Displaying all 17 publications

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  1. Cheng YC, Stanne TM, Giese AK, Ho WK, Traylor M, Amouyel P, et al.
    Stroke, 2016 Feb;47(2):307-16.
    PMID: 26732560 DOI: 10.1161/STROKEAHA.115.011328
    BACKGROUND AND PURPOSE: Although a genetic contribution to ischemic stroke is well recognized, only a handful of stroke loci have been identified by large-scale genetic association studies to date. Hypothesizing that genetic effects might be stronger for early- versus late-onset stroke, we conducted a 2-stage meta-analysis of genome-wide association studies, focusing on stroke cases with an age of onset <60 years.

    METHODS: The discovery stage of our genome-wide association studies included 4505 cases and 21 968 controls of European, South-Asian, and African ancestry, drawn from 6 studies. In Stage 2, we selected the lead genetic variants at loci with association P<5×10(-6) and performed in silico association analyses in an independent sample of ≤1003 cases and 7745 controls.

    RESULTS: One stroke susceptibility locus at 10q25 reached genome-wide significance in the combined analysis of all samples from the discovery and follow-up stages (rs11196288; odds ratio =1.41; P=9.5×10(-9)). The associated locus is in an intergenic region between TCF7L2 and HABP2. In a further analysis in an independent sample, we found that 2 single nucleotide polymorphisms in high linkage disequilibrium with rs11196288 were significantly associated with total plasma factor VII-activating protease levels, a product of HABP2.

    CONCLUSIONS: HABP2, which encodes an extracellular serine protease involved in coagulation, fibrinolysis, and inflammatory pathways, may be a genetic susceptibility locus for early-onset stroke.

    Matched MeSH terms: Stroke/etiology; Stroke/genetics*
  2. Gopalan Y, Shuaib IL, Magosso E, Ansari MA, Abu Bakar MR, Wong JW, et al.
    Stroke, 2014 May;45(5):1422-8.
    PMID: 24699052 DOI: 10.1161/STROKEAHA.113.004449
    Previous cell-based and animal studies showed mixed tocotrienols are neuroprotective, but the effect is yet to be proven in humans. Thus, the present study aimed to evaluate the protective activity of mixed tocotrienols in humans with white matter lesions (WMLs). WMLs are regarded as manifestations of cerebral small vessel disease, reflecting varying degrees of neurodegeneration and tissue damage with potential as a surrogate end point in clinical trials.
  3. King A, Shipley M, Markus H, ACES Investigators
    Stroke, 2011 Oct;42(10):2819-24.
    PMID: 21852607 DOI: 10.1161/STROKEAHA.111.622514
    Improved methods are required to identify patients with asymptomatic carotid stenosis at high risk for stroke. The Asymptomatic Carotid Emboli Study recently showed embolic signals (ES) detected by transcranial Doppler on 2 recordings that lasted 1-hour independently predict 2-year stroke risk. ES detection is time-consuming, and whether similar predictive information could be obtained from simpler recording protocols is unknown.
    Matched MeSH terms: Stroke/etiology; Stroke/ultrasonography*
  4. Kasiman K, Eikelboom JW, Hankey GJ, Lee SP, Lim JP, Lee JH, et al.
    Stroke, 2009 Jun;40(6):2209-11.
    PMID: 19372453 DOI: 10.1161/STROKEAHA.108.535237
    Increased total homocysteine (tHcy) is a risk factor for stroke. This study examines whether the efficacy of B-vitamins in reducing tHcy is modified by ethnicity in a Singaporean ischemic stroke population.
    Matched MeSH terms: Stroke/blood*
  5. Venketasubramanian N, Tan LC, Sahadevan S, Chin JJ, Krishnamoorthy ES, Hong CY, et al.
    Stroke, 2005 Mar;36(3):551-6.
    PMID: 15692124
    Stroke prevalence data among mixed Asian populations are lacking. Prevalence rates of stroke were studied among Singaporeans aged > or =50 years of Chinese, Malay, and Indian origin.
    Matched MeSH terms: Stroke/ethnology*; Stroke/epidemiology*
  6. Sahathevan R, Linden T, Villemagne VL, Churilov L, Ly JV, Rowe C, et al.
    Stroke, 2016 Jan;47(1):113-9.
    PMID: 26578658 DOI: 10.1161/STROKEAHA.115.010528
    Cardiovascular risk factors significantly increase the risk of developing Alzheimer disease. A possible mechanism may be via ischemic infarction-driving amyloid deposition. We conducted a study to determine the presence of β-amyloid in infarct, peri-infarct, and hemispheric areas after stroke. We hypothesized that an infarct would trigger β-amyloid deposition, with deposition over time.
    Matched MeSH terms: Stroke/metabolism*; Stroke/radionuclide imaging*
  7. Wong KS
    Stroke, 1999 Nov;30(11):2326-30.
    PMID: 10548666
    BACKGROUND AND PURPOSE: In Asia, there has been no international study to investigate the risk factors for early death in patients with ischemic stroke and intracerebral hemorrhage.

    METHODS: We conducted a prospective study of consecutive patients with acute stroke who were admitted to 36 participating hospitals in China, India, Indonesia, Korea, Malaysia, the Philippines, Singapore, Taiwan, Thailand, and Vietnam. With the use of a simple identical data sheet, we recorded the demographics and cardiovascular risk factors of each patient. Early death was defined as death on discharge from the acute hospital.

    RESULTS: We enrolled 2403 patients with ischemic stroke and 783 patients with intracerebral hemorrhage. Among patients with ischemic stroke, previous use of antiplatelet drugs (adjusted odds ratio [OR] 0.53; 95% confidence interval [CI] 0. 30 to 0.95) and relatively young age group 56 to 75 years (OR 0.65; 95% CI 0.42 to 1.00) were protective factors; atrial fibrillation (OR 2.23; 95% CI 1.40 to 3.57), ischemic heart disease (OR 2.03; 95% CI 1.37 to 3.05), diabetes (OR 1.52; 95% CI 1.04 to 2.22), and ex-smoker status (OR 2.18; 95% CI 1.18 to 4.05) were risk factors for early death. Among patients with intracerebral hemorrhage, hypertension (OR 0.56; 95% CI 0.38 to 0.82) and young age group 56 to 75 years old (OR 0.55; 95% CI 0.34 to 0.87) were associated with lower death rate, whereas diabetes (OR 1.74; 95% CI 1.01 to 2.98) was a risk factor for early death.

    CONCLUSIONS: In Asian patients with stroke, previous use of antiplatelet drugs nearly halved the risk of early death in patients with ischemic stroke, whereas atrial fibrillation, ischemic heart disease, diabetes, and ex-smoker status were risk factors for early death. Among patients with intracerebral hemorrhage, diabetes was associated with early death, whereas young age group and hypertension were associated with lower death rates, though no clear explanation for the hypertension association could be discerned from the data available.

    Matched MeSH terms: Stroke/mortality*
  8. Law ZK, Ali A, Krishnan K, Bischoff A, Appleton JP, Scutt P, et al.
    Stroke, 2020 01;51(1):121-128.
    PMID: 31735141 DOI: 10.1161/STROKEAHA.119.026128
    Background and Purpose- Blend, black hole, island signs, and hypodensities are reported to predict hematoma expansion in acute intracerebral hemorrhage. We explored the value of these noncontrast computed tomography signs in predicting hematoma expansion and functional outcome in our cohort of intracerebral hemorrhage. Methods- The TICH-2 (Tranexamic acid for IntraCerebral Hemorrhage-2) was a prospective randomized controlled trial exploring the efficacy and safety of tranexamic acid in acute intracerebral hemorrhage. Baseline and 24-hour computed tomography scans of trial participants were analyzed. Hematoma expansion was defined as an increase in hematoma volume of >33% or >6 mL on 24-hour computed tomography. Poor functional outcome was defined as modified Rankin Scale of 4 to 6 at day 90. Multivariable logistic regression was performed to identify predictors of hematoma expansion and poor functional outcome. Results- Of 2325 patients recruited, 2077 (89.3%) had valid baseline and 24-hour scans. Five hundred seventy patients (27.4%) had hematoma expansion while 1259 patients (54.6%) had poor functional outcome. The prevalence of noncontrast computed tomography signs was blend sign, 366 (16.1%); black hole sign, 414 (18.2%); island sign, 200 (8.8%); and hypodensities, 701 (30.2%). Blend sign (adjusted odds ratio [aOR] 1.53 [95% CI, 1.16-2.03]; P=0.003), black hole (aOR, 2.03 [1.34-3.08]; P=0.001), and hypodensities (aOR, 2.06 [1.48-2.89]; P<0.001) were independent predictors of hematoma expansion on multivariable analysis with adjustment for covariates. Black hole sign (aOR, 1.52 [1.10-2.11]; P=0.012), hypodensities (aOR, 1.37 [1.05-1.78]; P=0.019), and island sign (aOR, 2.59 [1.21-5.55]; P=0.014) were significant predictors of poor functional outcome. Tranexamic acid reduced the risk of hematoma expansion (aOR, 0.77 [0.63-0.94]; P=0.010), but there was no significant interaction between the presence of noncontrast computed tomography signs and benefit of tranexamic acid on hematoma expansion and functional outcome (P interaction all >0.05). Conclusions- Blend sign, black hole sign, and hypodensities predict hematoma expansion while black hole sign, hypodensities, and island signs predict poor functional outcome. Noncontrast computed tomography signs did not predict a better response to tranexamic acid. Clinical Trial Registration- URL: https://www.isrctn.com. Unique identifier: ISRCTN93732214.
  9. Ovesen C, Jakobsen JC, Gluud C, Steiner T, Law Z, Flaherty K, et al.
    Stroke, 2021 08;52(8):2629-2636.
    PMID: 34000834 DOI: 10.1161/STROKEAHA.120.032426
    BACKGROUND AND PURPOSE: The computed tomography angiography or contrast-enhanced computed tomography based spot sign has been proposed as a biomarker for identifying on-going hematoma expansion in patients with acute intracerebral hemorrhage. We investigated, if spot-sign positive participants benefit more from tranexamic acid versus placebo as compared to spot-sign negative participants.

    METHODS: TICH-2 trial (Tranexamic Acid for Hyperacute Primary Intracerebral Haemorrhage) was a randomized, placebo-controlled clinical trial recruiting acutely hospitalized participants with intracerebral hemorrhage within 8 hours after symptom onset. Local investigators randomized participants to 2 grams of intravenous tranexamic acid or matching placebo (1:1). All participants underwent computed tomography scan on admission and on day 2 (24±12 hours) after randomization. In this sub group analysis, we included all participants from the main trial population with imaging allowing adjudication of spot sign status.

    RESULTS: Of the 2325 TICH-2 participants, 254 (10.9%) had imaging allowing for spot-sign adjudication. Of these participants, 64 (25.2%) were spot-sign positive. Median (interquartile range) time from symptom onset to administration of the intervention was 225.0 (169.0 to 310.0) minutes. The adjusted percent difference in absolute day-2 hematoma volume between participants allocated to tranexamic versus placebo was 3.7% (95% CI, -12.8% to 23.4%) for spot-sign positive and 1.7% (95% CI, -8.4% to 12.8%) for spot-sign negative participants (Pheterogenity=0.85). No difference was observed in significant hematoma progression (dichotomous composite outcome) between participants allocated to tranexamic versus placebo among spot-sign positive (odds ratio, 0.85 [95% CI, 0.29 to 2.46]) and negative (odds ratio, 0.77 [95% CI, 0.41 to 1.45]) participants (Pheterogenity=0.88).

    CONCLUSIONS: Data from the TICH-2 trial do not support that admission spot sign status modifies the treatment effect of tranexamic acid versus placebo in patients with acute intracerebral hemorrhage. The results might have been affected by low statistical power as well as treatment delay. Registration: URL: http://www.controlled-trials.com; Unique identifier: ISRCTN93732214.

  10. Law ZK, Al-Shahi Salman R, Bath PM, Steiner T, Sprigg N
    Stroke, 2018 08;49(8):e271-e272.
    PMID: 30355046 DOI: 10.1161/STROKEAHA.118.022071
  11. Bosch J, Lonn EM, Dagenais GR, Gao P, Lopez-Jaramillo P, Zhu J, et al.
    Stroke, 2021 08;52(8):2494-2501.
    PMID: 33985364 DOI: 10.1161/STROKEAHA.120.030790
    Background and Purpose: The HOPE-3 trial (Heart Outcomes Prevention Evaluation–3) found that antihypertensive therapy combined with a statin reduced first stroke among people at intermediate cardiovascular risk. We report secondary analyses of stroke outcomes by stroke subtype, predictors, treatment effects in key subgroups.

    Methods: Using a 2-by-2 factorial design, 12 705 participants from 21 countries with vascular risk factors but without overt cardiovascular disease were randomized to candesartan 16 mg plus hydrochlorothiazide 12.5 mg daily or placebo and to rosuvastatin 10 mg daily or placebo. The effect of the interventions on stroke subtypes was assessed.

    Results: Participants were 66 years old and 46% were women. Baseline blood pressure (138/82 mm Hg) was reduced by 6.0/3.0 mm Hg and LDL-C (low-density lipoprotein cholesterol; 3.3 mmol/L) was reduced by 0.90 mmol/L on active treatment. During 5.6 years of follow-up, 169 strokes occurred (117 ischemic, 29 hemorrhagic, 23 undetermined). Blood pressure lowering did not significantly reduce stroke (hazard ratio [HR], 0.80 [95% CI, 0.59–1.08]), ischemic stroke (HR, 0.80 [95% CI, 0.55–1.15]), hemorrhagic stroke (HR, 0.71 [95% CI, 0.34–1.48]), or strokes of undetermined origin (HR, 0.92 [95% CI, 0.41–2.08]). Rosuvastatin significantly reduced strokes (HR, 0.70 [95% CI, 0.52–0.95]), with reductions mainly in ischemic stroke (HR, 0.53 [95% CI, 0.37–0.78]) but did not significantly affect hemorrhagic (HR, 1.22 [95% CI, 0.59–2.54]) or strokes of undetermined origin (HR, 1.29 [95% CI, 0.57–2.95]). The combination of both interventions compared with double placebo substantially and significantly reduced strokes (HR, 0.56 [95% CI, 0.36–0.87]) and ischemic strokes (HR, 0.41 [95% CI, 0.23–0.72]).

    Conclusions: Among people at intermediate cardiovascular risk but without overt cardiovascular disease, rosuvastatin 10 mg daily significantly reduced first stroke. Blood pressure lowering combined with rosuvastatin reduced ischemic stroke by 59%. Both therapies are safe and generally well tolerated.

    Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT00468923.

    Matched MeSH terms: Stroke/drug therapy; Stroke/prevention & control*
  12. Tan KS, Lin RT, Yoon BW, Suwanwela N, Mehndiratta MM, Venketasubramanian N
    Stroke, 2021 12;52(12):e844-e845.
    PMID: 34807747 DOI: 10.1161/STROKEAHA.121.035397
    Matched MeSH terms: Stroke*
  13. Venketasubramanian N, Anderson C, Mehndiratta M, Lin RT, Tan KS, Huang CY
    Stroke, 2017 09;48(9):e252-e254.
    PMID: 28754827 DOI: 10.1161/STROKEAHA.117.017044
    Matched MeSH terms: Stroke*
  14. Yoon BW, Toyoda K, Tan KS, Fong WC, Suwanwela NC, Venketasubramanian N
    Stroke, 2024 Jan;55(1):e8-e9.
    PMID: 37982241 DOI: 10.1161/STROKEAHA.123.044175
  15. Wang X, Yang J, Moullaali TJ, Sandset EC, Woodhouse LJ, Law ZK, et al.
    Stroke, 2024 Feb 27.
    PMID: 38410986 DOI: 10.1161/STROKEAHA.123.044358
    OBJECTIVE: To investigate whether an earlier time to achieving and maintaining systolic blood pressure (SBP) at 120 to 140 mm Hg is associated with favorable outcomes in a cohort of patients with acute intracerebral hemorrhage.

    METHODS: We pooled individual patient data from randomized controlled trials registered in the Blood Pressure in Acute Stroke Collaboration. Time was defined as time form symptom onset plus the time (hour) to first achieve and subsequently maintain SBP at 120 to 140 mm Hg over 24 hours. The primary outcome was functional status measured by the modified Rankin Scale at 90 to 180 days. A generalized linear mixed models was used, with adjustment for covariables and trial as a random effect.

    RESULTS: A total of 5761 patients (mean age, 64.0 [SD, 13.0], 2120 [36.8%] females) were included in analyses. Earlier SBP control was associated with better functional outcomes (modified Rankin Scale score, 3-6; odds ratio, 0.98 [95% CI, 0.97-0.99]) and a significant lower risk of hematoma expansion (0.98, 0.96-1.00). This association was stronger in patients with bigger baseline hematoma volume (>10 mL) compared with those with baseline hematoma volume ≤10 mL (0.006 for interaction). Earlier SBP control was not associated with cardiac or renal adverse events.

    CONCLUSIONS: Our study confirms a clear time relation between early versus later SBP control (120-140 mm Hg) and outcomes in the one-third of patients with intracerebral hemorrhage who attained sustained SBP levels within this range. These data provide further support for the value of early recognition, rapid transport, and prompt initiation of treatment of patients with intracerebral hemorrhage.

  16. Law ZK, Appleton JP, Scutt P, Roberts I, Al-Shahi Salman R, England TJ, et al.
    Stroke, 2022 Apr;53(4):1141-1148.
    PMID: 34847710 DOI: 10.1161/STROKEAHA.121.035191
    BACKGROUND: Seeking consent rapidly in acute stroke trials is crucial as interventions are time sensitive. We explored the association between consent pathways and time to enrollment in the TICH-2 (Tranexamic Acid in Intracerebral Haemorrhage-2) randomized controlled trial.

    METHODS: Consent was provided by patients or by a relative or an independent doctor in incapacitated patients, using a 1-stage (full written consent) or 2-stage (initial brief consent followed by full written consent post-randomization) approach. The computed tomography-to-randomization time according to consent pathways was compared using the Kruskal-Wallis test. Multivariable logistic regression was performed to identify variables associated with onset-to-randomization time of ≤3 hours.

    RESULTS: Of 2325 patients, 817 (35%) gave self-consent using 1-stage (557; 68%) or 2-stage consent (260; 32%). For 1507 (65%), consent was provided by a relative (1 stage, 996 [66%]; 2 stage, 323 [21%]) or a doctor (all 2-stage, 188 [12%]). One patient did not record prerandomization consent, with written consent obtained subsequently. The median (interquartile range) computed tomography-to-randomization time was 55 (38-93) minutes for doctor consent, 55 (37-95) minutes for 2-stage patient, 69 (43-110) minutes for 2-stage relative, 75 (48-124) minutes for 1-stage patient, and 90 (56-155) minutes for 1-stage relative consents (P<0.001). Two-stage consent was associated with onset-to-randomization time of ≤3 hours compared with 1-stage consent (adjusted odds ratio, 1.9 [95% CI, 1.5-2.4]). Doctor consent increased the odds (adjusted odds ratio, 2.3 [1.5-3.5]) while relative consent reduced the odds of randomization ≤3 hours (adjusted odds ratio, 0.10 [0.03-0.34]) compared with patient consent. Only 2 of 771 patients (0.3%) in the 2-stage pathways withdrew consent when full consent was sought later. Two-stage consent process did not result in higher withdrawal rates or loss to follow-up.

    CONCLUSIONS: The use of initial brief consent was associated with shorter times to enrollment, while maintaining good participant retention. Seeking written consent from relatives was associated with significant delays.

    REGISTRATION: URL: https://www.isrctn.com; Unique identifier: ISRCTN93732214.

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