Evaluation of C-terminal Agrin Fragment as a marker of muscle wasting in patients after acute stroke during early rehabilitation

Abstract

BackgroundC‐terminal Agrin Fragment (CAF) has been proposed as a novel biomarker for sarcopenia originating from the degeneration of the neuromuscular junctions. In patients with stroke muscle wasting is a common observation that predicts functional outcome. We aimed to evaluate agrin sub‐fragment CAF22 as a marker of decreased muscle mass and physical performance in the early phase after acute stroke.MethodsPatients with acute ischaemic or haemorrhagic stroke (n = 123, mean age 70 ± 11 y, body mass index BMI 27.0 ± 4.9 kg/m2) admitted to inpatient rehabilitation were studied in comparison to 26 healthy controls of similar age and BMI. Functional assessments were performed at begin (23 ± 17 days post stroke) and at the end of the structured rehabilitation programme (49 ± 18 days post stroke) that included physical assessment, maximum hand grip strength, Rivermead motor assessment, and Barthel index. Body composition was assessed by bioelectrical impedance analysis (BIA). Serum levels of CAF22 were measured by ELISA.ResultsCAF22 levels were elevated in stroke patients at admission (134.3 ± 52.3 pM) and showed incomplete recovery until discharge (118.2 ± 42.7 pM) compared to healthy controls (95.7 ± 31.8 pM, p < 0.001). Simple regression analyses revealed an association between CAF22 levels and parameters of physical performance, hand grip strength, and phase angle, a BIA derived measure of the muscle cellular integrity. Improvement of the handgrip strength of the paretic arm during rehabilitation was independently related to the recovery of CAF22 serum levels only in those patients who showed increased lean mass during the rehabilitation.ConclusionsCAF22 serum profiles showed a dynamic elevation and recovery in the subacute phase after acute stroke. Further studies are needed to explore the potential of CAF22 as a serum marker to monitor the muscle status in patients after stroke.

Phase Angle as a Biomarker for Frailty and Postoperative Mortality: The BICS Study

“…This finding reinforces the notion that a low PA is associated with sarcopenia, a key biological substrate of the frailty syndrome that results from accelerated age‐related loss of skeletal muscle mass and strength 31. PA has previously been shown to correlate with biomarkers of muscle degeneration32 and to decrease after muscle injury,33, 34, 35 supporting the biological plausibility of a link between decreased PA and not only low muscle mass, but also impaired muscle function. More important, the addition of low PA to risk models that included the SPPB demonstrated incremental prognostic value, highlighting the complementary relationship between PA and existing frailty scales.…”

Muscle wasting and sarcopenia in heart failure: a brief overview of the current literature

“…36 Cheung et al recently reported that testosterone deprivation selectively decreases lower limb muscle function, predominantly affecting muscles that support body weight and muscles that accelerate the body forward during walking and mediate balance. 51 Sensitivity and specificity 1076 Editorial of biomarkers such as C-terminal agrin fragment and other such candidates remain however unsatisfying. 37,38 Anorexia, on the other hand, plays also a major role in the pathogenesis of wasting in both sarcopenia and cachexia.…”

“…[46][47][48][49] An interesting candidate biomarker Cterminal agrin fragment has been used in patients with HF 50 and in patients after acute stroke. 51 Sensitivity and specificity 1076 Editorial of biomarkers such as C-terminal agrin fragment and other such candidates remain however unsatisfying. 52 Another interesting approach is the assessment of handgrip strength using a handgrip dynamometer.…”

MicroRNAs in muscle wasting

“…[17][18][19][20][21] Several other circulating factors like GDF-15, 22 activin A, 23 and low testosterone 24 have been associated with muscle loss and survival in sarcopenia and cachexia and therefore can be considered potential biomarkers, but need to be validated in large trials. 1 This is of particular importance in muscle wasting, as there are very few blood-based biomarkers such as myostatin or agrinin that correlated with muscle mass.…”