Serum myostatin levels are independently associated with skeletal muscle wasting in patients with heart failure

Furihata, Takaaki; Kinugawa, Shintaro; Fukushima, Arata; Takada, Shingo; Homma, Tsuneaki; Masaki, Yoshihiro; Abe, Takahiro; Yokota, Takashi; Oba, Koji; Okita, Koichi; Tsutsui, Hiroyuki

doi:10.1016/j.ijcard.2016.06.231

Cited by 52 publications

(45 citation statements)

References 30 publications

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“…The plasma concentrations for the proteins and polypeptides reported in the present paper are generally higher than other reports in the literature that used antibody‐based approaches, including ELISA and immunoaffinity‐SRM. Circulating GDF8 concentrations by ELISA‐based approaches have yielded highly discrepant results for healthy adults, with means or medians ranging from about 3–120 ng/mL . The mean protein concentrations of both GDF8 mature protein and propeptide reported in the present study are somewhat similar to published GDF8 concentrations using ELISA and immunoaffinity SRM .…”

Section: Discussionsupporting

confidence: 65%

A targeted proteomic assay for the measurement of plasma proteoforms related to human aging phenotypes

et al. 2017

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Circulating polypeptides and proteins have been implicated in reversing or accelerating aging phenotypes, including growth/differentiation factor 8 (GDF8), GDF11, eotaxin, and oxytocin. These proteoforms, which are defined as the protein products arising from a single gene due to alternative splicing and post-translational modifications, have been challenging to study. Both GDF8 and GDF11 have known antagonists such as follistatin (FST), and WAP, Kazal, immunoglobulin, Kunitz and NTR domain-containing proteins 1 and 2 (WFIKKN1, WFIKKN2). We developed a novel multiplexed selected reaction monitoring (SRM) assay using liquid chromatography-tandem mass spectrometry to measure five proteins related to GDF8 and GDF11 signaling, and in addition, eotaxin and oxytocin. Eighteen peptides consisting of 54 transitions were monitored and validated in pooled human plasma. In twenty-four adults, the mean (SD) concentrations (ng/mL) were as follows: GDF8 propeptide, 11.0 (2.4); GDF8 mature protein, 25.7 (8.0); GDF11 propeptide, 21.3 (10.9); GDF11 mature protein, 16.5 (12.4); FST, 29.8 (7.1); FST cleavage form FST303, 96.4 (69.2); WFIKKN1, 38.3 (8.3); WFIKKN2, 32.2 (10.5); oxytocin, 1.9 (0.9); and eotaxin, 2.3 (0.5). This novel multiplexed SRM assay should facilitate the study of the relationships of these proteoforms with major aging phenotypes.

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Section: Discussionsupporting

confidence: 65%

A targeted proteomic assay for the measurement of plasma proteoforms related to human aging phenotypes

et al. 2017

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“…In the heart failure literature, wasting changes in skeletal muscle were described among patients with advanced heart failure . A variety of systemic and humoral mechanisms were presented as possible biological interactions occurring as cross‐talk between skeletal muscle and the diseased heart . In contrast, although our cohort was 65 years of age and older, they did not have clinical heart failure, as evidenced by low BNP levels.…”

Section: Discussionmentioning

confidence: 81%

Associations between Skeletal Muscle and Myocardium in Aging: A Syndrome of “Cardio‐Sarcopenia”?

Keng

Gao

Teo

et al. 2019

J American Geriatrics Society

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Objectives The link between skeletal muscle and heart disease remains intriguing. It is unknown how skeletal muscle may be associated with aspects of myocardial structure and function, particularly in the presence of aging‐related sarcopenia. We hypothesize that among aging adults with sarcopenia, alterations in myocardial structure and/or function may exist, resulting in a syndrome of “cardio‐sarcopenia.” Methods Participants derived from a community cohort study underwent same‐day bioimpedance body composition analysis that measured skeletal muscle in sites such as the trunk, upper limb, and lower limb, and echocardiography for assessment of myocardial structure and function. Sarcopenia was diagnosed using the Asian Working Group for Sarcopenia criteria. Results We studied a total of 378 participants, of whom 88 (23.3%) had sarcopenia. Participants with sarcopenia had smaller left ventricular (LV) sizes (lower LV internal diameter end diastole (4.1 ± .7 vs 4.5 ± .6 cm; P < .0001), lower LV internal diameter end systole (2.3 ± .5 vs 2.5 ± .4 cm; P = .010), lower LV posterior wall end diastole (.7 ± .1 vs .8 ± .1 cm; P = .0036), and lower LV posterior wall end systole (1.4 ± .3 vs 1.5 ± .2 cm; P = .0031). Sarcopenic participants also had lower LV mass (106 ± 35 vs 126 ± 53; P = .0014) and lower left atrial (LA) volume (33 ± 13 vs 36 ± 13; P = .033). Adjusting for age and diabetes mellitus, skeletal muscle mass was associated with LV diameter (β = .06; 95% confidence interval [CI] = .03‐.09; P < .0001), LV mass (β = 4.04; 95% CI = 1.78‐6.29; P = .001), LA diameter (β = .05; 95% CI = .01‐.09; P = .007), and LA volume (β = 1.26; 95% CI = .38‐2.13; P = .005). A positive linear correlation was observed between LV mass and handgrip strength (r = .25; P < .0001). Conclusion Among a community sample of older adults with preserved heart function, sarcopenia is associated with reductions in LV and LA sizes. Skeletal muscle mass was independently associated with specific indices of myocardial structure. J Am Geriatr Soc 67:2568–2573, 2019

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“…To the best of our knowledge, this is the first report of the association between serum myostatin and lower skeletal muscle mass among healthy community‐living older adults; lower serum DHEA levels and low serum myostatin status were independent risk factors of low RASM in men. Although the muscle‐wasting effect of myostatin is well‐established, the relationship between serum myostatin and skeletal muscle mass in humans is complex and remains controversial; moreover, reported associations were observed in patients with COPD or heart failure . Age‐related loss of muscle mass was associated inversely with serum myostatin among frail older adults, and circulating myostatin in male patients with COPD also negatively correlated with skeletal mass calculated using a validated formula .…”

Section: Discussionmentioning

confidence: 99%

“…Age‐related loss of muscle mass was associated inversely with serum myostatin among frail older adults, and circulating myostatin in male patients with COPD also negatively correlated with skeletal mass calculated using a validated formula . Conversely, others have reported skeletal muscle wasting associated with lower myostatin levels, especially in heart failure patients with compensatory status, cachexia, or undertaking exercise training . This inconsistent evidence makes it difficult to assess the potential of serum myostatin as a biomarker for sarcopenia.…”

Section: Discussionmentioning

confidence: 99%

“…Serum myostatin was also negatively associated with skeletal muscle mass in male patients with chronic obstructive pulmonary disease (COPD) . Conversely, decreased plasma myostatin levels in heart‐failure patients with cachexia suggest that lower myostatin may prevent loss of skeletal muscle and progression of cachexia . Besides these inconsistencies, little is known about the relationship between serum myostatin and skeletal muscle mass among healthy individuals.…”

Section: Introductionmentioning

confidence: 99%

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Healthy community‐living older men differ from women in associations between myostatin levels and skeletal muscle mass

Peng

Lee

Liu

et al. 2018

J cachexia sarcopenia muscle

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BackgroundMyostatin is a negative regulator of muscle growth but the relationship between serum myostatin levels and muscle mass is unclear. This study investigated the association between serum myostatin levels and skeletal muscle mass among healthy older community residents in Taiwan, to evaluate the potential of serum myostatin as a biomarker for diagnosing sarcopenia and/or evaluating the effect of its treatment.MethodsStudy data were excerpted from a random subsample of the I‐Lan Longitudinal Aging Study population. Serum myostatin levels were determined and categorized into tertiles (low, medium, high). Relative appendicular skeletal muscle mass (RASM) was calculated as appendicular lean body mass by dual‐energy X‐ray absorptiometry divided by height squared (kg/m2). Low muscle mass was defined as recommended by the Asian Working Group for Sarcopenia.ResultsThe analytic study sample comprised 463 adults (mean age: 69.1 years; 49.5% men). Compared with subjects with normal RASM, those with lower RASM were older and frailer, with significantly higher prevalence of malnutrition, lower serum dehydroepiandrosterone (DHEA) levels, and were more likely to have low serum myostatin status. Multivariable logistic regression analysis showed that male sex (OR 3.60, 95% CI 1.30–9.92), malnutrition (OR 4.39, 95% CI 1.56–12.36), DHEA (OR 0.99, 95% CI 0.99–1.00), and low myostatin (OR 3.23, 95% CI 1.49–7.01) were all independent risk factors for low RASM (all P < 0.05). In men, DHEA (OR 0.99, 95% CI 0.98–1.00) and low myostatin (OR 4.89, 95% CI 1.79–13.37) were significantly associated with low RASM (both P < 0.05); however, only malnutrition was associated with low RASM in women (OR 13.59, 95% CI 2.22–83.25, P < 0.05).ConclusionsAmong healthy community‐living older adults, low serum myostatin levels were associated with low skeletal muscle mass in men, but not in women. Our results do not support using serum myostatin levels to diagnose sarcopenia, or to monitor how it responds to treatments. Further research is needed to understand why men apparently differ from women in the interrelationship between their myostatin levels and muscle mass.

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Serum myostatin levels are independently associated with skeletal muscle wasting in patients with heart failure

Abstract: Background: It has been reported that skeletal muscle mass and strength are decreased

Cited by 52 publications

References 30 publications

A targeted proteomic assay for the measurement of plasma proteoforms related to human aging phenotypes

A targeted proteomic assay for the measurement of plasma proteoforms related to human aging phenotypes

Associations between Skeletal Muscle and Myocardium in Aging: A Syndrome of “Cardio‐Sarcopenia”?

Healthy community‐living older men differ from women in associations between myostatin levels and skeletal muscle mass

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