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.

Keywords: NHANES; all-cause mortality; cancer; cardiovascular disease; obesity; phenotypic age acceleration.

Figure 1

Study flow chart.

Figure 2

Kaplan-Meier survival curve of all-cause mortality (A), CVD mortality (B), and cancer mortality (C) according to phenotypic age acceleration among obese adults. CVD, cardiovascular disease.

Figure 3

The dose-response association of the age acceleration residual with all-cause mortality (A), CVD mortality (B), and cancer mortality (C) among obese adults. This spline model was adjusted for age, gender, race, marital status, PIR group, educational level, HEI-2015, physical active, smoking status, and alcohol intake, CVD, hypertension, hyperlipidemia, diabetes, and cancer. HEI-2015, Healthy Eating Index-2015; PIR, poverty income ratio; CVD, cardiovascular disease.

Figure 4

Subgroup analyses of the association of the phenotypic age acceleration with all-cause mortality among obese adults. CVD, cardiovascular disease; PAA, phenotypic age acceleration.