Abstract Body: Introduction. Extensive research has shown an association between BMI and subclinical atherosclerosis in children. However, BMI is a time-varying risk factor, which changes substantially during childhood. To date, no study has investigated how BMI at different developmental stages contributes to subclinical atherosclerosis. The Bayesian Relevant Life Course Model (BRLM) is an ideal tool for evaluating how a time-varying exposure affects health outcomes later in life. In this study, we applied this novel approach to examine the association between life course BMI from early childhood to young adulthood and subclinical atherosclerosis in young adulthood.

Method. Data were from Southern California’s Children’s Health Study and its follow-up assessment, MetaAir2 (2003 to 2025). Indicators of subclinical atherosclerosis were evaluated by ultrasound at a mean age of 25 years including carotid artery intima-media thickness (IMT), distensibility, and lipid deposition (determined by gray-- scale median of intima media, IM-GSM). BMI was obtained at mean ages 6.5 (early childhood), 11 (mid-childhood), 15 (adolescence), and 25 years (young adulthood). We used BRLM to investigate: 1) the overall association of BMI measured across 19 years with subclinical atherosclerosis, and 2) the distribution of BMI-atherosclerosis association across the 4 stages. Analyses were adjusted for age, sex, race, ethnicity, adult physical activity level, and parental education level.

Results. Among 324 participants, the lifetime effect of BMI on IMT had a posterior mean of 4.4mm (95% CrI: 2.7, 6.4), providing strong evidence of a positive association. The contributions of each life stage were 9.7%, 15.3%, 34.3%, and 40.7% for early childhood, mid-childhood, adolescence, and young adulthood, respectively, supporting a sensitive-period hypothesis, in which all stages contributed to IMT, but young adulthood contributed greater weights. For IM-GSM, the posterior mean association with BMI was –1.19 (95% CrI: –1.54, –0.87). Stage contributions were 8.3%, 8.4%, 10.9%, and 72.4%, suggesting a critical-period effect for arterial wall lipid deposition dominated by young adulthood. The results for distensibility were similar to IM-GSM.

Conclusion. Life course BMI significantly impacts measures of subclinical atherosclerosis in early adulthood. Current BMI impacts lipid deposition and distensibility, while BMI’s impact on thickness is more cumulative, with slightly stronger effects from young adulthood.