Long-term chronic intermittent hypoxia: a particular form of chronic high-altitude pulmonary hypertension

Abstract

In some subjects, high-altitude hypobaric hypoxia leads to high-altitude pulmonary hypertension. The threshold for the diagnosis of high-altitude pulmonary hypertension is a mean pulmonary artery pressure of 30 mmHg, even though for general pulmonary hypertension is ≥25 mmHg. High-altitude pulmonary hypertension has been associated with high hematocrit findings (chronic mountain sickness), and although these are two separate entities, they have a synergistic effect that should be considered. In recent years, a new condition associated with high altitude was described in South America named long-term chronic intermittent hypoxia and has appeared in individuals who commute to work at high altitude but live and rest at sea level. In this review, we discuss the initial epidemiological pattern from the early studies done in Chile, the clinical presentation and possible molecular mechanism and a discussion of the potential management of this condition.

Keywords: chronic hypoxia; epidemiology; high altitude; high altitude pulmonary hypertension; intermittent hypoxia.

Fig. 1.

A proposed scheme of events and factors involved in the development of high-altitude pulmonary hypertension; body mass index; partial pressure of O₂; mean pulmonary artery pressure. *Notably, excessive erythrocytosis has not been demonstrated to play a role in long term chronic intermittent hypoxia.

Fig. 2.

A proposed scheme for high-altitude pulmonary hypertension progression and some of its mechanisms in the pulmonary vasculature; endothelin-1; reactive oxygen species; hypoxia-inducible factor-1α; nitric oxid; and interleukin 1 and 6.

Fig. 3.

Scheme showing differences in pulmonary vasculature remodeling between chronic intermittent hypoxia and chronic hypoxia. (Reproduced with permission from Brito et al.)