Copeptin and Arginine Vasopressin at High Altitude: Relationship to Plasma Osmolality and Perceived Exertion

Purpose: A diuresis is a key part of acclimatisation to high altitude (HA). Arginine vasopressin (AVP) is a hormone involved in salt and water balance and may potentially have a role in the development of altitude illness. ProAVP (copeptin) is more stable than AVP and is assayed by a straightforward, automated method. We investigated the relationship of AVP to copeptin and the copeptin response to exercise and altitude illness in a large cohort during a field study at HA.

Methods: 48 subjects took part in a 10-day trek at HA. Venous blood samples were taken at 3,833, 4,450 and 5,129 m post-trek (exercise) and the following day at rest. Daily recordings of symptoms of altitude illness, oxygen saturations and perceived exertion were carried out.

Results: AVP and copeptin levels increased with exercise and correlated closely (ρ 0.621 p < 0.001), this was strongest in the stressed state when AVP secretion was highest, at 5,129 m post-exercise (ρ 0.834 p < 0.001). On two-way ANOVA, both altitude (F = 3.5; p = 0.015) and exercise (F = 10.2; p = 0.002) influenced copeptin levels (interaction F = 2.2; p = 0.08). AVP levels were influenced by exercise (F = 14.4; p = 0.0002) but not altitude (F = 2.0; p = 0.12) with no overall group interactions (F = 1.92.6; p = 0.06). There was no association between copeptin or arginine vasopressin and altitude illness. Copeptin correlated with the Borg RPE score and was significantly higher in the group with a Borg score ≥15 (7.9 vs. 3.7 p < 0.001).

Conclusion: We have shown that arginine vasopressin and copeptin levels correlate and are suppressed below 5,129 m. Furthermore, we have demonstrated that exertion, rather than altitude illness or increasing osmolality, is the stimulus for increases in copeptin.