Article  PubMed  Google Scholar 

  29. Seidler, A. L. et al. The effect of aircraft, road, and railway traffic noise on stroke - results of a case-control study based on secondary data. Noise Health 20, 152–161 (2018).

    PubMed  PubMed Central  Google Scholar 

  30. Halonen, J. I. et al. Road traffic noise is associated with increased cardiovascular morbidity and mortality and all-cause mortality in London. Eur. Heart J. 36, 2653–2661 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  31. Pyko, A. et al. Long-term transportation noise exposure and incidence of ischaemic heart disease and stroke: a cohort study. Occup. Environ. Med. 76, 201–207 (2019).

    Article  PubMed  Google Scholar 

  32. Cai, Y. et al. Road traffic noise, air pollution and incident cardiovascular disease: A joint analysis of the HUNT, EPIC-Oxford and UK Biobank cohorts. Env. Int. 114, 191–201 (2018).

    Article  CAS  Google Scholar 

  33. Sorensen, M. et al. Long-term exposure to road traffic noise and nitrogen dioxide and risk of heart failure: a cohort study. Environ. Health Perspect. 125, 097021 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  34. Seidler, A. et al. Aircraft, road and railway traffic noise as risk factors for heart failure and hypertensive heart disease-A case-control study based on secondary data. Int. J. Hyg. Environ. Health https://doi.org/10.1016/j.ijheh.2016.09.012 (2016).

    Article  PubMed  Google Scholar 

  35. Carey, I. M. et al. Traffic pollution and the incidence of cardiorespiratory outcomes in an adult cohort in London. Occup. Env. Med. 73, 849–856 (2016).

    CAS  Google Scholar 

  36. Dimakopoulou, K. et al. Is aircraft noise exposure associated with cardiovascular disease and hypertension? Results from a cohort study in Athens, Greece. Occup. Environ. Med. 74, 830–837 (2017).

    Article  PubMed  Google Scholar 

  37. Basner, M. et al. Auditory and non-auditory effects of noise on health. Lancet 383, 1325–1332 (2014).

    Article  PubMed  Google Scholar 

  38. Schmidt, F. P. et al. Effect of nighttime aircraft noise exposure on endothelial function and stress hormone release in healthy adults. Eur. Heart J. 34, 3508–3514a (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Basner, M. & McGuire, S. WHO environmental noise guidelines for the european region: a systematic review on environmental noise and effects on sleep. Int. Environ. Res. Public Health 15, 519 (2018).

    Article  Google Scholar 

  40. Roswall, N. et al. Nighttime road traffic noise exposure at the least and most exposed facades and sleep medication prescription redemption - a Danish cohort study. Sleep 43, zsaa029 (2020).

    Article  PubMed  Google Scholar 

  41. Beutel, M. E. et al. Noise annoyance predicts symptoms of depression, anxiety and sleep disturbance 5 years later. Findings from the Gutenberg Health Study. Eur. J. Public. Health 30, 516–521 (2020).

    Article  PubMed  Google Scholar 

  42. Fuks, K. B. et al. Long-term exposure to ambient air pollution and traffic noise and incident hypertension in seven cohorts of the European study of cohorts for air pollution effects (ESCAPE). Eur. Heart J. 38, 983–990 (2017).

    CAS  PubMed  Google Scholar 

  43. Thacher, J. D. et al. Road traffic noise exposure and filled prescriptions for antihypertensive medication: a danish cohort study. Env. Health Perspect. 128, 57004 (2020).

    Article  CAS  Google Scholar 

  44. Zeeb, H. et al. Traffic noise and hypertension - results from a large case-control study. Env. Res. 157, 110–117 (2017).

    Article  CAS  Google Scholar 

  45. Pyko, A. et al. Transportation noise and incidence of hypertension. Int. J. Hyg. Env. Health 221, 1133–1141 (2018).

    Article  Google Scholar 

  46. McHill, A. W. & Wright, K. P. Jr. Role of sleep and circadian disruption on energy expenditure and in metabolic predisposition to human obesity and metabolic disease. Obes. Rev. 18 (Suppl. 1), 15–24 (2017).

    Article  PubMed  Google Scholar 

  47. Cappuccio, F. P., D’Elia, L., Strazzullo, P. & Miller, M. A. Quantity and quality of sleep and incidence of type 2 diabetes: a systematic review and meta-analysis. Diabetes Care 33, 414–420 (2010).

    Article  PubMed  Google Scholar 

  48. Sorensen, M. et al. Long-term exposure to road traffic noise and incident diabetes: a cohort study. Environ. Health Perspect. 121, 217–222 (2013).

    Article  PubMed  Google Scholar 

  49. Clark, C. et al. Association of long-term exposure to transportation noise and traffic-related air pollution with the incidence of diabetes: a prospective cohort study. Environ. Health Perspect. 125, 087025 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  50. Eze, I. C. et al. Long-term exposure to transportation noise and air pollution in relation to incident diabetes in the SAPALDIA study. Int. J. Epidemiol. 46, 1115–1125 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  51. Ohlwein, S. et al. Indoor and outdoor road traffic noise and incident diabetes: Results from a longitudional German cohort study. Environ. Epidemiol. 3, e037 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  52. Jorgensen, J. T. et al. Long-term exposure to road traffic noise and incidence of diabetes in the danish nurse cohort. Env. Health Perspect. 127, 57006 (2019).

    Article  Google Scholar 

  53. Vienneau, D., Eze, I. C., Probst-Hensch, N. & Röösli, M. Association between transportation noise and cardio-metabolic diseases: an update of the WHO meta-analysis. Proceedings of the 23rd International Conference on Acoustics 1543–1550 (ICA, 2019).

  54. Pyko, A. et al. Long-term exposure to transportation noise in relation to development of obesity-a cohort study. Environ. Health Perspect. 125, 117005 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  55. Foraster, M. et al. Long-term exposure to transportation noise and its association with adiposity markers and development of obesity. Env. Int. 121, 879–889 (2018).

    Article  Google Scholar 

  56. Christensen, J. S. et al. Long-term exposure to residential traffic noise and changes in body weight and waist circumference: A cohort study. Environ. Res. 143, 154–161 (2015).

    Article  CAS  PubMed  Google Scholar 

  57. Sorensen, M., Sorensen, T. I. A., Ketzel, M. & Raaschou-Nielsen, O. Exposure to traffic noise and gestational weight gain and postpartum weight retention: a cohort study. Occup. Env. Med. 77, 107–114 (2020).

    Article  Google Scholar 

  58. Eriksson, C. et al. Long-term aircraft noise exposure and body mass index, waist circumference, and type 2 diabetes: a prospective study. Environ. Health Perspect. 122, 687–694 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  59. Pyko, A. et al. Exposure to traffic noise and markers of obesity. Occup. Environ. Med. 72, 594–601 (2015).

    Article  PubMed  Google Scholar 

  60. Christensen, J. S. et al. Road traffic and railway noise exposures and adiposity in adults: a cross-sectional analysis of the danish diet, cancer, and health cohort. Environ. Health Perspect. 124, 329–335 (2016).

    Article  CAS  PubMed  Google Scholar 

  61. Foraster, M. et al. Long-term transportation noise annoyance is associated with subsequent lower levels of physical activity. Env. Int. 91, 341–349 (2016).

    Article  Google Scholar 

  62. Roswall, N. et al. Residential exposure to traffic noise and leisure-time sports — a population-based study. Int. J. Hyg. Env. Health 220, 1006–1013 (2017).

    Article  Google Scholar 

  63. Roswall, N. et al. Associations between residential traffic noise exposure and smoking habits and alcohol consumption — a population-based study. Env. Pollut. 236, 983–991 (2018).

    Article  CAS  Google Scholar 

  64. Clark, C. & Paunovic, K. WHO environmental noise guidelines for the European region: a systematic review on environmental noise and quality of life, wellbeing and mental health. Int. Environ. Res. Public Health 15, 2400 (2018).

    Article  Google Scholar 

  65. He, S. et al. Residential noise exposure and the longitudinal risk of hospitalization for depression after pregnancy: Postpartum and beyond. Env. Res. 170, 26–32 (2019).

    Article  CAS  Google Scholar 

  66. Orban, E. et al. Residential road traffic noise and high depressive symptoms after five years of follow-up: results from the heinz nixdorf recall study. Env. Health Perspect. 124, 578–585 (2016).

    Article  CAS  Google Scholar 

  67. Seidler, A. et al. Association between aircraft, road and railway traffic noise and depression in a large case-control study based on secondary data. Environ. Res. 152, 263–271 (2017).

    Article  CAS  PubMed  Google Scholar 

  68. Clark, C., Crumpler, C. & Notley, A. H. Evidence for environmental noise effects on health for the United Kingdom policy context: a systematic review of the effects of environmental noise on mental health, wellbeing, quality of life, cancer, dementia, birth, reproductive outcomes, and cognition. Int. J. Environ. Res. Public Health 17, 393 (2020).

    Article  PubMed Central  Google Scholar 

  69. Jarup, L. et al. Hypertension and exposure to noise near airports: the HYENA study. Environ. Health Perspect. 116, 329–333 (2008).

    Article  PubMed  Google Scholar 

  70. Vienneau, D. et al. Facades, floors and maps - Influence of exposure measurement error on the association between transportation noise and myocardial infarction. Env. Int. 123, 399–406 (2019).

    Article  CAS  Google Scholar 

  71. Babisch, W. Stress hormones in the research on cardiovascular effects of noise. Noise Health 5, 1–11 (2003).

    CAS  PubMed  Google Scholar 

  72. Münzel, T. et al. Environmental noise and the cardiovascular system. J. Am. Coll. Cardiol. 71, 688–697 (2018).

    Article  PubMed  Google Scholar 

  73. Babisch, W. et al. Noise annoyance–a modifier of the association between noise level and cardiovascular health? Sci. Total. Environ. 452-453, 50–57 (2013).

    Article  CAS  PubMed  Google Scholar 

  74. Hahad, O. et al. Annoyance to different noise sources is associated with atrial fibrillation in the Gutenberg Health Study. Int. J. Cardiol. 264, 79–84 (2018).

    Article  PubMed  Google Scholar 

  75. Meyer, T. & Wirtz, P. H. Mechanisms of mitochondrial redox signaling in psychosocial stress-responsive systems: new insights into an old story. Antioxid. Redox Signal. 28, 760–772 (2018).

    Article  CAS  PubMed  Google Scholar 

  76. Xia, N. & Li, H. Loneliness, social isolation, and cardiovascular health. Antioxid. Redox Signal. 28, 837–851 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Daiber, A. et al. Environmental noise induces the release of stress hormones and inflammatory signaling molecules leading to oxidative stress and vascular dysfunction-Signatures of the internal exposome. Biofactors 45, 495–506 (2019).

    CAS  PubMed  Google Scholar 

  78. Münzel, T. et al. Effects of noise on vascular function, oxidative stress, and inflammation: mechanistic insight from studies in mice. Eur. Heart J. 38, 2838–2849 (2017).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  79. Münzel, T. et al. Airborne disease: a case of a Takotsubo cardiomyopathie as a consequence of nighttime aircraft noise exposure. Eur. Heart J. 37, 2844 (2016).

    Article  PubMed  Google Scholar 

  80. Wallerath, T. et al. Down-regulation of the expression of endothelial NO synthase is likely to contribute to glucocorticoid-mediated hypertension. Proc. Natl Acad. Sci. USA 96, 13357–13362 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Yang, S. & Zhang, L. Glucocorticoids and vascular reactivity. Curr. Vasc. Pharmacol. 2, 1–12 (2004).

    Article  PubMed  Google Scholar 

  82. Osborne, M. T. et al. A neurobiological mechanism linking transportation noise to cardiovascular disease in humans. Eur. Heart J. 41, 772–782 (2020).

    Article  PubMed  Google Scholar 

  83. Münzel, T., Steven, S., Hahad, O. & Daiber, A. The sixth sense is involved in noise-induced stress responses and vascular inflammation: evidence for heightened amygdalar activity in response to transport noise in man. Eur. Heart J. 41, 783–785 (2020).

    Article  PubMed  Google Scholar 

  84. Jansen, G. The effect of noise during physical work. Int. Z. Angew. Physiol. 20, 233–239 (1964).

    CAS  PubMed  Google Scholar 

  85. Jansen, G. & Klensch, H. Alteration of the ballistogram by sound impressions and by music. Int. Z. Angew. Physiol. 20, 258–270 (1964).

    CAS  PubMed  Google Scholar 

  86. Jansen, G. Effects of noise on health. Ger. Med. Mon. 13, 446–448 (1968).

    CAS  PubMed  Google Scholar 

  87. Babisch, W., Ising, H., Gallacher, J. E., Sharp, D. S. & Baker, I. A. Traffic noise and cardiovascular risk: the Speedwell study, first phase. Outdoor noise levels and risk factors. Arch. Env. Health 48, 401–405 (1993).

    Article  CAS  Google Scholar 

  88. Lusk, S. L., Gillespie, B., Hagerty, B. M. & Ziemba, R. A. Acute effects of noise on blood pressure and heart rate. Arch. Env. Health 59, 392–399 (2004).

    Article  Google Scholar 

  89. Dratva, J. et al. Transportation noise and blood pressure in a population-based sample of adults. Environ. Health Perspect. 120, 50–55 (2011).

    Article  PubMed  PubMed Central  Google Scholar 

  90. Haralabidis, A. S. et al. Acute effects of night-time noise exposure on blood pressure in populations living near airports. Eur. Heart J. 29, 658–664 (2008).

    Article  PubMed  Google Scholar 

  91. Bagheri Hosseinabadi, M., Khanjani, N., Münzel, T., Daiber, A. & Yaghmorloo, M. Chronic occupational noise exposure: effects on DNA damage, blood pressure, and serum biochemistry. Mutat. Res. 841, 17–22 (2019).

    Article  CAS  Google Scholar 

  92. Schmidt, F. et al. Nighttime aircraft noise impairs endothelial function and increases blood pressure in patients with or at high risk for coronary artery disease. Clin. Res. Cardiol. 104, 23–30 (2015).

    Article  CAS  PubMed  Google Scholar 

  93. Herzog, J. et al. Acute exposure to nocturnal train noise induces endothelial dysfunction and pro-thromboinflammatory changes of the plasma proteome in healthy subjects. Basic. Res. Cardiol. 114, 46 (2019).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  94. Schmidt, F. P. et al. The impact of aircraft noise on vascular and cardiac function in relation to noise event number – a randomized trial. Cardiovasc Res. https://doi.org/10.1093/cvr/cvaa204 (2020).

    Article  PubMed  PubMed Central  Google Scholar 

  95. Kim, A. et al. Effects of self-reported sensitivity and road-traffic noise levels on the immune system. PLoS ONE 12, e0187084 (2017).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  96. Cai, Y. et al. Long-term exposure to road traffic noise, ambient air pollution, and cardiovascular risk factors in the HUNT and lifelines cohorts. Eur. Heart J. 38, 2290–2296 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  97. Thiesse, L. et al. Transportation noise impairs cardiovascular function without altering sleep: The importance of autonomic arousals. Environ. Res. 182, 109086 (2020).

    Article  CAS  PubMed  Google Scholar 

  98. Eze, I. C. et al. Genome-Wide DNA methylation in peripheral blood and long-term exposure to source-specific transportation noise and air pollution: The SAPALDIA study. Environ. Health Perspect. 128, 67003 (2020).

    Article  CAS  PubMed  Google Scholar 

  99. Foraster, M. et al. Exposure to road, railway, and aircraft noise and arterial stiffness in the SAPALDIA study: annual average noise levels and temporal noise characteristics. Environ. Health Perspect. 125, 097004 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  100. Kalsch, H. et al. Are air pollution and traffic noise independently associated with atherosclerosis: the Heinz Nixdorf Recall Study. Eur. Heart J. 35, 853–860 (2014).

    Article  PubMed  Google Scholar 

  101. Hennig, F. et al. Investigation of air pollution and noise on progression of thoracic aortic calcification: results of the Heinz Nixdorf Recall Study. Eur. J. Prev. Cardiol. 27, 965–974 (2020).

    Article  PubMed  Google Scholar 

  102. Atanackovic, D., Brunner-Weinzierl, M. C., Kroger, H., Serke, S. & Deter, H. C. Acute psychological stress simultaneously alters hormone levels, recruitment of lymphocyte subsets, and production of reactive oxygen species. Immunol. Invest. 31, 73–91 (2002).

    Article  CAS  PubMed  Google Scholar 

  103. Herbert, T. B. et al. Cardiovascular reactivity and the course of immune response to an acute psychological stressor. Psychosom. Med. 56, 337–344 (1994).

    Article  CAS  PubMed  Google Scholar 

  104. Altura, B. M., Altura, B. T., Gebrewold, A., Ising, H. & Gunther, T. Noise-induced hypertension and magnesium in rats: relationship to microcirculation and calcium. J. Appl. Physiol. 72, 194–202 (1992).

    Article  CAS  PubMed  Google Scholar 

  105. Wu, C. C., Chen, S. J. & Yen, M. H. Effects of noise on blood pressure and vascular reactivities. Clin. Exp. Pharmacol. Physiol. 19, 833–838 (1992).

    Article  CAS  PubMed  Google Scholar 

  106. Wu, C. C., Chen, S. J. & Yen, M. H. Attenuation of endothelium-dependent relaxation in mesenteric artery during noise-induced hypertension. J. Biomed. Sci. 1, 49–53 (1994).

    Article  CAS  PubMed  Google Scholar 

  107. Lenzi, P. et al. DNA damage associated with ultrastructural alterations in rat myocardium after loud noise exposure. Environ. Health Perspect. 111, 467–471 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  108. Frenzilli, G. et al. Effects of loud noise exposure on DNA integrity in rat adrenal gland. Environ. Health Perspect. 112, 1671–1672 (2004).

    Article  PubMed  PubMed Central  Google Scholar 

  109. Turner, J. G., Parrish, J. L., Hughes, L. F., Toth, L. A. & Caspary, D. M. Hearing in laboratory animals: strain differences and nonauditory effects of noise. Comp. Med. 55, 12–23 (2005).

    CAS  PubMed  Google Scholar 

  110. Baldwin, A. L. & Bell, I. R. Effect of noise on microvascular integrity in laboratory rats. J. Am. Assoc. Lab. Anim. Sci. 46, 58–65 (2007).

    CAS  PubMed  Google Scholar 

  111. Reif, R., Zhi, Z., Dziennis, S., Nuttall, A. L. & Wang, R. K. Changes in cochlear blood flow in mice due to loud sound exposure measured with Doppler optical microangiography and laser Doppler flowmetry. Quant. Imaging Med. Surg. 3, 235–242 (2013).

    PubMed  PubMed Central  Google Scholar 

  112. Fetoni, A. R. et al. The redox protein p66(shc) mediates cochlear vascular dysfunction and transient noise-induced hearing loss. Sci. Rep. 6, 25450 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  113. Lousinha, A. et al. Infrasound induces coronary perivascular fibrosis in rats. Cardiovasc. Pathol. 37, 39–44 (2018).

    Article  PubMed  Google Scholar 

  114. Wang, X., Lai, Y., Zhang, X. & Zhao, J. Effect of low-frequency but high-intensity noise exposure on swine brain blood barrier permeability and its mechanism of injury. Neurosci. Lett. 662, 122–128 (2018).

    Article  CAS  PubMed  Google Scholar 

  115. Kröller-Schön, S. et al. Crucial role for Nox2 and sleep deprivation in aircraft noise-induced vascular and cerebral oxidative stress, inflammation, and gene regulation. Eur. Heart J. 39, 3528–3539 (2018).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  116. Hink, U. et al. Mechanisms underlying endothelial dysfunction in diabetes mellitus. Circ. Res. 88, E14–E22 (2001).

    Article  CAS  PubMed  Google Scholar 

  117. Mollnau, H. et al. Effects of angiotensin II infusion on the expression and function of NAD(P)H oxidase and components of nitric oxide/cGMP signaling. Circ. Res. 90, E58–E65 (2002).

    Article  PubMed  Google Scholar 

  118. Oelze, M. et al. Vasodilator-stimulated phosphoprotein serine 239 phosphorylation as a sensitive monitor of defective nitric Oxide/cGMP signaling and endothelial dysfunction. Circ. Res. 87, 999–1005 (2000).

    Article  CAS  PubMed  Google Scholar 

  119. Münzel, T. et al. Effects of tobacco cigarettes, e-cigarettes, and waterpipe smoking on endothelial function and clinical outcomes. Eur. Heart J. 41, 4057–4070 (2020).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  120. Steven, S. et al. Exacerbation of adverse cardiovascular effects of aircraft noise in an animal model of arterial hypertension. Redox Biol. 34, 101515 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  121. Kvandova, M. et al. Environmental aircraft noise aggravates oxidative DNA damage, granulocyte oxidative burst and nitrate resistance in Ogg1(-/-) mice. Free Radic. Res. 54, 280–292 (2020).

    Article  CAS  PubMed  Google Scholar 

  122. Daiber, A. et al. Oxidative stress and inflammation contribute to traffic noise-induced vascular and cerebral dysfunction via uncoupling of nitric oxide synthases. Redox Biol. 34, 101506 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  123. Campeau, S. et al. Hypothalamic pituitary adrenal axis responses to low-intensity stressors are reduced after voluntary wheel running in rats. J. Neuroendocrinol. 22, 872–888 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  124. Burow, A., Day, H. E. & Campeau, S. A detailed characterization of loud noise stress: Intensity analysis of hypothalamo-pituitary-adrenocortical axis and brain activation. Brain Res. 1062, 63–73 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  125. Eraslan, E., Akyazi, I., Erg, L. E. E. & Matur, E. Noise stress changes mRNA expressions of corticotropin-releasing hormone, its receptors in amygdala, and anxiety-related behaviors. Noise Health 17, 141–147 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  126. Gannouni, N. et al. Qualitative and quantitative assessment of noise at moderate intensities on extra-auditory system in adult rats. Noise Health 15, 406–411 (2013).

    Article  PubMed  Google Scholar 

  127. Said, M. A. & El-Gohary, O. A. Effect of noise stress on cardiovascular system in adult male albino rat: implication of stress hormones, endothelial dysfunction and oxidative stress. Gen. Physiol. Biophys. 35, 371–377 (2016).

    Article  CAS  PubMed  Google Scholar 

  128. Schiavone, S., Jaquet, V., Trabace, L. & Krause, K. H. Severe life stress and oxidative stress in the brain: from animal models to human pathology. Antioxid. Redox Signal. 18, 1475–1490 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  129. Wright, J. W., Dengerink, H. A., Miller, J. M. & Goodwin, P. C. Potential role of angiotensin II in noise-induced increases in inner ear blood flow. Hear. Res. 17, 41–46 (1985).

    Article  CAS  PubMed  Google Scholar 

  130. Ye, S., Zhong, H., Yanamadala, S. & Campese, V. M. Oxidative stress mediates the stimulation of sympathetic nerve activity in the phenol renal injury model of hypertension. Hypertension 48, 309–315 (2006).

    Article  CAS  PubMed  Google Scholar 

  131. Lob, H. E. et al. Induction of hypertension and peripheral inflammation by reduction of extracellular superoxide dismutase in the central nervous system. Hypertension 55, 277–283 (2010).

    Article  CAS  PubMed  Google Scholar 

  132. Neri, M. et al. Correlation between cardiac oxidative stress and myocardial pathology due to acute and chronic norepinephrine administration in rats. J. Cell. Mol. Med. 11, 156–170 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  133. Lee, H. Y. et al. The ethanol extract of Aquilariae Lignum ameliorates hippocampal oxidative stress in a repeated restraint stress mouse model. BMC Complement. Altern. Med. 17, 397 (2017).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  134. Grande, M. T. et al. Increased oxidative stress, the renin-angiotensin system, and sympathetic overactivation induce hypertension in kidney androgen-regulated protein transgenic mice. Free Radic. Biol. Med. 51, 1831–1841 (2011).

    Article  CAS  PubMed  Google Scholar 

  135. Rajagopalan, S. et al. Angiotensin II-mediated hypertension in the rat increases vascular superoxide production via membrane NADH/NADPH oxidase activation. Contribution to alterations of vasomotor tone. J. Clin. Invest. 97, 1916–1923 (1996).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  136. Mollnau, H. et al. Mechanisms of increased vascular superoxide production in an experimental model of idiopathic dilated cardiomyopathy. Arterioscler. Thromb. Vasc. Biol. 25, 2554–2559 (2005).

    Article  CAS  PubMed  Google Scholar 

  137. Chen, D. D., Dong, Y. G., Yuan, H. & Chen, A. F. Endothelin 1 activation of endothelin A receptor/NADPH oxidase pathway and diminished antioxidants critically contribute to endothelial progenitor cell reduction and dysfunction in salt-sensitive hypertension. Hypertension 59, 1037–1043 (2012).

    Article  CAS  PubMed  Google Scholar 

  138. Rajagopalan, S. et al. Role for endothelin-1 in angiotensin II-mediated hypertension. Hypertension 30, 29–34 (1997).

    Article  CAS  PubMed  Google Scholar 

  139. Jones, R. M. & Neish, A. S. Redox signaling mediated by the gut microbiota. Free Radic. Biol. Med. 105, 41–47 (2017).

    Article  CAS  PubMed  Google Scholar 

  140. Campbell, E. L. & Colgan, S. P. Control and dysregulation of redox signalling in the gastrointestinal tract. Nat. Rev. Gastroenterol. Hepatol. 16, 106–120 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  141. Cryan, J. F. & Dinan, T. G. Mind-altering microorganisms: the impact of the gut microbiota on brain and behaviour. Nat. Rev. Neurosci. 13, 701–712 (2012).

    Article  CAS  PubMed  Google Scholar 

  142. Collins, S. M., Surette, M. & Bercik, P. The interplay between the intestinal microbiota and the brain. Nat. Rev. Microbiol. 10, 735–742 (2012).

    Article  CAS  PubMed  Google Scholar 

  143. Cui, B. et al. Effects of chronic noise exposure on the microbiome-gut-brain axis in senescence-accelerated prone mice: implications for Alzheimer’s disease. J. Neuroinflammation 15, 190 (2018).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  144. Cui, B., Gai, Z., She, X., Wang, R. & Xi, Z. Effects of chronic noise on glucose metabolism and gut microbiota-host inflammatory homeostasis in rats. Sci. Rep. 6, 36693 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  145. Zymantiene, J. et al. Effects of long-term construction noise on health of adult female Wistar rats. Pol. J. Vet. Sci. 20, 155–165 (2017).

    Article  CAS  PubMed  Google Scholar 

  146. Hadizadeh, M., Hamidi, G. A. & Salami, M. Probiotic supplementation improves the cognitive function and the anxiety-like behaviors in the stressed rats. Iran. J. Basic. Med. Sci. 22, 506–514 (2019).

    PubMed  PubMed Central  Google Scholar 

  147. Karl, J. P. et al. Effects of psychological, environmental and physical stressors on the gut microbiota. Front. Microbiol. 9, 2013 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  148. Crnko, S., Du Pre, B. C., Sluijter, J. P. G. & Van Laake, L. W. Circadian rhythms and the molecular clock in cardiovascular biology and disease. Nat. Rev. Cardiol. 16, 437–447 (2019).

    Article  PubMed  Google Scholar 

  149. Park, J. S. et al. Identification of a circadian clock in the inferior colliculus and its dysregulation by noise exposure. J. Neurosci. 36, 5509–5519 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  150. Putker, M. & O’Neill, J. S. Reciprocal control of the circadian clock and cellular redox state - a critical appraisal. Mol. Cell 39, 6–19 (2016).

    Article  CAS  Google Scholar 

  151. Li, H. et al. Influence of mental stress and environmental toxins on circadian clocks: Implications for redox regulation of the heart and cardioprotection. Br. J. Pharmacol. 177, 5393–5412 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  152. Schmalen, I. et al. Interaction of circadian clock proteins CRY1 and PER2 is modulated by zinc binding and disulfide bond formation. Cell 157, 1203–1215 (2014).

    Article  CAS  PubMed  Google Scholar 

  153. Ordovas, J. M. & Smith, C. E. Epigenetics and cardiovascular disease. Nat. Rev. Cardiol. 7, 510–519 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  154. Kuznetsova, T., Prange, K. H. M., Glass, C. K. & de Winther, M. P. J. Transcriptional and epigenetic regulation of macrophages in atherosclerosis. Nat. Rev. Cardiol. 17, 216–228 (2020).

    Article  CAS  PubMed  Google Scholar 

  155. Miguel, V. et al. The role of MicroRNAs in environmental risk factors, noise-induced hearing loss, and mental stress. Antioxid. Redox Signal. 28, 773–796 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  156. Meerson, A. et al. Changes in brain microRNAs contribute to cholinergic stress reactions. J. Mol. Neurosci. 40, 47–55 (2010).

    Article  CAS  PubMed  Google Scholar 

  157. Greco, C. M. & Condorelli, G. Epigenetic modifications and noncoding RNAs in cardiac hypertrophy and failure. Nat. Rev. Cardiol. 12, 488–497 (2015).

    Article  CAS  PubMed  Google Scholar 

  158. Guo, L. et al. Effects of environmental noise exposure on DNA methylation in the brain and metabolic health. Environ. Res. 153, 73–82 (2017).

    Article  CAS  PubMed  Google Scholar 

  159. Sainani, K. Taking on the exposome - bringing bioinformatics tools to the environmental side of the health equation. Biomed. Comput. Rev. 2016, 14–21 (2016).

    Google Scholar 

  160. Héritier, H. et al. A systematic analysis of mutual effects of transportation noise and air pollution exposure on myocardial infarction mortality: a nationwide cohort study in Switzerland. Eur. Heart J. 40, 598–603 (2019).

    Article  PubMed  Google Scholar 

  161. Sorensen, M. et al. Combined effects of road traffic noise and ambient air pollution in relation to risk for stroke? Environ. Res. 133, 49–55 (2014).

    Article  PubMed  CAS  Google Scholar 

  162. Babisch, W. et al. Associations between traffic noise, particulate air pollution, hypertension, and isolated systolic hypertension in adults: the KORA study. Environ. Health Perspect. 122, 492–498 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  163. Vienneau, D. et al. Years of life lost and morbidity cases attributable to transportation noise and air pollution: A comparative health risk assessment for Switzerland in 2010. Int. J. Hyg. Env. Health 218, 514–521 (2015).

    Article  Google Scholar 

  164. Münzel, T. et al. Effects of gaseous and solid constituents of air pollution on endothelial function. Eur. Heart J. 39, 3543–3550 (2018).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  165. Daiber, A. et al. The “exposome” concept - how environmental risk factors influence cardiovascular health. Acta Biochim. Pol. 66, 269–283 (2019).

    CAS  PubMed  Google Scholar 

  166. Daiber, A. & Münzel, T. Special Issue “Impact of environmental pollution and stress on redox signaling and oxidative stress pathways”. Redox Biol. 37, 101621 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  167. Münzel, T. & Daiber, A. Environmental stressors and their impact on health and disease with focus on oxidative stress. Antioxid. Redox Signal. 28, 735–740 (2018).

    Article  PubMed  CAS  Google Scholar 

  168. European Commission. Science for environment policy. IN-DEPTH REPORT 13. Links between noise and air pollution and socioeconomic status https://ec.europa.eu/environment/integration/research/newsalert/pdf/air_noise_pollution_socioeconomic_status_links_IR13_en.pdf (2016).

  169. Knuuti, J. et al. 2019 ESC Guidelines for the diagnosis and management of chronic coronary syndromes. Eur. Heart J. 41, 407–477 (2020).

    Article  PubMed  Google Scholar 

  170. Harder, S. & Klinkhardt, U. Thrombolytics: drug interactions of clinical significance. Drug Saf. 23, 391–399 (2000).

    Article  CAS  PubMed  Google Scholar 

  171. Dzhambov, A. M. & Lercher, P. Road traffic noise exposure and depression/anxiety: an updated systematic review and meta-analysis. Int. J. Environ. Res. Public Health 16, 4134 (2019).

    Article  PubMed Central  Google Scholar 

  172. T. Münzel, et al. Environmental stressors and cardio-metabolic disease: part I-epidemiologic evidence supporting a role for noise and air pollution and effects of mitigation strategies. Eur. Heart J. 38, 550–556 (2017).

    PubMed  Google Scholar 

  173. Münzel, T., Gori, T., Babisch, W. & Basner, M. Cardiovascular effects of environmental noise exposure. Eur. Heart J. 35, 829–836 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  174. Münzel, T. Endothelial dysfunction: pathophysiology, diagnosis and prognosis. Dtsch. Med. Wochenschr. 133, 2465–2470 (2008).

    Article  PubMed  CAS  Google Scholar 

  175. Vrijheid, M. The exposome: a new paradigm to study the impact of environment on health. Thorax 69, 876–878 (2014).

    Article  PubMed  Google Scholar 

  176. European Commission https://ec.europa.eu/info/events/launch-event-european-human-exposome-network-2020_en (2020).

  177. Koay, G., Heffner, R. & Heffner, H. Behavioral audiograms of homozygous med(J) mutant mice with sodium channel deficiency and unaffected controls. Hear. Res. 171, 111–118 (2002).

    Article  CAS  PubMed  Google Scholar 

  178. Heffner, H. E., Heffner, R. S., Contos, C. & Ott, T. Audiogram of the hooded Norway rat. Hear. Res. 73, 244–247 (1994).

    Article  CAS  PubMed  Google Scholar 

  179. Martin, G. K., Lonsbury-Martin, B. L. & Kimm, J. A rabbit preparation for neuro-behavioral auditory research. Hear. Res. 2, 65–78 (1980).

    Article  CAS  PubMed  Google Scholar 

  180. Kojima, S. Comparison of auditory functions in the chimpanzee and human. Folia Primatol. 55, 62–72 (1990).

    Article  CAS  Google Scholar 

  181. Jackson, L. L., Heffner, R. S. & Heffner, H. E. Free-field audiogram of the Japanese macaque (Macaca fuscata). J. Acoust. Soc. Am. 106, 3017–3023 (1999).

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We gratefully acknowledge financial support in the form of vascular biology research grants from the Foundation Heart of Mainz (to T.M. and A.D.) and from the Boehringer Ingelheim Foundation for the collaborative research group ‘Novel and neglected cardiovascular risk factors: molecular mechanisms and therapeutic implications’ to study the effects of environmental risk factors on vascular function and oxidative stress. T.M. is a principal investigator of the DZHK (German Center for Cardiovascular Research), Partner Site Rhine-Main, Mainz, Germany. We also thank M. Neuser (University Medical Center Mainz, Germany) for her expert graphical assistance with the figures before submission.

Review criteria

For the mechanistic discussion of human data, we have mainly considered translational human studies from the past 20 years with a focus on the cardiovascular system or on stress, inflammatory and oxidative pathways related to cardiovascular disease. Experimental research on the cardiovascular or neuropsychological effects of transportation noise in humans is scarce. For the discussion on animal models, we focus on studies from the past 20 years that did not relate only to hearing loss. Research on the cardiovascular effects of non-auditory noise in animals is very rare. For the period before 2000, we selected only the landmark studies.

Author information

Authors and Affiliations

  1. Department of Cardiology, Cardiology I, University Medical Center of the Johannes Gutenberg-University, Mainz, Germany

    Thomas Münzel & Andreas Daiber

  2. German Center for Cardiovascular Research (DZHK), Partner Site Rhine-Main, Mainz, Germany

    Thomas Münzel & Andreas Daiber

  3. Danish Cancer Society, Copenhagen, Denmark

    Mette Sørensen

  4. Department of Natural Science and Environment, Roskilde University, Roskilde, Denmark

    Mette Sørensen

Authors
  1. Thomas Münzel
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Mette Sørensen
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Andreas Daiber
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

The authors contributed substantially to all aspects of the article.

Corresponding author

Correspondence to Thomas Münzel.

Ethics declarations

Competing interests

The authors declare no competing interests.

Additional information

Peer review information

Nature Reviews Cardiology thanks M. Röösli and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Münzel, T., Sørensen, M. & Daiber, A. Transportation noise pollution and cardiovascular disease. Nat Rev Cardiol 18, 619–636 (2021). https://doi.org/10.1038/s41569-021-00532-5

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41569-021-00532-5

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing