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.