Abstracts

INTRODUCTION

Anemia is defined as the pathological decrease in hemoglobin levels in the blood and is caused by several pathophysiological mechanisms.²⁴24 . Zakai NA, Katz R, Hirsch C, Shlipak MG, Chaves PHM, Newman AB, et al. A prospective study of anemia status, hemoglobin concentration, and mortality in an elderly cohort: the Cardiovascular Health Study. Arch Intern Med. 2005;165(19):2214-20. DOI:10.1001/archinte.165.19.2214 It is the most common hematologic dysfunction in older adults. Begué et al (2004) reported different prevalence rates of anemia in older adults: from 2.9% to 61.0% in men and 3.3% to 41.0% in women.⁴4 . Beghé C, Wilson A, Ershler WB. Prevalence and outcomes of anemia in geriatrics: a systematic review of the literature. Am J Med. 2004;116(Suppl 7A):3S-10S. DOI:10.1016/j.amjmed.2003.12.009 In most cases, hemoglobin levels are reduced approximately 1 g/dL below the expected levels.¹²12 . Makipour S, Kanapuru B, Ershler WB. Unexplained anemia in the elderly. Semin Hematol. 2008;45(4):250-4. DOI:10.1053/j.seminhematol.2008.06.003^,1616 . Paltiel O, Clarfield AM. Anemia in elderly people: risk marker or risk factor? CMAJ. 2009;181(3-4):129-30. DOI:10.1503/cmaj.091199

Anemia in older adults has multiple etiologies, with one-third cases attributed to nutritional deficiencies (iron, folate, and vitamin B₁₂) and one-third to chronic diseases (particularly renal diseases) and/or inflammation. The erythropoietic response is inadequate when there are high circulating levels of pro-inflammatory cytokines such as interleukin-6 (IL-6). The underlying mechanisms in the remaining one-third cases have not been elucidated yet.¹⁰10 . Guralnik JM, Eisenstaedt RS, Ferrucci L, Klein HG, Woodman RC. Prevalence of anemia in persons 65 years and older in the United States: evidence for a high rate of unexplained anemia. Blood. 2004;104(8):2263-8. DOI:10.1182/blood-2004-05-1812^,1212 . Makipour S, Kanapuru B, Ershler WB. Unexplained anemia in the elderly. Semin Hematol. 2008;45(4):250-4. DOI:10.1053/j.seminhematol.2008.06.003

The prevalence of anemia appears to increase with age. A study in the USA evaluated data from the Third National Health and Nutrition Examination Survey (NHANES III) and showed higher prevalence in older adults aged ≥ 85 years, particularly men. The prevalence among women was 8.5% in the age group of 65 to 74 years and 20.1% in the age group of > 85 years; in the same age groups, the prevalence among men was 7.8% and 26.1%, respectively.¹⁰10 . Guralnik JM, Eisenstaedt RS, Ferrucci L, Klein HG, Woodman RC. Prevalence of anemia in persons 65 years and older in the United States: evidence for a high rate of unexplained anemia. Blood. 2004;104(8):2263-8. DOI:10.1182/blood-2004-05-1812

Data on anemia in older adults in Brazil are limited. Cross-sectional studies performed in Pernambuco, Northeastern Brazil, Minas Gerais, and Sao Paulo, Southeastern Brazil, have showed prevalence between 4.5% and 11.0%.³3 . Barbosa DL, Arruda IKG, Diniz AS. Prevalência e caracterização da anemia em idosos do Programa de Saúde da Família. Rev Bras Hematol Hemoter. 2006;28(4):288-92. DOI:10.1590/S1516-84842006000400014^,2020 . Santos IS, Scazufca M, Lotufo PA, Menezes PR, Benseñor IM. Anemia and dementia among the elderly: the São Paulo Ageing & Health Study. Int Psychogeriatr. 2012;24(1):74-81. DOI:10.1017/S1041610211001724^,2121 . Silva CLA, Lima-Costa MF, Firmo JOA, Peixoto SV. Nível de hemoglobina entre idosos e sua associação com indicadores do estado nutricional e uso de serviços de saúde: Projeto Bambuí. Cad Saude Publica. 2012;28(11):2085-94. DOI: 10.1590/S0102-311X2012001100008

The objective of this study was to assess the prevalence of anemia and associated factors in older adults.

METHODS

Based on the results of the Saúde, Bem-Estar e Envelhecimento (SABE – Health, Welfare and Aging) study, a longitudinal study initiated in 2000 with a probability sample of 2,143 older adults (≥ 60 years) living in Sao Paulo, SP, we investigated the prevalence and factors associated with anemia in older adults. The reference sample (cohort A) was obtained by stratified two-stage sampling according to the censitary sectors of the city. Individuals aged ≥ 75 years were oversampled because of the higher mortality rate in this age group. Details regarding the sampling design of the initial study have been described in a previous publication.¹¹11 . Lebrão ML, Laurenti R. Saúde, bem-estar e envelhecimento: o estudo SABE no Município de São Paulo. Rev Bras Epidemiol. 2005;8(2):127-41. DOI:10.1590/S1415-790X2005000200005

In 2006, the second round of interviews was performed with 1,115 individuals. A new sample (cohort B, n = 298) of older adults aged 60-64 years was obtained following the same method used in the first visit, because this age group was not represented in the first cohort.

The third follow-up visit took place between 2010 and 2011, with 748 individuals from the initial sample and 242 from the 2006 sample. A third sample of older adults aged 60-64 years was included (cohort C, n = 355).

Almost half of the individuals from the initial cohort that were not represented in the period between the beginning of the study and the third follow-up visit died within this period (44.2%). A small percentage of individuals (20.9%) were lost to follow-up because of other reasons, such as moving to another city, refusal to respond, and individuals who were not found. Sampling weights were recalculated in 2010 according to the 2010 census in order to maintain a representative sample. Weights derived from posteriori stratification were incorporated to the weights related to the sample design.

The 2010 sample included 1,345 older adults (≥ 60 years) who represented approximately 1,338,138 older adults living in Sao Paulo. The final sample that was evaluated consisted of 1,256 individuals whose biochemical test results were available on the third visit (Figure 1).

The study involved home interviews in all follow-up visits. Each interview was performed by a single interviewer using a standard questionnaire that addressed the living and health conditions of older adults. Quantification of anthropometric data and physical performance tests were also conducted by trained nutritionists.

Blood collection and tests were included on the third visit (2010/2011). Participants were instructed to fast for 10h to 12h prior to blood withdrawal. Blood collection was performed at the residence of the older adults by trained nurse technicians using venous puncture in the sitting position. Hemoglobin levels were determined using an electronic counter at the Laboratório do Instituto do Coração da Faculdade de Medicina da Universidade de São Paulo. Participants received a copy of the test results. Details regarding the third follow-up visit of the SABE study can be found in the study of Corona et al.⁶6 . Corona LP, Andrade FCD, Duarte YAO, Lebrão ML. The association of hemoglobin concentration with disability and decreased mobility among older Brazilians. J Nutr Health Aging. 2014;18(3):336-41. DOI:10.1007/s12603-013-0389-9

Anemia was identified on the basis of blood hemoglobin levels using the World Health Organization hemoglobin cut-off points:²⁴24 . Zakai NA, Katz R, Hirsch C, Shlipak MG, Chaves PHM, Newman AB, et al. A prospective study of anemia status, hemoglobin concentration, and mortality in an elderly cohort: the Cardiovascular Health Study. Arch Intern Med. 2005;165(19):2214-20. DOI:10.1001/archinte.165.19.2214 12 g/dL for women and 13 g/dL for men.

Mean and standard deviation were calculated for continuous variables, and proportions were calculated for categorical variables. Differences between groups were estimated using the Wald test of mean equality and the Rao-Scott test; both tests consider sampling weights for the estimate of population with population weights.

Hierarchical logistic regression was performed to analyze factors associated with anemia. The conceptual model was based on the assumption that although demographic characteristics directly influence anemia, the occurrence of chronic conditions in older adults takes precedence. These conditions can have a stronger influence on the occurrence of anemia.¹1 . Alexandre TS, Corona LP, Nunes DP, Santos JLF, Duarte YAO, Lebrão ML. Similarities among factors associated with components of frailty in elderly: SABE Study. J Aging Health. 2014;26(3):441-57. DOI:10.1177/0898264313519818^,2626 . Zimmer Z, Martin LG, Nagin DS, Jones BL. Modeling disability trajectories and mortality of the oldest-old in China. Demography. 2012;49(1):291-314. DOI:10.1007/s13524-011-0075-7 The factors investigated were divided in two groups. The group of demographic variables was included first, followed by the clinical variables group. The variables selected in the first group were kept in the model despite the fact that statistic significance could not be maintained after the inclusion of the subsequent group, and remained as adjustment factors for the proximal group. Values of p ≤ 0.2 were selected for univariate analyses performed to select the variables intended for modeling. The groups were separated as follows:

• demographic characteristics (distal group): gender, age, and education (years of schooling);

• clinical characteristics (proximal group): presence of self-reported chronic diseases (hypertension, diabetes, cardiovascular disease, encephalic vascular accident, osteoporosis, and cancer), positive screening for depression symptoms, cognitive decline, and body mass index (kg/m²). The occurrence of depression symptoms was evaluated considering the Brazilian version of the Geriatric Depression Scale, with a score of ≥ 6 indicating positive results.¹⁸18 . Paradela EMP, Lourenço RA, Veras RP. Validation of geriatric depression scale in a general outpatient clinic. Rev Saude Publica. 2005;39(6):918-23. DOI:10.1590/S0034-89102005000600008 Screening for cognitive decline was performed using the modified version of the Mini Exame do Estado Mental (MEEM – Mini-Mental State Examination) that was validated for the SABE study. This scale has 13 items (maximum score of 19 points), it is less dependent on education, and the cut-off point used for positive screening is ≤ 12.¹¹11 . Lebrão ML, Laurenti R. Saúde, bem-estar e envelhecimento: o estudo SABE no Município de São Paulo. Rev Bras Epidemiol. 2005;8(2):127-41. DOI:10.1590/S1415-790X2005000200005

The model adjusted by the demographic variables was called “partial model”, whereas the “final model” was adjusted by the two groups. It was considered that identification of a statistically significant association (p < 0.05) between a given variable under study and the outcome in question, after adjustment for the potential variables of the same group and of the superior hierarchical groups, would indicate existence of an independent effect, inherent to the given variable.

The variables included in this analysis were evaluated on the third visit. Data analysis was performed with Stata^® version 11. The sampling weights were applied in all analyses.

This study was approved by the Comitê de Ética em Pesquisa da Faculdade de Saúde Pública of the Universidade de São Paulo (Process 2,044 of 2010). Participation was voluntary and all participants signed the informed consent form.

RESULTS

Approximately 60.4% of older adults in the study were females. The mean age of the participants was 70.4 years, and their average education was 5.3 years. Anemia was identified in 7.7% of the studied population, being present in 7.3% of men and 7.9% of women (Table 1).

The prevalence of anemia was higher in the following: 1) oldest adults; 2) those with less education; 3) those with positive screening for cognitive decline; 4) those who reported previous diagnosis of hypertension, diabetes, cancer, cardiovascular disease, encephalic vascular accident/embolus, osteoporosis, or three or more chronic diseases; and 5) those with depression symptoms. There was no significant difference related to the nutritional state.

Despite the fact that there was no difference in the prevalence of anemia between genders, the distribution of hemoglobin levels showed important differences between men and women. The distribution curve of hemoglobin levels among women was displaced to the left, toward the lower values, whereas among men, it was displaced to the right (Figure 2).

Regarding age groups, the distribution of hemoglobin levels showed similar curves among older adults aged 60-69 years and 70-79 years, whereas the distribution curve of older adults aged ≥ 80 years was displaced to the left, toward the lower values (Figure 3).

Age continued to be a significant factor after inclusion of the first group of variables in the hierarchical logistic regression model. Furthermore, age and presence of diabetes, depression symptoms, and cancer remained statistically significant after inclusion of the clinical variables in the final model (Table 2).

DISCUSSION

The prevalence of anemia in the population of older adults in Sao Paulo was 7.7%, which is slightly lower than the prevalence in developed countries such as the USA (10.6%).¹⁰10 . Guralnik JM, Eisenstaedt RS, Ferrucci L, Klein HG, Woodman RC. Prevalence of anemia in persons 65 years and older in the United States: evidence for a high rate of unexplained anemia. Blood. 2004;104(8):2263-8. DOI:10.1182/blood-2004-05-1812 In a systematic review by Gaskell et al⁸8 . Gaskell H, Derry S, Moore RA, McQuay HJ. Prevalence of anaemia in older persons: systematic review. BMC Geriatr. 2008;8:1. DOI:10.1186/1471-2318-8-1 (2008), the average prevalence of anemia in older adults in the community was 12.0%. This study included older adults aged ≥ 65 years, which could explain the higher prevalence. Furthermore, the few Brazilian studies on anemia in older adults show different prevalence rates: 4.5% in Bambuí, MG, and 10.0%-11.0% in Sao Paulo and Camaragibe, PE.³3 . Barbosa DL, Arruda IKG, Diniz AS. Prevalência e caracterização da anemia em idosos do Programa de Saúde da Família. Rev Bras Hematol Hemoter. 2006;28(4):288-92. DOI:10.1590/S1516-84842006000400014^,2020 . Santos IS, Scazufca M, Lotufo PA, Menezes PR, Benseñor IM. Anemia and dementia among the elderly: the São Paulo Ageing & Health Study. Int Psychogeriatr. 2012;24(1):74-81. DOI:10.1017/S1041610211001724^,2121 . Silva CLA, Lima-Costa MF, Firmo JOA, Peixoto SV. Nível de hemoglobina entre idosos e sua associação com indicadores do estado nutricional e uso de serviços de saúde: Projeto Bambuí. Cad Saude Publica. 2012;28(11):2085-94. DOI: 10.1590/S0102-311X2012001100008

It is possible that these inconsistences are because of the differences between the populations under investigation. The low prevalence in Bambuí²¹21 . Silva CLA, Lima-Costa MF, Firmo JOA, Peixoto SV. Nível de hemoglobina entre idosos e sua associação com indicadores do estado nutricional e uso de serviços de saúde: Projeto Bambuí. Cad Saude Publica. 2012;28(11):2085-94. DOI: 10.1590/S0102-311X2012001100008 can be attributed to the high level of involvement of the cohort population in health monitoring, which stimulated better health control and overall conditions in this population. The Camaragibe,³3 . Barbosa DL, Arruda IKG, Diniz AS. Prevalência e caracterização da anemia em idosos do Programa de Saúde da Família. Rev Bras Hematol Hemoter. 2006;28(4):288-92. DOI:10.1590/S1516-84842006000400014 study covered a population from the Northeast of Brazil, which is known to be less educated and to have less access to health services in addition to having higher exposure to food insecurity.⁹9 . Gubert MB, Benício MHD’A, Santos LMP. Estimativas de insegurança alimentar grave nos municípios brasileiros. Cad Saude Publica. 2010;26(8):1595-605. DOI:10.1590/S0102-311X2010000800013^,1919 . Salvato MA, Ferreira PCG, Duarte AJM’A. O impacto da escolaridade sobre a distribuição de renda. Estud Econ (São Paulo). 2010;40(4):753-91. DOI:10.1590/S0101-41612010000400001^,2222 . Travassos C, Oliveira EXG, Viacava F. Desigualdades geográficas e sociais no acesso aos serviços de saúde no Brasil: 1998 e 2003. Cienc Saude Coletiva. 2006:11(4):975-86. DOI:10.1590/S1413-81232006000400019 The Camaragipe population appears to have a demographic profile similar to that of the Sao Paulo population,²⁰20 . Santos IS, Scazufca M, Lotufo PA, Menezes PR, Benseñor IM. Anemia and dementia among the elderly: the São Paulo Ageing & Health Study. Int Psychogeriatr. 2012;24(1):74-81. DOI:10.1017/S1041610211001724 with a similar prevalence. This is because although the referred study²⁰20 . Santos IS, Scazufca M, Lotufo PA, Menezes PR, Benseñor IM. Anemia and dementia among the elderly: the São Paulo Ageing & Health Study. Int Psychogeriatr. 2012;24(1):74-81. DOI:10.1017/S1041610211001724 was performed in Sao Paulo, a big city with higher average years of schooling and more access to health services, the study covered neighborhoods of low demographic conditions in the Butantã region and included older adults aged ≥ 65 years. Our study, also performed in Sao Paulo with older adults, utilized a probability sample representative of the population. While providing more health services than smaller municipalities, Sao Paulo has older adults of all demographic levels and with different levels of access to the health services.

The proportion of anemic individuals did not differ between men and women. This is because menstrual blood loss ceases in older women, making the risk of anemia equal for both genders. Consistent with these findings, a study has reported that in the USA, the prevalence of anemia in adults is higher in women than in men; however, between 65 and 74 years of age, the prevalence is similar.¹⁰10 . Guralnik JM, Eisenstaedt RS, Ferrucci L, Klein HG, Woodman RC. Prevalence of anemia in persons 65 years and older in the United States: evidence for a high rate of unexplained anemia. Blood. 2004;104(8):2263-8. DOI:10.1182/blood-2004-05-1812 Several studies have discussed whether or not it is reasonable to use lower cut-off points for women even many years after menopause, because hemoglobin levels between 12 g/dL and 13g/dL are predictive of adverse consequences.⁵5 . Chaves PH, Semba RD, Leng SX, Woodman RC, Ferrucci L, Guralnik JM, et al. Impact of anemia and cardiovascular disease on frailty status of community-dwelling older women: The Women’s Health and Aging Studies I and II. J Gerontol A Biol Sci Med Sci. 2005;60(6):729-35. DOI:10.1093/gerona/60.6.729^,1010 . Guralnik JM, Eisenstaedt RS, Ferrucci L, Klein HG, Woodman RC. Prevalence of anemia in persons 65 years and older in the United States: evidence for a high rate of unexplained anemia. Blood. 2004;104(8):2263-8. DOI:10.1182/blood-2004-05-1812^,2525 . World Health Organization. Iron deficiency anaemia: assessment, prevention and control: a guide for programme managers. Geneva; 2001.

In the present study, the prevalence of anemia was higher in older adults aged ≥ 80 years, which corroborates with the findings of Guralnik et al¹⁰10 . Guralnik JM, Eisenstaedt RS, Ferrucci L, Klein HG, Woodman RC. Prevalence of anemia in persons 65 years and older in the United States: evidence for a high rate of unexplained anemia. Blood. 2004;104(8):2263-8. DOI:10.1182/blood-2004-05-1812 (2004). Approximately 8.0% of older adults aged 65-74 years and 20.0%-26.0% of older adults aged ≥ 85 years in the USA had anemia in 2004. In contrast, our results showed a prevalence rate of approximately 17.0% in older adults aged ≥ 80 years.

A few mechanisms can explain the correlation between prevalence of anemia and advanced age. The first is the increased erythropoietin (EPO) demand. Healthy older adults appear to have increased EPO levels to meet the increased demand. In other cases, the decreased capacity of renal hormone production leads to the development of anemia. Furthermore, aging is associated with increased expression of pro-inflammatory cytokines, which can contribute to EPO insensitivity. Thus, genetic variation in the expression of these cytokines can influence anemia development in older adults by the induction of hepcidin expression (inflammation-related anemia) and suppression of the formation of erythroid colonies by cytokines.²³23 . Vanasse GJ, Berliner N. Anemia in elderly patients: an emerging problem for the 21st century. Hematology Am Soc Hematol Educ Program. 2010;2010:271-5. DOI:10.1182/asheducation-2010.1.271

Among all factors examined, only age remained significantly associated with anemia in the first group in the hierarchical multiple regression model. Age continued to be significant even after inclusion of the clinical variables group, which showed an independent effect even after the main diseases associated with anemia were controlled.

The presence of diabetes, depression symptoms, and cancer remained significantly associated with anemia.

Diabetes is one of the main causes of chronic renal insufficiency. Even at subclinical stages, diabetes is responsible for a considerable portion of cases of anemia in older adults due to reduction of EPO secretion.⁷7 . El-Achkar TM, Ohmit SE, McCullough PA, Crook ED, Brown WW, Grimm R, et al. Higher prevalence of anemia with diabetes mellitus in moderate kidney insufficiency: The Kidney Early Evaluation Program. Kidney Int. 2005;67(4):1483-8. DOI:10.1111/j.1523-1755.2005.00226.x^,1313 . Mehdi U, Toto RD. Anemia, diabetes, and chronic kidney disease. Diabetes Care. 2009;32(7):1320-6. DOI:10.2337/dc08-0779 Approximately 12.0% of anemia cases in the USA are associated with renal disease.¹⁰10 . Guralnik JM, Eisenstaedt RS, Ferrucci L, Klein HG, Woodman RC. Prevalence of anemia in persons 65 years and older in the United States: evidence for a high rate of unexplained anemia. Blood. 2004;104(8):2263-8. DOI:10.1182/blood-2004-05-1812

Cancer is an important risk factor for anemia, particularly when it affects the digestive system, because it causes intermittent bleeding (generally unnoticeable), which leads to anemia.²2 . Balducci L. Anemia, cancer, and aging. Cancer Control. 2003;10(6):478-86. Another mechanism is the decreased response to EPO, mainly during chemotherapy.¹⁴14 . Miller CB, Jones RJ, Piantadosi S, Abeloff MD, Spivak JL. Decreased erythropoietin response in patients with the anemia of cancer. N Engl J Med. 1990;322(24):1689-92. DOI:10.1056/NEJM199006143222401

The association between anemia and depression was investigated in older adults. Such association had two possible directions of causality: anemia can lead to depression, but it can also be a consequence of depression. Anemia can lead to depression because of deficiencies of vitamins such as folate and vitamin B12, which cause a decrease in S-adenosyl-methionine production or an increase in homocysteine production. S-adenosyl-methionine functions as a cofactor in the synthesis of neurotransmitters including serotonin, and homocysteine accumulation can affect central nervous system receptors.¹⁷17 . Pan WH, Chang YP, Yeh WT, Guei YS, Lin BF, Wei IL, et al. Co-occurrence of anemia, marginal vitamin B6, and folate status and depressive symptoms in older adults. J Geriatr Psychiatry Neurol. 2012;25(3):170-8. DOI:10.1177/0891988712458365 In an Italian study, Onder et al¹⁵15 . Onder G, Penninx BW, Cesari M, Bandinelli S, Lauretani F, Bartali B, et al. Anemia is associated with depression in older adults: results from the InCHIANTI study. J Gerontol A Biol Sci Med Sci. 2005;60(9):1168-72. DOI:10.1093/gerona/60.9.1168 found an association between depression and a significantly increased risk for anemia (OR = 1.93). This result persisted even after exclusion of vitamin B12 deficiency and exclusion of patients with relevant comorbidities.¹⁵15 . Onder G, Penninx BW, Cesari M, Bandinelli S, Lauretani F, Bartali B, et al. Anemia is associated with depression in older adults: results from the InCHIANTI study. J Gerontol A Biol Sci Med Sci. 2005;60(9):1168-72. DOI:10.1093/gerona/60.9.1168 According to a study performed in Taiwan, anemia and marginal vitamin B6 deficiency were significantly associated with the presence of depression symptoms as well as the coexistence of anemia with low levels of vitamin B6 and folate.¹⁷17 . Pan WH, Chang YP, Yeh WT, Guei YS, Lin BF, Wei IL, et al. Co-occurrence of anemia, marginal vitamin B6, and folate status and depressive symptoms in older adults. J Geriatr Psychiatry Neurol. 2012;25(3):170-8. DOI:10.1177/0891988712458365

Depression can also play a role in the development of anemia. Fatigue and lack of interest in performing daily activities (such as shopping and cooking), which are common depression symptoms, can affect the quality of nutrition of older adults, facilitating the development of anemia. Malnutrition is a common condition among depressed individuals.¹⁵15 . Onder G, Penninx BW, Cesari M, Bandinelli S, Lauretani F, Bartali B, et al. Anemia is associated with depression in older adults: results from the InCHIANTI study. J Gerontol A Biol Sci Med Sci. 2005;60(9):1168-72. DOI:10.1093/gerona/60.9.1168

This study has a few limitations. It is not possible to determine the direction of the associations because this is a cross-sectional analysis. In addition, there are no data regarding other biological markers that could be important in determining the causes of anemia, particularly IL-6, folate, and vitamin B12.

Healthcare professionals should focus on diagnosing and treating anemia in older adults, particularly when it is associated with other health conditions such as diabetes, cancer, and depression. Anemia can be easily diagnosed and markedly affects the health of older adults. Its reversal may play an important role in improving the quality of life of this population.

REFERENCES

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