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

Caulfield, Lorna; Heslop, Philip; Walesby, Katherine; Sumukadas, Deepa; Sayer, Avan A.; Witham, Miles D.

doi:10.1016/j.jamda.2020.07.012

Cited by 13 publications

(13 citation statements)

References 40 publications

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Section: Methodsmentioning

confidence: 99%

“…To place the results of the perindopril analysis in context, we added the results of the LACE trial to our recent meta‐analysis of the effects of ACEi and ARBs on physical performance in older people. 13 Data were analysed in RevMan v5.3 (Cochrane Collaboration). Where standard deviations (SD) of change were not available, SDs were interpolated as the mean of baseline and follow‐up SDs.…”

Section: Methodsmentioning

confidence: 99%

“… 12 Some randomized controlled trials have suggested a beneficial effect of ACEi compared with placebo on physical performance in older people although other studies have failed to find such beneficial effects, and a recent systematic review did not find an overall benefit of either ACEi or angiotensin receptor blockers (ARBs) in this age group. 13 The conclusions of this review were limited by the lack of studies specifically enrolling older people with sarcopenia. Similarly, some studies suggest that leucine supplementation may have beneficial effects on muscle protein synthesis, uptake of amino acids, and consequent improvement in muscle strength.…”

Section: Introductionmentioning

confidence: 99%

“…Observational data show that older people taking angiotensin converting enzyme inhibitors (ACEi) have better preserved walk speed over a 3‐year period than those not taking ACEi 12 . Some randomized controlled trials have suggested a beneficial effect of ACEi compared with placebo on physical performance in older people although other studies have failed to find such beneficial effects, and a recent systematic review did not find an overall benefit of either ACEi or angiotensin receptor blockers (ARBs) in this age group 13 . The conclusions of this review were limited by the lack of studies specifically enrolling older people with sarcopenia.…”

Section: Introductionmentioning

confidence: 99%

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Effect of perindopril or leucine on physical performance in older people with sarcopenia: the LACE randomized controlled trial

Achison

Adamson

Akpan

et al. 2022

J cachexia sarcopenia muscle

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Background This trial aimed to determine the efficacy of leucine and/or perindopril in improving physical function in older people with sarcopenia. Methods Placebo‐controlled, parallel group, double‐blind, randomized two‐by‐two factorial trial. We recruited adults aged ≥ 70 years with sarcopenia, defined as low gait speed (<0.8 m/s on 4 m walk) and/or low handgrip strength (women < 20 kg, men < 30 kg) plus low muscle mass (using sex and body mass index category‐specific thresholds derived from normative UK BioBank data) from 14 UK centres. Eligible participants were randomized to perindopril 4 mg or placebo, and to oral leucine powder 2.5 g or placebo thrice daily. The primary outcome was the between‐group difference in the short physical performance battery (SPPB) score over 12‐month follow‐up by repeated‐measures mixed models. Results were combined with existing systematic reviews using random‐effects meta‐analysis to derive summary estimates of treatment efficacy. Results We screened 320 people and randomized 145 participants compared with an original target of 440 participants. For perindopril [n = 73, mean age 79 (SD 6), female sex 39 (53%), mean SPPB 7.1 (SD 2.3)] versus no perindopril [n = 72, mean age 79 (SD 6), female sex 39 (54%), mean SPPB 6.9 (SD 2.4)], median adherence to perindopril was lower (76% vs. 96%; P < 0.001). Perindopril did not improve the primary outcome [adjusted treatment effect −0.1 points (95%CI −1.2 to 1.0), P = 0.89]. No significant treatment benefit was seen for any secondary outcome including muscle mass [adjusted treatment effect −0.4 kg (95%CI −1.1 to 0.3), P = 0.27]. More adverse events occurred in the perindopril group (218 vs. 165), but falls rates were similar. For leucine [n = 72, mean age 78 (SD 6), female sex 38 (53%), mean SPPB 7.0 (SD 2.1)] versus no leucine [n = 72, mean age 79 (SD 6), female sex 40 (55%), mean SPPB 7.0 (SD 2.5)], median adherence was the same in both groups (76% vs. 76%; P = 0.99). Leucine did not improve the primary outcome [adjusted treatment effect 0.1 point (95%CI −1.0 to 1.1), P = 0.90]. No significant treatment benefit was seen for any secondary outcome including muscle mass [adjusted treatment effect −0.3 kg (95%CI −1.0 to 0.4), P = 0.47]. Meta‐analysis of angiotensin converting enzyme inhibitor/angiotensin receptor blocker trials showed no clinically important treatment effect for the SPPB [between‐group difference −0.1 points (95%CI −0.4 to 0.2)]. Conclusions Neither perindopril nor leucine improved physical performance or muscle mass in this trial; meta‐analysis did not find evidence of efficacy of either ACE inhibitors or leucine as treatments to improve physical performance.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Effect of perindopril or leucine on physical performance in older people with sarcopenia: the LACE randomized controlled trial

Achison

Adamson

Akpan

et al. 2022

J cachexia sarcopenia muscle

Self Cite

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“…Sarcopenia is highly prevalent in hypertensive older adults, and ACE inhibitors seem to have favorable effects on both disorders [60,61] . However, results from two systematic reviews and meta-analysis reveal that there is not enough evidence for using ACE inhibitors or ARBs as stand-alone therapies to improve physical performance in older people, either with or without a diagnosis of sarcopenia [62,63] .…”

Section: Treatmentmentioning

confidence: 99%

Sarcopenia in the setting of nonalcoholic fatty liver

Arrese¹,

Cabello-Verrugio²,

Arab³

et al. 2022

MTOD

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Nonalcoholic fatty liver is a worldwide common problem with more prevalence in non-Asian populations that is closely correlated with the muscle-related disorder sarcopenia. The incidence of both health issues has been observed to be strongly interlinked where presence of one exacerbates the other. Nonalcoholic fatty liver disease (NAFLD) pathophysiology increases the muscle loss, while the onset of NAFLD in sarcopenic patients aggravates the liver problems as compared to non-sarcopenic patients. Scarcity of research on the subject provides very little evidence about the cause and effect of disorders. No FDA approved drugs are available to date for NAFLD and sarcopenia. Research is underway to understand the complex biochemical pathways involved in the development of both disorders. This review is a small contribution toward understanding sarcopenia in the setting of NAFLD that provides insight on the common pathophysiological profile of sarcopenia and NAFLD and portrays a novel way of delving into the subject by introducing the concept of cortisol crosstalk with the muscle-liver axis. Sarcopenia and NAFLD are considered metabolism-related problems, and cortisol, being a glucocorticoid, plays an important role in metabolism of fats, carbohydrates, and proteins. Cushing’s syndrome, characterized by abnormally elevated concentrations of blood cortisol/enhanced intracellular activity, shares many pathologic conditions (such as insulin resistance, metabolic syndrome, abnormal levels of specific cytokines, and obesity) with NAFLD and sarcopenia. Hence, cortisol can be a potential biomarker in sarcopenia and NAFLD. As cortisol activity at cellular level is controlled by 11β-hydroxysteroid dehydrogenase type 1 and 2 (11β-HSD1/2) enzymes that convert inactive steroid precursor into active cortisol, these enzymes can be targeted for the study of sarcopenia and NAFLD. Combined studies on NAFLD and sarcopenia with respect to cortisol open a new avenue of research in the understanding of both disorders.

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Effects of losartan and exercise on muscle mass and exercise endurance of old mice

Lin

Chang²,

Chu³

et al. 2022

Experimental Gerontology

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

Cited by 13 publications

References 40 publications

Effect of perindopril or leucine on physical performance in older people with sarcopenia: the LACE randomized controlled trial

Effect of perindopril or leucine on physical performance in older people with sarcopenia: the LACE randomized controlled trial

Sarcopenia in the setting of nonalcoholic fatty liver

Effects of losartan and exercise on muscle mass and exercise endurance of old mice

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