Association Between Blood Hemoglobin Concentration and Mortality by Age and Sex

BACKGROUND: The 1959 World Health Organization (WHO) definition of anemia is widely used, but its relationship with mortality in the general adult population is uncertain. OBJECTIVE: To evaluate associations between baseline hemoglobin concentration and long-term mortality by age and sex. DESIGN: Prospective cohort study. SETTING: Population-based cohort in the United Kingdom. PARTICIPANTS: 502 188 adults (median age, 58 years; 54.4% women) recruited from 2006 to 2010; hemoglobin concentration was measured in 477 876 (95.2%). Analyses were stratified by sex and age (<60 vs. ≥60 years). Median follow-up was 13.6 years. MEASUREMENTS: Hemoglobin concentration categorized relative to WHO sex-specific thresholds (men, <13.0 g/dL; women, <12.0 g/dL). Outcomes were all-cause, cardiovascular, and cancer mortality. RESULTS: All-cause mortality showed a U-shaped association with hemoglobin concentration, with lowest risk 1 to 3 g/dL above the WHO threshold. In the primary adjusted model, the 10-year standardized cumulative incidence (SCI) was 4.5% in the reference group versus 12.5% among participants more than 2 g/dL below the threshold (absolute risk difference [ARD], +8.1 percentage points; 95% CI, 6.7 to 9.4 percentage points); over the entire follow-up, the adjusted hazard ratio (HR) was 2.87 (CI, 2.54 to 3.25). Among those 0 to 1 g/dL above the threshold, the 10-year SCI was 5.3% (ARD, +0.8 percentage points; CI, 0.7 to 1.0 percentage points) and the adjusted HR was 1.18 (CI, 1.15 to 1.21). Associations were less consistent in women younger than 60 years. Patterns for cardiovascular and cancer mortality were similar at low and borderline concentrations but attenuated at higher concentrations. LIMITATION: Single baseline hemoglobin concentration measurement; predominantly White population. CONCLUSION: Mortality was lowest at hemoglobin concentrations 1 to 3 g/dL above current WHO thresholds, with higher mortality below and above this range. These hypothesis-generating findings should not define new thresholds but may inform clinical interpretation and evaluation of borderline hemoglobin concentration values. PRIMARY FUNDING SOURCE: None.