Abstract
BACKGROUND: The 2024 European Association for the Study of Obesity (EASO) framework redefines obesity by incorporating central adiposity and morbidity. However, the phenotypic characterization of risk heterogeneity across the full BMI spectrum under this framework-and its prognostic implications for mortality and cardiovascular outcomes-remain to be elucidated. Therefore, we aimed to evaluate the ability of this new framework to improve phenotypic stratification and describe risk heterogeneity across BMI categories.</p>
METHODS AND RESULTS: In 451,615 UK Biobank participants (median follow-up, 15.1 years), obesity was defined using (1) the EASO framework (which reclassifies individuals with BMI 25-<30 kg/m² into 'EASO overweight' [WHtR <0.5 and/or absence of morbidity] and 'EASO new obesity' [WHtR ≥0.5 and the presence of at least one morbidity]), and (2) an extended EASO framework incorporating morbidity stratification across all BMI categories. Cox proportional hazards models estimated hazard ratios (HRs) for all-cause mortality and major adverse cardiovascular events (MACE). Applying the EASO framework reclassified 15.62% of individuals previously categorized as having overweight into the category of people with obesity. Consequently, the prevalence of obesity increased from 24.50% to 40.12%. Two distinct risk patterns emerged: all-cause mortality showed a V-shaped association across adiposity categories, whereas MACE risk increased linearly with higher adiposity. Compared with normal weight, EASO overweight had the lowest mortality (HR 0.82 [95% CI, 0.80-0.84]), while EASO new obesity showed a comparable risk (0.96 [0.94-0.99]). The highest mortality risk was observed in BMI obesity (1.05 [1.02-1.08]). For MACE, EASO overweight had no excess risk (1.04 [0.99-1.09]), whereas both EASO new obesity and BMI obesity faced the highest and most substantial risks, with HRs of 1.35 (1.29-1.42) and 1.38 (1.32-1.45), respectively. When stratified by morbidity, the V-shaped mortality association was preserved and MACE risk remained linear. Individuals with morbidity consistently exhibited higher risks across all adiposity categories, indicating a vertical shift in risk rather than a change in association shape.</p>
CONCLUSIONS: The EASO framework substantially increases obesity prevalence and better identifies individuals with adverse metabolic and cardiovascular profiles. Morbidity does not alter the overall pattern of mortality and cardiovascular risk across adiposity levels but consistently amplifies absolute risk, supporting a morbidity-integrated approach to obesity phenotyping and risk assessment.</p>