Longitudinal analysis of the relationship between physical function and mortality in ambulatory older men

Background. Low physical performance is an important characteristic of frailty and sarcopenia. In this study, we wanted to assess and compare the predictive value of physical function measurements for all-cause mortality in older men. Methods. Data are from a longitudinal study of a population-based sample of 352 ambulatory older men aged 71 to 86 at study baseline. The Rapid disability rating scale-2, 36-Item short form health survey, Hand grip strength, Five times sit-to-stand test, Standing balance, and Timed Up and Go test were determined at baseline. Associations with all-cause mortality were assessed using Cox proportional hazard analyses. Age, BMI, smoking status, education, physical activity, and cognitive status were included as confounders. Follow-up exceeded 15 years. Results. The mean age of participants was 76 ± 4.2 years. Average follow-up duration was 184 ± 2 months. Seventy-eight percent (273) of the 352 men died during follow-up, with a median survival time of 110 months. All examined physical function measurements were associated with all-cause mortality. The Timed Up and Go test was the best predictor (adjusted HR per SD increase = 1.58, 95% CI = 1.40-1.79, P < 0.001) for global mortality. Conclusions. Our findings demonstrate that physical function measurements are important in the evaluation of older persons. We encourage the use of the Timed Up and Go test as a reliable, quick and feasible screening tool in clinical settings

Thyroid hormone status within the physiological range affects bone mass and density in healthy men at the age of peak bone mass

Context: The hormonal factors involved in the regulation of peak bone mass (PBM) in men have not been fully investigated. Apart from gonadal steroids and somatotropic hormones, thyroid hormones are known to affect bone maturation and homeostasis and are additional candidate determinants of adult bone mass. Objective: We aimed to investigate between-subject physiological variation in free and total thyroid hormone concentrations, TSH, and thyroid binding globulin (TBG) in relation to parameters of bone mass, geometry, and mineral density in healthy men at the age of PBM. Design and setting: We recruited 677 healthy male siblings aged 25-45 years in a cross-sectional, population-based study. Areal and volumetric bone parameters were determined using dual-energy x-ray absorptiometry (DXA) and peripheral quantitative computed tomography (pQCT). Total and free thyroid hormones, TBG, and TSH were determined using immunoassays. Results: Free and total thyroid hormone concentrations were inversely associated with bone mineral density (BMD) and bone mineral content (BMC) at the hip and total body (free triiodothyronine (FT(3)), total T(3) (TT(3)), and total T(4) (TT(4))) and at the spine (FT(3)). TBG was negatively associated with BMC and areal BMD at all sites. At the radius, cortical bone area was inversely associated with TT(3), TT(4), and TBG, and trabecular bone density was inversely associated with free thyroxine, TT(4), and TBG. We observed inverse associations between cortical bone area at the mid-tibia and FT(3), TT(3), TT(4), and TBG. No associations between TSH and DXA or pQCT measurements were found. Conclusion: In healthy men at the age of PBM, between-subject variation in thyroid hormone concentrations affects bone density, with higher levels of FT(3), TT(3), TT(4), and TBG being associated with less favorable bone density and content

Functional changes during hospital stay in older patients admitted to an acute care ward : a multicenter observational study

Objectives: Changes in physical performance during hospital stay have rarely been evaluated. In this study, we examined functional changes during hospital stay by assessing both physical performance and activities of daily living. Additionally, we investigated characteristics of older patients associated with meaningful in-hospital improvement in physical performance. Methods: The CRiteria to assess appropriate Medication use among Elderly complex patients project recruited 1123 patients aged >= 65 years, consecutively admitted to geriatric or internal medicine acute care wards of seven Italian hospitals. We analyzed data from 639 participating participants with a Mini Mental State Examination score >= 18/30. Physical performance was assessed by walking speed and grip strength, and functional status by activities of daily living at hospital admission and at discharge. Meaningful improvement was defined as a measured change of at least 1 standard deviation. Multivariable logistic regression models predicting meaningful improvement, included age, gender, type of admission (through emergency room or elective), and physical performance at admission. Results: Mean age of the study participants was 79 years (range 65-98), 52% were female. Overall, mean walking speed and grip strength performance improved during hospital stay (walking speed improvement: 0.04 +/- 0.20 m/s, p<0.001; grip strength improvement: 0.43 +/- 5.66 kg, p = 0.001), no significant change was observed in activities of daily living. Patients with poor physical performance at admission had higher odds for in-hospital improvement. Conclusion: Overall, physical performance measurements show an improvement during hospital stay. The margin for meaningful functional improvement is larger in patients with poor physical function at admission. Nevertheless, most of these patients continue to have poor performance at discharge

Thyroid hormone levels within reference range are associated with heart rate, cardiac structure, and function in middle-aged men and women

Background: Triiodothyronine (T3) has many effects on the heart, and marked changes in cardiac function and structure occur in patients with (subclinical) thyroid disease. We investigated whether between-subject variation in thyroid hormone levels within the euthyroid range is also associated with heart rate and echocardiographic heart function and structure. Methods: Subjects were selected from the Asklepios study (n=2524), a population-representative random sample of patients aged between 35 and 55 years, free from overt cardiovascular disease at baseline. Analyses were restricted to 2078 subjects (1013 women and 1065 men), not using antihypertensive or thyroid medication nor having antithyroperoxidase antibody levels above clinical cut-off or thyrotropin (TSH) levels outside the reference range. All subjects were phenotyped in-depth and underwent comprehensive echocardiography, including diastolic evaluation. Thyroid function parameters were determined by automated electrochemiluminescence. Results: Heart rate was robustly positively associated with (quartiles of) free T3 (FT3) and T3, both in subjects with TSH levels within reference (0.27-4.2 μU/L) and in narrow TSH range (0.5-2.5 μU/L; p<0.0001). FT3 and T3 were negatively associated with left ventricular (LV) end-diastolic volume but positively associated with relative wall thickness. Total T3 (TT3) was associated with enhanced ventricular contraction (as assessed by tissue Doppler imaging). Free thyroxine, FT3, and TT3 were positively associated with late ventricular filling, and TT3 was associated with early ventricular filling. Conclusion: We have demonstrated a strong positive association between thyroid hormone levels within the euthyroid range and heart rate, and more subtle effects on cardiac function and structure. More specifically, we suggest a smaller LV cavity size (with increased relative wall thickness), an enhanced atrial and ventricular contraction, and LV relaxation with higher circulating thyroid hormones. These results illustrate that variation in thyroid hormone levels, even within the reference range, exerts effects on the heart

Triiodothyronine and free thyroxine levels are differentially associated with metabolic profile and adiposity-related cardiovascular risk markers in euthyroid middle-aged subjects

Background: We previously showed that in healthy young men a less favorable body composition is associated with higher FT3 levels within the euthyroid range. Besides, a higher FT3-to-FT4 ratio has been related to a less favorable metabolic phenotype and more placental growth in pregnant women. In the present study, we therefore investigated whether serum TSH, thyroid hormone levels and the FT3-to-FT4 ratio are associated with metabolic and adiposity-related cardiovascular risk markers in a healthy population of middle-aged euthyroid men and women. Methods: Thyroid parameters were measured in 2524 generally healthy subjects from the Asklepios study (35-55yrs, mean age 46 years). Analyses were restricted to 2315 subjects (1138 women and 1177 men), not using thyroid medication, not having anti-TPO levels above clinical cut-off values nor TSH levels outside the reference range (0.27-4.2 mU/L). Twenty-seven percent of the women and 47.5% of the men were overweight, while 13% of women and 17% of men were obese. Twenty percent of the subjects were active smokers. Serum thyroid function parameters were determined by electrochemiluminescence. Results: (F) T3 and the FT3-to-FT4 ratio were positively related to BMI, waist circumference and components of the metabolic syndrome, i.e. triglycerides, systolic and diastolic blood pressure and fasting plasma glucose, and negatively with HDL-cholesterol levels, whereas FT4 was negatively associated to BMI, waist circumference and triglycerides (all p-values <0.001). TSH related positively to total cholesterol levels (p<0.01), triglycerides and to systolic and diastolic blood pressure (all p<0.001). The FT3-to-FT4 ratio was further positively associated to the adiposity-related inflammation markers interleukin-6 (IL6) and high-sensitive CRP (hs-CRP) and to pulse wave velocity. All associations were adjusted for sex, age, height and smoking and most associations persisted after additional adjustment for weight or waist circumference. Conclusion: In healthy euthyroid middle-aged men and women, higher (F) T3 levels, lower FT4 levels and thus a higher FT3-to-FT4 ratio are consistently associated with various markers of unfavorable metabolic profile and cardiovascular risk

Genetic variations in the androgen receptor are associated with steroid concentrations and anthropometrics but not with muscle mass in healthy young men

OBJECTIVE: The relationship between serum testosterone (T) levels, muscle mass and muscle force in eugonadal men is incompletely understood. As polymorphisms in the androgen receptor (AR) gene cause differences in androgen sensitivity, no straightforward correlation can be observed between the interindividual variation in T levels and different phenotypes. Therefore, we aim to investigate the relationship between genetic variations in the AR, circulating androgens and muscle mass and function in young healthy male siblings. DESIGN: 677 men (25-45 years) were recruited in a cross-sectional, population-based sibling pair study. METHODS: Relations between genetic variation in the AR gene (CAGn, GGNn, SNPs), sex steroid levels (by LC-MS/MS), body composition (by DXA), muscle cross-sectional area (CSA) (by pQCT), muscle force (isokinetic peak torque, grip strength) and anthropometrics were studied using linear mixed-effect modelling. RESULTS: Muscle mass and force were highly heritable and related to age, physical activity, body composition and anthropometrics. Total T (TT) and free T (FT) levels were positively related to muscle CSA, whereas estradiol (E2) and free E2 (FE2) concentrations were negatively associated with muscle force. Subjects with longer CAG repeat length had higher circulating TT, FT, and higher E2 and FE2 concentrations. Weak associations with TT and FT were found for the rs5965433 and rs5919392 SNP in the AR, whereas no association between GGN repeat polymorphism and T concentrations were found. Arm span and 2D:4D finger length ratio were inversely associated, whereas muscle mass and force were not associated with the number of CAG repeats. CONCLUSIONS: Age, physical activity, body composition, sex steroid levels and anthropometrics are determinants of muscle mass and function in young men. Although the number of CAG repeats of the AR are related to sex steroid levels and anthropometrics, we have no evidence that these variations in the AR gene also affect muscle mass or function

A multicomponent approach to identify predictors of hospital outcomes in older in-patients : a multicentre, observational study

Background: The identification of older patients at risk of poor hospital outcomes (e.g. longer hospital stay, in-hospital mortality, and institutionalisation) is important to provide an effective healthcare service. Objective: To identify factors related to older patients’ clinical, nutritional, functional and socio-demographic profiles at admission to an acute care ward that can predict poor hospital outcomes. Design and Setting: The CRiteria to assess appropriate Medication use among Elderly complex patients project was a multicentre, observational study performed in geriatric and internal medicine acute care wards of seven Italian hospitals. Subjects: One thousand one hundred twenty-three consecutively admitted patients aged 65 years or older. Methods: Hospital outcomes were length of stay, in-hospital mortality, and institutionalisation. Results: Mean age of participants was 81 years, 56% were women. Median length of stay was 10 (7–14) days, 41 patients died during hospital stay and 37 were newly institutionalised. Number of drugs before admission, metastasized cancer, renal failure or dialysis, infection, falls at home during the last year, pain, and walking speed were independent predictors of LoS. Total dependency in activities of daily living and inability to perform grip strength test were independent predictors of inhospital mortality. Malnutrition and total dependency in activities of daily living were independent predictors of institutionalisation. Conclusions: Our results confirm that not only diseases, but also multifaceted aspects of ageing such as physical function and malnutrition are strong predictors of hospital outcomes and suggest that these variables should be systematically recorded