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  • Review Article
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Cardiovascular physiology and pathophysiology at high altitude

Nature Reviews Cardiology volume 21, pages 75–88 (2024)Cite this article

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Abstract

Oxygen is vital for cellular metabolism; therefore, the hypoxic conditions encountered at high altitude affect all physiological functions. Acute hypoxia activates the adrenergic system and induces tachycardia, whereas hypoxic pulmonary vasoconstriction increases pulmonary artery pressure. After a few days of exposure to low oxygen concentrations, the autonomic nervous system adapts and tachycardia decreases, thereby protecting the myocardium against high energy consumption. Permanent exposure to high altitude induces erythropoiesis, which if excessive can be deleterious and lead to chronic mountain sickness, often associated with pulmonary hypertension and heart failure. Genetic factors might account for the variable prevalence of chronic mountain sickness, depending on the population and geographical region. Cardiovascular adaptations to hypoxia provide a remarkable model of the regulation of oxygen availability at the cellular and systemic levels. Rapid exposure to high altitude can have adverse effects in patients with cardiovascular diseases. However, intermittent, moderate hypoxia might be useful in the management of some cardiovascular disorders, such as coronary heart disease and heart failure. The aim of this Review is to help physicians to understand the cardiovascular responses to hypoxia and to outline some recommendations that they can give to patients with cardiovascular disease who wish to travel to high-altitude destinations.

Key points

  • Acute exposure to high altitude stimulates the adrenergic system, increasing heart rate and cardiac output; although blood pressure remains stable, pulmonary artery pressure increases owing to hypoxic pulmonary vasoconstriction.

  • Prolonged exposure to high altitude induces a decrease in maximal heart rate through desensitization of the adrenergic pathway, as a protective mechanism against environmental conditions of low oxygen availability.

  • Long-term exposure to high altitude results in cardiac adaptations with no obvious dysfunction; stroke volume is slightly reduced owing to decreased left ventricular filling volume secondary to right ventricular overload.

  • High-altitude natives can develop chronic mountain sickness, associated with erythropoiesis, pulmonary hypertension and right heart failure, although genetic adaptations to hypoxia have been found in Tibetan and Ethiopian populations.

  • Patients with cardiovascular diseases can be at increased risk of adverse events at altitudes above 2,500 m, owing to hypoxaemia, high adrenergic activity and pulmonary hypertension.

  • Intermittent, moderate hypoxia might be useful in the conditioning of patients with cardiovascular diseases, such as coronary heart disease and heart failure.

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Fig. 1: Altitude, barometric pressure, air density and inspired oxygen pressure.
Fig. 2: Physiological effects of acute hypoxia.
Fig. 3: Effects of hypoxia on cardiomyocytes.
Fig. 4: Heart rate and arterial oxygen saturation at rest during a simulation of ascent to 8,848 m.
Fig. 5: Parallel linear decrease in arterial oxygen saturation and heart rate at maximal exercise as a function of altitude.
Fig. 6: Myocardial venous oxygen saturation at maximal exercise with and without autoregulation of maximal heart rate.
Fig. 7: Processes of adaptation to hypoxia.

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Authors and Affiliations

  1. Hypoxie et Poumon, Université Sorbonne Paris Nord, INSERM U1272, Paris, France

    Jean-Paul Richalet & François J. Lhuissier

  2. Unité de Recherche Pluridisciplinaire Sport Santé Société, ULR 7369-URePSSS, Université Littoral Côte d’Opale, Université Artois, Université Lille, CHU Lille, Dunkirk, France

    Eric Hermand

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Glossary

Anoxia

The absence of oxygen from the tissues of a living organism.

Duration of exposure to hypoxia

Acute: minutes or hours; prolonged: days or weeks; chronic: months, years or lifetime.

Hypobaric hypoxia

Decrease in oxygen pressure owing to a decrease in barometric pressure.

Hypoxaemia

Decrease in oxygen pressure in blood compared with normal value at sea level (100 mmHg).

Hypoxia

Decrease in oxygen pressure in a given milieu (such as ambient air, lung alveoli, blood or cells).

Normobaric hypoxia

Decrease in oxygen pressure owing to a decrease in the fraction of oxygen in the inspired air.

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Richalet, JP., Hermand, E. & Lhuissier, F.J. Cardiovascular physiology and pathophysiology at high altitude. Nat Rev Cardiol 21, 75–88 (2024). https://doi.org/10.1038/s41569-023-00924-9

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