Relationship between changes in the triglyceride glucose-body mass index and frail development trajectory and incidence in middle-aged and elderly individuals: a national cohort study.

BACKGROUND: Insulin resistance is linked to an increased risk of frailty, yet the comprehensive relationship between the triglyceride glucose-body mass index (TyG-BMI), which reflects weight, and frailty, remains unclear. This relationship is investigated in this study. METHODS: Data from 9135 participants in the China Health and Retirement Longitudinal Study (2011-2020) were analysed. Baseline TyG-BMI, changes in the TyG-BMI and cumulative TyG-BMI between baseline and 2015, along with the frailty index (FI) over nine years, were calculated. Participants were grouped into different categories based on TyG-BMI changes using K-means clustering. FI trajectories were assessed using a group-based trajectory model. Logistic and Cox regression models were used to analyse the associations between the TyG-BMI and FI trajectory and frail incidence. Nonlinear relationships were explored using restricted cubic splines, and a linear mixed-effects model was used to evaluate FI development speed. Weighted quantile regression was used to identify the primary contributing factors. RESULTS: Four classes of changes in the TyG-BMI and two FI trajectories were identified. Individuals in the third (OR = 1.25, 95% CI: 1.10-1.42) and fourth (OR = 1.83, 95% CI: 1.61-2.09) quartiles of baseline TyG-BMI, those with consistently second to highest (OR = 1.49, 95% CI: 1.32-1.70) and the highest (OR = 2.17, 95% CI: 1.84-2.56) TyG-BMI changes, and those in the third (OR = 1.20, 95% CI: 1.05-1.36) and fourth (OR = 1.94, 95% CI: 1.70-2.22) quartiles of the cumulative TyG-BMI had greater odds of experiencing a rapid FI trajectory. Higher frail risk was noted in those in the fourth quartile of baseline TyG-BMI (HR = 1.42, 95% CI: 1.28-1.58), with consistently second to highest (HR = 1.23, 95% CI: 1.12-1.34) and the highest TyG-BMI changes (HR = 1.58, 95% CI: 1.42-1.77), and those in the third (HR = 1.10, 95% CI: 1.00-1.21) and fourth quartile of cumulative TyG-BMI (HR = 1.46, 95% CI: 1.33-1.60). Participants with persistently second-lowest to the highest TyG-BMI changes (ß = 0.15, 0.38 and 0.76 respectively) and those experiencing the third to fourth cumulative TyG-BMI (ß = 0.25 and 0.56, respectively) demonstrated accelerated FI progression. A U-shaped association was observed between TyG-BMI levels and both rapid FI trajectory and higher frail risk, with BMI being the primary factor. CONCLUSION: A higher TyG-BMI is associated with the rapid development of FI trajectory and a greater frail risk. However, excessively low TyG-BMI levels also appear to contribute to frail development. Maintaining a healthy TyG-BMI, especially a healthy BMI, may help prevent or delay the frail onset.

Age-Adjusted Modified Frailty Index: Association With Hip Fracture Discharge Functional Dependence.

INTRODUCTION: Hip fractures are a common traumatic injury that carry significant morbidity and mortality, and prognostication of functional outcome is becoming increasingly salient. Across multiple surgical specialties, the five-item and 11-item Modified Frailty Index (mFI-5 and mFI-11) have been found to be convenient, quick, and sensitive tools for identifying patients at risk for perioperative complications. A prior study described the superiority of an Age-Adjusted Modified Frailty Index (aamFI) for predicting perioperative complications compared to the mFI-5 in an elective hip surgery. We sought to externally validate the aamFI in a multicenter hip fracture cohort and hypothesize that these risk scores would not only predict functional dependence (FD) at discharge, but that the aamFI would outperform the mFI-5 and mFI-11. METHODS: The Pennsylvania Trauma Systems Foundation registry was queried from 2010 to 2020 for CPT codes, ICD-9 and ICD-10 codes pertaining to hip fracture patients. Patients with missing locomotion and transfer mobility data were excluded. FD status was determined by discharge locomotion and transfer mobility scores per existing methodology. Univariable and Multivariable analysis as well as receiver operator characteristic curves were used to evaluate and compare the three indices for prediction of functional status at discharge. P value < 0.05 was considered significant. RESULTS: Twelve thousand seven hundred and forty patients met inclusion criteria (FD: 8183; functional independent 4557). On univariable logistic regression analysis, the mFI-11 (odds ratio [OR] 1.52, 95% confidence interval [CI] 1.47-1.58, P < 0.05), mFI-5 (OR 1.57, 95% CI 1.51-1.63), and aamFI (OR 1.57, 95% CI 1.52-1.62, P < 0.05) were associated with FD. On multivariable logistic regression analysis for predictors of FD, when controlling for age (for the mFI-11 and mFI-5), sex, injury severity score, and admission vitals (systolic blood pressure and respiratory rate), higher mFI-11 and mFI-5 scores independently predicted FD at discharge (OR 1.23, 95% CI 1.18-1.28, P < 0.05 and OR 1.23, 95% CI 1.18-1.29P < 0.05 respectively). Higher aaMFI scores had superior association with functional dependence (OR 1.59, 95% CI 1.54-1.64, P < 0.05). Receiver operator characteristic curves for the mFI-11, mFI-5, and aaMFI showed comparable diagnostic strength (area under curve [AUC] = 0.63 95% CI 0.62-0.64, P < 0.05; AUC = 0.63 95% CI 0.62-0.64, P < 0.05; and AUC = 0.67 95% CI 0.65-0.67, P < 0.05 respectively). CONCLUSIONS: The mFI-11, mFI-5, and aamFI are predictive of functional outcome following hip fracture. By including age, the aamFI retains the ease of use of the mFI-5 while improving its prognostic utility for functional outcome.

Assessing the Modified Frailty Index and Post-Operative Outcomes in Adhesive Small Bowel Obstruction: A Retrospective Cohort Study.

INTRODUCTION: Studies identifying predictors of postoperative outcomes in adhesive small bowel obstruction are limited. This study investigates the efficacy of the modified frailty index (mFI)to predict postoperative morbidity and mortality among patients undergoing surgery for adhesive small bowel obstruction. METHODS: A multicentre retrospective cohort study including patients undergoing surgery for adhesive small bowel obstruction after failed trial of nonoperative management between January 2015 and December 2020 was performed. Impact of frailty status using the mFI, stratified as frail (≥0.27) and robust (<0.27), on postoperative morbidity, mortality, length of stay, and discharge destination was evaluated using multiple logistic regression. RESULTS: Ninety-two robust patients (mean age 62.4 y, 68% female) and 41 frail patients (mean age 81.7 y, 63% female) were included. On simple stratification, frail patients had significantly increased 30-d morbidity (overall morbidity 80% versus 49%) and need for higher level of care on discharge (41% versus 9%). However, on multiple regression, functional dependence but not the mFI, was independently associated with worse 30-d overall morbidity (odds ratio [OR] 3.97, confidence interval [CI] 1.29-12.19) and lower likelihood of returning to preoperative disposition (OR 0.21, CI 0.05-0.91). The delay in operation beyond 5 d was independently associated with worse 30-d outcomes including overall morbidity and mortality (OR 7.54, CI 2.13-26.73) and decreased return to preoperative disposition (OR 0.14, CI 0.04-0.56). CONCLUSIONS: The mFI, although promising, was not independently predictive of outcomes following surgery for adhesive small bowel obstruction. Further adequately powered studies are required.

Frailty and cancer: Implications for oncology surgery, medical oncology, and radiation oncology.

Answer questions and earn CME/CNE The concept of frailty has become increasingly recognized as one of the most important issues in health care and health outcomes and is of particular importance in patients with cancer who are receiving treatment with surgery, chemotherapy, and radiotherapy. Because both cancer itself, as well as the therapies offered, can be significant additional stressors that challenge a patient's physiologic reserve, the incidence of frailty in older patients with cancer is especially high-it is estimated that over one-half of older patients with cancer have frailty or prefrailty. Defining frailty can be challenging, however. Put simply, frailty is a state of extreme vulnerability to stressors that leads to adverse health outcomes. In reality, frailty is a complex, multidimensional, and cyclical state of diminished physiologic reserve that results in decreased resiliency and adaptive capacity and increased vulnerability to stressors. In addition, over 70 different measures of frailty have been proposed. Still, it has been demonstrated that frail patients are at increased risk of postoperative complications, chemotherapy intolerance, disease progression, and death. Although international standardization of frailty cutoff points are needed, continued efforts by oncology physicians and surgeons to identify frailty and promote multidisciplinary decision making will help to develop more individualized management strategies and optimize care for patients with cancer. CA Cancer J Clin 2017;67:362-377. © 2017 American Cancer Society.

Prevalence and impact of frailty in patients undergoing colorectal cancer surgery: A systematic review and meta-analysis based on modified frailty index.

Frailty has been linked to unfavorable postoperative outcomes in patients with colorectal cancer (CRC). However, the prevalence of frailty among CRC surgery patients and its association with mortality and postoperative complications, as evaluated by the modified frailty index (mFI), have not been thoroughly investigated and necessitate clarification. PubMed, Web of Science, Embase, and CBM databases were systematically searched for relevant studies (up to January 2024), and the pooled prevalence and odds ratio (OR) estimate were calculated. A total of 16 studies containing 245 747 patients undergoing CRC surgery were included. The prevalence of frailty among CRC surgery patients was 31% (95% confidence interval [CI] = 20%-42%; I2 = 100%, p < 0.001). In patients undergoing CRC surgery, frailty was associated with a higher incidence of postoperative complications (OR = 1.94; 95% CI = 1.47-2.56; I2 = 91.9%, p < 0.001), but it did not exhibit any significant correlation with the 30-day mortality (OR = 5.17; 95% CI = 0.39-68.64; I2 = 94.4%, p < 0.001). Frailty is common in CRC surgery and exerts a significant negative impact on the postoperative outcomes. Future research could explore the potential of the mFI to facilitate a more streamlined and precise quantification of frailty, thereby establishing a refined understanding of its correlation with surgery prognosis.

The association of a frailty index derived from laboratory tests and vital signs with clinical outcomes in critical care patients with septic shock: a retrospective study based on the MIMIC-IV database.

PURPOSE: Frailty is a vulnerable state to stressors due to the loss of physiological reserve as a result of multisystem dysfunction. The physiological and laboratory-based frailty index (FI-Lab), depending on laboratory values and vital signs, is a powerful tool to capture frailty status. The aim of this study was to assess the relationship between FI-Lab and in-hospital mortality in patients with septic shock. METHODS: Baseline data for patients with sepsis in the intensive care unit were retrieved from the Critical Care Medicine Database (MIMIC-IV, v2.2). The primary outcome was mortality during hospitalization. The propensity score matching (PSM) method was used to analyze the basic conditions during hospitalization between groups.The FI-Lab was analysed for its relationship with in-hospital mortality using logistic regression according to continuous and categorical variables, respectively, and described using the restricted cubic spline (RCS). Survival was compared between groups using Kaplan-Meier (KM) curves. Subgroup analyses were used to improve the stability of the results. RESULTS: A total of 9219 patients were included. A cohort score of 1803 matched patients was generated after PSM. The analyses showed that non-surviving patients with septic shock in the ICU had a high FI-Lab index (P<0.001). FI-Lab, whether used as a continuous or categorical variable, increased with increasing FI-Lab and increased in-hospital mortality (P<0.001).Subgroup analyses showed similar results. RCS depicts this non-linear relationship. KM analysis shows the cumulative survival time during hospitalisation was significantly lower as FI-Lab increased (log-rank test, P<0.001). CONCLUSION: Elevated FI-Lab is associated with increased in-hospital mortality in patients with septic shock.

Dietary trajectories over 21 years and frailty in Norwegian older adults: the Tromsø Study 1994-2016.

PURPOSE: To investigate the association between five dietary trajectories over 21 years and frailty in Norwegian older adults. METHODS: This study used data from three surveys of the Tromsø Study. Diet was measured using food frequency questionnaires at baseline (Tromsø4, 1994-95), after 7 years (Tromsø5, 2001) and at the end of follow-up (Tromsø7, 2015-16). Survey-specific diet scores were constructed based on the Nordic Nutrition Recommendations 2023 and group-based trajectory modelling was used to derive dietary trajectories. At follow-up, frailty was assessed with a 41-item frailty index. Linear regression analysis was performed to assess the associations between dietary trajectories and frailty, adjusted for baseline variables. RESULTS: Among the 715 participants, 55% were women, with an average age of 54 years at baseline and 74 years at follow-up. The dietary trajectories 'moderately healthy' and 'healthy increase' were associated with a lower frailty index score at follow-up (ß = -0.02, 95% confidence interval (CI) = -0.04, -0.002, ß = -0.03, 95% CI = -0.06, -0.007), compared with the 'unhealthy' trajectory. CONCLUSION: Our findings suggest that maintaining a moderately healthy to very healthy diet from mid-life into older age is associated with a lower risk of frailty and supports the promotion of a healthy diet from adulthood to facilitate healthy ageing.

Higher plant-derived nitrate intake is associated with lower odds of frailty in a cross-sectional study of community-dwelling older women.

PURPOSE: Dietary nitrate intake is inversely related to numerous contributors towards frailty, including cardiovascular disease and poor physical function. Whether these findings extend to frailty remain unknown. We investigated if habitual nitrate intake, derived from plants or animal-based foods, was cross-sectionally associated with frailty in women. METHODS: Community-dwelling older Australian women (n = 1390, mean age 75.1 ± 2.7 years) completed a validated semi-quantitative food frequency questionnaire (FFQ). Nitrate concentrations in food were obtained from international nitrate databases. We adopted the Rockwood frailty index (FI) of cumulative deficits comprising 33 variables across multiple health domains (scored 0 to 1), which predicts increased hospitalisation and mortality risk. A FI ≥ 0.25 indicated frailty. Cross-sectional associations between nitrate intake (total plant and animal nitrate, separately) and frailty were analysed using multivariable-adjusted logistic regression models (including lifestyle factors), as part of restricted cubic splines. RESULTS: A non-linear inverse relationship was observed between total plant nitrate intake and frailty. Compared to women with the lowest plant nitrate intake (Quartile [Q]1), women with greater intakes in Q2 (OR 0.69 95%CI 0.56-0.84), Q3 (OR 0.67 95%CI 0.50-0.90) and Q4 (OR 0.66 95%CI 0.45-0.98) had lower odds for frailty. A nadir in the inverse association was observed once intakes reached ~ 64 mg/d (median Q2). No relationship was observed between total animal nitrate and frailty. CONCLUSION: Community-dwelling older women consuming low amounts of plant-derived nitrate were more likely to present with frailty. Consuming at least one daily serving (~ 75 g) of nitrate-rich green leafy vegetables may be beneficial in preventing frailty.

The brain insulin receptor gene network and associations with frailty index.

OBJECTIVE: To investigate longitudinal associations between variations in the co-expression-based brain insulin receptor polygenic risk score and frailty, as well as change in frailty across follow-up. METHODS: This longitudinal study included 1605 participants from the Helsinki Birth Cohort Study. Biologically informed expression-based polygenic risk scores for the insulin receptor gene network, which measure genetic variation in the function of the insulin receptor, were calculated for the hippocampal (hePRS-IR) and the mesocorticolimbic (mePRS-IR) regions. Frailty was assessed in at baseline in 2001-2004, 2011-2013 and 2017-2018 by applying a deficit accumulation-based frailty index. Analyses were carried out by applying linear mixed models and logistical regression models adjusted for adult socioeconomic status, birthweight, smoking and their interactions with age. RESULTS: The FI levels of women were 1.19%-points (95% CI 0.12-2.26, P = 0.029) higher than in men. Both categorical and continuous hePRS-IR in women were associated with higher FI levels than in men at baseline (P < 0.05). In women with high hePRS-IR, the rate of change was steeper with increasing age compared to those with low or moderate hePRS-IR (P < 0.05). No associations were detected between mePRS-IR and frailty at baseline, nor between mePRS-IR and the increase in mean FI levels per year in either sex (P > 0.43). CONCLUSIONS: Higher variation in the function of the insulin receptor gene network in the hippocampus is associated with increasing frailty in women. This could potentially offer novel targets for future drug development aimed at frailty and ageing.

Joint association of cardiovascular health and frailty with all-cause and cause-specific mortality: a prospective study.

BACKGROUND: Poor cardiovascular health (CVH) and physical frailty were reported to increase mortality risk, but their joint effects have not been fully elucidated. OBJECTIVES: 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.

The electronic frailty index and outcomes in patients with myocardial infarction.

BACKGROUND: Frailty is increasingly present in patients with acute myocardial infarction. The electronic Frailty Index (eFI) is a validated method of identifying vulnerable older patients in the community from routine primary care data. Our aim was to assess the relationship between the eFI and outcomes in older patients hospitalised with acute myocardial infarction. STUDY DESIGN AND SETTING: Retrospective cohort study using the DataLoch Heart Disease Registry comprising consecutive patients aged 65 years or over hospitalised with a myocardial infarction between October 2013 and March 2021. METHODS: Patients were classified as fit, mild, moderate, or severely frail based on their eFI score. Cox-regression analysis was used to determine the association between frailty category and all-cause mortality. RESULTS: In 4670 patients (median age 77 years [71-84], 43% female), 1865 (40%) were classified as fit, with 1699 (36%), 798 (17%) and 308 (7%) classified as mild, moderate and severely frail, respectively. In total, 1142 patients died within 12 months of which 248 (13%) and 147 (48%) were classified as fit and severely frail, respectively. After adjustment, any degree of frailty was associated with an increased risk of all-cause death with the risk greatest in the severely frail (reference = fit, adjusted hazard ratio 2.87 [95% confidence intervals 2.24 to 3.66]). CONCLUSION: The eFI identified patients at high risk of death following myocardial infarction. Automatic calculation within administrative data is feasible and could provide a low-cost method of identifying vulnerable older patients on hospital presentation.

Utility of the mFI-5 as a predictor of post-operative outcomes following gastrectomy for gastric cancer: an ACS-NSQIP analysis.

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. CONCLUSION: 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.

The risk analysis index demonstrates exceptional discrimination in predicting frailty's impact on neurosurgical length of stay quality metrics.

BACKGROUND: Quality measures determine reimbursement rates and penalties in value-based payment models. Frailty impacts these quality metrics across surgical specialties. We compared the discriminatory thresholds for the risk analysis index (RAI), modified frailty index-5 (mFI-5) and increasing patient age for the outcomes of extended length of stay (LOS [eLOS]), prolonged LOS within 30 days (pLOS), and protracted LOS (LOS > 30). METHODS: Patients ≥18 years old who underwent neurosurgical procedures between 2012 and 2020 were queried from the ACS-NSQIP. We performed receiver operating characteristic analysis, and multivariable analyses to examine discriminatory thresholds and identify independent associations. RESULTS: There were 411,605 patients included, with a median age of 59 years (IQR, 48-69), 52.2% male patients, and a white majority 75.2%. For eLOS: RAI C-statistic 0.653 (95% CI: 0.652-0.655), versus mFI-5 C-statistic 0.552 (95% CI: 0.550-0.554) and increasing patient age C-statistic 0.573 (95% CI: 0.571-0.575). Similar trends were observed for pLOS- RAI: 0.718, mFI-5: 0.568, increasing patient age: 0.559, and for LOS>30- RAI: 0.714, mFI-5: 0.548, and increasing patient age: 0.506. Patients with major complications had eLOS 10.1%, pLOS 26.5%, and LOS >30 45.5%. RAI showed a larger effect for all three outcomes, and major complications in multivariable analyses. CONCLUSION: Increasing frailty was associated with three key quality metrics that is, eLOS, pLOS, LOS > 30 after neurosurgical procedures. The RAI demonstrated a higher discriminating threshold compared to both mFI-5 and increasing patient age. Preoperative frailty screening may improve quality metrics through risk mitigation strategies and better preoperative communication with patients and their families.

Health-related quality of life measures provide information on the contributors, components, and consequences of frailty in HIV: a systematic mapping review.

PURPOSE: Frailty in HIV is extensively explored in epidemiological and clinical studies; it is infrequently assessed as an outcome in routine care. The focus on health-related quality of life (HRQL) measures in HIV presents a unique opportunity to understand frailty at a larger scale. The objective was to identify the extent to which generic and HIV-related HRQL measures capture information relevant to frailty. METHODS: A systematic mapping review using directed and summative content analyses was conducted. An online search in PubMed/Medline identified publications on frailty indices and generic and HIV-related HRQL measures. Directed content analysis involved identifying contributors, components, and consequences of frailty from the frailty indices based on the International Classification of Functioning, Disability, and Health framework. Summative content analysis summarized the results numerically. RESULTS: Electronic and hand search identified 447 review publications for frailty indices; nine reviews that included a total of 135 unique frailty indices. The search for generic and HIV-related HRQL measures identified 2008 records; five reviews that identified 35 HRQL measures (HIV-specific: 17; generic: 18). Of the 135 frailty indices, 88 cover more than one frailty dimension and 47 cover only physical frailty. Contributors to frailty, like sensory symptoms and nutrition, are extensively covered. Components of frailty such as physical capacity, cognitive ability, and mood are also extensively covered. Consequences of frailty namely self-rated health, falls, hospitalization, and health services utilization are incomprehensively covered. HRQL measures are informative for contributing factors, components of frailty, and a consequence of frailty. CONCLUSION: HRQL items and measures show a strong potential to operationalize multidimensional frailty and physical frailty. The study suggests that these measures, connected to evidence-based interventions, could be pivotal in directing resources toward vulnerable populations to mitigate the onset of frailty.

Sex-specific effects of frailty on cardiac structure and function: insights from preclinical models.

Advanced age is an independent risk factor for cardiovascular diseases in both sexes. This is thought to be due, in part, to age-dependent cellular, structural, and functional changes in the heart, a process known as cardiac aging. An emerging view is that cardiac aging leads to the accumulation of cellular and subcellular deficits that increase susceptibility to cardiovascular diseases. Still, people age at different rates, with those aging rapidly considered frail. Evidence suggests that frailty, rather than simply age, is a major risk factor for cardiovascular disease and predicts adverse outcomes in those affected. Recent studies in mouse models of frailty show that many adverse changes associated with cardiac aging are more prominent in mice with a high degree of frailty. This suggests that frailty sets the stage for late life cardiovascular diseases to flourish and raises the possibility that treating frailty may treat cardiovascular diseases. These studies show that ventricular dysfunction increases with frailty in males only, whereas atrial dysfunction increases with frailty in both sexes. These results may shed light on the reasons that men and women can be susceptible to different cardiovascular diseases as they age, and why frail individuals are especially vulnerable to these disorders.

Internet use and frailty in middle-aged and older adults: findings from developed and developing countries.

BACKGROUND: With increasing trend of internet use in all age groups, whether internet use can prevent frailty in middle-aged and older adults remains unclear. METHODS: Five cohorts, including Health and Retirement Study (HRS), China Health and Retirement Longitudinal Study (CHARLS), the Survey of Health, Ageing and Retirement in Europe (SHARE), English Longitudinal Study of Aging (ELSA), and Mexican Health and Aging Study (MHAS), were used in this study. Internet use, social isolation, and frailty status was assessed using similar questions. The Generalized estimating equations models, random effects meta-analysis, COX regression, and mediation analysis were utilized. RESULTS: In the multicohort study, a total of 155,695 participants were included in main analysis. The proportion of internet use was varied across countries, ranging from 5.56% in China (CHARLS) to 83.46% in Denmark (SHARE). According to the generalized estimating equations models and meta-analysis, internet use was inversely associated with frailty, with the pooled ORs (95%CIs) of 0.72 (0.67,0.79). The COX regression also showed that participants with internet use had a lower risk of frailty incidence. Additionally, the association was partially mediated by social isolation and slightly pronounced in participants aged 65 and over, male, not working for payment, not married or partnered, not smoking, drinking, and not co-residence with children. CONCLUSIONS: Our findings highlight the important role of internet use in preventing frailty and recommend more engagements in social communication and activities to avoid social isolation among middle-aged and older adults.

Exploration of the causality of frailty index on psoriasis: A Mendelian randomization study.

BACKGROUND: Frailty is associated with a variety of diseases, but the relationship between frailty and psoriasis remains unclear. METHODS: First, we conducted a two-sample Mendelian randomization based on genome-wide association studies (GWAS) to investigate genetic causality between frailty index and common diseases in dermatology. Inverse variance weighted was used to estimate causality. Second, expression quantitative trait locus (eQTLs) analysis was conducted to identify the genes affected by Single nucleotide polymorphisms (SNPs). Third, we performed function and pathway enrichment, transcriptome-wide association studies (TWAS) analysis based on eQTLs. RESULTS: It was shown that the rise of frailty index could increase the risk of psoriasis (IVW, beta = 0.916, OR = 2.500, 95%CI:1.418-4.408, p = 0.002) through Mendelian randomization (MR), and there was no heterogeneity and pleiotropy. There was no causality between the frailty index and other common diseases in dermatology. We found 31 eQTLs based on strongly correlated SNPs in the causality. TWAS analysis found that the expressions of four genes were closely related to psoriasis, including HLA-DQA1, HLA-DQA2, HLA-DRB1 and HLA-DQB1. CONCLUSION: It suggested that the frailty index had a significant positive causality on the risk of psoriasis, which was well documented by combined genomic, transcriptome, and proteome analyses.

Sex differences in the frailty phenotype and mortality in the I-Lan longitudinal aging study cohort.

BACKGROUND: Frailty is a common geriatric syndrome related to multiple adverse outcomes. Sex differences in its prevalence and impact on mortality remain incompletely understood. METHODS: This study was conducted with data from the I-Lan Longitudinal Aging Study, in which community-dwelling subjects aged > 50 years without coronary artery disease or diabetes were enrolled. Sex disparities in phenotypically defined frailty and sex-morality predictor interactions were evaluated. Sex- and frailty-stratified analyses of mortality were performed. RESULTS: The sample comprised 1371 subjects (51.4% women, median age 61 years). The median follow-up period was 6.3 (interquartile range, 5.8-7.0) years. The frailty prevalence did not differ between men (5.3%) and women (5.8%). Frail individuals were older and less educated and had poorer renal function than did non-frail individuals. Body composition trends differed between sexes, regardless of frailty. Relative to non-frail men, frail men had significantly lower body mass indices (BMIs; 24.5 vs. 23.4 kg/m2, p = 0.04) and relative appendicular skeletal muscle masses (7.87 vs. 7.05 kg/m2, p < 0.001). Frail women had significantly higher BMIs (25.2 vs. 23.9 kg/m2, p = 0.02) and waist circumferences (88 vs. 80 cm, p < 0.001) than did non-frail women. Frailty was an independent mortality predictor for men only [hazard ratio (95% confidence interval) = 3.395 (1.809-6.371), psex-frailty interaction = 0.03]. CONCLUSION: Frailty reflected poorer health in men than in women in the present cohort. This study revealed sex disparities in the impact of frailty on mortality among relatively healthy community-dwelling older adults.

Age- and sex-specific associations of frailty with mortality and healthcare utilization in community-dwelling adults from ontario, Canada.

BACKGROUND: Understanding how health trajectories are related to the likelihood of adverse outcomes and healthcare utilization is key to planning effective strategies for improving health span and the delivery of care to older adults. Frailty measures are useful tools for risk stratification in community-based and primary care settings, although their effectiveness in adults younger than 60 is not well described. METHODS: We performed a 10-year retrospective analysis of secondary data from the Ontario Health Study, which included 161,149 adults aged ≥ 18. Outcomes including all-cause mortality and hospital admissions were obtained through linkage to ICES administrative databases with a median follow-up of 7.1-years. Frailty was characterized using a 30-item frailty index. RESULTS: Frailty increased linearly with age and was higher for women at all ages. A 0.1-increase in frailty was significantly associated with mortality (HR = 1.47), the total number of outpatient (IRR = 1.35) and inpatient (IRR = 1.60) admissions over time, and length of stay (IRR = 1.12). However, with exception to length of stay, these estimates differed depending on age and sex. The hazard of death associated with frailty was greater at younger ages, particularly in women. Associations with admissions also decreased with age, similarly between sexes for outpatient visits and more so in men for inpatient. CONCLUSIONS: These findings suggest that frailty is an important health construct for both younger and older adults. Hence targeted interventions to reduce the impact of frailty before the age of 60 would likely have important economic and social implications in both the short- and long-term.

Sarcopenic obesity and pre-sarcopenia contribute to frailty in community-dwelling Italian older people: data from the FRASNET study.

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. CONCLUSION: Pre-sarcopenia and SO represent potentially treatable predictors of frailty.