P3712The omega-3 fatty acid eicosapentaenoic acid (EPA) is inversely associated with ischemic brain infarcts in elderly patients with atrial fibrillation

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
M F Reiner ◽  
P Baumgartner ◽  
A Wiencierz ◽  
S Aeschbacher ◽  
N Rodondi ◽  
...  

Abstract Background The association of individual omega-3 fatty acids (n-3 FAs) with ischemic stroke remains unclear. Experimental data strongly suggest that n-3 FAs reduce ischemic stroke due to their anti-thrombotic and anti-inflammatory properties. Yet, recent clinical trials yielded mixed results. While marine n-3 FA supplementation (1g/day) did not reduce stroke, icosapent ethyl, a purified eicosapentaenoic acid (EPA) ethyl ester (4g/day), significantly reduced stroke incidence in patients at high cardiovascular risk. In the current study, we examined the association of fish-derived EPA, docosapentaenoic acid (DPA), docosahexaenoic acid (DHA) and the plant-derived alpha-linolenic acid (ALA) with the prevalence of ischemic brain infarcts in elderly patients with atrial fibrillation. Methods In this cross-sectional analysis of the Swiss atrial fibrillation (swissAF) cohort study, we determined baseline whole blood n-3 FAs by gas chromatography according to the HS-Omega-3 Index methodology in 1665 patients aged ≥65 years with atrial fibrillation. Large non-cortical and cortical infarcts (LNCCI) were assessed by brain MRI. Total and individual n-3 FAs were correlated with the prevalence of LNCCI in a logit model with continuous factors. Analyses were adjusted for sex, age, body mass index, smoking, alcohol intake, family history of cardiovascular disease and atrial fibrillation, physical activity, hypertension, diabetes, chronic kidney disease, prior stroke, prior transient ischemic attack, aspirin, anticoagulation and type of atrial fibrillation. Results A total of 373 patients with LNCCI (22.4%) were identified. After adjustment, lower risk of LNCCI was associated with higher EPA (odds ratio [OR] 0.50 per increase of one percentage point EPA, 95% confidence interval [CI] 0.28–0.88) and a higher risk was detected with DPA (OR 2.39, 95% CI 1.43–4.01). No statistically significant association was detected with DHA (OR 1.13, 95% CI 0.94–1.35), ALA (OR 0.83, 95% CI 0.23–2.95) or total n-3 FAs (OR 1.03, 95% CI 0.92–1.16). Conclusions Higher levels of EPA are associated with a lower prevalence of ischemic infarcts in aged patients with atrial fibrillation. Unexpectedly, DPA shows a direct correlation with ischemic infarcts. This study demonstrates that individual n-3 FAs may differentially affect stroke risk and that supplementation of EPA may be an interesting strategy to prevent ischemic stroke in atrial fibrillation patients. Acknowledgement/Funding Swiss National Science Foundation

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.


Circulation ◽  
2020 ◽  
Vol 141 (Suppl_1) ◽  
Author(s):  
Aniqa Alam ◽  
Nemin Chen ◽  
Pamela L Lutsey ◽  
Richard MacLehose ◽  
J'Neka Claxton ◽  
...  

Background: Polypharmacy is highly prevalent in elderly individuals with chronic conditions, including atrial fibrillation (AF). The impact of polypharmacy on adverse outcomes and on treatment effectiveness in elderly AF patients remains unaddressed. Methods: We studied 338,810 AF patients ≥75 years of age with 1,761,660 active prescriptions [mean (SD), 5.1 (3.8) per patient] enrolled in the MarketScan Medicare Supplemental database in 2007-2015. Polypharmacy was defined as ≥5 active prescriptions at AF diagnosis based on outpatient pharmacy claims. AF treatments (oral anticoagulation, rhythm and rate control) and cardiovascular endpoints (ischemic stroke, bleeding, heart failure) were defined based on inpatient, outpatient and pharmacy claims. Multivariable Cox models were used to estimate associations of polypharmacy with cardiovascular endpoints and the interaction between polypharmacy and AF treatments in relation to cardiovascular endpoints. Results: Prevalence of polypharmacy was 52% (176,007 of 338,810). Patients with polypharmacy had increased risk of major bleeding [hazard ratio (HR) 1.16, 95% confidence interval (CI) 1.12, 1.20] and heart failure (HR 1.33, 95%CI 1.29, 1.36), but not of ischemic stroke (HR 0.96, 95%CI 0.92, 1.00), compared to those not with polypharmacy (Table). Polypharmacy status did not consistently modify the effectiveness of oral anticoagulants. However, rhythm control (vs. rate control) was more effective in preventing heart failure hospitalization in patients not with polypharmacy (HR 0.87, 95%CI 0.76, 0.99) than among those with polypharmacy (HR 0.98, 95%CI 0.91, 1.07, p for interaction = 0.02). Conclusion: Polypharmacy is frequent among elderly patients with AF, associated with adverse outcomes, and potentially affecting the effectiveness of AF treatments. Optimizing management of polypharmacy in elderly AF patients may lead to improved outcomes.


2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Jun Hwan Cho ◽  
Eue-Keun Choi ◽  
In-Ki Moon ◽  
Jin- Hyung Jung ◽  
Kyung-Do Han ◽  
...  

Abstract There is a paucity of information as to whether chromosomal abnormalities, including Down Syndrome, Turner Syndrome, and Klinefelter Syndrome, have an association with atrial fibrillation (AF) and ischemic stroke development. Data from 3660 patients with Down Syndrome, 2408 with Turner Syndrome, and 851 with Klinefelter Syndrome without a history of AF and ischemic stroke were collected from the Korean National Health Insurance Service (2007–2014). These patients were followed-up for new-onset AF and ischemic stroke. Age- and sex-matched control subjects (at a ratio of 1:10) were selected and compared with the patients with chromosomal abnormalities. Down Syndrome patients showed a higher incidence of AF and ischemic stroke than controls. Turner Syndrome and Klinefelter Syndrome patients showed a higher incidence of AF than did the control group, but not of stroke. Multivariate Cox regression analysis revealed that three chromosomal abnormalities were independent risk factors for AF, and Down Syndrome was independently associated with the risk of stroke. In conclusion, Down Syndrome, Turner Syndrome, and Klinefelter Syndrome showed an increased risk of AF. Down Syndrome patients only showed an increased risk of stroke. Therefore, AF surveillance and active stroke prevention would be beneficial in patients with these chromosomal abnormalities.


2021 ◽  
Vol 8 ◽  
Author(s):  
Peter Hämmerle ◽  
Christian Eick ◽  
Sven Poli ◽  
Steffen Blum ◽  
Vincent Schlageter ◽  
...  

Purpose: Silent brain infarcts (SBI) are frequently detected in patients with atrial fibrillation (AF), but it is unknown whether SBI are linked to autonomic dysfunction. We aimed to explore the association of autonomic dysfunction with SBI in AF patients.Methods: 1,358 AF patients without prior stroke or TIA underwent brain MRI and 5-min resting ECG. We divided our cohort into AF patients who presented in sinus rhythm (SR-group, n = 816) or AF (AF-group, n = 542). HRV triangular index (HRVI), standard deviation of normal-to-normal intervals, mean heart rate, root mean square root of successive differences of normal-to-normal intervals, 5-min total power and power in the low frequency, high frequency and very low frequency range were calculated. Primary outcome was presence of SBI in the SR group, defined as large non-cortical or cortical infarcts. Secondary outcomes were SBI volumes and topography.Results: Mean age was 72 ± 9 years, 27% were female. SBI were detected in 10.5% of the SR group and in 19.9% of the AF group (p < 0.001). HRVI <15 was the only HRV parameter associated with the presence of SBI after adjustment for clinical covariates in the SR group [odds ratio (OR) 1.67; 95% confidence interval (CI): 1.03–2.70; p = 0.037]. HRVI <15 was associated with larger brain infarct volumes [β (95% CI) −0.47 (−0.84; −0.09), p = 0.016] in the SR group and was more frequently observed in patients with right- than left-hemispheric SBI (p = 0.017).Conclusion: Impaired HRVI is associated with SBI in AF patients. AF patients with autonomic dysfunction might undergo systematic brain MRI screening to initiate intensified medical treatment.Clinical Trials Gov Identifier: NCT02105844.


Stroke ◽  
2005 ◽  
Vol 36 (11) ◽  
pp. 2362-2366 ◽  
Author(s):  
Yoko Miyasaka ◽  
Marion E. Barnes ◽  
Bernard J. Gersh ◽  
Stephen S. Cha ◽  
James B. Seward ◽  
...  

Neurology ◽  
2018 ◽  
Vol 91 (22) ◽  
pp. e2067-e2077 ◽  
Author(s):  
Grant Mair ◽  
Rüdiger von Kummer ◽  
Zoe Morris ◽  
Anders von Heijne ◽  
Nick Bradey ◽  
...  

ObjectiveTo determine whether alteplase alters the development of ischemic lesions on brain imaging after stroke.MethodsThe Third International Stroke Trial (IST-3) was a randomized controlled trial of IV alteplase for ischemic stroke. We assessed CT or brain MRI at baseline (pretreatment) and 24 to 48 hours posttreatment for acute lesion visibility, extent, and swelling, masked to all other data. We analyzed associations between treatment allocation, change in brain tissue appearances between baseline and follow-up imaging, and 6-month functional outcome in IST-3. We performed a meta-analysis of randomized trials of alteplase vs control with pre- and postrandomization imaging.ResultsOf 3,035 patients recruited in IST-3, 2,916 had baseline and follow-up brain imaging. Progression in either lesion extent or swelling independently predicted poorer 6-month outcome (adjusted odds ratio [OR] = 0.92, 95% confidence interval [CI] 0.88–0.96, p < 0.001; OR = 0.73, 95% CI 0.66–0.79, p < 0.001, respectively). Patients allocated alteplase were less likely than controls to develop increased lesion visibility at follow-up (OR = 0.77, 95% CI 0.67–0.89, p < 0.001), but there was no evidence that alteplase reduced progression of lesion extent or swelling. In meta-analysis of 6 trials including IST-3 (n = 4,757), allocation to alteplase was associated with a reduction in ischemic lesion extent on follow-up imaging (OR = 0.85, 95% CI 0.76–0.95, p = 0.004).ConclusionAlteplase was associated with reduced short-term progression in lesion visibility. In meta-analysis, alteplase reduced lesion extent. These findings may indicate that alteplase improves functional outcome by reducing tissue damage.Classification of evidenceThis study provides Class II evidence that IV alteplase impedes the progression of ischemic brain lesions on imaging after stroke.


2019 ◽  
Vol 6 ◽  
pp. 205435811987871 ◽  
Author(s):  
Mark Findlay ◽  
Rachael MacIsaac ◽  
Mary Joan MacLeod ◽  
Wendy Metcalfe ◽  
Manish M. Sood ◽  
...  

Background: Stroke is common in patients with end-stage renal disease (ESRD) treated with hemodialysis (HD) and associated with high mortality rate. In the general population, atrial fibrillation (AF) is a major risk factor for stroke and therapeutic anticoagulation is associated with risk reduction, whereas in ESRD the relationship is less clear. Objective: The purpose of this study is to demonstrate the influence of AF on stroke rates and probability in those on HD following competing risk analyses. Design: A national record linkage cohort study. Setting: All renal and stroke units in Scotland, UK. Patients: All patients with ESRD receiving HD within Scotland from 2005 to 2013 (follow-up to 2015). Measurements: Demographic, clinical, and laboratory data were linked between the Scottish Renal Registry, Scottish Stroke Care Audit, and hospital discharge data. Stroke was defined as a fatal or nonfatal event and mortality derived from national records. Methods: Associations for stroke were determined using competing risk models: the cause-specific hazards model and the Fine and Gray subdistribution hazards model accounting for the competing risk of death in models of all stroke, ischemic stroke, and first-ever stroke. Results: Of 5502 patients treated with HD with 12 348.6-year follow-up, 363 (6.6%) experienced stroke. The stroke incidence rate was 26.7 per 1000 patient-years. Multivariable regression on the cause-specific hazard for stroke demonstrated age, hazard ratio (HR) (95% confidence interval [CI]) = 1.04 (1.03-1.05); AF, HR (95% CI) = 1.88 (1.25-2.83); prior stroke, HR (95% CI) = 2.29 (1.48-3.54), and diabetes, HR (95% CI) = 1.92 (1.45-2.53); serum phosphate, HR (95% CI) = 2.15 (1.56-2.99); lower body weight, HR (95% CI) = 0.99 (0.98-1.00); lower hemoglobin, HR (95% CI) = 0.88 (0.77-0.99); and systolic blood pressure (BP), HR (95% CI) = 1.01 (1.00-1.02), to be associated with an increased stroke rate. In contrast, the subdistribution HRs obtained following Fine and Gray regression demonstrated that AF, weight, and hemoglobin were not associated with stroke risk. In both models, AF was significantly associated with nonstroke death. Limitations: Our analyses derive from retrospective data sets and thus can only describe association not causation. Data on anticoagulant use are not available. Conclusions: The incidence of stroke in HD patients is high. The competing risk of “prestroke” mortality affects the relationship between AF and risk of future stroke. Trial designs for interventions to reduce stroke risk in HD patients, such as anticoagulation for AF, should take account of competing risks affecting associations between risk factors and outcomes.


2021 ◽  
pp. 174749302110580
Author(s):  
Mukul Sharma ◽  
Eric E Smith ◽  
Lesly A Pearce ◽  
Kanjana S Perera ◽  
Scott E Kasner ◽  
...  

Background Covert brain infarcts are associated with important neurological morbidity. Their incidence in patients with embolic stroke of undetermined source (ESUS) is unknown. Aims To assess the incidence of covert brain infarcts and cerebral microbleeds using MRI in a prospective substudy of the NAVIGATE ESUS randomized trial and to evaluate the effects of antithrombotic therapies. Methods At 87 sites in 15 countries, substudy participants were randomly assigned to receive rivaroxaban 15 mg daily or aspirin 100 mg daily and underwent brain MRI near randomization and after study termination. The primary outcome was incident brain infarct (clinical ischemic stroke or covert brain infarct). Brain infarcts and microbleeds were ascertained centrally by readers unaware of treatment. Treatment effects were estimated using logistic regression. Results Among the 718 substudy participants with interpretable, paired MRIs, the mean age was 67 years and 61% were men with a median of 52 days between the qualifying ischemic stroke and randomization and a median of seven days between randomization and baseline MRI. During the median (IQR) 11 (12) month interval between scans, clinical ischemic strokes occurred in 27 (4%) participants, while 60 (9%) of the remaining participants had an incident covert brain infarct detected by MRI. Assignment to rivaroxaban was not associated with reduction in the incidence of brain infarct (OR 0.77, 95% CI 0.49, 1.2) or of covert brain infarct among those without clinical stroke (OR 0.85, 95% CI 0.50, 1.4). New microbleeds were observed in 7% and did not differ among those assigned rivaroxaban vs. aspirin (HR 0.95, 95% CI 0.52–1.7). Conclusions Incident covert brain infarcts occurred in twice as many ESUS patients as a clinical ischemic stroke. Treatment with rivaroxaban compared with aspirin did not significantly reduce the incidence of covert brain infarcts or increase the incidence of microbleeds, but the confidence intervals for treatment effects were wide. Registration: https://www.clinicaltrials.gov . Unique identifier: NCT 02313909


Neurology ◽  
2021 ◽  
pp. 10.1212/WNL.0000000000012675
Author(s):  
Lina Rydén ◽  
Simona Sacuiu ◽  
Hanna Wetterberg ◽  
Jenna Najar ◽  
Xinxin Guo ◽  
...  

Background and Objectives:Atrial fibrillation (AF) has been associated with cognitive decline and dementia. However, the mechanisms behind these associations are not clear. Examination of cerebrovascular pathology on MRI may shed light on how AF affects the brain. This study aimed to determine whether AF is associated with a broad range of cerebrovascular diseases, beyond the well-known association with symptomatic stroke, including silent infarcts and markers of small vessel disease, e.g. cerebral microbleeds (CMBs), white matter hyperintensities (WMHs), and lacunes, in a population-based sample of 70-year-olds.Methods:Data were obtained from the Gothenburg H70 Birth Cohort Studies, where individuals are invited based on birth-date. This study has a cross-sectional design and includes individuals born 1944 who underwent structural brain MRI in 2014-17. AF diagnoses were based on self-report, EKG, and register data. Symptomatic stroke was based on self-report, proxy-interviews, and register data. Brain infarcts and CMBs were assessed by a radiologist. WMH volumes were measured on FLAIR images using the Lesion Segmentation Tool. Multivariate logistic regression was used to study the association between AF and infarcts/CMBs, and multivariate linear regression was used to study the association between AF and WMHs.Results:A total of 776 individuals were included and 65 (8.4%) had AF. AF was associated with symptomatic stroke (OR 4.5, 95% CI 2.1-9.5), and MRI findings of large infarcts (OR 5.0, 95% CI 1.5-15.9), lacunes (OR 2.7, 95% CI 1.2-5.6), and silent brain infarcts (OR 3.5; 95% CI 1.6-7.4). Among those with symptomatic stroke, individuals with AF had larger WMH volumes (0.0137 ml/total intracranial volume (TIV), 95% CI 0.0074-0.0252) compared to those without AF (0.0043 ml/TIV, 95% CI 0.0029-0.0064). There was no association between AF and WMH volumes among those without symptomatic stroke. In addition, AF was associated to CMBs in the frontal lobe.Discussion:AF was associated with broad range of cerebrovascular pathologies. Further research is needed to establish whether cerebrovascular MRI markers can be added to current treatment guidelines to further personalise anticoagulant treatment in AF patients and to further characterize the pathogenetic processes underlying the associations between AF and cerebrovascular diseases, as well as dementia.


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