Establishing reference intervals for 25 common biochemical analytes in Tibetans living at very high altitude

Objectives: High altitude poses extreme living environment for humans, impacting human physiology and leading to physiological adaptations, including higher hemoglobin levels in highlanders. However, further understanding is required regarding the medical reference ranges at very high altitudes (>4,500 m). Therefore, we conducted a study involving 1,656 healthy individuals from the "Health Improvement at Very High Altitude (HI-VHA)" population to establish a reference range for 25 biochemical analyses in this population residing at very high altitudes. Methods: The HI-VHA project sampled 3,564 individuals from Tibet Autonomous Region above 4,500 m. After strict exclusion criteria, 1,656 healthy individuals were included to establish age and sex stratified reference intervals (RIs) for 25 biochemical analytes using serum samples. Results: RIs were generated following the statistical guidelines outlined in CLSI C28-A3. Among the 25 biochemical analytes studied, the levels of ALT, GLB, CREA, UA, HDLC, and HCY showed significant variations by gender, while ALB, AG, CHOL, and DBIL were influenced by age. LDLC was the only analyte affected by both gender and age. AST, TP, TBIL, IBIL, Glu, TG, LDLC, CRP, K, Na, Cl, Ca, Mg, and P, comprising 14 analytes, were not influenced by gender or age. Conclusions: We established the RIs for 25 biochemical analytes in the very high-altitude population. These RIs are crucial for disease diagnosis and health management of individuals living at very high altitudes. Moreover, an accurate identification of diseases commonly observed at very high altitudes provides insights into the biological adaptation mechanisms of humans residing in such environments.