Áine Merwick

Addition of brain and carotid imaging to the ABCD² score to identify patients at early risk of stroke after transient ischaemic attack: a multicentre observational study.

BACKGROUND The ABCD² score improves stratification of patients with transient ischaemic attack by early stroke risk. We aimed to develop two new versions of the score: one that was based on preclinical information and one that was based on imaging and other secondary care assessments. METHODS We analysed pooled data from patients with clinically defined transient ischaemic attack who were investigated while in secondary care. Items that contribute to the ABCD² score (age, blood pressure, clinical weakness, duration, and diabetes), other clinical variables, carotid stenosis, and abnormal acute diffusion-weighted imaging (DWI) were recorded and were included in multivariate logistic regression analysis of stroke occurrence at early time intervals after onset of transient ischaemic attack. Scores based on the findings of this analysis were validated in patients with transient ischaemic attack from two independent population-based cohorts. FINDINGS 3886 patients were included in the study: 2654 in the derivation sample and 1232 in the validation sample. We derived the ABCD³ score (range 0-9 points) by assigning 2 points for dual transient ischaemic attack (an earlier transient ischaemic attack within 7 days of the index event). C statistics (which indicate discrimination better than chance at >0·5) for the ABCD³ score were 0·78 at 2 days, 0·80 at 7 days, 0·79 at 28 days, and 0·77 at 90 days, compared with C statistics for the ABCD² score of 0·71 at 2 days (p=0·083), 0·71 at 7 days (p=0·012), 0·71 at 28 days (p=0·021), and 0·69 at 90 days (p=0·018). We included stenosis of at least 50% on carotid imaging (2 points) and abnormal DWI (2 points) in the ABCD³-imaging (ABCD³-I) score (0-13 points). C statistics for the ABCD³-I score were 0·90 at 2 days (compared with ABCD² score p=0·035), 0·92 at 7 days (p=0·001), 0·85 at 28 days (p=0·028), and 0·79 at 90 days (p=0·073). The 90-day net reclassification improvement compared with ABCD² was 29·1% for ABCD³ (p=0·0003) and 39·4% for ABCD³-I (p=0·034). In the validation sample, the ABCD³ and ABCD³-I scores predicted early stroke at 7, 28, and 90 days. However, discrimination and net reclassification of patients with early stroke were similar with ABCD³ compared with ABCD². INTERPRETATION The ABCD³-I score can improve risk stratification after transient ischaemic attack in secondary care settings. However, use of ABCD³ cannot be recommended without further validation. FUNDING Health Research Board of Ireland, Irish Heart Foundation, and Irish National Lottery.

Addition of Brain Infarction to the ABCD2 Score (ABCD2I) A Collaborative Analysis of Unpublished Data on 4574 Patients

Background and Purpose— The ABCD system was developed to predict early stroke risk after transient ischemic attack. Incorporation of brain imaging findings has been suggested, but reports have used inconsistent methods and been underpowered. We therefore performed an international, multicenter collaborative study of the prognostic performance of the ABCD2 score and brain infarction on imaging to determine the optimal weighting of infarction in the score (ABCD2I). Methods— Twelve centers provided unpublished data on ABCD2 scores, presence of brain infarction on either diffusion-weighted imaging or CT, and follow-up in cohorts of patients with transient ischemic attack diagnosed by World Health Organization criteria. Optimal weighting of infarction in the ABCD2I score was determined using area under the receiver operating characteristic curve analyses and random effects meta-analysis. Results— Among 4574 patients with TIA, acute infarction was present in 884 (27.6%) of 3206 imaged with diffusion-weighted imaging and new or old infarction was present in 327 (23.9%) of 1368 imaged with CT. ABCD2 score and presence of infarction on diffusion-weighted imaging or CT were both independently predictive of stroke (n=145) at 7 days (after adjustment for ABCD2 score, OR for infarction=6.2, 95% CI=4.2 to 9.0, overall; 14.9, 7.4 to 30.2, for diffusion-weighted imaging; 4.2, 2.6 to 6.9, for CT; all P<0.001). Incorporation of infarction in the ABCD2I score improved predictive power with an optimal weighting of 3 points for infarction on CT or diffusion-weighted imaging. Pooled areas under the curve increased from 0.66 (0.53 to 0.78) for the ABCD2 score to 0.78 (0.72 to 0.85) for the ABCD2I score. Conclusions— In secondary care, incorporation of brain infarction into the ABCD system (ABCD2I score) improves prediction of stroke in the acute phase after transient ischemic attack.

Carotid plaque inflammation on 18F-fluorodeoxyglucose positron emission tomography predicts early stroke recurrence.

Symptomatic carotid stenosis is associated with a 3‐fold risk of early stroke recurrence compared to other stroke subtypes. Current carotid imaging techniques rely on estimating plaque‐related lumen narrowing but do not evaluate intraplaque inflammation, a key mediator of plaque rupture and thromboembolism. Using combined 18F‐fluorodeoxyglucose positron‐emission tomography (FDG‐PET)/computed tomography, we investigated the relation between inflammation‐related FDG uptake and stroke recurrence.

Stroke Associated with Atrial Fibrillation – Incidence and Early Outcomes in the North Dublin Population Stroke Study

Background: Prospective population-based studies are important to accurately determine the incidence and characteristics of stroke associated with atrial fibrillation (AF), while avoiding selection bias which may complicate hospital-based studies. Methods: We investigated AF-associated stroke within the North Dublin Population Stroke Study, a prospective cohort study of stroke/transient ischaemic attack in 294,592 individuals, according to recommended criteria for rigorous stroke epidemiological studies. Results: Of 568 stroke patients ascertained in the first year, 31.2% (177/568) were associated with AF (90.4%, i.e. 160/177 ischaemic infarcts). The crude incidence rate of all AF-associated stroke was 60/100,000 person-years (95% CI = 52–70). Prior stroke was almost twice as common in AF compared to non-AF groups (21.9 vs. 12.8%, p = 0.01). The frequency of AF progressively increased across ischaemic stroke patients stratified by increasing stroke severity (NIHSS 0–4, 29.7%; 5–9, 38.1%; 10–14, 43.8%; ≥15, 53.3%, p < 0.0001). The 90-day trajectory of recovery of AF-associated stroke was identical to that of non-AF stroke, but Rankin scores in AF stroke remained higher at 7, 28 and 90 days (p < 0.001 for all). Discussion: AF-associated stroke occurred in one third of all patients and was associated with a distinct profile of recurrent, severe and disabling stroke. Targeted strategies to increase anticoagulation rates may provide a substantial benefit to prevent severe disabling stroke at a population level.

Stroke Subtype Classification to Mechanism-Specific and Undetermined Categories by TOAST, A-S-C-O, and Causative Classification System Direct Comparison in the North Dublin Population Stroke Study

Background and Purpose— Reliable etiologic classification of ischemic stroke may enhance clinical trial design and identification of subtype-specific environmental and genetic risk factors. Although new classification systems (Causative Classification System [CCS] and ASCO [A for atherosclerosis, S for small vessel disease, C for cardiac source, O for other cause]) have been developed to improve subtype assignment, few comparative data exist from large studies. We hypothesized that both CCS and ASCO would reduce the proportion of patients classified as cause undetermined compared with the Trial of ORG 10172 in Acute Stroke Treatment (TOAST) scheme in a large population-based stroke study. Methods— A single rater classified all first-ever ischemic strokes in the North Dublin Population Stroke Study, a population-based study of 294 529 North Dublin residents. Published algorithms for TOAST, CCS, and ASCO were applied. Results— In 381 first-ever ischemic stroke patients, CCS assigned fewer patients as cause undetermined (26.2% versus 39.4%; P<0.000001), with increased assignment of cardio-aortic embolism (relative increase 6.9%; P=0.004), large artery atherosclerosis (relative increase 44.1%; P=0.00006), small artery occlusion (relative increase 27.3%; P=0.00006), and other causes (relative increase 91.7%; P=0.001) compared with TOAST. When ASCO grade 1 evidence was applied, fewer patients were classified as small artery disease (relative decrease 29.1%; P=0.007) and more as large artery/atherothrombotic (relative increase 17.6%; P=0.03). ASCO grade 1 did not reduce the proportion of cause undetermined cases compared with TOAST (42.3% versus 39.4%; P=0.2). Agreement between systems ranged from good (&kgr;=0.61 for TOAST/ASCO grade 1 small artery category) to excellent (&kgr;=0.95 for TOAST/CCS and ASCO grade 1/CCS cardio/aorto-embolism category). Application of ASCO grades 1 to 3 indicated evidence of large artery/atherosclerosis (73.3%), cardio-embolism (31.3%), small artery (64.7%), and other cause (12%) in TOAST-undetermined cases. Conclusion— Both CCS and ASCO schemes showed good-to-excellent agreement with TOAST, but each had specific characteristics compared with TOAST for subtype assignment and data retention. The feasibility of a single combined classification system should be considered.

Population-Based Study of ABCD2 Score, Carotid Stenosis, and Atrial Fibrillation for Early Stroke Prediction After Transient Ischemic Attack The North Dublin TIA Study

Background and Purpose— Transient ischemic attack (TIA) etiologic data and the ABCD2 score may improve early stroke risk prediction, but studies are required in population-based cohorts. We investigated the external validity of the ABCD2 score, carotid stenosis, and atrial fibrillation for prediction of early recurrent stroke after TIA. Methods— Patients with TIA in the North Dublin city population (N=294 529) were ascertained by using overlapping hospital and community sources. The relations between individual ABCD2 items, carotid stenosis, atrial fibrillation, and early stroke were examined. Results— In confirmed TIA cases (n=443), carotid stenosis predicted 90-day stroke (hazard ratio=2.56; 95% CI, 1.27 to 5.15, P=0.003). Stroke risk rose with increasing grade of carotid stenosis, ranging from 5.4% (95% CI, 3.3% to 8.7%) with <50% stenosis to 17.2% (95% CI, 9.7% to 29.7%) with severe stenosis/occlusion (hazard ratio=3.3; 95% CI, 1.5 to 7.4, P=0.002). In confirmed TIA cases (n=443), the ABCD2 score performed no better than chance for prediction of 90-day stroke (c-statistic=0.55; 95% CI, 0.45 to 0.64), largely related to the 24.2% (8/33) of patients who experienced a recurrence and had low ABCD2 scores (0–3). However, in nonspecialist-suspected TIA cases (n=700), the predictive utility improved for stroke at 28 (c-statistic=0.61; 95% CI, 0.50 to 0.72) and 90 (c-statistic=0.61; 95% CI, 0.52 to 0.71) days. Conclusions— In a population-based TIA cohort, significant predictive information was provided by carotid stenosis. The ABCD2 score had predictive utility in patients with TIA suspected by nonspecialists. Low scores occurred in several patients with stroke recurrences, suggesting that caution is needed before using the score in isolation.

Diagnostic Usefulness of the ABCD2 Score to Distinguish Transient Ischemic Attack and Minor Ischemic Stroke From Noncerebrovascular Events. The North Dublin TIA Study

Background and Purpose— Transient ischemic attack (TIA) diagnosis is frequently difficult in clinical practice. Noncerebrovascular symptoms are often misclassified as TIA by nonspecialist physicians. Clinical prediction rules such as ABCD2 improve the identification of patients with TIA at high risk of early stroke. We hypothesized that the ABCD2 score may partly improve risk stratification due to improved discrimination of true TIA and minor ischemic stroke (MIS) from noncerebrovascular events. Methods— Consecutive patients with TIA were identified within a prospective population-based cohort study of stroke and TIA. The cohort was expanded by inclusion of patients with MIS and noncerebrovascular events referred to a daily TIA clinic serving the population. Diagnosis was assigned by a trained stroke physician independent of ABCD2 score. Results— Five hundred ninety-four patients were included (292 [49.2%] TIA, 45 [7.6%] MIS, and 257 [43.3%] noncerebrovascular). The mean ABCD2 score showed a graded increase across diagnostic groups (MIS mean 4.8 [SD 1.4] versus TIA mean 3.9 [SD 1.5] versus noncerebrovascular mean 2.9 [SD 1.5]; P<0.00001). The ABCD2 score discriminated well between noncerebrovascular and cerebrovascular events—TIA (c-statistic 0.68; 95% CI, 0.64 to 0.72), any vascular event (TIA+MIS; c-statistic 0.7; 95% CI, 0.66 to 0.74), and MIS (c-statistic 0.81; 95% CI, 0.75 to 0.87)—from noncerebrovascular events. Of ABCD2 items, unilateral weakness (OR, 4.5; 95% CI, 3.1 to 6.6) and speech disturbance (OR, 2.5; 95% CI, 1.6, 4.1) were most likely overrepresented in TIA compared with noncerebrovascular groups. Conclusion— The ABCD2 score had significant diagnostic usefulness for discrimination of true TIA and MIS from noncerebrovascular events, which may contribute to its predictive usefulness.

Association between acute statin therapy, survival, and improved functional outcome after ischemic stroke: the North Dublin Population Stroke Study.

Background and Purpose— Statins improve infarct volume and neurological outcome in animal stroke models. We investigated the relationship between statin therapy and ischemic stroke outcome in the North Dublin Population Stroke Study. Methods— A population-based prospective cohort study was performed using rigorous ascertainment methods. Prestroke and acute (≤72 hours) poststroke medications were recorded. Modified Rankin score and fatality were assessed at 7, 28, and 90 days and 1 year. Results— Of 448 ischemic stroke patients, statins were prescribed before stroke onset in 30.1% (134/445) and were begun acutely (≤72 hours) in an additional 42.5% (189/445). On logistic regression analysis, adjusting for age, prestroke disability (modified Rankin scale), NIHSS score, hypertension, and aspirin, new poststroke statin therapy was independently associated with improved early and late survival (compared with statin untreated patients: OR for death, 0.12; CI, 0.03–0.54 at 7 days; OR, 0.19; CI, 0.07–0.48 at 90 days; OR, 0.26; CI, 0.12–0.55 at 1 year; P≤0.006 for all). Similar findings were observed for statin therapy before stroke onset (adjusted OR for death compared with statin-untreated-patients, 0.04; CI, 0.00–0.33; P=0.003 at 7 days; OR, 0.23; CI, 0.09–0.58; P=0.002 at 90 days; OR, 0.48; CI, 0.23–1.01; P=0.05 at 1 year). Conclusions— Statin therapy at stroke onset and newly begun statins were associated with improved early and late outcomes, supporting data from experimental studies. Randomized trials of statin therapy for treatment of acute stroke are needed.

Reduction in Early Stroke Risk in Carotid Stenosis With Transient Ischemic Attack Associated With Statin Treatment

Background and Purpose— Statins reduce stroke risk when initiated months after transient ischemic attack (TIA)/stroke and reduce early vascular events in acute coronary syndromes, possibly via pleiotropic plaque stabilization. Few data exist on acute statin use in TIA. We aimed to determine whether statin pretreatment at TIA onset modified early stroke risk in carotid stenosis. Methods— We analyzed data from 2770 patients with TIA from 11 centers, 387 with ipsilateral carotid stenosis. ABCD2 score, abnormal diffusion weighted imaging, medication pretreatment, and early stroke were recorded. Results— In patients with carotid stenosis, 7-day stroke risk was 8.3% (95% confidence interval [CI], 5.7–11.1) compared with 2.7% (CI, 2.0%–3.4%) without stenosis (P<0.0001; 90-day risks 17.8% and 5.7% [P<0.0001]). Among carotid stenosis patients, nonprocedural 7-day stroke risk was 3.8% (CI, 1.2%–9.7%) with statin treatment at TIA onset, compared with 13.2% (CI, 8.5%–19.8%) in those not statin pretreated (P=0.01; 90-day risks 8.9% versus 20.8% [P=0.01]). Statin pretreatment was associated with reduced stroke risk in patients with carotid stenosis (odds ratio for 90-day stroke, 0.37; CI, 0.17–0.82) but not nonstenosis patients (odds ratio, 1.3; CI, 0.8–2.24; P for interaction, 0.008). On multivariable logistic regression, the association remained after adjustment for ABCD2 score, smoking, antiplatelet treatment, recent TIA, and diffusion weighted imaging hyperintensity (adjusted P for interaction, 0.054). Conclusions— In acute symptomatic carotid stenosis, statin pretreatment was associated with reduced stroke risk, consistent with findings from randomized trials in acute coronary syndromes. These data support the hypothesis that statins started acutely after TIA symptom onset may also be beneficial to prevent early stroke. Randomized trials addressing this question are required.

Incidence, Event Rates, and Early Outcome of Stroke in Dublin, Ireland: The North Dublin Population Stroke Study

Background and Purpose— The World Health Organization has emphasized the importance of international population-based data for unbiased surveillance of stroke incidence and outcome. To date, few such studies have been conducted using recommended gold-standard ascertainment methods. We conducted a large, population-based stroke study in Dublin, Ireland. Methods— Using gold-standard ascertainment methods, individuals with stroke and transient ischemic attack occurring over a 12-month period (December 1, 2005–November 30, 2006) in North Dublin were identified. Disability was assessed using the modified Rankin score and stroke severity (<72 hours) by the National Institutes of Health Stroke Scale. Stroke-related deaths were confirmed by review of medical files, death certificates, pathology, and coroners records. Crude and standardized (to European and World Health Organization standard populations) rates of incidence, risk factors, severity, and early outcome (mortality, case-fatality, disability) were calculated, assuming a Poisson distribution for the number of events. Results— Seven hundred one patients with new stroke or transient ischemic attack were ascertained (485 first-ever stroke patients, 83 recurrent stroke patients, 133 first-ever transient ischemic attack patients). Crude frequency rates (all rates per 1000 person-years) were: 1.65 (95% CI, 1.5–1.79; first-ever stroke), 0.28 (95% CI, 0.22–0.35; recurrent stroke), and 0.45 (95% CI, 0.37–0.53; first-ever transient ischemic attack). Age-adjusted stroke rates were higher than those in 9 other recent population-based samples from high-income countries. High rates of subtype-specific risk factors were observed (atrial fibrillation, 31.3% and smoking, 29.1% in ischemic stroke; warfarin use, 21.2% in primary intracerebral hemorrhage; smoking, 53.9% in subarachnoid hemorrhage; P<0.01 for all compared with other subtypes). Compared with recent studies, 28-day case-fatality rates for primary intracerebral hemorrhage (41%; 95% CI, 29.2%–54.1%) and subarachnoid hemorrhage (46%; 95% CI, 28.8%–64.5%) were greater in Dublin. Conclusions— Using gold-standard methods for case ascertainment, we found high incidence rates of stroke in Dublin compared with those in similar high-income countries; this is likely explained in part by high rates of subtype-specific risk factors.