Body weight changes and incidence of cachexia after stroke

Background: Body weight loss is a frequent complication after stroke, and its adverse effect on clinical outcome has been shown in several clinical trials. The purpose of this prospective longitudinal single-centre observational study was to investigate dynamical changes of body composition and body weight after ischemic stroke and an association with functional outcome. Methods: Sixty-seven consecutive patients (age 69 ± 11 years, body mass index 27.0 ± 4.1 kg/m2, 42% female patient, mean ± SD) with acute ischemic stroke with mild to moderate neurological deficit (National Institute of Health Stroke Scale median 4, ranged 0–12) were analysed in the acute phase (4 ± 2 days) and at 12 months (389 ± 26 days) follow-up. Body composition was examined by dual energy X-ray absorptiometry. Cachexia was defined according to the consensus definition by body weight loss ≥5% within 1 year and additional clinical signs. Lean tissue wasting was considered if a ratio of upper and lower limbs lean mass sum to squared height (kg/m2) was ≤5.45 kg/m2 for female patient and ≤7.25 kg/m2 for male patient. Results: According to the body weight changes after 12 months, 42 (63%) patients had weight gain or stable weight, 11 (16%) patients had moderate weight loss, and 14 (21%) patients became cachectic. A relative decline of 19% of fat tissue and 6.5% of lean tissue was observed in cachectic patients, while no changes of lean tissue were observed in non-cachectic patients after 12 months. The modified Rankin Scale was 48% higher (2.1 ± 1.6, P < 0.05), Barthel Index was 22% lower (71 ± 39, P < 0.01), and handgrip strength was 34% lower (21.9 ± 13.0, P < 0.05) in cachectic compared to non-cachectic patients after 12 months. The low physical performance if defined by Barthel Index <60 points was linked to the lean tissue wasting (OR 44.8, P < 0.01), presence of cachexia (OR 20.8, P < 0.01), and low body mass index <25 kg/m2 (OR 11.5, P < 0.05). After adjustment for cofounders, lean tissue wasting remained independently associated with the low physical performance at 12 months follow-up (OR 137.9, P < 0.05). Conclusions: In this cohort study, every fifth patient with ischemic stroke fulfilled the criteria of cachexia within 12 months after index event. The incidence of cachexia was 21%. Cachectic patients showed the lowest functional and physical capacity

A Mechanistic Link to Peripheral Endothelial Dysfunction

Background: Sleep‐disordered breathing (SDB) after acute ischemic stroke is frequent and may be linked to stroke‐induced autonomic imbalance. In the present study, the interaction between SDB and peripheral endothelial dysfunction (ED) was investigated in patients with acute ischemic stroke and at 1‐year follow‐up. Methods and Results: SDB was assessed by transthoracic impedance records in 101 patients with acute ischemic stroke (mean age, 69 years; 61% men; median National Institutes of Health Stroke Scale, 4) while being on the stroke unit. SDB was defined by apnea‐hypopnea index ≥5 episodes per hour. Peripheral endothelial function was assessed using peripheral arterial tonometry (EndoPAT‐2000). ED was defined by reactive hyperemia index ≤1.8. Forty‐one stroke patients underwent 1‐year follow‐up (390±24 days) after stroke. SDB was observed in 57% patients with acute ischemic stroke. Compared with patients without SDB, ED was more prevalent in patients with SDB (32% versus 64%; P<0.01). After adjustment for multiple confounders, presence of SDB remained independently associated with ED (odds ratio, 3.1; [95% confidence interval, 1.2–7.9]; P<0.05). After 1 year, the prevalence of SDB decreased from 59% to 15% (P<0.001). Interestingly, peripheral endothelial function improved in stroke patients with normalized SDB, compared with patients with persisting SDB (P<0.05). Conclusions: SDB was present in more than half of all patients with acute ischemic stroke and was independently associated with peripheral ED. Normalized ED in patients with normalized breathing pattern 1 year after stroke suggests a mechanistic link between SDB and ED

Iron deficiency in worsening heart failure is associated with reduced estimated protein intake, fluid retention, inflammation and antiplatelet use

AIMS: Iron deficiency (ID) is common in heart failure (HF) patients and negatively impacts symptoms and prognosis. The aetiology of ID in HF is largely unknown. We studied determinants and the biomarker profile of ID in a large international HF cohort. METHODS AND RESULTS: We studied 2357 worsening HF patients from the BIOSTAT-CHF cohort. ID was defined as transferrin saturation <20%. Univariable and multivariable logistic regression models were constructed to identify determinants for ID. We measured 92 cardiovascular markers (Olink Cardiovascular III) to establish a biomarker profile of ID. The primary endpoint was the composite of all-cause mortality and first HF rehospitalization. Mean age (±standard deviation) of all patients was 69 ± 12.0 years, 26.1% were female and median N-terminal pro B-type natriuretic peptide levels (+interquartile range) were 4305 (2360-8329) ng/L. Iron deficiency was present in 1453 patients (61.6%), with highest prevalence in females (71.1% vs. 58.3%; P < 0.001). Independent determinants of ID were female sex, lower estimated protein intake, higher heart rate, presence of peripheral oedema and orthopnoea, chronic kidney disease, lower haemoglobin, higher C-reactive protein levels, lower serum albumin levels, and P2Y12 inhibitor use (all P < 0.05). None of these determinants were sex-specific. The biomarker profile of ID largely consisted of pro-inflammatory markers, including paraoxonase 3 (PON3) and tartrate-resistant acid phosphatase type 5. In multivariable Cox proportional hazard regression analyses, ID was associated to worse outcome, independently of predictors of ID (hazard ratio 1.25, 95% confidence interval 1.06-1.46; P = 0.007). CONCLUSION: Our data suggest that the aetiology of ID in worsening HF is complex, multifactorial and seems to consist of a combination of reduced iron uptake (malnutrition, fluid overload), impaired iron storage (inflammation, chronic kidney disease), and iron loss (antiplatelets)

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

BACKGROUND C-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. METHODS Patients with acute ischaemic or haemorrhagic stroke (n = 123, mean age 70 ± 11 y, body mass index BMI 27.0 ± 4.9 kg/m(2)) 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. RESULTS CAF22 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. CONCLUSIONS CAF22 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

Innate immunity and remodelling

A wide variety of cardiac disease states can induce remodelling and lead to the functional consequence of heart failure. These complex disease states involve a plethora of parallel signal transduction events, which may be associated with tissue injury or tissue repair. Innate immunity is activated in hearts injured in different ways, evident as cytokine release from the heart, activation of toll-like receptors involved in recognizing danger, and activation of the transcription factor nuclear factor kappa B. Nuclear factor kappa B regulates gene programmes involved in inflammation as well as the resolution of inflammation. The impact of this is an enigma; while cytokines, toll-like receptors, and nuclear factor kappa B appear to elicit myocardial protection in studies of preconditioning, the literature strongly indicates a detrimental role for activation of innate immunity in studies of acute ischaemia–reperfusion injury. The impact of activation of cardiac innate immunity on the long-term outcome in in vivo models of hypertrophy and remodelling is less clear, with conflicting results as to whether it is beneficial or detrimental. More research using genetically engineered mice as tools, different models of evoking remodelling, and long-term follow-up is required for us to conclude whether activation of the innate immune system is good, bad, or unimportant in chronic injury models

Iron Behaving Badly: Inappropriate Iron Chelation as a Major Contributor to the Aetiology of Vascular and Other Progressive Inflammatory and Degenerative Diseases

The production of peroxide and superoxide is an inevitable consequence of aerobic metabolism, and while these particular "reactive oxygen species" (ROSs) can exhibit a number of biological effects, they are not of themselves excessively reactive and thus they are not especially damaging at physiological concentrations. However, their reactions with poorly liganded iron species can lead to the catalytic production of the very reactive and dangerous hydroxyl radical, which is exceptionally damaging, and a major cause of chronic inflammation. We review the considerable and wide-ranging evidence for the involvement of this combination of (su)peroxide and poorly liganded iron in a large number of physiological and indeed pathological processes and inflammatory disorders, especially those involving the progressive degradation of cellular and organismal performance. These diseases share a great many similarities and thus might be considered to have a common cause (i.e. iron-catalysed free radical and especially hydroxyl radical generation). The studies reviewed include those focused on a series of cardiovascular, metabolic and neurological diseases, where iron can be found at the sites of plaques and lesions, as well as studies showing the significance of iron to aging and longevity. The effective chelation of iron by natural or synthetic ligands is thus of major physiological (and potentially therapeutic) importance. As systems properties, we need to recognise that physiological observables have multiple molecular causes, and studying them in isolation leads to inconsistent patterns of apparent causality when it is the simultaneous combination of multiple factors that is responsible. This explains, for instance, the decidedly mixed effects of antioxidants that have been observed, etc...Comment: 159 pages, including 9 Figs and 2184 reference

URSODEOXYCHOLIC ACID IN PATIENTS WITH CHRONIC HEART FAILURE. A DOUBLE-BLIND, RANDOMIZED, PLACEBO-CONTROLLED, CROSSOVER TRIAL

Цель. Оценить влияние урсодеоксихолевой кислоты (УДХК) на функцию эндотелия и маркеры воспаления у больных хронической сердечной недостаточностью (ХСН). Введение. Эндотелиальная дисфункция, которая обычно наблюдается у больных ХСН, вносит вклад в возникающее при этом состоянии ограничение способности выполнять физические нагрузки. Бактериальные липополисахариды могут способствовать высвобождению провоспалительных цитокинов и усугублять эндотелиальную дисфункцию. УДХК — желчная кислота, используемая при лечении заболеваний печени с холестазом, обладает противовоспалительным и цитопротекторными свойствами и может способствовать образованию смешанных мицелл вокруг липополисахарида. Эти свойства могут быть полезными для улучшения периферического кровотока у пациентов с ХСН. Материал и методы. Проведено проспективное одноцентровое двойное слепое рандомизированное плацебо-контролируемое перекрестное исследование УДХК у 17 пациентов мужского пола с клинически стабильной ХСН [II/III функционального класса по New York Heart Association (NYHA) с фракцией выброса левого желудочка &lt;45%]. Пациенты рандомизированно получали лечение УДХК по 500 мг два раза/день в течение 4 нед и плацебо в течение еще 4 нед. Первичной конечной точкой исследования был пиковый постишемический периферический кровоток в верхней конечности, оцененный посредством тензометрической плетизмографии. Результаты. Исследование завершили 16 больных. Все больные хорошо перенесли лечение УДХК. По сравнению с применением плацебо, лечение УДХК значимо улучшало пиковый постишемический кровоток в верхней конечности (+18%; р=0,038), также при лечении УДХК наблюдалась тенденция к улучшению пикового постишемического кровотока в нижней конечности (+17%; р=0,079). У больных улучшалась функция печени: после лечения УДХК уровни γ-глутамилтрансферазы, аспартаттрансаминазы и растворимых рецепторов фактора некроза опухоли α 1-го типа были ниже, чем после применения плацебо (р&lt;0,05 для всех сравнений). Изменений результатов теста с 6-минутной ходьбой и функционального класса ХСН (NYHA) не выявлено; уровни фактора некроза опухоли α и интерлейкина-6 не изменились или повысились при лечении УДХК в сравнении с плацебо.  Заключение. УДХК хорошо переносится больными ХСН. Лечение УДХК улучшает периферическое кровообращение и связано с положительной динамикой уровней маркеров функции печени.</p