Bo Wang¹, Du Bowen¹, Wang Jian¹, Sun Kun¹
1- Xinhua hospital affiliated to Shanghai Jiao Tong University School of Medicine, China
Abstract Body
Introduction: Obesity and metabolic dysregulation drive cardiac remodeling, yet their distinct life-course impacts on specific structural and functional parameters remain poorly defined.
Objectives: To disentangle the independent and synergistic effects of body mass index (BMI) and metabolic score (MetScore) on cardiac structure and function across the life course.
Methods: This study utilized data from 3 prospective cohorts, including Shanghai Birth Cohort (SBC, age 7 , 1,391 participants), Avon Longitudinal Study of Parents and Children (ALSPAC, age 17 .5, 941 participants) and UK Biobank (UKB, age 40-60, 74,032 participants). Multivariable regression, one-sample Mendelian randomization (MR), metabolome-wide association studies (MWAS), and structural equation modeling (SEM) were employed to assess associations, causality , and mechanistic pathways.
Results: Across the life course, BMI associated more strongly with structural indices, whereas MetScore was more prominently linked to diastolic function; neither associated with systolicfunction. These divergent impacts were corroborated by one-sample MR. MWAS revealed thatMetScore could influence diastolic function via lipoprotein alterations (e.g., average diameter for HDL particles, proportion mediated: 13.59%) starting in adolescence and persisting into adulthood. Finally , SEM delineated two relatively independent yet intersecting pathways: BMI primarily drives structural alterations via hemodynamic load, while MetScore impairs diastolic function through lipidomic signatures.
Conclusions: BMI and metabolic dysregulation exert distinct and complementary influences on cardiac remodeling from childhood. BMI primarily drives structural alterations via hemodynamic load, whereas metabolic risk specifically targets diastolic function through lipidomic pathways. These independent pathways necessitate phenotype-tailored strategies for cardiovascular prevention across the life course.