Researchers are increasingly focused on the maladaptive consequences of high altitude polycythemia (HAPC), a condition affecting individuals living in elevated regions, and its potential link to cardiorespiratory issues and, more recently, retinal and choroidal microcirculation changes.
HAPC develops as a physiological response to the lower oxygen levels found at high altitudes. The body compensates by increasing the production of red blood cells, a process mediated by the release of erythropoietin (EPO) from the kidneys. This increase is triggered by the hypoxia-inducible factor (HIF), which activates the EPO gene, ultimately stimulating red blood cell production in the bone marrow. While initially adaptive, excessive red blood cell production can lead to HAPC, characterized by high blood viscosity and potential cardiorespiratory dysfunction, according to a review published in Frontiers in Medicine in August 2024.
A study published in PubMed in 2024 highlighted that prolonged hypoxia associated with HAPC can cause respiratory depression and severe hypoxemia, altering genetic and molecular mechanisms regulating erythropoiesis and apoptosis. This can result in excessive erythrocytosis (EE), a key component of chronic mountain sickness (CMS).
The incidence of EE varies significantly depending on the population and altitude. A 1992 study of a Tibetan population found an incidence of 2.39% at 3650 meters, while a study of Peruvians at 3825 meters reported 4.5%. The highest reported incidence, 44%, was observed in La Rinconada, Peru, at an elevation of 5200 meters.
Symptoms of polycythemia, whether at high altitude or other causes, can include headache, fatigue, dizziness, shortness of breath, and chest pain. Researchers are now investigating the impact of HAPC on the microcirculation of the retina and choroid, seeking to understand the etiology of high-altitude related retinopathy (HAR). A recent study quantified the effects of long-term high-altitude exposure on these circulatory systems, using HAPC as a proxy for understanding HAR development.
Further complicating the picture, research indicates that HAPC is not simply an adaptive response, but a maladaptation. The increased blood viscosity associated with the condition contributes to reduced flow-mediated dilation, potentially exacerbating cardiorespiratory problems. The maladaptive mechanisms under investigation include respiratory chemoreceptor passivation, sleep-related breathing disorders, sex hormones, iron metabolism, and hypoxia-related factors and pathways.
The authors of the Frontiers in Medicine review declared no conflicts of interest. No immediate plans for large-scale intervention studies or policy changes related to HAPC management have been announced by the West China Hospital, Sichuan University, where much of the research originates.
