Association between phenotypic age and mortality risk in individuals with obesity: a retrospective cohort study

Abstract

Objective: This study investigates the association between phenotypic age acceleration (PAA) and all-cause and cause-specific mortality in obese individuals. Methods: Data were drawn from the National Health and Nutrition Examination Survey (NHANES) between 1999 and 2018, including 9,925 obese adults (BMI ≥ 30 kg/m2). PAA, defined as phenotypic age exceeding chronological age, was assessed using clinical biomarkers. Kaplan-Meier survival analysis and Cox proportional hazards models were used to assess the relationship between PAA and all-cause, cardiovascular, and cancer mortality, adjusting for covariates such as age, gender, race, lifestyle, and health status. Subgroup and sensitivity analyses were performed to ensure the robustness of the findings. Results: During a median follow-up of 10.6 years, 1,537 deaths were recorded, including 419 from cardiovascular disease and 357 from cancer. PAA was significantly associated with all-cause mortality (HR = 1.84, 95% CI: 1.64–2.06), cardiovascular mortality (HR = 1.86, 95% CI: 1.50–2.31), and cancer mortality (HR = 1.47, 95% CI: 1.17–1.85). These associations remained significant after adjusting for multiple variables, and sensitivity analyses confirmed the robustness of the results. Conclusion: PAA is an independent predictor of all-cause, cardiovascular, and cancer mortality in obese individuals. This study highlights the importance of PAA in mortality risk assessment and health management in the obese population.