Impact of frailty phenotype on chronic disease accumulation and healthy life years lost: A multi-state analysis of the UK Biobank
- 1Department of Traditional Chinese Medicine, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, China
- 2The First Clinical Medical College, Beijing University of Chinese Medicine, Beijing, China
- 3Department of Traditional Chinese Medicine, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, China; Corresponding authors.
Abstract
Background: Frailty is a systemic vulnerability syndrome linked to adverse health outcomes, yet its role in shaping the dynamic trajectory from health through incident disease to multimorbidity remains poorly understood. Methods: Among 276,696 disease-free UK Biobank participants (mean age 55.3 years; 53.5% female; median follow-up of over 13 years), we evaluated baseline frailty phenotype (robust, pre-frail, frail) as a predictor of 43 chronic conditions using Cox models and restricted mean survival time (RMST) analysis. A four-state Markov multistate model mapped transitions across healthy, incident disease, multimorbidity, and death. Multimorbidity clustering was performed via multiple correspondence analysis and K-means. Population attributable fractions (PAFs) quantified the frailty-attributable disease burden. Results: Frailty was significantly associated with 42 of 43 conditions (97.7%). The frail group lost 2.72 years (95% CI, 2.64–2.81) of multimorbidity-free survival over 12 years. In multistate models, frailty was strongly associated with higher hazards of transition from healthy to incident disease (HR 1.77; 95% CI, 1.72–1.83) and from incident disease to multimorbidity (HR 1.73; 95% CI, 1.68–1.79), but showed attenuated associations with post-disease mortality. Four stable multimorbidity phenotypes were identified. PAF analysis indicated that eliminating pre-frailty and frailty could theoretically prevent 9.85% of incident disease events and 9.40% of multimorbidity progression, with pre-frailty contributing the majority of the attributable burden (7.83%). Conclusions: Baseline frailty was strongly associated with broad-spectrum chronic disease onset and accelerated multimorbidity accumulation. Systematic screening and early intervention targeting pre-frailty, particularly in middle-aged populations, holds substantial promise for delaying the multimorbidity trajectory.
Related
- Physical Frailty Accelerates Multimorbidity Accumulation Across Distinct Disease Patterns
- A blood test-derived skeletal muscle index combined with handgrip strength identifies a sarcopenia-related high-risk phenotype in non–dialysis-dependent chronic kidney disease
- Two-Step Sequential Screening for Frailty in Patients With Chronic Liver Disease: A Triage Efficiency Study of Liver Frailty Index Components.
- Dapagliflozin attenuates progression from prefrailty to frailty in patients with hypertension and chronic kidney disease.
- Association of Life-Course Stressful Life Events with Incident Chronic Kidney Disease: The Potential Mediating Role of Frailty.
BibTeX
@article{xing2026impact,
title = {{Impact of frailty phenotype on chronic disease accumulation and healthy life years lost: A multi-state analysis of the UK Biobank}},
author = {Xiaoming Xing and Cong Zhao and Menglin Li and Jiaqin Huang and Yu Chen and Wenting Sun and Yanqiao Yu and Xuenan Chen and Linlin Qiao and Yi Li and Xiaoguang Yan and Ye Li},
journal = {The Journal of Nutrition, Health and Aging},
year = {2026},
month = oct,
doi = {10.1016/j.jnha.2026.100967},
url = {https://doi.org/10.1016/j.jnha.2026.100967},
note = {CC BY},
}
RIS
TY - JOUR
TI - Impact of frailty phenotype on chronic disease accumulation and healthy life years lost: A multi-state analysis of the UK Biobank
AU - Xiaoming Xing
AU - Cong Zhao
AU - Menglin Li
AU - Jiaqin Huang
AU - Yu Chen
AU - Wenting Sun
AU - Yanqiao Yu
AU - Xuenan Chen
AU - Linlin Qiao
AU - Yi Li
AU - Xiaoguang Yan
AU - Ye Li
PY - 2026
DA - 2026/10/31
JO - The Journal of Nutrition, Health and Aging
DO - 10.1016/j.jnha.2026.100967
UR - https://doi.org/10.1016/j.jnha.2026.100967
AB - Background: Frailty is a systemic vulnerability syndrome linked to adverse health outcomes, yet its role in shaping the dynamic trajectory from health through incident disease to multimorbidity remains poorly understood. Methods: Among 276,696 disease-free UK Biobank participants (mean age 55.3 years; 53.5% female; median follow-up of over 13 years), we evaluated baseline frailty phenotype (robust, pre-frail, frail) as a predictor of 43 chronic conditions using Cox models and restricted mean survival time (RMST) analysis. A four-state Markov multistate model mapped transitions across healthy, incident disease, multimorbidity, and death. Multimorbidity clustering was performed via multiple correspondence analysis and K-means. Population attributable fractions (PAFs) quantified the frailty-attributable disease burden. Results: Frailty was significantly associated with 42 of 43 conditions (97.7%). The frail group lost 2.72 years (95% CI, 2.64–2.81) of multimorbidity-free survival over 12 years. In multistate models, frailty was strongly associated with higher hazards of transition from healthy to incident disease (HR 1.77; 95% CI, 1.72–1.83) and from incident disease to multimorbidity (HR 1.73; 95% CI, 1.68–1.79), but showed attenuated associations with post-disease mortality. Four stable multimorbidity phenotypes were identified. PAF analysis indicated that eliminating pre-frailty and frailty could theoretically prevent 9.85% of incident disease events and 9.40% of multimorbidity progression, with pre-frailty contributing the majority of the attributable burden (7.83%). Conclusions: Baseline frailty was strongly associated with broad-spectrum chronic disease onset and accelerated multimorbidity accumulation. Systematic screening and early intervention targeting pre-frailty, particularly in middle-aged populations, holds substantial promise for delaying the multimorbidity trajectory.
SN - 1760-4788
ER -