Abstract
BackgroundThe relationship between body size across the life course and risks of cardiovascular disease (CVD) and mortality remains incompletely understood, particularly regarding transitions from childhood to adulthood and potential sex-specific differences. We examined the independent and joint associations of childhood body size, adulthood body mass index (BMI), and life-course body size trajectories with incident CVD and mortality.MethodsWe analyzed data from 456,461 UK Biobank participants free of CVD at baseline. Childhood body size at age 10 was self-reported as thinner, about average, or plumper relative to peers. Adulthood BMI was measured and classified as normal weight (<25 kg/m²), overweight (25-29.9 kg/m²), or obesity (≥30 kg/m²). Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for incident CVD - including stroke, coronary artery disease (CAD), and heart failure (HF) - and all-cause and cause-specific mortality. Sex-stratified analyses were conducted to assess effect modification.ResultsDuring follow-up, 2703 participants developed stroke, 13,349 HF, and 37,365 CAD. Compared with average childhood body size, plumper childhood was associated with higher risks of HF (HR 1.21, 95% CI 1.14-1.28) and CAD (HR 1.08, 95% CI 1.04-1.11). Adulthood obesity was strongly associated with HF (HR 1.91, 95% CI 1.80-2.02), CAD (HR 1.59, 95% CI 1.53-1.64), and all-cause mortality (HR 1.16, 95% CI 1.12-1.20). Life-course transitions toward obesity showed the highest risks, particularly for thinner-to-obesity trajectories (HF: HR 2.18, 95% CI 2.00-2.39; CAD: HR 1.72, 95% CI 1.62-1.81; all-cause mortality: HR 1.21, 95% CI 1.14-1.28). Associations with stroke were weaker and mainly observed for thinner-to-obesity transitions (HR 1.24, 95% CI 1.02-1.52). Associations were generally stronger in women.ConclusionBody size across the life course is associated with CVD and mortality, with progression to obesity from childhood to adulthood conferring the greatest risk. These findings support life-course and sex-sensitive obesity prevention strategies.</p>