Cumulative burden of body mass index from childhood to mid-adulthood in relation to subclinical cardiovascular outcomes: the mediating role of cardiovascular risk factors

Background The long-term impact of body mass index (BMI) exposure and its developmental trajectories from childhood to adulthood on subclinical cardiovascular outcomes remains incompletely understood, especially across distinct life stages. Purpose This study aimed to examine these associations and evaluate the mediating roles of established cardiovascular risk factors. Methods We analyzed data from 2,446 participants in the Hanzhong Adolescent Hypertension Study, all of whom had at least four BMI measurements over a 36-year follow-up period. Cumulative burden and trends of BMI were quantified using total and incremental area under the curve (AUC). Multivariable logistic regression and mediation analyses were employed to assess associations and mediating pathways. Results Higher total and incremental BMI AUCs during childhood, adulthood, and across the life course were significantly associated with an increased risk of arterial stiffness in mid-adulthood. For childhood, the odds ratios (ORs) with 95% confidence intervals (CIs) were 1.18 (1.03-1.35) for total AUC and 2.54 (1.88-3.44) for incremental AUC; for adulthood, 1.25 (1.10-1.43) and 1.59 (1.41-1.80); and over the life course, 1.52 (1.34-1.73) and 1.89 (1.60-2.23). Similar associations were observed for left ventricular hypertrophy (LVH), with the strongest effect observed for childhood incremental AUC (OR = 3.70, 95% CI: 2.09-6.56). For high carotid intima-media thickness (cIMT), all BMI AUCs, except for incremental AUC in adulthood, were significantly associated with an increased risk, with the strongest association again observed for childhood incremental AUC (OR = 1.50, 95% CI: 1.12-2.02). Mediation analyses showed that mid-adulthood levels of blood pressure, triglycerides, fasting glucose, insulin, and total cholesterol partially explained these associations, with varying contributions by outcome and life stage. Systolic blood pressure was the dominant mediator, accounting for 43.9-66.9% of the BMI AUCs’ effect on arterial stiffness, and up to 49.1% and 15.1% for high cIMT and LVH, respectively. Conclusions Greater cumulative burden and increasing trends of BMI through the life course were associated with subclinical cardiovascular outcomes in mid-adulthood, with BMI increases during childhood demonstrating particularly strong effects. These associations were partially mediated by traditional cardiovascular risk factors, most notably blood pressure.