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[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.

[Objective]: To examine the association between cardiorespiratory fitness (CRF) at baseline and cardiovascular disease (CVD) risk in 6- to 10-year-olds (cross-sectional) and 2 years later (8- to 12-year-olds [longitudinal]) and whether changes with age in CRF are associated with CVD risk in children aged 8 to 12 years. [Patients and Methods]: Spanish primary schoolchildren (n=236) aged 6 to 10 years participated at baseline. Of the 23 participating primary schools, 22% (n=5) were private schools and 78% (n=18) were public schools. The dropout rate at 2-year follow-up was 9.7% (n=23). The 20-m shuttle run test was used to estimate CRF. The CVD risk score was computed as the mean of 5 CVD risk factor standardized scores: sum of 2 skinfolds, systolic blood pressure, insulin/glucose, triglycerides, and total cholesterol/high-density lipoprotein cholesterol. [Results]: At baseline, CRF was inversely associated with single CVD risk factors (all P<.05) and CVD risk score at baseline and follow-up (P<.001). Cardiorespiratory fitness cutoff points of 39.0 mL/kg per minute or greater in boys and 37.5 mL/kg per minute or greater in girls are discriminative to identify CVD risk in childhood (area under the curve, >0.85; P<.001) and to predict CVD risk 2 years later (P=.004). Persistent low CRF or the decline of CRF from 6-10 to 8-12 years of age is associated with increased CVD risk at age 8 to 12 years (P<.001). [Conclusion]: During childhood, CRF is a strong predictor of CVD risk and should be monitored to identify children with potential CVD risk.