Do ACE inhibitors improve the response to exercise training in functionally impaired older adults? A randomized controlled trial

<br>Background: Loss of muscle mass and strength with ageing is a major cause for falls, disability, and morbidity in older people. Previous studies have found that angiotensin-converting enzyme inhibitors (ACEi) may improve physical function in older people. It is unclear whether ACEi provide additional benefit when added to a standard exercise training program. We examined the effects of ACEi therapy on physical function in older people undergoing exercise training.</br> <b>Methods:</b> Community-dwelling people aged ≥65 years with functional impairment were recruited through general (family) practices. All participants received progressive exercise training. Participants were randomized to receive either 4 mg perindopril or matching placebo daily for 20 weeks. The primary outcome was between-group change in 6-minute walk distance from baseline to 20 weeks. Secondary outcomes included changes in Short Physical Performance Battery, handgrip and quadriceps strength, self-reported quality of life using the EQ-5D, and functional impairment measured using the Functional Limitations Profile.<p></p> <b>Results:</b> A total of 170 participants (n = 86 perindopril, n = 84 placebo) were randomized. Mean age was 75.7 (standard deviation [SD] 6.8) years. Baseline 6-minute walk distance was 306 m (SD 99). Both groups increased their walk distance (by 29.6 m perindopril, 36.4 m placebo group) at 20 weeks, but there was no statistically significant treatment effect between groups (−8.6m [95% confidence interval: −30.1, 12.9], p = .43). No statistically significant treatment effects were observed between groups for the secondary outcomes. Adverse events leading to withdrawal were few (n = 0 perindopril, n = 4 placebo).<p></p> <b>Interpretation:</b> ACE inhibitors did not enhance the effect of exercise training on physical function in functionally impaired older people.<p></p&gt

Acceptability and feasibility of magnetic femoral nerve stimulation in older, functionally impaired patients

Abstract Objective Magnetic femoral nerve stimulation to test muscle function has been largely unexplored in older people. We assessed acceptability, feasibility, along with reproducibility and correlation with other physical function measures. Results Study 1 recruited older people with sarcopenia. Stimulation was performed at baseline and 2 weeks along with six minute walk (6MW), maximum voluntary quadriceps contraction, short physical performance battery and grip strength. Acceptability was measured using visual analog scales. Study 2 used baseline data from a trial of older people. We correlated stimulation results with 6MW, maximal voluntary contraction and muscle mass. Maximum quadriceps twitch tension was measured in both studies, evoked using biphasic magnetic stimulation of the femoral nerve. In study 1 (n = 12), magnetic stimulation was well tolerated with mean discomfort rating of 9% (range 0–40%) on a visual analog scale. Reproducibility was poor (intraclass correlation coefficient 0.06; p = 0.44). Study 2 (n = 64) showed only weak to moderate correlations for maximum quadriceps twitch tension with other measures of physical function (6 minute walk test r = 0.24, p = 0.06; maximal voluntary contraction r = 0.26; p = 0.04). We conclude that magnetic femoral nerve stimulation is acceptable and feasible but poorly reproducible in older, functionally impaired people

Effect of Angiotensin System Inhibitors on Physical Performance in Older People - A Systematic Review and Meta-Analysis

Objective: Preclinical and observational data suggest that angiotensin converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARBs) may be able to improve physical performance in older people via direct and indirect effects on skeletal muscle. We aimed to summarize current evidence from randomised controlled trials in this area. Design: Systematic review and meta-analysis. Setting and Participants: Randomized controlled trials enrolling older people, comparing ACEi or ARB to placebo, usual care or another antihypertensive agent, with outcome data on measures of physical performance. Methods: We searched multiple electronic databases without language restriction between inception and the end of February 2020. Trials were excluded if the mean age of participants was <65 years or treatment was targeting specific diseases known to affect muscle function (for example heart failure). Data were sought on measures of endurance and strength. Standardized mean difference (SMD) treatment effects were calculated using random-effects models with RevMan software. Results: Eight trials (952 participants) were included. Six trials tested ACEi, 2 trials tested ARBs. The mean age of participants ranged from 66 to 79 years, and the duration of treatment ranged from 2 months to 1 year. Trials recruited healthy older people and people with functional impairment; no trials specifically targeted older people with sarcopenia. Risk of bias for all trials was low to moderate. No significant effect was seen on endurance outcomes [6 trials, SMD 0.04 (95% CI –0.22 to 0.29); P =.77; I2 = 53%], strength outcomes [6 trials, SMD –0.02 (95% CI –0.18 to 0.14), P =.83, I2 = 21%] or the short physical performance battery [3 trials, SMD –0.04 (95% CI –0.19 to 0.11), P =.60, I2 = 0%]. No evidence of publication bias was evident on inspection of funnel plots. Conclusions and Implications: Existing evidence does not support the use of ACE inhibitors or angiotensin receptor blockers as a single intervention to improve physical performance in older people

Social, environmental and psychological factors associated with objective physical activity levels in the over 65s

Objective: To assess physical activity levels objectively using accelerometers in community dwelling over 65 s and to examine associations with health, social, environmental and psychological factors. Design: Cross sectional survey. Setting: 17 general practices in Scotland, United Kingdom. Participants: Random sampling of over 65 s registered with the practices in four strata young-old (65–80 years), old-old (over 80 years), more affluent and less affluent groups. Main Outcome Measures: Accelerometry counts of activity per day. Associations between activity and Theory of Planned Behaviour variables, the physical environment, health, wellbeing and demographic variables were examined with multiple regression analysis and multilevel modelling. Results: 547 older people (mean (SD) age 79(8) years, 54% female) were analysed representing 94% of those surveyed. Accelerometry counts were highest in the affluent younger group, followed by the deprived younger group, with lowest levels in the deprived over 80 s group. Multiple regression analysis showed that lower age, higher perceived behavioural control, the physical function subscale of SF-36, and having someone nearby to turn to were all independently associated with higher physical activity levels (R2 = 0.32). In addition, hours of sunshine were independently significantly associated with greater physical activity in a multilevel model. Conclusions: Other than age and hours of sunlight, the variables identified are modifiable, and provide a strong basis for the future development of novel multidimensional interventions aimed at increasing activity participation in later life.Publisher PDFPeer reviewe

Leucine and ACE inhibitors as therapies for sarcopenia (LACE trial): study protocol for a randomised controlled trial

Background: Sarcopenia (the age-related loss of muscle mass and function) is a major contributor to loss of mobility, falls, loss of independence, morbidity and mortality in older people. Although resistance training is effective in preventing and reversing sarcopenia, many older people are sedentary and either cannot or do not want to exercise. This trial examines the efficacy of supplementation with the amino acid leucine and/or angiotensin converting enzyme inhibition to potentially improve muscle mass and function in people with sarcopenia. Promising preliminary data exist from small studies for both interventions, but neither has yet been tested in adequately powered randomised trials in patients with sarcopenia. Methods: Leucine and ACE inhibitors in sarcopenia (LACE) is a multicentre, masked, placebo-controlled, 2 × 2 factorial randomised trial evaluating the efficacy of leucine and perindopril (angiotensin converting enzyme inhibitor (ACEi)) in patients with sarcopenia. The trial will recruit 440 patients from primary and secondary care services across the UK. Male and female patients aged 70 years and over with sarcopenia as defined by the European Working Group on Sarcopenia (based on low total skeletal muscle mass on bioimpedance analysis and either low gait speed or low handgrip strength) will be eligible for participation. Participants will be excluded if they have a contraindication to, or are already taking, an ACEi, angiotensin receptor blocker or leucine. The primary clinical outcome for the trial is the between-group difference in the Short Physical Performance Battery score at all points between baseline and 12 months. Secondary outcomes include appendicular muscle mass measured using dual-energy X-ray absorptiometry, muscle strength, activities of daily living, quality of life, activity using pedometer step counts and falls. Participants, clinical teams, outcomes assessors and trial analysts are masked to treatment allocation. A panel of biomarkers including microRNAs, neurohormones, genetic polymorphisms and markers of inflammation relevant to muscle pathophysiology will be measured to explore predictors of response and further elucidate mechanisms underlying sarcopenia. Participants will receive a total of 12 months of either perindopril or placebo and either leucine or placebo. Discussion: The results will provide the first robust test of the overall clinical and cost-effectiveness of these novel therapies for older patients with sarcopenia. Trial registration: ISRCTN, ISRCTN90094835. Registered on 18 February 2015

Spironolactone for People Age 70 Years and Older With Osteoarthritic Knee Pain:A Proof‐of‐Concept Trial

Objective: To determine whether spironolactone could benefit older people with osteoarthritis (OA), based on a previous study showing that spironolactone improved quality of life. Methods: This parallel-group, randomized, placebo-controlled, double-blind trial randomized community-dwelling people ages ≥70 years with symptomatic knee OA to 12 weeks of 25 mg daily oral spironolactone or matching placebo. The primary outcome was between-group difference in change in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain subscale scores. Secondary outcomes included WOMAC stiffness and physical function subscores, EuroQol 5-domain (EQ-5D) 3L score, and mechanistic markers. Analysis was by intent to treat, using mixed-model regression, adjusting for baseline values of test variables. Results: A total of 421 people had eligibility assessed, and 86 were randomized. Mean ± SD age was 77 ± 5 years and 53 of 86 (62%) were women. Adherence to study medication was 99%, and all participants completed the 12-week assessment. No significant improvement was seen in the WOMAC pain score (adjusted treatment effect 0.5 points [95% confidence interval (95% CI) - 0.3, 1.3]; P = 0.19). No improvement was seen in WOMAC stiffness score (0.2 points [95% CI -0.6, 1.1]; P = 0.58), WOMAC physical function score (0.0 points [95% CI -0.7, 0.8]; P = 0.98), or EQ-5D 3L score (0.04 points [95% CI -0.04, 0.12]; P = 0.34). Cortisol, matrix metalloproteinase 3, and urinary C-telopeptide of type II collagen were not significantly different between groups. More minor adverse events were noted in the spironolactone group (47 versus 32), but no increase in death or hospitalization was evident. Conclusion: Spironolactone did not improve symptoms, physical function, or health-related quality of life in older people with knee OA

Associations between frailty, physical performance, and renal biomarkers in older people with advanced chronic kidney disease

Acknowledgments With thanks to the recruiting teams and participants who took part in the BiCARB trial. GS and MDW acknowledge support from the NIHR Newcastle Biomedical Research CentrePeer reviewedPublisher PD