Angiotensin-II blockage, muscle strength, and exercise capacity in physically independent older adults

Coelho, Vinícius A.; Probst, Vanessa S.; Nogari, Bruna M.; Teixeira, Denílson C.; Felcar, Josiane Marques; Santos, Denis Carlos dos; Gomes, M.V.; Andraus, Rodrigo Antônio Carvalho; Fernandes, Karen Barros Parron

doi:10.1589/jpts.28.547

Cited by 25 publications

(20 citation statements)

References 32 publications

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“…Some studies suggest that aldosterone blockade may reduce decline in physical function by reducing muscle strength, but the majority of studies on the RAS have examined angiotensin‐converting enzyme inhibitor (ACE‐I) use . Two investigations provide some evidence of a reduction in disability, exercise capacity, and muscle strength directly, and a review of studies showed a beneficial effect of ACE‐Is and angiotensin receptor blockers on exercise capacity, although the exact mechanisms are unclear . Our results indicated a protective association between RAS blockers and risk of decline but only in the low polypharmacy group, although sensitivity analysis showed that, if 15% or more of the decedents had declined, then the protective association lost significance, suggesting that this result is not robust to losses due to death.…”

Section: Discussionmentioning

confidence: 59%

Guideline‐Recommended Medications and Physical Function in Older Adults with Multiple Chronic Conditions

McAvay

Allore

Cohen

et al. 2017

J American Geriatrics Society

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Background The benefit or harm of a single medication recommended for one specific condition can be difficult to determine in patients with multiple chronic conditions and polypharmacy. There is limited information on the associations between guideline-recommended medications and physical function in older adults with multiple chronic conditions. Objectives To estimate the beneficial or harmful associations between guideline-recommended medications and decline in physical function in older adults with multiple chronic conditions. Design Prospective observational cohort. Setting National Participants Community dwelling adults aged 65 and older from the Medicare Current Beneficiary Survey study (N=3273). Participants with atrial fibrillation, coronary artery disease, depression, diabetes or heart failure were included. Measurements Self-reported decline in physical function, guideline-recommended medications, polypharmacy (taking fewer than 7 versus 7 or more concomitant medications), chronic conditions, socio-demographic, behavioral, and health risk factors. Results The risk of decline in function in the overall sample was highest in participants with heart failure (35.4%, 95% confidence interval (CI) = 26.3–44.5) and lowest for those with atrial fibrillation (20.6%, 95% CI = 14.9–26.2). In the overall sample, none of the six guideline-recommended medications was associated with decline un physical function across the five study conditions, although in the group with low polypharmacy exposure, there was lower risk of decline in those with heart failure taking renin angiotensin system blockers (hazard ratio (HR) = 0.40, 95% CI = 0.16–0.99) and greater risk of decline in physical function for participants with diabetes taking statins (HR= 2.27, 95% CI = 1.39–3.69). Conclusions In older adults with multiple chronic conditions, guideline-recommended medications for atrial fibrillation, coronary artery disease, depression, diabetes and heart failure were largely not associated with self-reported decline in physical function, although associations for some medications were present in those with a lower polypharmacy exposure.

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Section: Discussionmentioning

confidence: 59%

Guideline‐Recommended Medications and Physical Function in Older Adults with Multiple Chronic Conditions

McAvay

Allore

Cohen

et al. 2017

J American Geriatrics Society

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“…Medications commonly used in older individuals, such as ACEi, have been reported to attenuate age-related decline in physical performance (8,23,24,52) and increase life span (53)(54)(55). However, treatments with ACEi are not always effective (13) and determinants of inter-individual variation in response to ACEi are largely unknown.…”

Section: Discussionmentioning

confidence: 99%

Lisinopril Preserves Physical Resilience and Extends Life Span in a Genotype-Specific Manner in Drosophila melanogaster

Gabrawy

Campbell

Carbone

et al. 2019

The Journals of Gerontology: Series A

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Abstract Physical resiliency declines with age and comorbid conditions. In humans, angiotensin-converting enzyme (ACE) has been associated with attenuation of the decline in physical performance with age. ACE-inhibitor compounds, commonly prescribed for hypertension, often have beneficial effects on physical performance however the generality of these effects are unclear. Here, we tested the effects of the ACE-inhibitor Lisinopril on life span, and age-specific speed, endurance, and strength using three genotypes of the Drosophila melanogaster Genetic Reference Panel. We show that age-related decline in physical performance and survivorship varies with genetic background. Lisinopril treatment increased mean life span in all Drosophila Genetic Reference Panel lines, but its effects on life span, speed, endurance, and strength depended on genotype. We show that genotypes with increased physical performance on Lisinopril treatment experienced reduced age-related protein aggregation in muscle. Knockdown of skeletal muscle-specific Ance, the Drosophila ortholog of ACE, abolished the effects of Lisinopril on life span, implying a role for skeletal muscle Ance in survivorship. Using transcriptome profiling, we identified genes involved in stress response that showed expression changes associated with genotype and age-dependent responsiveness to Lisinopril. Our results demonstrate that Ance is involved in physical decline and demonstrate genetic variation in phenotypic responses to an ACE inhibitor.

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“…Two drug classes that inhibit RAS by directly targeting Ang II, the ACE inhibitors (ACEi) and the angiotensin receptor blockers (ARBs), are widely used in clinical practice to manage cardio-vascular disorders and chronic kidney disease [ 2 ]. More recent evidence suggests that administration of ACEi or ARBs can also improve physical function in older individuals with impairment of daily activities [ 5 ] and in physically independent elderly people [ 6 ]. Moreover, ACEi or ARB-induced blockade of RAS has been shown to reduce the incidence of type-2 diabetes in patients with heart failure or at risk for coronary artery disease [ 7 ] and ameliorate skeletal muscle insulin sensitivity in mammalian models [ 8 ].…”

Section: Introductionmentioning

confidence: 99%

Age- and Genotype-Specific Effects of the Angiotensin-Converting Enzyme Inhibitor Lisinopril on Mitochondrial and Metabolic Parameters in Drosophila melanogaster

Ederer

Jin

Bouslog

et al. 2018

IJMS

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The angiotensin-converting enzyme (ACE) is a peptidase that is involved in the synthesis of Angiotensin II, the bioactive component of the renin-angiotensin system. A growing body of literature argues for a beneficial impact of ACE inhibitors (ACEi) on age-associated metabolic disorders, mediated by cellular changes in reactive oxygen species (ROS) that improve mitochondrial function. Yet, our understanding of the relationship between ACEi therapy and metabolic parameters is limited. Here, we used three genetically diverse strains of Drosophila melanogaster to show that Lisinopril treatment reduces thoracic ROS levels and mitochondrial respiration in young flies, and increases mitochondrial content in middle-aged flies. Using untargeted metabolomics analysis, we also showed that Lisinopril perturbs the thoracic metabolic network structure by affecting metabolic pathways involved in glycogen degradation, glycolysis, and mevalonate metabolism. The Lisinopril-induced effects on mitochondrial and metabolic parameters, however, are genotype-specific and likely reflect the drug’s impact on nutrient-dependent fitness traits. Accordingly, we found that Lisinopril negatively affects survival under nutrient starvation, an effect that can be blunted by genotype and age in a manner that partially mirrors the drug-induced changes in mitochondrial respiration. In conclusion, our results provide novel and important insights into the role of ACEi in cellular metabolism.

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Angiotensin-II blockage, muscle strength, and exercise capacity in physically independent older adults

Cited by 25 publications

References 32 publications

Guideline‐Recommended Medications and Physical Function in Older Adults with Multiple Chronic Conditions

Guideline‐Recommended Medications and Physical Function in Older Adults with Multiple Chronic Conditions

Lisinopril Preserves Physical Resilience and Extends Life Span in a Genotype-Specific Manner in Drosophila melanogaster

Age- and Genotype-Specific Effects of the Angiotensin-Converting Enzyme Inhibitor Lisinopril on Mitochondrial and Metabolic Parameters in Drosophila melanogaster

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