Biomarkers of hypoxia, endothelial and circulatory dysfunction among climbers in Nepal with AMS and HAPE: a prospective case-control study.

BACKGROUND: The mechanisms underlying acute mountain sickness (AMS) and high-altitude pulmonary edema (HAPE) are not fully understood. We hypothesized that regulators of endothelial function, circulatory homeostasis, hypoxia and cell stress contribute to the pathobiology of AMS and HAPE. METHODS: We conducted a prospective case-control study of climbers developing altitude illness who were evacuated to the CIWEC clinic in Kathmandu, compared to healthy acclimatized climbers. ELISA was used to measure plasma biomarkers of the above pathways. RESULTS: Of the 175 participants, there were 71 cases of HAPE, 54 cases of AMS and 50 acclimatized controls (ACs). Markers of endothelial function were associated with HAPE: circulating levels of endothelin-1 (ET-1) were significantly elevated and levels of sKDR (soluble kinase domain receptor) were significantly decreased in cases of HAPE compared to AC or AMS. ET-1 levels were associated with disease severity as indicated by oxygen saturation. Angiopoietin-like 4 (Angptl4) and resistin, a marker of cell stress, were associated with AMS and HAPE irrespective of severity. Corin and angiotensin converting enzyme, regulators of volume homeostasis, were significantly decreased in HAPE compared to AC. CONCLUSION: Our findings indicate that regulators of endothelial function, vascular tone and cell stress are altered in altitude illness and may mechanistically contribute to the pathobiology of HAPE.