Response by Chang and Han to Letter Regarding Article, “Influence of Hemoglobin Concentration on Stroke Recurrence and Composite Vascular Events”

Background: Accumulating evidence suggests that high blood pressure (BP) increases the risk of cerebral oedema and haemorrhagic transformation of the ischaemic stroke (IS), and that low BP in acute ischaemic stroke (AIS) is associated with a poor prognosis. The best possible management of hypertension after AIS is still uncertain. Materials and Methods: English databases were searched to identify relevant randomized controlled trials assessing the effects of early BP lowering (started within the first 48 h) after IS on outcome from January 1990 to August 2015. We set strict inclusion criteria and used the Review Manager 5.2 software from Cochrane Collaboration to calculate the combined risk ratio (RR). Result: Eight studies met our criteria. Early BP lowering after AIS did not significantly affect the risk of early and long-term death (RR 1.22; 95% CI 0.69-2.16 and RR 1.03; 95% CI 0.62-1.71), early and long-term dependency (RR 1.02; 95% CI 0.94-1.10 and RR 1.07; 95% CI 0.84-1.36), early and long-term death or dependency (RR 1.04; 95% CI 0.94-1.19 and RR 1.00; 95% CI 0.95-1.05), long-term stroke recurrence (RR 0.74; 95% CI 0.49-1.11), long-term myocardial infarction (RR 0.99; 95% CI 0.27-3.61), and long-term vascular events (RR 0.97; 95% CI 0.72-1.31). Conclusion: Our results revealed neither support nor opposition to early BP lowering (started within 48 h) after AIS; individualized BP management based on the patients' condition may be a good choice.

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Abstract TP438: Japanese versus Non-Japanese Patients With Transient Ischemic Attack or Minor Stroke: Five-Year Risk of Stroke and Vascular Events

Stroke ◽

10.1161/str.51.suppl_1.tp438 ◽

2020 ◽

Vol 51 (Suppl_1) ◽

Author(s):

Shinichiro Uchiyama ◽

Takao Hoshino ◽

Hugo Charles ◽

Kenji Kamiyama ◽

Taizen Nakase ◽

...

Keyword(s):

Intracranial Hemorrhage ◽

Transient Ischemic Attack ◽

Japanese Patients ◽

Minor Stroke ◽

Stroke Recurrence ◽

Large Artery ◽

Vascular Events ◽

Minor Ischemic Stroke ◽

Ischemic Attack

Background: We have reported 5-year risk of stroke and vascular events after a transient ischemic attack (TIA) or minor ischemic stroke in patients enrolled into the TIAregistry.org, which was an international multicenter-cooperative, prospective registry (N Engl J Med 2018;378:2182-90). We conducted subanalysis on the 5-year follow-up data of Japanese patients in comparison with non-Japanese patients. Methods: The patients were classified into two groups on ethnicity, Japanese (n=345) and non-Japanese (n=3502), and their 5-year event rates were compared. We also determined predictors of five-year stroke in both groups. Results: Death from vascular cause (0.9% vs 2.7%, HR 0.28, 95% CI 0.09-0.89, p=0.031) and death from any cause (7.8% vs 9.9%, HR 0.67, 95% CI 0.45-0.99, p=0.045) were fewer in Japanese patients than in non-Japanese patients, while stroke (13.9% vs 7.2%, HR 1.78, 95% CI 1.31-2.43, p<0.001) and intracranial hemorrhage (3.2% vs 0.8%, HR 3.61. 95% CI 1.78-7.30, p<0.001) were more common in Japanese than non-Japanese patients during five-year follow-up period. Caplan-Meyer curves at five-years showed that the rates of stroke was also significantly higher in Japanese than non-Japanese patients (log-rank test, p=0.001). Predictors for stroke recurrence at five years were large artery atherosclerosis (HR 1.81, 95% CI 1.31-2.52, p<0.001), cardioembolism (HR 1.71, 95% CI 1.18-2.47, p=0.004), multiple acute infarction (HR 1.77, 95% CI 1.27-2.45, p<0.001) and ABCD 2 score 6 or 7 (HR 1.96, 95% CI 1.38-2.78, p<0.001) in non-Japanese patients, although only large artery atherosclerosis (HR 3.28, 95% CI 1.13-9.54, p=0.029) was a predictor for stroke recurrence in Japanese patients. Conclusions: Recurrence of stroke and intracranial hemorrhage were more prevalent in Japanese than non-Japanese patients. Large artery atherosclerosis was a predictor for stroke recurrence not only in non-Japanese patients but also in Japanese patients.

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Abstract P343: Relationship of Infarct Volume to Inflammation and Prognostic Significance in Patients With Acute Ischemic Stroke

Stroke ◽

10.1161/str.52.suppl_1.p343 ◽

2021 ◽

Vol 52 (Suppl_1) ◽

Author(s):

Lingling Ding ◽

Zixiao Li ◽

Yongjun Wang

Keyword(s):

Ischemic Stroke ◽

Deep Learning ◽

Acute Ischemic Stroke ◽

Functional Outcome ◽

Acute Inflammation ◽

Infarct Volume ◽

Prognostic Significance ◽

Stroke Recurrence ◽

Vascular Events ◽

Poor Functional Outcome

Background and Purpose: The diffusion weighted imaging (DWI) lesion volumes in acute ischemic stroke (AIS) can be automatically measured using deep learning-based segmentation algorithms. We aim to explore the prognostic significance of artificial intelligence-predicted infarct volume, and the association of markers of acute inflammation with the infarct volume. Methods: 12,598 AIS/TIA patients were included in this analysis. Intarct volume was automatically measured using a U-Net model for acute ischemic stroke lesion segmentation on DWI. Participants were divided into 5 subgroups according to infarct volume. Spearman’s correlations were employed to study the association between infarct volume and markers of acute inflammation. Multivariable logistic regression and Cox proportional hazards model were performed to explore the relationship between infarct volume and the incidence of poor functional outcome (modified Rankin scale score 3-6), stroke recurrence or combined vascular events at 3 months. Results: The U-Net model prediction correlated and agreed well with manual annotation ground truth for infarct volume (r=0.96; P<0.001). There were positive correlations between the infarct volume and markers of acute inflammation (neutrophil [r=0.175; P<0.001], hs-CRP [r=0.180; P<0.001], and IL-6 [r=0.225; P<0.001]). Compared with those without DWI lesions, patients with the largest infarct volume (4th Quartile) were nearly five times more likely to have poor functional outcome (mRS 3-6) (adjusted odds ratio, 4.70; 95% confidence intervals [CI], 3.29-6.72; P for trend<0.001) after adjustment for confounding factors and markers of acute inflammation. The infarct volume category was significantly associated with stroke recurrence (adjusted hazard ratios [HRs], 1.0, 1.43[0.95,2.17], 2.22[1.49,3.29], 2.06[1.40,3.05], 2.26[1.52,3.36]; P for trend<0.001) and combined vascular events(adjusted HRs, 1.0, 1.38[0.92,2.09], 2.25[1.53,3.32], 2.03[1.38,2.98], 2.28[1.54,3.36]; P for trend<0.001). Conclusions: Infarct volume measured automatically by deep learning-based tool was a strong predictor of poor functional outcome as well as stroke recurrence, with the potential for widespread adoption in both research and clinical settings.

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Abstract WP419: Secondary Prevention Of Cardiovascular Events With Lifestyle Intervention In Patients With Mild Ischemic Stroke - A Randomized Controlled Trial -

Stroke ◽

10.1161/str.44.suppl_1.awp419 ◽

2013 ◽

Vol 44 (suppl_1) ◽

Author(s):

Sumio Yamada ◽

Yuji Kono ◽

Kotaro Iwatsu ◽

Hisako Okumura ◽

Junko Yamaguchi ◽

...

Keyword(s):

Ischemic Stroke ◽

Lifestyle Intervention ◽

Lifestyle Modification ◽

Controlled Trial ◽

Intervention Group ◽

Stroke Recurrence ◽

Control Group ◽

Vascular Events ◽

Randomized Controlled ◽

New Onset

Introduction: Lifestyle modification is associated with a substantially decreased risk of cardiovascular events. However, the role of lifestyle intervention for the secondary prevention in patients with ischemic stroke (IS) is inadequately defined. We assessed the hypothesis that lifestyle intervention which comprised exercise, salt reduction and nutrition advice could reduce new onset of vascular events in patients with mild IS. Methods: We conducted a single-blind randomized controlled trial that enrolled 66 patients (45 men, 21 women; mean age, 63.5 yo) with acute mild ischemic stroke. The patients were randomly allocated to a lifestyle intervention group (n = 33) or control group (n = 33). We performed lifestyle interventions, which comprised exercise training, salt restriction and nutrition advice for 24 weeks. The primary endpoint was ospitalization due to stroke recurrence and new onset of coronary heart disease. We also evaluated blood pressure, serum lipid profile and hemoglobin A1c to compare the efficacy of the lifestyle modification intervention. Results: This trial was terminated earlier than expected because the prespecified early stopping rule for efficacy had been met. After 24 weeks intervention period, the intervention group showed a significant decrease in the clinic and home blood pressure and significant increase in the high density lipoprotein cholesterol (HDL-C) levels from the baseline to the 6-month assessment (clinic and home SBP, P <0.001; HDL-C, P =0.018), with significant differences between the randomized groups (clinic and home SBP, P <0.001; HDL-C, P =0.022). Median duration of follow-up was 2.9 years, 12 patients allocated the control group and 1 patient allocated the lifestyle intervention group had at least one major vascular event. A sequential plans analysis indicated that lifestyle intervention superior to control in interim analysis. Kaplan-Meier survival curves after log-rank test showed significant prognostic difference between randomized groups ( P =0.005). Conclusions: In conclusion, the results of this study indicate that lifestyle intervention is beneficial for preventing stroke recurrence and other vascular events.

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Intracranial Vertebrobasilar Calcification in Patients with Ischemic Stroke Is a Predictor of Recurrent Stroke, Vascular Disease, and Death: A Case-Control Study

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph17062013 ◽

2020 ◽

Vol 17 (6) ◽

pp. 2013

Author(s):

Jožef Magdič ◽

Nino Cmor ◽

Matevž Kaube ◽

Tanja Hojs Fabjan ◽

Larissa Hauer ◽

...

Keyword(s):

Ischemic Stroke ◽

Vascular Disease ◽

Recurrent Stroke ◽

Case Control ◽

University Hospital ◽

Stroke Recurrence ◽

Vascular Events ◽

Vertebrobasilar Artery ◽

The Impact

Intracranial artery calcification can be detected on nonenhanced brain computer tomography (NECT) and is a predictor of early vascular events. Here, we assessed the impact of vertebrobasilar artery calcification (VBC) on the long-term risk for recurrent stroke and vascular events. We performed a case-control trial of all consecutive stroke patients admitted to the University Hospital of Maribor, Slovenia over a period of 14 months. VBC was defined as presence of a hyperdense area within vertebrobasilar arteries that exceeds > 90 Hounsfield units as seen on NECT. Clinical follow-up information was obtained from the hospital documentation system and mortality registry of the district and included recurrent stroke, subsequent vascular events (myocardial infarction, heart failure, peripheral arterial occlusive disease), and death. We followed a total of 448 patients for a median of 1505 days (interquartile range, IQR 188-2479). Evidence for VBC was present in 243 (54.2%) patients. Median age was 76 years, recurrent stroke occurred in 33 (7.4%), any vascular events in 71 (15.8%), and death in 276 (61.6%). VBC was associated with a higher risk of recurrent stroke (hazard ratio, HR 3.13, 95% confidence interval (CI 1.35–7.20)) and vascular events (HR 2.05, 95% CI 1.21–3.47). Advanced age, male gender, and ischemic stroke involving the entire anterior circulation raised the likelihood for death. We conclude that the presence of VBC in patients with ischemic stroke is a short- and long-term prognostic factor for stroke recurrence and subsequent manifestation of acute vascular disease. Further understanding of the pathophysiology of VBC is warranted.

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Statin therapy in acute cardioembolic stroke with no guidance-based indication

Neurology ◽

10.1212/wnl.0000000000009397 ◽

2020 ◽

Vol 94 (19) ◽

pp. e1984-e1995 ◽

Cited By ~ 3

Author(s):

Hong-Kyun Park ◽

Ji Sung Lee ◽

Keun-Sik Hong ◽

Yong-Jin Cho ◽

Jong-Moo Park ◽

...

Keyword(s):

Statin Therapy ◽

Acute Stage ◽

Cardioembolic Stroke ◽

Rank Test ◽

Stroke Recurrence ◽

Vascular Events ◽

Weighting Method ◽

Stroke Registry ◽

Vascular Death ◽

Hazard Ratios

ObjectiveIt is uncertain whether patients with cardioembolic stroke and without a guidance-based indication for statin therapy should be administered a statin for prevention of subsequent vascular events. This study was performed to determine whether the statin therapy is beneficial in preventing major vascular events in this population.MethodsUsing a prospective multicenter stroke registry database, we identified patients with acute cardioembolic stroke who were hospitalized between 2008 and 2015. Patients who had other established indications for statin therapy according to current guidelines were excluded. Major vascular event was defined as a composite of stroke recurrence, myocardial infarction, and vascular death. We performed frailty model analysis with the robust sandwich variance estimator using the stabilized inverse probability of treatment weighting method to estimate hazard ratios of statin therapy on outcomes.ResultsOf 6,124 patients with cardioembolic stroke, 2,888 (male 44.6%, mean age 75.3 years, 95% confidence interval [CI] 74.8–75.8) were eligible, and 1,863 (64.5%) were on statin therapy during hospitalization. After a median follow-up of 359 days, cumulative incidences of major vascular events were 9.3% in the statin users and 20.5% in the nonusers (p < 0.001 by log-rank test). The adjusted hazard ratios of statin therapy were 0.39 (95% CI 0.31–0.48) for major vascular events, 0.81 (95% CI 0.57–1.16) for stroke recurrence, 0.28 (95% CI 0.21–0.36) for vascular death, and 0.53 (95% CI 0.45–0.61) for all-cause death.ConclusionStarting statin during the acute stage of ischemic stroke may reduce the risk of major vascular events, vascular death, and all-cause death in patients with cardioembolic stroke with no guidance-based indication for statin.

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Hydroxyurea as an Alternative to Blood Transfusions for the Prevention of Recurrent Stroke in Children With Sickle Cell Disease

Blood ◽

10.1182/blood.v94.9.3022 ◽

1999 ◽

Vol 94 (9) ◽

pp. 3022-3026 ◽

Cited By ~ 111

Author(s):

Russell E. Ware ◽

Sherri A. Zimmerman ◽

William H. Schultz

Keyword(s):

Sickle Cell Disease ◽

Iron Overload ◽

Sickle Cell ◽

Recurrent Stroke ◽

Fetal Hemoglobin ◽

Hemoglobin Concentration ◽

Stroke Recurrence ◽

Hematologic Toxicity ◽

Cell Disease ◽

F Cells

Abstract Children with sickle cell disease (SCD) and stroke receive chronic transfusions to prevent stroke recurrence. Transfusion risks including infection, erythrocyte allosensitization, and iron overload suggest a need for alternative therapies. We previously used hydroxyurea (HU) and phlebotomy in two young adults with SCD and stroke as an alternative to transfusions. We have now prospectively discontinued transfusions in 16 pediatric patients with SCD and stroke. Reasons to discontinue transfusions included erythrocyte alloantibodies or autoantibodies, recurrent stroke on transfusions, iron overload, noncompliance, and deferoxamine allergy. HU was started at 15 mg/kg/d and escalated to 30 mg/kg/d based on hematologic toxicity. Patients with iron overload underwent phlebotomy. The children have been off transfusions 22 months, (range, 3 to 52 months). Their average HU dose is 24.9 ± 4.2 mg/kg/d, hemoglobin concentration is 9.4 ± 1.3 g/dL, and mean corpuscular volume (MCV) is 112 ± 9 fL. Maximum percentage fetal hemoglobin (%HbF) is 20.6% ± 8.0% and percentage HbF-containing erythrocytes (%F cells) is 79.3% ± 14.7%. Fourteen patients underwent phlebotomy with an average of 8,993 mL (267 mL/kg) removed. Serum ferritin has decreased from 2,630 to 424 ng/mL, and 4 children have normal ferritin values. Three patients (19%) had neurological events considered recurrent stroke, each 3 to 4 months after discontinuing transfusions, but before maximal HU effects. These preliminary data suggest some children with SCD and stroke may discontinue chronic transfusions and use HU therapy to prevent stroke recurrence. Phlebotomy is well-tolerated and significantly reduces iron overload. Modifications in HU therapy to raise HbF more rapidly might increase protection against stroke recurrence.

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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 ◽

10.1371/journal.pone.0254562 ◽

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.

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