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H.J.C.M. Wouters et al.
regression analysis to investigate whether anemia was an independent risk factor for HRQoL. This analysis showed that anemia, adjusted for body mass index, being a current smoker, multiple drug use, educational level and living situation independently increased the risk of having a lower total HRQoL (OR 1.28; 95% CI: 1.00 – 1.64; P=0.046).
Since anemia had a particular impact on overall sur- vival and HRQoL in subjects older than 60 years within the Lifelines cohort, the type of anemia in these individ- uals was further characterized (see the Methods section). In total 174 (35.0%) subjects were classified as having nutrient deficiency anemia, 81 (16.3%) as having ACI, and 242 (48.7%) as having unexplained anemia (Online Supplementary Table S1). Compared with individuals from the general population, a significantly larger pro- portion of individuals with ACI had a HRQoL score lower than the cut-off value in seven of the eight sub- scales (all except mental health) (Table 2). Nutrient defi- ciency anemia was associated with a significantly lower score in only one subscale (physical functioning). Individuals with unexplained anemia had a significantly lower score in the subscale bodily pain. These results were more explicit in men than in women (Online Supplementary Tables S2 and S3). In order to determine which type of anemia was an independent risk factor for HRQoL in individuals older than 60 years, we performed logistic regression analysis in individuals older than 60 years (Table 3 and Online Supplementary Table S4). After adjusting for body mass index, being a current smoking, multiple drug use, educational level and living situation, ACI was associated with a higher risk of having a score below the cut-off in all seven subscales which were affected by anemia (i.e. all subscales except mental health) (Table 3). Overall survival was significantly lower in individuals with ACI than in those with nutrient defi- ciency anemia or unexplained anemia (Figure 3).
Although the difference between the median values of the hemoglobin concentration decreased during aging, (Online Supplementary Figure S5), the definition of anemia is based on hemoglobin concentrations obtained in younger adults. Consequently, there are persistent dis- cussions regarding whether the definition of anemia in older individuals is appropriate or should be corrected using a higher hemoglobin threshold. Because of the clear correlation between anemia in individuals older than 60 years and survival and HRQoL, we used these associations to reassess the definition of anemia in indi- viduals older than 60 years. We assumed that anemia should be considered in the case that a certain hemoglo- bin level was associated with a significant (negative) impact on HRQoL. Logistic regression was used to model the relationship between hemoglobin concentra- tion and total HRQoL in both men and women. These analyses revealed that men older than 60 years with a hemoglobin concentration between 13.0-13.7 g/dL (8.0- 8.5 mmol/L) (just above the current WHO defined threshold) did not have a lower HRQoL compared with men with a hemoglobin concentration >13.7 g/dL (8.5 mmol/L), suggesting that the current threshold which defines anemia in men is appropriate. However, when specifically comparing women older than 60 years with a hemoglobin concentration between 12.0-13.0 g/dL (7.5-8.0 mmol/L) (considered anemic for men but not anemic for women according to the current WHO defi- nition), this group had a lower HRQoL than that of women with a hemoglobin concentration >13.0 g/dL (8.0 mmol/L). These data strongly suggest that the optimal definition of anemia for women older than 60 years should be a hemoglobin concentration <13.0 g/dL (8.0 mmol/L) (Figure 4). So, in the case that HRQoL is used to define anemia, there would be no difference in the defi- nition between older men and women. Due to the limit- ed number of deaths among groups of individuals divid-
Table 2. Percentage of individuals older than 60 years with anemia with HRQoL below the sex- and age-specific cut-off value for the different HRQoL subscales as a function of their type of anemia.
Physical functioning
Social functioning
Physical role functioning
Emotional role functioning
Mental health
Vitality
Bodily pain
General health
General population older than 60 years (N=18152)
4869 (26.8)
5482 (30.2)
3820 (21.0)
1936 (10.7)
5216 (28.7)
4820 (26.5)
5618 (30.9)
5104 (28.1)
Nutrient deficiency anemia (N=174)
67 (38.5)* P <0.001
53 (30.5)
49 (28.2)
20 (11.5)
42 (24.1)
49 (28.2)
60 (34.5)
60 (34.5)
Anemia of chronic inflammation (N=81)
40 (49.4)* P<0.001
41 (50.6)*
P<0.001 41 (50.6)*
P<0.001 17 (21.0)*
P=0.003
26 (32.1)
39 (47.0)*
P<0.001 40 (49.4)*
P<0.001
40 (49.4)*
P<0.001
Unexplained anemia (N=242)
78 (32.2)
85 (26.0)
63 (26.0)
30 (12.4)
72 (29.8)
75 (31.0)
95 (39.3)* P=0.006
79 (32.6)
Data are given as n (%) below the sex- and age-specific cut-off value for the different HRQoL subscales.* P-value <0.01 between individuals from the non-anemic group of the general population and individuals with the given type of anemia.
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haematologica | 2019; 104(3)