Association of Serum Asymmetric Dimethylarginine With Muscle Strength and Gait Speed: A Cross-Sectional Study of the HEIJO-KYO Cohort

Obayashi, Kenji; Saeki, Keigo; Maegawa, Taeko; Sakai, Takahide; Kitagawa, Maiko; Otaki, Naoto; Kataoka, Hiroshi; Kurumatani, Norio

doi:10.1002/jbmr.2773

Cited by 14 publications

(10 citation statements)

References 28 publications

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“…There is some laboratory evidence that elevated levels of ADMA may contribute to skeletal muscle proteolysis [ 15 ], which may also be a mechanism for reduced physical capacity in the STS-10 performance found in our study. Association of ADMA with the loss of physical fitness was confirmed for patients with heart failure [ 16 ] and in non-uremic elderly persons [ 17 ]. Currently no specific, clinically applicable means to lower the ADMA level is available for renal failure patients.…”

Section: Discussionmentioning

confidence: 99%

Association of Uremic Toxins and Inflammatory Markers with Physical Performance in Dialysis Patients

Pajek

Jerman

Osredkar

et al. 2018

Toxins

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Association of higher serum levels of uremic toxins and inflammatory markers with poorer physical performance is understudied. We measured the six-minute walk test (6MWT), 10 repetition sit-to-stand test (STS-10), handgrip strength (HGS), and Human Activity Profile (HAP) questionnaire score in 90 prevalent hemodialysis patents, with low comorbidity to reduce the potential confounding of concomitant disease. Midweek pre-dialysis serum levels of asymmetric dimethyl-arginine (ADMA), β2-microglobulin (B2M), high-sensitivity C-reactive protein (hs-CRP), indoxyl sulfate (IS), insulin-like growth factor 1 (IGF-1), interleukin 6 (IL-6), myostatin, and urea were analyzed as predictor parameters of physical performance measures in adjusted models. Serum levels of most measured toxins were not significantly related to performance, except for ADMA, which was significantly related to poorer performance in the STS-10 test (B = 0.11 ± 0.03 s, p < 0.01). Higher hs-CRP was associated with poorer results in the 6MWT (B = −2.6 ± 0.97 m, p < 0.01) and a lower HAP score (B = −0.36 ± 0.14, p = 0.01). There were no other significant associations found. We conclude that inflammation may be a more important pathway to physical impediment than uremic toxemia. This suggests that there is a large physical rehabilitation potential in non-inflamed uremic patients.

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Section: Discussionmentioning

confidence: 99%

Association of Uremic Toxins and Inflammatory Markers with Physical Performance in Dialysis Patients

Pajek

Jerman

Osredkar

et al. 2018

Toxins

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“…Cardiovascular risk factors, including hypertension (Kazama et al 2003(Kazama et al , 2004, dyslipidemia, smoking, low circulating IGF-1 levels (Toth et al 2015a), and obesity (Tucsek et al 2014b), which are all important risk factors for cognitive decline in elderly patients (Gorelick et al 2011;Iadecola et al 2009;Miralbell et al 2013), also inhibit NO mediation of neurovascular coupling and microvascular dilations by promoting oxidative stress, uncoupling endothelial NO synthase and/or by upregulating asymmetric dimethylarginine (ADMA), an endogenous inhibitor of NO synthase. In that regard, it is important that a significant association between serum ADMA level and slower gait speed was demonstrated among elderly individuals (Obayashi et al 2016). Type 2 diabetes mellitus (Duarte et al 2015) also leads to neurovascular dysfunction, which is associated with increased risk for brain function loss and long-term cognitive impairment (Biessels and Reijmer 2014;Brundel et al 2012Brundel et al , 2014de Bresser et al 2010;Palta et al 2014;Reijmer et al 2011;Ruis et al 2009;Ryan et al 2014Ryan et al , 2016van den Berg et al 2008van den Berg et al , 2009van den Berg et al , 2010.…”

Section: Discussionmentioning

confidence: 99%

Pharmacologically induced impairment of neurovascular coupling responses alters gait coordination in mice

et al. 2017

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There is correlative evidence that impaired cerebral blood flow (CBF) regulation, in addition to promoting cognitive impairment, is also associated with alterations in gait and development of falls in elderly people. CBF is adjusted to neuronal activity via neurovascular coupling (NVC) and this mechanism becomes progressively impaired with age. To establish a direct cause-andeffect relationship between impaired NVC and gait abnormalities, we induced neurovascular uncoupling pharmacologically in young C57BL/6 mice by inhibiting the synthesis of vasodilator mediators involved in NVC. Treatment of mice with the epoxygenase inhibitor MSPPOH, the NO synthase inhibitor L-NAME, and the COX inhibitor indomethacin significantly decreased NVC mimicking the aging phenotype. Pharmacologically induced neurovascular uncoupling significantly decreased the dynamic gait parameter duty cycle, altered footfall patterns, and significantly increased phase dispersion, indicating impaired interlimb coordination. Impaired NVC also tended to increase gait variability. Thus, selective experimental disruption of NVC causes subclinical gait abnormalities, supporting the importance of CBF in both cognitive function and gait regulation.

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“…Nitric oxide plays an important role in skeletal muscle physiology including regulating inflammatory processes during muscle repair . A cross‐sectional study of 550 older individuals associated a significant inverse association between serum markers of nitrous oxide competition (asymmetric dimethylarginine) and physical mobility performance measured through gait speed and muscle strength . We speculate that the biological mechanism that underlies our findings may similarly relate to the availability of endogenous nitrous oxide.…”

Section: Discussionmentioning

confidence: 57%

Effect of Gastric Acid Suppressants on Response to a Physical Activity Intervention and Major Mobility Disability in Older Adults: Results from the Lifestyle Interventions for Elders (LIFE) Study

et al. 2019

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OBJECTIVES Proton pump inhibitors (PPIs) and histamine 2 receptor antagonists (H 2 RAs) are associated with pharmacologic effects that may be detrimental to mobility and response to physical activity. Mobility disability and injurious fall outcomes in PPI and H 2 RA users were compared with nonusers in this secondary analysis of data from the Lifestyle Interventions for Elders (LIFE) study. METHODS Participants ages 70-89 years were randomized to a physical activity (PA) or successful aging intervention and evaluated by medication use. Confounders included baseline demographic characteristics, physical function, cognitive function, sleep quality, and acid reflux symptoms that were adjusted via propensity score weighting. Outcomes were incident and persistent major mobility disability (MMD and pMMD) and injurious falls. Weighted proportional hazard models evaluated independent and interaction effects of PPIs and H 2 RAs. RESULTSNo interaction was found between PPIs and H 2 RAs and the PA intervention. Drug use associations were significant for H 2 RAs (hazard ratio [HR] 1.74 [95% confidence interval [CI] 1.12-2.68]) and PPIs (HR 1.32 [95% CI 1.02-1.70]) compared with nonusers for pMMD. PPIs were associated with increased injurious falls compared with nonusers (HR 1.44 [95% CI 1.06-1.96]). Pooling of data from the H 2 RA and PPI exposure groups showed a 26% increase in MMD (HR 1.26 [95% CI 1.07-1.48]), a 44% increase in pMMD (HR 1.44 [95% CI 1.16-1.77]), and a 48% increase in injurious falls (HR 1.48 [95% CI 1.15-1.91]) compared with nonusers. All direct comparisons between PPIs and H 2 RAs were nonsignificant. Adjusted PA vs SA intervention 0.80 (0.67-0.95)* 0.73 (0.58-0.92)* 0.94 (0.71-1.25) H2RA vs non-user 1.29 (0.89-1.85) 1.74 (1.12-2.68)* 1.65 (0.95-2.86) PPI vs non-user 1.14 (0.94-1.39) 1.32 (1.02-1.70)* 1.44 (1.06-1.96)* PPI vs H2RA 0.89 (0.61-1.30) 0.76 (0.48-1.20) 0.87 (0.49-1.54) (PPI or H2RA) vs non-user 1.50 (1.19-1.91)* 1.44 (1.16-1.77)* 1.48 (1.15-1.91)* Unadjusted interaction PA vs SA (H2RA) 0.78 (0.40-1.52) 0.54 (0.23-1.25) 0.89 (0.31-2.58) PA vs SA (PPI) 0.92 (0.67-1.26) 0.82 (0.55-1.24) 0.94 (0.65-1.38) PA vs SA (non-user) 0.80 (0.64-0.99)* 0.73 (0.54-0.99)* 0.95 (0.65-1.38) Adjusted interaction PA vs SA (H2RA) 0.71 (0.35-1.41) 0.58 (0.25-1.36) 0.84 (0.29-2.45) PA vs SA (PPI) 0.87 (0.63-1.20) 0.81 (0.53-1.22) 0.93 (0.57-1.52) PA vs SA (non-user) 0.78 (0.63-0.97)* 0.72 (0.53-0.97)* 0.98 (0.67-1.43) 95% CI = 95% confidence interval; HR = hazard ratio; MMD = Major Mobility Disability; PA = Physical Activity; pMMD = Persistent Major Mobility Disability; SA = Successful Aging. *Indicative of statistical significance p<0.05.

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Association of Serum Asymmetric Dimethylarginine With Muscle Strength and Gait Speed: A Cross-Sectional Study of the HEIJO-KYO Cohort

Cited by 14 publications

References 28 publications

Association of Uremic Toxins and Inflammatory Markers with Physical Performance in Dialysis Patients

Association of Uremic Toxins and Inflammatory Markers with Physical Performance in Dialysis Patients

Pharmacologically induced impairment of neurovascular coupling responses alters gait coordination in mice

Effect of Gastric Acid Suppressants on Response to a Physical Activity Intervention and Major Mobility Disability in Older Adults: Results from the Lifestyle Interventions for Elders (LIFE) Study

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