OBJECTIVE: Limited literature shows the existence of sex differences in the long-term prognosis of heart failure (HF) patients with frailty. In this study, whether sex differences exist in the impact of frailty on death from cardiovascular causes in patients with HF was investigated by conducting a retrospective cohort study.
RESULTS: Data from the National Health and Nutrition Examination Survey (NHANES) study (2009-2018) were used to conduct a retrospective cohort study of 958 participants with HF. Patients were grouped based on sex and frailty index (FI). The relationship between death from cardiovascular causes and baseline frailty was assessed by Cox proportional hazard analysis and the Kaplan-Meier (K-M) plot. The study population had an age of 67.3 ± 12.3. Among them, around 54.5% were male. A median follow-up of 3.6 years was performed. After that, females who died from cardiovascular causes exhibited higher baseline FI values, while males did not show this trend (P < 0.05; P = 0.1253). Cox regression analysis demonstrated a significant association between FI and cardiovascular mortality in females (most frail: hazard ratio (HR) = 3.65, 95% confidence interval (CI): 1.07 ~ 12.39, P < 0.05; per 1-unit increase in FI: HR = 1.78, 95% CI: 1.33 ~ 2.39, P < 0.001). A dose-response association between FI and cardiovascular mortality was presented by restricted cubic splines.
CONCLUSIONS: Frailty is related to an increased risk of cardiovascular mortality in HF patients, particularly female patients.

OBJECTIVE: To investigate the potential linear relationship between serum concentrations of klotho and frailty.
METHODS: A retrospective analysis was conducted on the data of 9,597 middle-aged and older adults (aged 40-79 years) from the five cycles of the National Health and Nutrition Examination Survey (NHANES). Frailty was assessed using the Frailty Index, calculated as a percentage of accumulated deficits across 53 health items. Restricted cubic spline curves, subgroup analyses and logistic regression models were employed to evaluate the specific linear trend connection between circulating klotho protein concentration and frailty.
RESULTS: When taking Klotho into account as a continuous component in Models 1 and 2, there was a substantial association between the increasing Klotho level and the reduced risk of frailty. Model 3 revealed a strong negative correlation between the Klotho and Frailty, suggesting that high levels of Klotho protein decreases the frailty prevalence [Odd ratio (OR): 0.25; 95% confidence interval (CI): 0.15-0.43]. Furthermore, according to the quartile analyses, after fully adjusting for the covariates, it was observed that, comparing to the lowest quartile of Klotho, the highest quartile of Klotho demonstrated lowest risk of frailty (OR 0.69; 95% CI 0.58-0.81, Ptrend < 0.001). The restricted cubic spline curves showed a linear relationship and an inverse association between frailty and the Klotho levels (Plinearity < 0.001; Pnon-linearity = 0.736).
CONCLUSIONS: Klotho is inversely and linearly associated with physical frailty in the general population (aged 40-79 years), specifically in the population with an age < 65 and body mass index (BMI) ≥ 25 kg/m2. More necessary prospective studies should be done to further investigate the mechanisms underlying frailty and aging and to elucidate individual frailty causes.

BACKGROUND: The ageing process is characterized by a change of body composition with an increase of fat mass and a reduction of muscle mass. Above a certain threshold these alterations configure a condition named sarcopenic obesity (SO). SO is associated with physical frailty in Asian and Brazilian populations. SO impacts on physical frailty in other ethnic groups but its influence on general frailty which is multidimensional and includes cognitive, social and physical factors, remain insufficiently explored in the Italian population.
METHODS: Frailty was measured in community dwelling Italian older adults enrolled in the FRASNET study with the frailty index (FI). The FI quantifies frailty as the ratio of the number of present health deficits to the total number of health deficits considered. Regression analyses were performed to assess the association between body composition categories and frailty. Classification and regression tree models were run to evaluate the frailty predictors.
RESULTS: One Thousand One Hundred Fourteen participants of the FRASNET study were included in the present analysis. The sample was composed for the 60.5% by females and its median age was 72 years. The median FI score was 0.11 (IQR 0.07-0.20); 234 individuals (21%) were frail (FI ≥ 0.25). SO (B 0.074, 95% C.I. 0.05-0.1, p < 0.001) and pre-sarcopenia (without obesity B 0.03, 95% C.I, 0.007-0.044, p < 0.001, with obesity B 0.11, 95% C.I. 0.05-0.16, p < 0.001) were associated with frailty. Fat mass percentage predicted frailty in people aged 65-70 years whereas, muscle strength predicted general frailty in people aged 70-81 years.
CONCLUSIONS: Pre-sarcopenia and SO represent potentially treatable predictors of frailty.

BACKGROUND: Oral health is a relevant component for overall health. Oral disease onset at an early age and may harm several health dimensions, especially among older people, and has been associated with frailty.
OBJECTIVE: To evaluate associations between the Frailty Index (FI) and self-reported oral diseases among older, community-dwelling Japanese people.
METHODS: Cross-sectional and prospective analyses were performed.
METHODS: We analyzed data from 2,529 participants at the baseline and four-year follow-up of the Nihon University Japanese Longitudinal Study of Aging, which had a four-year follow-up.
METHODS: We used the self-reported number of teeth, self-reported satisfaction with dentures, and self-reported ability to chew hard food as independent variables. We computed an FI that included 40 deficits as the dependent variable. The FI score ranged from 0 to 1, with a higher score associated with adverse health outcomes and mortality. Considering a gamma distribution and controlling for age, gender, marital status, education, working status, and residence area, we fitted generalized linear models.
RESULTS: We found that dissatisfied denture users had a 2.1% (95% CI 1.006-3.279) higher frailty score than non-denture users at the baseline and a 2.1% (95% CI 0.629-3.690) higher frailty score than non-denture users at the four-year follow-up. In the cross-sectional analysis, with each additional reported tooth at the baseline, the FI score was lower by 1.5% (95% CI -2.878 to -0.208) at the four-year follow-up. In both the cross-sectional and the prospective analyses, the FI scores increased as the ability to chew hard food decreased.
CONCLUSIONS: Self-reported oral diseases are associated with the FI score cross-sectionally and prospectively. Identifying factors prospectively associated with frailty may improve strategies for the next generation of older people. Considering oral diseases may help clinicians personalize treatment plans for older people.

BACKGROUND: Several indexes based on clinical and laboratory tests to identify frailty and to predict mortality have been produced. Only two studies, mixing clinical and laboratory parameters were made about a frailty index made of laboratory tests (FI-Lab) and mortality in older patients hospitalized for COVID-19. The aim of this study was to explore the accuracy and precision of an FI-Lab constructed with some common bio-humoral tests and mortality in a cohort of patients hospitalized for COVID-19.
METHODS: The FI-Lab was constructed using 40 different bio-humoral tests during the first four days of hospitalization, with a score from 0 to 1. The association between FI-Lab and mortality was assessed using a multivariate Cox\'s regression analysis, reported as hazard ratios (HRs) and 95% confidence intervals (CIs). The accuracy of the FI-Lab was reported as area under the curve (AUC) and the precision with the C-Index.
RESULTS: 376 patients (mean age: 65 years; 53.7% males) were initially included. During the follow-up period, 41 deceased. After adjusting for five different factors, an FI-Lab value >0.54, the median value of our cohort, was associated with a relative risk about five times greater than lower values. Modeling FI-LAB as a continous variable, each increase in 0.01 points was associated with an increased risk in mortality of 8.4% (HR=1.084; 95%CI: 1.039-2.044). The FI-Lab was highly accurate (AUC=0.91; 95%CI: 0.87-0.95) and precise (C-Index=0.81) in predicting death.
CONCLUSIONS: A simple index based on common laboratory tests can be used to predict mortality among older people hospitalized for COVID-19.

BACKGROUND: Gastric cancer is the 5th most common malignancy worldwide. Surgical treatment for the disease can often be highly morbid, especially in elderly patients. The modified 5-item frailty index (mFI-5), a recently developed tool for assessing patient frailty, has been shown to be an effective predictor of post-operative outcomes in various surgical fields. This study aims to assess the utility of the mFI-5 in predicting adverse postoperative outcomes following gastrectomy for gastric cancer.
METHODS: The National Surgical Quality Improvement Program (NSQIP) database was queried for patients who underwent partial or total gastrectomy for gastric cancer between 2011 and 2021. The mFI-5 score was calculated based on the presence of hypertension, congestive heart failure, diabetes mellitus, chronic obstructive pulmonary disease, and partially or fully dependent functional status. Patients were stratified into 3 groups according to mFI-5 score (mFI-5 = 0, mFI-5 = 1, mFI-5 ≥ 2). Univariate analysis and multivariate logistic regression were used to evaluate the association between mFI-5 score and post-operative outcomes.
RESULTS: 7438 patients were identified (mFI-5 = 0: 3032, mFI-5 = 1: 2805, mFI-5 ≥ 2: 1601). mFI-5 ≥ 2 was an independent predictor of overall complications (OR 1.43, p < 0.001), serious complications (OR 1.42, p < 0.001), pneumonia (OR 1.43, p = 0.010), MI (OR 2.91, p = 0.005), and readmission within 30 days (OR 1.33, p = 0.008). Patients with higher frailty were more likely to experience unplanned intubation (OR 2.06, p < 0.001; OR 2.47, p < 0.001), failure to wean from the ventilator (OR 1.68, p = 0.003; OR 2.00, p < 0.001), acute renal failure (OR 3.25, p = 0.003; OR 3.27, p = 0.005), 30-day mortality (OR 1.73, p = 0.009; OR 1.94, p = 0.004), and non-home discharge (OR 1.34, p = 0.001; OR 1.74, p < 0.001) relative to non-frail patients.
CONCLUSIONS: Higher frailty, as indicated by an increased mFI-5 score, raises the risk of serious post-operative complications in patients with gastric cancer undergoing gastrectomy. The mFI-5 has the potential to help identify high-risk patients and enhance pre-operative discussions and optimization.

BACKGROUND: Poor cardiovascular health (CVH) and physical frailty were reported to increase mortality risk, but their joint effects have not been fully elucidated.
OBJECTIVE: We aimed to explore the separate and joint effects of CVH and frailty on mortality based on two perspectives of Life\'s Essential 8 (LE8) and Framingham Risk Score (FRS).
METHODS: 21 062 participants in the National Health and Nutrition Examination Survey (NHANES) from 2007 to 2018 were involved in this study. CVH was evaluated by the LE8 and FRS, and categorized into low, moderate and high CVH groups. Cox proportional hazard models were applied to estimate the separate and joint associations of CVH and frailty index (FI) with all-cause, cardiovascular disease (CVD) and cancer mortality.
RESULTS: Over a median follow-up period of 87 months (95% CI: 86.0-88.0), 2036 deaths occurred. The separate linear dose-response relationships between CVH, frailty and mortality were observed (nonlinear P > .05). The combination of low CVH/frailty was negatively associated with all-cause mortality [hazard ratio (HR) and 95%CI: low LE8*FI, 5.30 (3.74, 7.52); high FRS*FI, 4.34 (3.20, 5.88)], CVD mortality [low LE8*FI, 6.57 (3.54, 12.22); high FRS*FI, 7.29 (3.92, 13.55)] and cancer mortality [low LE8*FI, 1.99 (1.14, 3.25); high FRS*FI, 2.32 (1.30, 4.15)], with high CVH/fit group as reference. Further stratified analyses showed that the combined burden of mortality from frailty and low CVH was greater among the young and females.
CONCLUSIONS: Low CVH and frailty were independently and jointly correlated with greater risk of all-cause, CVD and cancer deaths, especially among the young and females.

OBJECTIVE: To examine the association of lifestyle behaviours (LSB) with physical activity (PA) and frailty; also, to examine if associations differ by sex and age.
METHODS: 24,828 individuals [49.6 ± 17.6 years (range: 20-85), 51.6 % female] from the National Health and Nutrition Examination Survey (cycles 2009-2018) were included. Individuals were divided into Active (≥150 min/week of moderate-to-vigorous physical activity (MVPA)) and Inactive (<150 min/week MVPA) based on self-reported PA. Frailty was measured by a 46-item Frailty Index (FI). LSB consisted of stationary time, sleep, diet quality, and alcohol and smoking habits. LSB was summed into a score [0-5]. Linear regression models were used with each LSB in isolation and the summed LSB with frailty.
RESULTS: There were 7,495 (30.1 %) Active and 17,333 (69.8 %) Inactive individuals. The FI was lower in the Active participants (Active: 0.10 ± 0.08; Inactive: 0.15 ± 0.12; p < 0.01). A worse LSB score was associated with an increased FI in all behaviours but females who binge drink and smoke (p-all>0.14). For inactive individuals, all LSBs were associated with an increased FI except those who binge drink and male smokers (p = 0.08). There was a significant association between increased summed LSB and an increased FI (β range: Active, 0.024-0.037; Inactive, 0.028, 0.046. p-all<0.01); the Active group had a lower FI at every age group than the Inactive group (p < 0.001).
CONCLUSIONS: PA was associated with a lower FI even among those with a poor LSB score. This association is dependent on age, with older individuals reporting a stronger association.

UNASSIGNED: The frailty index (FI) is commonly used to estimate frailty in end-stage kidney disease (ESKD) patients. The Clinical Frailty Scale (CFS) is a less time-consuming alternative. We aimed to determine the test performance of the CFS for pre-dialysis and dialysis patients and patients receiving conservative therapy from the Dialysis Centre Apeldoorn.
UNASSIGNED: In this cross-sectional study, haemodialysis, peritoneal dialysis, pre-dialysis patients and patients receiving conservative therapy from the Dialysis Centre Apeldoorn were included and subjected to frailty assessment. Nephrologists not familiar with the CFS completed the frailty score after medical consultation. The sensitivity, specificity and area under the curve (AUC) of the CFS were determined. The FI was used as the gold standard.
UNASSIGNED: Included were 144 patients, of whom 60 (41.7%) were considered frail according to the FI. The mean age was 67.4 ± 13.5 years and 56 (38.9%) were female. The cut-off point of the CFS for \'vulnerable\' (CFS ≥4) had a sensitivity of 63.3%, a specificity of 81.0% and an AUC of 0.72. The cut-off point of the CFS for \'frail\' (CFS ≥5) had a sensitivity of 50.0%, a specificity of 91.7% and an AUC of 0.71.
UNASSIGNED: The CFS is a quick and easy-to-use tool for the determination of frailty in ESKD patients with a high prevalence of frailty. Nevertheless, the sensitivity of the CFS in the present study was considered too low to implement into daily clinical practice. The sensitivity might be increased by training nephrologists in the use of the CFS.

Frailty reflects age-related damage to multiple physiological systems. Executive dysfunction is often a presenting symptom of diseases characterized by cognitive impairment. A decline in cardiovascular health is associated with worse executive function. We tested the hypothesis that higher frailty would be associated with executive dysfunction and that cardiovascular health would mediate this relationship. Middle- and older-aged adults at baseline (n = 29,591 [51% female]) and 3-year follow-up (n = 25,488 [49% females]) from the Canadian Longitudinal Study on Aging (comprehensive cohort) were included. Frailty was determined at baseline from a 61-item index, a cumulative cardiovascular health score was calculated from 30 variables at baseline, and participants completed a word-color Stroop task as an assessment of executive function. Multiple linear regressions and mediation analyses of cardiovascular health were conducted between frailty, Stroop interference-condition reaction time, and cardiovascular health in groups stratified by both age and sex (middle-aged males [MM], middle-aged females [MF], older-aged males [OM], older-aged females [OF]). Frailty (MM, 0.15 ± 0.05; MF, 0.16 ± 0.06; OM, 0.21 ± 0.06; OF, 0.23 ± 0.06) was negatively associated with cardiovascular health (MM, 0.12 ± 0.08; MF, 0.11 ± 0.07; OM, 0.20 ± 0.10; OF, 0.18 ± 0.09; β > 0.037, p < 0.001), as well as the Stroop reaction time at 3-year follow-up (MM, 23.7 ± 7.9; MF, 23.1 ± 7.3; OM, 32.9 ± 13.1; OF, 30.9 ± 12.0; β > 2.57, p < 0.001) across all groups when adjusted for covariates. Cardiovascular health was a partial (~ 10%) mediator between frailty and reaction time, aside from MFs. In conclusion, higher frailty levels are associated with executive dysfunction, which was partially mediated by cardiovascular health. Strategies to improve frailty and better cardiovascular health may be useful for combatting the age-related decline in executive function.