Papers by Catharina Mathe
The American Journal of Cardiology, 2015
Although degenerative aortic valve stenosis (AS) is common with increasing age, limited data exis... more Although degenerative aortic valve stenosis (AS) is common with increasing age, limited data exist regarding the prevalence and prognostic impact of its various valve area-gradient patterns in patients ≥80 years. To test this, echocardiograms were obtained in 542 randomly selected subjects aged ≥80 years recruited in the Belgium Cohort Study of the Very Elderly study (BFC80+). Subjects were divided into 3 groups: no or mild AS, moderate AS, and severe AS. Patients with severe AS were further stratified into those with high mean gradients (HG-AS) and those with paradoxically low mean gradients (LG-AS). Prevalence of moderate-to-severe AS was 14.7% and that of severe AS was 5.9%. In patients with severe AS, most (72%) exhibited paradoxical LG-AS. All patients with severe HG-AS were asymptomatic at the time of inclusion, whereas 48% of those with severe paradoxical LG-AS had significant symptoms. During follow-up, there were 2 aortic valve replacements and 230 deaths, of which 100 (43%) were of cardiovascular origin. Five-year overall survival rate was significantly worse in severe HG-AS than in any of the other groups (22 ± 14% vs 62 ± 2% in no or mild AS, 48 ± 7% in moderate AS, and 43 ± 10% in severe paradoxical LG-AS, p <0.01). Survival rate was similar among severe paradoxical LG-AS with and without low flow. In conclusion, in this large population-based sample of subjects ≥80 years, the prevalence of severe AS was 5.9%. Most of these subjects presented with the severe paradoxical LG-AS and a third of them were symptomatic. In this elderly community, severe HG-AS is a major determinant of prognosis, even in the absence of symptoms, whereas severe paradoxical LG-AS seems to behave similarly to moderate AS.
Experimental Gerontology, 2015
Certain inflammatory biomarkers increase with age, provide information about general burden of il... more Certain inflammatory biomarkers increase with age, provide information about general burden of illness and could cause or reflect any collateral damage to healthy cells and organs. However, comparative studies to predict adverse outcomes are missing. Therefore, our study validated and identified the principal prognostic marker to predict important adverse outcomes in the oldest old from an extensive battery of serum inflammatory markers. A large battery of potential 'inflammaging' markers (IL-1α, IL1-β, IL-4, IL-6, IL-8, IL-10, TNF-α, IFN-γ, EGF, VEGF, MCP-1, usCRP, prealbumin) was assessed in a representative sample of 415 heterogenic individuals 80years of age or older in the BELFRAIL study. Kaplan-Meier, Cox proportional hazards and CART analyses determined the overall prognostic value of these markers for predicting all-cause, cardiovascular and non-cardiovascular mortality as well as hospitalization. Serum IL-6 and usCRP levels were strongly associated with time of survival, independent of cause of death. Serum IL-6 levels had the most robust dose-response relationship with mortality. To a lesser extent, IL-10 and IL-1β were associated with all-cause mortality but were restricted to non-cardiovascular or cardiovascular mortality, respectively. Having a low IL-6 at baseline (<1.77pg/ml) could predict 90% of those who were not at risk for all-cause mortality after 3years, even after adjusting for confounders. Similarly, we observed an 83.6% chance of identifying those cases with 0 or 1 hospitalization using low IL-6 serum levels. The results suggest that a single measurement of low IL-6 serum levels is the first choice to guide clinical practice in the oldest old and could summarize the short-term risk of death and hospitalization.
International journal of cardiology, Jan 5, 2015
Conflicting evidence exists about the value of general practitioners' (GPs') diagnoses of... more Conflicting evidence exists about the value of general practitioners' (GPs') diagnoses of chronic heart failure (CHF), especially in older persons. Therefore, the relationship between GPs' judgement of CHF and objective cardiac abnormalities and their respective prognostic value for 5-year mortality in patients aged 80 and older was studied. These analyses were embedded within the prospective, population-based BELFRAIL study. At baseline, 525 patients (mean age 85±3.7years, 37% men) were clinically assessed by their GPs, had NT-proBNP levels determined and received a detailed echocardiography at home. GPs were asked to judge the presence of CHF and to list their arguments in favour or against CHF. Cause-specific mortality was collected until 5.2±0.25years after baseline. GPs suspected CHF in 154 patients (29%). The prevalence of objective cardiac abnormalities was 35% (n=183). GPs' judgement predicted objective cardiac abnormalities inaccurately (sensitivity 45% (95%...
The journal of nutrition, health & aging, 2012
Hypovitaminosis D is common in older adults in western society. In the Netherlands, only 18 % of ... more Hypovitaminosis D is common in older adults in western society. In the Netherlands, only 18 % of patients 65 years and older have normal 25-OH-vitamin D levels (1). In the same age group, chronic kidney disease (CKD), defined as an estimated glomerular filtration rate (eGFR) <60 ml/min/1.73m², has a prevalence of approximately 30% (2-4). Therefore, many older adults suffer from CKD and hypovitaminosis D.
European Geriatric Medicine, 2012
European Geriatric Medicine, 2012
Age and Ageing, 2014
previous studies have demonstrated an association between cytomegalovirus (CMV) infection and mor... more 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. data obtained from a prospective observational cohort study (2008-2012) of 549 community-dwelling persons in Belgium aged 80 and older. seventy-six percent were anti-CMV seropositive of whom 37.5% had an anti-CMV IgG titre in the highest tertile (&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;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). 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.
Journal of Clinical Epidemiology, 2015
Objectives: To assess and compare the ability of two measures of multimorbidity and a simple dise... more 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.
AGE, 2014
The chronic inflammatory state at old age may contribute to the pathophysiology of or reflect chr... more The chronic inflammatory state at old age may contribute to the pathophysiology of or reflect chronic conditions resulting in loss of physical and mental functioning. Therefore, our objective was to examine the predictive value of a large battery of serum inflammatory markers as risk indicators for global functional decline and its specific physical and mental determinants in the oldest old. Global functional decline and specific aspects of physical and mental functional decline were assessed during an average of 1.66 years (±0.21) in a sample of 303 persons aged 80 years or older of the BELFRAIL study. Serum levels of 14 inflammatory proteins, including cytokines, growth factors, and acute phase proteins, were measured at baseline. Almost 20 % of the participants had a significant global functional decline over time. Interleukin (IL)-6 serum levels were uniquely positively associated with global functional decline, even after correcting for multiple confounders (odds ratio 1.51). Odds ratios for the individual aspects (physical dependency, physical performance, cognition, and depression) of functioning were lower, and composite scores of physical or mental decline were not significant. The proportion of global functional decline exhibited a dose-response curve with increasing levels of IL-6. Thus, IL-6 is an independent risk indicator for accelerated global functional decline in the oldest old. Our results suggest that simple serum levels of IL-6 may be very useful in short-term identification or evaluation of global functional status in the oldest old.
Peptides, 2012
The hypothesis that natriuretic peptides could be used to identify 'pancardiac' damage has been p... more The hypothesis that natriuretic peptides could be used to identify 'pancardiac' damage has been proposed. However, multiple factors are known to influence circulating levels of natriuretic peptides, especially in the very old. Therefore, the impact of confounders on the association between natriuretic peptide levels and cardiac dysfunction was further explored in subjects aged 80 and older. A diagnostic cross-sectional study embedded within the BELFRAIL study (n = 567) was performed. Baseline BNP and NT-proBNP levels were measured and echocardiograms were performed at the subject's home. Cardiac dysfunction was defined as systolic dysfunction, valvular heart disease or isolated severe diastolic dysfunction. Several functional and structural echocardiographic parameters were independently related to circulating levels of natriuretic peptides. Cystatin C, BMI,  blockers, diabetes, heart frequency, usCRP, age and sex were identified as confounders. The prevalence of cardiac dysfunction was 17.1% in the subjects without and 30.8% in the subjects with chronic atrial fibrillation (CAF) or pacemaker (PM). Only in subjects with CAF or PM the C statistic for cardiac dysfunction improved after correcting for confounders. The post-test probability for a negative test (PTP−) ranged from 3.7% to 12.2% and the PTP+ ranged from 21.9% to 62.2% in different strata of confounders. According to these data adjusting for identified confounders does not improve the diagnostic accuracy of the natriuretic peptides for cardiac dysfunction, except in subjects with CAF or PM. Stratifying for individual confounders showed that different cut-off values could be used to optimize the diagnostic characteristics of natriuretic peptides.
Journal of the American Geriatrics Society, 2012
Journal of the American Geriatrics Society, 2014
To evaluate the predictive value of muscle strength and physical performance in the oldest old fo... more 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. A prospective, observational, population-based follow-up study. Three well-circumscribed areas of Belgium. Five hundred sixty participants aged 80 and older were followed for 33.5 months (interquartile range 31.1-35.6 months). Grip strength, Short Physical Performance Battery (SPPB) score, and muscle mass were measured at baseline; ADLs at baseline and after 20 months; and all-cause mortality and time to first hospitalization from inclusion onward. Kaplan-Meier curves and Cox proportional hazards models were calculated for all-cause mortality and hospitalization. Logistic regression analysis was used to determine predictors of decline in ADLs. Kaplan-Meier curves showed significantly higher all-cause mortality and hospitalization in subjects in the lowest tertile of grip strength and SPPB score. The adjusted Cox proportional hazards model showed that participants with high grip strength or a high SPPB score had a lower risk of mortality and hospitalization, independent of muscle mass, inflammatory markers, and comorbidity. A relationship was found between SPPB score and decline in ADLs, independent of muscle mass, inflammation, and comorbidity. In people aged 80 and older, physical performance is a strong predictor of mortality, hospitalization, and disability, and muscle strength is a strong predictor of mortality and hospitalization. All of these relationships were independent of muscle mass, inflammatory markers, and comorbidity.
The Journals of Gerontology Series A: Biological Sciences and Medical Sciences, 2014
A subset of older people is at increased risk of hospitalization and dependency. Emerging evidenc... more 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.
International Journal of Cardiology, 2012
Little is known about the relationship between cardiac dysfunction and poor functioning in the el... more Little is known about the relationship between cardiac dysfunction and poor functioning in the elderly. This study sought to describe the prevalence of cardiac dysfunction in the very elderly and to investigate the correlation between echocardiographic abnormalities and indicators of poor functioning. A cross-sectional analysis within the BELFRAIL (BF(C80+)) study of 567 subjects aged 80 years and older. The clinical research assistant performed an examination including performance testing, questionnaires and technical examinations. Echocardiography was performed at the subject&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s home by a cardiologist using a portable system. The mean age of the participants was 84.7 years and 62.9% were women. Severe cardiac dysfunction was found in 19.3% and was defined as systolic dysfunction (5.8%), valvular heart disease (10.4%) or isolated severe diastolic dysfunction (3.1%). Severe cardiac dysfunction showed to be an independent identifier of poor performance (OR 1.8 (95% CI 1.1-3.2)), a low LAPAQ (LASA Physical Activity Questionnaire) score (OR 1.9 (95% CI 1.2-3.3)) and a high GDS-15 (Geriatric Depression Scale) score (OR 1.7 (95% CI 1.0-2.9)). This relationship was mainly explained by the independent correlation between aortic stenosis and poor functioning. Classic indicators of systolic and diastolic dysfunction were not able to identify participants with poor functioning. This study shows the very elderly represent a heterogeneous group of subjects with a high prevalence of comorbidities, among whom poor functioning might be triggered by multiple causes. Severe cardiac dysfunction, and more specifically aortic stenosis, showed an independent relationship with poor functioning.
Archives of Gerontology and Geriatrics, 2013
Archives of Gerontology and Geriatrics, 2012
The American Journal of Cardiology, 2013
Studies estimating the added value of natriuretic peptide levels and electrocardiographic finding... more Studies estimating the added value of natriuretic peptide levels and electrocardiographic findings beyond all relevant clinical information to identify cardiac dysfunction remain scarce. The aim of this study was to assess the presence of clinically relevant cardiac dysfunction in an unselected population of subjects aged ‡80 years. A cross-sectional analysis using an "intention-to-diagnose" strategy was performed within the BELFRAIL study (n [ 567). Baseline B-type natriuretic peptide and N-terminal proeB-type natriuretic peptide levels were determined and echocardiography was performed at subjects' homes. Logistic regression analysis and classification and regression tree analysis were used as complementary analytic tools. Cardiac dysfunction was present in 17% of subjects without and 31% of subjects with chronic atrial fibrillation (AF) or pacemaker. In subjects without chronic AF or pacemaker, the clinical model showed a C-statistic of 0.79 (95% confidence interval 0.74 to 0.85). The combination of natriuretic peptides with normal results on electrocardiography increased, only marginally, the C-statistic. In subjects with chronic AF or pacemaker, the clinical model showed a very high C-statistic of 0.90 (95% confidence interval 0.82 to 0.98). Classification and regression tree analysis showed that an additional 58 subjects (13%) were correctly classified using natriuretic peptides and electrocardiographic findings among those without chronic AF or pacemaker. Of participants with chronic AF or pacemaker, >90% were correctly classified. In conclusion, in a large population-based sample of patients aged ‡80 years, the clinical model possessed high accuracy to identify cardiac dysfunction in daily practice. Among subjects without chronic AF or pacemaker, a larger number were correctly classified by integrating natriuretic peptides and electrocardiographic findings in the strategy. Ó 2013 Elsevier Inc. All rights reserved. (Am J Cardiol 2013;-:-e-) Natriuretic peptide levels and electrocardiographic (ECG) findings have been generally accepted as valuable tools for the diagnosis of heart failure. 1 Moreover, their mainly exclusionary characteristics have also been demonstrated in unselected elderly populations for detecting cardiac dysfunction. 2 However, previous studies have calculated the diagnostic characteristics of a single natriuretic peptide or ECG test as though the diagnostic procedure were a univariate activity and previous clinical knowledge had no clinical impact. 3 Studies estimating the added value of natriuretic peptide levels and ECG findings in addition to medical history and clinical examination, which is representative of current clinical practice, remain scarce. 4 Therefore, a cross-sectional "intention-to-diagnose" analysis 5 was performed within the BELFRAIL cohort to determine the added value of natriuretic peptide levels and ECG findings beyond medical history, the presence of symptoms and signs, and routine laboratory tests to identify cardiac dysfunction. Thus, the goal of this study was to investigate, under real-life conditions, the possible gain of implementing natriuretic peptide testing and electrocardiography to assess the presence of clinically relevant cardiac dysfunction as a risk factor for symptomatic heart failure and death in an unselected population of subjects aged !80 years.
Age and Ageing, 2013
Hypovitaminosis D is common in older adults in western society. In the Netherlands, only 18 % of ... more Hypovitaminosis D is common in older adults in western society. In the Netherlands, only 18 % of patients 65 years and older have normal 25-OH-vitamin D levels (1). In the same age group, chronic kidney disease (CKD), defined as an estimated glomerular filtration rate (eGFR) <60 ml/min/1.73m², has a prevalence of approximately 30% (2-4). Therefore, many older adults suffer from CKD and hypovitaminosis D.
AGE, 2014
The large burden and coexistence of physical disability, cognitive impairment, and depression in ... more The large burden and coexistence of physical disability, cognitive impairment, and depression in the oldest old makes summary markers of global functioning of great value, allowing for risk stratification. Inflammation may be a common underlying cause or represents a final common pathway. The present study investigated the association between elevated serum inflammatory markers and global functioning and its underlying aspects. A representative sample of 415 communitydwelling elderly subjects participating in the BELFRAIL study, with a mean age of 85 years, was included in the present analysis. Data on physical performance, dependence, and mental aspects of functioning and serum levels of 15 inflammatory proteins, including cytokines, chemokines, and acute-phase proteins, were assessed. Interleukin (IL)-6 was negatively associated with global functioning (odds ratio (OR) 4.35). The odds ratios for C-reactive protein (CRP) (OR 2.37) and the combined score of IL-6 and CRP (OR 2.59) were lower or not significant. IL-6 was significantly associated with physical dependence and cognitive function, and only a highly elevated serum level was associated with physical performance. Physical dependence was associated with a highly elevated CRP serum level. The proportion of functionally impaired older persons with elevated IL-6 was 81.93 %, giving a low positive predictive value (0.38), but a high negative predictive value (0.87). So, IL-6 is strongly associated with global functioning and all of the individual aspects of functioning, except suspected depression, in communitydwelling persons 80 years and older.
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Papers by Catharina Mathe