Skip to content
2000
image of Elevated Perspectives: Unraveling Cardiovascular Dynamics in High-Altitude Realms

Abstract

High-altitude regions pose distinctive challenges for cardiovascular health because of decreased oxygen levels, reduced barometric pressure, and colder temperatures. Approximately 82 million people live above 2400 meters, while over 100 million people visit these heights annually. Individuals ascending rapidly or those with pre-existing cardiovascular conditions are particularly vulnerable to altitude-related illnesses, including Acute Mountain Sickness (AMS) and Chronic Mountain Sickness (CMS). The cardiovascular system struggles to adapt to hypoxic stress, which can lead to arrhythmias, systemic hypertension, and right ventricular failure. Pathophysiologically, high-altitude exposure triggers immediate increases in cardiac output and heart rate, often due to enhanced sympathetic activity. Over time, acclimatisation involves complex changes, such as reduced stroke volume and increased blood volume. The pulmonary vasculature also undergoes significant alterations, including hypoxic pulmonary vasoconstriction and vascular remodelling, contributing to conditions, like pulmonary hypertension and high-altitude pulmonary edema. Genetic adaptations in populations living at high altitudes, such as gene variations linked to hypoxia response, further influence these physiological processes.

Regarding cardiovascular disease risk, stable coronary artery disease patients generally do not face significant adverse outcomes at altitudes up to 3500 meters. However, those with unstable angina or recent cardiac interventions should avoid high-altitude exposure to prevent exacerbation. Remarkably, high-altitude living correlates with reduced cardiovascular mortality rates, possibly due to improved air quality and hypoxia-induced adaptations. Additionally, there is a higher incidence of congenital heart disease among children born at high altitudes, highlighting the profound impact of hypoxia on heart development. Understanding these dynamics is crucial for managing risks and improving health outcomes in high-altitude environments.

Loading

Article metrics loading...

/content/journals/ccr/10.2174/011573403X308818241030051249
2024-11-05
2025-01-18
Loading full text...

Full text loading...

References

  1. Tremblay J.C. Ainslie P.N. Global and country-level estimates of human population at high altitude. Proc. Natl. Acad. Sci. USA 2021 118 18 e2102463118 10.1073/pnas.2102463118 33903258
    [Google Scholar]
  2. Mallet R.T. Burtscher J. Richalet J.P. Millet G.P. Burtscher M. Impact of high altitude on cardiovascular health: Current perspectives. Vasc. Health Risk Manag. 2021 17 317 335 10.2147/VHRM.S294121 34135590
    [Google Scholar]
  3. Burtscher M. Gatterer H. Burtscher J. Mairbäurl H. Extreme terrestrial environments: Life in thermal stress and hypoxia. A narrative review. Front. Physiol. 2018 9 572 10.3389/fphys.2018.00572 29867589
    [Google Scholar]
  4. Berendsen R.R. Bärtsch P. Basnyat B. Strengthening altitude knowledge: A delphi study to define minimum knowledge of altitude illness for laypersons traveling to high altitude. High Alt. Med. Biol. 2022 23 4 330 337 10.1089/ham.2022.0083 36201281
    [Google Scholar]
  5. Wu T.Y. Ding S.Q. Liu J.L. Jia J.H. Chai Z.C. Dai R.C. Who are more at risk for acute mountain sickness: A prospective study in Qinghai-Tibet railroad construction workers on Mt. Tanggula. Chin. Med. J. (Engl.) 2012 125 8 1393 1400 22613641
    [Google Scholar]
  6. Hurtado A. Escudero E. Pando J. Sharma S. Johnson R.J. Cardiovascular and renal effects of chronic exposure to high altitude. Nephrol. Dial. Transplant. 2012 27 Suppl. 4 iv11 iv16 10.1093/ndt/gfs427 23258804
    [Google Scholar]
  7. Crawford J.E. Amaru R. Song J. Natural selection on genes related to cardiovascular health in high-altitude adapted andeans. Am. J. Hum. Genet. 2017 101 5 752 767 10.1016/j.ajhg.2017.09.023 29100088
    [Google Scholar]
  8. Penaloza D. Arias-Stella J. The heart and pulmonary circulation at high altitudes: Healthy highlanders and chronic mountain sickness. Circulation 2007 115 9 1132 1146 10.1161/CIRCULATIONAHA.106.624544 17339571
    [Google Scholar]
  9. Huang L. 2022; Editorial: Cardiovascular responses and diseases at high altitude. Front. Cardiovasc. Med. 9 1024263 10.3389/fcvm.2022.1024263
    [Google Scholar]
  10. Burtscher M. Effects of living at higher altitudes on mortality: A narrative review. Aging Dis 2013 5 4 278 280 10.14336/ad.2014.0500274
    [Google Scholar]
  11. Zittermann A. Gummert J.F. Sun, vitamin D, and cardiovascular disease. J. Photochem. Photobiol. B 2010 101 2 124 129 10.1016/j.jphotobiol.2010.01.006 20138781
    [Google Scholar]
  12. Riley C.J. Gavin M. Physiological changes to the cardiovascular system at high altitude and its effects on cardiovascular disease. High Alt. Med. Biol. 2017 18 2 102 113 10.1089/ham.2016.0112 28294639
    [Google Scholar]
  13. Luks AM Hackett PH Medical conditions and high-altitude travel N Engl J Med 386 4 364 373 10.1056/NEJMra2104829 35081281 2022
    [Google Scholar]
  14. Wong B.W. Marsch E. Treps L. Baes M. Carmeliet P. Endothelial cell metabolism in health and disease: Impact of hypoxia. EMBO J. 2017 36 15 2187 2203 10.15252/embj.201696150 28637793
    [Google Scholar]
  15. Spiekerkoetter E. Kawut S.M. de Jesus Perez V.A. New and emerging therapies for pulmonary arterial hypertension. Annu. Rev. Med. 2019 70 1 45 59 10.1146/annurev‑med‑041717‑085955 30216732
    [Google Scholar]
  16. Sydykov A. Mamazhakypov A. Maripov A. Pulmonary hypertension in acute and chronic high altitude maladaptation disorders. Int. J. Environ. Res. Public Health 2021 18 4 1692 10.3390/ijerph18041692 33578749
    [Google Scholar]
  17. Firth A.L. Won J.Y. Park W.S. Regulation of ca(2+) signaling in pulmonary hypertension. Korean J. Physiol. Pharmacol. 2013 17 1 1 8 10.4196/kjpp.2013.17.1.1 23439762
    [Google Scholar]
  18. Wang Y.X. Zheng Y.M. Role of ROS signaling in differential hypoxic Ca2+ and contractile responses in pulmonary and systemic vascular smooth muscle cells. Respir. Physiol. Neurobiol. 2010 174 3 192 200 10.1016/j.resp.2010.08.008 20713188
    [Google Scholar]
  19. Rao M. Li J. Qin J. Left ventricular function during acute high-altitude exposure in a large group of healthy young Chinese men. PLoS One 2015 10 1 e0116936 10.1371/journal.pone.0116936 25629435
    [Google Scholar]
  20. Dhar P. Sharma V.K. Hota K.B. Autonomic cardiovascular responses in acclimatized lowlanders on prolonged stay at high altitude: A longitudinal follow up study. PLoS One 2014 9 1 e84274 10.1371/journal.pone.0084274 24404157
    [Google Scholar]
  21. Schmitz-Spanke S. Schipke J.D. Potential role of endothelin-1 and endothelin antagonists in cardiovascular diseases. Basic Res. Cardiol. 2000 95 4 290 298 10.1007/s003950070048 11005584
    [Google Scholar]
  22. Kohan D.E. Rossi N.F. Inscho E.W. Pollock D.M. Regulation of blood pressure and salt homeostasis by endothelin. Physiol. Rev. 2011 91 1 1 77 10.1152/physrev.00060.2009 21248162
    [Google Scholar]
  23. Rauen T. Hedrich C.M. Tenbrock K. Tsokos G.C. cAMP responsive element modulator: A critical regulator of cytokine production. Trends Mol. Med. 2013 19 4 262 269 10.1016/j.molmed.2013.02.001 23491535
    [Google Scholar]
  24. Foulquier S. Daskalopoulos E.P. Lluri G. Hermans K.C.M. Deb A. Blankesteijn W.M. WNT signaling in cardiac and vascular disease. Pharmacol. Rev. 2018 70 1 68 141 10.1124/pr.117.013896 29247129
    [Google Scholar]
  25. Lang M. Faini A. Caravita S. Blood pressure response to six-minute walk test in hypertensive subjects exposed to high altitude: Effects of antihypertensive combination treatment. Int. J. Cardiol. 2016 219 27 32 10.1016/j.ijcard.2016.04.169 27261929
    [Google Scholar]
  26. Parati G. Agostoni P. Basnyat B. Clinical recommendations for high altitude exposure of individuals with pre-existing cardiovascular conditions. Eur. Heart J. 2018 39 17 1546 1554 10.1093/eurheartj/ehx720 29340578
    [Google Scholar]
  27. Milledge J.S. West J.B. Schoene R.B. High Altitude Medicine and Physiology. Boca Raton CRC Press 2007 10.1201/b13371
    [Google Scholar]
  28. Lambert M. Capuano V. Olschewski A. Ion channels in pulmonary hypertension: A therapeutic interest? Int. J. Mol. Sci. 2018 19 10 3162 10.3390/ijms19103162 30322215
    [Google Scholar]
  29. Storz JF High-altitude adaptation: Mechanistic insights from integrated 118 genomics and physiology Mol Biol Evol 2021 38 7 2677 2691 10.1093/molbev/msab064 33751123
    [Google Scholar]
  30. Beall C.M. Cavalleri G.L. Deng L. Natural selection on EPAS1 (HIF2α) associated with low hemoglobin concentration in Tibetan highlanders. Proc. Natl. Acad. Sci. USA 2010 107 25 11459 11464 10.1073/pnas.1002443107 20534544
    [Google Scholar]
  31. Roach R.C. Hackett P.H. Oelz O. Lake Louise AMS Score Consensus Committee The 2018 Lake Louise acute mountain sickness score. High Alt. Med. Biol. 2018 19 1 4 6 10.1089/ham.2017.0164 29583031
    [Google Scholar]
  32. Brito J. Siqués P. León-Velarde F. De La Cruz J.J. López V. Herruzo R. Chronic intermittent hypoxia at high altitude exposure for over 12 years: Assessment of hematological, cardiovascular, and renal effects. High Alt. Med. Biol. 2007 8 3 236 244 10.1089/ham.2007.8310 17824824
    [Google Scholar]
  33. Imray C. Wright A. Subudhi A. Roach R. Acute mountain sickness: Pathophysiology, prevention, and treatment. Prog. Cardiovasc. Dis. 2010 52 6 467 484 10.1016/j.pcad.2010.02.003 20417340
    [Google Scholar]
  34. Pena E. El Alam S. Siques P. Brito J. Oxidative stress and diseases associated with high-altitude exposure. Antioxidants 2022 11 2 267 10.3390/antiox11020267 35204150
    [Google Scholar]
  35. León-Velarde F. Maggiorini M. Reeves J.T. Consensus statement on chronic and subacute high altitude diseases. High Alt. Med. Biol. 6 2 147 157 10.1089/ham.2005.6.147
    [Google Scholar]
  36. Brito J. Siques P. Pena E. Long‐term chronic intermittent hypoxia: A particular form of chronic high‐altitude pulmonary hypertension. Pulm. Circ. 2020 10 S1 Suppl. 5 12 10.1177/2045894020934625 33110494
    [Google Scholar]
  37. Beall C.M. Adaptation to high altitude: Phenotypes and genotypes. Annu. Rev. Anthropol. 2014 43 1 251 272 10.1146/annurev‑anthro‑102313‑030000
    [Google Scholar]
  38. Hasan A. Relationship of high altitude and congenital heart disease. Indian Heart J. 2016 68 1 9 12 10.1016/j.ihj.2015.12.015 26896259
    [Google Scholar]
  39. Dehnert C. Bärtsch P. Can patients with coronary heart disease go to high altitude? High Alt. Med. Biol. 2010 11 3 183 188 10.1089/ham.2010.1024 20919884
    [Google Scholar]
  40. Macovei L. Macovei C.M. Macovei D.C. Coronary syndromes and high-altitude exposure - A comprehensive review. Diagnostics (Basel) 2023 13 7 1317 10.3390/diagnostics13071317 37046535
    [Google Scholar]
  41. Faeh D. Gutzwiller F. Bopp M. Group S.N.C.S. Lower mortality from coronary heart disease and stroke at higher altitudes in Switzerland. Circulation 2009 120 6 495 501 10.1161/CIRCULATIONAHA.108.819250 19635973
    [Google Scholar]
  42. Burtscher M. Lower mortality rates in those living at moderate altitude. Aging (Albany NY) 2016 8 10 2603 2604 10.18632/aging.101057 27705903
    [Google Scholar]
  43. Li J.J. Liu Y. Xie S.Y. Newborn screening for congenital heart disease using echocardiography and follow-up at high altitude in China. Int. J. Cardiol. 2019 274 106 112 10.1016/j.ijcard.2018.08.102 30195837
    [Google Scholar]
  44. Vallecilla C. Khiabani R.H. Sandoval N. Fogel M. Briceño J.C. Yoganathan A.P. Effect of high altitude exposure on the hemodynamics of the bidirectional Glenn physiology: Modeling incremented pulmonary vascular resistance and heart rate. J. Biomech. 2014 47 8 1846 1852 10.1016/j.jbiomech.2014.03.021 24755120
    [Google Scholar]
  45. He S. Zhao F. Liu X. Prevalence of congenital heart disease among school children in Qinghai Province. BMC Pediatr. 2022 22 1 331 10.1186/s12887‑022‑03364‑5 35672682
    [Google Scholar]
  46. Zheng J.Y. Qiu Y.G. Li D.T. Prevalence and composition of CHD at different altitudes in Tibet: A cross-sectional study. Cardiol. Young 2017 27 8 1497 1503 10.1017/S1047951117000567 28393753
    [Google Scholar]
  47. Zheng J.Y. Tian H.T. Zhu Z.M. Prevalence of symptomatic congenital heart disease in Tibetan school children. Am. J. Cardiol. 2013 112 9 1468 1470 10.1016/j.amjcard.2013.07.028 24012023
    [Google Scholar]
  48. Mikołajczak K. Czerwińska K. Pilecki W. Poręba R. Gać P. Poręba M. The impact of temporary stay at high altitude on the circulatory system. J. Clin. Med. 2021 10 8 1622 10.3390/jcm10081622 33921196
    [Google Scholar]
  49. Kujaník S. Snincák M. Vokál’ J. Podracký J. Koval’ J. Periodicity of arrhythmias in healthy elderly men at the moderate altitude. Physiol. Res. 2000 49 2 285 287 10984096
    [Google Scholar]
  50. Díaz LA Chronic cor pulmonale: Clinical epidemiological aspects in high altitude adults Rev Per Cardiol 2009 35 1 44 52
    [Google Scholar]
  51. Hernández S.P. Lázaro S.M. Alcalá J.E. Macías C.B. Cor pulmonale. Medicine (Baltimore) 2017 12 35 2116 2126
    [Google Scholar]
  52. Waligóra M. Tyrka A. Miszalski-Jamka T. Urbańczyk-Zawadzka M. Podolec P. Kopeć G. Right atrium enlargement predicts clinically significant supraventricular arrhythmia in patients with pulmonary arterial hypertension. Heart Lung 2018 47 3 237 242 10.1016/j.hrtlng.2018.01.004 29454666
    [Google Scholar]
  53. Smith B. Genuardi M.V. Koczo A. Atrial arrhythmias are associated with increased mortality in pulmonary arterial hypertension. Pulm. Circ. 2018 8 3 1 9 10.1177/2045894018790316 29969045
    [Google Scholar]
  54. Naeije R. Dedobbeleer C. Pulmonary hypertension and the right ventricle in hypoxia. Exp. Physiol. 2013 98 8 1247 1256 10.1113/expphysiol.2012.069112 23625956
    [Google Scholar]
  55. Kaya A. Bayramoğlu A. Bektaş O. The prognostic value of altitude in patients with heart failure with reduced ejection fraction. Anatol. J. Cardiol. 2019 22 6 300 308 10.14744/AnatolJCardiol.2019.81535 31789616
    [Google Scholar]
  56. Agostoni P. Cattadori G. Guazzi M. Effects of simulated altitude-induced hypoxia on exercise capacity in patients with chronic heart failure. Am. J. Med. 2000 109 6 450 455 10.1016/S0002‑9343(00)00532‑5 11042233
    [Google Scholar]
  57. Kim J. Franco A.D. Seoane T. Right ventricular dysfunction impairs effort tolerance independent of left ventricular function among patients undergoing exercise stress myocardial perfusion imaging. Circ. Cardiovasc. Imaging 2016 9 11 e005115 10.1161/CIRCIMAGING.116.005115
    [Google Scholar]
  58. Sonaglioni A. Caminati A. Nicolosi G.L. Lombardo M. Harari S. Influence of chest wall conformation on spirometry parameters and outcome in mild-to-moderate idiopathic pulmonary fibrosis. Intern. Emerg. Med. 2022 17 4 989 999 10.1007/s11739‑021‑02889‑4 35059991
    [Google Scholar]
/content/journals/ccr/10.2174/011573403X308818241030051249
Loading
/content/journals/ccr/10.2174/011573403X308818241030051249
Loading

Data & Media loading...

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test