North Dublin Population Stroke Study Research Articles

Suboptimal lipid management before and after ischaemic stroke and TIA-the North Dublin Population Stroke Study.

Few population-based studies have assessed lipid adherence to international guidelines for primary and secondary prevention in stroke/transient ischaemic attack (TIA) patients. This study aims to evaluate adherence to lipid-lowering therapy (LLT) guidelines amongst patients with ischaemic stroke/TIA. Using hot and cold pursuit methods from multiple hospital/community sources, all stroke and TIA cases in North Dublin City were prospectively ascertained over a 1-year period. Adherence to National Cholesterol Education Programme (NCEP) III guidelines, before and after index ischaemic stroke/TIA, was assessed. Amongst 616 patients (428 ischaemic stroke, 188 TIA), total cholesterol was measured following the qualifying event in 76.5% (471/616) and low-density lipoprotein (LDL) in 60.1% (370/616). At initial stroke/TIA presentation, 54.1% (200/370) met NCEP III LDL goals. Compliance was associated with prior stroke (odds ratio [OR] 2.19, p = 0.02), diabetes (OR 1.91, p = 0.04), hypertension (OR 1.57, p = 0.03), atrial fibrillation (OR 1.78, p = 0.01), pre-event LLT (OR 2.85, p < 0.001) and higher individual LDL goal (p = 0.001). At stroke/TIA onset, 32.7% (195/596) was on LLT. Nonetheless, LDL exceeded individual NCEP goal in 29.2% (56/192); 21.6% (53/245) warranting LLT was not on treatment prior to stroke/TIA onset. After index stroke/TIA, 75.9% (422/556) was on LLT; 15.3% (30/196) meeting NCEP III criteria was not prescribed a statin as recommended. By 2years, actuarial survival was 72.8% and 11.9% (59/497) experienced stroke recurrence. No association was observed between initial post-event target adherence and 2-year outcomes. In this population-based study, LLT recommended by international guidelines was under-used, before and after index stroke/TIA. Strategies to improve adherence are needed.

Renal dysfunction and chronic kidney disease in ischemic stroke and transient ischemic attack: A population-based study.

Background and purpose The prevalence of chronic kidney disease (estimated glomerular filtration rate (eGFR) <60 mL/min per 1.73 m2 for ≥3 months, chronic kidney disease (CKD)) in ischemic stroke and transient ischemic attack (TIA) is unknown, as estimates have been based on single-point estimates of renal function. Studies investigating the effect of renal dysfunction (eGFR < 60 mL/min per 1.73 m2, renal dysfunction) on post-stroke outcomes are limited to hospitalized cohorts and have provided conflicting results. Methods We investigated rates, determinants and outcomes of renal dysfunction in ischemic stroke and TIA in the North Dublin Population Stroke Study. We also investigate the persistence of renal dysfunction in 90-day survivors to determine the prevalence of CKD. Ascertainment included hot and cold pursuit using multiple overlapping sources. Survival analysis was performed using Kaplan-Meier survival curves and Cox proportional hazards modeling. Results In 547 patients (ischemic stroke in 76.4%, TIA in 23.6%), the mean eGFR at presentation was 63.7 mL/min/1.73 m2 (SD 22.1). Renal dysfunction was observed in 44.6% (244/547). Among 90-day survivors, 31.2% (139/446) met criteria for CKD. After adjusting for age and stroke severity, eGFR < 45 mL/min/1.73 m2 (hazard ratio 2.53, p = 0.01) independently predicted 28-day fatality but not at two years. Poor post-stroke functional outcome (Modified Rankin Scale 3-5) at two years was more common in those with renal dysfunction (52.5% vs. 20.6%, p < 0.001). After adjusting for age, stroke severity and pre-stroke disability, renal dysfunction (OR 2.17, p = 0.04) predicted poor functional outcome. Conclusion Renal dysfunction and CKD are common in ischemic stroke and TIA. Renal dysfunction is associated with considerable post-stroke morbidity and mortality. Further studies are needed to investigate if modifiable mechanisms underlie these associations.

Rates, Predictors, and Outcomes of Early and Late Recurrence After Stroke: The North Dublin Population Stroke Study.

Few recent studies have investigated the rates and predictors of early and late stroke recurrence using prospective population-based methodology. We investigated recurrent stroke at 2 years in the North Dublin Population Stroke Study (NDPSS). Patients were ascertained from December 2005 to 2006 from overlapping community and hospital sources using hot and cold pursuit. Stroke recurrence, survival, and functional outcome were ascertained at 72 hours, 7 days, 28 days, 90 days, 1 year, and 2 years. Of 567 patients, cumulative 2-year stroke recurrence rate was 10.8% and case fatality was 38.6%. Recurrence subtype was associated with initial stroke subtype (P<0.001). On multivariable Cox regression, hyperlipidemia (adjusted hazard ratio, 3.32; P=0.005) and prior stroke (adjusted hazard ratio, 2.92; P=0.01) were independent predictors of 2-year recurrence in 28-day survivors. Despite rigorous ascertainment, recurrent stroke rates were lower in current study than in earlier studies. Our data suggest that large sample sizes may be needed for future secondary prevention trials in patients treated with modern preventive medications.

Rates and Determinants of 5-Year Outcomes After Atrial Fibrillation-Related Stroke: A Population Study.

Demographic trends in atrial fibrillation (AF) incidence may yield a substantial rise in the societal burden of AF-related stroke (AF-stroke). Accurate population-wide outcome data are essential to inform health service planning to improve AF-stroke prevention, and provision of rehabilitation, nursing home, and community supports for AF-stroke survivors. We investigated rates and determinants of 5-year fatality, stroke recurrence, functional outcomes, and prescribing of secondary prevention medications in AF-stroke in the North Dublin Population Stroke Study. Ascertainment included hot and cold pursuit using multiple overlapping sources. Survival analysis was performed using lifetables and Kaplan-Meier survival curves, and Cox proportional hazard modeling was performed to identify predictors of death and recurrent stroke. Five hundred sixty-eight patients with new stroke were identified, including 177 (31.2%) AF-stroke. At 5 years, 39.2% (confidence interval, 31.5-46.8) of ischemic AF-stroke patients were alive. Congestive heart failure, hypertension, age <65, 65-74 years, and ≥75 years, diabetes mellitus, prior stroke, transient ischemic attack or thromboembolism, vascular disease and female sex (CHA2DS2-VASc) score (hazard ratio [HR], 1.34; P<0.001), CHADS2 score (HR 1.42, P=0.004), National Institute of Health Stroke Scale (HR, 1.09; P<0.0001), and subtherapeutic international normalized ratio (<2.0) at stroke onset (HR, 3.29; P=0.003) were independently associated with 5-year fatality, whereas warfarin (HR, 0.40; P=0.001) and statin use after index stroke (HR, 0.52; P=0.005) were associated with improved survival. The 5-year recurrence rate after ischemic AF-stroke was 21.5% (confidence interval, 14.5-31.3). Trends toward greater risk of recurrence were observed for persistent AF (HR, 3.09; P=0.07) and CHA2DS2-VASc score (HR, 1.34; P=0.07). Nursing home care was needed for 25.9% of patients. AF-stroke is associated with considerable long-term morbidity, fatality, stroke recurrence, and nursing home requirement. Adequately resourced national AF strategies to improve AF detection and prevention are needed.

Falls and fractures 2 years after acute stroke: the North Dublin Population Stroke Study

Stroke patients are at increased risk of falls and fractures. The aim of this study was to determine the rate, predictors and consequences of falls within 2 years after stroke in a prospective population-based study in North Dublin, Ireland. Prospective population-based cohort study. 567 adults aged >18 years from the North Dublin Population Stroke Study. Participants were enrolled from an Irish urban population of 294,592 individuals, according to recommended criteria. Patients were followed for 2 years. Outcome measures included death, modified Rankin Scale (mRS), fall and fracture rate. At 2 years, 23.5% (124/522) had fallen at least once since their stroke, 14.2% (74/522) had 2 or more falls and 5.4% (28/522) had a fracture. Of 332 survivors at 2 years, 107 (32.2%) had fallen, of whom 60.7% (65/107) had 2 or more falls and 23.4% (25/107) had fractured. In a multivariable model controlling for age and gender, independent risk factors for falling within the first 2 years of stroke included use of alpha-blocker medications for treatment of hypertension (P = 0.02). When mobility measured at Day 90 was included in the model, patients who were mobility impaired (mRS 2-3) were at the highest risk of falling within 2 years of stroke [odds ratio (OR) 2.30, P = 0.003] and those functionally dependent (mRS 4-5) displayed intermediate risk (OR 2.02, P = 0.03) when compared with independently mobile patients. Greater attention to falls risk, fall prevention strategies and bone health in the stroke population are required.

Abstract 171: A Population-based Comparison of Total Costs: The Economic Burden of Atrial Fibrillation-Associated Stroke

Introduction Accurate health economics data is essential for service planning and clinical guideline development. Stroke associated with atrial fibrillation (AF) is characteristically more severe and disabling than non-AF stroke. Few data exist on the economic impact of AF-stroke compared to non-AF-stroke in population-based samples. Methods The North Dublin Population Stroke Study is a population-based prospective study of incident stroke in Dublin, Ireland. Both direct (healthcare-related) and indirect costs were calculated over a 2-year post-stroke period for individual patients, using data for survival and disability, discharge destination, outpatient and family practitioner visits, community supports, and ongoing treatment. Acute inpatient care was costed using the casemix approach, measuring the resource use per hospitalization (index stroke plus post-stroke admissions). Length of stay was used to cost rehabilitation and nursing home admissions. Indirect costs of illness were calculated using in-hospital length of stay to determine loss of productivity. Total costs were compared for AF-stroke and non-AF stroke, calculated at 2007 prices and converted to US$ (2007 rates). Results Of 568 ischemic and hemorrhagic incident stroke patients, 31% (177) had AF-associated stroke. 2-year fatality was higher in AF-stroke patients (50.3% versus 35.1%, p=0.001). Total 2-year median cost was $34,982 for AF-stroke patients (25-75% IQR $14,213-$88,283) compared to median cost of $17,736 (25-75% IQR $10,803-45,838] in non-AF stroke patients (p&lt;0.001). Inpatient care contributed 47% of total costs: cost per AF-stroke patient (index stroke) was median $14,257 (IQR $10,286-$40,989) compared to median $10,624 per non-AF stroke patient (IQR $9,482-26,241, p=0.002). Long-term institutional care was the second highest cost contributor with greater proportions of living AF stroke patients in nursing homes (2-year mean cost $23,997(±standard deviation [SD] $68,585) versus non-AF-stroke (mean $12,988 (±SD $51,561, p=0.002 for cost comparison). Community supports (2-year mean $5,487 ±SD $13,283 versus $3,808 ±SD $11,844 (p=0.1), post-stroke specialized equipment (mean $2,729±$8,927 vs $2,122±$8,267, p=0.2), and repeat hospital admission (mean $3,580±$12,124 vs $1,951±$8,446, p=0.4) costs were non-significantly higher in patients with AF-stroke. In linear regression models, AF was an independent predictor of total costs after adjusting for age (p=0.02, β 0.1) but the association was lost on adding stroke severity (72-hour Rankin score) (p=0.1, β 0.07). Conclusion In this population study, AF-associated stroke was associated with substantially higher costs for hospitalisation and community support after discharge. With ageing populations and increasing stroke burden, AF-stroke is likely to account for an increasing proportion of overall cost to health services.

Stroke recurrence within the time window recommended for carotid endarterectomy

In the North Dublin Population Stroke Study, we investigated the risk of recurrent stroke within the 14-day time window recommended for endarterectomy. In a population-based prospective cohort study, all ischemic stroke patients were identified over 1 year and categorized into those with (CS-positive) and without (CS-negative) ipsilateral carotid stenosis (CS) (≥50% lumen narrowing). Nonprocedural stroke recurrence was determined at 72 hours and 7 and 14 days. Of 365 ischemic stroke patients with carotid imaging, 51 were excluded due to posterior circulation or nonlateralizing stroke, ipsilateral carotid occlusion, or intracranial stenosis, leaving 314 included for analysis (36 CS-positive and 278 CS-negative). Recurrent stroke occurred in 5.6% (2/36) CS-positive and 0.4% (1/278) CS-negative patients by 72 hours of symptom onset (p =0.003), 5.6% (2/36) CS-positive and 0.7% (2/278) CS-negative patients (p =0.01) by 7 days, and in 8.3% (3/36) CS-positive and 1.8% (5/278) CS-negative patients by 14 days (p =0.02). On multivariable Cox regression analysis, CS was the only independent predictor of recurrence at 72 hours (adjusted hazard ratio [HR] 36.1, 95% confidence interval [CI] 1.6-837.5, p =0.03), and 7 days (HR 9.1, 1.1-79.2, p =0.05), with a trend at 14 days (HR 4.6, 0.9-22.8, p =0.06). Although only a minority of patients with symptomatic CS had a recurrent stroke within 14 days, early recurrent stroke risk was high, particularly within the first 72 hours. Earlier carotid revascularization or improved acute medical treatment may reduce recurrence in this high-risk group.

Letter by Reeves Regarding Article, “Association Between Acute Statin Therapy, Survival, and Improved Functional Outcome After Ischemic Stroke: The North Dublin Population Stroke Study”

To the Editor: I read with interest the article showing substantially reduced mortality for patients who were given statins either prestroke or shortly after onset in a cohort of 448 incident ischemic stroke patients from Dublin, Ireland.1 The 28-day and 90-day case fatality rates in the overall cohort were 12.3% and 17.8%, respectively, which are similar to estimates derived from other contemporary cohort studies.2–4 It is of interest, however, to examine the Kaplan-Meier survival curves in Figure 2, which show that the group not treated …

Response to Letter by Reeves Regarding Article, “Association Between Acute Statin Therapy, Survival, and Improved Functional Outcome After Ischemic Stroke: The North Dublin Population Stroke Study”

Response: We thank Professor Reeves1 for his interest in our work. As he correctly states, it is possible that treatment selection bias favoring less-impaired patients (confounding by indication) may have partially contributed to the findings reported in the North Dublin cohort. This is an inherent limitation to observational studies examining outcome and medication exposure, including statins. We highlighted this key point in our article, …

Association Between Acute Statin Therapy, Survival, and Improved Functional Outcome After Ischemic Stroke

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. 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. 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). 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.

Stroke Subtype Classification to Mechanism-Specific and Undetermined Categories by TOAST, A-S-C-O, and Causative Classification System

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. 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. 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 (kappa=0.61 for TOAST/ASCO grade 1 small artery category) to excellent (kappa=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. 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.

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.