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1 Center on Aging and Health
Departments of 2 Medicine
3 Epidemiology, The Johns Hopkins University, Baltimore, Maryland.
4 Program of Studies, Debates, Research and Care on the Elderly–UNATI, Rio de Janeiro State University–UERJ, Brazil.
5 Ortho Biotech Clinical Affairs, Bridgewater, New Jersey.
6 Laboratory of Clinical Investigation, Gerontology Research Center, National Institute on Aging, Baltimore, Maryland.
7 Laboratory of Epidemiology, Demography, and Biometry, National Institute on Aging, Bethesda, Maryland.
Address correspondence to Paulo H. M. Chaves, MD, PhD, Assistant Professor of Medicine and Epidemiology, The Johns Hopkins Center on Aging and Health, 2024 East Monument Street, Suite 2-700, Baltimore, MD 21205. E-mail: pchaves{at}jhsph.edu
Background. The physiological basis of the geriatric syndrome of frailty, a clinical state of increased vulnerability to adverse outcomes such as disability and mortality, remains to be better characterized. We examined the cross-sectional relationship between hemoglobin (Hb) and a recently-validated measure of frailty in community-dwelling older women, and whether this relationship was modified by cardiovascular disease (CVD) status.
Methods. Data were pooled from women 70–80 years old participating in the Women's Health and Aging Studies I and II (Baltimore, MD, 1992–1996) with known frailty status and Hb 
10 g/dL (n = 670). Logistic regression was used to model the relationship between frailty and Hb, adjusting for demographics, major chronic diseases, and physiologic and functional impairments.
Results. Prevalence of frailty was 14%. Frailty risk was highest at the lowest Hb levels, and lowest at mid-normal Hb levels (e.g., 13–14 g/dL). Mildly low and low-normal Hb concentrations were independently associated with frailty. Compared to an Hb concentration equal to 13.5 g/dL, the adjusted odds of being frail were 1.9 (95% confidence interval: 1.1–3.4) and 1.5 (95% confidence interval: 1.0–2.1) times higher for Hb concentrations equal to 11.5 g/dL and 12 g/dL, respectively. A statistically significant (p <.05) multiplicative interaction between Hb level and CVD status with respect to frailty risk was observed.
Conclusion. In community-dwelling older women, mildly low and low-normal Hb levels were independently associated with increased frailty risk. This risk was synergistically modified by the presence of CVD. These results suggest that mild anemia, and even low-normal Hb levels are independent, potentially modifiable risk factors for frailty in community-dwelling older adults.
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