Hemoglobin Exhibits a U-Shaped Association with Obstructive Sleep Apnea at High Altitude: Machine-Learning and...

Chronic high-altitude hypoxia induces adaptive erythrocytosis, but the relationship between hemoglobin (Hb) and obstructive sleep apnea (OSA) remains unclear. We examined the association between Hb levels and OSA severity and explored short-term changes in sleep-related outcomes after erythrocytapheresis.

250 men residing ≥1 year above 3,000 m were recruited at 3,860 m. OSA was assessed by portable polysomnography (apnea-hypopnea index, AHI; oxygenation). Participants were stratified by Hb level (<170, 170-210, and ≥210 g/L). Machine-learning classification and restricted cubic spline (RCS) analyses were used to evaluate nonlinear Hb-OSA associations. In the substudy, 15 participants with Hb >240 g/L underwent erythrocytapheresis, and 15 contemporaneous participants with high-altitude polycythemia (HAPC) received oxygen therapy alone. Sleep was reassessed within 24-48 h.

A U-shaped relationship between Hb and AHI was observed, with the lowest AHI in the 170-210 g/L group (P < 0.001). RCS analysis confirmed a significant nonlinear association (P < 0.001). The machine-learning model for OSA classification achieved an AUC of 0.873, with BMI, daytime SpO₂, and Hb deviation contributing to risk stratification. In the exploratory substudy, erythrocytapheresis was associated with larger short-term reductions in Hb and AHI, and with improved nocturnal oxygenation, compared with oxygen therapy alone.

Hb showed a nonlinear, U-shaped association with OSA at high altitude. Intermediate Hb levels (170-210 g/L) were associated with more favorable sleep-related indices. Erythrocytapheresis was associated with short-term improvement in sleep-related measures among participants with HAPC, supporting further controlled evaluation.