Myocardial Fibrosis and Steatosis in Patients with Aortic Stenosis: Roles of Myostatin and Ceramides.

Aortic stenosis (AS) involves progressive valve obstruction and a remodeling response of the left ventriculum (LV) with systolic and diastolic dysfunction. The roles of interstitial fibrosis and myocardial steatosis in LV dysfunction in AS have not been completely characterized. We enrolled 31 patients (19 women and 12 men) with severe AS undergoing elective aortic valve replacement. The subjects were clinically evaluated, and transthoracic echocardiography was performed pre-surgery. LV septal biopsies were obtained to assess fibrosis and apoptosis and fat deposition in myocytes (perilipin 5 (PLIN5)), or in the form of adipocytes within the heart (perilipin 1 (PLIN1)), the presence of ceramides and myostatin were assessed via immunohistochemistry. After BMI adjustment, we found a positive association between fibrosis and apoptotic cardiomyocytes, as well as fibrosis and the area covered by PLIN5. Apoptosis and PLIN5 were also significantly interrelated. LV fibrosis increased with a higher medium gradient (MG) and peak gradient (PG). Ceramides and myostatin levels were higher in patients within the higher MG and PG tertiles. In the linear regression analysis, increased fibrosis correlated with increased apoptosis and myostatin, independent from confounding factors. After adjustment for age and BMI, we found a positive relationship between PLIN5 and E/A and a negative correlation between septal S', global longitudinal strain (GLS), and fibrosis. Myostatin was inversely correlated with GLS and ejection fraction. Fibrosis and myocardial steatosis altogether contribute to ventricular dysfunction in severe AS. The association of myostatin and fibrosis with systolic dysfunction, as well as between myocardial steatosis and diastolic dysfunction, highlights potential therapeutic targets.

The Mini Sarcopenia Risk Assessment (MSRA) Questionnaire score as a predictor of skeletal muscle mass loss.

BACKGROUND: Previous studies showed a strong relationship between reduction of appendicular muscle mass and worsening disability; hence, accuracy in assessing muscle mass is considered a key feature for a sarcopenia screening tool. AIM: The aim of the study was to evaluate if the 7 items of Mini Sarcopenia Risk Assessment (MSRA) questionnaire predict muscle mass loss in a population of community-dwelling elderly subjects over a 5.5-y follow-up. METHODS: The study included 159 subjects, 92 women and 67 men aged 71.5 ± 2.2 years and with mean body mass index of 26.7 ± 4.0 kg/m2. Appendicular skeletal muscle mass (ASMM) as measured with Dual-Energy X-ray absorptiometry (DXA), was obtained at baseline and after 2 and 5.5 years of follow-up where the skeletal muscle index (SMI) was calculated. RESULTS: A significant reduction of ASMM and SMI was observed at two and 5.5 years of follow-up, in both, men and women. Repeated-measures analysis of variance (ANOVA) found a significant time effect on ASMM for both subjects with MSRA > 30 and ≤ 30 (P < 0.01 and P < 0.001). The group × time interaction was significant (P < 0.001), after even considering separately subjects with normal muscle mass and low muscle mass at baseline (P < 0.05 and P = 0.005). Similar results were obtained for SMI. Considering only the subjects with normal SMI at baseline, subjects with MSRA questionnaire ≤ 30 showed 5.7 (95% CI 1.73-19.03) higher risk of exceeding the low muscle mass threshold. CONCLUSION: In a population of community-dwelling elderly men and women, MSRA score of 30 is predictive of a steeper decline in ASMM and SMI and of a higher risk of exceeding the low muscle mass EWGSOP threshold.

Predictors of self-reported adherence to direct oral anticoagulation in a population of elderly men and women with non-valvular atrial fibrillation.

There is a general lack of studies evaluating medication adherence with self-report scales for elderly patients in treatment with direct oral anticoagulants (DOACs). The aim of the study was to assess the degree of adherence to DOAC therapy in a population of elderly outpatients aged 65 years or older affected by non-valvular atrial fibrillation (NVAF), using the 4-item Morisky Medication Adherence Scale, and to identify potential factors, including the geriatric multidimensional evaluation, which can affect adherence in the study population. A total of 103 subjects, anticoagulated with DOACs for NVAF in primary or secondary prevention, were eligible; 76 showed adequate adhesion to anticoagulant therapy, while 27 showed inadequate adherence. Participants underwent biochemical assessment and Morisky Scale, Instrumental Activities of Daily Living, CHA2DS2-VASc, HAS-BLED, mental status and nutritional evaluations were performed. 2% of subjects assumed Dabigatran at low dose, while 7.8% at standard dose, 9.7% assumed low-dose of Rivaroxaban and 30.1% at standard dose, 6.8% assumed Apixaban at low dose and 39.7% at standard dose, and finally 1% assumed Edoxaban at low dose and 2.9% at standard dose. Most subjects took the DOACs without help (80.6%), while 16 subjects were helped by a family member (15.5%) and 4 were assisted by a caregiver (3.9%). Binary logistic regression considered inappropriate adherence as a dependent variable, while age, male sex, polypharmacotherapy, cognitive decay, caregiver help for therapy assumption, duration of DOAC therapy and double daily administration were considered as independent variables. The double daily administration was an independent factor, determining inappropriate adherence with an OR of 2.88 (p = 0.048, CI 1.003-8.286).

The Role of Ultrasound Muscle Parameters for Myosteatosis and Myofibrosis Measurement in Young, Older, and Obese Subjects.

OBJECTIVES: The aim of the study was to compare quantitative and qualitative ultrasound parameters between healthy young adults and post-acute hospitalized older adults with and without physical disability, as well as between normal weight and overweight/obese persons. DESIGN: Cross-sectional observational study. SETTING AND PARTICIPANTS: A total of 120 individuals were recruited: 24 healthy young adults, 24 normal weight and 24 overweight/obese community-dwelling adults, and 48 post-acute hospitalized older adults with different degrees of functional autonomy. METHODS: The rectus femoris cross-sectional area (CSA), subcutaneous adipose tissue (SCAT) thickness, echogenicity, strain elastography, and compressibility were measured with ultrasound echography. RESULTS: Post-acute older adults with a good level of autonomy showed higher echogenicity, a higher compressibility index and elastometry strain, and lower rectus femoris thickness and CSA as compared with young persons. Post-acute individuals with physical disability showed lower echogenicity and a greater stiffness compared with their still autonomous counterparts. Normal weight individuals showed lower stiffness as evaluated with elastometry and a lower SCAT thickness, as compared with individuals with age-matched overweight or obesity. From multiple regression analyses, using CSA as an independent variable, an inverse association with female sex and age was observed, explaining 16% and 51% of variance. Echogenicity was directly associated with age (34% of variance) and with the Barthel index (6% of variance). Elastometry showed association with age and body mass index (BMI), 30% and 16% of variance, respectively. Considering compressibility as a dependent variable, a direct association with age and an inverse association with BMI were observed, with 5% and 11% of variance respectively. CONCLUSIONS AND IMPLICATIONS: Muscle mass decreases with age and with physical disability. Echogenicity, which increases with age and disability level, seems to be associated with myofibrosis. Conversely, elastometry seems useful in the characterization of muscle quality in overweight or obese individuals and as a reliable indirect measure of myosteatosis.

Sarcopenia, sarcopenic obesity, and arterial stiffness among older adults.

Background: Aging is associated with a higher prevalence of sarcopenia, sarcopenic obesity (SO), and increased arterial stiffening, with possible detrimental effects on morbidity and mortality. The aim of this study was to assess the relationships between sarcopenia, SO, and different indexes of arterial stiffness in older adults. Methods: A total of 77 hospitalized patients (mean age 78.68 ± 9.65 years) were evaluated, obtaining anthropometric variables, biochemical samples, handgrip test, and body composition assessment. Arterial stiffness was evaluated by measuring both carotid-femoral pulse wave velocity (cfPWV), a proxy for central stiffness, and cardio-ankle vascular index (CAVI), as well as considering peripheral arteries. The population was sorted into four subgroups: obese, sarcopenic, SO, and controls. Results: The highest CAVI (11.31 ± 2.58) was found in sarcopenic patients. SO had the highest value of cfPWV (15.18 ± 8.44 m/s), even after adjustment for significant covariates. In multiple regressions, SO diagnosis resulted as a significant predictor of cfPWV (p = 0.03, R2 = 0.20), and sarcopenia diagnosis resulted as a predictor of CAVI (p = 0.042, R2 = 0.12). Conclusions: In conclusion, a positive correlation is found between sarcopenia, SO, and arterial stiffness among older subjects. In particular, greater central arterial stiffness is associated with SO, outlining a remarkable effect on the cardiovascular risk profile.

Arterial stiffness and cardiovascular risk in patients with nephrolithiasis: a 10-year prospective study.

BACKGROUND: Nephrolithiasis is frequently associated with cardiovascular diseases. These conditions present common risk factors: systemic inflammation that promotes oxidative stress leading to arterial wall stiffening may also play a role in plaque formation predisposing to nephrolithiasis. OBJECTIVES: The aim of this study was to evaluate arterial stiffness indices at baseline and after a 10-year follow-up, in patients with nephrolithiasis compared with patients without. METHODS: A total of 82 patients (37 men; mean age 45 ±â€Š13 years) were enrolled at the Geriatrics and Nephrology Outpatient Clinic: 66 were diagnosed with nephrolithiasis, whereas the control group consisted of 16 individuals. At baseline and after 10 years, they underwent clinical evaluation and arterial stiffness measurement, such as carotid-femoral pulse wave velocity (CF-PWV), by arterial applanation tonometry. RESULTS: At baseline, when compared with the control group, patients with nephrolithiasis showed higher SBP and CF-PWV. After 10 years, patients with nephrolithiasis, but not those without, showed a significant raise in CF-PWV, even after adjustment for age and sex. In a stepwise regression model, with CF-PWV changes during the follow-up as the dependent variable, and age, sex, follow-up years, Δ mean arterial pressure, BMI, hypertension and nephrolithiasis as independent variables, nephrolithiasis was proved to be the only significant predictor of ΔCF-PWV, accounting for 6% of the variance. CONCLUSION: Our study shows higher baseline CF-PWV and greater increase in ΔCF-PWV within 10 years in individuals with nephrolithiasis than in those without, demonstrating an increased cardiovascular risk for nephrolithiasis patients.

Central and peripheral fat and subclinical vascular damage in older women.

OBJECTIVE: the aim of this study was to evaluate the relationship between fat distribution and arterial compliance in a group of elderly women, in particular to test a possible independent role of abdominal fat mass and peripheral fat mass on subclinical vascular damage, defined by a pulse wave velocity (PWV) >12 m/s. METHODS: in 96 women with age range 60-80 years (68.65 ± 4.98 years) and BMI range from 18.8 to 41.2 kg/m(2) (27.07 ± 4.61 kg/m(2)), we evaluated the body mass index, waist circumference, systolic and diastolic blood pressure, fasting glucose, cholesterol, LDL and HDL cholesterol, triglycerides and body composition by dual energy X-ray absorptiometry (DXA). Arterial stiffness was assessed by carotid-femoral (PWVcf) and carotid-radial pulse wave velocity (PWVcr). RESULTS: significant associations were found between PWVcf, age, waist circumference, BMI and trunk fat assessed by DXA, as well as TG and HDL cholesterol. After adjustment for the total fat mass a negative statistically significant association between PWVcf and leg fat mass was shown. In multiple regression analyses the mean arterial pressure, trunk fat mass and leg fat mass were significant predictors of vascular damage with OR, respectively, of 1.06 (CI: 1.01-1.11), 1.25 (CI: 1.06-1.48) and 0.73 (CI: 0.53-0.99). CONCLUSIONS: the results of this study show, in a sample of apparently healthy elderly women, that central and peripheral adiposity are independent predictors, with an opposite effect on subclinical vascular damage, confirming and strengthening the protective role of the gluteal-femoral fat on cardiovascular risk even in elderly.

Cardio-Ankle Vascular Index and Aging: Differences between CAVI and CAVI0.

BACKGROUND: Cardio-ankle vascular index (CAVI) and CAVI0 (a mathematical expression derived from CAVI, supposed to be less dependent on blood pressure), can describe arterial stiffness, considering a wide proportion of the arterial tree. The aim of this study was to examine the relationship between CAVI, CAVI0 and aging, looking at the differences between the two arterial stiffness indexes. METHODS: A total of 191 patients (68 male, mean age 68.3 ± 14.4 years) referred to the Geriatric Ward and Outpatient Clinic at Verona University Hospital were included and underwent a comprehensive clinical evaluation. CAVI and CAVI0 were obtained for each. RESULTS: CAVI0 steeply rises in the elderly age strata, widening the gap between CAVI and CAVI0. An inverse relationship is evident between CAVI0 and DBP in older patients, and CAVI0 is shown to be dependent on age, DBP and age-DBP interaction (R2 = 0.508). Age modifies the effect of DBP on CAVI0, but not on CAVI. CONCLUSIONS: The real new findings of our study are that the association between CAVI0 and diastolic blood pressure (DBP) is modified by age, whereas the association between CAVI and DBP is not modified by age. From a clinical point of view, these are very important findings, as DBP decreases with aging, affecting in elderly populations the reliability of CAVI0, which strictly depends on DBP in the formula to calculate it. To monitor the effect of CV therapies, progression of CV diseases and to evaluate clinical outcomes in elderly populations, we suggest using CAVI and not CAVI0.

Senescent adipocytes as potential effectors of muscle cells dysfunction: An in vitro model.

Recently, there has been a growing body of evidence showing a negative effect of the white adipose tissue (WAT) dysfunction on the skeletal muscle function and quality. However, little is known about the effects of senescent adipocytes on muscle cells. Therefore, to explore potential mechanisms involved in age-related loss of muscle mass and function, we performed an in vitro experiment using conditioned medium obtained from cultures of mature and aged 3 T3-L1 adipocytes, as well as from cultures of dysfunctional adipocytes exposed to oxidative stress or high insulin doses, to treat C2C12 myocytes. The results from morphological measures indicated a significant decrease in diameter and fusion index of myotubes after treatment with medium of aged or stressed adipocytes. Aged and stressed adipocytes presented different morphological characteristics as well as a different gene expression profile of proinflammatory cytokines and ROS production. In myocytes treated with different adipocytes' conditioned media, we demonstrated a significant reduction of gene expression of myogenic differentiation markers as well as a significant increase of genes involved in atrophy. Finally, a significant reduction in protein synthesis as well as a significant increase of myostatin was found in muscle cells treated with medium of aged or stressed adipocytes compared to controls. In conclusion, these preliminary results suggest that aged adipocytes could influence negatively trophism, function and regenerative capacity of myocytes by a paracrine network of signaling.

Correlation between epicardial adipose tissue and atrial fibrillation burden in coronary artery bypass graft surgery.

AIMS: Recent studies suggest an association between epicardial adipose tissue (EAT) and atrial fibrillation. The aim of the study is to evaluate the quantitative and qualitative characteristics of EAT in relation to atrial fibrillation burden after coronary artery bypass graft (CABG). METHODS: This prospective single-centre study included patients undergoing CABG. The patients underwent transthoracic echocardiography and collection of a bioptic sample containing right appendage and EAT during CABG for histological characterization. After surgery, clinical and telemetry data were collected. RESULTS: Fifty-six consecutive patients were enrolled. The mean postsurgical hospitalization was 7.9 ±â€Š3.7 days. Twenty-two patients had at least one episode of atrial fibrillation. In the atrial fibrillation group, there was a bigger atrial volume, a higher degree of diastolic disfunction, a thicker layer of EAT and an older median age in comparison with the group that did not develop it. EAT with a cut-off of 4 mm was a predictor of atrial fibrillation with an odds ratio (OR) of 1.49 (confidence interval (CI) 1.09-2.04), 73% of sensibility and 89% of specificity. From the histological analyses, the patients with atrial fibrillation had a significantly higher percentage of fibrosis. At univariate analysis, atrial volume [OR 1.05, CI 1.01-1.09, P = 0.022], E/A rate (OR 0.04, CI 0.02-0.72 P = 0.29), the percentage of fibrosis (OR 1.12, CI 1.00-1.25, P = 0.045) and age (OR 1.17, CI 1.07-1.28, P = 0.001) were predictors of atrial fibrillation. At multivariate analysis, atrial volume (P = 0.027), fibrosis (P = 0.003) and age (P = 0.039) were independent predictors of atrial fibrillation. CONCLUSION: Postcardiac surgical atrial fibrillation is frequent. EAT thickness, atrial volume, fibrosis and age are predictors of postcardiac surgical atrial fibrillation.

Arterial Stiffness, Subendocardial Impairment, and 30-Day Readmission in Heart Failure Older Patients.

Arterial stiffness and subendocardial perfusion impairment may play a significant role in heart failure (HF) outcomes. The aim of the study was to examine the main predictors of 30-day readmission in geriatric patients, hospitalized with HF, explore hemodynamical parameters, arterial stiffness indexes, and subendocardial viability ratio (SEVR). In total, 41 hospitalized patients, affected by HF, were included; they underwent clinical evaluation, routine laboratory testing, and echocardiography. At the time of admission, after the achievement of clinical stability (defined as switching from intravenous to oral diuretic therapy), and at discharge, arterial tonometry was performed to evaluate carotid-femoral pulse wave velocity (PWVcf) and SEVR (then corrected for hemoglobin concentration and oxygen saturation). Through the evaluations, a significant progressive decrease in PWVcf was described (17.79 ± 4.49, 13.54 ± 4.54, and 9.94 ± 3.73 m/s), even after adjustment for age, gender, mean arterial pressure (MAP) variation, and left ventricular ejection fraction (LVEF). A significant improvement was registered for both SEVR (83.48 ± 24.43, 97.94 ± 26.84, and 113.29 ± 38.02) and corrected SEVR (12.74 ± 4.69, 15.71 ± 5.30, and 18.55 ± 6.66) values, and it was still significant when adjusted for age, gender, MAP variation, and LVEF. After discharge, 26.8% of patients were readmitted within 30 days. In a multivariate binary logistic regression analysis, PWVcf at discharge was the only predictor of 30-day readmission (odds ratio [OR] 1.957, 95% CI 1.112-3.443). In conclusion, medical therapy seems to improve arterial stiffness and subendocardial perfusion in geriatric patients hospitalized with heart failure. Furthermore, PWVcf is a valid predictor of 30-day readmission. Its feasibility in clinical practice may provide an instrument to detect patients with HF at high risk of rehospitalization.

The Correlation of Arterial Stiffness Parameters with Aging and Comorbidity Burden.

The aim of the study was to evaluate the relationships between carotid-femoral pulse wave velocity (PVW-cf), cardio-ankle vascular index (CAVI) and CAVI0 (which is a mathematical elaboration of CAVI, theoretically less dependent on blood pressure), age and comorbidity burden. Furthermore, 183 patients (119 female, mean age 67.5 ± 14.3 years) referred to the Geriatric Ward and Outpatient Clinic at Verona University Hospital were included; demographic, clinical and blood analysis data were collected. Charlson Comorbidity Index (CCI), PVW-cf, CAVI and CAVI 0 were obtained. Significant correlations were found between CAVI, CAVI0, PVW-cf and both age (r = 0.698, r = 0.717, r = 0.410, respectively p < 0.001 for all) and CCI, (r = 0.654; r = 0.658; r = 0.448 respectively and p < 0.001 for all), still significant after adjustment for several variables. In a stepwise multiple regression model, considering several variables, CCI was the only predictor of PWV-cf, whereas age and CCI were significant predictors of both CAVI and CAVI 0. In conclusion, all arterial stiffness indexes are associated with CCI and aging; the latter correlation is more evident for CAVI and CAVI 0 than for PVW-cf. Arterial stiffness parameters can complement the characterization of patients affected by a remarkable comorbidity burden across aging; arterial stiffening might mirror the complexity of these individuals.

The Role of Obesity, Body Composition, and Nutrition in COVID-19 Pandemia: A Narrative Review.

The coronavirus disease 2019 (COVID-19) pandemic has spread worldwide, infecting nearly 500 million people, with more than 6 million deaths recorded globally. Obesity leads people to be more vulnerable, developing worse outcomes that can require hospitalization in intensive care units (ICU). This review focused on the available findings that investigated the link between COVID-19, body composition, and nutritional status. Most studies showed that not only body fat quantity but also its distribution seems to play a crucial role in COVID-19 severity. Compared to the body mass index (BMI), visceral adipose tissue and intrathoracic fat are better predictors of COVID-19 severity and indicate the need for hospitalization in ICU and invasive mechanical ventilation. High volumes of epicardial adipose tissue and its thickness can cause an infection located in the myocardial tissue, thereby enhancing severe COVID-related myocardial damage with impairments in coronary flow reserve and thromboembolism. Other important components such as sarcopenia and intermuscular fat augment the vulnerability in contracting COVID-19 and increase mortality, inflammation, and muscle damage. Malnutrition is prevalent in this population, but a lack of knowledge remains regarding the beneficial effects aimed at optimizing nutritional status to limit catabolism and preserve muscle mass. Finally, with the increase in patients recovering from COVID-19, evaluation and treatment in those with Long COVID syndrome may become highly relevant.

The Role of Crosstalk between Adipose Cells and Myocytes in the Pathogenesis of Sarcopenic Obesity in the Elderly.

As a result of aging, body composition changes, with a decline in muscle mass and an increase in adipose tissue (AT), which reallocates from subcutaneous to visceral depots and stores ectopically in the liver, heart and muscles. Furthermore, with aging, muscle and AT, both of which have recognized endocrine activity, become dysfunctional and contribute, in the case of positive energy balance, to the development of sarcopenic obesity (SO). SO is defined as the co-existence of excess adiposity and low muscle mass and function, and its prevalence increases with age. SO is strongly associated with greater morbidity and mortality. The pathogenesis of SO is complex and multifactorial. This review focuses mainly on the role of crosstalk between age-related dysfunctional adipose and muscle cells as one of the mechanisms leading to SO. A better understanding of this mechanisms may be useful for development of prevention strategies and treatments aimed at reducing the occurrence of SO.

Impaired subendocardial perfusion in patients with metabolic syndrome.

BACKGROUND: Metabolic Syndrome (MS) is associated to vascular damage, increased arterial stiffness, and impaired myocardial perfusion. Subendocardial viability ratio (SEVR) is a noninvasive estimation of myocardial workload, oxygen supply, and perfusion. The aim of the study was to describe the relation between arterial stiffness, SEVR, and cardio-metabolic risk factors. METHODS: A cohort of 55 patients, aged 59.9 ± 10.8 years, was studied; 28 subjects (50.9%) had metabolic syndrome. All patients underwent a clinical evaluation and blood venous sampling, to assess glico-lipid profile. Applanation tonometry was performed, to obtain pulse wave analysis and SEVR values. RESULTS: In the overall study population, SEVR showed negative associations with mean (r = -0.301; p = 0.026) and systolic (borderline relation, r = -0.257; p = 0.058) arterial pressure. Metabolic syndrome patients presented lower level of SEVR (p = 0.012), even after adjusting for age, sex, and mean arterial pressure (p = 0.040). Subdividing the study population by the number of metabolic syndrome components, SEVR significantly decreased as the number of Metabolic Syndrome components increased (p for trend 0.005). In a logistic backward regression analysis, both metabolic syndrome and mean arterial pressure resulted significant predictors of SEVR, accounting for 18% of variance. CONCLUSION: The reduced SEVR in metabolic syndrome patients could be an important pathophysiological determinant of the increased cardiovascular risk.

Relationships between subendocardial perfusion impairment, arterial stiffness and orthostatic hypotension in hospitalized elderly individuals.

BACKGROUND: Orthostatic hypotension is an independent risk factor for cardiovascular morbidity and mortality. Arterial stiffness has been shown to be a pathophysiological mechanism linking orthostatic hypotension and increased cardiovascular risk. This study aims to evaluate the relationship between arterial stiffness, orthostatic hypotension and subendocardial viability ratio (SEVR) and moreover to identify the main predictors of orthostatic hypotension, carotid-femoral pulse wave velocity (PWV-cf) and SEVR. METHODS: Seventy-five patients were enrolled (mean age 82.95 ±â€Š6.45) in Verona's AOUI Geriatric ward. They underwent blood pressure, heart rate, body weight measurements and also comorbidity, arterial stiffness (PWV-cf measured by applanation tonometry), SEVR and biochemical indexes. RESULTS: Prevalence of orthostatic hypotension was 46.6%. Even after adjustment for age, sex, glomerular filtration rate and mean arterial pressure, SEVR values corrected for arterial oxygen and haemoglobin content were statistically lower in orthostatic hypotension patients (P = 0.05) and PWV-cf values were statistically higher in orthostatic hypotension individuals (P = 0.042). In a binary logistic regression, PWV-cf was the only significant predictor of orthostatic hypotension (odds ratio 1.123; P = 0.039; confidence interval = 1.006--1.17).In a backward logistic regression model sex, creatinine clearance and orthostatic hypotension were significant predictors of SEVR corrected for O2 content. Mean arterial pressure, creatinine clearance and orthostatic hypotension were significant predictors of PWV-cf. CONCLUSION: This study shows that orthostatic hypotension is related to increased arterial stiffness, confirming its higher prevalence in elderly patients. Orthostatic hypotension was also associated with reduced values of corrected SEVR, showing a relevant consequence of orthostatic hypotension on subendocardial perfusion impairment.

Disability assessment in an Italian cohort of patients with obesity using an International Classification of Functioning, Disability and Health (ICF)-derived questionnaire.

BACKGROUND: Obesity is a clinical condition that contributes to the development of related disability in different areas (physical, psychological and social). Multidisciplinary treatment calls for specific instruments able to evaluate all related functional problems. We have developed a tool (an ICF-based assessment instrument, the ICF-OB schedule) to evaluate obesity-related disability, composed of an inventory of 71-items from the WHO International Classification of Functioning, Disability and Health (ICF). AIM: The aim of the present study was to validate this new tool for the definition of obesity-related disability. We also sought to examine the relationship between obesity disability, an index of multimorbidity (Cumulative Illness Rating Scale [CIRS]) and a well-validated score of perceived obesity-related disability (Italian Obesity Society Test for Obesity-Related Disability [TSD-OC]). DESIGN: Process validation of the ICF-OB schedule. SETTING: Baseline conditions of out- and in-patients. POPULATION: A large cohort of obese patients recruited from 9 multidisciplinary centers belonging to the Italian Obesity Society (SIO) network, which provide specialized obesity care. METHODS: A total of 353 patients (F: 70%, age: 50.2±12.7yrs, BMI: 41.4±8.3kg/m2) were enrolled between January 2017 and June 2018. The ICF-OB was used to define patients' functioning and disability profiles in order to set and appraise rehabilitation goals. RESULTS: We described the distribution of body functions (BF), body structures (BS) and activities and participations (A&P) categories and the agreement rates were significant for the majority of these. The ICF-OB was more often significantly associated, and with stronger coefficients, with patients' comorbidities as described by the CIRS rather than with Body Mass Index (BMI). The TSD-OC also presented a strong association with A&P indexes. CONCLUSIONS: The complexity of clinical condition, that generates disability in obesity might be well identified with the use of this new instrument that appear significant related to the perceived disability for each patients and also with their multimorbidity. CLINICAL REHABILITATION IMPACT: The ICF-OB shows great promise as a tool for goal setting in the rehabilitation of obese patients.

Adipokines and Arterial Stiffness in the Elderly.

INTRODUCTION: The aim of this study was to evaluate the relationship between adipokines and arterial stiffness in a group of 85 elderly subjects and the role of leptin and adiponectin on subclinical vascular damage, defined by a PWV>10 m/s. METHODS: In each subject, we evaluated anthropometry, body composition by DXA (fat mass, fat mass%, lean mass), metabolic variables, leptin, adiponectin, systolic, diastolic, mean arterial pressure and pulse pressure (SBP, DBP, MAP, PP), carotid-femoral pulse wave velocity (cfPWV) and carotid-radial pulse wave velocity (crPWV). RESULTS: In the study population, significant associations were observed between cfPWV and crPWV, age, SBP, MAP, waist circumference, fat body mass and leptin. The study population was subdivided in 2 subgroups according to adipokine patterns: group 1 included patients with high adiponectin and low leptin, and group 2 patients had high leptin and low adiponectin. SBP, PP, cfPWV were significantly higher in subjects with high leptin and low adiponectin (group 2). Even after adjustment for gender, fat mass%, MAP, HDL cholesterol and triglycerides, cfPWV was higher in group 2 than group 1. In a logistic binary regression on the entire population, considering subclinical vascular damage as a dependent variable and age, gender, MAP, fat mass%, triglycerides, HDL cholesterol and category of subjects with high leptin and low adiponectin as independent variables, MAP and category of subjects with high leptin and low adiponectin were significant predictors (OR, respectively, 1.09 and 3.61). CONCLUSION: In conclusion, in the elderly, the presence at the same time of high leptin levels and low adiponectin levels seems to have synergic effects on arterial stiffness.

Worsening Disability and Hospitalization Risk in Sarcopenic Obese and Dynapenic Abdominal Obese: A 5.5 Years Follow-Up Study in Elderly Men and Women.

Background/Objectives: A general lack of studies comparing the effect of both dynapenic abdominal obesity and sarcopenic obesity on worsening disability and hospitalization risk should be recognized. The aim of the current study was to evaluate, with a 5.5-year follow-up, the prognostic value of sarcopenic obesity and dynapenic abdominal obesity definitions on worsening disability and hospitalization risk in a sample of older adults. Subjects/Methods: In 177 women and 97 men aged 68-78 years, the following outcomes were evaluated at baseline: appendicular skeletal muscle mass (ASMM), percent fat mass (FM%), leg isometric strength, body mass index (BMI), lipid profile, vitamin D3, albumin, fibrinogen, glycemia, physical activity level, income, smoking status, and comorbidities. The rate of reported disabilities and hospitalization were also assessed at baseline, 1, 2, 3, and 5.5-years follow-up. The study population was classified into: (i) non-sarcopenic/obese (NS/O), sarcopenic/non-obese (S/NO), sarcopenic/obese (S/O), non-sarcopenic/non-obese (NS/NO, reference category) according to relative ASMM/FM% tertiles; (ii) non-dynapenic/abdominal obese (ND/AO), dynapenic/non-abdominal obese (D/NAO), dynapenic/abdominal obese (D/AO), non-dynapenic/non-abdominal obese (ND/NAO, reference category) according to muscle strength/waist circumference tertiles. Results: The prevalence of D/AO and S/O was 12.0 and 8.0%, respectively. Only 2 subjects were both D/NAO and S/O (0.8%). D/NAO subjects showed a worsening disability risk of 1.69 times (95% CI: 1.11-2.57), ND/AO subjects showed a 2-fold increased risk (95% CI: 1.34-2.98), while being D/AO more than trebled the risk, even after adjustment for confounding factors (HR: 3.39, 95%; CI: 1.91-6.02). By dividing the study population according to the relative ASMM/FM% tertiles, no groups showed an increased risk of worsening disability. The hospitalization risk, even after adjustment for potential confounders, was 1.84 (95% CI: 1.06-3.19) for D/AO. Dividing the study population according to the relative ASMM/FM% tertiles, no groups showed increased risk of hospitalization. Conclusions: Our results showed that dynapenic abdominal obesity and sarcopenic obesity seem to indicate two distinct phenotypes associated with different health risk profiles. The distribution of participants in waist circumference and muscle strength tertiles allowed for a more accurate risk stratification for worsening disability and hospitalization.

Weight Loss and Hypertension in Obese Subjects.

Arterial hypertension is strongly related to overweight and obesity. In obese subjects, several mechanisms may lead to hypertension such as insulin and leptin resistance, perivascular adipose tissue dysfunction, renal impairment, renin-angiotensin-aldosterone-system activation and sympathetic nervous system activity. Weight loss (WL) seems to have positive effects on blood pressure (BP). The aim of this review was to explain the mechanisms linking obesity and hypertension and to evaluate the main studies assessing the effect of WL on BP. We analysed studies published in the last 10 years (13 studies either interventional or observational) showing the effect of WL on BP. Different WL strategies were taken into account-diet and lifestyle modification, pharmacological intervention and bariatric surgery. Although a positive effect of WL could be identified in each study, the main difference seems to be the magnitude and the durability of BP reduction over time. Nevertheless, further follow-up data are needed: there is still a lack of evidence about long term effects of WL on hypertension. Hence, given the significant results obtained in several recent studies, weight management should always be pursued in obese patients with hypertension.