Frailty in middle adulthood and associations with negative health-related outcomes in NHANES

Background: Frailty represents a state of compromised ability to cope with environmental stressors and is associated with negative health-related outcomes in older adults. The study objective is to investigate the prevalence and whether frailty associates with negative health-related outcomes in middle-aged adults. Methods: Data were sourced from three 2-year cycles of NHANES surveys and combined with Public-use Linked Mortality Files. A frailty index incorporating thirty variables was developed according to recommended criteria. “Prefrail” individuals were defined with a frailty index value ranging from 0.08 to 0.25, while “Frail” ≥0.25. A 10-year survival analysis was conducted using the Kaplan-Meier estimator, stratified by frailty state, and hazard ratios were calculated. Associations between frailty and outcomes were quantified using logistic regression models. Bootstrapped C-index and Brier score were calculated in the overall sample and stratified by decades of age. Results: In a sample of 5,745 middle-aged adults, 11% were identified as frail. Over a median follow-up of 5.9 years, 3% of participants died. The frailty index increased with age and its determinants differed across decades of age. Frail, middle aged, individuals faced a three-to-fourfold higher mortality risk, with a C-index of around 65%. Additionally, frailty was associated with a higher likelihood of hospitalization, increased health-care utilization, and changes in health status. Multimorbidity represented a confounder of frailty in the fourth decade, but not in the fifth. Conclusion: Frailty associates with negative health-related outcomes in middle-aged adults, emphasizing the importance of a comprehensive assessment. Multimorbidity only partially accounts for this association.