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 47 48 49 50 51 Key points 52 53 • Acute exposure to high altitude stimulates the adrenergic system, 54 increasing heart rate and cardiac output; although blood pressure remains 55 stable, pulmonary artery pressure increases owing to hypoxic pulmonary 56 vasoconstriction. 57 58 • Prolonged exposure to high altitude induces a decrease in maximal heart 59 rate through desensitization of the adrenergic pathway, as a protective 60 mechanism against environmental conditions of low oxygen availability. 61 62 • Long-term exposure to high altitude results in cardiac adaptations with 63 no obvious dysfunction; stroke volume is slightly reduced owing to 64 decreased left ventricular filling volume secondary to right ventricular 65 overload. 66 67 • High-altitude natives can develop chronic mountain sickness, associated 68 with erythropoiesis, pulmonary hypertension and right heart failure, 69 although genetic adaptations to hypoxia have been found in Tibetan and 70 Ethiopian populations. 71 72 • Patients with cardiovascular diseases can be at increased risk of adverse 73 events at altitudes above 2,500 m, owing to hypoxaemia, high adrenergic 74 activity and pulmonary hypertension. 75 76 • Intermittent, moderate hypoxia might be useful in the conditioning of 77 patients with cardiovascular diseases, such as coronary heart disease and 78 heart failure.