scholarly journals Epigenome-Wide Analyses Identify Two Novel Associations With Recurrent Stroke in the Vitamin Intervention for Stroke Prevention Clinical Trial

2018 ◽  
Vol 9 ◽  
Author(s):  
Nicole M. Davis Armstrong ◽  
Wei-Min Chen ◽  
Michael S. Brewer ◽  
Stephen R. Williams ◽  
Michèle M. Sale ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Stroke Prevention ◽  
Recurrent Stroke ◽  
Prevention Clinical Trial ◽  
Novel Associations

scholarly journals Secondary Prevention by Structured Semi-Interactive Stroke Prevention Package in India (SPRINT INDIA) study protocol

2019 ◽  
Vol 15 (1) ◽  
pp. 109-115
Author(s):  
Mahesh Pundlik Kate ◽  
Deepti Arora ◽  
Shweta Jain Verma ◽  
PN Sylaja ◽  
Vishnu Renjith ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Coronary Artery ◽  
Secondary Prevention ◽  
Acute Stroke ◽  
Stroke Prevention ◽  
Recurrent Stroke ◽  
Standard Of Care ◽  
Clinical Trial Registry ◽  
Cardiovascular Morbidity And Mortality ◽  
Recurrent Strokes

Rationale Recurrent stroke, cardiovascular morbidity, and mortality are important causes of poor outcome in patients with index stroke. Despite the availability of best medical management recurrent stroke occur in up to 15–20% of patients with stroke in India. Education for stroke prevention could be a strategy to prevent recurrent strokes. Hypothesis We hypothesize that a structured semi-interactive stroke prevention package can reduce the risk of recurrent strokes, acute coronary artery syndrome, and death in patients with sub-acute stroke at the end of one year. Design Secondary Prevention by Structured Semi-Interactive Stroke Prevention Package in INDIA (SPRINT INDIA) is a multi-center stroke trial involving 25 centers under the Indian Stroke Clinical Trial Network. Patients with first ever sub-acute stroke within two days to three months of onset, age 18–85 years, mRS <5, showing recent stroke in imaging are included. Participants or caregivers able to read and complete tasks suggested in a stroke prevention workbook and have a cellular device for receiving short message service and watching videos. A total of 5830 stroke patients speaking 11 different languages are being randomized to intervention or control arm. Patients in the intervention arm are receiving a stroke prevention workbook, regular educational short messages, and videos. All patients in the control arm are receiving standard of care management. Summary Structured semi-interactive stroke prevention package may reduce the risk of recurrent strokes, acute coronary artery syndrome, and death in patients with sub-acute stroke. Trial registration This trial is registered with clinicaltrials.gov (NCT03228979) and CTRI (Clinical Trial Registry India; CTRI/2017/09/009600).

scholarly journals DNA methylation analyses identify an intronic ZDHHC6 locus associated with time to recurrent stroke in the Vitamin Intervention for Stroke Prevention (VISP) clinical trial

PLoS ONE ◽  
2021 ◽  
Vol 16 (7) ◽  
pp. e0254562
Author(s):  
Nicole M. Davis Armstrong ◽  
Wei-Min Chen ◽  
Fang-Chi Hsu ◽  
Michael S. Brewer ◽  
Natalia Cullell ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Dna Methylation ◽  
Stroke Prevention ◽  
Recurrent Stroke ◽  
University Hospital ◽  
Stroke Recurrence ◽  
Primary Analysis ◽  
Vascular Events ◽  
Network Analyses ◽  
Epigenetic Biomarkers

Aberrant DNA methylation profiles have been implicated in numerous cardiovascular diseases; however, few studies have investigated how these epigenetic modifications contribute to stroke recurrence. The aim of this study was to identify methylation loci associated with the time to recurrent cerebro- and cardiovascular events in individuals of European and African descent. DNA methylation profiles were generated for 180 individuals from the Vitamin Intervention for Stroke Prevention clinical trial using Illumina HumanMethylation 450K BeadChip microarrays, resulting in beta values for 470,871 autosomal CpG sites. Ethnicity-stratified survival analyses were performed using Cox Proportional Hazards regression models for associations between each methylation locus and the time to recurrent stroke or composite vascular event. Results were validated in the Vall d’Hebron University Hospital cohort from Barcelona, Spain. Network analyses of the methylation loci were generated using weighted gene coexpression network analysis. Primary analysis identified four significant loci, cg04059318, ch.2.81927627R, cg03584380, and cg24875416, associated with time to recurrent stroke. Secondary analysis identified three loci, cg00076998, cg16758041, and cg02365967, associated with time to composite vascular endpoint. Locus cg03584380, which is located in an intron of ZDHHC6, was replicated in the Vall d’Hebron University Hospital cohort. The results from this study implicate the degree of methylation at cg03584380 is associated with the time of recurrence for stroke or composite vascular events across two ethnically diverse groups. Furthermore, modules of loci were associated with clinical traits and blood biomarkers including previous number of strokes, prothrombin fragments 1 + 2, thrombomodulin, thrombin-antithrombin complex, triglyceride levels, and tissue plasminogen activator. Ultimately, these loci could serve as potential epigenetic biomarkers that could identify at-risk individuals in recurrence-prone populations.

Maximizing Patient Recruitment and Retention in a Secondary Stroke Prevention Clinical Trial: Lessons Learned from the STAND FIRM Study

2016 ◽  
Vol 25 (6) ◽  
pp. 1371-1380 ◽  
Author(s):  
Tharshanah Thayabaranathan ◽  
Dominique A. Cadilhac ◽  
Velandai K. Srikanth ◽  
Sharyn M. Fitzgerald ◽  
Roger G. Evans ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Stroke Prevention ◽  
Lessons Learned ◽  
Patient Recruitment ◽  
Secondary Stroke Prevention ◽  
Recruitment And Retention ◽  
Prevention Clinical Trial

scholarly journals Multi-omic analysis of stroke recurrence in African Americans from the Vitamin Intervention for Stroke Prevention (VISP) clinical trial

PLoS ONE ◽  
2021 ◽  
Vol 16 (3) ◽  
pp. e0247257
Author(s):  
Nicole M. Davis Armstrong ◽  
Kelsey J. Spragley ◽  
Wei-Min Chen ◽  
Fang-Chi Hsu ◽  
Michael S. Brewer ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Dna Methylation ◽  
African Americans ◽  
Stroke Prevention ◽  
Recurrent Stroke ◽  
European Ancestry ◽  
Sphingolipid Metabolism ◽  
Stroke Recurrence ◽  
High Risk Population ◽  
Vascular Events

African Americans endure a nearly two-fold greater risk of suffering a stroke and are 2–3 times more likely to die from stroke compared to those of European ancestry. African Americans also have a greater risk of recurrent stroke and vascular events, which are deadlier and more disabling than incident stroke. Stroke is a multifactorial disease with both heritable and environmental risk factors. We conducted an integrative, multi-omic study on 922 plasma metabolites, 473,864 DNA methylation loci, and 556 variants from 50 African American participants of the Vitamin Intervention for Stroke Prevention clinical trial to help elucidate biomarkers contributing to recurrent stroke rates in this high risk population. Sixteen metabolites, including cotinine, N-delta-acetylornithine, and sphingomyelin (d17:1/24:1) were identified in t-tests of recurrent stroke outcome or baseline smoking status. Serum tricosanoyl sphingomyelin (d18:1/23:0) levels were significantly associated with recurrent stroke after adjusting for covariates in Cox Proportional Hazards models. Weighted Gene Co-expression Network Analysis identified moderate correlations between sphingolipid markers and clinical traits including days to recurrent stroke. Integrative analyses between genetic variants in sphingolipid pathway genes identified 29 nominal associations with metabolite levels in a one-way analysis of variance, while epigenomic analyses identified xenobiotics, predominately smoking-associated metabolites and pharmaceutical drugs, associated with methylation profiles. Taken together, our results suggest that metabolites, specifically those associated with sphingolipid metabolism, are potential plasma biomarkers for stroke recurrence in African Americans. Furthermore, genetic variation and DNA methylation may play a role in the regulation of these metabolites.

Stroke with Transfusions Changing to Hydroxyurea (SWiTCH): A Phase 3 Randomized Clinical Trial for Treatment of Children with Sickle Cell Anemia, Previous Stroke, and Iron Overload

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 844-844 ◽  
Author(s):  
Russell E. Ware ◽  
Ronald W Helms
Keyword(s):  
Clinical Trial ◽  
Iron Overload ◽  
Recurrence Rate ◽  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
Stroke Prevention ◽  
Recurrent Stroke ◽  
Stroke Recurrence ◽  
Secondary Stroke Prevention ◽  
Study Enrollment

Abstract Abstract 844 Stroke occurs in 5–10% of children with sickle cell anemia (SCA) and has a very high (50-90%) risk of recurrence without therapy. Chronic monthly erythrocyte transfusions are administered to prevent recurrent stroke, but their long term use is limited by incomplete protection and serious side effects, including alloimmunization and iron overload. An alternative to transfusion for secondary stroke prevention in SCA is needed, ideally one that also improves the management of transfusional iron overload. Stroke With Transfusions Changing to Hydroxyurea (SWiTCH) was an NHLBI-sponsored Phase III multicenter randomized controlled clinical trial for children with SCA, stroke, and iron overload (NCT00122980). The primary goal of SWiTCH was to compare 30 months of alternative therapy (hydroxyurea and phlebotomy) with standard therapy (transfusions and chelation) for the prevention of secondary stroke and reduction of transfusional iron overload. SWiTCH had several distinctive study features with novel methodological and design components, including a composite primary endpoint containing both stroke recurrence rate and iron burden, a transfusion overlap period in the alternative arm to reduce the risk of recurrent stroke until a stable hydroxyurea dose was reached, and an inclusive independent stroke adjudication process for all suspected new neurological events. An increased number of recurrent stroke events were predicted to occur in the alternative arm compared to the standard arm, but this risk would be balanced by improved management of transfusional iron burden by repeated phlebotomy. A total of 161 pediatric subjects (83 male, 78 female) with SCA, documented stroke, and iron overload were enrolled in SWiTCH between October 2006 and April 2009; after screening 133 were randomized and received study treatment (67 participants in the alternative arm, 66 in the standard arm). The average age at enrollment was 12.9 ± 4.0 years with an average of 7.0 ± 3.7 years of chronic transfusions for secondary stroke prevention; 12% had already suffered a recurrent stroke before study enrollment. The average baseline liver iron concentration (LIC) by biopsy was 15.5 ± 10.1 mg Fe per gm dry weight liver and most subjects were receiving oral chelation treatment at the time of study enrollment. At study enrollment, 28% of subjects had previously known RBC alloantibodies (most within the CDE-Kell antigen systems) and 16% had previous RBC autoantibody formation. Baseline laboratory and clinical parameters were well-balanced between treatment arms, although a higher number of subjects with moya-moya were randomized to hydroxyurea/phlebotomy. A scheduled interim data analysis was performed after 1/3 of the subjects had completed all exit studies. This analysis (which occurred with ∼80% of all patient-years of study treatment completed) concluded that the LIC was not statistically different between the two treatment arms so no increased stroke risk was justified. Accordingly, following review by the Data and Safety Monitoring Board, the NHLBI terminated the SWiTCH trial in May 2010; at that time, the on-study stroke recurrence rate was 7 of 67 participants in the alternative arm compared to 0 of 66 participants in the standard arm. At the completion of all study treatment, the recurrent stroke events remained at 7 versus 0 (alternative versus standard arm), while TIA events occurred in 6 and 9 subjects respectively, and deaths were equivalent (1 and 1, both unrelated to treatment). SWiTCH primary and secondary endpoint analyses are currently in progress and details of the study results will be presented. Disclosures: Off Label Use: Hydroxyurea is used to reduce complications of sickle cell anemia.

scholarly journals How to increase the value of self-reported health service data by using data linkage: a case study

2020 ◽  
Vol 30 (Supplement_5) ◽  
Author(s):  
W Peng ◽  
J Maguire ◽  
A Hayen ◽  
J Adams ◽  
D Sibbritt
Keyword(s):  
Data Collection ◽  
Health Service ◽  
Health Services ◽  
Stroke Prevention ◽  
Data Linkage ◽  
Recurrent Stroke ◽  
Service Planning ◽  
Stroke Survivors ◽  
Reported Data

Abstract Background This is a case study for recurrent stroke prevention. Lifestyle factors account for about 80% of the risk of recurrent stroke. Most health services studies examining stroke prevention rely on stroke survivors' self-reported lifestyle behaviour data. How can researchers increase the value of collected self-reported data to provide additional information for more comprehensive assessments? Methods 45 and Up Study is the largest ongoing study in the Southern Hemisphere focusing on the health of people aged 45 years and older living in NSW, Australia. This case study linked self-reported longitudinal lifestyle data in the 45 and Up Study, with corresponding mortality data (i.e. NSW Registry of Births, Deaths and Marriages & NSW Cause of Death Unit Record File) and hospital data (i.e. NSW Admitted Patient Data Collection) via the Centre for Health Record Linkage (CHeReL). The main outcome measures are health services, clinical outcomes, and mortality rates for stroke care. The analyses will include descriptive analysis, multivariate regression analysis, and survival analysis. Results A total of 8410 stroke survivors who participated in the 45 and Up Study were included in this data linkage study. From January 2006 to December 2015, 99249 hospital claims (mean: 13 times admission to hospital per person) and 2656 death registration records have been linked to these participants. The mean age of the stroke survivors was 72 (SD = 11) years, with 56% being males. These results are preliminary and more analyses will be conducted by using quality of life status, clinical diagnosis, comorbidities, and procedures. Conclusions Data linkage enables researchers to generate comprehensive findings on health services studies and gain a more holistic understanding of the determinants and outcomes of stroke prevention with lower data collection costs and less burden on participants. Key messages Data linkage brings about a new opportunity for self-reported data on health services utilisation. It is a cost-effective way to enhance existing self-reported data via the data linkage approach to increase its usefulness for informing health service planning.

Abstract P252: Discharge Antithrombotic Therapy for Ischemic Stroke Patients With Prior Aspirin Failure

Stroke ◽  
2021 ◽  
Vol 52 (Suppl_1) ◽  
Author(s):  
Ying Xian ◽  
Haolin Xu ◽  
Deepak L Bhatt ◽  
Gregg C Fonarow ◽  
Eric E Smith ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Stroke Prevention ◽  
Antithrombotic Therapy ◽  
Recurrent Stroke ◽  
Oral Anticoagulants ◽  
The United States ◽  
Future Research ◽  
Large Artery ◽  
Secondary Stroke Prevention ◽  
Stroke Registry

Introduction: Aspirin is one of the most commonly used medications for cardiovascular disease and stroke prevention. Many older patients who present with a first or recurrent stroke are already on aspirin monotherapy, yet little evidence is available to guide antithrombotic strategies for these patients. Method: Using data from the American Heart Association Get With The Guidelines-Stroke Registry, we described discharge antithrombotic treatment pattern among Medicare beneficiaries without atrial fibrillation who were discharged alive for acute ischemic stroke from 1734 hospitals in the United States between October 2012 and December 2017. Results: Of 261,634 ischemic stroke survivors, 100,016 (38.2%) were on prior aspirin monotherapy (median age 78 years; 53% women; 79.4% initial stroke and 20.6% recurrent stroke). The most common discharge antithrombotics (Figure) were 81 mg aspirin monotherapy (20.9%), 325 mg aspirin monotherapy (18.2%), clopidogrel monotherapy (17.8%), and dual antiplatelet therapy (DAPT) of 81 mg aspirin and clopidogrel (17.1%). Combined, aspirin monotherapy, clopidogrel monotherapy, and DAPT accounted for 86.8% of discharge antithrombotics. The rest of 13.2% were discharged on either aspirin/dipyridamole, warfarin or non-vitamin K antagonist oral anticoagulants with or without antiplatelet, or no antithrombotics at all. Among patients with documented stroke etiology (TOAST criteria), 81 mg aspirin monotherapy (21.2-24.0%) was the most commonly prescribed antithrombotic for secondary stroke prevention. The only exception was those with large-artery atherosclerosis, in which, 25.3% received DAPT of 81 mg aspirin and clopidogrel at discharge. Conclusion: Substantial variations exist in discharge antithrombotic therapy for secondary stroke prevention in ischemic stroke with prior aspirin failure. Future research is needed to identify best management strategies to care for this complex but common clinical scenario.

scholarly journals Thoracoscopic Ablation with Appendage Ligation versus Medical Therapy for Stroke Prevention a Proof-of-Concept Randomized Trial

2016 ◽  
Vol 11 (2) ◽  
pp. 99-105 ◽  
Author(s):  
Thomas M. Beaver ◽  
Vishnumurthy Shushrutha Hedna ◽  
Anna Y. Khanna ◽  
William M. Miles ◽  
Catherine C. Price ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Medical Management ◽  
Stroke Prevention ◽  
Normal Sinus Rhythm ◽  
Recurrent Stroke ◽  
Outcome Variable ◽  
Concept Design ◽  
Proof Of Concept ◽  
Surgical Morbidity

Objective Atrial fibrillation (AF) has a demonstrable effect on quality of life (QOL). Recurrent stroke occurs in 10% of patients with AF. The objective of this study was to demonstrate proof of concept that thoracoscopic pulmonary vein isolation and atrial appendage ligation (TPVIAL) could prevent recurrent stroke and could potentially improve QOL in patients with AF with a previous stroke. Methods The study was a National Institutes of Health-funded single-center proof-of-concept design that randomized 23 patients with AF-related stroke to TPVIAL (n = 12) or to medical management (n = 11). Quality of life was the primary outcome variable; secondary end points included restoration of rhythm, recurrent stroke, and surgical morbidity. Results Quality-of-life subscores at 3 and 6 months revealed improvements in energy and decreases in fatigue in the TPVIAL arm [baseline, 33 (19.8); 3 months, 49.5 (20.6), P = 0.01; 6 months, 55.5 (14.4), P = 0.03]. At 12-month follow-up, there were no recurrent strokes in the TPVIAL group. In the medically treated arm, two patients at 6 months (P = 0.22) and three total patients at 12 months (P = 0.09) had recurrent ischemic stroke. There was one death in the medical management arm. In the TPVIAL arm, no AF recurrence occurred in patients with paroxysmal AF, and one patient had recurrence of persistent and long-standing AF. Seven patients in the TPVIAL arm discontinued warfarin therapy for secondary stroke prevention. Conclusions This small proof-of-concept study showed that TPVIAL improved QOL on two subscores and restored normal sinus rhythm in all but one patient, and it showed the potential to prevent secondary stroke. A larger study will be needed.

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