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Racial Impact of Anemia And Mortality in The Elderly
Abstract & Commentary
By Andrew Artz, MD, MS, Division of Hematology/Oncology University of Chicago, Chicago, IL Dr. Artz reports no financial relationship to this field of study.
Synopsis: Anemia is a common problem associated with increased mortality among older adults. The higher prevalence of anemia in black older adults compared to white older adults has raised concern whether different hemoglobin (Hb) thresholds should differ by race. Patel and colleagues evaluated a biracial population of community-dwelling adults 71 to 82 years. They used the standard WHO anemia criteria f of Hb < 13 g/dL (130 g/L) for men and < 12 g/dL (120 g/L) for women. In whites, anemia predicted for increased age adjusted-mortality. However, in blacks, anemia status did not influence mortality. Mobility disability also developed more often in whites having anemia but not in anemic blacks. In this study, anemia by WHO criteria was associated with increased mortality in whites but not blacks. Further study on outcomes and anemia etiologies by race will be needed before developing Hb thresholds that define anemia by race.
Source: Kushang Patel, et al. Blood. 2007;109:4663-4670.
Anemia is a common problem among older adults occurring in over 10%1,2 and up to 50% in hospitalized or institutionalized elderly.3,4 Epidemiologic research has uncovered a striking independent association between anemia in the elderly and adverse outcomes. Anemia prognosticates for functional impairment, increased hospitalization, and increased mortality. The hemoglobin (Hb) threshold below which anemia is defined has generated considerable controversy. The World Health Organization (WHO) standard of Hb < 13 g/dL for men and < 12 g/dL for women remains the most common benchmark. However, epidemiologic studies have shown the lowest mortality occurs when Hb was 14-15 g/dL for women and 15-16 g/dL for men. Hb varies by race, such that blacks have lower median Hb concentrations and higher anemia prevalence. In one population-based study of older adults, anemia prevalence was 28% for blacks and 9% for whites.1 This has led to proposals for a lower Hb threshold to define anemia in blacks.5
The limited data on the adverse effect of anemia by race led Patel and investigators to examine racial variation of anemia on mortality and mobility. The study population comprised community-dwelling adults aged 70- 79 years from the Health ABC study. They evaluated 1018 black and 1583 white adults aged 71 to 82 years. Whites were randomly selected but all blacks were recruited. Anemia was defined by the WHO criteria of < 13 g/dL for men and < 12 g/dL for women. Mortality and mobility difficulty were longitudinally assessed.
Among blacks, 26% of men and 21% of women had anemia at baseline compared to 14% of white men and 7% of white women. In whites, anemia increased the chance of developing mobility difficulty although in women, the statistical significance was reduced after multi-variable adjustment. In blacks, anemia did not predict for developing mobility difficulty. For whites, anemia was associated with an increased mortality in men (HR = 1.96, 95% CI: 1.35-2.83) and women (HR = 2.86, 95% CI:1.69-4.82). Anemia had no statistical impact on mortality in black men (HR = 1.15, 95% CI: 0.77 - 1.72) or women (HR = 1.39), 95% CI: 0.91-2.14). The only threshold showing an increase in mortality for blacks was found in black men having Hb value 2 g/dL below the WHO threshold (ie < 11 g/dL).
Anemia occurs in over 10% of adults 65 years and older. Further, an emerging body of data has shown that anemia, and even mildly reduced Hb (eg, Hb < 14 g/dL), is associated with worse survival. Anemia prevalence is three-fold higher in older blacks compared to older whites but data on the adverse impact by race has been limited.
In this observational study, Patel and colleagues showed increased mobility difficulty and confirm other reports of worse survival among anemic older whites. However, anemia as defined by the WHO criteria did not increase mobility difficulty or mortality in blacks. The authors suggest considering using Hb lower than the WHO threshold of < 13 g/dL for men and < 12 g/dL in elderly blacks.
Although the analysis was careful, study limitations may preclude generalization. The recruitment strategies for blacks and whites differed as did number of patients lacking baseline Hb values (56% in blacks compared to 39% in whites). This may have led to bias that abrogated the mortality impact of anemia. Further, the data conflict with another recent study showing increased mortality in older anemic blacks.6 In addition, we do not know if anemia might lead to other important impairments, such as quality of life.
Oncologists are frequently referred anemic elderly adults without cancer. The main struggle, however, is not the prognostic impact but the necessary evaluation. Should one rest on a focused history, physical and laboratory evaluation? Or, should one complete an exhaustive evaluation, including endoscopy and a bone marrow evaluation to find a cause? Unfortunately, no evidence based guideline exists as to the appropriate evaluation and most studies show no proximate cause in approximately 1/3rd of cases.1,7 Even should the results of this manuscript be validated that anemia by WHO threshold does not predict mortality in blacks, it will not prove that we should employ a lower Hb threshold in defining anemia in elderly blacks. Some blacks may have a lower Hb due to genetic changes, such as a-thalassemia,8 which may lower the population based median Hb. However, defining anemia on a population basis using a lower Hb threshold runs a serious risk of missing important causes. Only a rigorous study documenting anemia etiology by race and Hb threshold will clarify the Hb concentration where we can safely defer an etiologic evaluation.
Finally, we must recognize that observational data on Hb and mortality do not necessarily dictate Hb criteria for corrective therapy. The Hb concentration where treatment should be initiated and the target Hb concentration must be guided by prospective interventional trials. This analysis raises the provocative hypothesis that race should be analyzed in these interventional trials.
This manuscript should increase awareness of anemia in older adults and the markedly higher prevalence in blacks. It is likely that genetic differences account, at least in part, to the lower median Hb in blacks and higher anemia prevalence. However, whether a lower Hb threshold should be used for all blacks remains unknown. For now, it seems premature to use a lower Hb value for etiologic evaluation in blacks compared to whites until further data are published.
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