To determine specific physiological correlates of the geriatric syndrome of frailty that warrant further investigation.
Population-based case-control study.
General Clinical Research Center at Johns Hopkins Bayview Medical Center.
Community-dwelling adults aged 74 and older from Baltimore, Maryland.
Frailty status was determined using a recently validated screening tool that consists of weight loss, fatigue, low levels of physical activity, and measurements of grip strength and walking speed. Serum interleukin-6 (IL-6) was measured using enzyme-linked immunosorbent assay, and standard complete blood count was performed using a Coulter counter.
Eleven frail and 19 nonfrail subjects with mean age +/- standard deviation of 84.9 +/- 6.7 vs 81.3 +/- 4.1 years, respectively, completed the study. The frail subjects had significantly higher serum IL-6 levels and significantly lower hemoglobin and hematocrit than the nonfrail subjects (4.4 +/-2.9 vs 2.8 +/- 1.6 pg/mL, 12.1 +/- 1.1 vs 13.9 +/- 1.0 g/dL, and 35.8% +/- 3.1% vs 40.6% +/- 2.8%, respectively). No significant difference was observed in mean corpuscular volume, red blood cell distribution width, or white blood cell and platelet counts between the frail and nonfrail groups. Furthermore, there was an inverse correlation between serum IL-6 level and hemoglobin (Pearson's correlation coefficient: -0.46) and hematocrit (-0.48) in the frail group but not in the nonfrail group.
These results suggest that frail subjects have evidence of inflammation and lower hemoglobin and hematocrit levels. This subclinical anemia is normocytic and is hence unlikely due to myelosuppression or iron deficiency and is potentially related to the increased chronic inflammatory state marked by serum IL-6 elevation. Further studies are indicated to better characterize the immune and hematological changes that underlie frailty.
"Moreover, the authors of the CHAMP study accepted that their results were unexpected, as high tissue expression of SIRT1 was generally considered to be beneficial, it was induced by CR and expected to be higher in younger animals. There are some biological parameters which have been used as biomarkers of frailty, namely inflammation (Leng et al., 2002, 2004, 2007, 2009), central adiposity, serum albumin, oxidative stress (Wu et al., 2009), vitamin-E (Ble et al., 2006), and 25 hydrooxy vitamin-D level (Hirani et al., 2013). These parameters are, however, nonspecific and do not indicate any mechanistic pathway. "
[Show abstract][Hide abstract] ABSTRACT: Frailty has emerged as a major health issue among older patients. A consensus on definition and diagnosis is yet to be achieved. Various biochemical abnormalities have been reported in frailty. Activation of sirtuins, a conserved family of NAD-dependent proteins, is one of the many mimics of calorie restriction which improves lifespan and health in experimental animals. In this cross-sectional study, we assessed the circulating sirtuin levels in 119 (59.5%) nonfrail and 81 (40.5%) frail individuals, diagnosed by Fried's criteria. Serum SIRT1, SIRT2, and SIRT3 were estimated by surface plasmon resonance (SPR) and Western blot. Serum sirtuins level in mean+SD; SIRT1 (nonfrail –4.67 ± 0.48 ng/μL; frail – 3.72 ± 0.48 ng/μL; P < 0.0001), SIRT2 (nonfrail – 15.18 ± 2.94 ng/μL; frail – 14.19 ± 2.66 ng/μL; P = 0.016), and SIRT3 (nonfrail-7.72 ± 1.84 ng/μL; frail – 6.12 ± 0.97 ng/μL; P < 0.0001) levels were significantly lower among frail patients compared with the nonfrail. In multivariable regression analysis, lower sirtuins level were significantly associated with frailty after adjusting age, gender, diabetes mellitus, hypertension, cognitive status (Mini Mental State Examination scores) and number of comorbidities. For detecting the optimum diagnostic cutoff value a ROC analysis was carried out. The area under curve for SIRT1 was 0.9037 (cutoff – 4.29 ng/μL; sensitivity – 81.48%; specificity – 79.83%) and SIRT3 was 0.7988 (cutoff – 6.61 ng/μL; sensitivity – 70.37%; specificity – 70.59%). This study shows that lower circulating SIRT1 and SIRT3 levels can be distinctive marker of frailty.
"Direct association between frailty and elevated circulating levels of interleukin (IL)-6, a proinflammatory cytokine, was first observed in community-dwelling older adults.22 A large number of studies in many cohorts of older adults and under various care settings have since provided evidence supporting the role of chronic inflammation and immune activation in the pathogenesis of the frailty syndrome.23–25 "
[Show abstract][Hide abstract] ABSTRACT: Frailty is a common and important geriatric syndrome characterized by age-associated declines in physiologic reserve and function across multiorgan systems, leading to increased vulnerability for adverse health outcomes. Two major frailty models have been described in the literature. The frailty phenotype defines frailty as a distinct clinical syndrome meeting three or more of five phenotypic criteria: weakness, slowness, low level of physical activity, self-reported exhaustion, and unintentional weight loss. The frailty index defines frailty as cumulative deficits identified in a comprehensive geriatric assessment. Significant progress has recently been made in understanding the pathogenesis of frailty. Chronic inflammation is likely a key pathophysiologic process that contributes to the frailty syndrome directly and indirectly through other intermediate physiologic systems, such as the musculoskeletal, endocrine, and hematologic systems. The complex multifactorial etiologies of frailty also include obesity and specific diseases. Major clinical applications include risk assessment and stratification. This can be applied to the elderly population in the community and in a variety of care settings. Frailty may also be useful for risk assessment in surgical patients and those with cardiovascular diseases, cancer, or human immunodeficiency virus infection, as well as for assessment of vaccine effectiveness in older adults. Currently, exercise and comprehensive geriatric interdisciplinary assessment and treatment are key interventions for frailty. As understanding of the biologic basis and complexity of frailty further improves, more effective and targeted interventional strategies and innovative geriatric-care models will likely be developed.
"In a recent systematic review, the prevalence of frailty in community-dwelling elderly subjects varied between 4% and 59% . Many age-related diseases and geriatric syndromes are more prevalent in frail older persons than in the nonfrail [1,7,9,14-16,28-39] but most of this work was done in non-hospitalized older persons. "
[Show abstract][Hide abstract] ABSTRACT: The prevalence and significance of frailty are seldom studied in hospitalized patients. Aim of this study is to evaluate the prevalence of frailty and to determine the extent that frailty predicts delirium, falls and mortality in hospitalized older patients.
In a prospective study of 220 older patients, frailty was determined using the Cardiovascular Health Study (CHS) and the Study of Osteoporotic Fracture (SOF) frailty index. Patients were classified as nonfrail, prefrail, and frail, according to the specific criteria. Covariates included clinical and laboratory parameters. Outcome variables included in hospital delirium and falls, and 6-month mortality.
The CHS frailty index was available in all 220 patients, of which 1.5% were classified as being nonfrail, 58.5% as prefrail, and 40% as frail. The SOF frailty index was available in 204 patients, of which 16% were classified as being nonfrail, 51.5% as prefrail, and 32.5% as frail. Frailty, as identified by the CHS and SOF indexes, was a significant risk factor for 6-month mortality. However, after adjustment for multiple risk factors, frailty remained a strong independent risk factor only for the model with the CHS index (OR 4.7, 95% CI 1.7-12.8). Frailty (identified by CHS and SOF indexes) was not found to be a risk factor for delirium or falls.
Frailty, as measured by the CHS index, is an independent risk factor for 6-month mortality. The CHS and the SOF indexes have limited value as risk assessment tools for specific geriatric syndromes (e.g., falls and delirium) in hospitalized older patients.
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