Thomas Jeerakathil

The high risk of stroke immediately after transient ischemic attack A population-based study

Background: The risk of stroke is elevated in the first 48 hours after TIA. Previous prognostic models suggest that diabetes mellitus, age, and clinical symptomatology predict stroke. The authors evaluated the magnitude of risk of stroke and predictors of stroke after TIA in an entire population over time. Methods: Administrative data from four different databases were used to define TIA and stroke for the entire province of Alberta for the fiscal year (April 1999–March 2000). The age-adjusted incidence of TIA was estimated using direct standardization to the 1996 Canadian population. The risk of stroke after a diagnosis of TIA in an Alberta emergency room was defined using a Kaplan-Meier survival function. Cox proportional hazards modeling was used to develop adjusted risk estimates. Risk assessment began 24 hours after presentation and therefore the risk of stroke in the first few hours after TIA is not captured by our approach. Results: TIA was reported among 2,285 patients for an emergency room diagnosed, age-adjusted incidence of 68.2 per 100,000 population (95% CI 65.3 to 70.9). The risk of stroke after TIA was 9.5% (95% CI 8.3 to 10.7) at 90 days and 14.5% (95% CI 12.8 to 16.2) at 1 year. The risk of combined stroke, myocardial infarction, or death was 21.8% (95% CI 20.0 to 23.6) at 1 year. Hypertension, diabetes mellitus, and older age predicted stroke at 1 year but not earlier. Conclusions: Although stroke is common after TIA, the early risk is not predicted by clinical and demographic factors. Validated models to identify which patients require urgent intervention are needed.

Admission Hyperglycemia Predicts a Worse Outcome in Stroke Patients Treated With Intravenous Thrombolysis

OBJECTIVE Admission hyperglycemia has been associated with worse outcomes in ischemic stroke. We hypothesized that hyperglycemia (glucose >8.0 mmol/l) in the hyperacute phase would be independently associated with increased mortality, symptomatic intracerebral hemorrhage (SICH), and poor functional status at 90 days in stroke patients treated with intravenous tissue plasminogen activator (IV-tPA). RESEARCH DESIGN AND METHODS Using data from the prospective, multicenter Canadian Alteplase for Stroke Effectiveness Study (CASES), the association between admission glucose >8.0 mmol/l and mortality, SICH, and poor functional status at 90 days (modified Rankin Scale >1) was examined. Similar analyses examining glucose as a continuous measure were conducted. RESULTS Of 1,098 patients, 296 (27%) had admission hyperglycemia, including 18% of those without diabetes and 70% of those with diabetes. After multivariable logistic regression, admission hyperglycemia was found to be independently associated with increased risk of death (adjusted risk ratio 1.5 [95% CI 1.2–1.9]), SICH (1.69 [0.95–3.00]), and a decreased probability of a favorable outcome at 90 days (0.7 [0.5–0.9]). An incremental risk of death and SICH and unfavorable 90-day outcomes was observed with increasing admission glucose. This observation held true for patients with and without diabetes. CONCLUSIONS In this cohort of IV-tPA–treated stroke patients, admission hyperglycemia was independently associated with increased risk of death, SICH, and poor functional status at 90 days. Treatment trials continue to be urgently needed to determine whether this is a modifiable risk factor for poor outcome.

Prevalence and Predictors of Paroxysmal Atrial Fibrillation on Holter Monitor in Patients With Stroke or Transient Ischemic Attack

Background and Purpose— Our aims were to quantify the yield of Holter monitor for detection of paroxysmal atrial fibrillation (PAF) in patients with stroke and TIA, and to determine potential predictors of PAF to allow more focused testing. Methods— We reviewed records of 1128 consecutive patients attending a university stroke clinic from September 2005 to September 2006 and identified 426 patients with definite TIA or stroke. We abstracted clinical, cardiac imaging, and neuroimaging data. Logistic regression analysis was performed to determine independent predictors of PAF on Holter monitor. Results— Overall, 413 of 426 patients (65±15 years; male, 49.8%) with a definite TIA (53%) or stroke (47%) underwent Holter monitoring for a mean of 22.6 hours. PAF occurred in 39 patients (9.2%) all older than age 55 years. PAF lasting >30 seconds was evident in 11 patients (2.5%). The other 28 patients had PAF <30 seconds (6.5%). In multivariate analyses, number of acute (odds ratio [OR], 1.7 for each 1 lesion increase; 95% confidence interval [CI], 1.2–2.6; P=0.0047) and chronic (OR, 1.6 for each 1 lesion increase; 95% CI, 1.2–2.3; P=0.0001) infarcts on brain CT, number of chronic infarcts on MRI (OR, 3.0 for each 1 lesion increase; 95% CI, 1.7–5.1; P<0.0001), and any acute cortical infarct on imaging (OR, 5.8; 95% CI, 1.9–17.8; P=0.0023) were associated with PAF. Conclusions— PAF is present in 9.2% of patients with definite stroke or TIA. Age older than 55 years and presence of acute or chronic brain infarcts on neuroimaging are strongly associated with PAF.

Postthrombolysis Blood Pressure Elevation Is Associated With Hemorrhagic Transformation

Background and Purpose— Reliable predictors of hemorrhagic transformation (HT) after stroke thrombolysis have not been identified. We analyzed hemorrhage in a randomized trial of tissue plasminogen activator (t-PA) vs placebo in ischemic stroke patients. We hypothesized that acute diffusion-weighted imaging (DWI) lesion volumes would be larger and blood pressures would be higher in patients with HT. Methods— HT was assessed 2 to 5 days after treatment in 97 patients. Hemorrhage was assessed by using susceptibility-weighted imaging sequences and was classified as petechial hemorrhagic infarction (HI) or parenchymal hematoma (PH). Results— PH was more frequent in t-PA– (11/49) than in placebo- (4/48) treated patients (P=0.049). Patients with PH had larger DWI lesion volumes (63.1±56.1 mL) than did those without HT (27.6±39.0 mL, P=0.033). There were no differences in baseline systolic blood pressure (SBP) between patients with and without hemorrhage. Weighted average SBP 24 hours after treatment was higher in patients with PH (159.4±18.8 mL, P<0.011) relative to those without HT (143.1±20.0 mL). Multinomial logistic regression indicated that PH was predicted by DWI lesion volume (odds ratio=1.16 per 10 mL; 95% CI, 1.03 to 1.30), atrial fibrillation (odds ratio=9.33; 95% CI, 2.30 to 37.94), and 24-hour weighted average SBP (odds ratio=1.59 per 10 mm Hg; 95% CI, 1.14 to 2.23). Conclusions— Pretreatment DWI lesion volume and postthrombolysis BP are both predictive of HT. Consideration should be given to excluding patients with very large baseline DWI volumes from t-PA therapy and to more stringent BP control after stroke thrombolysis.

Short-Term Risk for Stroke Is Doubled in Persons With Newly Treated Type 2 Diabetes Compared With Persons Without Diabetes A Population-Based Cohort Study

Background and Purpose— Cardiovascular risk factors are suboptimally treated in diabetes, possibly because of the impression that there is a long delay between diagnosis and the development of macrovascular complications such as stroke. We determined the incidence of stroke in people newly treated for type 2 diabetes. Methods— We conducted an inception cohort study with the use of linked administrative databases from Saskatchewan Health. Subjects entered the type 2 diabetes cohort on receipt of their first prescription for an oral antidiabetic drug. We defined incident stroke as any hospital admission with International Classification of Diseases, Ninth Revision, codes 430 to 438 inclusive. Age-standardized incidence rates were compared between the diabetes cohort and the general population. Results— There were 12 272 subjects in the diabetes cohort, the mean±SD age was 64±13.6 years, and 55% were male. During a mean 5-year follow-up, 9.1% of the diabetes cohort had a stroke. The age-standardized incidence rate for stroke was 642 per 100 000 person-years in subjects with diabetes, compared with 313 per 100 000 person-years in the general population (rate ratio=2.1, 95% CI=1.8 to 2.3). The relative short-term risk for stroke in the diabetes cohort compared with the general population ranged from 1.8 (95%=CI 1.6 to 1.9) in persons >75 years to 5.6 (95% CI=2.5 to 9.3) in the 30- to 44-year category. Conclusions— The risk of stroke is high within 5 years of treatment for type 2 diabetes and more than double the rate for the general population. This further supports the need for aggressive early cardiovascular risk factor management in type 2 diabetes.

Socioeconomic Status, Hospital Volume, and Stroke Fatality in Canada

Background and Purpose— Low socioeconomic status is associated with stroke fatality; however, the mechanism behind this association is uncertain. We sought to determine whether residence in a low-income neighborhood was associated with admission to low-volume facilities and whether this contributed to differences in fatality after stroke. Methods— All hospitalizations for ischemic stroke from April 2003 to March 2004 were identified from a national administrative database containing patient-level sociodemographic, diagnostic, procedural, and administrative information. Patients were assigned to income quintiles based on the median income of their primary neighborhood of residence and then categorized as low income (quintiles 1 and 2) or high income (quintiles 3 through 5). Hospitals were categorized as low or high volume on the basis of their annual number of stroke admissions. Multivariable analyses were performed to compare stroke fatality at 7 days and at discharge in patients in low- and high-income groups seen at low- and high-volume facilities. Results— Overall, 25 228 patients with ischemic stroke were included in the analysis. Those from high-income areas were more likely to be admitted to high-volume hospitals. Fatality at 7 days was 8.4%, 8.2%, 7.7%, 7.1, and 6.6% (&khgr;2=0.002) for income quintiles 1 (lowest) to 5 (highest), respectively. Low-income patients admitted to low-volume hospitals had the highest risk-adjusted stroke fatality. Conclusions— Patients from low-income areas presenting with acute stroke are more likely to be seen in low-volume facilities. This subgroup of patients had a higher risk-adjusted fatality than those from high-income areas seen at high-volume facilities. Understanding the pathways through which socioeconomic status affects health care may lead to strategies for quality improvement.

Acute Perfusion and Diffusion Abnormalities Predict Early New MRI Lesions 1 Week After Minor Stroke and Transient Ischemic Attack

Background and Purpose— Transient ischemic attack and minor stroke are associated with high ischemic recurrence in the first week. We prospectively studied the correlation between baseline diffusion/perfusion deficits and development of new ischemic lesions. Methods— Patients with transient ischemic attack and those with minor stroke (n=50) underwent MRI at admission. Acute perfusion-weighted imaging deficit (Tmax+2-second delay) and diffusion-weighted imaging (DWI) lesion volumes were measured planimetrically. Follow-up scans were examined for new DWI/fluid-attenuated inversion recovery lesions at Days 7 and 30. Results— Twenty-eight patients (56%) had acute DWI lesions. New DWI lesions developed in 9 of 50 patients (18%) at 1 week and 11 of 50 (cumulative 22%) at 4 weeks. Patients with new infarcts were more likely to have baseline DWI lesions (&khgr;2=8.264, P=0.003). Baseline DWI lesion volume was significantly larger in those who developed new lesions at Day 7 (median, 13.2 mL; interquartile range, 12 versus median 0.1 mL; interquartile range, 2 mL; P<0.001) and Day 30 (11.1 mL; interquartile range, 13 mL versus 0.1 mL; interquartile range, 13 mL; P<0.001). Thirty-eight patients had baseline perfusion-weighted imaging. Patients with recurrent lesions were more likely to have baseline perfusion deficits (&khgr;2=19.5, P<0.0001). All new lesions developed within the baseline hypoperfused regions. Baseline DWI lesion volume predicted new lesion development at day 7 (OR, 1.17 per mL; CI, 1.05 to 1.30; P=0.005) and Day 30 (OR, 1.39 per mL; CI, 1.03 to 1.26; P=0.009) by regression analysis. Conclusions— Early recurrence of stroke is much more likely in patients with larger baseline DWI and perfusion-weighted imaging lesions. MRI lesion “recurrence” appears to be related to completion of the natural history of the original cerebrovascular syndrome rather than de novo events in most patients.

Oxfordshire Community Stroke Project Classification Poorly Differentiates Small Cortical and Subcortical Infarcts

Background and Purpose— The Oxfordshire Community Stroke Project (OCSP) is a common clinical stroke classification tool. We evaluated the accuracy of OCSP classification with a prospective magnetic resonance imaging (MRI) study. Methods— Stroke/transient ischemic attack patients presenting within 48 hours of onset were included in the study (n=130). Following computed tomography scan, OCSP classification, total anterior circulation infarcts (TACI), partial anterior circulation infarcts (PACI), lacunar circulation infarcts (LACI), and posterior circulation infarcts (POCI) were performed by 3 independent examiners. All patients underwent diffusion-weighted MRI with planimetric volume measurement and classification into OCSP categories, organized by lesion location. Results— Patients were clinically classified as TACI (12 patients), PACI (62 patients), LACI (38 patients), and POCI (18 patients). In 101 patients with diffusion-weighted MRI lesions, correct classification rates were: TACI (83.3%), PACI (83%), LACI (39%), and POCI (86%). OCSP had the following sensitivity (SE), specificity (SP), and positive predictive value (PPV): TACI (SE, 100%; SP, 98%; PPV, 83%), PACI (SE, 73%; SP, 78%; PPV, 83%), LACI (SE, 47%; SP, 83%; PPV, 39%), and POCI (SE, 92%; SP, 98%; PPV, 86%). Sixty-one percent of patients in the LACI group had radiographic appearances consistent with PACI, and 15% of those classified as PACI had lacunar infarcts. No differences in stroke severity existed between patients classified correctly (median National Institutes of Health Stroke Scale [NIHSS]=4; interquartile range [IQR]=7) or incorrectly (median NIHSS=3; IQR=3). Patients classified correctly had larger infarct volume (median=6.75 mL; IQR=33.2) than did those who were incorrectly classified (1.86 mL; IQR=5; P=0.008). Conclusions— OCSP classification does not permit accurate discrimination between lacunar and small-volume cortical infarcts. Differential patterns of investigation for stroke etiology should not be based solely on clinical criteria.

Circulating endothelial progenitor cells and age-related white matter changes

Background and Purpose— The objective was to evaluate the relationship between circulating endothelial progenitor cells (EPC) and age-related white matter changes (ARWMC). Endothelial dysfunction plays a role in the development of ARWMC. EPC incorporate into sites endothelial damage and are thought to be involved in the repair of vascular risk factor induced endothelial injury. ARWMC can be evaluated using CT or MRI. Methods— In 172 individuals, circulating EPC were defined by the surface markers CD31 and von Willebrand factor. ARWMC were rated on CT scan using the ARWMC scale and divided into 3 groups based on ARWMC scale score (ARWMC score 0 [none], score 1–10 [mild-to-moderate], score >10 [severe]). Severity of ARWMC was correlated with levels of EPC and vascular risk factors. Results— On univariate analysis, EPC were found to be significantly lower in patients with severe ARWMC (P=0.01). ARWMC were also associated with hypertension (P<0.001), age (P<0.001), creatinine clearance (P=0.031), C-reactive protein (P<0.001), and use of angiotensin-converting enzyme or angiotensin receptor blocker (P=0.004). Multiple logistic regression analysis identified EPC level, age, hypertension, and hypertriglyceridemia as significant independent predictors of severe ARWMC. Conclusions— Levels of circulating EPC were significantly lower in patients with severe ARWMC. Other variables significantly associated with severe ARWMC were age, hypertension, and hypertriglyceridemia. Further study is required to delineate the pathophysiological relationship between EPC, vascular risk factors, and ARWMC.

The Intracerebral Haemorrhage Acutely Decreasing Arterial Pressure Trial: ICH ADAPT

The majority of intracerebral haemorrhage patients present with markedly elevated blood pressure immediately after symptom onset. Management of blood pressure in the first 24 h is extremely controversial and lends itself to two competing rationales. There is some evidence that early treatment may improve outcome, potentially by reducing the rate of haematoma expansion. It is also possible that this will reduce cerebral blood flow and therefore exacerbate the cerebral injury, particularly in the region surrounding the haematoma. Only a trial that includes both randomisation of patients to two different blood pressure management strategies and actual measurement of cerebral blood flow can effectively address this pressing debate. This is the only unequivocal way to demonstrate the haemodynamic effects of rapid blood pressure reduction. The Intracerebral Haemorrhage Acutely Decreasing Arterial Pressure Trial is designed to test the hypothesis that blood pressure reduction does not result in significant or harmful changes in cerebral blood flow in acute intracerebral haemorrhage. Two hours after randomisation to a systolic blood pressure target of <150 or <180 mmHg, cerebral blood flow is measured using computed tomography perfusion, which is the primary end-point of the trial. A study of this type is critical to establishing the safety of early blood pressure treatment and is necessary for planning larger efficacy trials in a rational manner. This trial is registered with clinicaltrials.gov (NCT00963976).