High-Altitude Residence, Blood Biomarkers, and Chronic Disease Risk in Middle-Aged and Older Chinese Adults

Background/Objectives: The goal of the study is to examine associations of baseline residential elevation with blood biomarkers and newly reported multisystem chronic diseases among middle-aged and older adults, and to explore whether routine blood indicators may lie on these pathways. Methods: We analyzed 2011, 2015, and 2018 data from the China Health and Retirement Longitudinal Study (CHARLS). Wave 1 provided residential elevation, covariates, and 14 biomarkers; Wave 3 provided intermediate biomarkers; and Wave 4 identified 13 chronic disease outcomes based on participants' reports of having received a physician diagnosis. High elevation was defined as ≥1500 m. Baseline and longitudinal samples included 11,371 and 9270 participants. Analyses used multivariable linear regression, attrition-weighted Cox models, logistic sensitivity models, restricted cubic splines, and exploratory mediation analysis. Results: High-elevation residence was associated with 9 of 14 biomarkers. Among 182 biomarker-disease Cox models, 35 associations had false-discovery-rate-adjusted q < 0.05, including 32 involving outcomes with at least 50 newly reported cases in the high-elevation group. Direct multiple-imputation inverse-probability-weighted (MI-IPW) Cox models showed that high-elevation residence was associated with higher estimated hazards over the interview interval for newly reported lung disease, kidney disease, arthritis, and hypertension; the first three associations remained significant in weighted logistic models. MI-IPW sensitivity analyses retained 31 of the 32 event-reliable biomarker-disease findings. No indirect effect survived multiple-comparison correction, including after excluding participants who had reported the relevant disease by Wave 3. Among the eight outcomes examined using restricted cubic splines, only kidney disease showed nominal evidence of nonlinearity (p = 0.017). Conclusions: Baseline residential elevation was associated with distinct biomarker patterns and heterogeneous disease risks. Routine blood biomarkers were prospectively associated with later disease reporting but did not provide stable evidence of mediation. These observational findings support cautious, disease-specific interpretation and further prospective and mechanistic research.