Do people living at high altitudes develop Pulmonary Arterial Hypertension (PAH)?

High Altitude and Pulmonary Arterial Hypertension

People living at high altitudes can develop pulmonary hypertension, with the risk increasing significantly at elevations above 2,500 meters due to hypoxia-induced pulmonary vasoconstriction. 1

Physiological Response to High Altitude

• At high altitudes, the decreased barometric pressure leads to reduced partial pressure of oxygen in inspired air (hypobaric hypoxia), triggering pulmonary vasoconstriction within minutes of exposure 2
• The body compensates through increased pulmonary ventilation, increased cardiac output by raising heart rate, changes in vascular tone, and eventually an increase in hemoglobin concentration 3
• Pulmonary vasoconstriction is a direct response to acute hypoxia, cold exposure, and increased ventilation 3

Pulmonary Arterial Pressure at High Altitude

• The combined mean systolic pulmonary artery pressure in high-altitude dwellers (>2,500m) is significantly higher (25.3 mmHg) compared to low-altitude populations (18.4 mmHg) 4
• Arterial oxygen saturation is correspondingly lower at high altitude (90.4%) compared to sea level (98.1%) 4, 5
• The diagnostic threshold for high-altitude pulmonary hypertension (HAPH) uses a modified mean pulmonary artery pressure of at least 30 mmHg, which differs from the 25 mmHg used for other types of pulmonary hypertension 1

Risk Factors and Prevalence

• Despite elevated pulmonary pressures compared to sea level, true pulmonary hypertension appears to be relatively rare among permanent residents at altitudes where most high-altitude populations live (3,600-4,350m) 4
• Genetic factors play a significant role in determining who develops HAPH, as not all high-altitude residents are affected 1
• Individuals with pre-existing pulmonary hypertension are at greater risk when exposed to high altitude, as their compensatory mechanisms may be limited 2

Clinical Manifestations

• The clinical presentation of high-altitude pulmonary hypertension includes fatigue, shortness of breath, cognitive deficits, cough, and in advanced cases, hepatosplenomegaly and right-sided heart failure 1
• Patients with pulmonary arterial hypertension who live at moderately high altitude (≥4000 ft/1219m) have higher pulmonary vascular resistance and are more likely to require supplemental oxygen 6
• Interestingly, despite higher pulmonary vascular resistance, these patients may demonstrate better functional capacity as measured by 6-minute walk distance, suggesting a possible "high-altitude phenotype" of PAH 6

Management Recommendations

• Patients with known pulmonary hypertension should consider using supplemental oxygen when exposed to altitudes >1500-2000m 3
• For patients with WHO Group 1 PAH with functional class III-IV symptoms, in-flight oxygen administration should be considered, as well as for those with PaO2 consistently <60 mmHg 3
• Treatment options for HAPH include descent to lower altitude whenever possible, oxygen therapy, and medications such as endothelin receptor antagonists, phosphodiesterase-5 inhibitors, fasudil, and acetazolamide 1

Special Considerations

• Patients with congenital heart disease and concurrent pulmonary hypertension should be particularly careful when going to high altitude, as elevated pulmonary pressure due to pre-existing conditions worsens the effects of high-altitude exposure 3
• The increase in pulmonary vascular resistance at high altitude can worsen right-to-left shunting in patients with cyanotic heart conditions 3
• Pulmonary hypertension in healthy highlanders appears to be related to delayed postnatal remodeling of distal pulmonary arterial branches, with the magnitude increasing with altitude level and degree of exercise 7

Long-term Effects and Adaptation

• There is reversal of pulmonary hypertension after prolonged residence at sea level, indicating the condition's potential reversibility 7
• Chronic mountain sickness can develop when the capacity for altitude adaptation is lost, resulting in moderate to severe pulmonary hypertension with accentuated hypoxemia and exaggerated polycythemia 7
• This condition represents a significant public health problem in mountainous regions worldwide 7