More intensive CMV-infection in chronic heart failure patients contributes to higher T-lymphocyte differentiation degree.

Immunosenescence in chronic heart failure (CHF) is characterized by a high frequency of differentiated T-lymphocytes, contributing to an inflammatory status and a deficient ability to generate immunocompetent responses. CMV is the best known inducer of T-lymphocyte differentiation, and is associated with the phenomenon of immunosenescence. In this study, we included 58 elderly chronic heart failure patients (ECHF), 60 healthy elderly controls (HEC), 40 young chronic heart failure patients (YCHF) and 40 healthy young controls (HYC). High differentiation of CD8+ T-lymphocytes was found in CMV-seropositive patients; however, the differentiation of CD4+ T-lymphocytes was increased in CMV-seropositive but also in CHF patients. Anti-CMV antibody titers showed positive correlation with more differentiated CD4+ and CD8+ subsets and inverse correlation with CD4/CD8 ratio. Immunosenescence found in CHF patients is mainly due to the dynamics of CMV-infection, since the differentiation of T-lymphocyte subsets is related not only to CMV-infection, but also to anti-CMV antibody titers.

Frequent participation in high volume exercise throughout life is associated with a more differentiated adaptive immune response.

Exercise induces changes in the immune system depending on its intensity and duration. For example, transient states of immunodepression can be induced after acute intense physical activity whereas beneficial anti-inflammatory effects of moderate chronic exercise on many diseases and longevity have been described. To study the impact of high volume exercise over a lifetime on aspects of immunity we compared immunological features of 27 young and 12 elderly athletes with 30 young and 26 elderly non-athletes stratified by their CMV serostatus. We characterized blood leukocyte and lymphocyte subpopulations by flow cytometry, quantified TREC content, and measured activation and proliferation ability of T-lymphocytes in the presence of anti-CD3. NK-cells functionality was determined in response to K-562, 721.221 and 721.221-AEH cell-lines. High volume physical activity reduced the total number of circulating leukocytes, neutrophils, and lymphocytes. In the lymphocyte compartment, athletes had higher frequencies of NK-cells and CD8+ T-lymphocytes, whereas CD4+ T-lymphocytes were present at significantly lower levels in CMV-seropositive athletes. We found, in the high volume physical activity individuals, a higher degree of differentiation in CD4+ T-lymphocytes. CD8+ T-lymphocytes from young athletes had reduced TREC content and lower frequencies of recent thymic emigrants. Furthermore, the functional ability of CD4+ and CD8+ T-lymphocytes was significantly impaired in young but not in elderly athletes, and may be compensated for significantly higher activation and degranulation of NK-cells. In conclusion, high volume exercise throughout life appears to be associated with increased levels of biomarkers that are associated with an aging immune system, which are partially reduced with physiological aging.

[Current and lifetime depression as a risk factor for hospital admission in patients older than 74 years attended in an emergency department]. / Antecedentes y presencia de trastornos depresivos como factor de riesgo de ingreso hospitalario en pacientes mayores de 74 años atendidos en un servicio de urgencias.

INTRODUCTION: Depression is especially frequent in the elderly. In addition to impairing quality of life, this disorder can affect the outcome of medical diseases. The objective is to analyze whether depressive disorders in elderly individuals attending an emergency room for medical complaints constitute a risk factor for admission. MATERIAL AND METHODS: All patients aged more than 74 years old attending the Emergency Department of the Hospital Universitario Central de Asturias who required comprehensive geriatric assessment from 2004 to 2005 were included in this study. Sociodemographic variables and data on functional, cognitive and emotional status before attendance at the emergency department were collected. A logistic regression analysis was performed to determine whether there was an independent association between depression and admission to the Geriatric Service. RESULTS: A total of 1016 patients (62.32% women) were evaluated. The mean age was 87.4 years. The Barthel index before admission to the emergency department was 71.8 (95% confidence interval [CI]: Depression was diagnosed in 17.4% of the patients (75.7% women). Of the whole sample, 721 patients (71.0%) were admitted to a geriatric service, while 79.7% of patients with depression were admitted (p=0.002). After multivariate regression analysis adjusted by age, sex, marital status, institutionalization, living arrangements, Barthel index and cognitive status before admission, depression was independently associated with a greater risk for admission to a geriatric service (odds ratio: 1.83, 95% CI: 1.20-2.78). CONCLUSIONS: Depression and mood disorders constitute an independent risk factor for admission to a geriatric service in patients aged more than 74 years assessed by comprehensive geriatric methodology in an emergency department.

[Risk factors associated with functional impairment at discharge and at three months after discharge in elderly individuals hospitalized for heart failure]. / Variables asociadas a deterioro funcional al alta y a los 3 meses en ancianos hospitalizados por insuficiencia cardíaca.

OBJECTIVE: To determine the characteristics of elderly persons hospitalized for congestive heart failure and identify the factors associated with functional impairment or death at discharge and 3 months later. MATERIAL AND METHODS: We performed a prospective observational study that included 162 patients admitted to an Acute Geriatric Care Unit with a diagnosis of heart failure from February to July 2007. Socio-demographic, clinical, functional and cognitive factors were recorded during admission. Functional and vital measurements were reported at discharge and 3 months later. RESULTS: The incidence of mortality or functional decline was 48.8% at discharge and was 37.3% 3 months later. In the final model, predictors of functional impairment or mortality at discharge were days of hospital stay and a worse Pfeiffer test score (odds ratio [OR]: 1.74; 95% confidence interval [CI]: 1.33-2.29). Three months after discharge, independent prognostic factors were age (OR: 1.09; 95% CI: 1.02-1.17), hyponatremia (OR: 0.85; 95% CI: 0.77-0.94), length of QRS in milliseconds (OR: 0.98; 95% CI: 0.97-0.99), absence of ventricular hypertrophy (OR: 0.42; 95% CI: 0.19-0.94), and a poor result in the Pfeiffer Test (OR: 1.40; 95% CI: 1.13-1.73). CONCLUSIONS: Cognitive evaluation during hospital admission for heart failure in the elderly helps to select individuals at risk of functional impairment or death at discharge and 3 months later.

[Risk factors for 4-year mortality in older adults. Toledo Study]. / Factores de riesgo de mortalidad a los 4 años en personas mayores. Estudio Toledo.

INTRODUCTION: multiple factors contribute to mortality in older adults. Measures of physical and cognitive function are strong predictors of mortality, but the extent to which function, health-related quality of life and other factors contribute independently to mortality risk is not known. MATERIAL AND METHODS: we performed a prospective study of a representative sample of people aged 65 years and older (n=3,214) followed-up for 4 years. Individuals from the sample were interviewed to obtain information about sociodemographic characteristics, comorbidity, functional status, health-related quality of life, and healthcare utilization. The main outcome measure was 4-year mortality. To assess the independent impact of each risk factor on mortality, several multivariate survival models were built using the Cox proportional hazard model. RESULTS: in the 4 years of monitoring, 478 people died (14.9%). The variables independently associated with mortality risk were age 75 years or older (HR = 1.93), male gender (HR = 1.73), heart disease (HR = 1.32), chronic respiratory disease (HR = 1.78), activities of daily living disability (HR = 1.55), instrumental activities of daily living disability (HR = 2.19), cognitive impairment (HR = 1.39), poor health-related quality of life (HR = 1.85) and hospital admission in the year prior to the interview (HR = 1.51). CONCLUSIONS: objective measures of physical and cognitive function are independent predictors of 4-year mortality in the elderly. Poor health-related quality of life is associated with mortality. The magnitude of this association is comparable to that of other well-know predictors of mortality. Instruments to measure health-related quality of life can be useful to evaluate health requirements in the elderly.

Immunosenescence and inflammation characterize chronic heart failure patients with more advanced disease.

BACKGROUND: Chronic heart failure (CHF) is characterized by an inflammatory status with high levels of cytokines such as IL-6. We hypothesized that patients with CHF may develop immunosenescence due to inflammation and that this may be associated with a worse stage of the disease. METHODS AND RESULTS: We compared the immunological features of 58 elderly CHF patients (ECHF), 40 young CHF patients (YCHF), 60 healthy elderly controls (HEC) and 40 healthy young controls (HYC). We characterized leukocyte and lymphocyte subpopulations by flow cytometry, and IL-6 concentration by ELISA. The extent of CHF was classified according to functional and/or morphological criteria: New York Heart Association functional class, AHA/ACC heart failure stages, left ventricular ejection fraction, and left ventricular hypertrophy. CHF patients showed an increased number of leukocytes, neutrophils and monocytes, but a decreased number of lymphocytes. CHF patients had significantly lower levels of B-cells and CD4+ T-cells, increased NK-cells in YCHF, and increased CD8+ T-cells only in ECHF. CHF was associated with high differentiation in CD4+ and CD8+ T-lymphocyte subsets. Aging of T-lymphocyte subpopulations and high IL-6 levels were associated with a worse clinical status. IL-6 also correlated positively with the number of highly differentiated T-lymphocytes and with their accelerated aging. CONCLUSIONS: We conclude that CHF patients show a higher degree of immunosenescence than age-matched healthy controls. T-lymphocyte differentiation and IL-6 levels are increased in patients with an advanced clinical status and may contribute to disease impairment through a compromised adaptive immune response due to accelerated aging of their immune system.

Relationship between functional ability in older people, immune system status, and intensity of response to CMV.

Shorter survival in the elderly has been associated with deterioration of the immune system and also with functional disability. To analyze the relationship between functional and immune impairment in older individuals, we studied 100 elderly who lived in a nursing home, were age matched, and grouped according to their functional status. We characterized cell subpopulations by flow cytometry, quantified TREC by RT-PCR, and measured the T-cell proliferation and activation response (IFN-γ by ELISPOT, CD69) against anti-CD3 and CMV. Specific antibody titers against influenza virus and CMV were determined by ELISA. Individuals with worse functional status had significantly higher levels of NK cells and fewer B cells. These poorly functioning elders also had a significantly lower proportion of CD4+ T cells, increased CD8+ T cells, and a decreased CD4/CD8 ratio. TREC levels in CD4+ T cells were significantly lower in individuals with a high disability. Lower TREC levels correlated with a lower frequency of naïve T-cell subpopulations (CD45RA+CCR7+) and higher percentages of effector cells (CD45RA-CCR7-). The functionally impaired group had lower anti-CD3 responses, but gradually increased responses against CMV. Similarly, the higher CMV titers were found in elderly with worse functional status. On the contrary, the functional response in vivo, and the titer of antibodies generated after vaccination against influenza virus, was higher in individuals with better performance status. In summary, we concluded that the functional decline of elderly individuals was clearly associated with the aging of their immune system, and the intensity of the response to CMV.

Mortality and functional evolution at one year after hospital admission due to heart failure (HF) in elderly patients.

The aim of this observational study was to describe the characteristics (including functional measures) of the elderly patients hospitalized in the acute geriatric unit (AGU) and diagnosed with HF as well as to determine the variables associated with mortality at one year after discharge. A prospective study including patients aged 70 and over hospitalized for acute decompensated HF was performed. The baseline measures were demographics, comorbidity, clinical, functional and cognitive status. The outcome for this study was death within one year from the index hospital admission date. During the length of the study, 32.7% patients died (20.7% within the first three months). The clinical features associated with HF-related mortality in the univariate analysis were institutionalization, a higher dependence in performing basic activities or instrumental activities of daily living (IADL). Older age did not correlate with mortality, nor did left ventricular hypertrophy (LVH), the ejection fraction or the pharmacological treatment at discharge. After performing the logistic regression analysis, the only variable independently related to a higher mortality risk at one year was the preadmission dependence in performing basic activities of daily living (BADL). The results of this study highlight that preadmission functional and sociodemographic variables are the best predictors of mortality at one year, surpassing the classic prognostic factors. Performing an adequate assessment at the time of admission, which should include a functional evaluation, may help us to better classify patients and to offer them a customized therapeutic plan with better prognostic capabilities.