Borderline Anemia May Carry Higher Risk Than Current Thresholds Suggest

In older adults, both high and low values have been linked to adverse outcomes, including cognitive decline, cardiovascular disease, hospitalization, and death. Although anemia is commonly defined by the World Health Organization (WHO) as hemoglobin below 12 g/dL in women and 13 g/dL in men, a new study shows that borderline low levels just above these thresholds are also associated with increased mortality.

University of Glasgow researchers conducted a prospective cohort analysis of nearly half a million UK Biobank participants followed for more than 10 years. The investigation assessed the relationship between baseline hemoglobin concentration and long-term mortality risk using multiple statistical approaches. The study, titled “Association between blood haemoglobin concentration and mortality by age and sex: a prospective cohort study,” was published in Annals of Internal Medicine.

The analysis demonstrated a U-shaped association between hemoglobin and mortality, with the greatest risk at both extremes. The lowest all-cause mortality risk occurred at hemoglobin concentrations 1 to 3 g/dL above current WHO anemia thresholds in both men and women. Notably, individuals with “borderline anemia,” defined as values just above the diagnostic cutoff, had a higher mortality risk than those with higher hemoglobin within the WHO-defined normal range.

Hemoglobin testing is routine across care settings, yet current anemia thresholds have remained largely unchanged for five decades. Although higher-than-normal hemoglobin levels, or polycythemia, are rare, affecting about 7 per 100,000 people in the UK, anemia is common and has been associated with cognitive, cardiovascular, and hospitalization risks in older adults. The researchers emphasize that the study shows association rather than causation and does not demonstrate that investigating or treating people just above current thresholds would improve outcomes. Instead, the findings point to areas for future research and add to broader debate over how well long-standing diagnostic cutoffs reflect current risk.

“The most important purpose of clinical diagnostic criteria is to inform the management of patients. Currently, many clinicians do not even recognise a person has anaemia until its moderately severe, for example less than 11 g/dL. Showing that borderline anaemia is associated with increased risk and a high prevalence of iron deficiency should encourage investigation and treatment of a broad range of patients with mild/borderline anaemia,” said Professor John Cleland, Professor of Cardiology and senior author of the study.

“The very large study population, long follow-up and consistency across several statistical approaches make this a robust association. However, this remains an observational study. The next question is whether low-normal haemoglobin can help identify treatable underlying conditions and improve patient care,” said Professor Paul Welsh, Professor of Molecular Epidemiology and Director of the Glasgow Biomarker Research Unit at the University of Glasgow.

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