Abstract T MP57: Coexisting Cerebrovascular Disease and Risk of Occult Atrial Fibrillation in Patients With Embolic Stroke of Undetermined Source

Stroke ◽  
2015 ◽  
Vol 46 (suppl_1) ◽  
Author(s):  
Esther Rojo ◽  
María Sandín-Fuentes ◽  
Ana I Calleja ◽  
Gabriel Largaespada ◽  
Elisa Cortijo ◽  
...  

Background and objective: Secondary prevention after embolic stroke of undetermined source (ESUS) remains a clinical problem. Presence of asymptomatic cerebral large-artery atherosclerosis or small vessel disease could be aprioristically taken as an indicator of a lower risk for an occult cardiac source of emboli, thus influencing our secondary prevention strategy. We aimed to study the relationship between presence and degree of coexisting cerebrovascular disease and the risk of occult paroxysmal atrial fibrillation (OPAF) in ESUS patients. Methods: Longitudinal prospective study in patients fulfilling ESUS criteria after complete neurovascular and cardiac diagnostic workup, who were implanted with a subcutaneous REVEAL-XT loop-recorder to detect OPAF and followed-up for≥ 6 months. At baseline, cerebral large-artery atherosclerosis was assessed with cervical and transcranial ultrasound. Brain magnetic resonance imaging was used to evaluate small vessel disease. Periventricular (PV) and subcortical (SC) white matter hiperintensities (WMH) were categorized using the Fazekas score. Results: We studied 136 ESUS patients from October 2010 to December 2013 (71 men, mean age 67), who were followed-up for a mean time of 594 days. OPAF was detected in 56 (41%) of them. No relationship was found between extracranial or intracranial atherosclerosis and OPAF. Kaplan-Meier curves and crude Cox-regression analyses found associations between OPAF risk and age, smoking, CHA2DS2VASC score, presence of lacunar infarctions, and presence and degree of PVWMH & SCWMH. A multivariable-adjusted Cox regression model identified grade 2-3 PVWMH (HR 3.6, [2.0-6.5], p<0.001) and age as independent predictors of OPAF. Conclusion: Coexisting small vessel disease, specifically in the form of periventricular WMH, is a predictor of OPAF in ESUS patients. Presence of large-artery atherosclerosis does not lower the risk for OPAF. Therefore, OPAF should be actively pursued in ESUS patients regardless the coexistence of asymptomatic cerebrovascular disease.

Author(s):  
Hugh Markus ◽  
Anthony Pereira ◽  
Geoffrey Cloud

This chapter on common causes of ischaemic stroke reviews the major pathologies underlying ischaemic stroke, namely large-artery disease, cardioembolism, and small-vessel disease. Large-vessel extra- and intracranial atherosclerotic cerebrovascular disease is covered. Cardioembolic aetiologies of stroke including atrial fibrillation and valvular heart disease are discussed. Small-vessel disease causing lacunar stroke and possible heterogonous pathologies underlying this subtype are covered. Dolichoectasia of arteries as a potential cause of stroke and the newer concept of embolic stroke of undetermined source are also discussed.


Neurology ◽  
2020 ◽  
Vol 94 (24) ◽  
pp. e2581-e2591 ◽  
Author(s):  
Sandro Marini ◽  
Marios K. Georgakis ◽  
Jaeyoon Chung ◽  
Jonathan Q.A. Henry ◽  
Martin Dichgans ◽  
...  

ObjectiveLeveraging large-scale genetic data, we aimed to identify shared pathogenic mechanisms and causal relationships between impaired kidney function and cerebrovascular disease phenotypes.MethodsWe used summary statistics from genome-wide association studies (GWAS) of kidney function traits (chronic kidney disease diagnosis, estimated glomerular filtration rate [eGFR], and urinary albumin-to-creatinine ratio [UACR]) and cerebrovascular disease phenotypes (ischemic stroke and its subtypes, intracerebral hemorrhage [ICH], and white matter hyperintensities [WMH] on brain MRI). We (1) tested the genetic overlap between them with polygenic risk scores (PRS), (2) searched for common pleiotropic loci with pairwise GWAS analyses, and (3) explored causal associations by employing 2-sample Mendelian randomization.ResultsA PRS for lower eGFR was associated with higher large artery stroke (LAS) risk (p = 1 × 10−4). Multiple pleiotropic loci were identified between kidney function traits and cerebrovascular disease phenotypes, with 12q24 associated with eGFR and both LAS and small vessel stroke (SVS), and 2q33 associated with UACR and both SVS and WMH. Mendelian randomization revealed associations of both lower eGFR (odds ratio [OR] per 1-log decrement, 2.10; 95% confidence interval [CI], 1.38–3.21) and higher UACR (OR per 1-log increment, 2.35; 95% CI, 1.12–4.94) with a higher risk of LAS, as well as between higher UACR and higher risk of ICH.ConclusionsImpaired kidney function, as assessed by decreased eGFR and increased UACR, may be causally involved in the pathogenesis of LAS. Increased UACR, previously proposed as a marker of systemic small vessel disease, is involved in ICH risk and shares a genetic risk factor at 2q33 with manifestations of cerebral small vessel disease.


Stroke ◽  
2020 ◽  
Vol 51 (2) ◽  
pp. 655-658 ◽  
Author(s):  
Eiko Higuchi ◽  
Sono Toi ◽  
Yuka Shirai ◽  
Takao Hoshino ◽  
Kentaro Ishizuka ◽  
...  

Background and Purpose— Embolic stroke of undetermined source (ESUS) has been proposed to cause thromboembolic infarction from unknown but potential embolic sources. However, an embolus remains undetected in ESUS. The goal of this study was to characterize the prevalence and risk factors of microembolic signals (MESs) in ESUS. Methods— We examined 108 patients with acute ischemic stroke in the internal carotid artery territory or transient ischemic attack within 14 days of symptom onset and who were admitted to our hospital between April 2017 and March 2019. MESs were monitored in the middle cerebral artery on transcranial Doppler for 60 minutes. We examined the prevalence and number of MES in ESUS and other stroke subtypes, such as cardioembolism, large artery atherosclerosis, cerebral small vessel disease, and transient ischemic attack. The present study was registered in University Hospital Medical Information Network Clinical Trials Registry (UMIN000031913). Results— MESs were detected in 33 (31%) of 108 patients. ESUS showed the highest proportion (12/24 [50%]), followed by large artery atherosclerosis (8/20 [40%]), cardioembolism (6/18 [33%]), transient ischemic attack (4/24 [17%]), and cerebral small vessel disease (3/21 [14%]). Univariate analysis showed that higher systolic blood pressure, body mass index, hemoglobin A1c, and ESUS were significantly associated with MES. In multiple logistic regression analysis, ESUS remained significantly associated with MES after adjustment for described covariates from univariate analysis (odds ratio, 2.86 [95% CI, 1.01–8.08]). Conclusions— This study demonstrated significant association of ESUS with MES, supporting the embolic nature of this stroke subtype. Registration— URL: https://upload.umin.ac.jp . Unique identifier: UMIN000031913.


2020 ◽  
Vol 40 (9) ◽  
Author(s):  
Qian You ◽  
Qing Peng ◽  
Zemou Yu ◽  
Haiqiang Jin ◽  
Jing Zhang ◽  
...  

Abstract Background: Sphingolipids mainly consist of ceramides (Cer), sphingomyelins (SM) and glycosphingolipids. Sphingolipids are related with coronary heart disease and metabolic disease, but there’re few studies about cerebrovascular disease. The purpose was to detect sphingolipids in plasma of patients with large artery atherosclerosis (LAA) cerebrovascular disease and cerebral small vessel disease (CSVD) to explore the similarities and differences of pathogenesis of the two subtypes. Methods: 20 patients with LAA cerebrovascular disease, 20 patients with age-related CSVD, 10 patients with Fabry disease and 14 controls were enrolled from October 2017 to January 2019. Ultra-high performance liquid chromatography-quadruple-time-of-flight mass spectrometry/mass spectrometry was used to determine sphingolipids. Univariate combined with multivariate analysis was used for comparison. Receiver operating characteristic curves were used to determine sensitivities and specificities. Results: 276 sphingolipids were detected, including 39 Cer, 3 ceramide phosphates, 72 glycosphingolipids and 162 SM. (1) Cer (d36:3), Cer (d34:2), Cer (d38:6), Cer (d36:4) and Cer (d16:0/18:1) were increased in LAA; SM (d34:1), Cer (d34:2), Cer (d36:4), Cer (d16:0/18:1), Cer (d38:6), Cer (d36:3) and Cer (d32:0) were increased in age-related CSVD. (2) Cer (d36:4) and SM (d34:1) were increased in age-related CSVD compared with LAA. (3) Total trihexosyl ceramides were increased in Fabry group compared with control (P&lt;0.05); SM (d34:1) was increased in Fabry group. Conclusions: Ceramides are increased in both LAA and age-related CSVD, which may be related to similar risk factors and pathophysiological process of arteriosclerosis; SM is increased in both age-related CSVD and Fabry disease, suggesting that increased SM may be associated with CSVD. Glycosphingolipids, trihexosylceramides in particular, are increased in Fabry disease.


2021 ◽  
Author(s):  
Wei-Ju Lee ◽  
Kun-Hsien Chou ◽  
Pei-Lin Lee ◽  
Li-Ning Peng ◽  
Pei-Ning Wang ◽  
...  

Abstract The present study aimed to determine whether a recently proposed cerebral small vessel disease (CSVD) classification scheme could differentiate the 5-year all-cause mortality in middle-to-old aged asymptomatic CSVD. Stroke-free and non-demented participants recruited from the community-based I-Lan Longitudinal Aging Study underwent baseline brain magnetic resonance imaging (MRI) between 2011 and 2014 and were followed-up between 2018 and 2019. The study population was classified into control (non-CSVD) and CSVD type 1–4 groups based on MRI markers. We determined the association with mortality using Cox regression models, adjusting for the age, sex, and vascular risk factors. A total of 735 participants were included. During a mean follow-up of 5.7 years, 62 (8.4%) died. There were 335 CSVD type 1 (57.9 ± 5.9 years), 249 type 2 (65.6 ± 8.1 years), 52 type 3 (67.8 ± 9.2 years), and 38 type 4 (64.3 ± 9.0 years). Among the four CSVD types, CSVD type 4 individuals had significantly higher all-cause mortality (adjusted hazard ratio = 3.7, 95% confidence interval = 1.3−10.8) compared to controls. This novel MRI-based CSVD classification scheme was able to identify individuals at risk of mortality at an asymptomatic, early stage of disease and might be applied for future community-based health research and policy.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Wei-Ju Lee ◽  
Kun-Hsien Chou ◽  
Pei-Lin Lee ◽  
Li-Ning Peng ◽  
Pei-Ning Wang ◽  
...  

AbstractThe present study aimed to determine whether a recently proposed cerebral small vessel disease (CSVD) classification scheme could differentiate the 5-year all-cause mortality in middle-to-old aged asymptomatic CSVD. Stroke-free and non-demented participants recruited from the community-based I-Lan Longitudinal Aging Study underwent baseline brain magnetic resonance imaging (MRI) between 2011 and 2014 and were followed-up between 2018 and 2019. The study population was classified into control (non-CSVD) and CSVD type 1–4 groups based on MRI markers. We determined the association with mortality using Cox regression models, adjusting for the age, sex, and vascular risk factors. A total of 735 participants were included. During a mean follow-up of 5.7 years, 62 (8.4%) died. There were 335 CSVD type 1 (57.9 ± 5.9 years), 249 type 2 (65.6 ± 8.1 years), 52 type 3 (67.8 ± 9.2 years), and 38 type 4 (64.3 ± 9.0 years). Among the four CSVD types, CSVD type 4 individuals had significantly higher all-cause mortality (adjusted hazard ratio = 5.0, 95% confidence interval 1.6–15.3) compared to controls. This novel MRI-based CSVD classification scheme was able to identify individuals at risk of mortality at an asymptomatic, early stage of disease and might be applied for future community-based health research and policy.


Nutrients ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 651
Author(s):  
Martin F. Reiner ◽  
Philipp Baumgartner ◽  
Andrea Wiencierz ◽  
Michael Coslovsky ◽  
Nicole R. Bonetti ◽  
...  

The omega-3 fatty acid (n-3 FA) eicosapentaenoic acid (EPA) reduces stroke in patients with atherosclerotic cardiovascular disease. Whether EPA affects stroke or cerebral small vessel dis-ease in patients with atrial fibrillation (AF) remains uncertain. EPA, docosahexaenoic acid (DHA), docosapentaenoic acid (DPA), and alpha-linolenic acid (ALA) were determined by gas chromatography in 1657 AF patients from the Swiss Atrial Fibrillation study. All patients underwent brain MRI to detect ischemic brain infarcts, classified as large noncortical or cortical infarcts (LNCCIs); markers of small vessel disease, classified as small noncortical infarcts (SNCIs), number of microbleeds, and white matter lesion (WML) volumes. Individual and total n-3 FAs (EPA + DHA + DPA + ALA) were correlated with LNCCIs and SNCIs using logistic regression, with numbers of microbleeds using a hurdle model, and WML volumes using linear regression. LNCCIs were detected in 372 patients (22.5%). EPA correlated inversely with the prevalence of LNCCIs (odds ratio [OR] 0.51 per increase of 1 percentage point EPA, 95% confidence interval [CI] 0.29–0.90). DPA correlated with a higher LNCCI prevalence (OR 2.48, 95%CI 1.49–4.13). No associations with LNCCIs were found for DHA, ALA, and total n-3 FAs. Neither individual nor total n-3 FAs correlated with markers of small vessel disease. In conclusion, EPA correlates inversely with the prevalence of ischemic brain infarcts, but not with markers of small vessel disease in patients with AF.


2021 ◽  
pp. 1-4
Author(s):  
Oscar H. Del Brutto ◽  
Robertino M. Mera

A total of 590 older adults of Amerindian ancestry living in rural Ecuador received anthropometric measurements and a brain magnetic resonance imaging to estimate the total cerebral small vessel disease (cSVD) score. A fully adjusted ordinal logistic regression model, with categories of the total cSVD score as the dependent variable, disclosed significant associations between the waist circumference, the waist-to-hip, and the waist-to-height ratios – but not the body mass index (BMI) – and the cSVD burden. Indices of abdominal obesity may better correlate with severity of cSVD than the BMI in Amerindians. Phenotypic characteristics of this population may account for these results.


2015 ◽  
Vol 36 (1) ◽  
pp. 72-94 ◽  
Author(s):  
Anna Poggesi ◽  
Marco Pasi ◽  
Francesca Pescini ◽  
Leonardo Pantoni ◽  
Domenico Inzitari

The term cerebral small vessel disease (SVD) refers to a group of pathologic processes with various etiologies that affect small arteries, arterioles, venules, and capillaries of the brain. Magnetic resonance imaging (MRI) correlates of SVD are lacunes, recent small subcortical infarcts, white-matter hyperintensities, enlarged perivascular spaces, microbleeds, and brain atrophy. Endothelial dysfunction is thought to have a role in the mechanisms leading to SVD-related brain changes, and the study of endothelial dysfunction has been proposed as an important step for a better comprehension of cerebral SVD. Among available methods to assess endothelial function in vivo, measurement of molecules of endothelial origin in peripheral blood is currently receiving selective attention. These molecules include products of endothelial cells that change when the endothelium is activated, as well as molecules that reflect endothelial damage and repair. This review examines the main molecular factors involved in both endothelial function and dysfunction, and the evidence linking endothelial dysfunction with cerebral SVD, and gives an overview of clinical studies that have investigated the possible association between endothelial circulating biomarkers and SVD-related brain changes.


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