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

Iron deficiency in patients with heart failure with preserved ejection fraction and its association with reduced exercise capacity, muscle strength and quality of life

Background: The prevalence of iron deficiency (ID) in outpatients with heart failure with preserved ejection fraction (HFpEF) and its relation to exercise capacity and quality of life (QoL) is unknown. Methods: 190 symptomatic outpatients with HFpEF (LVEF 58 ± 7%; age 71 ± 9 years; NYHA 2.4 ± 0.5; BMI 31 ± 6 kg/m2) were enrolled as part of SICA-HF in Germany, England and Slovenia. ID was defined as ferritin &lt; 100 or 100–299 µg/L with transferrin saturation (TSAT) &lt; 20%. Anemia was defined as Hb &lt; 13 g/dL in men, &lt; 12 g/dL in women. Low ferritin-ID was defined as ferritin &lt; 100 µg/L. Patients were divided into 3 groups according to E/e′ at echocardiography: E/e′ ≤ 8; E/e′ 9–14; E/e′ ≥ 15. All patients underwent echocardiography, cardiopulmonary exercise test (CPX), 6-min walk test (6-MWT), and QoL assessment using the EQ5D questionnaire. Results: Overall, 111 patients (58.4%) showed ID with 89 having low ferritin-ID (46.84%). 78 (41.1%) patients had isolated ID without anemia and 54 patients showed anemia (28.4%). ID was more prevalent in patients with more severe diastolic dysfunction: E/e′ ≤ 8: 44.8% vs. E/e′: 9–14: 53.2% vs. E/e′ ≥ 15: 86.5% (p = 0.0004). Patients with ID performed worse during the 6MWT (420 ± 137 vs. 344 ± 124 m; p = 0.008) and had worse exercise time in CPX (645 ± 168 vs. 538 ± 178 s, p = 0.03). Patients with low ferritin-ID had lower QoL compared to those without ID (p = 0.03). Conclusion: ID is a frequent co-morbidity in HFpEF and is associated with reduced exercise capacity and QoL. Its prevalence increases with increasing severity of diastolic dysfunction

Muscle wasting as an independent predictor of survival in patients with chronic heart failure

Background: Skeletal muscle wasting is an extremely common feature in patients with heart failure, affecting approximately 20% of ambulatory patients with even higher values during acute decompensation. Its occurrence is associated with reduced exercise capacity, muscle strength, and quality of life. We sought to investigate if the presence of muscle wasting carries prognostic information. Methods: Two hundred sixty‐eight ambulatory patients with heart failure (age 67.1 ± 10.9 years, New York Heart Association class 2.3 ± 0.6, left ventricular ejection fraction 39 ± 13.3%, and 21% female) were prospectively enrolled as part of the Studies Investigating Co‐morbidities Aggravating Heart Failure. Muscle wasting as assessed using dual‐energy X‐ray absorptiometry was present in 47 patients (17.5%). Results During a mean follow‐up of 67.2 ± 28.02 months, 95 patients (35.4%) died from any cause. After adjusting for age, New York Heart Association class, left ventricular ejection fraction, creatinine, N‐terminal pro‐B‐type natriuretic peptide, and iron deficiency, muscle wasting remained an independent predictor of death (hazard ratio 1.80, 95% confidence interval 1.01–3.19, P = 0.04). This effect was more pronounced in patients with heart failure with reduced than in heart failure with preserved ejection fraction. Conclusions: Muscle wasting is an independent predictor of death in ambulatory patients with heart failure. Clinical trials are needed to identify treatment approaches to this co‐morbidity

Intestinal blood flow in patients with chronic heart failure: A link with bacterial growth, gastrointestinal symptoms, and cachexia

Background: Blood flow in the intestinal arteries is reduced in patients with stable heart failure (HF) and relates to gastrointestinal (GI) symptoms and cardiac cachexia. Objectives: The aims of this study were to measure arterial intestinal blood flow and assess its role in juxtamucosal bacterial growth, GI symptoms, and cachexia in patients with HF. Methods: A total of 65 patients and 25 controls were investigated. Twelve patients were cachectic. Intestinal blood flow and bowel wall thickness were measured using ultrasound. GI symptoms were documented. Bacteria in stool and juxtamucosal bacteria on biopsies taken during sigmoidoscopy were studied in a subgroup by fluorescence in situ hybridization. Serum lipopolysaccharide antibodies were measured. Results: Patients showed 30% to 43% reduced mean systolic blood flow in the superior and inferior mesenteric arteries and celiac trunk (CT) compared with controls (p < 0.007 for all). Cachectic patients had the lowest blood flow (p < 0.002). Lower blood flow in the superior mesenteric artery and CT was correlated with HF severity (p < 0.04 for all). Patients had more feelings of repletion, flatulence, intestinal murmurs, and burping (p < 0.04). Burping and nausea or vomiting were most severe in patients with cachexia (p < 0.05). Patients with lower CT blood flow had more abdominal discomfort and immunoglobulin A–antilipopolysaccharide (r = 0.76, p < 0.02). Antilipopolysaccharide response was correlated with increased growth of juxtamucosal but not stool bacteria. Patients with intestinal murmurs had greater bowel wall thickness of the sigmoid and descending colon, suggestive of edema contributing to GI symptoms (p < 0.05). In multivariate regression analysis, lower blood flow in the superior mesenteric artery, CT (p < 0.04), and inferior mesenteric artery (p = 0.056) was correlated with the presence of cardiac cachexia. Conclusions: Intestinal blood flow is reduced in patients with HF. This may contribute to juxtamucosal bacterial growth and GI symptoms in patients with advanced HF complicated by cachexia

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

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

Right ventricular and liver function in patients with chronic heart failure and cardiac cachexia

Hintergrund: Die Pathophysiologie der kardialen Kachexie ist zurzeit nicht vollständig geklärt. Wir untersuchten den Zusammenhang zwischen rechtsventrikulärer (RV) und hepatischer Funktion und kardialer Kachexie. Methoden: Wir schlossen 118 Patienten mit linksventrikulärer Ejektionsfraktion (LVEF) ≤40% ein und unterteilten diese in drei Gruppen: Patienten in New York Heart Association (NYHA)-Klasse II (n=59), NYHA-Klasse III ohne Kachexie (n=41) und NYHA-Klasse III mit Kachexie (n=18). Bei allen Patienten wurden Blutanalysen, Echokardiographie und Spiroergometrie durchgeführt. Ergebnisse: Eine eingeschränkte systolische RV-Funktion (tricuspid annular plane systolic excursion [TAPSE] ≤15 mm) bestand bei 80% der kachektischen Patienten. Beim Vergleich der Patienten in NYHA-Klasse II mit nicht-kachektischen und mit kachektischen Patienten in NYHA-Klasse III fanden wir einen kontinuierlichen Abfall der systolischen RV-Funktion (Median TAPSE 19 [Interquartilsabstand; IQR: 16-23] mm vs. 16 [IQR: 13-19] mm vs. 14 [IQR: 9-15] mm; Kruskal-Wallis p10 mmHg: 6.8 vs. 27.5 vs. 75.0%; p<0.001) als Hinweis auf eine höhergradige Rechtsherzinsuffizienz bei kardialer Kachexie. Die systolische und diastolische Funktion des linken Ventrikels unterschieden sich zwischen den kachektischen und nicht-kachektischen Patienten in NYHA-Klasse III nicht signifikant. Die Serumkonzentration der alkalischen Phosphatase und des direkten Bilirubins korrelierten mit TAPSE und RAP und waren am höchsten in den kachektischen Patienten (alle p-Werte ≤0.002), was auf eine stauungsbedingte Cholestase hinweisen könnte. Im Vergleich zu nicht- kachektischen Patienten wiesen kachektische Patienten niedrigere Serumkonzentration von Albumin auf. Die multivariable Regressionsanalyse zeigte eine unabhängige Assoziation von eingeschränkter RV-Funktion, cholestatischen Leberfunktionsparametern und Albumin mit kardialer Kachexie. Zusammenfassung: Patienten mit kardialer Kachexie zeigen häufiger eine höhergradige Rechtsherzinsuffizienz, cholestatische Leberdysfunktion und Hypoalbuminämie im Vergleich zu nicht-kachektischen Patienten im gleichen Krankheitsstadium und mit ähnlicher linksventrikulärer Funktion.Background: The mechanisms involved in cardiac cachexia remain poorly understood. We examined the association of right ventricular (RV) and hepatic dysfunction with cardiac cachexia. Methods: We prospectively enrolled 118 patients with left ventricular ejection fraction (LVEF) ≤40% who were subgrouped as follows: New York Heart Association (NYHA) class II (n=59), NYHA class III without cachexia (n=41) and NYHA class III with cachexia (n=18). All patients underwent blood collection, echocardiography and exercise testing. Results: Reduced systolic RV function (tricuspid annular plane systolic excursion [TAPSE] ≤15 mm), was present in 80% of cachectic patients. When comparing NYHA class II patients vs. non-cachectic and cachectic NYHA class III patients we found a stepwise decrease in systolic RV function (median TAPSE 19 [interquartile range; IQR: 16-23] mm vs. 16 [IQR: 13-19] mm vs. 14 [IQR: 9-15] mm, respectively; Kruskal-Wallis p<0.001) and an increase in right atrial pressure (RAP; >10 mmHg: 6.8 vs. 27.5 vs. 75.0%, respectively; p<0.001), indicating a higher degree of congestive right heart failure in cardiac cachexia. Systolic and diastolic function of the left ventricle did not differ between non-cachectic and cachectic patients in NYHA class III. Serum alkaline phosphatase and direct bilirubin correlated with TAPSE and RAP, and were highest in cachectic patients (all p≤0.002), suggesting cholestatic dysfunction due to liver congestion. As expected, cachectic patients had lower levels of serum albumin compared to non-cachectic patients. In multivariable regression analysis, RV dysfunction, cholestatic liver parameters and albumin were independently associated with the presence of cardiac cachexia. Conclusion: Patients with cardiac cachexia display a more pronounced degree of right heart failure, cholestatic liver dysfunction and hypoalbuminemia compared to non-cachectic patients of similar LVEF and NYHA class