Scientists have explained the association of low hemoglobin levels with the risk of death

People with hemoglobin levels, which are not yet formally considered anemia, had a higher risk of death than participants with levels slightly above the disease threshold. Researchers from the University of Glasgow came to this conclusion after analyzing the data of more than 500 thousand people — the details of the study are in the Izvestia material.

Why hemoglobin was important

The scientists decided to test how the concentration of this protein in the blood is associated with the long-term risk of death, if we consider not only people with already diagnosed anemia, but also those whose indicators are close to established thresholds. To do this, the scientists compared the hemoglobin concentration of the participants with the current anemia thresholds of the World Health Organization. These values differ for men and women. The work was published in the journal Annals of Internal Medicine (AoIM).

The researchers analyzed three outcomes: mortality from any cause, death from cardiovascular disease, and death from cancer. As a result, the relationship between hemoglobin concentration and mortality was not linear, but U-shaped: the risk was higher at both lower and higher values of the indicator.

How researchers tested the connection between blood and health

The researchers analyzed data from 502,188 adults. Their data were used to assess the relationship between baseline hemoglobin concentration and subsequent mortality. The median follow-up period was 13.6 years. During this time, scientists tracked deaths from any cause, and also separately analyzed deaths from cardiovascular diseases and cancer.

Participants with a hemoglobin concentration 1-3 g/dl higher than the current anemia threshold set by the World Health Organization (WHO) had the lowest risk of death. At values below this range, the risk increased, but the same trend was observed at higher hemoglobin concentrations.

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The risk increased even before the formal anemia

Of particular interest are the participants whose hemoglobin was directly near the threshold of anemia. Formally, they might not fall into the category of people with anemia, but their indicators already differed from the range associated with the lowest mortality. In the original study, the researchers divided the participants according to how much their hemoglobin differed from the corresponding WHO threshold. The threshold was 13 g/dl for men and 12 g/dl for women.

At the same time, the highest risk was observed in people with significantly lower indicators. In the primary adjusted model, the 10-year standardized cumulative probability of death was 4.5% in the control group and 12.5% among participants whose hemoglobin was more than 2 g/dl below the WHO threshold. For the entire follow-up period, the adjusted risk of death for this group was 2.87.

Thus, the study showed that the association with the risk of death is not limited to a situation where hemoglobin has already dropped below the diagnostic threshold. At the same time, the authors themselves do not propose to consider any borderline indicator as anemia.

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The connection was found for different causes of death

The researchers separately assessed mortality from cardiovascular diseases and cancer along with overall mortality. This approach allowed us to check whether the discovered pattern persists with different outcomes. The main result of the study concerned overall mortality: a U-shaped dependence was revealed for it, and the minimum risk corresponded to the hemoglobin level 1-3 g/dl above the WHO threshold of anemia. Higher and lower values were associated with increased risk.

At the same time, the study was observational. Therefore, the discovered relationship shows a link between hemoglobin concentration and mortality, but does not in itself prove that a change in hemoglobin levels is the direct cause of death.

There is no suggestion to change anemia thresholds yet.

The authors believe that the results obtained require further study of the hemoglobin boundary values. They can help doctors to better interpret the indicators of patients who are near the current thresholds of anemia, and identify people at increased risk. However, the researchers separately emphasize that the results are not grounds for changing existing anemia thresholds. The work is rather of a nature that forms new hypotheses for further research.

Thus, the main conclusion of the study is not that the established boundary between normal hemoglobin levels and anemia is incorrect. Scientists have shown that the relationship between hemoglobin concentration and mortality can be more complicated than simply dividing people into two groups — with and without anemia.