Adiposity as a full mediator of the influence of cardiorespiratory fitness and inflammation in schoolchildren: The FUPRECOL Study

Highlights

• Fit and normal weight youths have lower levels of hs-CRP.

• The influence of CRF on hs-CRP was fully mediated by adiposity.

• Programmes aimed at increasing CRF and reducing adiposity in childhood may be important for reducing systemic inflammation.

Abstract

Background and aims

Studies in the paediatric population have shown inconsistent associations between cardiorespiratory fitness and inflammation independently of adiposity. The purpose of this study was (i) to analyse the combined association of cardiorespiratory fitness and adiposity with high-sensitivity C-reactive protein (hs-CRP), and (ii) to determine whether adiposity acts as a mediator on the association between cardiorespiratory fitness and hs-CRP in children and adolescents.

Methods and results

This cross-sectional study included 935 (54.7% girls) healthy children and adolescents from Bogotá, Colombia. The 20 m shuttle run test was used to estimate cardiorespiratory fitness. We assessed the following adiposity parameters: body mass index, waist circumference, and fat mass index and the sum of subscapular and triceps skinfold thickness. High sensitivity assays were used to obtain hs-CRP. Linear regression models were fitted for mediation analyses examined whether the association between cardiorespiratory fitness and hs-CRP was mediated by each of adiposity parameters according to Baron and Kenny procedures. Lower levels of hs-CRP were associated with the best schoolchildren profiles (high cardiorespiratory fitness + low adiposity) (p for trend <0.001 in the four adiposity parameters), compared with unfit and overweight (low cardiorespiratory fitness + high adiposity) counterparts. Linear regression models suggest a full mediation of adiposity on the association between cardiorespiratory fitness and hs-CRP levels.

Conclusions

Our findings seem to emphasize the importance of obesity prevention in childhood, suggesting that having high levels of cardiorespiratory fitness may not counteract the negative consequences ascribed to adiposity on hs-CRP.

Introduction

Adipose tissue is a well-known source of inflammation, considered as a complex and highly active metabolic endocrine organ that produces various cytokines [1]. Chronic inflammation is considered an important pathogenic mechanism for the onset and progression of cardiovascular diseases (CVD) [2]. C-reactive protein is an acute-phase protein synthesized in the liver, its altered levels induce endothelial dysfunction, and accelerate progression of atherosclerosis [3]. High-sensitivity C-reactive protein (hs-CRP) one of the most commonly measured biomarkers of inflammation in clinical settings [4]; is an independent predictor of cardiovascular risk [4], [5] and a potential marker for the early detection of subjects at risk [6].

In addition to excess adiposity, low cardiorespiratory fitness and low muscular strength are independently associated with increased risk of CVD in youngsters, as well as with premature mortality [7]. Cardiorespiratory fitness has been related with lower concentrations of hs-CRP in adults [8]; and high levels of cardiorespiratory fitness during childhood associate with lower levels of inflammatory biomarkers in adulthood [9]. However, such associations are not well established in youth populations. Some studies have showed negative associations between cardiorespiratory fitness and hs-CRP [10], [11], whereas others have not [12], [13]. Moreover, in many of these studies, the results are not presented independently of adiposity, a potential confounder or mediator variable of the relationship between hs-CRP and cardiorespiratory fitness [2]. The National Health and Nutrition Examination Survey suggests that body mass index (BMI) is the best predictor of hs-CRP levels in children and adolescents [14]. Therefore, studies in the paediatric population have shown an inconsistent association between cardiorespiratory fitness and chronic inflammation independent of adiposity levels or weight status.

Given the positive influence of physical fitness on chronic inflammation and its relationships with adiposity [2], it would be useful to clarify whether cardiorespiratory fitness is independently protective of chronic low-grade inflammation, or whether its influence is mediated by adiposity in youths. Mediation analysis is a statistical method that can be used to elucidate the processes underlying an association between two variables and the extent to which the association can be modified, mediated, or confounded by a third variable [15].

Latin American children and adolescents exhibit high levels of overweight and obesity combined (7.1%) [16], and therefore identifying youths who have high levels of fatness, but are fit or, conversely, who have healthy body composition but are unfit, is of high public health importance. It will further improve our understanding on the health-risk within adiposity categories and may help to inform the development of targeted interventions for different phenotypes. Therefore, the objective of the present study was two-fold: to analyse the combined association of cardiorespiratory fitness and adiposity with high-sensitivity C-reactive protein, and to determine if adiposity acts as a mediator on the association between cardiorespiratory fitness and hs-CRP in children and adolescents from Bogotá, Colombia.