Prefrailty, Impairment in Physical Function, and Risk of Incident Heart Failure Among Older Adults

Matthew W. Segar MD, MS; Sumitabh Singh MBBS; Parag Goyal MD, MSc; Scott L. Hummel MD, MS; Mathew S. Maurer MD; Daniel E. Forman MD; Javed Butler MD, MPH, MBA; Ambarish Pandey MD, MSCS


J Am Geriatr Soc. 2021;69(9):2486-2497. 

In This Article

Abstract and Introduction


Objective: Evaluate the association between prefrailty and the risk of heart failure (HF) among older adults.

Design, Setting, and Participants: This prospective, community-based cohort study included participants from the Atherosclerotic Risk in Communities study who underwent detailed frailty assessment using Fried Criteria and physical function assessment using the Short Performance Physical Battery (SPPB) score. Individuals with prevalent HF and frailty were excluded.

Main Outcomes and Measures: Adjusted association between prefrailty (vs robust), physical function measures (SPPB score, grip strength, and gait speed), and incident HF (overall and HF subtypes, HF with reduced [HFrEF, EF < 50%] and preserved ejection fraction [HFpEF]) were assessed using Cox proportional hazards models.

Results: Among 5210 participants (mean age 75 years, 58% women), 2565 (49.2%) were identified as prefrail. In cross-sectional analysis, prefrail individuals had a higher burden of chronic myocardial injury (troponin, Std β = 0.08 [0.05–0.10]) and neurohormonal stress (NT-ProBNP, Std β = 0.03 [0.02–0.05]) after adjustment for potential confounders. Over a median follow-up of 4.6 years, there were 232 (4.5%) HF events (HFrEF: 102; HFpEF: 97). Prefrailty was associated with an increased risk of HF after adjusting for potential clinical confounders and cardiac biomarkers (aHR [95% CI] = 1.65 [1.24–2.20]). Among HF subtypes, prefrailty was associated with an increased risk of HFpEF but not HFrEF (aHR [95% CI] = 1.73 [1.11–2.70] and 1.38 [0.90–2.10], respectively). A lower SPPB score was also associated with an increased risk of overall HF and HFpEF, but not HFrEF. Among individual components, increased gait speed were associated with a lower risk of HFpEF, but not HFrEF.

Conclusions and Relevance: Subtle abnormalities in physiological reserve (prefrailty) and impairment in physical function (SPPB) were both significantly associated with a higher risk of incident HF, particularly HFpEF. These findings highlight the potential role of routine assessment of geriatric syndromes for early identification of HF risk.


Heart failure with preserved ejection fraction (HFpEF) is the most common phenotype of heart failure (HF) encountered in older individuals. HFpEF is characterized by exercise intolerance and often clinical volume overload despite preserved left ventricular ejection fraction.[1–3] In addition to a high risk of mortality and hospitalization, HFpEF is also associated with functional impairment and poor quality-of-life.[4,5] Unlike heart failure with reduced ejection fraction (HFrEF), HFpEF continues to be refractory to available medical therapies highlighting the need for novel approaches to its prevention.[6–8]

An important first step to prevention is identifying intermediate phenotypes that may underlie the progression from at-risk stage to clinical HFpEF. Frailty is a state of reduced physiologic reserve with increased vulnerability and poor resolution of homeostasis following stress that predisposes individuals to an increased risk of adverse outcomes.[9] Prior studies have identified key similarities in the pathophysiology of HFpEF and frailty and implicated frailty as an important factor in the development and progression of HFpEF.[10–12] The transition from a robust state to frailty is often encountered among older individuals and most likely occurs through the subclinical accumulation of several metabolic and physiologic impairments.[13–15] Prefrailty, an intermediate stage that precedes frailty, represents an early stage of physiologic impairment that may be potentially reversible with effective multimodality interventions.[16–19] The association of prefrailty and other measures of functional impairments with the risk of HF and its subtypes, HFpEF and HFrEF, among community-dwelling adults is not well-established. A better understanding of the contribution of geriatric syndromes such as prefrailty to development of HFpEF may facilitate primary care physicians and geriatricians to identify these older high-risk patients and target them with preventive strategies aimed at reducing progression to frailty and downstream HF.[4,20,21] Accordingly, in this study, we evaluated the association of the presence of prefrailty and other objective measures of functional impairment with the risk of incident HF and its subtypes among community-dwelling older adults.