La gran altitud es un ambiente extremo que impone fuertes desafíos para el ser humano que se expone por actividades laborales, recreativas o que vive en esta condición. La exposición a hipoxia hipobárica genera una serie de adaptaciones fisiológicas dadas por el entorno geográfico y las condiciones ambientales extremas asociadas. Estas respuestas de aclimatación pueden ser heterogéneas, siendo el resultado de cambios evolutivos y de la existencia de comorbilidades o patologías asociadas. En este contexto, el objetivo de este artículo es identificar la evidencia científica acerca de los efectos de la altitud geográfica en la presión arterial, desde los aspectos fisiológicos a las implicaciones clínicas en reposo y ejercicio. Asimismo, se abordan los mecanismos subyacentes y las posibles implicaciones clínicas en hipoxia aguda e hipoxia intermitente crónica.

Authors: Morin Lang[1], Grzegorz Bilo[2,3], Sergio Caravita[2,4], Gianfranco Parati[2,3]

Affiliation:
[1] Department of Rehabilitation Sciences and Human Movement, Faculty of Health Sciences, University of Antofagasta, Antofagasta, Chile
[2] Istituto Auxologico Italiano, Istituto di Ricovero e Cura a Carattere Scientifico, Department of Cardiovascular, Neural and Metabolic Sciences, San Luca Hospital, Milan, Italy
[3] Department of Medicine and Surgery, University of Milano-Bicocca, Milan, Italy
[4] Department of Management, Information and Production Engineering, University of Bergamo, Dalmine, Italy

E-mail: morin.lang@uantof.cl

Author address:
[1] Avenida Angamos 601
Antofagasta, Chile

Citation: Lang M, Bilo G, Caravita S, Parati G. Blood pressure and high altitude: physiological response and clinical management. Medwave 2021;21(4):e8194 doi: 10.5867/medwave.2021.04.8194

Submission date: 11/12/2020

Acceptance date: 19/4/2021

Publication date: 13/5/2021

Origin: Not commissioned

Type of review: Externally peer-reviewed by three reviewers, double-blind

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1. Bärtsch P, Gibbs JS. Effect of altitude on the heart and the lungs. Circulation. 2007 Nov 6;116(19):2191-202. | CrossRef | PubMed |
2. Parati G, Agostoni P, Basnyat B, Bilo G, Brugger H, Coca A, et al. Clinical recommendations for high altitude exposure of individuals with pre-existing cardiovascular conditions: A joint statement by the European Society of Cardiology, the Council on Hypertension of the European Society of Cardiology, the European Society of Hypertension, the International Society of Mountain Medicine, the Italian Society of Hypertension and the Italian Society of Mountain Medicine. Eur Heart J. 2018 May 1;39(17):1546-1554. | CrossRef | PubMed |
3. Williams B, Mancia G, Spiering W, Agabiti Rosei E, Azizi M, Burnier M, et al. 2018 Practice Guidelines for the management of arterial hypertension of the European Society of Cardiology and the European Society of Hypertension. Blood Press. 2018 Dec;27(6):314-340. | CrossRef | PubMed |
4. Keyes LE, Mather L, Duke C, Regmi N, Phelan B, Pant S, et al. Older age, chronic medical conditions and polypharmacy in Himalayan trekkers in Nepal: an epidemiologic survey and case series. J Travel Med. 2016 Aug 8;23(6):taw052. | CrossRef | PubMed |
5. Higgins JP, Tuttle T, Higgins JA. Altitude and the heart: is going high safe for your cardiac patient? Am Heart J. 2010 Jan;159(1):25-32. | CrossRef | PubMed |
6. Hansen J, Sander M. Sympathetic neural overactivity in healthy humans after prolonged exposure to hypobaric hypoxia. J Physiol. 2003 Feb 1;546(Pt 3):921-9. | CrossRef | PubMed |
7. Bilo G, Caldara G, Styczkiewicz K, Revera M, Lombardi C, Giglio A, et al. Effects of selective and nonselective beta-blockade on 24-h ambulatory blood pressure under hypobaric hypoxia at altitude. J Hypertens. 2011 Feb;29(2):380-7. | CrossRef | PubMed |
8. Wolfel EE, Selland MA, Mazzeo RS, Reeves JT. Systemic hypertension at 4,300 m is related to sympathoadrenal activity. J Appl Physiol (1985). 1994 Apr;76(4):1643-50. | CrossRef | PubMed |
9. Veglio M, Maule S, Cametti G, Cogo A, Lussiana L, Madrigale G, et al. The effects of exposure to moderate altitude on cardiovascular autonomic function in normal subjects. Clin Auton Res. 1999 Jun;9(3):123-7. | CrossRef | PubMed |
10. Parati G, Bilo G, Faini A, Bilo B, Revera M, Giuliano A, Lombardi C, et al. Changes in 24 h ambulatory blood pressure and effects of angiotensin II receptor blockade during acute and prolonged high-altitude exposure: a randomized clinical trial. Eur Heart J. 2014 Nov 21;35(44):3113-22. | CrossRef | PubMed |
11. Torlasco C, Bilo G, Giuliano A, Soranna D, Ravaro S, Oliverio G, et al. Effects of acute exposure to moderate altitude on blood pressure and sleep breathing patterns. Int J Cardiol. 2020 Feb 15;301:173-179. | CrossRef | PubMed |
12. Bilo G, Villafuerte FC, Faini A, Anza-Ramírez C, Revera M, Giuliano A, et al. Ambulatory blood pressure in untreated and treated hypertensive patients at high altitude: the High Altitude Cardiovascular Research-Andes study. Hypertension. 2015 Jun;65(6):1266-72. | CrossRef | PubMed |
13. Halliwill JR, Minson CT. Effect of hypoxia on arterial baroreflex control of heart rate and muscle sympathetic nerve activity in humans. J Appl Physiol (1985). 2002 Sep;93(3):857-64. | CrossRef | PubMed |
14. Bilo G, Revera M, Bussotti M, Bonacina D, Styczkiewicz K, Caldara G, et al. Effects of slow deep breathing at high altitude on oxygen saturation, pulmonary and systemic hemodynamics. PLoS One. 2012;7(11):e49074. | CrossRef | PubMed |
15. Siqués P, Brito J, Banegas JR, León-Velarde F, de la Cruz-Troca JJ, López V, et al. Blood pressure responses in young adults first exposed to high altitude for 12 months at 3550 m. High Alt Med Biol. 2009 Winter;10(4):329-35. | CrossRef | PubMed |
16. Aryal N, Weatherall M, Bhatta YK, Mann S. Blood Pressure and Hypertension in Adults Permanently Living at High Altitude: A Systematic Review and Meta-Analysis. High Alt Med Biol. 2016 Sep;17(3):185-193. | CrossRef | PubMed |
17. Bilo G, Acone L, Anza-Ramírez C, Macarlupú JL, Soranna D, Zambon A, et al. Office and Ambulatory Arterial Hypertension in Highlanders: HIGHCARE-ANDES Highlanders Study. Hypertension. 2020 Dec;76(6):1962-1970. | CrossRef | PubMed |
18. Cheong HI, Janocha AJ, Monocello LT, Garchar AC, Gebremedhin A, Erzurum SC, et al. Alternative hematological and vascular adaptive responses to high-altitude hypoxia in East African highlanders. Am J Physiol Lung Cell Mol Physiol. 2017 Feb 1;312(2):L172-L177. | CrossRef | PubMed |
19. Insalaco G, Romano S, Salvaggio A, Braghiroli A, Lanfranchi P, Patruno V, et al. Blood pressure and heart rate during periodic breathing while asleep at high altitude. J Appl Physiol (1985). 2000 Sep;89(3):947-55. | CrossRef | PubMed |
20. Naeije R. Physiological adaptation of the cardiovascular system to high altitude. Prog Cardiovasc Dis. 2010 May-Jun;52(6):456-66. | CrossRef | PubMed |
21. Caravita S, Faini A, Baratto C, Bilo G, Macarlupu JL, Lang M, et al. Upward Shift and Steepening of the Blood Pressure Response to Exercise in Hypertensive Subjects at High Altitude. J Am Heart Assoc. 2018 Jun 9;7(12):e008506. | CrossRef | PubMed |
22. Salvi P, Revera M, Faini A, Giuliano A, Gregorini F, Agostoni P, et al. Changes in subendocardial viability ratio with acute high-altitude exposure and protective role of acetazolamide. Hypertension. 2013 Apr;61(4):793-9. | CrossRef | PubMed |
23. Caravita S, Faini A, Bilo G, Revera M, Giuliano A, Gregorini F, et al. Ischemic changes in exercise ECG in a hypertensive subject acutely exposed to high altitude. Possible role of a high-altitude induced imbalance in myocardial oxygen supply-demand. Int J Cardiol. 2014 Feb 15;171(3):e100-2. | CrossRef | PubMed |
24. Wyss CA, Koepfli P, Fretz G, Seebauer M, Schirlo C, Kaufmann PA. Influence of altitude exposure on coronary flow reserve. Circulation. 2003 Sep 9;108(10):1202-7. | CrossRef | PubMed |
25. Lang M, Faini A, Caravita S, Bilo G, Anza-Ramìrez C, Villafuerte FC, et al. Blood pressure response to six-minute walk test in hypertensive subjects exposed to high altitude: effects of antihypertensive combination treatment. Int J Cardiol. 2016 Sep 15;219:27-32. | CrossRef | PubMed |
26. Caravita S, Faini A, Bilo G, Villafuerte FC, Macarlupu JL, Lang M. Blood Pressure Response to Exercise in Hypertensive Subjects Exposed to High Altitude and Treatment Effects. J Am Coll Cardiol. 2015 Dec 22;66(24):2806-2807. | CrossRef | PubMed |
27. Valentini M, Revera M, Bilo G, Caldara G, Savia G, Styczkiewicz K, et al. Effects of beta-blockade on exercise performance at high altitude: a randomized, placebo-controlled trial comparing the efficacy of nebivolol versus carvedilol in healthy subjects. Cardiovasc Ther. 2012 Aug;30(4):240-8. | CrossRef | PubMed |
28. SONAMI SNdMdC. Mapa Minero de Chile. [On line] | Link |
29. MINSAL.(2013). Guía Técnica sobre Exposición Ocupacional a Hipobaria Intermitente Crónica por Gran Altitud. [On line] | Link |
30. Farias JG, Jimenez D, Osorio J, Zepeda AB, Figueroa CA, Pulgar VM. Acclimatization to chronic intermittent hypoxia in mine workers: a challenge to mountain medicine in Chile. Biol Res. 2013;46(1):59-67. | CrossRef | PubMed |
31. Richalet JP, Donoso MV, Jiménez D, Antezana AM, Hudson C, Cortès G, et al. Chilean miners commuting from sea level to 4500 m: a prospective study. High Alt Med Biol. 2002 Summer;3(2):159-66. | CrossRef | PubMed |
32. Brito J, Siqués P, León-Velarde F, De La Cruz JJ, 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 Fall;8(3):236-44. | CrossRef | PubMed |
33. Brito J, Siques P, López R, Romero R, León-Velarde F, Flores K, et al. Long-Term Intermittent Work at High Altitude: Right Heart Functional and Morphological Status and Associated Cardiometabolic Factors. Front Physiol. 2018 Mar 22;9:248. | CrossRef | PubMed |
34. Wu TY, Ding SQ, Liu JL, Yu MT, Jia JH, Chai ZC, et al. Who should not go high: chronic disease and work at altitude during construction of the Qinghai-Tibet railroad. High Alt Med Biol. 2007 Summer;8(2):88-107. | CrossRef | PubMed |
35. Lawes CM, Vander Hoorn S, Rodgers A; International Society of Hypertension. Global burden of blood-pressure-related disease, 2001. Lancet. 2008 May 3;371(9623):1513-8. | CrossRef | PubMed |
36. Social SSdS. (2018). Estudio de los efectos de la exposición intermitente a gran altitud sobre la salud de trabajadores de faenas mineras. [On line] | Link |
37. Parati G, Ochoa JE, Torlasco C, Salvi P, Lombardi C, Bilo G. Aging, High Altitude, and Blood Pressure: A Complex Relationship. High Alt Med Biol. 2015 Jun;16(2):97-109. | CrossRef | PubMed |
38. Somers VK, Mark AL, Abboud FM. Potentiation of sympathetic nerve responses to hypoxia in borderline hypertensive subjects. Hypertension. 1988 Jun;11(6 Pt2):608-12. | CrossRef | PubMed |
39. Krapf R, Jaeger P, Hulter HN. Chronic respiratory alkalosis induces renal PTH-resistance, hyperphosphatemia and hypocalcemia in humans. Kidney Int. 1992 Sep;42(3):727-34. | CrossRef | PubMed |
40. Halperin JL, Levine GN, Al-Khatib SM, Birtcher KK, Bozkurt B, Brindis RG, et al. Further Evolution of the ACC/AHA Clinical Practice Guideline Recommendation Classification System: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Circulation. 2016 Apr 5;133(14):1426-8. | CrossRef | PubMed |
41. Parati G, Revera M, Giuliano A, Faini A, Bilo G, Gregorini F, et al. Effects of acetazolamide on central blood pressure, peripheral blood pressure, and arterial distensibility at acute high altitude exposure. Eur Heart J. 2013 Mar;34(10):759-66. | CrossRef | PubMed |

Bärtsch P, Gibbs JS. Effect of altitude on the heart and the lungs. Circulation. 2007 Nov 6;116(19):2191-202. | CrossRef | PubMed |

Parati G, Agostoni P, Basnyat B, Bilo G, Brugger H, Coca A, et al. Clinical recommendations for high altitude exposure of individuals with pre-existing cardiovascular conditions: A joint statement by the European Society of Cardiology, the Council on Hypertension of the European Society of Cardiology, the European Society of Hypertension, the International Society of Mountain Medicine, the Italian Society of Hypertension and the Italian Society of Mountain Medicine. Eur Heart J. 2018 May 1;39(17):1546-1554. | CrossRef | PubMed |

Williams B, Mancia G, Spiering W, Agabiti Rosei E, Azizi M, Burnier M, et al. 2018 Practice Guidelines for the management of arterial hypertension of the European Society of Cardiology and the European Society of Hypertension. Blood Press. 2018 Dec;27(6):314-340. | CrossRef | PubMed |

Keyes LE, Mather L, Duke C, Regmi N, Phelan B, Pant S, et al. Older age, chronic medical conditions and polypharmacy in Himalayan trekkers in Nepal: an epidemiologic survey and case series. J Travel Med. 2016 Aug 8;23(6):taw052. | CrossRef | PubMed |

Higgins JP, Tuttle T, Higgins JA. Altitude and the heart: is going high safe for your cardiac patient? Am Heart J. 2010 Jan;159(1):25-32. | CrossRef | PubMed |

Hansen J, Sander M. Sympathetic neural overactivity in healthy humans after prolonged exposure to hypobaric hypoxia. J Physiol. 2003 Feb 1;546(Pt 3):921-9. | CrossRef | PubMed |

Bilo G, Caldara G, Styczkiewicz K, Revera M, Lombardi C, Giglio A, et al. Effects of selective and nonselective beta-blockade on 24-h ambulatory blood pressure under hypobaric hypoxia at altitude. J Hypertens. 2011 Feb;29(2):380-7. | CrossRef | PubMed |

Wolfel EE, Selland MA, Mazzeo RS, Reeves JT. Systemic hypertension at 4,300 m is related to sympathoadrenal activity. J Appl Physiol (1985). 1994 Apr;76(4):1643-50. | CrossRef | PubMed |

Veglio M, Maule S, Cametti G, Cogo A, Lussiana L, Madrigale G, et al. The effects of exposure to moderate altitude on cardiovascular autonomic function in normal subjects. Clin Auton Res. 1999 Jun;9(3):123-7. | CrossRef | PubMed |

Parati G, Bilo G, Faini A, Bilo B, Revera M, Giuliano A, Lombardi C, et al. Changes in 24 h ambulatory blood pressure and effects of angiotensin II receptor blockade during acute and prolonged high-altitude exposure: a randomized clinical trial. Eur Heart J. 2014 Nov 21;35(44):3113-22. | CrossRef | PubMed |

Torlasco C, Bilo G, Giuliano A, Soranna D, Ravaro S, Oliverio G, et al. Effects of acute exposure to moderate altitude on blood pressure and sleep breathing patterns. Int J Cardiol. 2020 Feb 15;301:173-179. | CrossRef | PubMed |

Bilo G, Villafuerte FC, Faini A, Anza-Ramírez C, Revera M, Giuliano A, et al. Ambulatory blood pressure in untreated and treated hypertensive patients at high altitude: the High Altitude Cardiovascular Research-Andes study. Hypertension. 2015 Jun;65(6):1266-72. | CrossRef | PubMed |

Halliwill JR, Minson CT. Effect of hypoxia on arterial baroreflex control of heart rate and muscle sympathetic nerve activity in humans. J Appl Physiol (1985). 2002 Sep;93(3):857-64. | CrossRef | PubMed |

Bilo G, Revera M, Bussotti M, Bonacina D, Styczkiewicz K, Caldara G, et al. Effects of slow deep breathing at high altitude on oxygen saturation, pulmonary and systemic hemodynamics. PLoS One. 2012;7(11):e49074. | CrossRef | PubMed |

Siqués P, Brito J, Banegas JR, León-Velarde F, de la Cruz-Troca JJ, López V, et al. Blood pressure responses in young adults first exposed to high altitude for 12 months at 3550 m. High Alt Med Biol. 2009 Winter;10(4):329-35. | CrossRef | PubMed |

Aryal N, Weatherall M, Bhatta YK, Mann S. Blood Pressure and Hypertension in Adults Permanently Living at High Altitude: A Systematic Review and Meta-Analysis. High Alt Med Biol. 2016 Sep;17(3):185-193. | CrossRef | PubMed |

Bilo G, Acone L, Anza-Ramírez C, Macarlupú JL, Soranna D, Zambon A, et al. Office and Ambulatory Arterial Hypertension in Highlanders: HIGHCARE-ANDES Highlanders Study. Hypertension. 2020 Dec;76(6):1962-1970. | CrossRef | PubMed |

Cheong HI, Janocha AJ, Monocello LT, Garchar AC, Gebremedhin A, Erzurum SC, et al. Alternative hematological and vascular adaptive responses to high-altitude hypoxia in East African highlanders. Am J Physiol Lung Cell Mol Physiol. 2017 Feb 1;312(2):L172-L177. | CrossRef | PubMed |

Insalaco G, Romano S, Salvaggio A, Braghiroli A, Lanfranchi P, Patruno V, et al. Blood pressure and heart rate during periodic breathing while asleep at high altitude. J Appl Physiol (1985). 2000 Sep;89(3):947-55. | CrossRef | PubMed |

Naeije R. Physiological adaptation of the cardiovascular system to high altitude. Prog Cardiovasc Dis. 2010 May-Jun;52(6):456-66. | CrossRef | PubMed |

Caravita S, Faini A, Baratto C, Bilo G, Macarlupu JL, Lang M, et al. Upward Shift and Steepening of the Blood Pressure Response to Exercise in Hypertensive Subjects at High Altitude. J Am Heart Assoc. 2018 Jun 9;7(12):e008506. | CrossRef | PubMed |

Salvi P, Revera M, Faini A, Giuliano A, Gregorini F, Agostoni P, et al. Changes in subendocardial viability ratio with acute high-altitude exposure and protective role of acetazolamide. Hypertension. 2013 Apr;61(4):793-9. | CrossRef | PubMed |

Caravita S, Faini A, Bilo G, Revera M, Giuliano A, Gregorini F, et al. Ischemic changes in exercise ECG in a hypertensive subject acutely exposed to high altitude. Possible role of a high-altitude induced imbalance in myocardial oxygen supply-demand. Int J Cardiol. 2014 Feb 15;171(3):e100-2. | CrossRef | PubMed |

Wyss CA, Koepfli P, Fretz G, Seebauer M, Schirlo C, Kaufmann PA. Influence of altitude exposure on coronary flow reserve. Circulation. 2003 Sep 9;108(10):1202-7. | CrossRef | PubMed |

Lang M, Faini A, Caravita S, Bilo G, Anza-Ramìrez C, Villafuerte FC, et al. Blood pressure response to six-minute walk test in hypertensive subjects exposed to high altitude: effects of antihypertensive combination treatment. Int J Cardiol. 2016 Sep 15;219:27-32. | CrossRef | PubMed |

Caravita S, Faini A, Bilo G, Villafuerte FC, Macarlupu JL, Lang M. Blood Pressure Response to Exercise in Hypertensive Subjects Exposed to High Altitude and Treatment Effects. J Am Coll Cardiol. 2015 Dec 22;66(24):2806-2807. | CrossRef | PubMed |

Valentini M, Revera M, Bilo G, Caldara G, Savia G, Styczkiewicz K, et al. Effects of beta-blockade on exercise performance at high altitude: a randomized, placebo-controlled trial comparing the efficacy of nebivolol versus carvedilol in healthy subjects. Cardiovasc Ther. 2012 Aug;30(4):240-8. | CrossRef | PubMed |

SONAMI SNdMdC. Mapa Minero de Chile. [On line] | Link |

MINSAL.(2013). Guía Técnica sobre Exposición Ocupacional a Hipobaria Intermitente Crónica por Gran Altitud. [On line] | Link |

Farias JG, Jimenez D, Osorio J, Zepeda AB, Figueroa CA, Pulgar VM. Acclimatization to chronic intermittent hypoxia in mine workers: a challenge to mountain medicine in Chile. Biol Res. 2013;46(1):59-67. | CrossRef | PubMed |

Richalet JP, Donoso MV, Jiménez D, Antezana AM, Hudson C, Cortès G, et al. Chilean miners commuting from sea level to 4500 m: a prospective study. High Alt Med Biol. 2002 Summer;3(2):159-66. | CrossRef | PubMed |

Brito J, Siqués P, León-Velarde F, De La Cruz JJ, 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 Fall;8(3):236-44. | CrossRef | PubMed |

Brito J, Siques P, López R, Romero R, León-Velarde F, Flores K, et al. Long-Term Intermittent Work at High Altitude: Right Heart Functional and Morphological Status and Associated Cardiometabolic Factors. Front Physiol. 2018 Mar 22;9:248. | CrossRef | PubMed |

Wu TY, Ding SQ, Liu JL, Yu MT, Jia JH, Chai ZC, et al. Who should not go high: chronic disease and work at altitude during construction of the Qinghai-Tibet railroad. High Alt Med Biol. 2007 Summer;8(2):88-107. | CrossRef | PubMed |

Lawes CM, Vander Hoorn S, Rodgers A; International Society of Hypertension. Global burden of blood-pressure-related disease, 2001. Lancet. 2008 May 3;371(9623):1513-8. | CrossRef | PubMed |

Social SSdS. (2018). Estudio de los efectos de la exposición intermitente a gran altitud sobre la salud de trabajadores de faenas mineras. [On line] | Link |

Parati G, Ochoa JE, Torlasco C, Salvi P, Lombardi C, Bilo G. Aging, High Altitude, and Blood Pressure: A Complex Relationship. High Alt Med Biol. 2015 Jun;16(2):97-109. | CrossRef | PubMed |

Somers VK, Mark AL, Abboud FM. Potentiation of sympathetic nerve responses to hypoxia in borderline hypertensive subjects. Hypertension. 1988 Jun;11(6 Pt2):608-12. | CrossRef | PubMed |

Krapf R, Jaeger P, Hulter HN. Chronic respiratory alkalosis induces renal PTH-resistance, hyperphosphatemia and hypocalcemia in humans. Kidney Int. 1992 Sep;42(3):727-34. | CrossRef | PubMed |

Halperin JL, Levine GN, Al-Khatib SM, Birtcher KK, Bozkurt B, Brindis RG, et al. Further Evolution of the ACC/AHA Clinical Practice Guideline Recommendation Classification System: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Circulation. 2016 Apr 5;133(14):1426-8. | CrossRef | PubMed |

Parati G, Revera M, Giuliano A, Faini A, Bilo G, Gregorini F, et al. Effects of acetazolamide on central blood pressure, peripheral blood pressure, and arterial distensibility at acute high altitude exposure. Eur Heart J. 2013 Mar;34(10):759-66. | CrossRef | PubMed |