Cardiovascular health across childhood and adolescence and proteomic biomarkers in late adolescence

Aims

The American Heart Association’s Life’s Essential 8 cardiovascular health (CVH) construct strongly predicts cardiovascular disease (CVD), yet biological processes associated with early-life CVH trajectories are unclear. We examined associations of CVH score and trajectory parameters across childhood with cardiovascular-related proteins.

Methods and results

We derived CVH scores (0–100 points) in 424 children at median ages 3.2, 7.7, 13, and 17.5y. Segmented mixed-effect models estimated three CVH trajectory parameters: timing of inflection when CVH declines and slope before and after inflection. We assayed 92 proteins from plasma samples in late adolescence (17.5y). Linear regression models assessed cross-sectional (CVH in late adolescence) and longitudinal (CVH trajectory parameters) associations with proteins, with false discovery rate correction via Benjamini–Hochberg method. Mean (SD) late-adolescent CVH was 75.5 (10.5) points. Cardiovascular health slope before inflection was 0.6 (1.4) points/y, timing of inflection was 10.1y (0.7), and slope after inflection was −1.2 (1.2) points/y. Cross-sectionally, a 1-SD higher CVH was associated with 29 differentially abundant proteins (DAPs); five showed robust associations with log2–fold change ≥|0.2| (higher FGF-21, HAOX1, IL-1ra, LEP, and lower GH). Longitudinally, 1-SD increments in CVH trajectory parameters were associated with up to 13 DAPs; specifically, we observed robust associations of timing of CVH inflection with higher LEP and CVH slope after inflection with higher IL-1ra, LEP, and SERPINA12. These DAPs implicated lipid metabolism, inflammation, and glyoxylate/oxalate production pathways.

Conclusion

We identified novel protein biomarkers reflecting adolescent CVH and cumulative impact of childhood CVH trajectories, which may inform preventive strategies early in life to alter CVD progression.