Objective
To translate data relating childhood cardiovascular (CV) risk factors and adult CV disease and type 2 diabetes mellitus (T2DM) to clinically actionable values.

Study design
A prospective observational study (n=38,589) in the International Childhood Cardiovascular Cohort (i3C) Consortium. Children at age 3 through 19 years were enrolled in the 1970s and 1980s and followed for over 30 years. Five childhood CV risk factors (smoking, body mass index [BMI], systolic blood pressure [SBP], triglycerides [TG], and total cholesterol [TC]) were related to adult CV events. Secondary analyses in a subset included low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), glucose and insulin level. Age- and sex-specific z-scores were calculated for each risk factor, and a combined-risk z-score was calculated by averaging z-scores for the 5 key CV risk factors. Risk factor z-scores were back-transformed to natural units for clinical interpretation, with hazard ratios for adult CV events presented in color coded tables (green: no increased risk; orange: 1.4 to <2.0-fold increased risk; red: at least doubling of risk). Risk levels for development of adult T2DM based on BMI, glucose, and insulin were similarly calculated and presented.

Results
Increased risk for CV events was observed at levels lower than currently defined abnormal clinical thresholds except for TC. Doubling of risk was observed at high normal levels just below the clinical cut point for abnormality. Risk for adult T2DM began at levels of BMI and glucose currently considered normal.

Conclusion
Based on data showing significant relationships between childhood CV risk factors and adult CV events and T2DM, this study shows that risk in childhood begins below levels currently considered normal.