Blood hemoglobin levels that are considered borderline for anemia under current World Health Organization (WHO) thresholds may need further investigation, research in more than half a million adults suggests.
The findings, in the Annals of Internal Medicine, showed a U-shaped curve between hemoglobin levels and the risk of subsequent death, with the lowest risk above WHO anemia thresholds.
The results do not necessarily mean that thresholds for anemia—in which the number of red blood cells or the hemoglobin concentration within them is lower than normal—should be updated.
However, the new discovery could offer prognostic information and help clinicians interpret borderline hemoglobin levels, inform management, and identify those at risk of adverse outcomes who require investigation and treatment.
“Our observations suggest that values up to 1 g/dl above the current WHO definition for anemia (borderline anemia) may warrant investigation rather than automatic reassurance, particularly in people with a high prevalence of iron deficiency, such as older adults and those with CVD,” reported the University of Glasgow researchers.
Hemoglobin is a crude marker of red blood cell mass, with both high and low levels signaling underlying health problems. It can have several causes, such as nutrient deficiency, infections, inflammation, inherited or gynecological disorders.
The most common dietary reason is a lack of iron, although deficiencies in folate, vitamins B12 and A are also important causes.
It is a serious global public health problem that particularly affects young children, menstruating adolescent girls and women, particularly during pregnancy and after childbirth. WHO estimates that 40% of children six to 59 months of age, 37% of pregnant women, and 30% of women 15 to 49 years of age worldwide are anemic.
Using information on 502,188 adults enrolled in the UK Biobank, Malek Ahmad, MBBS, and co-workers studied how hemoglobin levels were linked with future mortality. Hemoglobin concentrations were compared with WHO sex-specific anemia thresholds for defining anemia, which are below 13.0 g/dl for men and below 12.0 g/dl for women.
Deaths from any cause, or from cardiovascular disease or cancer were then tracked over a median follow-up of 13.6 years.
The researchers reported a U-shaped relationship between hemoglobin levels and mortality, with the lowest risk at hemoglobin concentrations 1 to 3 g/dl above current WHO anemia thresholds.
“The U-shaped association between hemoglobin concentration and adverse outcomes is biologically plausible,” they explained.
“At low concentrations, anemia reduces the oxygen-carrying capacity of the blood, leading to a compensatory increase in cardiac output. Chronic increases in atrial and ventricular volumes and heart rate may have deleterious effects on the myocardium, especially when compounded by the effects of aging.”
They added: “Failure to increase cardiac output adequately may induce tissue hypoxia. Neurohormonal activation may impair endothelial function, promote oxidative stress, and accelerate end-organ damage.
“Conversely, elevated hemoglobin concentrations might increase blood viscosity and shear stress, potentially promoting thromboembolic events.”
