Preclinical obesity, clinical obesity with cardiac phenotypes and CVD mortality

Background Current BMI-based diagnostic paradigm for obesity can both underestimate and overestimate adiposity and provide inadequate information about health. The Lancet Diabetes & Endocrinology Commission proposed a novel classification framework for obesity on January, 2025. The effects of different obesity stages on CVD mortality and cardiac phenotypes remain unknown. Purpose To evaluate the associations between obesity status with cause-specific mortality and cardiac phenotypes. Methods This study analyzed data from UK Biobank participants with available data for obesity classification. Participants were stratified into non-obesity, preclinical obesity, and clinical obesity groups using The Lancet Diabetes & Endocrinology Commission definitions. The primary outcomes were all-cause mortality, CVD mortality, and non-CVD mortality. The associations between obesity with ECG, CMR, and plasma myocardial injury biomarker were also evaluated. Multivariable Cox models and multivariable linear models were applied for the associations between obesity status with mortality and cardiac measurements, respectively. Results The overall cohort included 439317 participants, with 160430 classified as non-obesity, 86815 as preclinical obesity, and 192072 as clinical obesity. During a median follow-up of 14.7 years, 38381 all-cause death, 14135 CVD death, and 24246 non-CVD death were observed. Compared to non-obesity, preclinical obesity was not significantly associated with all-cause mortality, CVD mortality, or non-CVD mortality (Figure 1). Compared to non-obesity, clinical obesity significantly increased the risk for all-cause mortality (adjusted HR 1.12, P<0.001), CVD mortality (aHR 1.28, P<0.001), and non-CVD mortality (aHR 1.06, P<0.001) (Figure 1). When compared to preclinical obesity, clinical obesity was associated with nearly 12%, 41%, and 4% increased risk of all-cause mortality (aHR 1.12, P<0.001), CVD mortality (aHR 1.41, P<0.001), and non-CVD mortality (aHR 1.04, P=0.038). Compared to preclinical obesity, clinical obesity was associated with significantly higher plasma levels of NT-proBNP and troponin I. Additionally, clinical obesity exhibited significant correlations with ECG alterations, including prolonged P-wave duration, PR interval, QRS duration, and QTc interval, accompanied by shortened RR interval, elevated ventricular rate, significant altered P-wave axis and R-wave axis (all P<0.05), compared to preclinical obesity (Figure 2). Regarding to CMR phenotypes, compared to preclinical obesity, clinical obesity was associated with enlarged left ventricular (LV) volume, increased LV wall thickness, increased LV mass, and impaired LV strain, as well as enlarged left atrial (LA) volume and decreased LA function (Figure 2). Conclusions Compared to preclinical obesity, clinical obesity confers 41% excess CVD mortality risk, accompanied by cardiac remodeling, proarrhythmic electrophysiological shifts, and myocardial injury.Figure 1 Figure 2