Relationships between sedentary behaviour, physical activity levels and red blood cell distribution width in children and adolescents

Introduction

Cardiovascular disease (CVD) is the most common cause of mortality and morbidity worldwide,¹ often manifesting clinically in middle or old age. Emerging findings, however, have demonstrated that some risk factors for CVD are present in childhood² and that these factors are associated with an elevated lifetime risk for CVD.³ An attempt to discover the early predictors of CVD has provided the impetus for extensive work focused on the discovery of novel biomarkers and pathways in the early detection, prevention and management of CVD.¹

Red blood cell distribution width (RDW), an indicator of anisocytosis, or increased variation in red blood cell (RBC) size, is a novel biomarker for CVD.⁴ Higher RDW is strongly associated with adverse clinical outcomes in patients with CVD,^5,6 cerebrovascular disease,⁷ and is a predictor of all-cause CVD mortality. Although the pathophysiologic mechanism by which RDW is linked to CVD remains uncertain, most of the proposed mechanisms reflect an underlying inflammatory condition, oxidative stress or dyslipidemia.⁸ Since RDW has the potential to provide prognostic information about CVD risk without significant cost burden,⁹ there is interest in exploring the factors that alter RDW levels and, subsequently CVD risk.

It is well known that prolonged sedentary behavior (SB) and reduced physical activity (PA) are risk factors for CVD and major contributors to CVD mortality.^10-12 There are several possible biological mechanisms by which increased PA contributes to reducing CVD risk including improved body composition, enhanced lipid metabolism,¹³ reduced blood pressure (BP)¹⁴ and reduced systemic inflammation.¹⁵ Specifically, C-reactive protein (CRP), a protein associated with chronic inflammation, is a strong predictor of CVD risk that can be decreased with increased PA and reduced SB.¹⁶ Exploring mechanisms linking SB, PA and CVD are warranted¹⁷ in order to refine screening strategies and to monitor the short-term effects of interventions on long-term CVD risk.

While there is evidence that increased RDW levels are associated with lower PA, higher SB, and the presence of CVD in adults,^9,18,19 these relationships have not been explored in children and adolescents. If a similar association between RDW, SB and PA exist in children and adolescents, RDW may represent a potential target for CVD prevention. Identification of modifiable risk factors for CVD is important in the younger population before signs of CVD appear. In addition, changes in child PA behaviour may result in better PA habits in adolescence and ultimately in the adulthood.²⁰

The purpose of this study was to describe the relationships between objectively measured SB, PA and RDW among children and adolescents, and to determine whether these relationships were independent of known factors affecting RDW.

Materials and Methods

Results

Physical activity

Participants wore the accelerometer for an average of 5 days. Mean wear time was 14.8 (SD 2.3) and 14.5 (SD 2.1) hours per day for boys and girls, respectively. There were significant differences in SB, MPA, and VPA and in both average length of sedentary and active bouts between boys and girls (P < 0.001, for all), but not in LPA and sedentary breaks.

Volume of sedentary time and all PA intensities across RDW-Q in both boys and girls are presented in Figure 1. Boys in the highest RDW-Q spent an average of 498 minutes in SB, 39 minutes in LPA, 38 minutes in MPA, and 14 minutes in VPA compared to 487, 38, 37, and 13 minutes for boys in the lowest RDW-Q. Girls in the highest RDW-Q spent an average of 522 minutes in SB, 36 minutes in LPA, 24 minutes in MPA and 5 minutes in VPA compared to 516, 36, 22 and 5 minutes, for those in the lowest RDW-Q (Table 1). Although both boys and girls in the highest RDW-Q spent more sedentary time than those in lowest RDW-Q, the difference was not significant. Among girls, average MPA was significantly greater in the highest RDW-Q compared to the lowest, but lower than the second and third RDW-Q (P = 0.041). The associations between average sedentary bout length and number of sedentary breaks with RDW for both sexes were not significant.

Figure 1. Sedentary behavior and physical activity across RDW-Q in boys and girls.
SB: sedentary behaviour; LPA: light physical activity; MPA: moderate physical activity; VPA: vigorous physical activity, RDW-Q: red blood cell distribution width quartile.

Discussion

The results of this study are consistent with previous studies with adults that reported associations between RDW, sedentary time and moderate PA.^9,18,25 Though the underlying mechanism of the association between RDW and CVD remains unclear, there is strong evidence of a positive association between RDW and CVD and all-cause of CVD mortality in adults.^19,25,26 In addition, previous studies with adults demonstrated that moderate-to-vigorous PA was independently associated with reduced odds of elevated RDW.^9,25

Various theories exist about the mechanisms involved in the relationships between SB and PA and RDW. One of the mechanisms is via the influences of inflammation on anisocytosis.²⁵ Prolonged SB increases inflammatory cytokines while PA has an anti-inflammatory effect. Inflammatory conditions target endothelium, and promote vascular dysfunction with subsequent atherosclerosis.²⁷ It is unclear if RDW is an independent CVD risk factor or a marker of an underlying inflammatory state.⁸ However, in large studies, the association between higher RDW levels and CVD remained significant after adjusting for a number of confounding variables.^5,6

For boys, the SB and MPA multivariable analysis explained nearly 20% and 19% of the variance of RDW, respectively. Although the magnitude of these estimated effects was smaller when compared to adults, it is important to consider the potential clinical significance of these findings. The stronger association in adults may be due to the accumulation of the effects of SB and PA over time. It is possible that increasing sedentary time may augment risks associated with elevated RDW, whereas increasing MPA may have a beneficial effect. From a public health perspective, this finding is important, as reducing sedentary time may be a particularly important message for boys. Further longitudinal and interventional research to examine the effects of changing SB and PA on CVD risk factors, including RDW, in children and adolescents is required.

Sedentary behavior has recently gained much interest as a risk factor for CVD morbidity and mortality.¹¹ Developing findings suggest that increased SB is associated with CVD risk factors such as obesity, metabolic syndrome (MetS), and changes in lipoprotein lipase activity, independent of PA.²⁸ Former studies in children and adolescents demonstrated associations between prolonged SB with MetS and cardiovascular health.²⁸ Conversely, another study conducted on young children using NHANES database showed that diet and PA (using questionnaires) were not significantly associated with CVD risk factors or indicators of body fat.²⁹ There is accumulating evidence that higher PA is strongly associated with a lower risk of CVD in adults and this relationship holds in young individuals.³⁰ Increased PA in childhood can reduce CVD risks and may protect against atherosclerosis, if PA levels are maintained in young and middle adulthood.³⁰

Increased SB and decreased PA were associated with higher RDW in boys and not girls. Sex differences in CVD disease risk have been demonstrated in children in other studies. For example, Füssenich et al,³¹ reported higher PA levels in boys, and also found significant differences in composite CVD risk scores between active and inactive boys but not in girls. In addition, previous research using NHANES data demonstrated that prevalence of CVD risk factors and MetS was higher in boys compared to girls.³² Increased prevalence of risk factors for boys appears to exist despite the fact that boys were more physically active and less sedentary.²¹

The difference between boys and girls is consistent with our knowledge regarding the later onset of CVD in women.³³ Despite the fact that higher weight, BMI, WC, and SBP were associated with elevated RDW levels in girls but not in boys, relationships between the SB and PA variables and RDW were not significant. These results are consistent with previous work by Botton et al,³⁴ who also found same similar sex-related associations between BMI, and WC with CVD risk factors. It is possible that CVD protective factors may attenuate the influence of PA levels on CVD risk factors, including RDW, in girls.³³ Although CVD is a major cause of death in women, mean age of onset is 7-10 years later than men.³³ Sex hormones may play a role attenuating the risk of CVD which could account for the sex-related differences in the relationships between SB, PA and RDW in this study.³⁵ Other sex specific differences including different influences of CVD risk factors have been noted in the literature such as smoking, physical inactivity, dietary habits, MetS and emotional stress.³⁴ These results further support sex specific analyses of risk factors related to CVD.

The cross-sectional design is a limitation of this study, since causality cannot be established. In addition, although the accelerometer is the most widely accepted way for assessing PA, accelerometry is limited by the inability to differentiate between different sedentary behaviour patterns which may not have the same association with health outcomes. Although we adjusted all models for potential confounders, the influence of latent variables especially sex-specific factors cannot be discounted.

Conclusion

This study demonstrated an association between RDW, SB and MPA in boys, but not in girls. As the magnitude of differences were small, additional research may be needed to confirm these findings and their clinical significance, to clarify underlying mechanisms and to explore causal relationships. Prospective studies are also needed to evaluate the effects of activity modification on RDW levels and the potential influence on CVD risk. Future work in this area should consider sex-specific differences in children and adolescents.

Ethical approval

No ethical approval was required for this study. NHANES data collection was approved by the ethics committee at the National Center for Health Statistics. Consent was obtained from all participants prior to data collection.

Competing interests

The authors declare no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Authors’ contributions

All authors were involved in the conceptualization of the study. NH and VEE performed the data analysis and interpretation. NH drafted the manuscript and acted as corresponding author. TM and LPW supervised the development of work, assisted with data interpretation and manuscript revision.

Acknowledgments

No funding was used to prepare this manuscript. Dr L.P.-W is supported by the Canadian Child Health Clinician Scientist Training Program (CCHCSP), the Women and Children’s Health Research Institute (WCHRI) through the generous support of the Stollery Children’s Hospital Foundation, and Alberta Policy Wise for Children and Families. VE is supported by Alberta Innovates Clinician Fellowship Award (#201600292).

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