Transthyretin Concentrations in Acute Stroke Patients Predict Convalescent Rehabilitation

Isono, Naofumi; Imamura, Yuki; Ohmura, Keiko; Ueda, Norihide; Kawabata, Shinji; Furuse, Motomasa; Kuroiwa, Toshihiko

doi:10.1016/j.jstrokecerebrovasdis.2017.02.020

Cited by 11 publications

(9 citation statements)

References 25 publications

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“…The lower limit of the normal TTR range is approximately 200 mg/L, which is consistent with clinical investigations showing that below this cut-off level, the likelihood of serious complications may be increased [72,73]. In adult subjects, the threshold of 100 mg/L has ominous prognostic significance [74,75] likely due to exhaustion of LBM resources [60]. Cut-off values ranging from 200 mg/L to 100 mg/L thus define a gray zone between which TTR concentrations may fluctuate and predict either the best or the worst outcome.…”

Section: Future Prospectssupporting

confidence: 78%

Plasma transthyretin is a nutritional biomarker in human morbidities

Ingenbleek

2022

Front. Med.

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Transthyretin (TTR) is a small liver-secreted plasma protein that shows close correlations with changes in lean body mass (LBM) during the entire human lifespan and agglomerates the bulk of nitrogen (N)-containing substrates, hence constituting the cornerstone of body building. Amino acids (AAs) dietary restriction causes inhibition of TTR production and impairs the accretion of LBM reserves. Inflammatory disorders result in cytokine-induced abrogation of TTR synthesis and urinary leakage of nitrogenous catabolites. Taken together, the data indicate that malnutrition and inflammation may similarly suppress the production of TTR through distinct and unrelated pathophysiological mechanisms while operating in concert to downsize LBM stores. The hepatic synthesis of TTR integrates both machineries, acting as a marker of reduced LBM resources still available for defense and repair processes. TTR operates as a universal surrogate analyte that allows for the grading of residual LBM capacity to reflect disease burden. Measurement of TTR is a simple, rapid, and inexpensive micro-method that may be reproduced on a daily basis, hence ideally suited for the follow-up of the most intricated clinical situations and as a reliable predictor of any morbidity outcome.

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Section: Future Prospectssupporting

confidence: 78%

Plasma transthyretin is a nutritional biomarker in human morbidities

Ingenbleek

2022

Front. Med.

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“…The facilitated Aβ clearance in losartan-treated SHRSP is further supported by increased proliferation of CP cells, which are the major intracerebral producers of TTR. Noteworthy in this context is a decrease in TTR in AD-like transgenic mice [60] and the fact that a low blood level of TTR is predictive of a poor outcome in stroke patients [61].…”

Section: Discussionmentioning

confidence: 99%

Intranasal Losartan Decreases Perivascular Beta Amyloid, Inflammation, and the Decline of Neurogenesis in Hypertensive Rats

et al. 2019

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The contribution of the local angiotensin receptor system to neuroinflammation, impaired neurogenesis, and amyloid beta (Aβ) accumulation in Alzheimer's disease (AD) and in hypertension is consistent with the remarkable neuroprotection provided by angiotensin receptor blockers (ARBs) independent of their blood pressure-lowering effect. Considering the causal relationship between hypertension and AD and that targeting cerebrovascular pathology with ARBs does not necessarily require their systemic effects, we tested intranasal losartan in the rat model of chronic hypertension (spontaneously hypertensive strokeprone rats, SHRSP). Intranasal losartan at a subdepressor dose decreased mortality, neuroinflammation, and perivascular content of Aβ by enhancing key players in its metabolism and clearance, including insulin-degrading enzyme, neprilysin, and transthyretin. Furthermore, this treatment improved neurologic deficits and increased brain IL-10 concentration, hippocampal cell survival, neurogenesis, and choroid plexus cell proliferation in SHRSP. Losartan (1 μM) also reduced LDH release from cultured astroglial cells in response to toxic glutamate concentrations. This effect was completely blunted by IL-10 antibodies. These findings suggest that intranasal ARB treatment is a neuroprotective, neurogenesis-inducing, and Aβ-decreasing strategy for the treatment of hypertensive stroke and cerebral amyloid angiopathy acting at least partly through the IL-10 pathway.

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“…Patients with values below the cut-off line of 200 mg/L incur an increasing risk of serious infectious or metabolic events, as predicted in maintenance dialysis [136], retrospective elective spine surgery [137], cardiac surgery [138], and digestive carcinoma [139]. Values below 100 mg/L bear an ominous prognostic significance, as documented in critically ill patients [140], acute kidney injury [141,142], ischemic/hemorrhagic stroke [143], and cancer [144]. These last investigations identify a nadir level likely resulting from the exhaustion of mobilizable LBM resources that participate actively in defense and repair mechanisms and are characterized by rapid turnover rates.…”

Section: Ttr As a Biomarker Of Sarcopenia In Elderly Personsmentioning

confidence: 99%

Plasma Transthyretin as A Biomarker of Sarcopenia in Elderly Subjects

Ingenbleek¹

2019

Nutrients

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Skeletal muscle (SM) mass, the chief component of the structural compartment belonging to lean body mass (LBM), undergoes sarcopenia with increasing age. Decreased SM in elderly persons is a naturally occurring process that may be accelerated by acute or chronic nutritional deficiencies and/or inflammatory disorders, declining processes associated with harmful complications. A recently published position paper by European experts has provided an overall survey on the definition and diagnosis of sarcopenia in elderly persons. The present review describes the additional contributory role played by the noninvasive transthyretin (TTR) micromethod. The body mass index (BMI) formula is currently used in clinical studies as a criterion of good health to detect, prevent, and follow up on the downward trend of muscle mass. The recent upsurge of sarcopenic obesity with its multiple subclasses has led to a confused stratification of SM and fat stores, prompting workers to eliminate BMI from screening programs. As a result, investigators are now focusing on indices of protein status that participate in SM growth, maturation, and catabolism that might serve to identify sarcopenia trajectories. Plasma TTR is clearly superior to all other hepatic biomarkers, showing the same evolutionary patterns as those displayed in health and disease by both visceral and structural LBM compartments. As a result, this TTR parameter maintains positive correlations with muscle mass downsizing in elderly persons. The liver synthesis of TTR is downregulated in protein-depleted states and suppressed in cytokine-induced inflammatory disorders. TTR integrates the centrally-mediated regulatory mechanisms governing the balance between protein accretion and protein breakdown, emerging as the ultimate indicator of LBM resources. This review proposes the adoption of a gray zone defined by cut-off values ranging from 200 mg/L to 100 mg/L between which TTR plasma values may fluctuate and predict either the best or the worst outcome. The best outcome occurs when appropriate dietary, medicinal and surgical decisions are undertaken, resuming TTR synthesis which manifests rising trends towards pre-stress levels. The worst occurs when all therapeutic means fail to succeed, leading inevitably to complete exhaustion of LBM and SM metabolic resources with an ensuing fatal outcome. Some patients may remain unresponsive in the middle of the gray area, combining steady clinical states with persistent stagnant TTR values. Using the serial measurement of plasma TTR values, these last patients should be treated with the most aggressive and appropriate therapeutic strategies to ensure the best outcome.

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Transthyretin Concentrations in Acute Stroke Patients Predict Convalescent Rehabilitation

Cited by 11 publications

References 25 publications

Plasma transthyretin is a nutritional biomarker in human morbidities

Plasma transthyretin is a nutritional biomarker in human morbidities

Intranasal Losartan Decreases Perivascular Beta Amyloid, Inflammation, and the Decline of Neurogenesis in Hypertensive Rats

Plasma Transthyretin as A Biomarker of Sarcopenia in Elderly Subjects

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