Fried Frailty Phenotype Research Articles

Development of the Lung Transplant Frailty Scale (LT-FS)

Existing measures of frailty developed in community dwelling older adults may misclassify frailty in lung transplant candidates. We aimed to develop a novel frailty scale for lung transplantation with improved performance characteristics. We measured the short physical performance battery (SPPB), fried frailty phenotype (FFP), Body Composition, and serum Biomarkers representative of putative frailty mechanisms. We applied a 4-step established approach (identify frailty domain variable bivariate associations with the outcome of waitlist delisting or death; build models sequentially incorporating variables from each frailty domain cluster; retain variables that improved model performance ability by c-statistic or AIC) to develop 3 candidate "Lung Transplant Frailty Scale (LT-FS)" measures: 1 incorporating readily available clinical data; 1 adding muscle mass, and 1 adding muscle mass and research-grade Biomarkers. We compared construct and predictive validity of LT-FS models to the SPPB and FFP by ANOVA, ANCOVA, and Cox proportional-hazard modeling. In 342 lung transplant candidates, LT-FS models exhibited superior construct and predictive validity compared to the SPPB and FFP. The addition of muscle mass and Biomarkers improved model performance. Frailty by all measures was associated with waitlist disability, poorer HRQL, and waitlist delisting/death. LT-FS models exhibited stronger associations with waitlist delisting/death than SPPB or FFP (C-statistic range: 0.73-0.78 vs. 0.57 and 0.55 for SPPB and FFP, respectively). Compared to SPPB and FFP, LT-FS models were generally more strongly associated with delisting/death and improved delisting/death net reclassification, with greater improvements with increasing LT-FS model complexity (range: 0.11-0.34). For example, LT-FS-Body Composition hazard ratio for delisting/death: 6.0 (95%CI: 2.5, 14.2), SPPB HR: 2.5 (95%CI: 1.1, 5.8), FFP HR: 4.3 (95%CI: 1.8, 10.1). Pre-transplant LT-FS frailty, but not SPPB or FFP, was associated with mortality after transplant. The LT-FS is a disease-specific physical frailty measure with face and construct validity that has superior predictive validity over established measures.

Gender Differences in Determinants of the Components of the Frailty Phenotype among Older Adults in India: Findings from LASI Wave-1.

This study examines the gender-specific determinants of the components of frailty in a community-dwelling setting in India. Using data from the Longitudinal Ageing Study in India (LASI) Wave-1, this study employed 30,978 (14,885 male and 16,093 female) older adults (aged 60+) to fulfil the study objective. The modified Fried frailty phenotype criteria defines frailty by the five components: exhaustion, weak grip strength, slow walking speed, unintentional weight loss, and low physical activity. The result showed grip strength (79.1%) as the most discriminant component among males, and physical activity (81.6%) as the most discriminant component among females. The results also indicated that grip strength (male: 98.0%, female: 93.5%) and physical activity (male: 94.8%, female: 96.9%) showed a sensitivity of more than 90%, which appears to be a good indicator of frailty. Combining this dual marker increased the accuracy to 99.97% among male and 99.98% among female samples. The findings suggested adding grip strength and physical activity as a proxy measure of frailty, which can increase the precision of screening without a large additional investment of time, training, or cost.

Patient-Reported Frailty and Functional Status in Heart Failure With Preserved Ejection Fraction: Insights From VITALITY-HFpEF

BackgroundThe association between frailty and health status in patients with heart failure with preserved ejection fraction (HFpEF) is not well known. ObjectivesThe authors examined the association between: 1) patient-reported frailty, measured by the Fried frailty phenotype, Kansas City Cardiomyopathy Questionnaire Physical Limitation Score (KCCQ-PLS), 6-minute walking distance (6MWD), and other baseline characteristics; 2) baseline frailty compared with KCCQ-PLS and 24-week 6MWD; 3) frailty and changes in KCCQ-PLS and 6MWD; and 4) vericiguat and frailty at 24 weeks. MethodsIn a post hoc analysis, patients in the VITALITY-HFpEF (Patient-reported Outcomes in Vericiguat-treated Patients With HFpEF) trial were categorized as not frail (0 symptoms), prefrail (1-2 symptoms), and frail (≥3 symptoms) according to patient-reported number of frailty symptoms. Correlations and linear regression models were used to examine the association between frailty and other measures, and between frailty and KCCQ-PLS at baseline with 24-week 6MWD. ResultsAmong 739 patients, 27.3% were not frail, 37.6% were prefrail, and 35.0% were frail at baseline. Frail patients were older, more likely to be women, and less likely to be from Asia. Baseline KCCQ-PLS and 6MWD (mean ± SD) among not frail, prefrail, and frail patients was 68.2 ± 23.2, 61.7 ± 22.6, and 48.4 ± 23.8 and 328.5 ± 117.1 m, 310.8 ± 98.9 m, and 250.7 ± 104.3 m (P < 0.01 for both). After accounting for baseline 6MWD, frailty status at baseline, but not KCCQ-PLS, was significantly associated with 6MWD at 24 weeks. By 24 weeks, 47.5% of patients had no change in frailty, 45.5% had become less frail, and 7.0% had become more frail. Treatment with vericiguat did not alter frailty status at 24 weeks. ConclusionsPatient-reported frailty is modestly correlated with both the KCCQ-PLS and 6MWD but offers prognostic insight into 6MWD at 24 weeks. (Patient-reported Outcomes in Vericiguat-treated Patients With HFpEF [VITALITY-HFpEF]; NCT03547583)

Prevalence, measurement, and implications of frailty in stroke survivors: An analysis of three global aging cohorts.

Our understanding of the relationship between frailty and stroke, beyond the acute phase of stroke, is limited. We aimed to estimate the prevalence of frailty in stroke survivors using differing methods of assessment and describe relationships with stroke outcomes. We used data from three international population surveys (American Health and Retirement Survey/English Longitudinal Study of Ageing/Survey for Health and Retirement in Europe) of aging. Frailty status was assessed using the Fried frailty phenotype, a 40-item frailty index (FI) and the clinical frailty scale (CFS). We created estimates of frailty prevalence and assessed association of frailty with outcomes of mortality/hospital admission/recurrent stroke at 2 years follow-up using logistic regression models adjusted for age/sex. Additional analyses explored effects of adding cognitive measures to frailty assessments and of missing grip strength data. Across 9617 stroke survivors, using the frailty phenotype, 23.8% (n = 2094) identified as frail; with CFS, 30.1% (n = 2906) were moderately or severely frail; using FI, 22.7% (n = 2147) had moderate frailty and 31.9% (n = 3021) had severe frailty. Frailty was associated with increased risk of mortality/hospitalization/recurrent stroke using all three measures. Adding cognitive variables to the FI produced minimal difference in prevalence of frailty. People with physical frailty (phenotype or CFS) plus cognitive impairment had a greater risk of mortality than people with an equivalent level of frailty but no cognitive impairment. Excluding people unable to provide grip strength underestimated frailty prevalence. Frailty is common in stroke and associated with poor outcomes, regardless of measure used. Adding cognitive variables to frailty phenotype/CFS measures identified those at greater risk of poor outcomes. Physical and cognitive impairments in stroke survivors do not preclude frailty assessment.

The Impact of Improving Nutrition Status, Pre-habilitation, Optimization of Cardiac Hemodynamics Including use of Temporary Mechanical Support When Indicated on the Reduction of Frailty in Patients Evaluated for Advanced Heart Failure Therapies

Background: Advanced frailty and age are associated with increased mortality, adverse surgical and transplant outcomes. Aside from bridge-to-transplant ventricular assist device (VAD) implant, minimal literature exists regarding reversing frailty. The aim of this study was to assess interventions used by Lutheran Heart Transplant (HTx) and VAD Program on reducing frailty and the impact on short-term operative outcomes.&#x0D; Methods: A retrospective chart review of 29 patients evaluated in the Lutheran HTx and VAD program was performed. Data collected included biomarker and demographic data for June 2020 to present. The study population was analyzed and then stratified by their modified Fried Frailty Phenotype (mFFP) score. Independent analysis was performed for HTx and VAD cohorts. Fisher’s exact and t-tests were used to analyze categorical and continuous variables, respectively (alpha = 0.05).&#x0D; Results: 18 out of 29 patients (62%) were classified as frail at initial assessment. Significant improvements were observed in bilirubin (p=0.017), creatinine (p=0.001), eGFR (p=0.001), lactic acid (p=0.002), and prealbumin (p=0.002) for the total study population. Frail patients experienced longer intubation (3 vs 4 days) and hospitalization (20 vs 23 days) times post-HTx. Due to limited sample size, we were unable to analyze the VAD cohort by mFFP score.&#x0D; Conclusions: Significant improvements were seen in kidney function and nutrition status as indicated by creatinine, eGFR, and prealbumin data. However, the available data was insufficient to examine the interventions impact on frailty as described by the Fried Frailty Phenotype. Similar to other studies, frailty was associated with increased intubation and hospitalization duration post-HTx.

Validity Properties of a Self-reported Modified Frailty Phenotype Among People With HIV in Clinical Care in the United States.

Modifications to Fried's frailty phenotype (FFP) are common. We evaluated a self-reported modified frailty phenotype (Mod-FP) used among people with HIV (PWH). Among 522 PWH engaged in two longitudinal studies, we assessed validity of the four-item Mod-FP compared with the five-item FFP. We compared the phenotypes via receiver operator characteristic curves, agreement in classifying frailty, and criterion validity via association with having experienced falls. Mod-FP classified 8% of PWH as frail, whereas FFP classified 9%. The area under the receiver operator characteristic curve for Mod-FP classifying frailty was 0.93 (95% CI = 0.91-0.96). We observed kappa ranging from 0.64 (unweighted) to 0.75 (weighted) for categorizing frailty status. Both definitions found frailty associated with a greater odds of experiencing a fall; FFP estimated a slightly greater magnitude (i.e., OR) for the association than Mod-FP. The Mod-FP has good performance in measuring frailty among PWH and is reasonable to use when the gold standards of observed assessments (i.e., weakness and slowness) are not feasible.

1310 FRAILTY, LONELINESS AND SOCIAL ISOLATION IN THE UK BIOBANK COHORT

Abstract Background Three challenges for ageing populations are frailty (a state of reduced physiological reserve), social isolation (objective lack of social connections), and loneliness (subjective experience of feeling alone). These are associated with adverse outcomes. This study aims to examine how frailty in combination with loneliness or social isolation is associated with all-cause mortality and hospitalisation rate using data from UK Biobank, a large population-based research cohort. Methods 502,456 UK Biobank participants were recruited 2006-2010. Baseline data assessed frailty (via two measures: Fried frailty phenotype, Rockwood frailty index), social isolation, and loneliness. Adjusted cox-proportional hazards models assessed association between frailty in combination with loneliness or social isolation and all-cause mortality. Negative binomial regression models assessed hospitalisation rate. Findings Frailty, social isolation, and loneliness are common in UK Biobank (frail as per frailty phenotype 3.38%, frail as per frailty index 4.68%, social isolation 9.04%, loneliness 4.75%). Social isolation/loneliness were more common in frailty/pre-frailty. Frailty is associated with increased mortality regardless of social isolation/loneliness. Hazard ratios for frailty (frailty phenotype) were 3.38 (3.11-3.67) with social isolation and 2.89 (2.75-3.05) without social isolation, 2.94 (2.64-3.27) with loneliness and 2.9 (2.76-3.04) without loneliness. Social isolation was associated with increased mortality at all levels of frailty; loneliness only in robust/pre-frail. Frailty was also associated with hospitalisation regardless of social isolation/loneliness. Incidence rate ratios for frailty (frailty phenotype) were 3.93 (3.66-4.23) with social isolation and 3.75 (3.6-3.9) without social isolation, 4.42 (4.04-4.83) with loneliness and 3.69 (3.55-3.83) without loneliness. At all levels frailty, social isolation/loneliness are associated with increased hospitalisation Results were similar using the frailty index definition. Conclusion Social isolation is relevant at all levels frailty. Risk of loneliness is more pronounced in those who are robust or pre-frail. Proactive identification of loneliness, regardless of physical health status may provide opportunities for intervention.

Clinical effect of nighttime snacking on patients with hepatitis B cirrhosis.

Nighttime snacking is an effective intervention to avoid abnormal protein consumption caused by prolonged fasting. This article aims to evaluate the clinical efficacy of nighttime snacking on patients with hepatitis B cirrhosis and to provide new ideas for clinical nutritional intervention. The study participants were randomly assigned to the control group (n = 30) and the observation group (n = 30); the former was administered medical system treatment and routine dietary intervention, and the latter was administered the same treatment with the addition of nighttime snacking. After 3 months of intervention with different dietary guidance, the dry body weight body mass index (BMI), upper arm muscle circumference (AMC), grip strength, triceps skinfold thickness (TSF), third lumbar skeletal muscle index (L3-SMI), albumin (ALB), total bilirubin (T-BIL), cholinesterase (CHE), Fried's frailty phenotype score, Child-Pugh score and various cirrhosis complication rates were compared between the two groups. There was no significant difference in the baseline data between the two groups before the dietary intervention. After 3 months of regular dietary guidance in the control group, the grip strength increased compared with the baseline data (p < 0.05), while the dry body weight BMI, AMC, TSF, L3-SMI, ALB, T-BIL, CHE, prothrombin time, international normalized ratio, prothrombin activity, and Child-Pugh scores were not significantly different (p > 0.05). After 3 months of dietary guidance with nighttime snacking in the observation group, the dry body weight BMI, grip strength, TSF, L3-SMI, and CHE scores all increased, compared with the baseline data, while the Child-Pugh score decreased compared with the baseline level (all p < 0.05). After 3 months of intervention, the Child-Pugh score of the observation group showed a more significant decrease than the control group, while the dry body weight BMI, grip strength, ALB and CHE scores were all significantly higher than those in the control group (all p < 0.05). Overall, the improvement rate was significantly higher in the observation group than in the control group (p < 0.05). Nighttime snacking for hepatitis B cirrhosis patients with nutritional risk is beneficial in terms of the recovery of liver synthesis functions, improvements in clinical indicators, sarcopenia corrections and improvements in malnutrition-related complications.

Resting metabolic rate in relation to incident disability and mobility decline among older adults: the modifying role of frailty.

Alterations in resting metabolic rate (RMR), the largest component of daily total energy expenditure, with aging have been shown in various studies. However, little is known about the associations between RMR and health outcomes in later life. To analyze whether RMR is associated with incident disability and mobility decline in a 10-year longitudinal study, as well as the moderating role of frailty in these associations. Data from 298 older adults aged 70 and over from the Frailty and Dependence in Albacete (FRADEA) study in Spain were used, including a baseline measurement in 2007-2009 and a follow-up measurement 10years later. RMR was measured by indirect calorimetry. Outcomes were incident disability in basic activities of daily living (BADL, Barthel Index), incident disability in instrumental ADL (IADL, Lawton index), and mobility decline (Functional Ambulation Categories scores). Fried's frailty phenotype was used as an indicator of frailty. Logistic regression analyses were conducted. Fully adjusted and stratified analyses revealed that only in the pre-frail/frail group, a higher RMR was associated with a lower risk of incident BADL disability (OR = 0.47, 95% CI = 0.23-0.96, p = 0.037), incident IADL disability (OR = 0.39, 95% CI = 0.18-0.84, p = 0.017), and mobility decline (OR = 0.30, 95% CI = 0.14-0.64, p = 0.002). To our knowledge, this is the first study looking at the associations between RMR and functional health using a longitudinal research design. The results suggest that RMR could be used as an early identifier of a specific resilient group within the pre-frail and frail older population, with a lower risk of further health decline.

Frailty and Mortality Risk in COPD: A Cohort Study Comparing the Fried Frailty Phenotype and Short Physical Performance Battery.

Identifying frailty in people with chronic obstructive pulmonary disease (COPD) is deemed important, yet comparative characteristics of the most commonly used frailty measures in COPD are unknown. This study aimed to compare how the Fried Frailty Phenotype (FFP) and Short Physical Performance Battery (SPPB) characterise frailty in people with stable COPD, including prevalence of and overlap in identification of frailty, disease and health characteristics of those identified as living with frailty, and predictive value in relation to survival time. Cohort study of people with stable COPD attending outpatient clinics. Agreement between frailty classifications was described using Cohen's Kappa. Disease and health characteristics of frail versus not frail participants were compared using t-, Mann-Whitney U and Chi-Square tests. Predictive value for mortality was examined with multivariable Cox regression. Of 714 participants, 421 (59%) were male, mean age 69.9 years (SD 9.7), mean survival time 2270 days (95% CI 2185-2355). Similar proportions were identified as frail using the FFP (26.2%) and SPPB (23.7%) measures; classifications as frail or not frail matched in 572 (80.1%) cases, showing moderate agreement (Kappa = 0.469, SE = 0.038, p < 0.001). Discrepancies seemed driven by FFP exhaustion and weight loss criteria and the SPPB balance component. People with frailty by either measure had worse exercise capacity, health-related quality of life, breathlessness, depression and dependence in activities of daily living. In multivariable analysis controlling for the Age Dyspnoea Obstruction index, sex, BMI, comorbidities and exercise capacity, both the FFP and SPPB had predictive value in relation to mortality (FFP aHR = 1.31 [95% CI 1.03-1.66]; SPPB aHR = 1.29 [95% CI 0.99-1.68]). In stable COPD, both the FFP and SPPB identify similar proportions of people living with/without frailty, the majority with matching classifications. Both measures can identify individuals with multidimensional health challenges and increased mortality risk and provide additional information alongside established prognostic variables.

Healthcare Utilization and Costs According to Frailty Transitions After Two Years: A Korean Frailty and Aging Cohort Study.

Korea's aging population has raised several challenges, especially concerning healthcare costs. Consequently, this study evaluated the association of frailty transitions with healthcare utilization and costs for older adults aged 70 to 84. This study linked the frailty status data of the Korean Frailty and Aging Cohort Study to the National Health Insurance Database. We included 2,291 participants who had frailty measured by Fried Frailty phenotype at baseline in 2016-2017 and follow-up in 2018-2019. We conducted a multivariate regression analysis to determine the association between their healthcare utilization and costs by frailty transition groups. After 2 years, changes from "pre-frail" to "frail" (Group 6) and "frail" to "pre-frail" (Group 8) were significantly associated with increased inpatient days (P < 0.001), inpatient frequency (P < 0.001), inpatient cost (P < 0.001 and P < 0.01, respectively), and total healthcare cost (P < 0.001) than "robust" to "robust" (Group 1) older adults. A transition to frailty from "pre-frail" to "frail" (Group 6) resulted in a $2,339 total healthcare cost increase, and from "frail" to "pre-frail" (Group 8), a $1,605, compared to "robust" to "robust" older adults. Frailty among community-dwelling older adults is economically relevant. Therefore, it is crucial to study the burden of medical expenses and countermeasures for older adults to not only provide appropriate medical services but also to prevent the decline in their living standards due to medical expenses.

Incidence of frailty and construction of prediction model in elderly male patients with chronic obstructive pulmonary disease

The incidence of frailty was studied and prediction model was constructed for the elderly male patients with chronic obstructive pulmonary disease (COPD). Total of 266 elderly males having COPD were selected, and Fried Frailty Phenotype was employed to investigate their frailty status. According to the clinical experience, literature and reports; age, BMI (Body Mass Index), course and condition of COPD, laboratory findings, lung function, life quality, nutritional status and disease acceptance were designated as independent variables; and the incidence of frailty was taken as dependent variable. A binary logistic regression model was applied to analyze the factors affecting incidence of frailty, and a prediction model was constructed for the clinical screening of elderly male COPD patients at high frailty risk. The scores of 266 elderly male COPD patients investigated by frailty phenotype (FP) phenotype ranged from 0 to 5, and mean score was 1.83 ± 0.43. Total of 103 patients scored more than 3 among these patients. The frailty detection rate was 38.72%. Multi-factors logistic regression analysis suggested that age, hospitalization for acute exacerbation of COPD within a year, and interleukin 6 (IL-6) levels were the risk factors for incidence of frailty in elderly male COPD patients, while FEV1 (Forced Expiratory Volume in 1 second) and MNA-SF (Mini Nutritional Assessment Short-Form) levels were the protective factors. COPD frailty was higher in elderly men. Age, inflammatory response, lung function, disease control and nutritional status were the independent factors affecting incidence of frailty. Strengthening the screening for frailty in elderly patients and monitoring their inflammatory response, lung function, and nutritional status were significant in reducing incidence and improving prognosis.

Sex Differences in Frailty Factors and Their Capacity to Identify Frailty in Older Adults Living in Long-Term Nursing Homes.

Frailty is a phenomenon that precedes adverse health events in older people. However, there is currently no consensus for how to best measure frailty. Several studies report that women have a higher prevalence of frailty than men, but there is a gap in studies of the high rates of frailty in older people living in long-term nursing homes (LTNHs) stratified by sex. Therefore, we analyzed health parameters related to frailty and measured their capacity to identify frailty stratified by sex in older people living in LTNHs. According to the Fried Frailty Phenotype (FFP), anxiety increased the risk of frailty in women, while for men functionality protected against the risk of frailty. Regarding the Tilburg Frailty Indicator (TFI), functionality had a protective effect in men, while for women worse dynamic balance indicated a higher risk of frailty. The analyzed parameters had a similar capacity for detecting frailty measured by the TFI in both sexes, while the parameters differed in frailty measured by the FFP. Our study suggests that assessment of frailty in older adults should incorporate a broad definition of frailty that includes not only physical parameters but also psycho-affective aspects as measured by instruments such as the TFI.

DEVELOPMENT OF PREDICTIVE MODELS FOR INCIDENT FRAILTY IN OLDER ADULTS: MACHINE LEARNING APPROACHES

Abstract Frailty is not only a clinical symptom accompanying adverse health outcomes but also a syndrome that involves a dynamic transition between varying phases. This study aimed to develop machine learning (ML) models for predicting incident frailty over a 2-year follow-up period among Korean community-dwelling adults aged 70 years and older. We conducted prospective analyses (n=2,408) among participants who underwent measurement of frailty status at baseline and 2-year follow-up from the Korean Frailty and Aging Cohort Study. Frailty was defined as the presence of three or more of five components using the Fried frailty phenotype. A total of 2,250 participants classified as non-frail at baseline and 116 (5.2%) with incident frailty during the 2-year follow-up. 32 variables selected by stepwise analysis were used as inputs among 77 variables composed of sociodemographic and clinical characteristics. The different ML models such as Logistic Regression(LR), K-Nearest Neighbor(KNN), Gaussian Naïve Base(NB), Support Vector Machine(SVM), and Random Forest(RF) with the 10-fold cross validation were compared. A feature selection, grid search, and data resampling methods were applied to find the best inputs and models. The best performing inputs of 16 variables were found and Gaussian NB achieved the highest accuracy of 0.82 and F1-score of 0.79 in predicting frailty incidence after 2-years with selected 16 inputs, followed by RF (accuracy 0.82, F1-score 0.76) and LR (accuracy 0.80, F1-score 0.76). We developed ML models for predicting frailty and is expected to contribute to the early prediction of frail older adults and timely intervention in clinical and community settings.

THE LONGITUDINAL RELATIONSHIPS BETWEEN SOCIAL ISOLATION AND HEALTH OUTCOMES: THE ROLE OF PHYSICAL FRAILTY

Abstract Social isolation is a public health issue that is linked to poor health outcomes. However, the mechanisms underlying this association remain unclear. The main objective of this study was to explore whether changes in frailty moderated the relationship between changes in social isolation and changes in health outcomes over two years. We examined the mediating role of changes in frailty when the moderation hypothesis was not supported. A series of latent growth models (LGMs) were used to test our objectives using data from three waves of the FRéLE study among 1643 Canadian community-dwelling older adults aged 65 years and over. Missing data were handled by pattern mixture models with the assumption of missing not at random. We measured social isolation through social participation, social networks, and social support from different sources of social ties. We assessed frailty using the Fried frailty phenotype. Our moderation results revealed that high levels of changes in social participation, support from friends, nuclear, and extended family members, and social contacts with friends were associated with greater changes in cognitive and mental health among frail older adults with diminished physiological reserves compared to robust older adults. Additionally, changes in frailty mediated the effects of changes in social participation and social contacts and support from friends on changes in chronic conditions. This longitudinal study suggests that frailty moderated the relationships between social isolation and mental and cognitive health but not physical health. Overall, social support and strong friendship ties are key determinants of frail older adults’ health.

THE PHYSIOLOGIC COMPLEXITY OF BEAT-TO-BEAT BLOOD PRESSURE FLUCTUATION IS ASSOCIATED WITH FRAILTY IN OLDER ADULTS

Abstract Background Beat-to-beat blood pressure (BP) is an important cardiovascular output and regulated by neurophysiologic elements over multiple temporal scales. The multiscale dynamics of beat-to-beat BP fluctuation has thus been characterized using “BP complexity” and has been linked to age-related adverse health outcomes. We here aimed to examine the relationship of BP complexity to frailty, and if BP complexity mediates the association between arterial stiffness and frailty. Method: A total of 350 older adults completed assessments for frailty (i.e., Fried frailty phenotype criteria), arterial stiffness (i.e., average brachial-ankle pulse wave velocity), and beat-to-beat finger BP. The complexity of beat-to-beat systolic (SBP) and diastolic (DBP) BP series were measured using multiscale entropy. The relationships between frailty, BP complexity and arterial stiffness were examined using ANOVA and linear regression models. The effects of BP complexity on the association between arterial stiffness and frailty were examined using mediation analyses. Results Compared to non-frail, pre-frail and frail groups had significantly elevated lower SBP and DBP complexity (F&amp;gt;11, p&amp;lt; 0.001), and greater arterial stiffness (F=16, p&amp;lt; 0.001). Greater arterial stiffness was associated with lower BP complexity (β&amp;lt;-0.42, p&amp;lt; 0.001). SBP and DBP complexity mediated the association between arterial stiffness and frailty (indirect effects&amp;gt;0.28), account for at least 47% of its total effects on frailty (Mediated proportion: SBP: 50%, DBP: 47%). Conclusion This study demonstrates that BP complexity is associated with frailty in older adults, and mediates the association between arterial stiffness and frailty, suggesting that this metric would serve as a marker to characterize important functions in older adults.

Longitudinal association of lung function with frailty among older adults: the English Longitudinal Study of Ageing.

To investigate the effect of baseline lung function on the trajectory of frailty over time. This longitudinal study included 3,658 adults aged 60 and over (average age 70.4years old and 46.4% males) at baseline from the English Longitudinal Study of Ageing. Lung function indicators included forced vital capacity (FVC) and forced expiratory volume in the first second (FEV1), both measured at baseline examination. Frailty was defined based on Fried's frailty phenotype criteria, the measurement was repeated for four times. Linear mixed-effect regression model was applied to estimate the association of baseline lung function with the trajectory of frailty over time. Frailty score increased significantly over time (β = 0.030, P < 0.001). Linear mixed-effect regression model identified significant interactions between FVC (β =-0.018, P < 0.001) or FEV1 (β =-0.022, P < 0.001) and time on frailty. Poor baseline lung function might accelerate the speed of frailty. Lung function might be an important predictor of the development and progression of frailty among older adults.

Association of Frailty With Health-Related Quality of Life in Liver Transplant Recipients

Frailty has been recognized as a risk factor for mortality after liver transplant (LT) but little is known of its association with functional status and health-related quality of life (HRQL), termed global functional health, in LT recipients. To evaluate the association between pre-LT and post-LT frailty with post-LT global functional health. This prospective cohort study was conducted at 8 US LT centers and included adults who underwent LT from October 2016 to February 2020. Frail was defined by a pre-LT Liver Frailty Index (LFI) score of 4.5 or greater. Global functional health at 1 year after LT, assessed using surveys (Short Form-36 [SF-36; summarized by physical component scores (PFC) and mental component summary scores (MCS)], Instrumental Activities of Daily Living scale) and performance-based tests (LFI, Fried Frailty Phenotype, and Short Physical Performance Battery). Of 358 LT recipients (median [IQR] age, 60 [53-65] years; 115 women [32%]; 25 [7%] Asian/Pacific Islander, 21 [6%] Black, 54 [15%] Hispanic White, and 243 [68%] non-Hispanic White individuals), 68 (19%) had frailty pre-LT. At 1 year post-LT, the median (IQR) PCS was lower in recipients who had frailty vs those without frailty pre-LT (42 [31-53] vs 50 [38-56]; P = .002), but the median MCS was similar. In multivariable regression, pre-LT frailty was associated with a -5.3-unit lower post-LT PCS (P < .001), but not MCS. The proportion who had difficulty with 1 or more Instrumental Activities of Daily Living (21% vs 10%) or who were unemployed/receiving disability (38% vs 29%) was higher in recipients with vs without frailty. In a subgroup of 210 recipients with LFI assessments 1 year post-LT, 13% had frailty at 1 year post-LT. Recipients who had frailty post-LT reported lower adjusted SF-36-PCS scores (coefficient, -11.4; P < .001) but not SF-36-MCS scores. Recipients of LT who had frailty vs those without frailty 1 year post-LT also had worse median (IQR) Fried Frailty Phenotype scores (1 [1-2] vs 1 [0-1]) and higher rates of functional impairment by a Short Physical Performance Battery of 9 or less (42% vs 20%; P = .01). In this cohort study, pre-LT frailty was associated with worse global functional health 1 year after LT. The presence of frailty after LT was also associated with worse HRQL in physical, but not mental, subdomains. These data suggest that interventions and therapeutics that target frailty that are administered before and/or early post-LT may help to improve the health and well-being of LT recipients.

Association between metabolic syndrome and risk of both prevalent and incident frailty in older adults: Findings from The Irish Longitudinal Study on Ageing (TILDA)

ObjectivesMetabolic syndrome (MetS) is a risk factor for cardiovascular disease, diabetes, and all-cause mortality. Frailty is a condition of decreased multi-system physiological reserve where one has increased vulnerability to stressors. This study aimed to examine if MetS is associated with prevalent and incident frailty over a 4-year follow-up period in an aged population. MethodsThis study used data from waves 1 (2009–2011) and 3 (2014–2015) of The Irish Longitudinal Study on Ageing. Those aged <50 years or without baseline health assessment data were excluded. Baseline MetS status was determined using the National Cholesterol Education Program Third Adult Treatment Panel criteria. Frailty status was identified at both waves, operationalised using Fried's frailty phenotype (FP) and Rockwood's frailty index (FI). Ordinal logistic regression examined the cross-sectional association between MetS and prevalent frailty status. Those with prevalent pre-frailty or frailty were excluded and ordinal logistic regression models examined the association between MetS and incident frailty. Lastly, MetS' longitudinal associations with the five individual components of Fried's FP were examined. Models were adjusted for age, sex, education, smoking, chronic disease history and renal function. ResultsOrdinal logistic regression models (n > 5100), showed MetS was associated with prevalent frailty as assessed by both FP (odds ratio (OR) 1.29, p < 0.001) and FI (OR 1.65, p < 0.001). Of those who were non-frail at baseline, 2247 participants had longitudinal FP data, while 3546 participants had longitudinal FI data. Models demonstrated that MetS was associated with an increased likelihood of incident frailty for both FP (OR 1.57, p < 0.001) and FI (OR 1.29, p = 0.014). MetS was found to be associated with incident low physical activity (OR 1.57, p = 0.001) and incident unintentional weight loss (OR 1.59, p = 0.025). ConclusionsMetS in those ≥50 years was found to be associated with an increased likelihood of incident frailty over a 4-year period, by 57 % when measured by FP and 29 % by FI. MetS should be considered a risk factor for frailty and be taken into considered in any comprehensive geriatric assessment given frailty's dynamic nature and MetS being potentially modifiable.

Frail Phenotype in Patients With Inflammatory Bowel Disease.

Recent retrospective studies have shown that frailty is common in hospitalized patients with inflammatory bowel disease (IBD) and enhances the risk of drug-related infections, postsurgery complications, hospital readmissions, and mortality, independently of age and comorbidities. We carried out a descriptive cohort study to evaluate the frequency of frail phenotype in IBD and analyzed the risk factors associated with this condition. Frail phenotype was assessed in IBD patients by using the Fried frailty phenotype. Univariate and multivariate analyses were conducted to assess the risk factors for frail phenotype. Serum levels of interleukin (IL)-6 were quantified in patients with a frail or a fit phenotype by ELISA. Three hundred eighty-six IBD outpatients (198 Crohn's disease and 188 ulcerative colitis) were prospectively enrolled from December 2021 to April 2022. Frail phenotype was diagnosed in 64 of 386 (17%) IBD patients and was significantly associated with female gender, active disease, and current use of steroids. Multivariate analysis showed that active disease was a risk factor for frail phenotype (odds ratio, 11.5; 95% confidence interval, 3.9-33.9). No difference in IL-6 serum levels was seen between patients with a frail phenotype and those who were fit. This is the first prospective study showing that frail phenotype occurs in nearly one-fifth of IBD patients. Data indicate that active IBD is an independent risk factor for frail phenotype in IBD.