Deepa Sumukadas

Effect of perindopril on physical function in elderly people with functional impairment: a randomized controlled trial

Background: Physical function and exercise capacity decline with age and are a major source of disability in older people. Recent evidence suggests a potential role for the renin–angiotensin system in modulating muscle function. We sought to examine the effect of the angiotensin-converting-enzyme (ACE) inhibitor perindopril on physical function in elderly people with functional impairment who had no heart failure or left ventricular systolic dysfunction. Methods: In this double-blind randomized controlled trial, participants aged 65 years and older who had problems with mobility or functional impairment were randomly assigned to receive either perindopril or placebo for 20 weeks. The primary outcome was the change in the 6-minute walking distance over the 20 weeks. Secondary outcomes were changes in muscle function, daily activity levels, self-reported function and health-related quality of life. Results: A total of 130 participants were enrolled in the study (mean age 78.7, standard deviation 7.7 years); 95 completed the trial. At 20 weeks, the mean 6-minute walking distance was significantly improved in the perindopril group relative to the placebo group (mean between-group difference 31.4 m, 95% confidence interval [CI] 10.8 to 51.9 m; p = 0.003). There was a significant impact on health-related quality of life: although the mean score for part 1 of the EQ-5D questionnaire deteriorated over time in the placebo group, quality of life was maintained in the perindopril group, for a between-group difference of 0.09 (p = 0.046). There were no significant differences between the 2 groups in the other outcomes. Interpretation: Use of the ACE inhibitor perindopril improved exercise capacity in functionally impaired elderly people who had no heart failure and maintained health-related quality of life. The degree of improvement was equivalent to that reported after 6 months of exercise training. (International Standard Randomised Controlled Trial Register no. ISRCTN67679521).

Optimal management of sarcopenia

Sarcopenia is the progressive generalized loss of skeletal muscle mass, strength, and function which occurs as a consequence of aging. With a growing older population, there has been great interest in developing approaches to counteract the effects of sarcopenia, and thereby reduce the age-related decline and disability. This paper reviews (1) the mechanisms of sarcopenia, (2) the diagnosis of sarcopenia, and (3) the potential interventions for sarcopenia. Multiple factors appear to be involved in the development of sarcopenia including the loss of muscle mass and muscle fibers, increased inflammation, altered hormonal levels, poor nutritional status, and altered renin–angiotensin system. The lack of diagnostic criteria to identify patients with sarcopenia hinders potential management options. To date, pharmacological interventions have shown limited efficacy in counteracting the effects of sarcopenia. Recent evidence has shown benefits with angiotensin-converting enzyme inhibitors; however, further randomized controlled trials are required. Resistance training remains the most effective intervention for sarcopenia; however, older people maybe unable or unwilling to embark on strenuous exercise training programs.

Day length and weather conditions profoundly affect physical activity levels in older functionally impaired people

Background: Regular physical activity is vital for maintaining the health and independence of older people. Few objective data exist on the effect of weather on physical activity levels in this group. The objective of this study was to evaluate the effect of weather using an objective measure of physical activity. Methods: This was a retrospective study of 127 participants, >65 years old, who were enrolled in a previous randomised controlled trial. The main outcome was daily activity counts measured using the RT3 triaxial accelerometer over 1-week periods. These were correlated with local weather data including daily maximum temperature, sunshine, precipitation and wind speed that were obtained from the metrological office. Results: The mean age of the subjects was 78.6 years; 90/127 were female; and 720 usable daily counts were obtained for the 127 participants. The mean daily counts showed a striking seasonal variation, with maximum activity in June and minimum in February (137 557 vs 65 010 counts per day, p<0.001). Day length, mean maximum temperature and mean daily sunshine were able to explain 72.9% of the monthly variance in daily activity levels. Daily counts showed moderate correlation with day length (r = 0.358, p<0.001), maximum temperature (r = 0.345, p<0.001), duration of sunshine (r = 0.313, p<0.001) and rain (r = −0.098, p = 0.008) but not with wind speed (r = 0.093, p = 0.12). Multivariate analysis showed that day length, sunshine duration and maximum temperature were independent predictors of daily activity (adjusted R2 = 0.16). Conclusions: Physical activity levels among older people are much higher in summer than in winter. Day length, sunshine duration and maximum temperature have a significant influence on physical activity levels.

Temporal trends in anticholinergic medication prescription in older people: repeated cross-sectional analysis of population prescribing data

BACKGROUND in older people, medications with anticholinergic (antimuscarinic) effects are associated with adverse clinical outcomes, the risk increasing with increasing anticholinergic exposure. Many anticholinergics are recognised as potentially inappropriate and efforts to reduce prescription have been ongoing. We examined temporal trends of anticholinergic prescription and exposure in older people. METHODS : anonymised data on all prescribed medication dispensed to people ≥65 years in Tayside, Scotland were obtained for the years 1995 (n = 67,608) and 2010 (n = 73,465). The Anticholinergic Risk Scale (ARS) was adapted (mARS) to include newer medications and medications identified in other scales as having moderate to strong anticholinergic activity. An individuals mARS score was the sum of scores for individual medications. Differences in prescription of anticholinergic medications and mARS scores between 1995 and 2010 were examined. RESULTS : a significantly higher proportion of older people received any anticholinergic medication in 2010 compared with 1995 (23.7 versus 20.7%; P < 0.001). High anticholinergic exposure (mARS scores ≥3) was seen in 7.3% in 1995 and 9.9% in 2010 (P < 0.001). Prescription of individual anticholinergic medication was small-only three medications were prescribed to >2% of people. The risk of high anticholinergic exposure increased in those with polypharmacy, social deprivation, those living in care homes and women. CONCLUSION : despite increasing evidence of adverse outcomes, the proportion of older people prescribed anticholinergic medications and the proportion with a high anticholinergic exposure has increased between 1995 and 2010. Prescription of individual drug is small so cumulative anticholinergic scores may help future efforts to reduce anticholinergic prescription in older people.

Sarcopenia – A Potential Target for Angiotensin-Converting Enzyme Inhibition?

Society is ageing. There has been a steady increase in the number of people aged 65 years and over throughout the 20th century and this trend is predicted to continue worldwide. This has resulted in an increase in the incidence of sarcopenia, which is a loss of muscle mass and function with age. Maintenance of muscular function into old age is critical to sustaining normal daily activity and functional independence. Sarcopenia is associated with increased morbidity and mortality. Till now most efforts to counteract sarcopenia have met with limited success. We postulate that targeting the renin-angiotensin system through angiotensin-converting enzyme (ACE) inhibition could play a role in countering sarcopenia. ACE inhibitors could work by preventing mitochondrial decline and improving endothelial function and muscle metabolism. We describe the literature to support our hypothesis that sarcopenia may be a potential therapeutic target for ACE inhibitors.

Using the RT3 accelerometer to measure everyday activity in functionally impaired older people

Background and aims: Triaxial accelerometry may provide a simple measure of physical activity in older people, but the effect of different walking aids and accelerometer placements on measurement is not known. This study aimed to examine the effect of accelerometer placement, use of walking aids, and different types of physical activity on Stay-Healthy RT3 triaxial accelerometer readings in older people. Methods: Twenty subjects aged over 65 years and five younger volunteers were recruited from Medicine for the Elderly services. Subjects performed six minutes each of standardized standing activity, sitting activity, sitting at rest, walking, and stair climbing. Counts generated from RT3 accelerometers worn anteriorly over both hips were recorded in subjects using different walking aids during these standardized activities. Results: There were significant differences between counts generated by the left and right hip positions. The intraclass correlation coefficient of RT3 counts between left and right hip positions was 0.48, 0.39 and 0.99 for sedentary tasks (standing, sitting and rest), stair and walking tasks respectively. Counts ranged between 250–3000 min−1 during the walking task. Counts were proportional to the distance walked. Resting, sitting or standing all generated counts below 250 min−1, but there was no clear demarcation between these activities. The use of different walking aids did not affect the counts generated for any activity. Conclusions: Walking can be distinguished from other activities by upper and lower cutoffs. The RT3 accelerometer should be used on the same side of the body. Different walking aids do not appear to affect RT3 counts in older people.

ACE inhibitors for sarcopenia—as good as exercise training?

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Do ACE Inhibitors Improve the Response to Exercise Training in Functionally Impaired Older Adults? A Randomized Controlled Trial

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. Methods. 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. Results. 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). Interpretation. ACE inhibitors did not enhance the effect of exercise training on physical function in functionally impaired older people.

Proton Pump Inhibitors are Associated with Lower Magnesium Levels in Older People with Chronic Kidney Disease

Medical Research Council, the Arthritis Research Campaign, the British Heart Foundation, the National Osteoporosis Society, Wellcome Trust, and the University of Southampton. Author Contributions: CRG: Had the idea for the study, conducted the statistical analysis, and wrote the first draft of the manuscript. HES: Acquisition and interpretation of data and preparation of manuscript. HB: Interpretation of data and revision of manuscript. EB: Acquisition of data and revision of the manuscript. CC and AAS: Acquisition of participants and data, interpretation of data, and revision of manuscript. All authors approved the final version of the manuscript. Sponsor’s Role: The sponsors had no role in the design, methods, subject recruitment, data collections, analysis, or preparation of the paper.

Does oral sodium bicarbonate therapy improve function and quality of life in older patients with chronic kidney disease and low-grade acidosis (the BiCARB trial)? Study protocol for a randomized controlled trial

BackgroundMetabolic acidosis is more common with advancing chronic kidney disease, and has been associated with impaired physical function, impaired bone health, accelerated decline in kidney function and increased vascular risk. Although oral sodium bicarbonate is widely used to correct metabolic acidosis, there exist potential risks of therapy including worsening hypertension and fluid overload. Little trial evidence exists to decide whether oral bicarbonate therapy is of net benefit in advanced chronic kidney disease, particularly in older people who are most commonly affected, and in whom physical function, quality of life and vascular health are at least as important outcomes as decline in renal function.Methods/DesignBiCARB is a multi-centre, double-blind, placebo controlled, randomised trial evaluating the clinical and cost-effectiveness of oral sodium bicarbonate in the management of older people with chronic kidney disease and severely reduced glomerular filtration rate (GFR) who have a mild degree of metabolic acidosis. The trial will recruit 380 patients from renal, Medicine for the Elderly, and primary care services across centres in the United Kingdom. Male and female patients aged 60 years and older with an estimated glomerular filtration rate of <30 mL/min/1.73 m2, not on dialysis, and with serum bicarbonate concentrations <22 mmol/L will be eligible for participation. The primary clinical outcome for the trial is the between-group difference in the Short Physical Performance Battery score at 12 months. Secondary outcomes include muscle strength, quality of life measured using the EQ-5D score and KDQoL tools, cost effectiveness, renal function, presence of albuminuria and blood pressure. Markers of bone turnover (25-hydroxyvitamin D, 1,25-hydroxyvitamin D, tartrate-resistant acid phosphatase-5b and bone-specific alkaline phosphatase) and vascular health (B-type natriuretic peptide) will be measured. Participants will receive a total of 24 months of either bicarbonate or placebo. The results will provide the first robust test of the overall clinical and cost-effectiveness of this commonly used therapy in older patients with severely reduced kidney function.Trial registrationwww.isrctn.com; ISRCTN09486651, registered 17 February 2012