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H.J.C.M. Wouters et al.
Figure 3. Kaplan-Meier curves of survival of indi- viduals with different types of anemia.
have an impact on the HRQoL of patients with cancer, HIV/AIDS and chronic kidney disease.39 In older individ- uals a positive effect of erythropoiesis-stimulating agents on QoL has been shown in patients with chronic kidney disease,40 and chemotherapy-induced anemia.41 In one randomized, blinded, placebo-controlled trial in predom- inantly African-American elderly women with ACI or unexplained anemia an increase of the hemoglobin con- centration by 2 g/dL led to improvements in QoL as measured by the Functional Assessment of Chronic Illness Therapy instrument.42
The most pronounced association between HRQoL and anemia was observed in older individuals and in sub- scales related to physical health. This suggests that younger individuals can compensate better for the phys- ical consequences of anemia, limiting the impact of ane- mia on their HRQoL. For older individuals these com- pensatory mechanisms might be limited compared to those in younger persons. The ability to engage in phys- ical activities is known to be important for maintaining QoL in older persons.43,44
In this study we defined anemia according to the WHO criteria, which define anemia as a hemoglobin concentration <13.0 g/dL (8.0 mmol/L) in adult men and <12.0 g/dL (7.5 mmol/L) in adult, non-pregnant women. This is the most commonly used definition of anemia, but the use of this definition in older/elderly populations has been criticized.11,12 The WHO criteria were derived from a small study population of healthy, young partici- pants nearly 50 years ago.20 Based on data from two large American databases, Beutler et al. proposed new, slightly higher cut-offs for white women older than 50 years and white men older than 60 years.12
Although the different distributions of median hemo- globin concentration between men and women (in gen- eral and in older individuals) suggest that it is ‘logic’ to use different definitions of anemia in men and women,
our data raise doubts about this logic. Indeed, HRQoL data from our study suggest that the definition of anemia in men – a hemoglobin concentration <13.0 g/dL (8.0 mmol/L) – should also be applied for women older than 60 years. Apparently, the hemoglobin values which start to hamper (physical) functioning do not differ between older men and women. We were not able to study the optimal definition of anemia in perspective of mortality because of the limited number of deaths in our cohort. Martinsson et al. observed an increased mortality defin- ing anemia as <14.0 g/dL (8.7 mmol/L) in men and <13.0 g/dL (8.0 mmol/L) in women.27 A recent, large study assessing the effect of hemoglobin concentrations on car- diovascular and all-cause mortality in nearly 300,000 par- ticipants showed that men with a hemoglobin concen- tration in the lower normal range had a higher risk of mortality whereas this was not observed in women.45
Our study has some strengths and limitations. It is the first study to investigate the possible effect of anemia on HRQoL in individuals of all ages in a very large cohort from the general population. Additionally, we used infor- mation on HRQoL from a large number of participants with a wide range of age, socio-economic status and co- morbidities. All subjects were uniformly characterized and were not aware of hemoglobin status when filling out the questionnaires, preventing the outcome of the questionnaire from being affected by the knowledge of a diagnosis of anemia.
Several potential limitations should be acknowledged. As mentioned earlier, the subtypes of anemia might have been misclassified due to a lack of clear classification cri- teria. Since this is a cross-sectional study, the analyses do not provide information about causality, for example for the fact that despite lower median hemoglobin concen- trations in older women than in older men, the impact of anemia on HRQoL occurred at the same hemoglobin concentration. Additionally, given the observational
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haematologica | 2019; 104(3)