Project R-16800

Lipidome-wide association study of adolescent hypertension and its early life determinants (Research)

Cardiovascular diseases begin decades before their clinical onset, yet the molecular processes that embed this early risk remain poorly understood. Lipids play a central role in energy metabolism, inflammation, and vascular integrity, but how the lipidome evolves during development to contribute to the origins of hypertension is largely unknown. DELHY aims to construct the first longitudinal map of human lipidomic development, from birth to adolescence, to identify specific lipid trajectories that precede the onset of hypertension, a condition that often persists into adulthood and amplifies lifelong cardiovascular risk. Using the ENVIRONAGE birth cohort, we will conduct a nested case-control study (incident hypertensive cases aged 9-12 years vs age- and sex-matched controls) with high-resolution lipidomic profiling (~2,000 species) across three developmental windows: birth, early childhood (4-6 years), and adolescence (9-12 years). Integrating longitudinal modeling and causal mediation analyses, DELHY will pinpoint lipid trajectories and critical windows through which early-life environmental exposures influence adolescent hypertension and related cardiovascular phenotypes, including cardiac and renal target organ damage. By revealing how lipid metabolism is developmentally programmed and environmentally modulated, DELHY will open a new mechanistic dimension to early-life cardiovascular research and advance the foundations of precision prevention in childhood.

01 November 2026 - 31 October 2027