Background The combined effect of cardiorespiratory fitness (CRF) and body mass index (BMI) on cardiovascular disease (CVD) risk in young people remains to be fully determined. We examined the individual and combined associations of CRF and BMI with clustered CVD risk factors, and the mediator role of BMI in the association between CRF and clustered CVD risk factors in children and adolescents. Methods 237 children (111 girls) and 260 adolescents (120 girls) were included in this cross‐sectional study. Height and weight were assessed and BMI was calculated. A CVD risk factor index (CVDRF‐I) was computed from: waist circumference, systolic blood pressure, triglycerides, high‐density lipoprotein cholesterol and glucose. CRF was assessed using the 20‐m shuttle run test. Regression analysis, analysis of covariance and mediation analysis (Baron and Kenny procedures) were used to test the independent and combined effect of CRF and BMI on CVDRF‐I, and to test mediation hypothesis, respectively. Results CRF was negatively associated with CVDRF‐I (all P < 0.05); however, after adjusting for BMI the associations were no longer significant in children and adolescents of both sex groups. Contrary, the association between BMI and CVDRF‐I was independent of CRF (all P < 0.001). The effect of CRF on CVDRF‐I was mediated by BMI. The percentage of the total effect of CRF on CVDRF‐I mediated by BMI for boys and girls children and boys and girls adolescents were 79.5%, 100%, 81.2% and 55.7%, respectively. Conclusions BMI is an independent predictor of CVDRF‐I and a mediator of the association between CRF and CVDRF‐I in children and adolescents. These results help to clarify the associations between CRF, weight status and cardiovascular health, suggesting that future CVD health would benefit from maintaining an optimal weight status.

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