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Background <p>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.</p> Methods <p>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.</p> Results <p>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.</p> Conclusion <p>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.</p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年4月19日

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  • Panaiotis Finamore,
  • Claudio Pedone,
  • Magnus Ekström,
  • David M. Mannino,
  • Raffaele Antonelli Incalzi,
  • Simone Scarlata

摘要

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.