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ESC Heart Failure Oct 2021Transthyretin amyloid cardiomyopathy (ATTR-CM) is a progressive, fatal disorder that remains underdiagnosed. The Tafamidis in Transthyretin Cardiomyopathy Clinical Trial...
AIMS
Transthyretin amyloid cardiomyopathy (ATTR-CM) is a progressive, fatal disorder that remains underdiagnosed. The Tafamidis in Transthyretin Cardiomyopathy Clinical Trial (ATTR-ACT) was the first large clinical trial to include both wild-type (ATTRwt) and hereditary (ATTRv) patients. A description of the natural history of ATTR-CM, utilizing data from placebo-treated patients in ATTR-ACT, will provide a greater understanding of presentation and progression of ATTR-CM and may aid in disease awareness, earlier diagnosis and treatment monitoring.
METHODS AND RESULTS
Changes in clinical endpoints (mortality, cardiovascular [CV]-related hospitalizations, 6-min walk test [6MWT] distance and Kansas City Cardiomyopathy Questionnaire Overall Summary [KCCQ-OS] score) from baseline to Month 30 in the 177 patients (134 ATTRwt, 43 ATTRv) who received placebo in ATTR-ACT were assessed. ATTRwt patients tended to have less severe disease at baseline. Over the duration of ATTR-ACT, there were 76 (42.9%) all-cause deaths, and 107 (60.5%) patients had a CV-related hospitalization. There was a lower proportion of all-cause deaths in ATTRwt (49, 36.6%) than ATTRv (27, 62.8%). There was a similar, steady decline in mean (SD) 6MWT distance from baseline to Month 30 in ATTRwt (93.9 [93.7] m) and ATTRv (89.1 [107.2] m) patients. The decline in mean (SD) KCCQ-OS score was less severe in ATTRwt (13.8 [20.7]) than ATTRv (21.0 [26.4]) patients.
CONCLUSIONS
Patients with ATTR-CM experience a severe, progressive disease. In ATTR-ACT, placebo-treated patients with ATTRv, compared with ATTRwt, had more severe disease at baseline, and their disease progressed more rapidly as shown by mortality, hospitalizations and quality of life over time.
Topics: Amyloid Neuropathies, Familial; Cardiomyopathies; Hospitalization; Humans; Prealbumin; Quality of Life
PubMed: 34432383
DOI: 10.1002/ehf2.13541 -
Molecular and Cellular Endocrinology Dec 2017Thyroid hormones (THs) are evolutionarily old hormones, having effects on metabolism in bacteria, invertebrates and vertebrates. THs bind specific distributor proteins... (Review)
Review
Thyroid hormones (THs) are evolutionarily old hormones, having effects on metabolism in bacteria, invertebrates and vertebrates. THs bind specific distributor proteins (THDPs) to ensure their efficient distribution through the blood and cerebrospinal fluid in vertebrates. Albumin is a THDP in the blood of all studied species of vertebrates, so may be the original vertebrate THDP. However, albumin has weak affinity for THs. Transthyretin (TTR) has been identified in the blood across different lineages in adults vs juveniles. TTR has intermediate affinity for THs. Thyroxine-binding globulin has only been identified in mammals and has high affinity for THs. Of these THDPs, TTR is the only one known to be synthesised in the brain and is involved in moving THs from the blood into the cerebrospinal fluid. We analysed the rates of evolution of these three THDPs: TTR has been most highly conserved and albumin has had the highest rate of divergence.
Topics: Albumins; Animals; Conserved Sequence; Evolution, Molecular; Gene Expression; Humans; Models, Molecular; Phylogeny; Prealbumin; Protein Binding; Protein Structure, Secondary; Protein Transport; Selection, Genetic; Thyroid Hormones; Thyroxine-Binding Globulin
PubMed: 28249735
DOI: 10.1016/j.mce.2017.02.038 -
Journal of the American Heart... Aug 2023
Topics: Humans; Aged; Prealbumin; Penetrance; Amyloidosis; Heart Failure; Health Disparate Minority and Vulnerable Populations
PubMed: 37486081
DOI: 10.1161/JAHA.123.030802 -
Medicine Oct 2021We designed this study to assess the effectiveness of prealbumin as an indicator of growth as well as a nutritional marker in neonates.Between March 2017 and June 2019,...
We designed this study to assess the effectiveness of prealbumin as an indicator of growth as well as a nutritional marker in neonates.Between March 2017 and June 2019, we measured serum prealbumin concentrations of 80 neonates in neonatal intensive care unit at birth, postnatal day 14 and 28, and classified them into 3 groups (early preterm, late preterm, and term infants). And we examined correlation among prealbumin levels, nutritional intake, and anthropometric measurements (weight, length, and head circumference) in neonates.Prealbumin measured on the 14th postnatal day in early preterm infants showed significant correlations with the length, weight, and head circumference z-scores. Prealbumin levels increased with time in the late preterm and term groups. At birth, prealbumin levels were the lowest in late preterm babies, implying that they are nutritionally deficient and need nutritional support. At postnatal day 28, the prealbumin levels of many preterm infants did not reach those seen in term babies at birth, suggesting the presence of extrauterine growth restriction.Prealbumin can be considered as an indicator of sufficient growth in early preterm infants.
Topics: Biomarkers; Body Weights and Measures; C-Reactive Protein; Gestational Age; Humans; Infant, Newborn; Intensive Care Units, Neonatal; Prealbumin; Retrospective Studies; Sex Factors
PubMed: 34678912
DOI: 10.1097/MD.0000000000027603 -
Medicina 2020
Topics: Amyloid Neuropathies, Familial; Heart; Humans; Prealbumin
PubMed: 32841141
DOI: No ID Found -
Der Nervenarzt Jun 2022Hereditary transthyretin-related amyloidosis (ATTRv) is a rare autosomal dominant disease and is fatal if left untreated. It is caused by mutations in the transthyretin... (Review)
Review
Hereditary transthyretin-related amyloidosis (ATTRv) is a rare autosomal dominant disease and is fatal if left untreated. It is caused by mutations in the transthyretin gene. All known mutations induce misfolding of the tetrameric transthyretin molecule and protein deposits in multiple organs. In peripheral nerves this result in sensorimotor and autonomic polyneuropathy and in cardiac muscle it causes cardiomyopathy. Untreated ATTRv is characterized by an irreversible and progressive course and death 7-11 years after symptom onset. Treatment options consist of TTR stabilizing drugs, such as tafamidis and active agents that selectively interfere at the mRNA level, the so-called gene silencers patisiran and inotersen. All forms of treatment aim to prevent amyloid tissue deposition in tissues and organ dysfunction. Patisiran works by RNA interference on endogenous mechanisms of gene expression. It results in the cleavage of TTR-mRNA using the cytoplasmatic RNA-induced silencing complex. Inotersen, an antisense oligonucleotide, degrades TTR-mRNA via activation of nuclear RNase H. Both mechanisms result in a significant reduction of TTR protein serum levels. The efficacy could be demonstrated by slowing or improving neuropathy progression in the phase III study APOLLO (patisiran) or the NEURO-TTR study (inotersen). Furthermore, the use of both agents led to an improvement in the quality of life in patients with ATTRv. Both forms of treatment are approved in Germany since August 2018 for polyneuropathy stages 1 and 2 according to Coutinho. The choice of treatment should be carried out individually considering drug formulation, contraindications and the necessary safety monitoring controls.
Topics: Amyloid Neuropathies, Familial; Genetic Therapy; Humans; Polyneuropathies; Prealbumin; Quality of Life; RNA, Messenger
PubMed: 35419654
DOI: 10.1007/s00115-022-01288-0 -
Ageing Research Reviews Sep 2021Inside and outside the brain, accumulation of amyloid fibrils plays key roles in the pathogenesis of fatal age-related diseases such as Alzheimer's and Parkinson's... (Review)
Review
Inside and outside the brain, accumulation of amyloid fibrils plays key roles in the pathogenesis of fatal age-related diseases such as Alzheimer's and Parkinson's diseases and wild-type transthyretin amyloidosis. Although the incidence of all amyloidoses increases with age, for some types of amyloidosis aging is known as the main direct risk factor, and these types are typically diseases of elderly people. More than 10 different precursor proteins are known to cause age-associated amyloidosis; these proteins include amyloid β protein, α-synuclein, transthyretin, islet amyloid polypeptide, atrial natriuretic factor, and the newly discovered epidermal growth factor-containing fibulin-like extracellular matrix protein 1. Except for intracerebral amyloidoses, most age-related amyloidoses have been little studied. Indeed, in view of the increasing life expectancy in our societies, understanding how aging is involved in the process of amyloid fibril accumulation and the effects of amyloid deposits on the aging body is extremely important. In this review, we summarize current knowledge about the nature of amyloid precursor proteins, the prevalence, clinical manifestations, and pathogenesis of amyloidosis, and recent advances in our understanding of age-related amyloidoses outside the brain.
Topics: Aged; Amyloid; Amyloid Neuropathies, Familial; Amyloid beta-Peptides; Brain; Humans; Prealbumin
PubMed: 34116224
DOI: 10.1016/j.arr.2021.101388 -
Revue Neurologique 2023Hereditary transthyretin amyloidosis (ATTRv) is a rare, lethal, autosomal dominant adult-onset genetic gain-of function (GOF) disorder provoked by mutations in the TTR... (Review)
Review
Hereditary transthyretin amyloidosis (ATTRv) is a rare, lethal, autosomal dominant adult-onset genetic gain-of function (GOF) disorder provoked by mutations in the TTR gene. Until recently, therapeutic options were limited and consisted mainly in liver transplantation and TTR-stabilizers. In the last few years, ATTRv has been at the center of major therapeutic breakthroughs, including development of effective small interfering RNA (siRNA) and antisense oligonucleotide (ASO) treatments targeting liver TTR mRNA. Both siRNA (patisiran) and ASO (inotersen) treatments are now commercially available and have dramatically improved ATTRv neurological outcome. Ongoing clinical trials currently evaluate another siRNA, vutrisiran and a novel ASO formulation, eplontersen. A CRISPR-Cas9-based TTR gene editing treatment is also currently evaluated, with encouraging preliminary results. These recent therapeutic developments demonstrate the shifting paradigm of ATTRv, a previously untreatable and lethal disorder and provide a proof-of-concept for developing siRNA, ASO and CRISPR-Cas9 treatments for other GOF genetic disorders.
Topics: Adult; Humans; Amyloid Neuropathies, Familial; RNA, Small Interfering; Liver; Mutation; Prealbumin
PubMed: 36150937
DOI: 10.1016/j.neurol.2022.07.006 -
Annals of Clinical and Laboratory... Jan 2021Prealbumin is a blood component tested for nutrition monitoring, which could be affected during inflammation. This study aimed to investigate the relationships between...
OBJECTIVE
Prealbumin is a blood component tested for nutrition monitoring, which could be affected during inflammation. This study aimed to investigate the relationships between prealbumin and C-reactive protein (CRP) in inflammatory rheumatic musculoskeletal diseases (RMDs), including Takayasu arteritis, antineutrophil cytoplasmic antibody-associated vasculitis, systemic lupus erythematosus, Behcet's disease and polymyositis/dermatomyositis.
METHODS
A total of 52 healthy controls and 508 RMD patients were included. We collected 3714 clinical and laboratory records from June 2011 to August 2019, and the longest follow-up period was eleven years. The associations between prealbumin and CRP, the globulin gap, the albumin-to-globulin ratio, and IgG were evaluated.
RESULTS
Prealbumin had a high correlation coefficient (r=-0.497, <0.001), consistent changes over time with CRP, and a high area under the curve [AUC=0.777 (95% CI 0.76-0.795)] for CRP. The statistical relationship between the prealbumin and CRP was not affected by sex, ethnicity or age. Among RMDs, prealbumin showed the strongest correlation with CRP in Takayasu arteritis (r=0.607, <0.001). In addition, a moderate relationship was observed between prealbumin and IgG, the globulin gap and the albumin-to-globulin ratio.
CONCLUSION
Prealbumin is closely related to CRP in Chinese patients with five chronic inflammatory RMDs, which may be due to the influence of chronic inflammation during the course of disease.
Topics: Adult; Biomarkers; C-Reactive Protein; Case-Control Studies; China; Female; Humans; Inflammation; Male; Middle Aged; Musculoskeletal Diseases; Prealbumin; ROC Curve; Rheumatic Diseases
PubMed: 33653784
DOI: No ID Found -
Cells Jul 2021Transthyretin (TTR) is a tetrameric protein transporting hormones in the plasma and brain, which has many other activities that have not been fully acknowledged. TTR is... (Review)
Review
Transthyretin (TTR) is a tetrameric protein transporting hormones in the plasma and brain, which has many other activities that have not been fully acknowledged. TTR is a positive indicator of nutrition status and is negatively correlated with inflammation. TTR is a neuroprotective and oxidative-stress-suppressing factor. The TTR structure is destabilized by mutations, oxidative modifications, aging, proteolysis, and metal cations, including Ca. Destabilized TTR molecules form amyloid deposits, resulting in senile and familial amyloidopathies. This review links structural stability of TTR with the environmental factors, particularly oxidative stress and Ca, and the processes involved in the pathogenesis of TTR-related diseases. The roles of TTR in biomineralization, calcification, and osteoarticular and cardiovascular diseases are broadly discussed. The association of TTR-related diseases and vascular and ligament tissue calcification with TTR levels and TTR structure is presented. It is indicated that unaggregated TTR and TTR amyloid are bound by vicious cycles, and that TTR may have an as yet undetermined role(s) at the crossroads of calcification, blood coagulation, and immune response.
Topics: Amyloid; Amyloidosis; Animals; Arthritis; Cardiovascular Diseases; Humans; Osteoporosis; Oxidative Stress; Prealbumin; Protein Conformation; Protein Stability
PubMed: 34359938
DOI: 10.3390/cells10071768