BACKGROUND: Previous observational studies have revealed a potentially robust bidirectional relationship between frailty and low back pain (LBP). However, the precise causal relationship remains unclear.
METHODS: To examine the potential causal association between frailty and LBP, we conducted bidirectional two-sample Mendelian randomization analysis (MR) study. Genetic data on frailty index (FI) and LBP were acquired from publicly available genome-wide association studies (GWAS). Various MR methodologies were utilized, such as inverse variance weighting (IVW), weighted median, and MR-Egger, to evaluate causality. Additionally, sensitivity analyses were conducted to evaluate the robustness of the findings.
RESULTS: Genetically predicted higher FI (IVW, odds ratio [OR] = 1.66, 95% CI 1.17-2.36, p = 4.92E-03) was associated with a higher risk of LBP. As for the reverse direction, genetic liability to LBP showed consistent associations with a higher FI (IVW, OR = 1.13, 95% CI 1.07-1.19, p = 2.67E-05). The outcomes from various MR techniques and sensitivity analyses indicate the robustness of our findings.
CONCLUSIONS: Our research findings provide additional evidence bolstering the bidirectional causal relationship between frailty and LBP.

OBJECTIVE: The aim was to predict the effectiveness of using frailty, defined by the frailty index (FI), for predicting recurrent pneumonia and death in patients over 50 years and older with vascular cognitive impairment (VCI) during long-term hospitalization.
METHODS: This retrospective cohort study was conducted at a teaching hospital in western China and included VCI patients aged ≥50 years undergoing long-term hospitalization. The relevant data were collected from the electronic medical record system. The FI was based on 31 parameters and groups were defined using a cutoff value (0.2) as robust (FI < 0.2) and FRAIL (≥0.2). The definition of recurrent pneumonia was a minimum of two episodes within a year, with the symptoms, signs, and imaging results of pneumonia disappearing completely between episodes, and a minimum interval between episodes of seven days. Death was recorded by the hospital as the result of cardiac and respiratory arrest and survival was defined as the interval between hospital admission and confirmed death. Logistic regression models were used to assess the association between FI and recurrent pneumonia, while associations between FI and death were assessed by Cox proportional hazards models.
RESULTS: A total of 252 long-term hospitalized VCI patients ≥50 years old were enrolled, of whom 115 were male (45.6 %). Ninety-seven patients (38.5 %) were defined as FRAIL. The median length of stay for hospitalized patients was 37 months. Overall, 215 patients developed pneumonia during hospitalization, which occurred an average of 14.5 months after admission, while 151 (59.9 %) had recurrent pneumonia, and 155 (61.5 %) died. Of these, 143 died in the hospital and 12 died after discharge. No significant differences were seen in the incidence of recurrent pneumonia between FRAIL and robust long-term hospitalized VCI patients (FRAIL vs. robust: 66.0 % vs. 56.1 %, P = 0.121) while FRAIL patients had a higher mortality rate than robust patients (FRAIL vs. robust: 71.1 % vs. 55.5 %, P = 0.013). After further Cox regression analysis and adjustment for possible confounders found to be significant in the univariate analysis (including age, sex, smoking history, and activities of daily living (ADL) score), FRAIL patients had a higher risk of death than healthy patients (HR = 1.595, 95 % CI: 1.149-2.213). In addition, based on Model 2, confounding variables that were not statistically significant in the univariate analysis but may have had an impact on the results (including marital status, educational level, drinking history, comorbidity and rehabilitation treatment) were incorporated into Model 3 for further correction. The result remained unchanged, namely, that compared with robust patients, FRAIL patients had a higher risk of death (HR = 1.771, 95 % CI: 1.228-2.554).
CONCLUSIONS: Frailty defined by the FI was effective for predicting the risk of mortality but not that of recurrent pneumonia in long-term hospitalized VCI patients aged 50 or older.

UNASSIGNED: The emergence of obstructive sleep apnea (OSA) is marked by a growing trend towards younger individuals, while its developmental trajectory remains shrouded in uncertainty, accompanied by intricate prognostic implications. While frailty and sleep problems often coexist, the relationship between them remains unclear. Hence, this study aims to utilize the National Health and Nutrition Examination Survey (NHANES) database from 2005 to 2008 to analyze and explore the relationship between the level of frailty index (FI) and the risk of OSA incidence and survival outcomes.
UNASSIGNED: Specialized weighted complex survey design analysis software was employed for data analysis. Multivariate logistic regression models and restricted cubic splines (RCS) were utilized to assess the association between FI and OSA incidence in all participants. Additionally, a Cox proportional hazards model was established to estimate the association between FI and the hazard ratios (HRs) for all-cause mortality and cardiovascular disease (CVD) mortality.
UNASSIGNED: A total of 8524 participants were included in this study. Compared to the Non-frail group (FI ≤ 0.1), OSA risk increased with higher FI levels. In Model 3, adjusted for multiple covariates, the Pro-frail group (0.1 0.3) [OR = 2.32, 95 % CI (1.55, 3.48)] exhibited an average 31 %, 62 %, and 132 % increase in OSA risk, respectively. RCS results demonstrated a nonlinear dose-response relationship between OSA risk and FI levels, with an increasing trend (P = 0.004). The Cox model indicated that, except for the Pro-frail group, OSA-related mortality risk also increased with higher FI levels, with a more pronounced effect on CVD-related mortality.
UNASSIGNED: This study supports the hypothesis that FI may be associated with an increased risk of OSA, with a higher emphasis on OSA-related mortality risk in Mildly frail and Moderately/Severely frail populations.

UNASSIGNED: Frailty is a severe, common co-morbidity associated with congestive heart failure (CHF). This retrospective cohort study assesses the association between frailty and the risk of mortality in critically ill CHF patients.
UNASSIGNED: Eligible patients with CHF from the Medical Information Base for Intensive Care IV database were retrospectively analyzed. The frailty index based on laboratory tests (FI_Lab) index was calculated using 33 variables to assess frailty status. The primary outcomes were in-hospital mortality and one-year mortality. The secondary outcomes were the incidence of acute kidney injury (AKI) and the administration of renal replacement therapy (RRT) in patients with concurrent AKI. Survival disparities among the FI_Lab subgroups were estimated with Kaplan-Meier survival analysis. The association between the FI_Lab index and mortality was examined with Cox proportional risk modeling.
UNASSIGNED: A total of 3273 adult patients aged 18 years and older were enrolled in the study, with 1820 men and 1453 women included. The incidence rates of in-hospital mortality and one-year mortality rate were 0.96 per 1,000 person-days and 263.8 per 1,000 person-years, respectively. Multivariable regression analysis identified baseline FI_Lab > 0.45 as an independent risk factor predicting in-hospital mortality (odds ratio = 3.221, 95% CI 2.341-4.432, p < 0.001) and one-year mortality (hazard ratio=2.152, 95% CI: 1.730-2.678, p < 0.001). In terms of predicting mortality, adding FI_Lab to the six disease severity scores significantly improved the overall performance of the model (all p < 0.001).
UNASSIGNED: We established a positive correlation between the baseline FI_Lab and the likelihood of adverse outcomes in critical CHF patients. Given its potential as a reliable prognostic tool for such patients, further validation of FI_Lab across multiple centers is recommended for future research.

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 (β = 0.15, 0.38 and 0.76 respectively) and those experiencing the third to fourth cumulative TyG-BMI (β = 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.
CONCLUSIONS: 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.

BACKGROUND: Exploring the association between Childhood Emotional Support (CES) and the mechanisms of aging is pivotal for understanding its potential to lessen the incidence of age-related pathologies and promote a milieu for healthy aging.
METHODS: Utilizing data from the UK Biobank comprising nearly 160,000 individuals, comprehensive analyses were conducted to explore associations between CES levels and age-related diseases, biological age and aging hallmarks. Cox proportional hazards regression models were used to investigate the relationship between CES and the risk of hospitalization for age-related diseases. Linear regression models were employed to explore the associations between CES and the frailty index (FI), Klemera-Doubal method (KDM) biological age acceleration, homeostatic dysregulation (HD), C-reactive protein (CRP), white blood cell (WBC) count, and telomere length.
RESULTS: The analyses revealed a significant association between higher CES levels and a decreased risk of hospitalization for age-related diseases in later life. After adjustments for covariates, the hazard ratio for age-related diseases was 0.87 (95 % confidence interval, 0.83-0.91, p < 0.001) in those with the highest CES level compared to those with the lowest CES level. Participants with the highest CES level exhibited lower FI scores (coefficient = -0.033, p < 0.001), reduced CRP level (coefficient = -0.097, p < 0.05) and lower WBC counts (coefficient = -0.034, p < 0.05). Stratified analyses based on genetic susceptibility further elucidated the protective role of CES against age-related diseases.
CONCLUSIONS: These findings underscore the potential of early interventions targeting CES to promote healthy aging and alleviating the burden of age-related diseases.

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: 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.

UNASSIGNED: Empirical research has consistently documented the concurrent manifestation of frailty and chronic kidney disease (CKD). However, the existence of a reverse causal association or the influence of confounding variables on these correlations remains ambiguous.
UNASSIGNED: Our analysis of 7,078 participants from National Health and Nutrition Examination Survey(NHANES) (1999-2018) applied weighted logistic regression and Mendelian Randomization (MR) to investigate the correlation between the frailty index (FI) and renal function. The multivariate MR analysis was specifically adjusted for type 2 diabetes and hypertension. Further analysis explored 3282 plasma proteins to link FI to CKD. A two-step network MR highlighted immune cells\' mediating roles in the FI-CKD relationship.
UNASSIGNED: Genetically inferred FI and various renal function markers are significantly correlated, as supported by NHANES analyses. Multivariate MR analysis revealed a direct causal association between the FI and CKD. Additionally, our investigation into plasma proteins identified Tmprss11D and MICB correlated with FI and CKD, respectively. A two-step network MR to reveal 15 immune cell types, notably Central Memory CD4+ T cells and Lymphocytes, as crucial mediators between FI and CKD.
UNASSIGNED: Our work establishes a causal connection between frailty and CKD, mediated by specific immune cell profiles. These findings highlight the importance of immune mechanisms in the frailty-CKD interplay and suggest that targeting shared risk factors and immune pathways could improve management strategies for these conditions. Our research contributes to a more nuanced understanding of frailty and CKD, offering new avenues for intervention and patient care in an aging population.