Objectives
To investigate the correlation between sarcopenia and arterial stiffness in Caucasians, centering on the relationship between skeletal mass index (SMI) and the cardio‐ankle vascular index ...(CAVI) to assess the use of CAVI in predicting sarcopenia.
Design Cross‐sectional Setting
United Kingdom.
Participants
UK adults aged 45 years and over (N = 366, n = 177 male, n = 189 female).
Measurements
Bioimpedance analysis was used to derive SMI. CAVI score was calculated using a vascular screening system. Handgrip strength was measured using a standard dynamometer.
Results
Average CAVI was significantly correlated with SMI (correlation coefficient (r) = −0.285, p < .001), with higher correlation in women (r = −0.416, p < .001) than men (r = −0.214, p = .01). CAVI had the highest correlation with SMI from appendicular muscle (fat‐free mass in men, r = −0.253, p = .002; predicted muscle mass in women, r = −0.436, p < .001). There was a significant difference in average CAVI between groups, with participants who were not sarcopenic having lower CAVI (8.98) than those who were sarcopenic (9.80) (p < .001, t‐test). Linear regression was performed using SMI as the dependent variable. After adjustment for age, average CAVI was a significant predictor of SMI in women (beta = −0.332, p < .001) but not men.
Conclusion
Indices of sarcopenia are independently associated with a higher CAVI, with greater correlation in women than men. The CAVI can be used to assess overall vascular compliance and may be a useful operator‐independent tool that can be used to measure sarcopenia and its cardiovascular implications in older adults. J Am Geriatr Soc 67:317–322, 2019.
Recent evidence suggests that nutritional interventions may improve muscle outcomes in malnutrition and sarcopenia.
We evaluated the effects of 2 high-quality oral nutritional supplements (ONS) ...differing in amount and type of key nutrients in older adult men and women.
A multicenter, randomized, double-blinded, controlled clinical trial.
Malnourished and sarcopenic men and women, 65 years and older (n = 330).
A 24-week intervention period with 2 energy-rich (330 kcal) ONS treatment groups: Control ONS (CONS, 14 g protein; 147 IU vitamin D3) versus Experimental ONS (EONS, 20 g protein; 499 IU vitamin D3; 1.5 g CaHMB) taken twice daily. Both ONS also contained other vitamins, minerals, and nutrients in varying amounts.
Isokinetic peak torque (PT, Nm) leg strength, grip strength (kg), and gait speed (m·s−1) were assessed at baseline and 12 and 24 weeks. Left and right leg muscle mass (LMM, kg) were assessed by dual-energy x-ray absorptiometry (DXA). Muscle quality (MQ) was leg strength expressed relative to the tested LMM (Nm·kg−1). Subgroup analyses were performed: severe sarcopenia (low skeletal mass index, low grip strength <30 kg men; <20 kg women, low gait speed <0.8 m·s−1) and mild-moderate sarcopenia (low skeletal mass index, normal gait speed, or normal grip strength).
Both ONS groups (EONS and CONS) improved PT, MQ, grip strength, and gait speed from baseline with no treatment differences. Those with severe sarcopenia (44%) exhibited lower baseline PT and MQ, with no differences in strength improvements between treatments. However, participants with mild-moderate sarcopenia exhibited higher baseline PT and MQ, with differences in strength improvements at 12 weeks (EONS > CONS, P = .032) in those with normal grip strength. There were no treatment differences based on sarcopenic severity for either grip strength or gait speed.
ONS improved strength outcomes in malnourished older adults with sarcopenia. In those with mild-moderate sarcopenia, but not severe sarcopenia, consumption of the EONS improved leg muscle strength and quality compared with the standard CONS.
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.
Muscular fatigue and injury are frequently observed in critically ill COVID-19 patients. The aim of this study was to determine whether different muscle adipose tissue depots are associated with ...mortality and muscle damage in patients affected by COVID-19 admitted to the ICU.
CT images were obtained in 153 ICU patients with COVID-19 (121 males and 32 females). Height, weight, body mass index (BMI), C-reactive protein, Creatine PhosphoKinase (CPK), muscle density, and intermuscular adipose tissue (IMAT) were measured.
Participants in the highest tertile of IMAT/muscle had the shorter 28-day survival from ICU admission as compared to subjects in the first tertile. Estimates derived from the Cox proportional hazard models, after adjustment for age, sex, and BMI, confirmed the results of the survival analysis (HR 3.94, 95% CI: 1.03-15.09). Participants in the lowest tertile of muscle density had the shorter survival at 28 days from ICU admission as compared to subjects in the highest tertile (HR 3.27, 95% CI: 1.18-4.61), but the relationship was no longer significant when age was included in the model. Subjects in the second muscle density tertile did not show an increased risk.Participants in the highest tertile of IMAT/muscle and those in the lowest tertile of muscle density showed both significantly higher CPK adjusted for weight values as evaluated during the first 8 days of hospitalization.
Our data seem to suggest that higher levels of IMAT/muscle and low muscle density are both associated with higher risk of ICU mortality and muscle injury as evaluated with CPK level.
The aim of the present study was to determine the relationship between body fat distribution, adipocytokines, inflammatory markers, fat intake and ectopic fat content of liver and pancreas in obese ...men and women. A total of 12 lean subjects (mean age 47.25 ± 14.88 years and mean BMI 22.85 ± 2), 38 obese subjects (18 men and 20 women) with mean age 49.1 ± 13.0 years and mean BMI 34.96 ± 4.21 kg/m2 were studied. Measurements: weight, height, BMI, waist circumference, as well as glucose, insulin, HOMA (homeostasis model assessment of insulin resistance), cholesterol, triglycerides, high‐density lipoprotein cholesterol, high sensitivity C‐reactive protein, daily energy intake, leptin, and adiponectin. Magnetic resonance was used to evaluate visceral, subcutaneous adipose tissue (SCAT) as well as liver and pancreas lipid content using in‐phase and out‐of‐phase magnetic resonance imaging (MRI) sequence. Obese subjects had significantly higher weight, waist circumference, SCAT, deep SCAT, visceral adipose tissue (VAT), liver and pancreatic lipid content than lean subjects. Obese women had significantly lower VAT, liver and pancreas lipid content regardless of same BMI. In multiple regression analyses, the variance of liver lipid content explained by gender and VAT was 46%. When HOMA was added into a multiple regression, a small increase in the proportion of variance explained was observed. A 59.2% of the variance of pancreas lipid content was explained by gender and VAT. In conclusion, obese men show higher VAT and ectopic fat deposition in liver and pancreas than obese women despite same BMI. Independent of overall adiposity, insulin resistance, adiponectin and fat intake, VAT, measured with MRI, is the main predictor of ectopic fat deposition in both liver and pancreas.
A significant epidemiological association between obesity and pancreatic ductal adenocarcinoma (PDAC) has previously been described, as well as a correlation between the degree of pancreatic ...steatosis, PDAC risk and prognosis. The underlying mechanisms are still not completely known.After co-culture of 3T3-L1 adipocytes and MiaPaCa2 with an in vitro transwell system we observed the appearance of fibroblast-like cells, along with a decrease in number and size of remaining adipocytes. RT-PCR analyses of 3T3-L1 adipocytes in co-culture showed a decrease in gene expression of typical markers of mature adipocytes, in parallel with an increased expression of fibroblast-specific and reprogramming genes. We found an increased WNT5a gene and protein expression early in MiaPaCa2 cells in co-culture. Additionally, EMSA of c-Jun and AP1 in 3T3-L1 demonstrated an increased activation in adipocytes after co-culture. Treatment with WNT5a neutralizing antibody completely reverted the activation of c-Jun and AP1 observed in co-cultured adipocytes.Increasing doses of recombinant SFRP-5, a competitive inhibitor for WNT5a receptor, added to the co-culture medium, were able to block the dedifferentiation of adipocytes in co-culture.These data support a WNT5a-mediated dedifferentiation process with adipocytes reprogramming toward fibroblast-like cells that might profoundly influence cancer microenvironment.
Summary There are relatively few prospective studies evaluating the combined effect of abdominal obesity and low muscle strength on worsening disability and on mortality. The study aimed at ...evaluating prospectively the prognostic value of dynapenic abdominal obesity definition on disability worsening in a 5.5-year follow-up and mortality in a 10-year follow-up. Methods In 93 men and 169 women aged between 66 and 78 years, leg isometric strength, waist circumference (WC), BMI, glycemia, HOMA, lipid profile, vitamin D3, albumin, fibrinogen, physical activity level, income, smoking status and comorbidities were evaluated at the baseline. Reported disabilities were measured at baseline, 1-y, 2-y, 3-y and 5.5-y follow-up and mortality rate was evaluated during a 10-y follow-up. The study population was categorized in dynapenic abdominal obese (D/AO), nondynapenic abdominal obese (ND/AO), dynapenic nonabdominal obese (D/NAO), nondynapenic nonabdominal obese (ND/NAO) according to muscle strength/WC tertiles. Results D/NAO subjects presented a disability worsening risk of 1.69 times (95%CI:1.11–2.57), ND/AO subjects showed a 2-fold increase in risk (95%CI:1.34–2.98), while being D/AO more than trebled the risk, even after considering confounding variables (HR:3.39,95%CI:1.91–6.02). Mortality risk after adjustment for other confounding variables was 1.57 (95%CI:1.16–2.13) for ND/AO and 2.46 (95%CI:1.34–4.52) for D/AO. Conclusions Dynapenic abdominal obese subjects are at higher risk of worsening disability and mortality than subjects with dynapenia or central fat distribution only.
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.
Decreases in whole-body lean mass can cause sarcopenia, a disease frequently found in the elderly. This condition is frequently associated with frailty and disability in aging as well as the onset ...and progression of several geriatric syndromes. Sarcopenia therefore must be managed with multidimensional approaches that include physical training, nutritional support, and metabolic and anabolic treatment. The purpose of our study was to assess the effect of an orally administered special mixture of amino acids (AAs) in elderly subjects with reduced lean body mass and sarcopenia. A randomized, open-label, crossover study was conducted in 41 elderly subjects (age range: 66–84 years) with sarcopenia, assigned to 2 distinct treatments (AAs and placebo). All subjects had normal body weight (body mass index within 19–23). The AA treatment consisted of 70.6 kcal/day (1 kcal = 4.2 kJ) of 8 g of essential AA snacks, given at 10:00 am and 5:00 pm . Lean mass was measured with dual-energy x-ray absorptiometry in leg, arm, and trunk tissues. Significant increases in whole-body lean mass in all areas were seen after 6 months and more consistently after 18 months of oral nutritional supplementation with AAs. Fasting blood glucose, serum insulin, and homeostatic model assessment of insulin resistance (an index of insulin resistance) significantly decreased during AA treatment. Furthermore, a significant reduction in serum tumor necrosis factor–α (TNF-α) and a significant increase in both insulin-like growth factor–1 (IGF-1) serum concentrations and in the IGF-1/TNF-α ratio were also found. No significant adverse effects were observed during AA treatment. These preliminary data indicate that nutritional supplements with the oral AA mixture significantly increased whole-body lean mass in elderly subjects with sarcopenia. The improvement in the amount of whole-body lean mass could be linked to increased insulin sensitivity and anabolic conditions related to IGF-1 availability.
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