Relation between use of angiotensin-converting enzyme inhibitors and muscle strength and physical function in older women: an observational study

Onder, Graziano; Penninx, Brenda W. J. H.; Balkrishnan, Rajesh; Fried, Linda P.; Chaves, Paulo H.M.; Williamson, Jeff D.; Carter, Christy S.; Bari, Mauro Di; Guralnik, Jack M.; Pahor, Marco

doi:10.1016/s0140-6736(02)08024-8

Cited by 307 publications

(245 citation statements)

References 27 publications

Supporting

Mentioning

233

Contrasting

Unclassified

Order By: Relevance

“…Hypertensive subjects on ACE inhibitors had faster gait velocity than those not on ACE inhibitors in our study, supporting previous reports, 19,20 In the Women's Health and Aging study, 19 ACE inhibitor use in hypertensive older women was associated with reduced decline in walking speed. The SAGE study 20 reported an association between ACE inhibitors and reduced functional decline in older adults with congestive heart failure.…”

Section: Discussionsupporting

confidence: 91%

“…Possible explanations for the effect of ACE inhibitors on gait include direct effects on muscle membrane, modulating proinflammatory responses triggered by angiotensin, and improved cardiac function. 19,20 The strengths of this study include the systematic gait evaluations using validated techniques and a nondisabled community-residing sample. There is a paucity of quantitative gait studies in this age group.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Gait Characteristics in Nondisabled Community-Residing Nonagenarians

Krishnamurthy

2006

Archives of Physical Medicine and Rehabilitation

View full text Add to dashboard Cite

Objective-To determine gait performance in community-residing nonagenarians.Design-Nested case-control study. Setting-Community.Participants-Thirty-one nondisabled nonagenarians (17 women) and 170 young-old controls (age range, 70-85y) participating in a longitudinal study. Interventions-Not applicable.Main Outcome Measures-Systematic clinical and quantitative gait assessments. We also examined the association of gait velocity with death over a 1-year period.Results-Nonagenarian men had better performance on all quantitative gait parameters examined compared with women. Male sex (β=.58; 95% confidence interval [CI], 9.95-38.89) and depressive symptoms (β=-.34; 95% CI, -6.73 to -0.04) were independently associated with gait velocity in multivariate linear regression models. The 6 hypertensive nonagenarians on angiotensin-converting enzyme (ACE) inhibitors had faster gait velocity (median, 103.1cm/s) compared with the 8 hypertensive nonagenarians not on ACE inhibitors (median, 77.5cm/s; P=.029). Nonagenarians had worse quantitative gait parameters compared with the young-old controls, though the differences were less marked when subjects with clinically normal gaits in both groups were compared. Gait velocity did not predict survival over 1-year follow-up.Conclusions-Gait characteristics in nondisabled community-residing nonagenarians are associated with male sex, depressive symptoms, and medications. The quantitative gait measures in this sample of nondisabled nonagenarians provide a yardstick to compare younger age groups. KeywordsGait; Nonagenarians; Rehabilitation The prevalence of nonagenarians (age range, 90-99y) in the population increased 8-fold between 1950 and 1990, and represents the fastest growing age segment behind centenarians who increased 20-fold during the same time span. 1,2 There is growing interest in defining Reprints to Joe Verghese, MD, Einstein Aging Study,

show abstract

Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 99%

Gait Characteristics in Nondisabled Community-Residing Nonagenarians

Krishnamurthy

2006

Archives of Physical Medicine and Rehabilitation

View full text Add to dashboard Cite

show abstract

“…Thus PIF has been found in the urine of weight-losing cancer patients, and when purified and administered to mice causes muscle atrophy (Cariuk et al, 1997). Ang II has also been linked with muscle wasting in congestive heart failure (Onder et al, 2002), and tumour necrosis factor-a, which may be linked to muscle wasting in sepsis, AIDS and parasitic infections, as well as cancer, has also been shown to activate PKR (Jeffrey et al, 2002). Burn injury, which also causes muscle atrophy, is also associated with an increased phosphorylation of eIF2a as a result of a 274% increase in phosphorylation of PKR (Kaneki et al, 2004).…”

Section: Discussionmentioning

confidence: 99%

Increased expression of phosphorylated forms of RNA-dependent protein kinase and eukaryotic initiation factor 2α may signal skeletal muscle atrophy in weight-losing cancer patients

et al. 2007

View full text Add to dashboard Cite

Previous studies suggest that the activation (autophosphorylation) of dsRNA-dependent protein kinase (PKR) can stimulate protein degradation, and depress protein synthesis in skeletal muscle through phosphorylation of the translation initiation factor 2 (eIF2) on the a-subunit. To understand whether these mediators are important in muscle wasting in cancer patients, levels of the phospho forms of PKR and eIF2a have been determined in rectus abdominus muscle of weight losing patients with oesophago-gastric cancer, in comparison with healthy controls. Levels of both phospho PKR and phospho eIF2a were significantly enhanced in muscle of cancer patients with weight loss irrespective of the amount and there was a linear relationship between phosphorylation of PKR and phosphorylation of eIF2a (correlation coefficient 0.76, P ¼ 0.005). This suggests that phosphorylation of PKR led to phosphorylation of eIF2a. Myosin levels decreased as the weight loss increased, and there was a linear relationship between myosin expression and the extent of phosphorylation of eIF2a (correlation coefficient 0.77, P ¼ 0.004). These results suggest that phosphorylation of PKR may be an important initiator of muscle wasting in cancer patients.

show abstract

“…Thus, treatment of patients with CHF with the angiotensin-converting enzyme (ACE) inhibitor enalapril, in combination with digoxin and a diuretic, produced both increased subcutaneous (s.c.) fat and greater muscle bulk, together with a significant elevation in plasma albumin (Adigun and Ajayi, 2001). Angiotensin-converting enzyme inhibitor treatment has also been shown to halt or slow the decline in muscle strength in elderly women with hypertension and without CHF (Onder et al, 2002). Angiotensin-converting enzyme degrades vasodilator kinases and generates vasoconstrictor angiotensin II (Ang II).…”

mentioning

confidence: 99%

Angiotensin II directly induces muscle protein catabolism through the ubiquitin–proteasome proteolytic pathway and may play a role in cancer cachexia

2005

View full text Add to dashboard Cite

The ability of angiotensin I (Ang I) and II (Ang II) to induce directly protein degradation in skeletal muscle has been studied in murine myotubes. Angiotensin I stimulated protein degradation with a parabolic dose -response curve and with a maximal effect between 0.05 and 0.1 mM. The effect was attenuated by coincubation with the angiotensin-converting enzyme (ACE) inhibitor imidaprilat, suggesting that angiotensin I stimulated protein degradation through conversion to Ang II. Angiotensin II also stimulated protein breakdown with a similar dose -response curve, and with a maximal effect between 1 and 2.5 mM. Total protein degradation, induced by both Ang I and Ang II, was attenuated by the proteasome inhibitors lactacystin (5 mM) and MG132 (10 mM), suggesting that the effect was mediated through upregulation of the ubiquitin -proteasome proteolytic pathway. Both Ang I and Ang II stimulated an increased proteasome 'chymotrypsin-like' enzyme activity as well as an increase in protein expression of 20S proteasome a-subunits, the 19S subunits MSS1 and p42, at the same concentrations as those inducing protein degradation. The effect of Ang I was attenuated by imidaprilat, confirming that it arose from conversion to Ang II. These results suggest that Ang II stimulates protein degradation in myotubes through induction of the ubiquitin -proteasome pathway. Protein degradation induced by Ang II was inhibited by insulin-like growth factor and by the polyunsaturated fatty acid, eicosapentaenoic acid. These results suggest that Ang II has the potential to cause muscle atrophy through an increase in protein degradation. The highly lipophilic ACE inhibitor imidapril (Vitort) (30 mg kg À1 ) attenuated the development of weight loss in mice bearing the MAC16 tumour, suggesting that Ang II may play a role in the development of cachexia in this model.

show abstract

Relation between use of angiotensin-converting enzyme inhibitors and muscle strength and physical function in older women: an observational study

Cited by 307 publications

References 27 publications

Gait Characteristics in Nondisabled Community-Residing Nonagenarians

Gait Characteristics in Nondisabled Community-Residing Nonagenarians

Increased expression of phosphorylated forms of RNA-dependent protein kinase and eukaryotic initiation factor 2α may signal skeletal muscle atrophy in weight-losing cancer patients

Angiotensin II directly induces muscle protein catabolism through the ubiquitin–proteasome proteolytic pathway and may play a role in cancer cachexia

Contact Info

Product

Resources

About