Cross-sectional associations between cardiorespiratory fitness and NMR-derived metabolic biomarkers in children - the PANIC study

Abstract

Objective: Cardiorespiratory fitness has been inversely associated with cardiovascular risk across the lifespan. Some studies in adults suggest that higher cardiorespiratory fitness is associated with cardioprotective metabolite profile, but the evidence in children is lacking. Therefore, we investigated the cross-sectional association of cardiorespiratory fitness with serum nuclear magnetic resonance derived metabolic biomarkers in children.

Methods: A population sample of 450 children aged 6-8 years was examined. Cardiorespiratory fitness was assessed by a maximal exercise test on a cycle ergometer and quantified as maximal power output normalised for lean body mass assessed by dual-energy X-ray absorbtiometry. Serum metabolites were assessed using a high throughput nuclear magnetic resonance platform. The data were analysed using linear regression analyses adjusted for age and sex and subsequently for body fat percentage (BF%) assessed by DXA.

Results: Cardiorespiratory fitness was directly associated with high density lipoprotein (HDL) cholesterol (β=0.138, 95% CI=0.042 to 0.135, p=0.005), average HDL particle diameter (β=0.102, 95% CI=0.004 to 0.199, p=0.041), and the concentrations of extra-large HDL particles (β=0.103, 95% CI=0.006 to 0.201, p=0.038), large HDL particles (β=0.122, 95% CI=0.025 to 0.220, p=0.014), and medium HDL particles (β=0.143, 95% CI=0.047 to 0.239, p=0.004) after adjustment for age and sex. Higher cardiorespiratory fitness was also associated with higher concentrations of ApoA1 (β=0.145, 95% CI=0.047 to 0.242, p=0.003), glutamine (β=0.161, 95% CI=0.064 to 0.257, p=0.001), and phenylalanine (β=0.187, 95% CI=0.091 to 0.283, p<0.001). However, only the direct associations of cardiorespiratory fitness with the concentrations of HDL cholesterol (β=0.114, 95% CI=0.018 to 0.210, p=0.021), medium HDL particles (β=0.126, 95% CI=0.030 to 0.223, p=0.010), ApoA1 (β=0.126, 95% CI=0.030 to 0.223, p=0.011), glutamine (β=0.147, 95% CI=0.050 to 0.224, p=0.003), and phenylalanine (β=0.217, 95% CI=0.122 to 0.311, p<0.001) remained statistically significant after further adjustment for BF%.

Conclusions: Higher cardiorespiratory fitness was associated with a cardioprotective biomarker profile in children. Most associations were independent of BF% suggesting that the differences in serum metabolites between children are driven by cardiorespiratory fitness and not adiposity.

Keywords: aerobic fitness; fitness; lipoproteins; metabolism; metabolomics; obesity; pediatrics.