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

The associations of long-term body mass index (BMI) exposure, including both cumulative burden and increasing trends from childhood to adulthood, with subclinical cardiovascular outcomes remain incompletely understood, especially across distinct life stages. This study aimed to examine these associations and evaluate the potential mediating roles of established cardiovascular risk factors. 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 increasing trends of BMI were quantified using total and incremental areas under the curve (AUCs). Multivariable logistic regression and exploratory multiple-mediator analyses were used to examine associations and potential indirect-effect patterns, respectively. 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, 1.59 (1.41–1.80) and 1.25 (1.10–1.43); 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). Exploratory multiple-mediator analyses suggested that mid-adulthood cardiovascular risk factors jointly mediated a substantial proportion of the associations between BMI AUCs and both brachial-ankle pulse wave velocity (baPWV) and cIMT. In contrast, the corresponding indirect-effect patterns for left ventricular mass index (LVMI) were weaker and less robust. Blood pressure consistently emerged as the most prominent contributor across all models. Greater cumulative BMI burden and increasing BMI trends throughout the life course were associated with subclinical cardiovascular outcomes in mid-adulthood, with childhood increases in BMI showing particularly strong associations. These associations were partially explained by traditional cardiovascular risk factors, most notably blood pressure.