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1.
Body weight changes and incidence of cachexia after stroke.
Scherbakov, N, Pietrock, C, Sandek, A, Ebner, N, Valentova, M, Springer, J, Schefold, JC, von Haehling, S, Anker, SD, Norman, K, et al
Journal of cachexia, sarcopenia and muscle. 2019;(3):611-620
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Abstract
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.
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Causes and Risk Factors of Cerebral Ischemic Events in Patients With Atrial Fibrillation Treated With Non-Vitamin K Antagonist Oral Anticoagulants for Stroke Prevention.
Paciaroni, M, Agnelli, G, Caso, V, Silvestrelli, G, Seiffge, DJ, Engelter, S, De Marchis, GM, Polymeris, A, Zedde, ML, Yaghi, S, et al
Stroke. 2019;(8):2168-2174
Abstract
Background and Purpose- Despite treatment with oral anticoagulants, patients with nonvalvular atrial fibrillation (AF) may experience ischemic cerebrovascular events. The aims of this case-control study in patients with AF were to identify the pathogenesis of and the risk factors for cerebrovascular ischemic events occurring during non-vitamin K antagonist oral anticoagulants (NOACs) therapy for stroke prevention. Methods- Cases were consecutive patients with AF who had acute cerebrovascular ischemic events during NOAC treatment. Controls were consecutive patients with AF who did not have cerebrovascular events during NOACs treatment. Results- Overall, 713 cases (641 ischemic strokes and 72 transient ischemic attacks; median age, 80.0 years; interquartile range, 12; median National Institutes of Health Stroke Scale on admission, 6.0; interquartile range, 10) and 700 controls (median age, 72.0 years; interquartile range, 8) were included in the study. Recurrent stroke was classified as cardioembolic in 455 cases (63.9%) according to the A-S-C-O-D (A, atherosclerosis; S, small vessel disease; C, cardiac pathology; O, other causes; D, dissection) classification. On multivariable analysis, off-label low dose of NOACs (odds ratio [OR], 3.18; 95% CI, 1.95-5.85), atrial enlargement (OR, 6.64; 95% CI, 4.63-9.52), hyperlipidemia (OR, 2.40; 95% CI, 1.83-3.16), and CHA2DS2-VASc score (OR, 1.72 for each point increase; 95% CI, 1.58-1.88) were associated with ischemic events. Among the CHA2DS2-VASc components, age was older and presence of diabetes mellitus, congestive heart failure, and history of stroke or transient ischemic attack more common in patients who had acute cerebrovascular ischemic events. Paroxysmal AF was inversely associated with ischemic events (OR, 0.45; 95% CI, 0.33-0.61). Conclusions- In patients with AF treated with NOACs who had a cerebrovascular event, mostly but not exclusively of cardioembolic pathogenesis, off-label low dose, atrial enlargement, hyperlipidemia, and high CHA2DS2-VASc score were associated with increased risk of cerebrovascular events.
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3.
Ischaemic stroke.
Campbell, BCV, De Silva, DA, Macleod, MR, Coutts, SB, Schwamm, LH, Davis, SM, Donnan, GA
Nature reviews. Disease primers. 2019;(1):70
Abstract
Stroke is the second highest cause of death globally and a leading cause of disability, with an increasing incidence in developing countries. Ischaemic stroke caused by arterial occlusion is responsible for the majority of strokes. Management focuses on rapid reperfusion with intravenous thrombolysis and endovascular thrombectomy, which both reduce disability but are time-critical. Accordingly, improving the system of care to reduce treatment delays is key to maximizing the benefits of reperfusion therapies. Intravenous thrombolysis reduces disability when administered within 4.5 h of the onset of stroke. Thrombolysis also benefits selected patients with evidence from perfusion imaging of salvageable brain tissue for up to 9 h and in patients who awake with stroke symptoms. Endovascular thrombectomy reduces disability in a broad group of patients with large vessel occlusion when performed within 6 h of stroke onset and in patients selected by perfusion imaging up to 24 h following stroke onset. Secondary prevention of ischaemic stroke shares many common elements with cardiovascular risk management in other fields, including blood pressure control, cholesterol management and antithrombotic medications. Other preventative interventions are tailored to the mechanism of stroke, such as anticoagulation for atrial fibrillation and carotid endarterectomy for severe symptomatic carotid artery stenosis.
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4.
Carotid Plaque Positron Emission Tomography Imaging and Cerebral Ischemic Disease.
Chaker, S, Al-Dasuqi, K, Baradaran, H, Demetres, M, Delgado, D, Nehmeh, S, Osborne, JR, Christos, PJ, Kamel, H, Gupta, A
Stroke. 2019;(8):2072-2079
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Abstract
Background and Purpose- The clinical utility of positron emission tomography (PET) imaging in evaluating carotid artery plaque vulnerability remains unclear. Two tracers of recent interest for carotid plaque imaging are 18F-fluorodeoxyglucose (18F-FDG) and 18F-sodium fluoride (18F-NaF). We performed a systematic review and meta-analysis evaluating the association between carotid artery 18F-FDG or 18F-NaF uptake and recent or future cerebral ischemic events. Methods- A systematic review of Ovid MEDLINE, Ovid EMBASE, and the Cochrane library was conducted from inception to December 2017 for articles evaluating PET tracer uptake in recently symptomatic versus asymptomatic carotid arteries, and articles evaluating carotid uptake in relation to future ischemic events. Cerebral ischemic events were defined as ipsilateral strokes, transient ischemic attacks, or amaurosis fugax. We quantitatively pooled studies by a random-effects model when 3 or more studies were amenable for analysis. We assessed the standardized mean difference between tracer uptake in the symptomatic versus asymptomatic carotid artery using Cohen's d metric. Results- After screening 4144 unique articles, 13 prospective cohort studies assessing carotid artery 18F-FDG uptake in patients with recent cerebral ischemia were eligible for review. Eleven cohorts of 290 subjects scanned with 18F-FDG were eligible for meta-analysis. We found that carotid arteries ipsilateral to recent ischemic events had significantly higher 18F-FDG uptake than asymptomatic arteries (Cohen's d =0.492; CI=0.130-0.855; P=0.008) as well as significant heterogeneity (Cochran's Q =31.5; P=0.0005; I2=68.3%). Meta-regression was not performed due to the limited number of studies in the analysis. Only 2 studies investigating 18F-NaF PET imaging, and another 2 articles investigating ischemic event recurrence were found. Conclusions- Recent ipsilateral cerebral ischemia may be associated with increased carotid 18F-FDG uptake on PET imaging regardless of degree of carotid stenosis, although significant heterogeneity was found, and these results should be interpreted with caution. Emerging evidence suggests a similar association may be present with 18F-NaF plaque uptake. More studies are warranted to provide definitive conclusions on the utility of 18F-FDG or 18F-NaF in carotid plaque evaluation before investigating carotid PET as a diagnostic tool for cerebral ischemic events.
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White matter hyperintensity quantification in large-scale clinical acute ischemic stroke cohorts - The MRI-GENIE study.
Schirmer, MD, Dalca, AV, Sridharan, R, Giese, AK, Donahue, KL, Nardin, MJ, Mocking, SJT, McIntosh, EC, Frid, P, Wasselius, J, et al
NeuroImage. Clinical. 2019;:101884
Abstract
White matter hyperintensity (WMH) burden is a critically important cerebrovascular phenotype linked to prediction of diagnosis and prognosis of diseases, such as acute ischemic stroke (AIS). However, current approaches to its quantification on clinical MRI often rely on time intensive manual delineation of the disease on T2 fluid attenuated inverse recovery (FLAIR), which hinders high-throughput analyses such as genetic discovery. In this work, we present a fully automated pipeline for quantification of WMH in clinical large-scale studies of AIS. The pipeline incorporates automated brain extraction, intensity normalization and WMH segmentation using spatial priors. We first propose a brain extraction algorithm based on a fully convolutional deep learning architecture, specifically designed for clinical FLAIR images. We demonstrate that our method for brain extraction outperforms two commonly used and publicly available methods on clinical quality images in a set of 144 subject scans across 12 acquisition centers, based on dice coefficient (median 0.95; inter-quartile range 0.94-0.95; p < 0.01) and Pearson correlation of total brain volume (r = 0.90). Subsequently, we apply it to the large-scale clinical multi-site MRI-GENIE study (N = 2783) and identify a decrease in total brain volume of -2.4 cc/year. Additionally, we show that the resulting total brain volumes can successfully be used for quality control of image preprocessing. Finally, we obtain WMH volumes by building on an existing automatic WMH segmentation algorithm that delineates and distinguishes between different cerebrovascular pathologies. The learning method mimics expert knowledge of the spatial distribution of the WMH burden using a convolutional auto-encoder. This enables successful computation of WMH volumes of 2533 clinical AIS patients. We utilize these results to demonstrate the increase of WMH burden with age (0.950 cc/year) and show that single site estimates can be biased by the number of subjects recruited.
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Adherence to the Mediterranean diet and risk of stroke and stroke subtypes.
Chen, GC, Neelakantan, N, Martín-Calvo, N, Koh, WP, Yuan, JM, Bonaccio, M, Iacoviello, L, Martínez-González, MA, Qin, LQ, van Dam, RM
European journal of epidemiology. 2019;(4):337-349
Abstract
Several meta-analyses including a small number of cohorts showed inverse associations between the Mediterranean Diet (MedDiet) and risk of stroke. However, it remains unclear whether such a relation varies by region of the study population or by major subtypes of stroke. We searched PubMed and EMBASE databases for relevant studies and we further included unpublished results from the Singapore Chinese Health Study (N = 57,078) and the Seguimiento Universidad de Navarra (SUN) study (N = 12,670). We used a random-effects model to calculate summary relative risk (RR) with 95% confidence intervals (CI) of stroke for each 4-point increment of the MedDiet score, roughly corresponding to the difference between extreme quintiles of the MedDiet score among participants of the included studies. The final analyses included 20 prospective cohort studies involving 682,149 participants and 16,739 stroke cases. The summary RRs for each 4-point increment of the MedDiet score were 0.84 (95% CI 0.81-0.88; I2 = 11.5%) for all combined, 0.76 (95% CI 0.65-0.89) for studies in Mediterranean populations and 0.86 (95% CI 0.83-0.89) for those in non-Mediterranean populations. Lower risk of stroke associated with higher MedDiet score also was observed in the analyses stratified by study population and methodological characteristics including study risk of bias, version of the MedDiet index, and definition of moderate alcohol consumption. The MedDiet was similarly associated with lower risk of ischemic stroke (RR 0.86, 95% CI 0.81-0.91; nine studies) and hemorrhagic stroke (RR 0.83, 95% CI 0.74-0.93; eight studies). Our meta-analysis suggests that adhering to the Mediterranean diet was associated with lower risk of stroke in both Mediterranean and non-Mediterranean populations, and for both ischemic stroke and hemorrhagic stroke risk.
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Direct Oral Anticoagulants Versus Vitamin K Antagonists in Real-life Patients With Atrial Fibrillation. A Systematic Review and Meta-analysis.
Escobar, C, Martí-Almor, J, Pérez Cabeza, A, Martínez-Zapata, MJ
Revista espanola de cardiologia (English ed.). 2019;(4):305-316
Abstract
INTRODUCTION AND OBJECTIVES To assess the effectiveness of direct oral anticoagulants vs vitamin K antagonists in real-life patients with atrial fibrillation. METHODS A systematic review was performed according to Cochrane methodological standards. The results were reported according to the PRISMA statement. The ROBINS-I tool was used to assess risk of bias. RESULTS A total of 27 different studies publishing data in 30 publications were included. In the studies with a follow-up up to 1 year, apixaban (HR, 0.93; 95%CI, 0.71-1.20) and dabigatran (HR, 0.95; 95%CI, 0.80-1.13) did not significantly reduce the risk of ischemic stroke vs warfarin, whereas rivaroxaban significantly reduced this risk (HR, 0.83; 95%CI, 0.73-0.94). Apixaban (HR, 0.66; 95%CI, 0.55-0.80) and dabigatran (HR, 0.83; 95%CI, 0.70-0.97) significantly reduced the major bleeding risk vs warfarin, but not rivaroxaban (HR, 1.02; 95%CI, 0.95-1.10), although with a high statistical heterogeneity among studies. Apixaban (HR, 0.56; 95%CI, 0.42-0.73), dabigatran (HR, 0.45; 95%CI, 0.39-0.51), and rivaroxaban (HR, 0.66; 95%CI, 0.49-0.88) significantly reduced the risk of intracranial bleeding vs warfarin. Reduced doses of direct oral anticoagulants were associated with a slightly better safety profile, but with a marked reduction in stroke prevention effectiveness. CONCLUSIONS Data from this meta-analysis suggest that, vs warfarin, the stroke prevention effectiveness and bleeding risk of direct oral anticoagulants may differ in real-life patients with atrial fibrillation.
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PCSK9 inhibition in patients with and without prior myocardial infarction or ischemic stroke: A pooled analysis of nine randomized-controlled studies of alirocumab.
Bruckert, E, Kereiakes, DJ, Koren, MJ, Louie, MJ, Letierce, A, Miller, K, Cannon, CP
Journal of clinical lipidology. 2019;(3):443-454
Abstract
BACKGROUND Patients with prior cardiovascular events are at very high risk of recurrent events and may benefit from low-density lipoprotein cholesterol (LDL-C) lowering beyond that achieved with maximally tolerated statins. OBJECTIVE To assess potential differences between the efficacy and safety of the proprotein convertase subtilisin/kexin type 9 inhibitor, alirocumab, in patients with vs without prior myocardial infarction (MI)/ischemic stroke. METHODS Data (n = 4880) were pooled from nine ODYSSEY phase 3 trials of alirocumab 75/150 mg or 150 mg every 2 weeks, mostly on background statins ± other lipid-lowering therapies. Analyses were performed according to statin status, alirocumab dose, and control (placebo or ezetimibe). RESULTS Baseline LDL-C, non-high-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and apolipoprotein B levels were lower and lipoprotein(a) higher in patients with than without prior MI/ischemic stroke. LDL-C levels were reduced from baseline to week 24 in patients with (51.1%-62.9%) and without (43.6%-58.3%) prior MI/ischemic stroke, with no significant interaction between prior MI/ischemic stroke status and LDL-C-lowering efficacy of alirocumab vs controls. Alirocumab significantly reduced other lipid/lipoproteins (including lipoprotein[a]) similarly in patients with/without MI/ischemic stroke. Week 24 LDL-C goal attainment rates for subgroups with/without prior MI/ischemic stroke on background statins were 74.1%-84.8% and 63.7%-74.7%, respectively. The safety profile of alirocumab was generally similar regardless of prior MI/ischemic stroke status. CONCLUSIONS Alirocumab significantly reduced LDL-C and other atherogenic lipids/lipoproteins in patients with prior MI/ischemic stroke, and the majority of this very high cardiovascular risk population achieved LDL-C goals; efficacy and safety results were similar in patients without prior MI/ischemic stroke.
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Myocardial infarction after acute ischaemic stroke: Incidence, mortality and risk factors.
Pana, TA, Wood, AD, Mamas, MA, Clark, AB, Bettencourt-Silva, JH, McLernon, DJ, Potter, JF, Myint, PK, ,
Acta neurologica Scandinavica. 2019;(3):219-228
Abstract
OBJECTIVES To determine the risk factor profiles associated with post-acute ischaemic stroke (AIS) myocardial infarction (MI) over long-term follow-up. METHODS This observational study includes prospectively identified AIS patients (n = 9840) admitted to a UK regional centre between January 2003 and December 2016 (median follow-up: 4.72 years). Predictors of post-stroke MI during follow-up were examined using logistic and Cox regression models for in-hospital and post-discharge events, respectively. MI incidence was determined using a competing risk non-parametric estimator. The influence of post-stroke MI on mortality was examined using Cox regressions. RESULTS Mean age (SD) of study participants was 77.3 (12.2) years (48% males). Factors associated with in-hospital MI (OR [95% CI]) were increasing blood glucose (1.80 [1.17-2.77] per 10 mmol/L), total leucocyte count (1.25 [1.01-1.54] per 10 × 109 /L) and CRP (1.05 [1.02-1.08] per 10 mg/L increase). Age (HR [95% CI] = 1.03 [1.01-1.06]), coronary heart disease (1.59 [1.01-2.50]), chronic kidney disease (2.58 [1.44-4.63]) and cancers (1.76 [1.08-2.89]) were associated with incident MI between discharge and one-year follow-up. Age (1.02 [1.00-1.03]), diabetes (1.96 [1.38-2.65]), congestive heart failure (2.07 [1.44-2.99]), coronary heart disease (1.81 [1.31-2.50]), hypertension [1.86 (1.24-2.79)] and peripheral vascular disease (2.25 [1.40-3.63]) were associated with incident MI between 1 and 5 years after discharge. Diabetes (2.01 [1.09-3.72]), hypertension (3.69 [1.44-9.45]) and peripheral vascular disease (2.46 [1.02-5.98]) were associated with incident MI between 5 and 10 years after discharge. Cumulative MI incidence over 10 years was 5.4%. MI during all follow-up periods (discharge-1, 1-5, 5-10 years) was associated with increased risk of death (respective HR [95% CI] = 3.26 [2.51-4.15], 1.96 [1.58-2.42] and 1.92 [1.26-2.93]). CONCLUSIONS In conclusion, prognosis is poor in post-stroke MI. We highlight a range of potential areas to focus preventative efforts.
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A Systematic Review of Neuroprotective Efficacy and Safety of DL-3-N-Butylphthalide in Ischemic Stroke.
Xu, ZQ, Zhou, Y, Shao, BZ, Zhang, JJ, Liu, C
The American journal of Chinese medicine. 2019;(3):507-525
Abstract
DL-3-n-butylphthalide (NBP) is widely used as a neuroprotective drug for ischemic stroke in China. There is, however, no established evidence on its efficacy and safety for patients with ischemic stroke. We, therefore, conducted a systematic review and meta-analysis. Major databases were searched to identify randomized controlled trials that assessed the efficacy and safety of NBP on ischemic stroke, reporting outcomes among patients treated with NBP alone or combined with standard anti-ischemic stroke drugs vs. standard anti-ischemic stroke drugs. Continuous data were validated, extracted and synthesized of standardized mean differences (SMDs) by random effects models, while dichotomous data were validated, extracted and synthesized of relative risk (RR) by random effects models. Twelve randomized controlled trials involving 1160 patients were identified. Results suggested that NBP monotherapy is not superior to standard anti-ischemic stroke drugs based on the Barthel Index (SMD, 0.25; 95% CI - 0.14 to 0.63; P=0.21 ) and the National Institutes of Health Stroke Scale (SMD, 0.73; 95% CI - 0.14 to 1.59; P=0.10 ). In contrast, the combination of NBP and standard anti-ischemic stroke drugs appears to be superior to standard drugs alone, again based on both the Barthel index (SMD, 1.65; 95% CI 1.25 to 2.04; P<0.01 ) and National Institutes of Health Stroke Scale (SMD, 1.40; 95% CI 0.72 to 2.09; P<0.01 ). However, the use of NBP may cause adverse event on the function of the liver (RR, 3.55; 95% CI 1.19 to 10.56; P<0.05 ). The combination use of NBP and standard anti-ischemic stroke drugs is more effective than standard drugs. However, more attention should be payed to the adverse effects on liver function. Our findings provided an established evidence of NBP as a neuroprotective drug, which may improve the current guideline for treatment of ischemic stroke.