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<p>Frailty is a heterogeneous aging phenotype that represents accumulated biological vulnerability among very old adults. How frailty relates to key late-life transitions at advanced ages remains incompletely understood. We examined the longitudinal association between frailty status and a composite endpoint of incident long-term care insurance certification (level ≥ 2) or death, and assessed whether circulating biomarkers (growth differentiation factor-15 [GDF-15] and N-terminal pro–B-type natriuretic peptide [NT-proBNP]) provided information beyond frailty. In this cohort study, 992 community-dwelling adults aged 85–89&#xa0;years in Japan, classified using physical frailty criteria at baseline as either robust, prefrail, or frail, were followed up to 7.5&#xa0;years. Risk over time was compared using Kaplan–Meier methods, and Cox proportional hazards models were used to estimate adjusted hazard ratios (aHRs). Kaplan–Meier curves showed clear separation across the frailty groups. In multivariable models, prefrail and frail status were associated with a higher risk of the composite endpoint (aHRs 1.62 and 2.13 vs. robust, respectively). After adjusting for frailty status and covariates, higher GDF-15 and NT-proBNP levels were independently associated with greater risk. The GDF-15 association was adequately described by a linear term, whereas NT-proBNP showed evidence of nonlinearity with a steeper gradient toward the upper range. As a supportive summary of risk stratification, 5-year discrimination changed only modestly after adding biomarkers. Frailty strongly stratified the risk of major late-life transitions, and baseline GDF-15 and NT-proBNP may help characterize residual biological heterogeneity beyond frailty, with contrasting dose–response patterns.</p>

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Frailty and major late-life transitions in very old adults: contrasting biomarker patterns of GDF-15 and NT-proBNP in the Kawasaki Aging and Wellbeing Project

  • 期刊论文

  • 发表日期：

    2026年6月17日

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  • Aiko Shiohama,
  • Takashi Sasaki,
  • Yukiko Abe,
  • Ryo Shikimoto,
  • Yasumichi Arai

摘要

Frailty is a heterogeneous aging phenotype that represents accumulated biological vulnerability among very old adults. How frailty relates to key late-life transitions at advanced ages remains incompletely understood. We examined the longitudinal association between frailty status and a composite endpoint of incident long-term care insurance certification (level ≥ 2) or death, and assessed whether circulating biomarkers (growth differentiation factor-15 [GDF-15] and N-terminal pro–B-type natriuretic peptide [NT-proBNP]) provided information beyond frailty. In this cohort study, 992 community-dwelling adults aged 85–89 years in Japan, classified using physical frailty criteria at baseline as either robust, prefrail, or frail, were followed up to 7.5 years. Risk over time was compared using Kaplan–Meier methods, and Cox proportional hazards models were used to estimate adjusted hazard ratios (aHRs). Kaplan–Meier curves showed clear separation across the frailty groups. In multivariable models, prefrail and frail status were associated with a higher risk of the composite endpoint (aHRs 1.62 and 2.13 vs. robust, respectively). After adjusting for frailty status and covariates, higher GDF-15 and NT-proBNP levels were independently associated with greater risk. The GDF-15 association was adequately described by a linear term, whereas NT-proBNP showed evidence of nonlinearity with a steeper gradient toward the upper range. As a supportive summary of risk stratification, 5-year discrimination changed only modestly after adding biomarkers. Frailty strongly stratified the risk of major late-life transitions, and baseline GDF-15 and NT-proBNP may help characterize residual biological heterogeneity beyond frailty, with contrasting dose–response patterns.