Increased Mortality Among Anemic Older Adults

Abstract & Commentary

By Andrew S. Artz, MD, Section of Hematology/Oncology, University of Chicago. Dr. Artz reports no financial relationship to this field of study.

Synopsis: Anemia in older adults is common. This observational study validates prior data by showing an independent association between anemia and increased risk of hospitalization and mortality. The relationship was non-linear. Outcomes were optimal at hemoglobin values of around 14-15 g/dL for women and 15-17 g/dL for men, with worse outcomes above and below these values. Interventional trials are warranted for anemic older adults.

Source: Culleton BF, et al. Impact of anemia on hospitalization and mortality in older adults. Blood. 2006:107:3841-3846.

Over 10% of community dwelling adults older than 65 years have anemia.1 The prevalence is estimated at 20-25% in those 85 years and older and 50% in hospitalized or institutionalized elderly. While an evaluation for anemia etiology remains essential in older adults, approximately one third or more will have no discernible cause.1,2

Considerable observational data have shown a negative and independent association between anemia and adverse outcomes, including inferior survival.3,4 The most common anemia definition used has been the WHO threshold of < 13 g/dL for men and < 12 g/dL for women. The WHO anemia threshold has been questioned, particularly among older adults, in light of emerging evidence of adverse outcomes even at hemoglobin concentrations above these values.5-7 Conversely, a few studies have suggested a reverse J-shaped curve, such that worse outcomes were identified at higher hemoglobin values, usually greater than 15-17 g/dL.5 Thus, the optimal hemoglobin concentration among older adults remains unclear.

Culleton and colleagues analyzed data available from adults 66 years or older from the Calgary Health Region in Canada. Among the 80,567 older adults in 2001, 18,076 had at least one hemoglobin value and creatinine measurement. After excluding patients who were institutionalized or on dialysis, 17,030 remained for the analysis. Four percent had a hemoglobin < 11 g/dL, whereas 13% met the WHO anemia definition. The median follow-up was 3.2 years. Anemia independently increased risk of hospitalization and mortality, even after stratification into different glomerular filtration rate categories to reduce the influence of chronic kidney disease. The best overall survival was found at a hemoglobin concentration of 14 to 15 g/dL for woman and 15-17 g/dL for men. Above these values, mortality risk increased (reverse J-shaped curve).

Commentary

This study by Culleton and colleagues supports prior data showing that hemoglobin concentrations considered "normal" for older adults, may have considerable adverse consequences. They also offer additional evidence for a reverse J-shaped curve by showing worse outcomes at high hemoglobin concentrations. Interestingly, similar adverse outcomes have been found in interventional cancer trials pushing hemoglobin above 14 g/dL.8

Clinicians practicing Hematology and/or Oncology are increasingly likely to see referrals for older anemic adults without overt cancer. The large observational studies leave many unanswered questions. Should a complete anemia evaluation be pursued at hemoglobin concentrations below 14 g/dL for women and 15 g/dL for men since outcomes are worse? How much of an extension of evaluation does anemia in older adults warrant (eg, bone marrow biopsy)? Another more challenging question arises whether Erythropoietin Stimulating Proteins (ESP) therapy should be instituted for anemic older adults in light of the adverse outcomes identified from the observational data. Outside of anemia related to cancer or chronic kidney disease, interventional data are too limited to recommend ESP therapy for older adults. In addition to difficulties obtaining ESP coverage outside of traditional treatment indications, we have no guidance about the adverse effects of hypertension and thrombotic risks, both of which may be elevated in older adults. Future studies of ESP therapy for anemia in older adults are warranted and could be designed to reduce hospitalization and mortality.

References

1. Guralnik JM, et al. Prevalence of anemia in persons 65 years and older in the United States: evidence for a high rate of unexplained anemia. Blood. 2004;104:2263-2268.

2. Artz AS, et al. Mechanisms of unexplained anemia in the nursing home. J Am Geriatr Soc. 2004;52:423-427.

3. Izaks GJ, et al. The definition of anemia in older persons. JAMA. 1999;281:1714-1717.

4. Penninx BW, et al. Anemia is associated with disability and decreased physical performance and muscle strength in the elderly. J Am Geriatr Soc. 2004;52:719-724.

5. Zakai NA, et al. A prospective study of anemia status, hemoglobin concentration, and mortality in an elderly cohort: the Cardiovascular Health Study. Arch Intern Med. 2005;165:2214-2220.

6. Beutler E, Waalen J. The definition of anemia: what is the lower limit of normal of the blood hemoglobin concentration? Blood. 2006;107:1747-1750.

7. Chaves PH, et al. What constitutes normal hemoglobin concentration in community-dwelling disabled older women? J Am Geriatr Soc. 2004;52:1811-1816.

8. Leyland-Jones B. Breast cancer trial with erythropoietin terminated unexpectedly. Lancet Oncol. 2003;4:459-460.