In our results, Hb levels were positively associated with SPPB in older adults without anemia – those with higher Hb levels presented better physical performance. To our knowledge, this is the first study to analyze this association in older adults without anemia in LMIC. Our results confirm previous findings by Hirani and colleagues’ in which increases in Hb levels are associated with better physical performance indicators, but their results were limited to men in Australia. We show that this finding is also relevant for older women. Therefore, even among older populations without anemia, lower levels of Hb are associated with worse physical performance.
Previous authors have already suggested that the WHO criteria for defining anemia in adults may not be adequate for older populations. These optimal Hb cutoffs for clinical decision-making were defined mainly based on statistical distribution considerations using apparently healthy people, rather than being developed through considerations of inflammation, the high prevalence of chronic conditions in older adults, and the physiological reduction in Hb concentration in the oldest old, factors that would shift the Hb distribution (1, 24–26).
One cause of the association between Hb and physical performance is the fact that Hb is responsible for tissue oxygenation, and lower Hb values can lead to local hypoxia in skeletal muscle and reduced muscle function (11). This effect is usually described in people with anemia. However, we found that lower Hb levels, even without anemia, can lead to lower physical function. This finding has not been underexplored in the literature. Zakai et al. (4) suggested that functional decline may occur in close temporal association with hemoglobin decline, reinforcing that analyzing Hb levels may be more informative than only diagnosing anemia, as we showed here.
Steensma and Tefferi (2007) discussed that formal definitions of anemia do not always address the complex relationship between Hb level and health outcomes. Many factors can affect a healthy person’s Hb value, including ethnic background, altitude of residence, smoking status, and physiologic fluctuations of plasma volume. Hence, the interpretation of blood count results remains the responsibility of the ordering physician, who should also refer to a patient’s baseline Hb level when a previous measurement is available (24). In the same study, Steensma and Tefferi point out that a growing body of medical literature supports a “low-normal” Hb level associated with a broad range of poorer health-related outcomes. For example, a previous cross-sectional study using data from the 2010 wave of SABE study showed that at a concentration of 12 g/dL, the probability of mobility difficulty was 9.1%. But at higher levels, the probability of mobility decreased by 7.4% at 13 g/dL and 6.1% at 14 g/dL (8). Furthermore, the association was consistent in both men and women (8).
Another important aspect of our study is the specificity of the relationship between Hb concentrations and physical function, which was consistent even after adjusting for age, years of education, number of chronic cardiometabolic conditions, number of other chronic diseases, grip strength, and BMI, showing an independent association. Those covariates included in our analyses were largely discussed in the literature as risk factors for worse physical function and disability. Some functional decline is expected with advanced age, even without disease, but this decline is slow and gradual (27). Some authors point out that other factors are determinants for this decline, such as education (8, 28, 29). It is also well known that physical function decline is higher with chronic diseases (30, 31). Our analysis also opted to consider cardiometabolic conditions separately because it was already discussed that those conditions have an important interaction with anemia in physical function (13, 22). We also adjusted for grip strength, which is one of the main indicators of physical decline in older ages (32–35), as well as higher BMI, which several publications have indicated, is a risk factor for poor physical performance, mainly in walking and chair-stand tests (27, 32, 36, 37).
We also performed sensitivity analyses to ensure that our results are robust. In analyses including all participants (those with and without anemia), results were similar, showing that the relationship between Hb levels and SPPB scores is consistent across a wider Hb range.
Interpretation of our results should consider some limitations. First, as with any other aging cohort, the loss to follow-up and death during the period is considerable. Another study based on SABE data shows that anemia predicts mortality among participants (6); lower hemoglobin values among the non-anemic may as well. This suggests that our study underestimates the effects of Hb on physical performance. Another limitation is that the time between the two measurements (five years) is considerably long, which could mask shorter fluctuations.
But our study has several strengths. First, it is the first study with a large representative sample of community-dwelling older adults in an LMIC, where a nutritional transition is still ongoing, and the causes and consequences of lower levels of Hb may represent a heavy burden in health services. Also, our analyses considered the levels of Hb over time in physical function, which is less common as even longitudinal studies typically consider Hb levels only at the baseline. We also showed effects stratified by sex which is important to target health care actions specifically for men and women. Most importantly, we showed that the effects of Hb levels are consistent in non-anemic individuals, which may alert health professionals to the importance of evaluating changes in Hb levels in all older adults, even without the formal diagnosis of anemia.