Mortality lowest above anemia thresholds

Hemoglobin values just above current anemia thresholds were associated with higher long-term mortality.
*Prospective cohort study; Level 2b (OCEBM).

Citation

Ahmad M, Cleland JGF, Maffia P, et al. Association Between Blood Hemoglobin Concentration and Mortality by Age and Sex. Annals of Internal Medicine. Published September 8, 2026. doi:10.7326/ANNALS-26-00057

Background

The World Health Organization anemia definition is widely used but was based on older, small population studies. This study tested how baseline hemoglobin relates to later death in a large modern adult cohort.

Patients

502,188 United Kingdom Biobank adults, aged 37 to 73 years; 477,876 had hemoglobin measured. The cohort was predominantly White and generally healthier than the general population.

Intervention

Baseline hemoglobin category, measured relative to sex-specific anemia thresholds: men 13.0 g/dL, women 12.0 g/dL.

Control

Hemoglobin 1 to 3 g/dL above the sex-specific threshold.

Outcome

All-cause mortality (primary); cardiovascular and cancer mortality (secondary).

Follow-up Period

Median 13.6 years.

Results

Hemoglobin category 10-year all-cause mortality Adjusted risk difference Adjusted hazard ratio
More than 2 g/dL below threshold 12.5% +8.1 percentage points (95% CI 6.7 to 9.4) 2.87 (95% CI 2.54 to 3.25)
0 to 1 g/dL above threshold 5.3% +0.8 percentage points (95% CI 0.7 to 1.0) 1.18 (95% CI 1.15 to 1.21)
More than 4 g/dL above threshold 5.7% +1.2 percentage points (95% CI 0.7 to 1.7) 1.31 (95% CI 1.21 to 1.41)

CI = confidence interval. Hazard ratio compares death rates over time with the reference group.

Cardiovascular and cancer mortality showed similar patterns at low and borderline hemoglobin levels. Associations were weaker in women younger than 60 years.

Limitations

Hemoglobin was measured once, so later changes were not captured. The observational design cannot prove causation. Iron studies were unavailable, and results may not generalize well to younger, frailer, or more diverse populations.

Funding

No specific study funding; investigators had public and charitable support.

Clinical Application

Do not redefine anemia yet; consider evaluating borderline hemoglobin, especially in older adults or symptomatic patients.