In this study we identify a novel independent association between the HPR and children’s CRF, having controlled for the usual and well-known confounding variables of age, sex, and body size. We have also identified that hemoglobin, platelets and CRF values are different according to regions of the city. Specifically, children and adolescents residing in the city center and periphery (urban area) showed lower CRF and hemoglobin levels compared to those in rural areas. Conversely, platelet counts were found to be higher in the center and periphery zones compared to rural zones.
The log ratio models for the association between platelet counts and hemoglobin with CRF, suggest that when including the residence location of participants as a fixed factor, the strength of association between variables decreases, confirming that urban (center and periphery) and rural city zones have a significant role in explaining the mechanism associated with these correlations.
The physiological mechanisms that justify the association between the three variables (platelets, hemoglobin, and CRF) are well-established in the literature and help us understand the complex relationship between place of residence, cardiorespiratory health, and blood indicators. Oxygen transport to the working muscles is dependent on hemoglobin count and consequently, higher levels of hemoglobin are associated with greater values for cardiovascular endurance in children 15. Similarly, platelets play an important role in the pathogenesis of cardiovascular disease and higher levels of cardiovascular endurance are associated with suppressed platelet adhesiveness and aggregation in adults 16. Thus, higher levels of hemoglobin and lower platelet levels are reflective of better cardiovascular health. Both hemoglobin and platelet counts have been independently related to cardiovascular disease in adults (17, 18)). Only recently has the PHR emerged as a prognostic biomarker in coronary artery disease 5. The study by Bao et al., (2021) 5 identified platelet to hemoglobin ratio as a robust predictor of all cause mortlaity in heart failure patients and suggested additional work was needed to reinforce their findings in other population groups. The current study fills this gap by demonstrating for the first time that platelet to hemoglobin ratio is associated with CRF in children, after accounting for known confounders. Of note, we also identify that place of residence influences platelet and hemoglobin counts, reinforcing prior research which has identified that urban versus rural residence influences CRF and cardiovascular risk in children 8 and cardiovascular health, including blood parameters in adults 19.
It is important to emphasize that in a general context, urban areas tend to have higher levels of air pollution due to a greater concentration of human activities such as traffic, industries, and the use of fossil fuels 20,21. These activities release pollutants such as carbon dioxide (CO2), nitrogen oxides (NOx), particulate matter, and other harmful chemical compounds into the air, consequently affecting CRF 20,21,22. In rural areas, it is expected that this pollution will be lower compared to urban areas, even though there are negative effects of agricultural activity on the atmosphere, such as burning, pesticide spraying, and fertilizer use 9,20,21,22,23,24.
However, the level of pollution in rural and urban areas in the context of this study is still quite different due to the extensive rural zone present in the municipality. These facts hypothetically justify the results of this study since air pollution is a common problem in large cities, and it can have negative effects on human health 9,20, as evidenced by the elevated platelets, low CRF, and hemoglobin levels in the subjects of this research. There are associations between exposure to air pollutants such as PM2.5 (particulate matter with a diameter less than 2.5 µm) and an increased risk of cardiovascular and respiratory diseases 20. Furthermore, air pollution has been linked to hematological effects, including alterations in blood cell levels, including platelets 9,20,22.
Regarding peripheral areas, it is worth considering the potential presence of vulnerability within municipalities in Brazil, and there are studies that have investigated the relationship between social vulnerability and overall health 25,26. Although it is very difficult to find direct research on the relationship between social vulnerability and the number of blood platelets, it is important to note that chronic stress and exposure to adverse factors associated with social vulnerability, such as a sedentary lifestyle, can affect the immune and hematological systems, including increasing platelet production 27,28,29,30. Chronic stress can trigger inflammatory and immune responses 28,30, while physical exercise and increased physical fitness can regulate this system beneficially 30, and there is a negative relationship between social vulnerability and CRF 25. However, the exact mechanisms for this complex network of associations are still the subject of intense research.
The present study strengthens its validity by incorporating a representative sample from a Brazilian city's population, providing a homogeneous analysis of the associations between environmental variables and health outcomes. However, it is important to acknowledge certain research limitations. Specifically, this study does not encompass an assessment of potential contributions to air pollution in rural areas from agricultural practices, food processing industries, or intensive animal farming. Therefore, caution must be taken when making inferences regarding these hypotheses. Furthermore, given the cross-sectional nature of the study, which focuses on residential areas, physical and physiological health, as well as immune profiles, the findings should be interpreted with caution as they are indicative of associations rather than causal relationships.
In conclusion, we have identified a novel independent association between the hemoglobin-to-platelet count ratio and children’s CRF, having controlled for the usual and well-known confounding variables of age, sex, and body size. The same ratio (inverted) has been identified as a predictor of mortality in elderly Chinese coronary artery disease patients. However, for the first time, the same ratio also appears to be a valuable predictor of CRF in children. We also provide evidence of a possible mechanism for the association, having identified a reduced hemoglobin-to-platelet count ratio observed in urban areas. These results confirm the need for more effective public health practices and policies related to the health effects of the built environment for children and adults in Brazil. We can also speculate that a similar change in health policy is necessary in cities worldwide, such as the introduction of ultra-low emission zones in London.