Qian-Li Xue1,2, Karen Bandeen-Roche2,3, Jing Tian2,3, Judith D Kasper4, Linda P Fried5. 1. Department of Medicine, School of Medicine, Johns Hopkins University, Baltimore, Maryland, USA. 2. Center on Aging and Health, Johns Hopkins Medical Institutions, Baltimore, Maryland, USA. 3. Department of Biostatistics, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, USA. 4. Department of Health Policy and Management, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, USA. 5. Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, New York, USA.
Abstract
OBJECTIVES: To investigate the rate and patterns of accumulation of frailty manifestations in relationship to all-cause mortality and whether there is a point in the progression of frailty beyond which the process becomes irreversible and death becomes imminent (a.k.a. point of no return). DESIGN: Longitudinal observational study. SETTING: Community or a non-nursing home residential care setting. PARTICIPANTS: Two thousand five hundred and fifty seven robust older adults identified at baseline in 2011 with follow-up for all-cause mortality between 2011 and 2018. MEASUREMENTS: Frailty was measured by the physical frailty phenotype. Cox models were used to study the relationships of the number of frailty criteria (0-5) at each point in time and its accumulation patterns with all-cause mortality. Markov state-transition models were used to study annual transitions between health states (i.e., frailty, recovery, and death) after becoming frail among those with frailty onset (n = 373). RESULTS: There was a nonlinear association between greater number of frailty criteria and increasing risk of mortality, with a notable risk acceleration after having accumulated all five criteria (hazard ratio (HR) = 32.6 vs none, 95% confidence interval (CI) = 15.7-67.5). In addition, the risk of one-year mortality tripled, and the likelihood of recovery (i.e., reverting to be robust or pre-frail) halved among those with five frailty criteria compared to those with three or four criteria. A 50% increase in mortality risk was also associated with frailty onset without (vs with) a prior history of pre-frailty (HR = 1.51, 95% CI = 1.20-1.90). CONCLUSION: Both the number and rate of accumulation of frailty criteria were associated with mortality risk. Although there was insufficient evidence to declare a point of no return, having all five-frailty criteria signals the beginning of a transition toward a point of no return. Ongoing monitoring of frailty progression could aid clinical and personal decision-making regarding timing of intervention and eventual transition from curative to palliative care.
OBJECTIVES: To investigate the rate and patterns of accumulation of frailty manifestations in relationship to all-cause mortality and whether there is a point in the progression of frailty beyond which the process becomes irreversible and death becomes imminent (a.k.a. point of no return). DESIGN: Longitudinal observational study. SETTING: Community or a non-nursing home residential care setting. PARTICIPANTS: Two thousand five hundred and fifty seven robust older adults identified at baseline in 2011 with follow-up for all-cause mortality between 2011 and 2018. MEASUREMENTS: Frailty was measured by the physical frailty phenotype. Cox models were used to study the relationships of the number of frailty criteria (0-5) at each point in time and its accumulation patterns with all-cause mortality. Markov state-transition models were used to study annual transitions between health states (i.e., frailty, recovery, and death) after becoming frail among those with frailty onset (n = 373). RESULTS: There was a nonlinear association between greater number of frailty criteria and increasing risk of mortality, with a notable risk acceleration after having accumulated all five criteria (hazard ratio (HR) = 32.6 vs none, 95% confidence interval (CI) = 15.7-67.5). In addition, the risk of one-year mortality tripled, and the likelihood of recovery (i.e., reverting to be robust or pre-frail) halved among those with five frailty criteria compared to those with three or four criteria. A 50% increase in mortality risk was also associated with frailty onset without (vs with) a prior history of pre-frailty (HR = 1.51, 95% CI = 1.20-1.90). CONCLUSION: Both the number and rate of accumulation of frailty criteria were associated with mortality risk. Although there was insufficient evidence to declare a point of no return, having all five-frailty criteria signals the beginning of a transition toward a point of no return. Ongoing monitoring of frailty progression could aid clinical and personal decision-making regarding timing of intervention and eventual transition from curative to palliative care.
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