ORCID Profile
0000-0002-7347-7761
Current Organisations
McMaster University
,
National University of Ireland Galway
,
Galway University Hospitals
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Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 09-2016
DOI: 10.1161/STROKEAHA.116.013378
Abstract: Atrial fibrillation (AF) is increasingly recognized as the single most important cause of disabling ischemic stroke in the elderly. We undertook an international survey to characterize the frequency of AF-associated stroke, methods of AF detection, and patient features. Consecutive patients hospitalized for ischemic stroke in 2013 to 2014 were surveyed from 19 stroke research centers in 19 different countries. Data were analyzed by global regions and World Bank income levels. Of 2144 patients with ischemic stroke, 590 (28% 95% confidence interval, 25.6–29.5) had AF-associated stroke, with highest frequencies in North America (35%) and Europe (33%) and lowest in Latin America (17%). Most had a history of AF before stroke (15%) or newly detected AF on electrocardiography (10%) only 2% of patients with ischemic stroke had unsuspected AF detected by poststroke cardiac rhythm monitoring. The mean age and 30-day mortality rate of patients with AF-associated stroke (75 years SD, 11.5 years 10% 95% confidence interval, 7.6–12.6, respectively) were substantially higher than those of patients without AF (64 years SD, 15.58 years 4% 95% confidence interval, 3.3–5.4 P .001 for both comparisons). There was a strong positive correlation between the mean age and the frequency of AF ( r =0.76 P =0.0002). This cross-sectional global s le of patients with recent ischemic stroke shows a substantial frequency of AF-associated stroke throughout the world in proportion to the mean age of the stroke population. Most AF is identified by history or electrocardiography the yield of conventional short-duration cardiac rhythm monitoring is relatively low. Patients with AF-associated stroke were typically elderly ( years old) and more often women.
Publisher: SAGE Publications
Date: 05-01-2021
Abstract: Recent randomised trials showed benefit for anti-inflammatory therapies in coronary disease but excluded stroke. The prognostic value of blood inflammatory markers after stroke is uncertain and guidelines do not recommend their routine measurement for risk stratification. We performed a systematic review and meta-analysis of studies investigating the association of C-reactive protein (CRP), interleukin-6 (IL-6) and fibrinogen and risk of recurrent stroke or major vascular events (MVEs). We searched EMBASE and Ovid Medline until 10/1/19. Random-effects meta-analysis was performed for studies reporting comparable effect measures. Of 2,515 reports identified, 39 met eligibility criteria (IL-6, n = 10 CRP, n = 33 fibrinogen, n = 16). An association with recurrent stroke was reported in 12/26 studies (CRP), 2/11 (fibrinogen) and 3/6 (IL-6). On random-effects meta-analysis of comparable studies, CRP was associated with an increased risk of recurrent stroke [pooled hazard ratio (HR) per 1 standard-deviation (SD) increase in log e -CRP (1.14, 95% CI 1.06–1.22, p 0.01)] and MVEs (pooled HR 1.21, CI 1.10–1.34, p 0.01). Fibrinogen was also associated with recurrent stroke (HR 1.26, CI 1.07–1.47, p 0.01) and MVEs (HR 1.31, 95% CI 1.15–1.49, p 0.01). Trends were identified for IL-6 for recurrent stroke (HR per 1-SD increase 1.17, CI 0.97–1.41, p = 0.10) and MVEs (HR 1.22, CI 0.96–1.55, p = 0.10). Despite evidence suggesting an association between inflammatory markers and post-stroke vascular recurrence, substantial methodological heterogeneity was apparent between studies. In idual-patient pooled analysis and standardisation of methods are needed to determine the prognostic role of blood inflammatory markers and to improve patient selection for randomised trials of inflammatory therapies.
Publisher: Massachusetts Medical Society
Date: 20-12-2018
Publisher: Springer Science and Business Media LLC
Date: 14-11-2022
Publisher: Elsevier BV
Date: 2015
Publisher: Elsevier BV
Date: 2018
Publisher: Elsevier BV
Date: 02-2017
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 10-01-2023
DOI: 10.1212/WNL.0000000000201388
Abstract: There is uncertainty about the association between alcohol consumption and stroke, particularly for low-moderate intake. We explored these associations in a large international study. INTERSTROKE, a case-control study, is the largest international study of risk factors for acute stroke. Alcohol consumption was self-reported and categorized by drinks/week as low (1–7), moderate (7–14 for females and 7–21 for males), or high ( for females and for males). Heavy episodic drinking (HED) was defined as drinks on ≥1 day per month. Multivariable conditional logistic regression was used to determine associations. We included 12,913 cases and 12,935 controls 25.0% (n = 6,449) were current drinkers, 16.7% (n = 4,318) former drinkers, and 58.3% (n = 15,076) never drinkers. Current drinkers were younger, male, smokers, active, and with higher-paid occupations. Current drinking was associated with all stroke (OR 1.14 95% CI 1.04–1.26) and intracerebral hemorrhage (ICH) (OR 1.50, 95% CI 1.21–1.84) but not ischemic stroke (OR 1.06 95% CI 0.95–1.19). HED pattern was associated with all stroke (OR 1.39 95% CI 1.21–1.59), ischemic stroke (OR 1.29 95% CI 1.10–1.51), and ICH (OR 1.76 95% CI 1.31–2.36). High level of alcohol intake was consistently associated with all stroke, ischemic stroke, and ICH. Moderate intake was associated with all stroke and ICH but not ischemic stroke. Low alcohol intake was not associated with stroke overall, but there were regional differences low intake was associated with reduced odds of stroke in Western Europe/North America (OR 0.66 95% CI 0.45–0.96) and increased odds in India (OR 2.18 95% CI 1.42–3.36) (p-interaction 0.037). Wine consumption was associated with reduced odds of all stroke and ischemic stroke but not ICH. The magnitudes of association were greatest in those without hypertension and current smokers. High and moderate intake were associated with increased odds of stroke, whereas low intake was not associated with stroke. However, there were important regional variations, which may relate to differences in population characteristics of alcohol consumers, types or patterns of consumption.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 23-05-2023
DOI: 10.1212/WNL.0000000000207249
Abstract: Symptoms of sleep disturbance are common and may represent important modifiable risk factors of stroke. We evaluated the association between a spectrum of sleep disturbance symptoms and the risk of acute stroke in an international setting. The INTERSTROKE study is an international case-control study of patients presenting with first acute stroke and controls matched by age (±5 years) and sex. Sleep symptoms in the previous month were assessed through a questionnaire. Conditional logistic regression estimated the association between sleep disturbance symptoms and acute stroke, expressed as odds ratios (ORs) and 95% CIs. The primary model adjusted for age, occupation, marital status, and modified Rankin scale at baseline, with subsequent models adjusting for potential mediators (behavioral/disease risk factors). Overall, 4,496 matched participants were included, with 1,799 of them having experienced an ischemic stroke and 439 an intracerebral hemorrhage. Short sleep ( hours: OR 3.15, 95% CI 2.09–4.76), long sleep ( hours: OR 2.67, 95% CI 1.89–3.78), impaired quality (OR 1.52, 95% CI 1.32–1.75), difficulty getting to sleep (OR 1.32, 95% CI 1.13–1.55) or maintaining sleep (OR 1.33, 95% CI 1.15–1.53), unplanned napping (OR 1.48, 95% CI 1.20–1.84), prolonged napping ( hour: OR 1.88, 95% CI 1.49–2.38), snoring (OR 1.91, 95% CI 1.62–2.24), snorting (OR 2.64, 95% CI 2.17–3.20), and breathing cessation (OR 2.87, 95% CI 2.28–3.60) were all significantly associated with an increased odds of acute stroke in the primary model. A derived obstructive sleep apnea score of 2–3 (2.67, 2.25–3.15) and cumulative sleep symptoms ( : 5.38, 4.03–7.18 ) were also associated with a significantly increased odds of acute stroke, with the latter showing a graded association. After an extensive adjustment, significance was maintained for most of the symptoms (not difficulty getting to/maintaining sleep and unplanned napping), with similar findings for stroke subtypes. We found that sleep disturbance symptoms were common and associated with a graded increased risk of stroke. These symptoms may be a marker of increased in idual risk or represent independent risk factors. Future clinical trials are warranted to determine the efficacy of sleep interventions in stroke prevention.
Publisher: Elsevier BV
Date: 03-2020
Publisher: Wiley
Date: 11-05-2020
Publisher: Massachusetts Medical Society
Date: 15-12-2016
DOI: 10.1056/NEJMC1612304
Publisher: Elsevier BV
Date: 08-2019
DOI: 10.1053/J.GASTRO.2019.04.041
Abstract: Antiplatelets and anticoagulants are associated with increased upper gastrointestinal bleeding. We evaluated whether proton pump inhibitor therapy could reduce this risk. We performed a 3 × 2 partial factorial double-blind trial of 17,598 participants with stable cardiovascular disease and peripheral artery disease. Participants were randomly assigned to groups given pantoprazole 40 mg daily or placebo, as well as rivaroxaban 2.5 mg twice daily with aspirin 100 mg once daily, rivaroxaban 5 mg twice daily, or aspirin 100 mg alone. The primary outcome was time to first upper gastrointestinal event, defined as a composite of overt bleeding, upper gastrointestinal bleeding from a gastroduodenal lesion or of unknown origin, occult bleeding, symptomatic gastroduodenal ulcer or ≥5 erosions, upper gastrointestinal obstruction, or perforation. There was no significant difference in upper gastrointestinal events between the pantoprazole group (102 of 8791 events) and the placebo group (116 of 8807 events) (hazard ratio, 0.88 95% confidence interval [CI], 0.67-1.15). Pantoprazole significantly reduced bleeding of gastroduodenal lesions (hazard ratio, 0.52 95% confidence interval, 0.28-0.94 P = .03) this reduction was greater when we used a post-hoc definition of bleeding gastroduodenal lesion (hazard ratio, 0.45 95% confidence interval, 0.27-0.74), although the number needed to treat still was high (n = 982 95% confidence interval, 609-2528). In a randomized placebo-controlled trial, we found that routine use of proton pump inhibitors in patients receiving low-dose anticoagulation and/or aspirin for stable cardiovascular disease does not reduce upper gastrointestinal events, but may reduce bleeding from gastroduodenal lesions. ClinicalTrials.gov ID: NCT01776424.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 26-02-2019
DOI: 10.1161/CIRCULATIONAHA.118.035864
Abstract: Strokes were significantly reduced by the combination of rivaroxaban plus aspirin in comparison with aspirin in the COMPASS trial (Cardiovascular Outcomes for People Using Anticoagulation Strategies). We present detailed analyses of stroke by type, predictors, and antithrombotic effects in key subgroups. Participants had stable coronary artery or peripheral artery disease and were randomly assigned to receive aspirin 100 mg once daily (n=9126), rivaroxaban 5 mg twice daily (n=9117), or rivaroxaban 2.5 mg twice daily plus aspirin (n=9152). Patients who required anticoagulation or had a stroke within 1 month, previous lacunar stroke, or intracerebral hemorrhage were excluded. During a mean follow-up of 23 months, fewer patients had strokes in the rivaroxaban plus aspirin group than in the aspirin group (83 [0.9% per year] versus 142 [1.6% per year] hazard ratio [HR], 0.58 95% CI, 0.44–0.76 P .0001). Ischemic/uncertain strokes were reduced by nearly half (68 [0.7% per year] versus 132 [1.4% per year] HR, 0.51 95% CI, 0.38–0.68 P .0001) by the combination in comparison with aspirin. No significant difference was noted in the occurrence of stroke in the rivaroxaban alone group in comparison with aspirin: annualized rate of 0.7% (HR, 0.82 95% CI, 0.65–1.05). The occurrence of fatal and disabling stroke (modified Rankin Scale, 3–6) was decreased by the combination (32 [0.3% per year] versus 55 [0.6% per year] HR, 0.58 95% CI, 0.37–0.89 P =0.01). Independent predictors of stroke were prior stroke, hypertension, systolic blood pressure at baseline, age, diabetes mellitus, and Asian ethnicity. Prior stroke was the strongest predictor of incident stroke (HR, 3.63 95% CI, 2.65–4.97 P .0001) and was associated with a 3.4% per year rate of stroke recurrence on aspirin. The effect of the combination in comparison with aspirin was consistent across subgroups with high stroke risk, including those with prior stroke. Low-dose rivaroxaban plus aspirin is an important new antithrombotic option for primary and secondary stroke prevention in patients with clinical atherosclerosis. URL: www.clinicaltrials.gov . Unique identifier: NCT01776424.
Publisher: SAGE Publications
Date: 30-07-2018
Abstract: Covert vascular disease of the brain manifests as infarcts, white matter hyperintensities, and microbleeds on MRI. Their cumulative effect is often a decline in cognition, motor impairment, and psychiatric disorders. Preventive therapies for covert brain ischemia have not been established but represent a huge unmet clinical need. The MRI substudy examines the effects of the antithrombotic regimens in COMPASS on incident covert brain infarcts (the primary outcome), white matter hyperintensities, and cognitive and functional status in a s le of consenting COMPASS participants without contraindications to MRI. COMPASS is a randomized superiority trial testing rivaroxaban 2.5 mg bid plus acetylsalicylic acid 100 mg and rivaroxaban 5 mg bid against acetylsalicylic acid 100 mg per day for the combined endpoint of MI, stroke, and cardiovascular death in in iduals with stable coronary artery disease or peripheral artery disease. T1-weighted, T2-weighted, T2*-weighted, and FLAIR images were obtained close to randomization and near the termination of assigned antithrombotic therapy biomarker and genetic s les at randomization and one month, and cognitive and functional assessment at randomization, after two years and at the end of study. Between March 2013 and May 2016, 1905 participants were recruited from 86 centers in 16 countries. Of these participants, 1760 underwent baseline MRI scans that were deemed technically adequate for interpretation. The mean age at entry of participants with interpretable MRI was 71 years and 23.5% were women. Coronary artery disease was present in 90.4% and 28.1% had peripheral artery disease. Brain infarcts were present in 34.8%, 29.3% had cerebral microbleeds, and 93.0% had white matter hyperintensities. The median Montreal Cognitive Assessment score was 26 (interquartile range 23–28). The COMPASS MRI substudy will examine the effect of the antithrombotic interventions on MRI-determined covert brain infarcts and cognition. Demonstration of a therapeutic effect of the antithrombotic regimens on brain infarcts would have implications for prevention of cognitive decline and provide insight into the pathogenesis of vascular cognitive decline.
Publisher: Springer Science and Business Media LLC
Date: 03-12-2018
DOI: 10.1038/S41467-018-07340-5
Abstract: Carotid artery intima media thickness (cIMT) and carotid plaque are measures of subclinical atherosclerosis associated with ischemic stroke and coronary heart disease (CHD). Here, we undertake meta-analyses of genome-wide association studies (GWAS) in 71,128 in iduals for cIMT, and 48,434 in iduals for carotid plaque traits. We identify eight novel susceptibility loci for cIMT, one independent association at the previously-identified PINX1 locus, and one novel locus for carotid plaque. Colocalization analysis with nearby vascular expression quantitative loci (cis-eQTLs) derived from arterial wall and metabolic tissues obtained from patients with CHD identifies candidate genes at two potentially additional loci, ADAMTS9 and LOXL4 . LD score regression reveals significant genetic correlations between cIMT and plaque traits, and both cIMT and plaque with CHD, any stroke subtype and ischemic stroke. Our study provides insights into genes and tissue-specific regulatory mechanisms linking atherosclerosis both to its functional genomic origins and its clinical consequences in humans.
Publisher: Springer Science and Business Media LLC
Date: 29-10-2019
DOI: 10.1186/S12872-019-1187-Z
Abstract: We characterised the phenotypic consequence of genetic variation at the PCSK9 locus and compared findings with recent trials of pharmacological inhibitors of PCSK9. Published and in idual participant level data (300,000+ participants) were combined to construct a weighted PCSK9 gene-centric score (GS). Seventeen randomized placebo controlled PCSK9 inhibitor trials were included, providing data on 79,578 participants. Results were scaled to a one mmol/L lower LDL-C concentration. The PCSK9 GS (comprising 4 SNPs) associations with plasma lipid and apolipoprotein levels were consistent in direction with treatment effects. The GS odds ratio (OR) for myocardial infarction (MI) was 0.53 (95% CI 0.42 0.68), compared to a PCSK9 inhibitor effect of 0.90 (95% CI 0.86 0.93). For ischemic stroke ORs were 0.84 (95% CI 0.57 1.22) for the GS, compared to 0.85 (95% CI 0.78 0.93) in the drug trials. ORs with type 2 diabetes mellitus (T2DM) were 1.29 (95% CI 1.11 1.50) for the GS, as compared to 1.00 (95% CI 0.96 1.04) for incident T2DM in PCSK9 inhibitor trials. No genetic associations were observed for cancer, heart failure, atrial fibrillation, chronic obstructive pulmonary disease, or Alzheimer’s disease – outcomes for which large-scale trial data were unavailable. Genetic variation at the PCSK9 locus recapitulates the effects of therapeutic inhibition of PCSK9 on major blood lipid fractions and MI. While indicating an increased risk of T2DM, no other possible safety concerns were shown although precision was moderate.
Publisher: Cold Spring Harbor Laboratory
Date: 08-11-2021
DOI: 10.1101/2021.11.06.21265795
Abstract: To determine the contribution of common genetic variants to risk of early onset ischemic stroke (IS). We performed a meta-analysis of genome-wide association studies of early onset IS, ages 18-59, using in idual level data or summary statistics in 16,927 cases and 576,353 non-stroke controls from 48 different studies across North America, Europe, and Asia. We further compared effect sizes at our most genome-wide significant loci between early and late onset IS and compared polygenic risk scores for venous thromboembolism between early versus later onset IS. We observed an association between early onset IS and ABO , a known stroke locus. The effect size of the peak ABO SNP, rs8176685, was significantly larger in early compared to late onset IS (OR 1.17 (95% C.I.: 1.11-1.22) vs 1.05 (0.99-1.12) p for interaction = 0.008). Analysis of genetically determined ABO blood groups revealed that early onset IS cases were more likely to have blood group A and less likely to have blood group O compared to both non-stroke controls and to late onset IS cases. Using polygenic risk scores, we observed that greater genetic risk for venous thromboembolism, another prothrombotic condition, was more strongly associated with early, compared to late, onset IS (p=0.008). The ABO locus, genetically predicted blood group A, and higher genetic propensity for venous thrombosis are more strongly associated with early onset IS, compared with late onset IS, supporting a stronger role of prothrombotic factors in early onset IS.
Publisher: Elsevier BV
Date: 08-2016
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 10-2020
DOI: 10.1161/STROKEAHA.120.029762
Abstract: Covert brain infarcts are associated with cognitive decline. It is not known whether therapies that prevent symptomatic stroke prevent covert infarcts. COMPASS compared rivaroxaban with and without aspirin with aspirin for the prevention of stroke, myocardial infarction, and vascular death in participants with stable vascular disease and was terminated early because of benefits of rivaroxaban 2.5 mg twice daily plus aspirin over aspirin. We obtained serial magnetic resonance imagings and cognitive tests in a consenting subgroup of COMPASS patients to examine treatment effects on infarcts, cerebral microbleeds, and white matter hyperintensities. Baseline and follow-up magnetic resonance imagings were completed in 1445 participants with a mean (SD) interval of 2.0 (0.7) years. Whole-brain T1, T2 fluid-attenuated inversion recovery, T2* sequences were centrally interpreted by blinded, trained readers. Participants had serial measurements of cognition and function. The primary end point was the proportion of participants with incident covert infarcts. Secondary end points were the composite of clinical stroke and covert brain infarcts, cerebral microbleeds, and white matter hyperintensities. At baseline, 493 (34.1%) participants had infarcts. Incident covert infarcts occurred in 55 (3.8%) participants. In the overall trial rivaroxaban plus aspirin reduced ischemic stroke by 49% (0.7% versus 1.4% hazard ratio [95% CI], 0.51 [0.38–0.68]). In the magnetic resonance imaging substudy the effects of rivaroxaban+aspirin versus aspirin were: covert infarcts: 2.7% versus 3.5% (odds ratio [95% CI], 0.77 [0.37–1.60]) Covert infarcts or ischemic stroke: 2.9% versus 5.3% (odds ratio [95% CI], 0.53 [0.27–1.03]). Incident microbleeds occurred in 6.6% of participants and 65.7% of participants had an increase in white matter hyperintensities volume with no effect of treatment for either end point. There was no effect on cognitive tests. Covert infarcts were not significantly reduced by treatment with rivaroxaban and aspirin but estimates for the combination of ischemic stroke and covert infarcts were consistent with the effect on ischemic stroke in the overall trial. URL: www.clinicaltrials.gov . Unique identifier: NCT01776424.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 27-02-2019
DOI: 10.1212/WNL.0000000000007174
Abstract: To assess whether long-term treatment with candesartan/hydrochlorothiazide, rosuvastatin, or their combination can slow cognitive decline in older people at intermediate cardiovascular risk. The Heart Outcomes Prevention Evaluation-3 (HOPE-3) study was a double-blind, randomized, placebo-controlled clinical trial using a 2 × 2 factorial design. Participants without known cardiovascular disease or need for treatment were randomized to candesartan (16 mg) plus hydrochlorothiazide (12.5 mg) or placebo and to rosuvastatin (10 mg) or placebo. Participants who were ≥70 years of age completed the Digit Symbol Substitution Test (DSST), the modified Montreal Cognitive Assessment, and the Trail Making Test Part B at baseline and study end. Cognitive assessments were completed by 2,361 participants from 228 centers in 21 countries. Compared with placebo, candesartan/hydrochlorothiazide reduced systolic blood pressure by 6.0 mm Hg, and rosuvastatin reduced low-density lipoprotein cholesterol by 24.8 mg/dL. Participants were followed up for 5.7 years (median), and 1,626 completed both baseline and study-end assessments. Mean participant age was 74 years (SD ±3.5 years) 59% were women 45% had hypertension and 24% had ≥12 years of education. The mean difference in change in DSST scores was −0.91 (95% confidence interval [CI] −2.25 to 0.42) for candesartan/hydrochlorothiazide compared with placebo, −0.54 (95% CI −1.88 to 0.80) for rosuvastatin compared with placebo, and −1.43 (95% CI −3.37 to 0.50) for combination therapy vs double placebo. No significant differences were found for other measures. Long-term blood pressure lowering with candesartan plus hydrochlorothiazide, rosuvastatin, or their combination did not significantly affect cognitive decline in older people. NCT00468923. This study provides Class II evidence that for older people, candesartan plus hydrochlorothiazide, rosuvastatin, or their combination does not significantly affect cognitive decline.
Publisher: Springer Science and Business Media LLC
Date: 03-06-2019
DOI: 10.1038/S41588-019-0449-0
Abstract: An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Publisher: Elsevier BV
Date: 03-2016
Publisher: Elsevier BV
Date: 03-2012
Publisher: Springer Science and Business Media LLC
Date: 30-09-2022
DOI: 10.1038/S41586-022-05165-3
Abstract: Previous genome-wide association studies (GWASs) of stroke — the second leading cause of death worldwide — were conducted predominantly in populations of European ancestry 1,2 . Here, in cross-ancestry GWAS meta-analyses of 110,182 patients who have had a stroke (five ancestries, 33% non-European) and 1,503,898 control in iduals, we identify association signals for stroke and its subtypes at 89 (61 new) independent loci: 60 in primary inverse-variance-weighted analyses and 29 in secondary meta-regression and multitrait analyses. On the basis of internal cross-ancestry validation and an independent follow-up in 89,084 additional cases of stroke (30% non-European) and 1,013,843 control in iduals, 87% of the primary stroke risk loci and 60% of the secondary stroke risk loci were replicated ( P 0.05). Effect sizes were highly correlated across ancestries. Cross-ancestry fine-mapping, in silico mutagenesis analysis 3 , and transcriptome-wide and proteome-wide association analyses revealed putative causal genes (such as SH3PXD2A and FURIN ) and variants (such as at GRK5 and NOS3 ). Using a three-pronged approach 4 , we provide genetic evidence for putative drug effects, highlighting F11, KLKB1, PROC, GP1BA, LAMC2 and VCAM1 as possible targets, with drugs already under investigation for stroke for F11 and PROC. A polygenic score integrating cross-ancestry and ancestry-specific stroke GWASs with vascular-risk factor GWASs (integrative polygenic scores) strongly predicted ischaemic stroke in populations of European, East Asian and African ancestry 5 . Stroke genetic risk scores were predictive of ischaemic stroke independent of clinical risk factors in 52,600 clinical-trial participants with cardiometabolic disease. Our results provide insights to inform biology, reveal potential drug targets and derive genetic risk prediction tools across ancestries.
Publisher: S. Karger AG
Date: 2021
DOI: 10.1159/000515239
Abstract: b i Background: /i /b Previous studies reported an association of renal impairment with stroke, but there are uncertainties underpinning this association. b i Aims: /i /b We explored if the association is explained by shared risk factors or is independent and whether there are regional or stroke subtype variations. b i Methods: /i /b INTERSTROKE is a case-control study and the largest international study of risk factors for first acute stroke, completed in 27 countries. We included in iduals with available serum creatinine values and calculated estimated glomerular filtration rate (eGFR). Renal impairment was defined as eGFR & #x3c mL/min/1.73 m sup /sup . Multivariable conditional logistic regression was used to determine the association of renal function with stroke. b i Results: /i /b Of 21,127 participants, 41.0% were female, the mean age was 62.3 ± 13.4 years, and the mean eGFR was 79.9 ± 23.5 mL/min/1.73 m sup /sup . The prevalence of renal impairment was higher in cases (22.9% vs. 17.7%, i /i & #x3c 0.001) and differed by region ( i /i & #x3c 0.001). After adjustment, lower eGFR was associated with increased odds of stroke. Renal impairment was associated with increased odds of all stroke (OR 1.35 95% CI: 1.24–1.47), with higher odds for intracerebral hemorrhage (OR 1.60 95% CI: 1.35–1.89) than ischemic stroke (OR 1.29 95% CI: 1.17–1.42) ( i /i sub interaction /sub 0.12). The largest magnitudes of association were seen in younger participants and those living in Africa, South Asia, or South America ( i /i sub interaction /sub & #x3c 0.001 for all stroke). Renal impairment was also associated with poorer clinical outcome (RRR 2.97 95% CI: 2.50–3.54 for death within 1 month). b i Conclusion: /i /b Renal impairment is an important risk factor for stroke, particularly in younger patients, and is associated with more severe stroke and worse outcomes.
Publisher: Elsevier BV
Date: 06-2018
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 26-02-2019
Publisher: BMJ
Date: 14-12-2020
DOI: 10.1136/HEARTJNL-2019-316515
Abstract: Hypertension is the most important modifiable risk factor for stroke globally. We hypothesised that country-income level variations in knowledge, detection and treatment of hypertension may contribute to variations in the association of blood pressure with stroke. We undertook a standardised case-control study in 32 countries (INTERSTROKE). Cases were patients with acute first stroke (n=13 462) who were matched by age, sex and site to controls (n=13 483). We evaluated the associations of knowledge, awareness and treatment of hypertension with risk of stroke and its subtypes and whether this varied by gross national income (GNI) of country. We estimated OR and population attributable risk (PAR) associated with treated and untreated hypertension. Hypertension was associated with a graded increase in OR by reducing GNI, ranging from OR 1.92 (99% CI 1.48 to 2.49) to OR 3.27 (2.72 to 3.93) for highest to lowest country-level GNI (p-heterogeneity .0001). Untreated hypertension was associated with a higher OR for stroke (OR 5.25 4.53 to 6.10) than treated hypertension (OR 2.60 2.32 to 2.91) and younger age of first stroke (61.4 vs 65.4 years p .01). Untreated hypertension was associated with a greater risk of intracerebral haemorrhage (OR 6.95 5.61 to 8.60) than ischaemic stroke (OR 4.76 3.99 to 5.68). The PAR associated with untreated hypertension was higher in lower-income regions, PAR 36.3%, 26.3%, 19.8% to 10.4% by increasing GNI of countries. Lifetime non-measurement of blood pressure was associated with stroke (OR 1.80 1.32 to 2.46). Deficits in knowledge, detection and treatment of hypertension contribute to higher risk of stroke, younger age of onset and larger proportion of intracerebral haemorrhage in lower-income countries.
Publisher: Oxford University Press (OUP)
Date: 16-11-2020
DOI: 10.1093/AJH/HPAA176
Abstract: Although low sodium intake (& g/day) and high potassium intake (& .5 g/day) are proposed as public health interventions to reduce stroke risk, there is uncertainty about the benefit and feasibility of this combined recommendation on prevention of stroke. We obtained random urine s les from 9,275 cases of acute first stroke and 9,726 matched controls from 27 countries and estimated the 24-hour sodium and potassium excretion, a surrogate for intake, using the Tanaka formula. Using multivariable conditional logistic regression, we determined the associations of estimated 24-hour urinary sodium and potassium excretion with stroke and its subtypes. Compared with an estimated urinary sodium excretion of 2.8–3.5 g/day (reference), higher (& .26 g/day) (odds ratio [OR] 1.81 95% confidence interval [CI], 1.65–2.00) and lower (& .8 g/day) sodium excretion (OR 1.39 95% CI, 1.26–1.53) were significantly associated with increased risk of stroke. The stroke risk associated with the highest quartile of sodium intake (sodium excretion & .26 g/day) was significantly greater (P & 0.001) for intracerebral hemorrhage (ICH) (OR 2.38 95% CI, 1.93–2.92) than for ischemic stroke (OR 1.67 95% CI, 1.50–1.87). Urinary potassium was inversely and linearly associated with risk of stroke, and stronger for ischemic stroke than ICH (P = 0.026). In an analysis of combined sodium and potassium excretion, the combination of high potassium intake (& .58 g/day) and moderate sodium intake (2.8–3.5 g/day) was associated with the lowest risk of stroke. The association of sodium intake and stroke is J-shaped, with high sodium intake a stronger risk factor for ICH than ischemic stroke. Our data suggest that moderate sodium intake—rather than low sodium intake—combined with high potassium intake may be associated with the lowest risk of stroke and expected to be a more feasible combined dietary target.
Publisher: Springer Science and Business Media LLC
Date: 12-03-2018
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 05-2008
DOI: 10.1161/STROKEAHA.107.497271
Abstract: For patients with ischemic stroke or transient ischemic attack caused by atherothromboembolism, immediate and long-term aspirin reduces the relative risk of recurrent stroke, MI, and death attributable to vascular causes. Oral anticoagulation is not more effective than aspirin. Long-term clopidogrel reduces the relative risk of stroke, MI, or vascular death by about 9% (0.3% to 16.5%) compared with aspirin. Any long-term benefits of clopidogrel combined with aspirin, compared with aspirin or clopidogrel alone, appear to be offset by increased major bleeding. The combination of aspirin and extended-release dipyridamole reduces the relative odds of stroke, MI, or vascular death by about 18% (odds ratio 0.82, 0.74 to 0.91) compared with aspirin alone without causing more bleeding. Cilostazole reduces the risk of stroke, MI, or vascular death by 39% compared to placebo. A large clinical trial comparing clopidogrel with the combination of aspirin and dipyridamole, in 000 patients with recent ( days) atherothrombotic ischemic stroke, is expected to report in 2008. Emerging antiplatelet therapies presently being evaluated for secondary prevention of atherothromboembolism include other P 2 Y 12 ADP receptor antagonists (prasugrel, cangrelor, AZD 6140), thromboxane receptor antagonists (eg, S18886 - terutroban), and thrombin receptor (PAR-1) antagonists (eg, SCH530348).
Publisher: SAGE Publications
Date: 11-08-2016
Abstract: Embolic strokes of undetermined source comprise up to 20% of ischemic strokes. The stroke recurrence rate is substantial with aspirin, widely used for secondary prevention. The New Approach riVaroxaban Inhibition of Factor Xa in a Global trial versus ASA to prevenT Embolism in Embolic Stroke of Undetermined Source international trial will compare the efficacy and safety of rivaroxaban, an oral factor Xa inhibitor, versus aspirin for secondary prevention in patients with recent embolic strokes of undetermined source. In patients with recent embolic strokes of undetermined source, rivaroxaban 15 mg once daily will reduce the risk of recurrent stroke (both ischemic and hemorrhagic) and systemic embolism (primary efficacy outcome) compared with aspirin 100 mg once daily. Double-blind, randomized trial in patients with embolic strokes of undetermined source, defined as nonlacunar cryptogenic ischemic stroke, enrolled between seven days and six months from the qualifying stroke. The planned s le size of 7000 participants will be recruited from approximately 480 sites in 31 countries between 2014 and 2017 and followed for a mean of about two years until at least 450 primary efficacy outcome events have occurred. The primary safety outcome is major bleeding. Two substudies assess (1) the relative effect of treatments on MRI-determined covert brain infarcts and (2) the biological underpinnings of embolic strokes of undetermined source using genomic and biomarker approaches. The New Approach riVaroxaban Inhibition of Factor Xa in a Global trial versus ASA to prevenT Embolism in Embolic Stroke of Undetermined Source trial is evaluating the benefits and risks of rivaroxaban for secondary stroke prevention in embolic strokes of undetermined source patients. Main results are anticipated in 2018.
Publisher: American Medical Association (AMA)
Date: 09-12-2022
DOI: 10.1001/JAMANETWORKOPEN.2022.44836
Abstract: Psychosocial stress is considered a modifiable risk factor for stroke. Given the prevalence of chronic and acute exposure to stress, it represents a potentially attractive target for population-health interventions. To determine the association of psychosocial stress with the risk of acute stroke and explore factors that might modify the association of stress with risk of acute stroke in a large international population. INTERSTROKE is an international retrospective case-control study of risk factors for first acute stroke in 32 countries in Asia, North and South America, Europe, Australia, the Middle East, and Africa. A total of 13 462 patients with stroke and 13 488 matched controls were recruited between January 11, 2007, and August 8, 2015. The present analyses were performed from June 1 to 30, 2021, and included 13 350 cases and 13 462 controls with available data on psychosocial stress. Psychosocial stress and occurrence of stressful life events within the preceding year were measured using a standardized questionnaire of self-reported stress at home and work. The association of stress with acute stroke and its subtypes was examined using multivariable conditional logistic regression and factors that might modify the association, particularly self-reported locus of control. Among 26 812 participants included in the analysis, the mean (SD) age of cases was 62.2 (13.6) years that of controls, 61.3 (13.3) years 7960 cases (59.6%) and 8017 controls (59.6%) were men. Several periods of stress and permanent stress were reported for 2745 cases (20.5%) and 1933 controls (14.4%), with marked regional variation in prevalence, with the lowest in China (201 of 3981 [5.0%] among controls and 364 of 3980 [9.1%] among cases) and highest in South East Asia (233 of 855 [26.1%] among controls and 241 of 782 [30.8%] among cases). Increased stress at home (odds ratio [OR], 1.95 [95% CI, 1.77-2.15]) and at work (OR, 2.70 [95% CI, 2.25-3.23]) and recent stressful life events (OR, 1.31 [95% CI, 1.19-1.43]) were associated with an increased risk of acute stroke on multivariable analyses (vs no self-reported stress). Higher locus of control at home was associated with a reduced odds of all stroke (OR, 0.73 [95% CI, 0.68-0.79]), and higher locus of control both at work and at home were associated with a lower odds of acute stroke and significantly diminished the association with stress at work (OR, 2.20 [95% CI, 1.88-2.58] P = .008 for interaction) and home (OR, 1.69 [95% CI, 1.44-1.98] P & .001 for interaction) for acute stroke. Psychosocial stress is a common risk factor for acute stroke. The findings of this case-control study suggest that higher locus of control is associated with lower risk of stroke and may be an important effect modifier of the risk associated with psychosocial stress.
Publisher: Elsevier BV
Date: 2018
Publisher: Elsevier BV
Date: 02-2022
Publisher: American Medical Association (AMA)
Date: 27-06-2012
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 18-10-2022
DOI: 10.1212/WNL.0000000000201006
Abstract: Current genome-wide association studies of ischemic stroke have focused primarily on late-onset disease. As a complement to these studies, we sought to identify the contribution of common genetic variants to risk of early-onset ischemic stroke. We performed a meta-analysis of genome-wide association studies of early-onset stroke (EOS), ages 18–59 years, using in idual-level data or summary statistics in 16,730 cases and 599,237 nonstroke controls obtained across 48 different studies. We further compared effect sizes at associated loci between EOS and late-onset stroke (LOS) and compared polygenic risk scores (PRS) for venous thromboembolism (VTE) between EOS and LOS. We observed genome-wide significant associations of EOS with 2 variants in ABO , a known stroke locus. These variants tag blood subgroups O1 and A1, and the effect sizes of both variants were significantly larger in EOS compared with LOS. The odds ratio (OR) for rs529565, tagging O1, was 0.88 (95% confidence interval [CI]: 0.85–0.91) in EOS vs 0.96 (95% CI: 0.92–1.00) in LOS, and the OR for rs635634, tagging A1, was 1.16 (1.11–1.21) for EOS vs 1.05 (0.99–1.11) in LOS p -values for interaction = 0.001 and 0.005, respectively. Using PRSs, we observed that greater genetic risk for VTE, another prothrombotic condition, was more strongly associated with EOS compared with LOS ( p = 0.008). The ABO locus, genetically predicted blood group A, and higher genetic propensity for venous thrombosis are more strongly associated with EOS than with LOS, supporting a stronger role of prothrombotic factors in EOS.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 27-09-2017
DOI: 10.1212/WNL.0000000000004560
Abstract: To determine whether common variants in familial cerebral small vessel disease (SVD) genes confer risk of sporadic cerebral SVD. We meta-analyzed genotype data from in iduals of European ancestry to determine associations of common single nucleotide polymorphisms (SNPs) in 6 familial cerebral SVD genes ( COL4A1 , COL4A2 , NOTCH3 , HTRA1 , TREX1 , and CECR1 ) with intracerebral hemorrhage (ICH) (deep, lobar, all 1,878 cases, 2,830 controls) and ischemic stroke (IS) (lacunar, cardioembolic, large vessel disease, all 19,569 cases, 37,853 controls). We applied data quality filters and set statistical significance thresholds accounting for linkage disequilibrium and multiple testing. A locus in COL4A2 was associated (significance threshold p 3.5 × 10 −4 ) with both lacunar IS (lead SNP rs9515201: odds ratio [OR] 1.17, 95% confidence interval [CI] 1.11–1.24, p = 6.62 × 10 −8 ) and deep ICH (lead SNP rs4771674: OR 1.28, 95% CI 1.13–1.44, p = 5.76 × 10 −5 ). A SNP in HTRA1 was associated (significance threshold p 5.5 × 10 −4 ) with lacunar IS (rs79043147: OR 1.23, 95% CI 1.10–1.37, p = 1.90 × 10 −4 ) and less robustly with deep ICH. There was no clear evidence for association of common variants in either COL4A2 or HTRA1 with non-SVD strokes or in any of the other genes with any stroke phenotype. These results provide evidence of shared genetic determinants and suggest common pathophysiologic mechanisms of distinct ischemic and hemorrhagic cerebral SVD stroke phenotypes, offering new insights into the causal mechanisms of cerebral SVD.
Publisher: Elsevier BV
Date: 2019
Publisher: Elsevier BV
Date: 05-2018
Publisher: Elsevier BV
Date: 03-2018
Publisher: Korean Stroke Society
Date: 31-05-2022
Abstract: Background and Purpose The association of dyslipidemia with stroke has been inconsistent, which may be due to differing associations within etiological stroke subtypes. We sought to determine the association of lipoproteins and apolipoproteins within stroke subtypes.Methods Standardized incident case-control STROKE study in 32 countries. Cases were patients with acute hospitalized first stroke, and matched by age, sex and site to controls. Concentrations of total cholesterol, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), apolipoprotein A1 (apoA1), and apoB were measured. Non-HDL-C was calculated. We estimated multivariable odds ratio (OR) and population attributable risk percentage (PAR%). Outcome measures were all stroke, ischemic stroke (and subtypes), and intracerebral hemorrhage (ICH).Results Our analysis included 11,898 matched case-control pairs 77.3% with ischemic stroke and 22.7% with ICH. Increasing apoB (OR, 1.10 95% confidence interval [CI], 1.06 to 1.14 per standard deviation [SD]) and LDL-C (OR, 1.06 95% CI, 1.02 to 1.10 per SD) were associated with an increase in risk of ischemic stroke, but a reduced risk of ICH. Increased apoB was significantly associated with large vessel stroke (PAR 13.4% 95% CI, 5.6 to 28.4) and stroke of undetermined cause. Higher HDL-C (OR, 0.75 95% CI, 0.72 to 0.78 per SD) and apoA1 (OR, 0.63 95% CI, 0.61 to 0.66 per SD) were associated with ischemic stroke (and subtypes). While increasing HDL-C was associated with an increased risk of ICH (OR, 1.20 95% CI, 1.14 to 1.27 per SD), apoA1 was associated with a reduced risk (OR, 0.80 95% CI, 0.75 to 0.85 per SD). ApoB/A1 (OR, 1.38 95% CI, 1.32 to 1.44 per SD) had a stronger magnitude of association than the ratio of LDL-C/HDL-C (OR, 1.26 95% CI, 1.21 to 1.31 per SD) with ischemic stroke (P .0001). Conclusions The pattern and magnitude of association of lipoproteins and apolipoproteins with stroke varies by etiological stroke subtype. While the directions of association for LDL, HDL, and apoB were opposing for ischemic stroke and ICH, apoA1 was associated with a reduction in both ischemic stroke and ICH. The ratio of apoB/A1 was the best lipid predictor of ischemic stroke risk.
Publisher: Cold Spring Harbor Laboratory
Date: 25-05-2018
DOI: 10.1101/329052
Abstract: We characterised the phenotypic consequence of genetic variation at the PCSK9 locus and compared findings with recent trials of pharmacological inhibitors of PCSK9. Published and in idual participant level data (300,000+ participants) were combined to construct a weighted PCSK9 gene-centric score (GS). Fourteen randomized placebo controlled PCSK9 inhibitor trials were included, providing data on 79,578 participants. Results were scaled to a one mmol/L lower LDL-C concentration The PCSK9 GS (comprising 4 SNPs) associations with plasma lipid and apolipoprotein levels were consistent in direction with treatment effects. The GS odds ratio (OR) for myocardial infarction (MI) was 0.53 (95%CI 0.42 0.68), compared to a PCSK9 inhibitor effect of 0.90 (95%CI 0.86 0.93). For ischemic stroke ORs were 0.84 (95%CI 0.57 1.22) for the GS, compared to 0.85 (95%CI 0.78 0.93) in the drug trials. ORs with type 2 diabetes mellitus (T2DM) were 1.29 (95% CI 1.11 1.50) for the GS, as compared to 1.00 (95%CI 0.96 1.04) for incident T2DM in PCSK9 inhibitor trials. No genetic associations were observed for cancer, heart failure, atrial fibrillation, chronic obstructive pulmonary disease, or Alzheimer’s disease – outcomes for which large-scale trial data were unavailable. Genetic variation at the PCSK9 locus recapitulates the effects of therapeutic inhibition of PCSK9 on major blood lipid fractions and MI. Apparent discordance between genetic associations and trial outcome for T2DM might be explained lack by a of statistical precision, or differences in the nature and duration of genetic versus pharmacological perturbation of PCSK9. This research was funded by the British Heart Foundation (SP/13/6/30554, RG/10/12/28456, FS/18/23/33512), UCL Hospitals NIHR Biomedical Research Centre, by the Rosetrees and Stoneygate Trusts. Evidence on the long-term efficacy and safety of therapeutic inhibition of PCSK9 is lacking. To explore potential long-term effects of PCSK9 inhibition, we characterised the phenotypic consequence of LDL-cholesterol lowering variants at the PCSK9 locus. A PCSK9 gene score comprising 4 SNPs recapitulated the effects of therapeutic inhibition of PCSK9 on major blood lipid fractions and risk of myocardial infarction, and was associated with an increased risk of type 2 diabetes. No associations with safety outcomes such as cancer, COPD, Alzheimer’s disease or atrial fibrillation were identified. Our findings suggest PCSK9 inhibition may be safe and effective during prolonged use.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 25-04-2023
DOI: 10.1212/WNL.0000000000207093
Abstract: Depression has been reported to be a risk factor of acute stroke, based largely on studies in high-income countries. In the INTERSTROKE study, we explored the contribution of depressive symptoms to acute stroke risk and 1-month outcome across regions of the world, within subpopulations and by stroke type. The INTERSTROKE is an international case-control study of risk factors of first acute stroke, conducted in 32 countries. Cases were patients with CT- or MRI-confirmed incident acute hospitalized stroke, and controls were matched for age, sex, and within sites. Standardized questions asked about self-reported depressive symptoms during the previous 12 months and the use of prescribed antidepressant medications were recorded. Multivariable conditional logistic regression was used to determine the association of prestroke depressive symptoms with acute stroke risk. Adjusted ordinal logistic regression was used to explore the association of prestroke depressive symptoms with poststroke functional outcome, measured with the modified Rankin scale at 1 month after stroke. Of 26,877 participants, 40.4% were women, and the mean age was 61.7 ± 13.4 years. The prevalence of depressive symptoms within the last 12 months was higher in cases compared with that in controls (18.3% vs 14.1%, p 0.001) and differed by region ( p interaction .001), with lowest prevalence in China (6.9% in controls) and highest in South America (32.2% of controls). In multivariable analyses, prestroke depressive symptoms were associated with greater odds of acute stroke (odds ratio [OR] 1.46, 95% CI 1.34–1.58), which was significant for both intracerebral hemorrhage (OR 1.56, 95% CI 1.28–1.91) and ischemic stroke (OR 1.44, 95% CI 1.31–1.58). A larger magnitude of association with stroke was seen in patients with a greater burden of depressive symptoms. While preadmission depressive symptoms were not associated with a greater odds of worse baseline stroke severity (OR 1.02, 95% CI 0.94–1.10), they were associated with a greater odds of poor functional outcome at 1 month after acute stroke (OR 1.09, 95% CI 1.01–1.19). In this global study, we recorded that depressive symptoms are an important risk factor of acute stroke, including both ischemic and hemorrhagic stroke. Preadmission depressive symptoms were associated with poorer functional outcome, but not baseline stroke severity, suggesting an adverse role of depressive symptoms in poststroke recovery.
Publisher: SAGE Publications
Date: 27-05-2021
DOI: 10.1177/17474930211019568
Abstract: Improving stroke services is critical for reducing the global stroke burden. The World Stroke Organization–World Health Organization– Lancet Neurology Commission on Stroke conducted a survey of the status of stroke services in low and middle-income countries (LMICs) compared to high-income countries. Using a validated World Stroke Organization comprehensive questionnaire, we collected and compared data on stroke services along four pillars of the stroke quadrangle (surveillance, prevention, acute stroke, and rehabilitation) in 84 countries across World Health Organization regions and economic strata. The World Health Organization also conducted a survey of non-communicable diseases in 194 countries in 2019. Fewer surveillance activities (including presence of registries, presence of recent risk factors surveys, and participation in research) were reported in low-income countries than high-income countries. The overall global score for prevention was 40.2%. Stroke units were present in 91% of high-income countries in contrast to 18% of low-income countries (p 0.001). Acute stroke treatments were offered in ∼ 60% of high-income countries compared to 26% of low-income countries (p = 0.009). Compared to high-income countries, LMICs provided less rehabilitation services including in-patient rehabilitation, home assessment, community rehabilitation, education, early hospital discharge program, and presence of rehabilitation protocol. There is an urgent need to improve access to stroke units and services globally especially in LMICs. Countries with less stroke services can adapt strategies from those with better services. This could include establishment of a framework for regular monitoring of stroke burden and services, implementation of integrated prevention activities and essential acute stroke care services, and provision of interdisciplinary care for stroke rehabilitation.
Publisher: S. Karger AG
Date: 2010
DOI: 10.1159/000306058
Abstract: Stroke is a major global health problem. It is the third leading cause of death and the leading cause of adult disability. INTERHEART, a global case-control study of acute myocardial infarction in 52 countries (29,972 participants), identified nine modifiable risk factors that accounted for % of population-attributable risk. However, traditional risk factors (e.g. hypertension, cholesterol) appear to exert contrasting risks for stroke compared with coronary heart disease, and the etiology of stroke is far more heterogeneous. In addition, our knowledge of risk factors for stroke in low-income countries is inadequate, where a very large burden of stroke occurs. Accordingly, a similar epidemiological study is required for stroke, to inform effective population-based strategies to reduce the risk of stroke. i Methods: /i INTERSTROKE is an international, multicenter case-control study. Cases are patients with a first stroke within 72 h of hospital presentation in whom CT or MRI is performed. Proxy respondents are used for cases unable to communicate. Etiological and topographical stroke subtype is documented for all cases. Controls are hospital- and community-based, matched for gender, ethnicity and age (±5 years). A questionnaire (cases and controls) is used to acquire information on known and proposed risk factors for stroke. Cardiovascular (e.g. blood pressure) and anthropometric (e.g. waist-to-hip ratio) measurements are obtained at the time of interview. Nonfasting blood s les and random urine s les are obtained from cases and controls. i Study Significance: /i An effective global strategy to reduce the risk of stroke mandates systematic measurement of the contribution of the major vascular risk factors within defined ethnic groups and geographical locations.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 08-2017
DOI: 10.1161/STROKEAHA.117.017322
Abstract: Mendelian strokes are rare genetic disorders characterized by early-onset small-vessel stroke. Although extensively studied among families with syndromic features, whether these genes affect risk among sporadic cases is unknown. We sequenced 8 genes responsible for Mendelian stroke in a case–control study of sporadic stroke cases (≤70 years). Participants included 1251 primary stroke cases of small-vessel pathology (637 intracerebral hemorrhage and 614 small-vessel ischemic stroke cases) and 1716 controls from the INTERSTROKE study (Study of the Importance of Conventional and Emerging Risk Factors of Stroke in Different Regions and Ethnic Groups of the World). Overall, the prevalence of canonical disease-causing mutations was 0.56% in cases and 0.23% in controls (odds ratio=1.89 95% confidence interval, 0.54–7.57 P =0.33). CADASIL (Cerebral Autosomal Dominant Arteriopathies with Subcortical Infarcts and Leukoencephalopathies) mutations were more frequent among cases (0.48%) than controls (0.23%) but were not significantly associated with stroke risk (odds ratio=2.03 95% confidence interval, 0.58–8.02 P =0.27). Next, we included all rare nonsynonymous mutations to investigate whether other types of mutations may contribute to stroke risk. Overall, 13.5% of cases and 14.2% of controls were carriers of at least one rare nonsynonymous mutation among the 8 Mendelian stroke genes. Mutation carriers were not at elevated risk of stroke (odds ratio=0.93 95% confidence interval, 0.75–1.16 P =0.55). In the absence of syndromic features and family history of stroke, screening for Mendelian mutations among small-vessel stroke patients is unlikely to have high diagnostic utility.
Publisher: SAGE Publications
Date: 11-04-2016
Abstract: Recent evidence supports that most non-lacunar cryptogenic strokes are embolic. Accordingly, these strokes have been designated as embolic strokes of undetermined source (ESUS). We undertook an international survey to characterize the frequency and clinical features of ESUS patients across global regions. Consecutive patients hospitalized for ischemic stroke were retrospectively surveyed from 19 stroke research centers in 19 different countries to collect patients meeting criteria for ESUS. Of 2144 patients with recent ischemic stroke, 351 (16%, 95% CI 15% to 18%) met ESUS criteria, similar across global regions (range 16% to 21%), and an additional 308 (14%) patients had incomplete evaluation required for ESUS diagnosis. The mean age of ESUS patients (62 years SD = 15) was significantly lower than the 1793 non-ESUS ischemic stroke patients (68 years, p ≤ 0.001). Excluding patients with atrial fibrillation ( n = 590, mean age = 75 years), the mean age of the remaining 1203 non-ESUS ischemic stroke patients was 64 years ( p = 0.02 vs. ESUS patients). Among ESUS patients, hypertension, diabetes, and prior stroke were present in 64%, 25%, and 17%, respectively. Median NIHSS score was 4 (interquartile range 2–8). At discharge, 90% of ESUS patients received antiplatelet therapy and 7% received anticoagulation. This cross-sectional global s le of patients with recent ischemic stroke shows that one-sixth met criteria for ESUS, with additional ESUS patients likely among those with incomplete diagnostic investigation. ESUS patients were relatively young with mild strokes. Antiplatelet therapy was the standard antithrombotic therapy for secondary stroke prevention in all global regions.
Publisher: Massachusetts Medical Society
Date: 03-03-2011
Location: Ireland
No related grants have been discovered for Martin O'Donnell.