Anemia and hemoglobin thresholds of 12.5 and 13.0 g/dL are associated with distinct cardiovascular and all-cause mortality risks in COPD

BACKGROUND: Anemia is a prevalent comorbidity in chronic obstructive pulmonary disease (COPD), yet prior studies have predominantly focused on all-cause mortality, leaving the non-linear relationship between hemoglobin and mortality-and clinically actionable thresholds-undefined. We aimed to identify distinct hemoglobin thresholds associated with cardiovascular and all-cause mortality and evaluate hemoglobin as a prognostic risk indicator in COPD. METHODS: This prospective cohort study utilized data from seven NHANES cycles (2005-2018), including 1338 U S. adults with COPD representing approximately 7.7 million non-institutionalized COPD patients. Weighted Cox proportional hazards models and restricted cubic spline analysis were conducted to explore the association between hemoglobin level and mortality in COPD. RESULTS: The weighted prevalence of anemia among U.S. adults with COPD was 10.5%. Anemia was significantly associated with all-cause mortality (HR = 2.32, 95% CI: 1.85-2.92) and cardiovascular mortality (HR = 3.75, 95% CI: 2.06-6.83). Each 1 g/dL hemoglobin increment was associated with 17% and 22% risk reductions, respectively. RCS analysis identified nonlinear relationships with thresholds at 12.5 g/dL for all-cause and 13.0 g/dL for cardiovascular mortality. Findings remained robust across all sensitivity analyses. CONCLUSIONS: Anemia and lower hemoglobin levels were independently associated with significantly increased risks of all-cause and cardiovascular mortality. Hemoglobin thresholds of 12.5 g/dL and 13.0 g/dL were identified for all-cause and cardiovascular mortality, respectively, as prognostic indicators warranting further validation. These findings underscore the importance of hemoglobin assessment in risk stratification; however, interventional studies are needed to determine whether correction of anemia improves survival in this population.