Study Finds Cognitive Frailty May Predict Worsened Heart Failure Outcomes

A new study from Japan has investigated possible associations between cognitive frailty and overall prognosis among elderly individuals who have heart failure.

Cognitive frailty has a likely association with worsened heart failure (HF) prognosis among individuals 65 years and older and may result in greater risks of HF-related hospitalization and all-cause mortality, according to new study findings in ESC Heart Failure.

This subanalysis of data from the FRAGILE-HF study used Fried criteria to diagnose physical frailty, Framingham criteria to diagnose HF, and Mini-Cog to diagnose cognitive impairment, with cognitive impairment defined as the impact of concurrent physical frailty and cognitive impairment, the study authors noted.

Current evidence for elderly individuals with HF shows a potential link between cognitive decline/physical frailty and poor prognosis, but less is known about the cognitive frailty’s impact on these individuals, “so the current study sought to investigate the prevalence and prognostic impact of cognitive frailty in elderly patients with HF,” they added.

The primary study end points at 1 year (March 2019) were risk of combined events, comprising hospitalization for HF and mortality, and mortality alone among patients with a first admission for decompensated HF at 1 of 15 hospitals across Japan between September 2016 and March 2018.

Overall, 23% had a diagnosis of cognitive frailty among the 4 patient groups analyzed (nonphysical frail/noncognitive impairment, physical frailty/noncognitive impairment, nonphysical frail/cognitive impairment, physical frailty/cognitive impairment). Close to 34% also met the criteria for the combined event end point during the 1-year follow-up.

In addition, patients with both HF and cognitive frailty were shown to have a higher event rate post discharge (P = .0146).

Unadjusted analysis was conducted first, and this showed a 49% greater risk of both all-cause mortality and HF rehospitalization in the presence of cognitive frailty (HR 1.49; 95% CI, 1.14-1.95; P = .004). Multivariate analysis produced similar results, with this risk rising to 55% (HR, 1.55; 95% CI, 1.13-2.13; P = .007).

All study participants had to be ambulatory at discharge to be included in the final analysis, which covered 1189 of FRAGILE-HF’s 1332 participants who were evaluated with the Fried criteria and Mini-Cog. Patients were considered physically frail if they fit at least 3 of the following criteria: weakness (hand grip), decreased walking speed, weight loss, fatigue, and decreased physical activity using the Fried phenotype.

Noncardiovascular-related deaths were excluded from the all-cause mortality outcome when the investigators performed Cox regression analysis, and this showed a significant association between cognitive frailty and cardiovascular-related deaths/HF rehospitalization (HR, 1.89; 95% CI; P = .021).

Results were consistent, too, following the authors’ sensitivity analyses that used grip strength, short physical performance battery (SPPB), and walking speed to determine influence of their physical frailty definition on their findings. “The prevalence of cognitive frailty, defined using grip strength, SPPB, and walking speed, was 25.4%, 28.1%, and 32.5%, respectively,” they wrote.

One final analysis via a Cox model adjusting for grip strength, performance on the SPPB, and walking speed showed cognitive impairment associated with greater risk of poor grip strength (HR, 1.55; 95% CI, 1.06-2.25; P = .021), reduced performance on the SPPB (HR, 1.37; 95% CI, 1.05-1.80; P = .019), and slower gait speed (HR, 1.41; 95% CI, 1.04-1.92; P = .027).

The authors said their large cohort size, their focus on patients with HF—in contrast to previous studies that have evaluated cognitive frailty outside the context of HF—and their ability “to demonstrate the prevalence and prognostic impact of cognitive frailty in a sufficient number of patients and events,” add strength to their findings.

“Moreover, we demonstrated that the negative prognostic impact of cognitive frailty remained constant regardless of the tool used to define physical frailty,” they wrote. “This additional result supports our conclusion that cognitive frailty was strongly associated with poor prognosis in elderly patients with HF.”

A proposed reason for the association of a poor prognosis in the presence of cognitive frailty among patients with HF may be their reduced cardiac output, they authors noted, which can lead to decreased cerebral blood flow.


Yamamoto S, Yamasaki S, Higuchi S, et al. Prevalence and prognostic impact of cognitive frailty in elderly patients with heart failure: sub-analysis of FRAGILE-HF. ESC Heart Fail. Published online February 19, 2022. doi:10.1002/ehf2.13844

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