Abstract
BACKGROUND: Chronic obstructive pulmonary disease (COPD) is the third leading cause of death globally. Hemoglobin (HGB) abnormalities, including anemia and secondary polycythemia, are common comorbidities in COPD patients, yet their association with mortality remains less clear. This study aimed to investigate the relationship between HGB levels and all-cause mortality in COPD patients and to evaluate whether HGB could serve as a treatable trait in COPD. METHODS: We conducted a retrospective observational cohort study using data from the National Health and Nutrition Examination Survey (NHANES, 2013-2018). A total of 544 COPD patients were included. Multivariable Cox regression was conducted to assess HGB-mortality associations, adjusting for age, sex, BMI, smoking status, and comorbidities. Nonlinear relationships were examined using generalized additive models with threshold effect analysis. Stratified analyses were performed by sex, age, and comorbidity status. RESULTS: Among 544 COPD patients, HGB levels demonstrated a significant nonlinear association with all-cause mortality, with a critical inflection point identified at 14.2 g/dL. Below this threshold, each 1g/dL in HGB was associated with reduced mortality (adjusted HR=0.73, 95% CI: 0.61-0.79, P<0.0001). Above 14.2g/dL, however, no significant association was observed (HR=1.24, 95% CI: 0.98-1.55, P=0.0775). Although stratified analyses suggested variation in HR across subgroups (including males, elderly >65 years, smokers, and those with cardiovascular disease), interaction tests did not reach statistical significance (all P-interaction >0.05), indicating no evidence of effect modification. Smoothing curves supported this nonlinear relationship, showing decreasing mortality risk with rising HGB until the threshold, beyond which risk stabilized with a slight non-significant upward trend. CONCLUSION: This study identifies a nonlinear relationship between HGB levels and mortality in COPD, establishing 14.2 g/dL as a critical threshold that supports anemia's inclusion in the COPD "treatable traits" framework. Below this value, increasing HGB is associated with reduced mortality, whereas above it no further benefit is observed. Clinicians should prioritize HGB monitoring in high-risk subgroups (elderly males, smokers, and cardiac comorbidities).