Page 67 - 2019_03-Haematologica-web

Anemia, survival and health-related quality of life
ed according to the various intervals of hemoglobin con- centration, survival could not be used to model the opti- mal definition of anemia.
Discussion
In this study we observed that anemia is associated with worse overall survival and is an independent risk factor for HRQoL in individuals older than 60 years, in contrast to younger individuals. Although consensus on the subclassification of anemia is lacking, our data sug- gest that particularly ACI was an independent risk factor for HRQoL in subscales representing physical function- ing. Furthermore, we observed that women (but not men) older than 60 years with a hemoglobin concentra- tion in the lower normal WHO range experienced decreased HRQoL. This suggests that the definition of anemia in women older than 60 years should be altered to a hemoglobin concentration <13.0 g/dL (8.0 mmol/L), which is comparable to the definition of anemia in men.
The prevalence of anemia according to the WHO crite- ria was 4.0% in the whole cohort and 2.8% among sub- jects older than 60 years, which is consistent with the findings of population-based studies from Sweden (3.8% in patients 44 - 73 years old)27 and Germany (3.2% in
Table 3. Risk of having a lower score than the (age- and sex- specific) 25th per- centile cut-off due to anemia per HRQoL subscale among individuals older than 60 years.
subjects 45-75 years old28 and 6.9% in subjects over 65 years old29). However, the prevalence of anemia in older individuals in our community-dwelling population was remarkably lower than that found in previous studies.3,4,30 A possible explanation for this discrepancy could be a participation bias in the Lifelines cohort, although earlier observations showed that the Lifelines study population is representative of the general population, with a low risk of selection.18 The relatively low prevalence of ane- mia in older individuals could also be related to the high quality and accessibility of the general health system nowadays, especially for older individuals. Furthermore, the prevalence of anemia and the types of anemia might differ according to race and geographical area.2,4
Anemia did not have an impact on survival in individ- uals younger than 60 years. In contrast, among individu- als older than 60 years, anemic subjects had a significant- ly decreased survival. The decreased survival in older anemic individuals is in accordance with that in multiple previous studies.7,9,10 In our study there was increased mortality in older individuals with ACI: this finding is partly in line with the findings of a study by Willems et al. who reported increased mortality in subjects with nutrient deficiency anemia and ACI, but not in those with unexplained anemia.31
Since an aging population results in an increased preva- lence of anemia, an understanding of the association between anemia and HRQoL is important. Remarkably, only a few, relatively small studies of community- dwelling populations have described this association. In a study of 717 subjects, Lucca et al. showed, after adjust- ment for a large number of demographic and clinical con- founders, that anemia in elderly Italians (65 - 84 years old) was significantly associated with lower disease-spe- cific QoL, measured with the Functional Assessment of Cancer Therapy-Anemia.32 Thein et al. studied an American cohort of 328 individuals and showed that anemia in subjects older than 65 years was independent- ly associated with impairments in multiple subscales of HRQoL (measured with the Short Form-36), especially in measures of functional limitation.33 Bang et al. also found that anemia was associated with physical impairment in 695 Korean individuals older than 65 years.34 Our data, in an unprecedented large cohort, confirms the relationship between anemia and HRQoL in older individuals (but not in younger individuals).
There is no worldwide accepted classification into sub- types of anemia. To be able to study the subtypes, we based our criteria on literature or reference values from the local laboratory. In addition to those criteria, we also analyzed the data with different classification criteria (see Online Supplementary Data for definitions). Although misclassification within the various subtypes of anemia cannot be excluded, our data suggest that the impact of anemia on HRQoL is mainly present in individuals with ACI (Online Supplementary Tables S5 and S6). The patho- physiology of ACI is multifactorial, including increased levels of inflammatory cytokines that lead to altered iron metabolism, with a key role for the iron regulatory pep- tide hormone hepcidin.35,36 Indeed, elevated levels of inflammatory markers, which are found in older anemic individuals, have been shown to be associated with physical disability.37,38 Our observation that anemia main- ly affects HRQoL of subjects with ACI is supported by studies showing that erythropoiesis-stimulating agents
HRQoL subscale
Physical functioning
Social functioning
Physical role functioning
Emotional role functioning
Vitality
Bodily pain
General health
Type of anemia
Nutritional deficiency anemia Anemia of chronic inflammation
Unexplained anemia
Nutritional deficiency anemia Anemia of chronic inflammation
Unexplained anemia
Nutritional deficiency anemia Anemia of chronic inflammation
Unexplained anemia
Nutritional deficiency anemia Anemia of chronic inflammation
Unexplained anemia
Nutritional deficiency anemia Anemia of chronic inflammation
Unexplained anemia
Nutritional deficiency anemia Anemia of chronic inflammation
Unexplained anemia
Nutritional deficiency anemia Anemia of chronic inflammation
Unexplained anemia
Odds ratio (95% CI)
1.16 (0.75 – 1.79)
3.30 (1.76 – 6.21) **P<0.001 1.04 (0.74 – 1.48)
0.89 (0.58 - 1.35)
2.39 (1.32 – 4.31) **P =0.004 1.04 (0.75 - 1.44)
1.15 (0.74 – 1.78)
3.75 (2.05- 6.83) **P<0.001 1.03 (0.72 - 1.48)
0.89 (0.49 – 1.59)
2.53 (1.31 – 4.90) **P=0.006 1.04 (0.66 – 1.65)
0.92 (0.60 - 1.42)
2.89 (1.59 – 5.24) **P<0.001 1.13 (0.81 - 1.57)
0.96 (0.63 - 1.45)
1.84 (1.02 – 3.33) *P=0.04
1.16 (0.84 – 1.60)
0.87 (0.57 - 1.34)
2.44 (1.33 – 4.45) **P =0.004 0.99 (0.71 – 1.38)
Adjusted for body mass index,smoking status,multiple drug use,educational level and living sit-
uation.Data are shown as odds ratio and 95% confidence interval (95% CI).**P-value <0.01; value <0.05.
*P-
haematologica | 2019; 104(3)
473