Effectiveness of the frailty index in predicting recurrent pneumonia and death in long-term hospitalized patients with vascular cognitive impairment.

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 50 years and older with vascular cognitive impairment (VCI) during long-term hospitalization. MEASUREMENTS: 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 AND IMPLICATIONS: 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.

Modified 5-Item Frailty Index (mFI-5) may predict postoperative outcomes after pancreatoduodenectomy for pancreatic Cancer.

BACKGROUND: Pancreatic Ductal Adenocarcinoma (PDAC) primarily affects older individuals with diminished physiological reserves. The Modified 5-Item Frailty Index (mFI-5) is a novel risk stratification tool proposed to predict postoperative morbidity and mortality. This study aimed to validate the mFI-5 for predicting surgical outcomes in patients undergoing pancreatoduodenectomy (PD) for PDAC. METHODS: Our retrospective PDAC database included patients who underwent PD between 2014 and 2023. Patients were stratified by mFI-5 scores (0 best - 5 worst), which assess preoperative CHF, diabetes mellitus, history of COPD or pneumonia, functional health status, and hypertension requiring medication. Associations between mFI-5 scores and outcomes, including postoperative complications and mortality, were analyzed using logistic regression, Cox proportional hazards models, and Kaplan-Meier survival analysis. RESULTS: Among 250 PDAC patients undergoing PD, 142 (56.8%) had mFI-5 scores ≤ 1, and 25 (10%) had scores ≥ 3. No patients had scores > 4. Higher mFI-5 scores correlated with older age (p < 0.001) and tobacco use (p = 0.036). Multivariate analysis identified age (RR 1.02, p = 0.038), ASA class (ASA III; RR 2.61, p < 0.001; ASA IV; RR 2.63, p = 0.026), and moderate alcohol consumption (RR 0.56, p = 0.038) as frailty predictors. An mFI-5 score > 2 independently associated with higher mortality (HR 2.08, p = 0.026). Median overall survival was significantly lower for patients with mFI-5 scores > 2 than for those with scores ≤ 2 (21.3 vs. 42.1 months, p = 0.022). CONCLUSIONS: The mFI-5 is a valuable tool for predicting postoperative morbidity and mortality in PDAC patients undergoing PD. Integrating frailty assessment into preoperative evaluations can enhance patient selection and surgical outcomes. Future research should focus on incorporating frailty assessments into surgical planning and patient management to improve outcomes in this vulnerable population.

Preoperative clinical characteristics and 12-month outcomes following operative or non-operative management of asymptomatic aortic aneurysms.

DESIGN: An observational cohort study conducted at a tertiary referral center for aortic surgery to describe the medical and surgical characteristics of patients assessed for abdominal aortic aneurysm repair and examine associations with 12-month outcome. METHODS: Patients with aortic aneurysms referred for discussion at the aortic multidisciplinary meeting (MDM). Data were collected via a prospectively maintained clinical database and included aneurysm characteristics, patient demographics, co-morbidities, geriatric syndromes, including frailty, management decision and 12-month mortality, both aneurysm-related and all-cause including cause of death. The operative and non-operative groups were compared statistically. RESULTS: 621 patients referred to aortic MDM; 292 patients listed for operative management, 141 patients continued on surveillance, 138 patients for non-operative management. There was a higher 12-month mortality rate in the non-operative group compared to the operative group (41% vs 7%, P = <0.001). In the non-operative group, 16 patients (29%) died of aneurysm rupture within 12 months, with 39 patients (71%) dying from other medical causes. Non-operatively managed patients were older, more likely to have cardiac and respiratory disease and more likely to be living with frailty, cognitive impairment and functional limitation, compared to the operative group. CONCLUSION: This study shows that preoperative geriatric syndromes and increased comorbidity lead to shared decision to non-operatively manage asymptomatic aortic aneurysms. Twelve-month mortality is higher in the non-operative group with the majority of deaths occurring due to cause other than aneurysm rupture. These findings support the need for preoperative comprehensive geriatric assessment followed by multispecialty discussion and shared decision making.

Multidimensional frailty as a predictor of mortality among older adults: a systematic review and meta-analysis.

OBJECTIVE: This systematic review examined studies that assessed the relationship between mortality risk and multidimensional frailty. The pooled risk of mortality was estimated via a meta-analysis. DESIGN: A systematic review and meta-analysis. METHODS: A systematic search for potentially eligible literature was conducted on January 2, 2023, using five electronic databases: Web of Science, CINAHL, PubMed, the Cochrane Library and Embase. This review included cohort or longitudinal studies examining the association between multidimensional frailty/prefrailty and mortality in older adults. The quality of the included studies was evaluated via the Quality in Prognosis Studies (QUIPS) tool. Two independent researchers identified eligible studies and extracted the data. The data analyses were performed via STATA, version 15.0. RESULTS: A total of 24 studies with 34,664 participants were included. The 24 studies were published between 2012 and 2022, with most studies being performed in Italy (n = 16). The sample sizes of the included studies ranged from 71 to 12,020. Most included studies were conducted in hospital settings. The QUIPS bias assessment results showed that the most frequent source of potential bias was study confounding. The meta-analysis results showed that multidimensional frailty was a significant predictor of mortality (HR = 5.48, 95% CI = 3.91-7.67, p < 0.001). In addition, multidimensional prefrailty was also a significant predictor of mortality (HR = 2.56, 95% CI = 2.17-3.02, p < 0.001). The results of the meta-analysis using the ORs revealed that multidimensional frailty was a risk factor for mortality in older people (OR = 4.59, 95% CI = 2.47-8.55, p < 0.05). CONCLUSIONS AND IMPLICATIONS: This systematic review of the relationship between multidimensional frailty and mortality found that multidimensional frailty/prefrailty is a predictor of mortality. More studies should be conducted in community dwelling populations and nursing homes.

Association between complete blood count-derived inflammatory markers and the risk of frailty and mortality in middle-aged and older adults.

Objective: This study aimed to evaluate the association between six complete blood count (CBC)-derived inflammatory markers [neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), platelet-to-lymphocyte ratio (PLR), systemic immune-inflammatory index (SII), systemic inflammatory response index (SIRI), and pan-immune inflammation value (PIV)] and the risk of frailty and mortality. Methods: Data were obtained from the National Health and Nutrition Examination Survey (NHANES) 1999-2018. Mortality was identified using the National Death Index until December 31, 2019. Multiple logistic regression analysis was conducted to evaluate the association between six CBC-derived inflammatory markers and frailty. The Cox regression model assessed the association between six CBC-derived inflammatory markers and mortality in frail populations. Restricted cubic spline (RCS) was used to visualize the association of the six CBC-derived inflammatory markers with mortality risk. The predictive value of CBC-derived inflammatory markers for mortality was further assessed using a random survival forest (RSF) approach. Results: This study analyzed data from a total of 16,705 middle-aged and older participants. Among them, 6,503 participants were frail, with a mortality rate of 41.47%. Multiple logistic regression analysis showed that NLR, MLR, PLR, SII, SIRI, and PIV were positively associated with frailty risk. The Cox regression model revealed that participants in the highest quartile had a significantly increased risk of death compared to those in the lowest quartile: NLR (HR = 1.73, 95% CI:1.54, 1.94), MLR (HR = 1.71, 95% CI:1.51, 1.93), PLR (HR = 1.28, 95%CI: 1.15, 1.43), SII (HR = 1.50, 95%CI:1.34, 1.68), SIRI (HR = 1.88, CI 95%:1.67, 2.12), PIV (HR = 1.55, 95%CI:1.38, 1.73). Random survival forest (RSF) analyses demonstrated that MLR had the highest predictive value for mortality risk middle-aged and older adult frail participants. Conclusion: The results suggest that CBC-derived inflammatory markers are associated with a higher risk of frailty as well as mortality in the middle and old-aged population of the United States.

Trajectories of Frailty and Clinical Outcomes in Older Adults With Atrial Fibrillation: Insights From the Shizuoka Kokuho Database.

BACKGROUND: The increasing prevalence of frailty has gained considerable attention due to its profound influence on clinical outcomes. However, our understanding of the progression of frailty and long-term clinical outcomes in older individuals with atrial fibrillation remains scarce. METHODS: Using data from 2012 to 2018 from a comprehensive claims database incorporating primary and hospital care records in Shizuoka, Japan, we selected patients aged ≥65 years with atrial fibrillation who initiated oral anticoagulant therapy. The trajectory of frailty was plotted using Sankey plots, illustrating the annual changes in their frailty according to the electronic frailty index during a 3-year follow-up after oral anticoagulant initiation, along with the incidence of clinical adverse outcomes. For deceased patients, we assessed their frailty status in the year preceding their death. RESULTS: Of 6247 eligible patients (45.1% women; mean age, 79.3±8.0 years) at oral anticoagulant initiation, 7.7% were categorized as fit (electronic frailty index, 0-0.12), 30.1% as mildly frail (>0.12-0.24), 35.4% as moderately frail (>0.24-0.36), and 25.9% as severely frail (>0.36). Over the 3-year follow-up, 10.4% of initially fit patients transitioned to moderately frail or severely frail. Conversely, 12.5% of severely frail patients improved to fit or mildly frail. Death, stroke, and major bleeding occurred in 23.4%, 4.1%, and 2.2% of patients, respectively. Among the mortality cases, 74.8% (N=1183) and 3.5% (N=55) had experienced moderately or severely frail and either a stroke or major bleeding in the year preceding their death, respectively. CONCLUSIONS: In a contemporary era of atrial fibrillation management, a minor fraction of older patients on oral anticoagulants died following a stroke or major bleeding. However, their frailty demonstrated a dynamic trajectory, and a substantial proportion of death was observed after transitioning to a moderately or severely frail state.

The association between frailty and the risk of mortality in critically ill congestive heart failure patients: findings from the MIMIC-IV database.

Background: 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. Methods: 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. Results: 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). Conclusions: 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.

The effect of frailty on mortality and hospital admission in patients with benign pleural disease in Wales: a cohort study.

BACKGROUND: Pleural disease is common, representing 5% of the acute medical workload, and its incidence is rising, partly due to the ageing population. Frailty is an important feature and little is known about disease progression in patients with frailty and pleural disease. We aimed to examine the effect of frailty on mortality and other relevant outcomes in patients diagnosed with pleural disease. METHODS: In this cohort study in Wales, the national Secure Anonymised Information Linkage databank was used to identify a cohort of individuals diagnosed with non-malignant pleural disease between Jan 1, 2005, and March 1, 2023, who were not known to have left Wales. Frailty was assessed at diagnosis of pleural disease using an electronic Frailty Index. The primary outcome was time from diagnosis to all-cause mortality for all patients. Data were analysed using multilevel mixed-effects Cox proportional hazards regression adjusting for the prespecified covariates of age, sex, Welsh Index of Multiple Deprivation quintile, smoking status, comorbidity, and subtype of pleural disease. FINDINGS: 54 566 individuals were included in the final sample (median age 66 years [IQR 47-77]; 26 477 [48·5%] were female and 28 089 [51·5%] were male). By the end of the study period, 25 698 (47·1%) participants had died, with a median follow-up of 1·0 years (IQR 0·2-3·6). There was an association between frailty and all-cause mortality, which increased as frailty worsened. Compared with fit individuals, there was increasing mortality for those with mild frailty (adjusted hazard ratio 1·11 [95% CI 1·08-1·15]; p<0·0001), moderate frailty (1·25 [1·20-1·31]; p<0·0001), and severe frailty (1·36 [1·28-1·44]; p<0·0001). INTERPRETATION: Independent of age and comorbidities, frailty status at diagnosis of pleural disease appeared to be useful as a prognostic indicator. Patients with moderate or severe frailty had a rapid decline in health. Future patients should be assessed for frailty at the time of diagnosis of pleural disease and might benefit from optimised care and advance care planning. FUNDING: Cardiff University's Wellcome Trust iTPA funding award.

Comparison of two different frailty screening scales for predicting mortality due to all causes in older inpatients.

OBJECTIVE: This study examines the relationship between two frailty screening tools and 90-day all-cause mortality in geriatric inpatients. METHODS: The study included patients aged ≥60 years who were admitted to the geriatrics unit of a university hospital between June 2021 and August 2022 and whose mortality status and duration of hospitalization data were obtained from the Health Ministry System. During hospitalization, the patients were screened using two different frailty scales: the Simpler Modified Fried Frailty Scale (sMFS) and the Clinical Frailty Scale (CFS). Patients scoring ≥5 on the CFS and ≥3 on the sMFS were considered frail. RESULTS: A total of 84 participants with a mean age of 78.3±7.6 years were included in this study, of which 36.9% were male. Of the total, 60.7% and 89.3% were considered frail according to the CFS and sMFS, respectively, and the prevalence of all-cause mortality within 90 days was 19%. A univariate analysis using the Kaplan-Meier survival method revealed CFS scores to be statistically significantly related to 90-day all-cause mortality (p<0.001), while sMFS scores were not found to be statistically significant (p=0.849). Furthermore, a statistically significant relationship was identified between CFS score and all-cause mortality in multivariate analysis with Cox regression analysis [(p<0.001), hazard ratio (HR): 3.078; (95% confidence interval: 1.746-5.425)]. CONCLUSION: An evaluation of frailty in hospitalized older adults using two different scales revealed the CFS to be superior to the sMFS in predicting all-cause mortality within 90 days.

The association of inflammatory markers with frailty and in-hospital mortality in older COVID-19 patients.

INTRODUCTION: During the COVID19 pandemic, older patients hospitalized for COVID-19 exhibited an increased mortality risk compared to younger patients. While ageing is associated with compromised immune responses and frailty, their contributions and interplay remain understudied. This study investigated the association between inflammatory markers and mortality and potential modification by frailty among older patients hospitalized for COVID-19. METHODS: Data were from three multicenter Dutch cohorts (COVID-OLD, CliniCo, Covid-Predict). Patients were 70 years or older, hospitalized for COVID-19and categorized into three frailty groups: fit (Clinical frailty score (CFS) 1-3), pre-frail (CFS 4-5), and frail (CFS 6-9). Immunological markers (lymphocyte count, neutrophil count, C-reactive protein, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and systemic inflammation index (SII)) were measured at baseline. Associations with in hospital mortality were examined using logistic regression. RESULTS: A total of 1697 patients were included from COVID-OLD, 656 from Covid-Predict, and 574 from CliniCo. The median age was 79, 77, and 78 years for each cohort. Hospital mortality rates were 33 %, 27 % and 39 % in the three cohorts, respectively. A lower CRP was associated with a higher frailty score in all three cohorts (all p < 0.01). Lymphocyte count, neutrophil count, NLR, PLR, or SII, were similar across frailty groups. Higher CRP levels were associated with increased in-hospital mortality risk across all frailty groups, across all cohorts (OR (95 % CI), 2.88 (2.20-3.78), 3.15 (1.95-5.16), and 3.28 (1.87-5.92)), and frailty did not modify the association between inflammatory markers and in-hospital mortality (all p-interaction>0.05). CONCLUSION: While frailty is a significant factor in determining overall outcomes in older patients, our study suggests that the elevated risk of mortality in older patients with frailty compared to fit patients is likely not explained by difference in inflammatory responses.

Nutritional risk and adverse health outcomes in Chinese community-dwelling older adults: A study based on the Elderly Nutritional Indicators for Geriatric Malnutrition Assessment (ENIGMA).

OBJECTIVES: Malnutrition and nutritional risk are risk factors for many adverse health outcomes in older adults, but they have rarely been assessed in China. The aim of this study was to evaluate the availability of Elderly Nutritional Indicators for Geriatric Malnutrition Assessment (ENIGMA), a nutritional scale originally developed to predict mortality, in assessing nutritional risks and predicting adverse health outcomes in Chinese community-dwelling older adults. METHODS: This was a population-based longitudinal cohort study (Chinese Longitudinal Healthy Longevity Survey), with a 4-y follow-up of 2063 community-dwelling adults aged 65 y or older. Nutritional risks were assessed via the use of ENIGMA and Geriatric Nutritional Risk Index (GNRI) at baseline (the 2014 wave). Cognitive impairment, functional limitation, and frailty were evaluated using the Chinese version of the Mini-Mental State Examination, Instrumental Activities of Daily Living/Instrumental Activities of Daily Living scale, and Frailty Index, respectively, at baseline and 4-y follow-up (the 2018 wave). Mortality was measured by survival status and duration of exposure to death from baseline to follow-up. The associations of nutritional risks with prevalent/incident cognitive impairment, functional limitation and frailty, and 4-y mortality were estimated using logistic regression and Cox proportional hazards regression models, adjusting for confounders. The discriminatory accuracy of ENIGMA and GNRI for these adverse health outcomes were compared by receiver operating characteristic analyses. RESULTS: According to ENIGMA, 48.6% of the Chinese community-dwelling older adults (age: 86.5±11.3 y) showed moderate and high nutritional risk. Nutritional risks defined by the ENIGMA were significantly associated with increased prevalence and incidence of cognitive impairment, functional limitation, and frailty (odds ratio ranging from 1.79 to 89.6, values ranging from P < 0.001 to 0.048) but were mostly insignificant for that defined by GNRI. With respect to 4-y mortality, nutritional risks as defined by GNRI showed better prediction effects than those defined by ENIGMA. Receiver operating characteristic analyses indicated that nutritional risks defined by ENIGMA had better discriminatory accuracy than those defined by GNRI for prevalent and incident cognitive impairment (C = 0.73 vs 0.64, P < 0.001; C = 0.65 vs 0.59, P = 0.015, respectively), functional limitation (C = 0.74 vs 0.63, P < 0.001 at baseline; C = 0.61 vs 0.56, P = 0.016 at follow-up), frailty (C = 0.85 vs 0.67, P < 0.001 at baseline; C = 0.64 vs 0.55, P < 0.001 at follow-up), and even 4-y mortality (C = 0.68 vs 0.64, P = 0.020). CONCLUSIONS: ENIGMA could serve as a nutritional risk screening tool that has a robust role in predicting cognitive impairment, functional limitation, and frailty in Chinese community-dwelling older adults. It may be recommended for early nutritional risk screening and has the potential to guide early nutritional intervention in communities and primary care settings in China.

Inappropriate prescribing and association with readmission or mortality in hospitalised older adults with frailty: a systematic review and meta-analysis.

BACKGROUND: Inappropriate prescribing (IP) is common in hospitalised older adults with frailty. However, it is not known whether the presence of frailty confers an increased risk of mortality and readmissions from IP nor whether rectifying IP reduces this risk. This review was conducted to determine whether IP increases the risk of adverse outcomes in hospitalised middle-aged and older adults with frailty. METHODS: A systematic review was conducted on IP in hospitalised middle-aged (45-64 years) and older adults (≥ 65 years) with frailty. This review considered multiple types of IP including potentially inappropriate medicines, prescribing omissions and drug interactions. Both observational and interventional studies were included. The outcomes were mortality and hospital readmissions. The databases searched included MEDLINE, CINAHL, EMBASE, World of Science, SCOPUS and the Cochrane Library. The search was updated to 12 July 2024. Meta-analysis was performed to pool risk estimates using the random effects model. RESULTS: A total of 569 studies were identified and seven met the inclusion criteria, all focused on the older population. One of the five observational studies found an association between IP and emergency department visits and readmissions at specific time points. Three of the observational studies were amenable to meta-analysis which showed no significant association between IP and hospital readmissions (OR 1.08, 95% CI 0.90-1.31). Meta-analysis of the subgroup assessing Beers criteria medicines demonstrated that there was a 27% increase in the risk of hospital readmissions (OR 1.27, 95% CI 1.03-1.57) with this type of IP. In meta-analysis of the two interventional studies, there was a 37% reduced risk of mortality (OR 0.63, 95% CI 0.40-1.00) with interventions that reduced IP compared to usual care but no difference in hospital readmissions (OR 0.83, 95% CI 0.19-3.67). CONCLUSIONS: Interventions to reduce IP were associated with reduced risk of mortality, but not readmissions, compared to usual care in older adults with frailty. The use of Beers criteria medicines was associated with hospital readmissions in this group. However, there was limited evidence of an association between IP more broadly and mortality or hospital readmissions. Further high-quality studies are needed to confirm these findings.

Measuring Frailty Using Self-Report or Automated Tools to Identify Risk of Cardiovascular Events and Mortality: The Million Veteran Program.

BACKGROUND: Frailty, a syndrome of physiologic vulnerability, increases cardiovascular disease (CVD) risk. Whether in person or automated frailty tools are ideal for identifying CVD risk remains unclear. We calculated 3 distinct frailty scores and examined their associations with mortality and CVD events in the Million Veteran Program, a prospective cohort of nearly 1 million US veterans. METHODS AND RESULTS: Veterans aged ≥50 years and enrolled from 2011 to 2018 were included. Two frailty indices (FI) based on the deficit accumulation theory were calculated: the questionnaire-based 36-item Million Veteran Program-FI and 31-item Veterans Affairs-FI using claims data. We calculated Fried physical frailty using the self-reported, 3-item Study of Osteoporotic Fractures. Multivariable-adjusted Cox models examined the association of frailty by each score with primary (all-cause and CVD mortality) and secondary (myocardial infarction, stroke, and heart failure) outcomes. In 190 688 veterans (69±9 years, 94% male, 85% White), 33, 233 (17%) all-cause and 10 115 (5%) CVD deaths occurred. Using Million Veteran Program-FI, 29% were robust, 42% pre-frail, and 29% frail. Frailty prevalence increased by age group (27% in 50-59 to 42% in ≥90 years). Using the Million Veteran Program-FI, over 6±2 years, frail veterans had a higher hazard of all-cause (hazard ratio [HR], 3.05 [95% CI, 2.95-3.16]) and CVD mortality (HR, 3.65 [95% CI, 3.43-3.90]). Findings were concordant for the Veterans Affairs-FI and Study of Osteoporotic Fractures frailty definitions, and remained significant even among younger veterans aged 50-59 years. CONCLUSIONS: Irrespective of frailty measure, frailty is associated with a higher risk of all-cause mortality and adverse CVD events. Further study of frailty in veterans aged <60 years old is warranted.

Declined intrinsic capacity predicts long-term mortality in Chinese older adults: Beijing Longitudinal Study of Aging.

BACKGROUND: Intrinsic capacity reflects an individual's functions and capacities across their lifetime. There are few studies on whether the level of intrinsic capacity can predict long-term mortality in Chinese populations. OBJECTIVE: To explore the effects of intrinsic capacity on long-term outcomes in older Chinese adults. METHODS: Data were obtained from the Beijing Longitudinal Study of Aging. Overall, 1699 community-dwelling adults aged ≥60 years were included and followed up for 8 years. Intrinsic capacity was determined according to the World Health Organization definition. The predictive ability for adverse outcomes was assessed using the age- and sex-adjusted Cox proportional hazards model. RESULTS: A decline in intrinsic capacity domains was observed in 729 (42.9 %) participants. Declines in the mobility, cognition, vitality, sensory and psychology domains were observed in 21.8 %, 15.1 %, 11.4 %, 9.10 %, and 14.2 % of the participants, respectively. Low intrinsic capacity was associated with worse physical performance, frailty, social frailty, chronic diseases, fracture, and falls. A greater decline in intrinsic capacity predicted an elevated 8-year mortality rate (decline in overall intrinsic capacity hazard ratio 2.91, 95 % confidence interval 2.44-3.47, P < 0.001; decline in one domain hazard ratio 2.11, 95 % confidence interval 1.71-2.61, P < 0.001; decline in two domains hazard ratio 3.54, 95 % confidence interval 2.81-4.45, P < 0.001; decline in three or more domains hazard ratio 5.30, 95 % confidence interval 4.09-6.87, P < 0.001); adjusted models did not affect prediction performance. Among the five domains of intrinsic capacity, cognition was the strongest predictor of mortality (hazard ratio 3.17, 95 % confidence interval 2.63-3.81, P < 0.001). CONCLUSIONS: Intrinsic capacity is useful in identifying older adults at higher risk of adverse outcomes, presenting significant implications for healthcare policies in China.

Frailty Is More Predictive of Mortality than Age in Patients With Hip Fractures.

OBJECTIVES: To investigate the association between the Comprehensive Geriatric Assessment-based Frailty Index and adverse outcomes in older adult patients undergoing hip fracture surgery. DESIGN: Retrospective cohort study. SETTING: Academic Level 1 Trauma Center. PATIENTS: All patients aged 65 or older who underwent surgical repair of a hip fracture between May 2018 and August 2020 were identified through institutional database review. OUTCOME MEASURES AND COMPARISONS: Data including demographics, FI, injury presentation, and hospital course were collected. Patients were grouped by FI as nonfrail (FI < 0.21), frail (0.21 ≤ FI < 0.45), and severely frail (FI > 0.45). Adverse outcomes of these groups were compared using Kaplan Meier survival analysis. Risk factors for 1-year rehospitalization and 2-year mortality were evaluated using Cox hazard regression. RESULTS: Three hundred sixteen patients were included, with 62 nonfrail, 185 frail, and 69 severely frail patients. The total population was on average 83.8 years old, predominantly white (88.0%), and majority female (69.9%) with an average FI of 0.33 (SD: 0.14). The nonfrail cohort was on average 78.8 years old, 93.6% white, and 80.7% female; the frail cohort was on average 84.5 years old, 92.4% white, and 71.9% female; and the severely frail cohort was on average 86.4 years old, 71.0% white, and 55.1% female. Rate of 1-year readmission increased with frailty level, with a rate of 38% in nonfrail patients, 55.6% in frail patients, and 74.2% in severely frail patients (P = 0.001). The same pattern was seen in 2-year mortality rates, with a rate of 2.8% in nonfrail patients, 36.7% in frail patients, and 77.5% in severely frail patients (P < 0.0001). Being classified as frail or severely frail exhibited greater association with mortality within 2 years than age, with hazard ratio of 17.81 for frail patients and 56.81 for severely frail patients compared with 1.19 per 5 years of age. CONCLUSIONS: Increased frailty as measured by the Frailty Index is significantly associated with increased 2-year mortality and 1-year hospital readmission rates after hip fracture surgery. Degree of frailty predicts mortality more strongly than age alone. Assessing frailty with the Frailty Index can identify higher-risk surgical candidates, facilitate clinical decision making, and guide discussions about goals of care with family members, surgeons, and geriatricians. LEVEL OF EVIDENCE: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Clinical trial results in context: comparison of baseline characteristics and outcomes of 38,510 RECOVERY trial participants versus a reference population of 346,271 people hospitalised with COVID-19 in England.

BACKGROUND: Randomised trials are essential to reliably assess medical interventions. Nevertheless, interpretation of such studies, particularly when considering absolute effects, is enhanced by understanding how the trial population may differ from the populations it aims to represent. METHODS: We compared baseline characteristics and mortality of RECOVERY participants recruited in England (n = 38,510) with a reference population hospitalised with COVID-19 in England (n = 346,271) from March 2020 to November 2021. We used linked hospitalisation and mortality data for both cohorts to extract demographics, comorbidity/frailty scores, and crude and age- and sex-adjusted 28-day all-cause mortality. RESULTS: Demographics of RECOVERY participants were broadly similar to the reference population, but RECOVERY participants were younger (mean age [standard deviation]: RECOVERY 62.6 [15.3] vs reference 65.7 [18.5] years) and less frequently female (37% vs 45%). Comorbidity and frailty scores were lower in RECOVERY, but differences were attenuated after age stratification. Age- and sex-adjusted 28-day mortality declined over time but was similar between cohorts across the study period (RECOVERY 23.7% [95% confidence interval: 23.3-24.1%]; vs reference 24.8% [24.6-25.0%]), except during the first pandemic wave in the UK (March-May 2020) when adjusted mortality was lower in RECOVERY. CONCLUSIONS: Adjusted 28-day mortality in RECOVERY was similar to a nationwide reference population of patients admitted with COVID-19 in England during the same period but varied substantially over time in both cohorts. Therefore, the absolute effect estimates from RECOVERY were broadly applicable to the target population at the time but should be interpreted in the light of current mortality estimates. TRIAL REGISTRATION: ISRCTN50189673- Feb. 04, 2020, NCT04381936- May 11, 2020.

Frailty and its association with long-term mortality among community-dwelling older adults aged 75 years and over.

BACKGROUND: Frailty, a significant risk factor for adverse outcomes and mortality, poses an emerging challenge with profound implications for public health and clinical practice. The measurement of frailty offers potential enhancements in healthcare services for older adults. The prevalence of frailty and its association with long-term mortality in a nationwide, unselected population of community-dwelling older adults, particularly those aged 75 and over, has not been previously studied on a large scale in Israel. METHODS: A retrospective cohort study was conducted at Meuhedet Health Maintenance Organization, Israel's third largest healthcare service provider, serving 1,276,000 people (13.8% of Israelis). The prevalence of frailty and its association with all-cause mortality were studied among older adults aged 75 years and over who were followed for 2-8 years. Frailty, defined by the cumulative deficit method, utilized clinical data from the preceding 10-year period, comprising 28 chronic diseases and age-related health deficits. RESULTS: The cohort included 43,737 older adults, with a median age of 77 years (IQR 75-82 years); among them, 19,300 (44.1%) were males. Overall, 19,396 (44.3%) older adults were frail: 12,260 (28.0%) mildly frail, 5,533 (12.7%) moderately frail and 1,603 (3.7%) severely frail. During the follow-up period 15,064 (34.4%) older adults died: 4,782 (39.0%) mildly frail, 3,016 (54.5%) moderately frail and 1,080 (67.4%) severely frail. Cox regression analysis demonstrated that mortality was associated with severe frailty (HR 2.63, 95%CI 2.45-2.80), moderate frailty (HR 2.05, 95%CI 1.96-2.14), and mild frailty (HR 1.45, 95%CI 1.39-1.51), independent of age, gender, and population sector. Among patients aged 90 years and over, no significant differences in cumulative survival were found between those with moderate and severe frailty (p = 0.408). CONCLUSIONS: Frailty is prevalent among community-dwelling Israeli older adults aged 75 years and over, and it is associated with long-term mortality. Considering its association with long-term mortality across frailty levels until the age of 90, early identification and intervention for frailty are recommended within this population. Policymakers should consider the use of the cumulative deficit method for evaluating frailty at both the population health and clinical levels.

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.

Frailty and all-cause and cancer-related mortality in cancer patients: A prospective cohort study.

PURPOSE: To evaluate the associations between frailty and all-cause and cancer-related mortality. Additionally, the objective is to compare the magnitude of these associations between older adults and younger adults. METHODS: We gathered baseline data from NHANES (1999-2018) and developed a cumulative index consisting of 39 items to evaluate frailty. The National Death Index database was utilized to track the survival status of individuals. The Cox regression model was employed to estimate the associations between frailty status and all-cause and cancer-related mortality. RESULTS: Ultimately, 3398 cancer patients were included in the analysis, comprising 910 younger adults and 2488 older adults. Compared to non-frail patients, the elevated all-cause and cancer-related mortality among pre-frail patients was not statistically significant (HRs = 1.312, 95%CI: 0.956-1.800, P = 0.092; HRs = 1.462, 0.811-2.635, P = 0.207). However, a significant elevation of both all-cause and cancer-related mortality risk was observed among frail patients (HRs = 2.213, 1.617-3.030, P < 0.001; HRs = 2.463, 95%CI = 1.370-4.429, P = 0.003). Frailty individuals demonstrated a more pronounced association with the prediction of all-cause mortality in younger (HRs = 2.230, 1.073-4.634, P = 0.032) than in older adults (HRs = 2.090, 1.475-2.960, P < 0.001). Sensitivity analysis consistently revealed robust results. RCS plots suggested a progressively escalating dose-response correlation between frailty and both all-cause and cancer-related mortality risk. CONCLUSIONS: Pre-frailty did not result in an increase in mortality risks compared to non-frailty. However, frailty caused a higher all-cause and cancer-related mortality risk than non-frailty. Identifying those at risk and implementing targeted interventions may contribute to extending healthy life expectancy, regardless of age.

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.