RESUMEN
Frailty is a clinical syndrome often present in older adults and characterized by a heightened vulnerability to stressors. The biological antecedents and etiology of frailty are unclear despite decades of research: frailty is associated with dysregulation in a wide range of physiological systems, but no specific cause has been identified. Here, we test predictions stemming from the hypothesis that there is no specific cause: that frailty is an emergent property arising from the complex systems dynamics of the broad loss of organismal homeostasis. Specifically, we use dysregulation of six physiological systems using the Mahalanobis distance approach in two cohorts of older adults to test the breadth, diffuseness, and nonlinearity of associations between frailty and system-specific dysregulation. We find clear support for the breadth of associations between frailty and physiological dysregulation: positive associations of all systems with frailty in at least some analyses. We find partial support for diffuseness: the number of systems or total amount of dysregulation is more important than the identity of the systems dysregulated, but results only partially replicate across cohorts. We find partial support for nonlinearity: trends are exponential but not always significantly so, and power is limited for groups with very high levels of dysregulation. Overall, results are consistent with-but not definitive proof of-frailty as an emergent property of complex systems dynamics. Substantial work remains to understand how frailty relates to underlying physiological dynamics across systems.
Asunto(s)
Fragilidad , Anciano , Envejecimiento , Anciano Frágil , Homeostasis , HumanosRESUMEN
BACKGROUND: Age-related changes in biological processes such as physiological dysregulation (the progressive loss of homeostatic capacity) vary considerably among older adults and may influence health profiles in late life. These differences could be related, at least in part, to the impact of intrinsic and extrinsic factors such as sex and physical activity level (PAL). OBJECTIVES: The objectives of this study were (1) to assess the magnitude and rate of changes in physiologi-cal dysregulation in men and women according to PAL and (2) to determine whether/how sex and PAL mediate the apparent influence of physiological dysregulation on health outcomes (frailty and mortality). METHODS: We used data on 1,754 community-dwelling older adults (age = 74.4 ± 4.2 years; women = 52.4%) of the Quebec NuAge cohort study. Physiological dysregulation was calculated based on Mahalanobis distance of 31 biomarkers regrouped into 5 systems: oxygen transport, liver/kidney function, leukopoiesis, micronutrients, and lipids. RESULTS: As expected, mean physiological dysregulation significantly increased with age while PAL decreased. For the same age and PAL, men showed higher levels of physiological dysregulation globally in 3 systems: oxygen transport, liver/kidney function, and leukopoiesis. Men also showed faster global physiological dysregulation in the liver/kidney and leukopoiesis systems. Overall, high PAL was associated with lower level and slower rate of change of physiological dysregulation. Finally, while mortality and frailty risk significantly increased with physiological dysregulation, there was no evidence for differences in these effects between sexes and PAL. CONCLUSION: Our results showed that both sex and PAL have a significant effect on physiological dysregulation levels and rates of change. Also, although a higher PAL was associated with lower level and slower rate of change of physiological dysregulation, there was no evidence that PAL attenuates the effect of physiological dysregulation on subsequent declines in health at the end of life. Substantial work remains to understand how modifiable behaviors impact the relationship between physiological dysregulation, frailty, and mortality in men and women.
Asunto(s)
Fragilidad , Anciano , Biomarcadores , Estudios de Cohortes , Ejercicio Físico , Femenino , Fragilidad/diagnóstico , Humanos , Masculino , QuebecRESUMEN
BACKGROUND: A greater fat-free mass (FFM) is purported to be associated with protective effects on insulin resistance (IR). However, recent studies suggested negative associations between FFM and IR. OBJECTIVES: (1) To explore the direction of the association between FFM and IR in a large heterogeneous sample after controlling for confounding factors. (2) To determine cut off values of FFM associated with an increased risk of IR. METHODS: Outcome variables were measured in 7044 individuals (48.6% women, 20-79 years; NHANES, 1999-2006): body composition [fat mass (FM), FFM and appendicular FFM (aFFM); DXA], FFM index [FFMI: FFM/height (kg/m2)], appendicular FFMI [aFFM/height (kg/m2)] and insulin resistance (HOMA-IR). Multivariate regression analyses were performed to determine the independent predictors of HOMA-IR in younger (20-49 years) and older (50-79 years) men and women. ROC analyses were used to determine FFM cut-offs to identify a higher risk of insulin resistance (HOMA-IR > 75th percentile). RESULTS: aFFMI was an independent predictor of IR in younger (men: ß = 0.21; women: ß = 0.31; all p ≤ 0.001) and older (men: ß = 0.11; women: ß = 0.37; all p ≤ 0.001) individuals. Thresholds for aFFMI at which the risk of IR was significantly increased were 8.96 and 8.39 kg/m2 in younger and older men, and 7.22 and 6.64 kg/m2 in younger and older women, respectively. CONCLUSION: Independently of age, a greater aFFMI was an independent predictor of IR. These results suggest revisiting how we envision the link between FFM and IR and explore potential mechanisms.
Asunto(s)
Glucemia/análisis , Distribución de la Grasa Corporal , Resistencia a la Insulina , Adulto , Factores de Edad , Anciano , Composición Corporal , Índice de Masa Corporal , Estudios Transversales , Femenino , Homeostasis , Humanos , Masculino , Persona de Mediana Edad , Encuestas Nutricionales , Factores Sexuales , Adulto JovenRESUMEN
PURPOSE: Maximum heart rate (HRmax) is commonly used to estimate exercise intensity. Since direct measurement of HRmax is not always practical, prediction equations were developed. However, most equations have not been properly validated in older adults at low and high risk of cardiovascular disease (CVD). We sought to: 1) assess the accuracy of commonly used equations to predict HRmax amongst adults at low and high CVD risk and, 2) determine if SuperLearner (SL) modeling combining base machine algorithms could improve HRmax prediction. METHODS: A total of 1208 participants (61.6 ± 7.3 years; 62.7% male) were included. HRmax was measured during a maximal cardiorespiratory exercise test. Predicted HRmax was estimated using the following published equations: Fox, Astrand, Tanaka, Gelish and Gulati, and a SL model. Bland-Altman analyses as well as performance indicators such as root mean squared error (RMSE) and Lin's CCC were performed. RESULTS: All predicted HRmax-derived equations were positively associated with measured HRmax (women; r = 0.31: men; r = 0.46, p ≤ 0.001) but to a greater extent using a SL model (women; r = 0.47: men; r = 0.59, p ≤ 0.001). Overall, all equations tended to overestimate measured HRmax, with a RMSE which varied between 10.4 and 12.3 bpm. Although the SL model outperformed other equations, with no significant difference between measured and predicted HRmax, RMSE remained high (11.3 bpm). Lack of accuracy was mainly observed among adults with low aerobic fitness and with CVD risk factors, such as obesity, diabetes, and hypertension. CONCLUSIONS: We showed that commonly used equations and the SL model have insufficient accuracy to predict HRmax among adults. The performance of the prediction equations varied considerably according to the population clinical characteristics such as the presence of CVD risk factors or a low aerobic fitness.
RESUMEN
Achieving the three therapeutics targets known as ABC (A1c ≤ 7.0%, LDL-C < 2.0 mmol/L, and resting BP < 130/80 mmHg), limiting sedentary behaviors as well as accumulating a total of 150 min/week of moderate-to-vigorous aerobic exercise reduce the risk of cardiovascular disease in type 2 diabetes (T2D) individuals. However, more recent data regarding the achievement of ABC over time in Canada is needed and it remains to be determined how sedentary behaviors and physical activity levels can influence its achievement. Analyses were performed using a total of 17 582 individuals (18-79 years) from the 2007-2017 Canadian Health Measures Survey. Sedentary behaviors and physical activity levels were estimated using an accelerometer for a total of 7 consecutive days and quartiles of physical activity were used to categorize individuals. The prevalence of T2D has increased from 2007 to 2017 in the Canadian population (from 4.80% to 8.38%) with a considerable number of undiagnosed patients. The achievement of ABC went from 11.53% [11.49%-11.57%] in 2007 to 14.84% [14.80%-14.89%] in 2017 in T2D individuals. Moderate-to-vigorous physical activity (MVPA) levels were positively but weakly correlated to the achievement of the ABC (r = 0.044; p = 0.001), while sedentary time and light physical activity were not (r < -0.014; p = 0.266). Only 8.8% of individuals with the lowest level of MVPA (Q1) reached the ABC while 15.1% of the most active individuals (Q4) reached the triple target. In addition to physical activity, other important factors such as body mass index and medication use should also be considered as modifiable contributing factors.
Asunto(s)
Diabetes Mellitus Tipo 2 , Humanos , Diabetes Mellitus Tipo 2/epidemiología , Diabetes Mellitus Tipo 2/terapia , Objetivos , Canadá/epidemiología , Ejercicio FísicoRESUMEN
BACKGROUND AND OBJECTIVES: There is an urgent need to better understand frailty and its predisposing factors. Although numerous cross-sectional studies have identified various risk and protective factors of frailty, there is a limited understanding of longitudinal frailty progression. Furthermore, discrepancies in the methodologies of these studies hamper comparability of results. Here, we use a coordinated analytical approach in 5 independent cohorts to evaluate longitudinal trajectories of frailty and the effect of 3 previously identified critical risk factors: sex, age, and education. RESEARCH DESIGN AND METHODS: We derived a frailty index (FI) for 5 cohorts based on the accumulation of deficits approach. Four linear and quadratic growth curve models were fit in each cohort independently. Models were adjusted for sex/gender, age, years of education, and a sex/gender-by-age interaction term. RESULTS: Models describing linear progression of frailty best fit the data. Annual increases in FI ranged from 0.002 in the Invecchiare in Chianti cohort to 0.009 in the Longitudinal Aging Study Amsterdam (LASA). Women had consistently higher levels of frailty than men in all cohorts, ranging from an increase in the mean FI in women from 0.014 in the Health and Retirement Study cohort to 0.046 in the LASA cohort. However, the associations between sex/gender and rate of frailty progression were mixed. There was significant heterogeneity in within-person trajectories of frailty about the mean curves. DISCUSSION AND IMPLICATIONS: Our findings of linear longitudinal increases in frailty highlight important avenues for future research. Specifically, we encourage further research to identify potential effect modifiers or groups that would benefit from targeted or personalized interventions.
RESUMEN
Menopause transition is associated with detrimental changes in physical activity, body composition, and metabolic profile. Although physical activity energy expenditure (PAEE) is inversely associated with metabolic syndrome (MetS) in individuals at higher risk of cardiovascular disease, the association is unknown in low-risk individuals. The aim of the study was to investigate the association between PAEE and MetS (prevalence and severity) in inactive overweight or obese postmenopausal women with a low Framingham Risk Score (<10%). Cross-sectional data of 126 participants were divided into quartiles based on PAEE (Quartile (Q)1 = lowest PAEE) while fat-free mass (FFM) and fat mass were measured by dual-energy X-ray absorptiometry. MetS prevalence was significantly different between Q1 and Q4 (37.9% vs 13.3%, p = 0.03). After controlling for potential confounders, MetS severity was negatively associated with PAEE (B = -0.057, p < 0.01) and positively with FFM (B = 0.038, p < 0.001). Moderation analyses indicated that a greater FFM exacerbated the association between PAEE and MetS severity in Q1 and Q2 (PAEE × FFM; B = -0.004; p = 0.1). Our results suggest that displaying a low FRS and lower PAEE increase MetS prevalence and severity. In addition, greater FFM interacts with lower PAEE to worsens MetS severity, while higher PAEE lessened this effect. Novelty: Inactive individuals displaying higher daily PAEE also have a lower MetS prevalence. Greater FFM is associated with a worse MetS severity where a higher PAEE mitigated this deleterious effect in our cohort.
Asunto(s)
Composición Corporal , Metabolismo Energético , Ejercicio Físico , Síndrome Metabólico/epidemiología , Obesidad , Sobrepeso , Estudios Transversales , Femenino , Humanos , Persona de Mediana Edad , Posmenopausia , Factores de RiesgoRESUMEN
OBJECTIVES: First, to establish the respective ability of body mass index (BMI), waist circumference (WC), and relative fat mass index (RFM), to estimate body fat (BF%) measured by DXA (DXA-BF%) and correctly identify postmenopausal women living with obesity (BF%â>â35). Second, to identify the best indicator of successful weight-loss intervention in postmenopausal women living with obesity. METHODS: A total of 277 women (age: 59.8â±â5.3ây; BF%: 43.4â±â5.3) from five weight-loss studies with complete data for anthropometric measurements [BMIâ=âweight/height (kg/m2); WC (cm)] and BF% were pooled together. Statistical performance indicators were determined to assess ability of RFM [64-(20â×âheight/waist circumference) + (12â×âsex)], BMI and WC to estimate BF% before and after weight-loss intervention and to correctly identify postmenopausal women living with obesity. RESULTS: Compared with RFM (râ=â0.51; r2â=â0.27; RMSEâ=â4.4%; Lin's CCCâ=â0.46) and WC (râ=â0.49; r2â=â0.25; RMSEâ=â4.8%; Lin's CCCâ=â0.41), BMI (râ=â0.73; r2â=â0.52; RMSEâ=â3.7%; Lin's CCCâ=â0.71) was the best anthropometric index to estimate DXA-BF% and correctly identify postmenopausal women living with obesity (sensitivity + specificity: BMIâ=â193; RFMâ=â152; WCâ=â158), with lower misclassification error, before weight-loss intervention. After weight-loss, the change in BMI was strongly correlated with change in DXA-BF%, indicating that the BMI is the best indicator of success weight-loss intervention. CONCLUSION: In the absence of more objective measures of adiposity, BMI is a suitable proxy measure for BF% in postmenopausal women, for whom a lifestyle intervention is relevant. Furthermore, BMI can be used as an indicator to assess success of weight-loss intervention in this subpopulation.
Asunto(s)
Adiposidad , Posmenopausia , Absorciometría de Fotón , Anciano , Composición Corporal , Índice de Masa Corporal , Femenino , Humanos , Persona de Mediana Edad , Obesidad/terapia , Circunferencia de la CinturaRESUMEN
BACKGROUND: The aim of this study was to identify modifiable risk factors associated with isolated impaired fasting glucose (IFG), isolate impaired glucose tolerance (IGT), or combined IFG-IGT in men and women aged 50 years and older. METHODS: Cross-sectional analyses were performed in 703 men and women aged between 50 and 80 years old from NHANES (2007-2008). Outcome variables: IFG and IGT (ADA 2003), estimated body composition, cardiometabolic profile, and socio-demographic, dietary, and lifestyle factors. RESULTS: First, 235 had normal glucose tolerance (men = 38.3%, women = 61.7%), 243 had IFG (men = 61.7%, women = 38.3%), 67 had IGT (men = 40.3%, women = 59.7%) and 158 had both conditions (men = 57.0%, women = 43.0%). The only common determinant of both IFG and IGT was triglyceride levels. High total fat mass index (FMI) and high total fat-free mass index (FFMI) were independently associated with IFG; while high C-reactive protein (CRP) levels were independently associated with IGT. Finally, combined IFG-IGT was associated with inadequate fiber intake, high FMI, FFMI, and CRP levels. CONCLUSIONS: Middle-age and older individuals presented different modifiable risk factors depending on whether they had IFG or IGT. IFG was associated with deteriorated body composition and lipids, whereas IGT was associated with deteriorated lipids and inflammatory factors. IFG-IGT, on the other hand, was associated with a larger number of risk factors, including worsen body composition, cardiometabolic and dietary factors. To prevent the transition to type 2 diabetes, specific clinical interventions targeting these risk factors should be considered.
RESUMEN
To document changes in prevalence of the metabolic syndrome (MetS) in the United States adult population between 1999 and 2014 and to explore how variations in the dietary intakes explain changes in MetS prevalence and its components over time. A total of 38 541 individuals (aged 20-85 years; National Health and Nutrition Examination Survey 1999-2014) were studied. Outcome variables were MetS, waist circumference (WC), plasma high-density lipoprotein cholesterol (HDL-c), triglycerides, fasting glucose (FG) levels, resting systolic and diastolic blood pressure, dietary intakes (total daily energy, carbohydrates, proteins, fats, sodium, and alcohol intakes), the poverty income ratio (PIR) and sociodemographic data (age, sex, ethnicity). Overall, the prevalence of the MetS significantly increased between 1999 and 2014 (27.9% to 31.5%). High plasma FG levels and high WC increased between 1999 and 2014, while the prevalence of the other components of MetS decreased or remained stable. Interestingly, a significant peak in MetS prevalence was observed in 2007-2008 compared with 1999-2006 (34.4% vs 27.6%), accompanied by a concomitant increase in WC and plasma FG levels, as well as a decrease in plasma HDL-c. Finally, significant decreases were observed for the PIR, total daily energy intake, sodium, and all macronutrient intakes in 2007-2008 compared with 1999-2006 (all P < 0.01). Results showed that the MetS prevalence significantly increased between 1999 and 2014 in the United States adult population, with a peak in 2007-2008. Interestingly, the 2007-2008 peak in MetS prevalence was accompanied by decreases in the PIR, total daily energy, and macronutrients intakes, suggesting potential impact of the 2007-2008 recession.
Asunto(s)
Recesión Económica , Síndrome Metabólico/economía , Síndrome Metabólico/epidemiología , Encuestas Nutricionales , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Prevalencia , Estados Unidos/epidemiología , Adulto JovenRESUMEN
Obesity in older adults results from several interacting factors. Consequently, interventions have shown mitigated effects. We determined (a) the different subgroups of older adults with obesity based on clusters of associated comorbidities and (b) the trajectory of these clusters to assess their stability over 3 years and factors contributing to transitions. Obese men (n = 193; body mass index [BMI] = 33.15 ± 2.69 kg/m2 ) and women (n = 220; BMI = 33.71 ± 3.71 kg/m2 ) aged between 68 and 82 years were studied. Outcome variables were body composition, strength, physical capacity (PC), nutrition, psychological and physical health and social participation. Cluster analyses, stratified by sex, were used to identify obesity profiles at baseline and follow-up. Three profiles were identified, based on general health (GH), psychological health (PH) and PC: Cluster 1: healthy obese (GH+, PH+, PC+); Cluster 2: obese with low PC (GH+/-, PH+/-, PC-); Cluster 3: unhealthy obese (GH-, PH-, PC-). After 3 years, 61.2% and 70.2% of men and women remained in their initial cluster, compared to 20.4% and 13.7% who transitioned towards a worse health cluster and 18.3% and 16.0% who transitioned towards a more favourable cluster, partly explained by changes in physical health for men and physical health and PH for women. The results of this study show that targeting physical function in men and physical health and PH functions in women could prevent further health decline in older adults with obesity. Further studies are needed to investigate the role of these clusters in the prediction of cardiometabolic complications and mortality.
Asunto(s)
Envejecimiento Saludable , Estado Nutricional , Obesidad/epidemiología , Aptitud Física , Factores de Edad , Anciano , Anciano de 80 o más Años , Composición Corporal , Índice de Masa Corporal , Trayectoria del Peso Corporal , Análisis por Conglomerados , Comorbilidad , Tolerancia al Ejercicio , Femenino , Evaluación Geriátrica/métodos , Humanos , Masculino , Salud Mental , Fuerza Muscular , Evaluación Nutricional , Obesidad/diagnóstico , Obesidad/fisiopatología , Obesidad/psicología , Fenotipo , Pronóstico , Quebec/epidemiología , Factores de Riesgo , Factores Sexuales , Factores de TiempoRESUMEN
High level of cardiac Troponin T (hs-cTnT) in geriatric population has been considered as an age-related phenomenon, which may question the interpretation of the increase of hs-cTnT in this population. The challenge is what is the primary cause of the increased hs-cTnT levels in elderly patients without AMI. OBJECTIVE: The aim of the current study was to determine the impact of aging on hs-cTnT levels in elderly patients without acute cardiac events but in the presence of comorbidities. METHODS: Sociodemographic and clinical data were collected from 6977 medical records of patients aged ≥65â¯years without acute coronary events but for whom hs-cTnT measurements were available. The patients were stratified based on age, troponin levels and the number of comorbidities. RESULTS: The results suggested that the likelihood of increased hs-cTnT was related to the presence of comorbidities independently of their number (pâ¯<â¯0.05). The adjusted odds ratio (AOR) for both advanced age and having comorbidity was statistically significant, however for the old group (74â¯≥â¯ageâ¯≥â¯84â¯years) the chance of having elevated troponin regarding age compared to the presence of comorbidity was 1.070 vs. 1.216, whereas for the old-old group (≥85â¯years) it was found to be 1.071 vs. 1.311. Besides statistical significance for age, from a clinical standpoint, the AOR of 1.070 may not be considered clinically relevant. CONCLUSION: Increased hs-cTnT levels were associated with the presence of pre-existing comorbidities independently of age. Increased hs-cTnT levels in the elderly should always be considered as pathological, and a specific etiology should be searched.
RESUMEN
OBJECTIVE: A sex-specific standard waist circumference (WC) is widely used to determine cardiometabolic risk across ages even though aging impacts the link between fat distribution and cardiometabolic risk. The objective was to propose WC thresholds that better predict metabolic abnormalities according to sex, age, and body mass index (BMI) categories. METHODS: First, receiver operating characteristic analyses were performed to identify optimal age (20-49, 50-64, and 65-80 years) and BMI (normal weight, overweight, obese I, and obese II+) specific WC thresholds to correctly identify at-risk individuals, that is, presenting ≥2 cardiometabolic risk factors of metabolic syndrome (n = 23,482; NHANES 2007-2014). Second, cross-validation analyses (n = 18,686; NHANES 1999-2006) were used to validate these WC optimal thresholds. Univariate logistic regression models with WC as an independent predictor were performed to quantify odds of being at-risk for each age and BMI subgroups. RESULTS: When age and BMI categories were considered in the identification of optimal WC thresholds, sensitivity to correctly identify at-risk individuals significantly improved. CONCLUSIONS: Our results indicate that the use of WC thresholds that are specific to age and BMI subcategories significantly increases the capacity to accurately identify at-risk individuals. They would thus be highly appropriate for clinicians in the context of efficient cardiometabolic risk assessment and intervention recommendations.
Asunto(s)
Índice de Masa Corporal , Pesos y Medidas Corporales/normas , Enfermedades Cardiovasculares/diagnóstico , Enfermedades Cardiovasculares/etiología , Síndrome Metabólico/diagnóstico , Síndrome Metabólico/etiología , Circunferencia de la Cintura/fisiología , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Presión Sanguínea/fisiología , Pesos y Medidas Corporales/métodos , Enfermedades Cardiovasculares/epidemiología , Femenino , Humanos , Lípidos/análisis , Lípidos/sangre , Masculino , Síndrome Metabólico/epidemiología , Persona de Mediana Edad , Valores de Referencia , Medición de Riesgo , Factores de Riesgo , Factores Sexuales , Adulto JovenRESUMEN
OBJECTIVE: To compare the effects of a caloric restriction (CR) on body composition, lipid profile, and glucose homeostasis in obese postmenopausal women with and without metabolic syndrome (MetS). METHODS: Secondary analyses were performed on 73 inactive obese postmenopausal women (age 57.7â±â4.8 years; body mass index 32.4â±â4.6âkg/m) who participated in the 6-month CR arm of a study of the Montreal-Ottawa New Emerging Team. The harmonized MetS definition was used to categorize participants with MetS (nâ=â20, 27.39%) and without MetS (nâ=â53, 72.61%). Variables of interest were: body composition (dual-energy X-ray absorptiometry), body fat distribution (computed tomography scan), glucose homeostasis at fasting state and during a euglycemic/hyperinsulinemic clamp, fasting lipids, and resting blood pressure. RESULTS: By design, the MetS group had a worse cardiometabolic profile, whereas both groups were comparable for age. Fifty-five participants out of 73 displayed no change in MetS status after the intervention. Twelve participants out of 20 (or 60.0%) in the MetS group had no more MetS after weight loss (Pâ=âNS), whereas 6 participants out of 53 (or 11.3%) in the other group developed the MetS after the intervention (Pâ=âNS). Overall, indices of body composition and body fat distribution improved significantly and similarly in both groups (P between 0.03 and 0.0001). Furthermore, with the exception of triglyceride levels and triglycerides/high-density lipoprotein cholesterol ratio, which decrease significantly more in the MetS group (Pâ≤â0.05), no difference was observed between groups for the other variables of the cardiometabolic profile. CONCLUSIONS: Despite no overall significant effects on MetS, heteregeneous results were obtained in response to weight loss in the present study, with some improving the MetS, whereas other displaying deteriorations. Further studies are needed to identify factors and phenotypes associated with positive and negative cardiometabolic responses to CR intervention.