Borderline anaemia linked to increased mortality risk, study finds
People with haemoglobin levels just above the threshold currently used to diagnose anaemia may face a higher risk of death than those with higher haemoglobin concentrations within the normal range, according to new research from the University of Glasgow.
The study, published in the Annals of Internal Medicine, analysed data from almost 500,000 UK Biobank participants followed for more than 10 years, making it one of the largest studies to examine the relationship between haemoglobin concentration and mortality.
Researchers found a U-shaped association between haemoglobin concentration and mortality, with the highest risks occurring at both low and high concentrations. However, the lowest risk of death from any cause was associated with haemoglobin levels 1–3 g/dL above current World Health Organization (WHO) thresholds, in both men and women.
Importantly, participants with what the researchers describe as ‘borderline anaemia’ had a higher mortality risk than people with higher haemoglobin levels within the WHO-defined normal range.
Haemoglobin is the protein in red blood cells responsible for carrying oxygen around the body. Its concentration is routinely measured in primary and secondary care, with the WHO currently defining anaemia as haemoglobin below 12 g/dL in women and 13 g/dL in men; thresholds that have remained largely unchanged for almost half a cetury.
“Our data show that the lowest risk of death is associated with a ‘definitely normal’ haemoglobin, 1 to 3 g/dL above the conventional WHO definition of anaemia,” said Dr Malek Ahmad, clinician-scientist at the University of Glasgow and first author of the study. “Risk already starts to increase with ‘borderline anaemia’, before haemoglobin falls below the current WHO threshold.”
Anaemia is common and can have a range of causes, including iron deficiency, vitamin B12 or folate deficiency, chronic inflammation and conditions affecting blood-cell production. Iron deficiency can in turn result from inadequate dietary intake, impaired absorption or blood loss.
The researchers say the findings raise questions about whether the current binary distinction between anaemic and non-anaemic patients adequately reflects the relationship between haemoglobin and long-term health.
However, they stress that the study demonstrates an association rather than a causal relationship. It does not establish that investigating or treating people with haemoglobin concentrations just above the current WHO threshold would improve health or reduce mortality.
“The current WHO thresholds have served clinical practice for decades, but our findings suggest that the relationship between haemoglobin concentration and long-term health is more nuanced than a single diagnostic cut-off can capture,” said Dr Pierpaolo Pellicori, consultant cardiologist at Queen Elizabeth University Hospital and Senior Lecturer at the University of Glasgow. “Whether this should influence clinical practice is an important question for future research.”
The researchers suggest that further work should establish whether low-normal or borderline haemoglobin levels can help identify underlying, potentially treatable conditions, and whether intervention in these patients improves outcomes. Pic: CDC
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