Wim Adriaensen

Muscle Strength and Physical Performance as Predictors of Mortality, Hospitalization, and Disability in the Oldest Old

To evaluate the predictive value of muscle strength and physical performance in the oldest old for all‐cause mortality; hospitalization; and the onset of disability, defined as a decline in activities of daily living (ADLs), independent of muscle mass, inflammatory markers, and comorbidities.

The relationship between grip strength and muscle mass (MM), inflammatory biomarkers and physical performance in community-dwelling very old persons.

The main consequence of the loss of MM and muscle strength is limitations of physical performance and disability in older people. It is unclear whether a decline in functional capacity results from the loss of MM and/or the qualitative impairment of the muscle tissue. The aim of our research was to investigate the relationship between physical performance and grip strength, inflammatory markers and MM in a population of community-dwelling very old persons. This study is a cross-sectional analysis within the BELFRAIL-study, a cohort study of subjects aged 80 years and older (n=567). MM was assessed by bioelectrical impedance. Interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) concentrations were determined on fasting blood samples. Logistic regression analysis was build using a low physical performance level evaluated according to Short Physical Performance Battery (SPPB) (dependent variable) and grip strength, pro-inflammatory status and MM (independent variables) adjusted for age and for the total number of chronic diseases. Low SPPB scores were associated with grip strength scores for women (OR 0.86 (95% CI 0.77-0.96)), and for men (OR 0.89 (95% CI 0.81-0.96)). The relationships between low SPPB and MM or inflammatory profile were not significant. Our results show that low physical performance remains associated with low grip strength even after considering other risk factors for sarcopenia in the oldest old and support the hypothesis that low muscle strength is a better indicator than low MM. The role of an inflammatory component in the age-related loss of muscle strength and function could not be confirmed.

No relation between vitamin D status and physical performance in the oldest old: results from the Belfrail study

BACKGROUND vitamin D deficiency is a well-known cause of bone loss and fractures but its association, especially among the oldest old, with muscle weakness is less obvious. OBJECTIVE to investigate the relationship between 25-hydroxyvitamin D (25-OHD) and muscle performance in persons aged 80 years and older. METHODS baseline results of the Belfrail study, a prospective, population-based cohort study were used to study balance, grip strength and gait speed in relation to 25-OHD serum levels in 367 subjects. RESULTS a sufficient 25-OHD serum level of 30 ng/ml or more was found in 12.8% of the population. The prevalence of vitamin deficiency (20-29 ng/ml), insufficiency (10-19 ng/ml) and severe insufficiency (<10 ng/ml) was 21.5, 33 and 32.7%, respectively. No significant relation between balance, gait speed and grip strength, and serum 25-OHD was detected neither in bivariate analysis nor after adjustment for age, gender, level of education, institutionalisation, smoking status, body mass index, co-morbidity, level of activity, season, CRP, renal function, serum calcium parathyroid hormone levels, vitamin D intake and use of loop or thiazide diuretics. CONCLUSION in this cohort of octogenarians vitamin D deficiency was highly prevalent. We could not confirm the findings of previous studies showing an association between serum 25-OHD and physical performance in elderly.

CD4:8 Ratio >5 Is Associated With a Dominant Naive T-Cell Phenotype and Impaired Physical Functioning in CMV-Seropositive Very Elderly People: Results From the BELFRAIL Study

A subset of older people is at increased risk of hospitalization and dependency. Emerging evidence suggests that immunosenescence reflected by an inverted CD4:8 ratio and cytomegalovirus (CMV) seropositivity plays an important role in the pathophysiology of functional decline. Nevertheless, the relation between CD4:8 ratio and functional outcome has rarely been investigated. Here, CD4:8 ratio and T-cell phenotypes of 235 community-dwelling persons aged ≥81.5 years in the BELFRAIL study and 25 younger persons (mean age 28.5 years) were analyzed using polychromatic flow cytometry. In the elderly persons, 7.2% had an inverted CD4:8 ratio, which was associated with CMV seropositivity, less naive, and more late-differentiated CD4+ and CD8+ T cells. However, 32.8% had a CD4:8 ratio >5, a phenotype associated with a higher proportion of naive T cells and absent in young donors. In CMV seropositives, this subgroup had lower proportions of late-differentiated CD4+ and CD8+ T cells and weaker anti-CMV immunoglobulin G reactivity. This novel naive T-cell-dominated phenotype was counterintuitively associated with a higher proportion of those with impaired physical functioning in the very elderly people infected with CMV. This underscores the notion that in very elderly people, not merely CMV infection but also the state of its accompanying immune dysregulation is of crucial importance with regard to physical impairment.

The glomerular filtration rate estimated by new and old equations as a predictor of important outcomes in elderly patients

BackgroundThe prevalence of chronic kidney disease (CKD) increases with age, and new glomerular filtration rate-estimating equations have recently been validated. The epidemiology of CKD in older individuals and the relationship between a low estimated glomerular filtration rate as calculated by these equations and adverse outcomes remains unknown.MethodsData from the BELFRAIL study, a prospective, population-based cohort study of 539 individuals aged 80 years and older, were used. For every participant, five equations were used to calculate estimated glomerular filtration rate based on serum creatinine and/or cystatin C values: MDRD, CKD-EPIcreat, CKD-EPIcyst, CKD-EPIcreatcyst, and BIS equations. The outcomes analyzed included mortality combined with the necessity of new renal replacement therapy, severe cardiovascular events, and hospitalization.ResultsDuring the follow-up period, which was an average of 2.9 years, 124 participants died, 7 required renal replacement therapy, 271 were hospitalized, and 73 had a severe cardiovascular event. The prevalence of estimated glomerular filtration rate values <60 mL/min/1.73 m2 differed depending on the equation used as follows: 44% (MDRD), 45% (CKD-EPIcreat), 75% (CKD-EPIcyst), 65% (CKD-EPIcreatcyst), and 80% (BIS). All of the glomerular filtration rate-estimating equations revealed that higher cardiovascular mortality was associated with lower estimated glomerular filtration rates and that higher probabilities of hospitalization were associated with estimated glomerular filtration rates <30 mL/min/1.73 m2. A lower estimated glomerular filtration rate did not predict a higher probability of severe cardiovascular events, except when using the CKD-EPIcyst equation. By calculating the net reclassification improvement, CKD-EPIcyst and CKD-EPIcreatcyst were shown to predict mortality (+25% and +18%) and severe cardiovascular events (+7% and +9%) with the highest accuracy. The BIS equation was less accurate in predicting mortality (-12%).ConclusionHigher prevalence of CKD were found using the CKD-EPIcyst, CKD-EPIcreatcyst, and BIS equations compared with the MDRD and CKD-EPIcreat equations. The new CKD-EPIcreatcyst and CKD-EPIcyst equations appear to be better predictors of mortality and severe cardiovascular events.

Multimorbidity measures were poor predictors of adverse events in patients aged ≥80 years: a prospective cohort study

OBJECTIVES To assess and compare the ability of two measures of multimorbidity and a simple disease count (DC) to predict health outcomes in a population of patients aged ≥80 years. STUDY DESIGN AND SETTING A prospective, observational, and population-based cohort study including 567 individuals [3.0 years (standard deviation ± 0.25) follow-up]. RESULTS Of the patients, 37.6% were reported with five or more diseases. Multimorbidity was measured by means of a modified Charlson comorbidity index [mCCI; median score, 5 (range, 4-15)], Cumulative Illness Rating Scale [CIRS; median score, 4 (range, 1-11)], and a simple DC of 22 selected chronic conditions [median score, 4 (range, 0-13)]. All measures were independently related to mortality [adjusted hazard ratio (HR) mCCI, 2.5 (confidence interval {CI}: 1.5, 4.1); CIRS, 2.1 (CI: 1.4, 3.2); DC, 2.1 (CI: 1.4, 3.2)] and hospitalization [adjusted HR DC, 2.3 (CI: 1.7, 3.1); mCCI, 2.1 (CI: 1.5, 3.0), CIRS, 1.9 (CI: 1.5, 2.6)] but not to functional decline. Areas under the curve for mortality and hospitalization were all below 0.70. Net reclassification improvements did not indicate that any one measure provided a significant benefit over the others. CONCLUSION In this population, the mCCI, CIRS, and unweighted DC predicted mortality and hospitalization but not functional decline. There is no clear advantage of using one measure over another.

A framework provided an outline toward the proper evaluation of potential screening strategies.

OBJECTIVES Screening tests are often introduced into clinical practice without proper evaluation, despite the increasing awareness that screening is a double-edged sword that can lead to either net benefits or harms. Our objective was to develop a comprehensive framework for the evaluation of new screening strategies. STUDY DESIGN AND SETTING Elaborating on the existing concepts proposed by experts, a stepwise framework is proposed to evaluate whether a potential screening test can be introduced as a screening strategy into clinical practice. The principle of screening strategy evaluation is illustrated for cervical cancer, which is a template for screening because of the existence of an easily detectable and treatable precursor lesion. RESULTS The evaluation procedure consists of six consecutive steps. In steps 1-4, the technical accuracy, place of the test in the screening pathway, diagnostic accuracy, and longitudinal sensitivity and specificity of the screening test are assessed. In steps 5 and 6, the impact of the screening strategy on the patient and population levels, respectively, is evaluated. The framework incorporates a harm and benefit trade-off and cost-effectiveness analysis. CONCLUSION Our framework provides an outline toward the proper evaluation of potential screening strategies before considering implementation.

Prognostic value of circulating cytokines on overall survival and disease-free survival in cancer patients

Through their tumor-promoting and/or tumor-suppressive properties, cytokines can influence progression of cancer. We systematically reviewed the current literature on the prognostic value of the circulating cytokines IL-1α/β, IL-6, IL-8, IL-10, IL-12, TNF-α, TGF-β and IFN-γ to predict overall and disease-free survival in any type of cancer patients. PubMed was systematically searched and based on eligibility assessment using our five criteria of the Reporting Recommendations for Tumor Marker Prognostic Studies (REMARK) checklist, six unique studies were reviewed. Elevated IL-6 and IL-10 levels seem independently associated with worse prognosis in terms of overall and disease-free survival. The prognostic value of IL-1α/β, IL-8, IL-12, TNF-α, TGF-β and IFN-γ could not be demonstrated. The small number of selected studies underlines the need for large well-designed prospective studies, using the REMARK checklist as a guideline, to determine which cytokines have prognostic value on survival in cancer patients.

Airflow limitation by the Global Lungs Initiative equations in a cohort of very old adults.

The cut-off for forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) defining airflow limitation for chronic obstructive pulmonary disease (COPD) is still contested. We assessed airflow limitation prevalence by the lower limit of normal (LLN) of Global Lungs Initiative (GLI) 2012 reference values and its predictive ability for all-cause mortality and hospitalisation in very old adults (aged ≥80 years) compared with the fixed cut-off. In a Belgian population-based prospective cohort of 411 very old adults, airflow limitation prevalence by the 5th percentile of GLI 2012 z-scores (GLI-LLN) and fixed cut-off (0.70) were compared with COPD reported by general practitioners (GPs). Survival and Cox regression multivariable analysis assessed the association of airflow limitation by both cut-offs with 5-year all-cause mortality and first hospitalisation at 3 years. 9.2% had airflow limitation by GLI-LLN and 27% by fixed cut-off, without good agreement (kappa coefficient ≤0.40) with GP-reported COPD (9%). Only airflow limitation by GLI-LLN was independently associated with mortality (adjusted hazard ratio 2.10, 95% CI 1.30–3.38). FEV1/FVC <0.70 but ≥GLI-LLN (17.8%) had no significantly higher risk for mortality or hospitalisation. In a cohort of very old adults, airflow limitation by GLI-LLN has lower prevalence than by fixed cut-off, independently predicts all-cause mortality and does not miss individuals with significantly higher all-cause mortality and hospitalisation. Airflow limitation by GLI 2012 equations is better at predicting survival than fixed ratio in very old adults http://ow.ly/K0xMi

No relation between CMV infection and mortality in the oldest old: results from the Belfrail study

OBJECTIVE previous studies have demonstrated an association between cytomegalovirus (CMV) infection and mortality in adults. In this prospective study, it was investigated whether these findings could be confirmed in the oldest old. METHODOLOGY data obtained from a prospective observational cohort study (2008-2012) of 549 community-dwelling persons in Belgium aged 80 and older. RESULTS seventy-six percent were anti-CMV seropositive of whom 37.5% had an anti-CMV IgG titre in the highest tertile (>250 IU/ml). After a median time of follow-up of 1,049 days, 127 deaths occurred. Cox proportional hazard models failed to show an association between CMV serostatus and all-cause mortality. Among persons seropositive for CMV, after adjusting for multiple confounders an anti-CMV in the highest tertile was statistically significantly associated with all-cause mortality (hazard ratio: 1.64, 95% confidence interval: 1.08, 2.48). CONCLUSION in contrast to previous findings, a positive CMV serostatus was not associated with an increased risk for all-cause mortality in this cohort of very old people. This is probably the result of a survival effect. CMV seropositive subjects with high anti-CMV titres were at higher risk for all-cause mortality compared with other individuals. This may reflect CMV infection reactivation to be more common in the end stages of life.