Prediction of All-Cause Mortality by Obesity Metabolic Phenotypes: A Waist Circumference-Driven Risk Stratification Study

Background and Aims: The limitations of body mass index (BMI) in assessing obesity-related mortality risk are increasingly apparent. This study investigates whether a risk stratification based on waist circumference (WC) and metabolic status provides a superior prediction of all-cause mortality and examines how age and sex modify these associations. Methods: A prospective cohort study was conducted in rural Ningxia, China, including 2703 participants at baseline (2008–2012) and 2071 followed up (2019–2020). Participants were categorized into four phenotypes based on BMI or WC and metabolic status: metabolically healthy normal weight, metabolically healthy with obesity (MHO), metabolically unhealthy normal weight (MUNW), and metabolically unhealthy with obesity (MUO). Cox regression models were used to estimate hazard ratios (HRs) for all-cause mortality. Results: During follow-up, 193 deaths were recorded. When obesity was defined by BMI, only MUO was significantly associated with increased mortality (fully adjusted HR = 1.659, 95% confidence interval [CI]: 1.122–2.452, P = 0.011). When defined by WC, both MHO (HR = 1.823, 95% CI: 1.037–3.203, P = 0.037) and MUO (HR = 1.964, 95% CI: 1.273–3.029, P = 0.002) showed significantly higher risks. Subgroup analyses revealed that WC-defined MHO conferred increased mortality only in men and in younger participants (<64 years). Conclusion: In conclusion, WC is a superior predictor of all-cause mortality to BMI, particularly in men. The MHO phenotype is not uniformly benign, especially when defined by central adiposity. Therefore, we recommend risk stratification based on WC, metabolic status, age, and sex.