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Updated: Jun 26, 2026
Frailty Assessment in an Aging Mouse Model
Published on: September 23, 2025
Physiological complexity underlying heart rate dynamics and frailty status in community-dwelling older women
Paulo H M Chaves1, Ravi Varadhan, Lewis A Lipsitz
1Departments of cMedicine and dEpidemiology, Division of Geriatrics Medicine and Gerontology, Center on Aging and Health, Johns Hopkins University, Baltimore, Maryland 21205, USA. pchaves@jhsph.edu
Objectives:
To assess whether less physiological complexity underlying regulation of heart rate dynamics, as indicated by lower approximate entropy for heart rate (ApEn(HR)), is associated with frailty. For supporting validity, relationships between frailty and traditional linear indices of heart rate variability (HRV) were also assessed.
Design:
Cross-sectional.
Setting:
Women's Health and Aging Study I, a community-based observational study, 1992 to 1995.
Participants:
Subset of 389 community-dwelling women aged years and older with moderate to severe disability with ApEn(HR) data (convenience sampling).
Measurements:
Electrocardiographic Holter recordings obtained over 2- to 3-hour periods were processed for ApEn(HR) and HRV measures. ApEn(HR) is a nonlinear statistic that quantifies the regularity of heart rate fluctuations over time. Lower ApEn(HR) is characteristic of heart rate time series containing a high proportion of repetitive patterns. Frailty was defined according to validated phenotype criteria.
Results:
Median ApEn(HR) was lower in frail than in nonfrail subjects (P=.02). Lower ApEn(HR) (top quartile) was associated with lower likelihood of frailty than higher ApEn(HR) (bottom three quartiles) (odds ratio=0.47, 95% confidence interval=0.26-0.86), even after adjustment for major confounders. Frailty was consistently associated with lower HRV as assessed using time- and frequency-domain indices.
Conclusion:
This study supports the notion that less physiological complexity marks frailty and provides an empirical basis to the concept of frailty as a syndrome of homeostatic impairment. Future research will determine whether noninvasive measures of physiological complexity underlying heart rate dynamics might be useful for screening and monitoring of clinical vulnerability in older adults.
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