Stroke in young adults is more common in India and Sri Lanka and the reasons for this are not well understood. The current study was conducted to elucidate the risk factors and radiologic features in young people (age < 45 years) with ischemic stroke. Sociodemographic data, stroke risk factor information, and laboratory investigations were recorded in 41 cases with first-ever ischemic stroke. Most common risk factors for stroke in the 15- to 45-year-old age group were: hypertension, 8 (21%); family history of stroke, 7 (18%); transient ischemic attack, 6 (16%); hyperlipidemia, 3 (8.0%); and diabetes, two (5%). Age group younger than 15 years included 3 girls and one had a mass attached to the posterior mitral valve leaflet. Our observations underscore the importance of the presence of hypertension, family history of stroke, and transient ischemic attack in young adults and thus to adopt preventative strategies.
Stroke in young; Sri Lanka; family history
Sleep apnea affects over half of acute ischemic stroke patients and is associated with poor stroke outcomes. This pilot study assessed the feasibility of a randomized, sham-controlled continuous positive airway pressure trial in acute ischemic stroke patients.
Subjects identified to have sleep apnea based on an apnea-hypopnea index ≥ 5 on overnight polysomnography or portable respiratory monitoring within 7 days of stroke symptom onset were randomized to receive active or sham continuous positive airway pressure for 3 months. Objective usage was ascertained by compliance data cards. Subjects, treating physicians, and outcome assessors were masked to intervention allocation.
Among 87 consented subjects, 74 were able to complete sleep apnea screening, 54 (73%) of whom had sleep apnea; 32 agreed to randomization. Of the 15 who commenced active titration, 11 (73%) took the device home, and 8 (53%) completed the 3 month follow-up. Of the 17 subjects who commenced sham titration, 11 (65%) took the sham device home and completed the 3 month follow-up. The median cumulative usage hours over the 90 days were similar in the active group (53 hours (IQR: 22, 173)) and the sham group (74 hours (17, 94)) and blinding to condition was successfully maintained.
This first-ever, randomized, sham-controlled trial of continuous positive airway pressure in patients with recent stroke and sleep apnea showed that sham treatment can be an effective placebo.
An evidenced based approach to detecting and treating dysphagia needs to be informed by costs and risks associated with pneumonia. In this study the cost of pneumonia during hospitalization after stroke and the effect of pneumonia on mortality were estimated. The effect of pneumonia on mortality and cost for different levels of risk were also analyzed.
The data come from the 2005 and 2006 Nationwide Inpatient Sample. Regression models, including the propensity for pneumonia, were used to estimate the in hospital mortality associated pneumonia, and the marginal cost of pneumonia on the hospitalization. A stratified analysis based on quintile of propensity for pneumonia was also undertaken.
There were 183, 976 hospitalizations for stroke in the sample. The adjusted relative risk of death associated with pneumonia was 2.0 (95% CI 1.9–2.1). The average marginal cost of pneumonia on the hospitalization was $27,633 (95% CI $27,078–$27,988). The quintile of hospitalizations with the highest propensity for pneumonia had the highest average marginal cost associated with pneumonia and the lowest adjusted relative risk of death. There was an inverse relationship between adjusted relative risk of death and propensity for pneumonia.
Pneumonia after stroke is associated with higher mortality and hospitalization costs. Patients with the lowest risk for pneumonia have the highest risk for death associated with pneumonia. Screening is important at all levels of risk.
Patients with recent transient ischemic attack or stroke caused by 70–99% stenosis of a major intracranial artery are at high risk of recurrent stroke on usual medical management, suggesting the need for alternative therapies for this disease.
The Stenting and Aggressive Medical Management for Preventing Recurrent stroke in Intracranial Stenosis trial is an ongoing, randomized, multicenter, two-arm trial that will determine whether intracranial angioplasty and stenting adds benefit to aggressive medical management alone for preventing the primary endpoint (any stroke or death within 30 days after enrollment or after any revascularization procedure of the qualifying lesion during follow-up, or stroke in the territory of the symptomatic intracranial artery beyond 30 days) during a mean follow-up of 2 years in patients with recent TIA or stroke caused by 70–99% stenosis of a major intracranial artery. Aggressive medical management in both arms consists of aspirin 325 mg per day, clopidogrel 75mg per day for 90 days after enrollment, intensive risk factor management primarily targeting systolic blood pressure < 140 mm Hg (< 130 mm Hg in diabetics) and low density cholesterol < 70 mg / dl, and a lifetsyle modification program. The sample size required todetect a 35% reduction in the rate of the primary endpoint from angioplasty and stenting based on the log-rank test with an alpha of 0.05, 80% power, and adjusting for a 2% loss to follow-up and 5% crossover from the medical to the stenting arm is 382 patients per group.
This is the first randomized trial to compare intracranial angioplasty and stenting with medical therapy and to incorporate intensive management of multiple risk factors and a lifestyle modification program in the study design. Hopefully, the results of the trial will lead to more effective therapy for this high-risk disease.
Our goal was to develop decision guides to predict the presence of a high risk source of embolus and to predict a change in management following transesophageal echocardiography (TEE) in subjects who present with a first cerebral ischemic event. We conducted a retrospective review of subjects ≥18 years who underwent TEE after a first ischemic event and were admitted to our stroke service from 2004-2007 (n=287). A high risk source of embolus and a change in clinical management (including medication changes or subsequent testing) were analyzed as separate endpoints using multivariate techniques and receiver-operator characteristic curves. 14.3% of subjects had a high risk source while an additional 61.3% had a potential (or low risk) source of embolus. Increasing age and no history of diabetes mellitus were independently associated with a high risk source of embolus. TEE would be recommended for non-diabetic individuals who are ≥66 years (sensitivity: 68%, specificity: 76%). The area under the curve (AUC) for detecting a high risk source was 0.773. TEE results changed medications or clinical management in 30.3% of patients. Current smokers were less likely to undergo a change in management. The AUC was uninformative (0.56) for predicting changes in management. Subjects presenting with a first ischemic event who are ≥66 years may benefit from TEE. While changes in management occurred in at least 30% of our cohort, no factors could be identified that predicted a change in management better than chance alone.
Transesophageal echocardiography; cardioembolic sources; patient care management
The workup of patients with suspected subarachnoid haemorrhage (SAH) presenting late is complicated by loss of diagnostic sensitivity of CT brain imaging and cerebrospinal fluid (CSF) bilirubin levels.
A prospective, longitudinal study on CSF ferritin levels in SAH.
Serial CSF samples from 14 aneurysmal SAH cases requiring extraventricular drainage (EVD) were collected. The control group consisted of 44 patients presenting with headaches suspicious of SAH. In 9 cases a traumatic spinal tap occurred. CSF ferritin levels were significantly higher following SAH compared to controls (p<0.0001). The upper reference range of CSF ferritin is 12 ng/mL and there was no significant difference between a traumatic (mean 9.0 ng/mL) or normal spinal tap (3.9 ng/mL, p=0.59). CSF ferritin levels increased following the SAH from an average of 65 ng/mL (day 1) to 1750 ng/mL (day 11, p<0.01). Both the Fisher and Columbia CT score significantly correlated with CSF ferritin levels.
CSF ferritin levels increase after a SAH and may potentially provide additional diagnostic information in patients with suspected SAH who present late to clinic.
ferritin; bilirubin; biomarker; subarachnoid haemorrhage; cerebrospinal fluid
Patients with minor ischemic stroke (MIS) are frequently excluded from thrombolytic therapy. Denial of therapy to these patients, however, remains controversial. We compared outcomes in patients with MIS who received IV t-PA with those untreated.
We selected adult patients with stroke onset within 3 hours from a prospectively collected stroke registry. MIS was defined as an admission National Institutes of Health Stroke Scale (NIHSS) score ≤5. The primary outcome was a 90 day mRS of 0–1. Secondary outcomes were Barthel index (BI) ≥95 at 90 days, symptomatic intracranial hemorrhage (sICH) and death. Multivariable logistic regression was performed to determine the association between outcomes, adjusting for age, history of diabetes and admission NIHSS. Reasons for t-PA exclusion were obtained.
We identified 133 patients with MIS; 59 patients received IV t-PA. Admission NIHSS was higher in the t-PA treated group (mean±SD); 3.4±1.4; 1.9±1.3; p< 0.0001. Other baseline characteristics were not significantly different between groups. At 90 days, 57.6% in the t-PA and 68.9% in the untreated group had a mRS of 0–1 (OR 0.93, 95% CI: 0.39–2.2, p=0.87). BI of 95–100 was achieved in 75% of patients in the IV t-PA group vs. 78.9% in the untreated group; (OR 1.18, 95% CI: 0.43–3.23, p=0.74).There were 3 deaths (5.1%) in the IV t-PA group vs. 3 (4.1%) in the controls.
In our sample, patients with MIS treated with IV t-PA have similar outcomes as patients not receiving thrombolysis. A randomized trial or larger observational study is needed confirm or reject these findings.
Recruitment challenges are common in acute stroke clinical trials. In a population-based study, we determined eligibility and actual enrollment for a successful, phase II acute stroke clinical trial. We hypothesized that missed opportunities for enrollment of eligible patients occurred frequently, despite the success of the trial.
In 2005, acute ischemic stroke (AIS) cases in our region were identified at all 17 local hospitals as part of an epidemiologic study. The Combined Approach to Lysis Utilizing Eptifibatide and rt-PA (CLEAR) trial assessed the safety of this combination in AIS patients within 3 hours of symptom onset. In 2005, we determined the proportion of AIS patients who were eligible for CLEAR and the proportion that were actually enrolled.
At 8 participating hospitals, 33 (2.8%) of 1175 AIS patients were eligible for CLEAR. Of 33 eligible patients, 18 (54.5%) were approached for enrollment, 4 (12.1%) refused, 1 (3.0%) was not consentable, and 13 (39.4%) were enrolled. Of the 15 not approached for enrollment in the trial, 10 were evaluated by the stroke team; 7 received rt-PA. Enrollment was not associated with night or weekend presentation.
Although the CLEAR trial was successful in meeting its delineated recruitment goals, our findings suggest enrollment could have been more efficient. Three out of 4 patients approached for enrollment participated in the trial. Eligible patients who were not approached and those treated with rt-PA but not enrolled represent targets for improving enrollment rates.
clinical trials; emergency medicine; acute stroke; thrombolysis
Stroke patients often display deficits in language function such as correctly naming objects. Our aim was to evaluate the reliability and the patterns of post-stroke language recovery using a picture identification task during fMRI at 4T.
Material and Methods
4 healthy and 4 left MCA stroke subjects with chronic (>1 year) aphasia. Ten fMRI scans were performed for each subject over a 10-week period using a picture identification task. Active condition involved presenting subjects with a panel of 4 figures (e.g., drawings of 4 animals) every 6 seconds; subjects indicated which figure matched the written name in the center. Control condition was same/different judgment task of pairs of geometric figures (squares, octagons or combination) presented every 6 seconds. Thirty-second active/control blocks were repeated 5 times each; responses were recorded.
Patients and controls exhibited similar demographic characteristics: age (46 vs. 53 years), personal handedness (EHI; 89 vs. 95), familial handedness (93 vs. 95) or years of education (14.3 vs. 14.8). For the active condition, controls performed better than patients (97.7% vs. 89.1%, p<0.001); performance was similar for the control condition (99.5% vs. 98.8%, p=0.23). During fMRI, controls exhibited bilateral, L>R positive blood oxygenation-level dependent (BOLD) activations in frontal and temporal language areas and symmetric retro-splenial and posterior cingulate areas and symmetric negative BOLD activations in bilateral fronto-temporal language networks. However, the patient group showed positive BOLD activations predominantly in peri-stroke areas and negative BOLD activations in the unaffected (right) hemisphere. Both the control and patient groups displayed high activation reliability (as measured by the ICC) in left frontal and temporal language areas, although the ICC in frontal regions of the patients was spread over a much larger peri-stroke area.
This study documents the utility of the picture identification task for post-stroke language recovery evaluation. Study data suggest that adult stroke patients utilize functional peri-stroke areas to perform language functions.
stroke; aphasia; aphasia recovery; language; functional MRI
The goal most often stated by persons with stroke is improved walking function. The purpose of this study was to determine the effects of isokinetic strength training on walking performance, muscle strength, and health-related quality of life in survivors of chronic stroke.
Twenty participants (age, 61.2 ± 8.4 years) with chronic stroke were randomized into 2 groups. The experimental group undertook maximal concentric isokinetic strength training, whereas the control group received passive range of motion of the paretic lower extremity 3 times a week for 6 weeks. The Kin-Com Isokinetic Dynamometer (Chattanooga Group Inc., TN) was used for both the strengthening and passive range of motion exercises. The Mann-Whitney U test was used to compare the changes in scores (postintervention minus baseline) between the control and experimental groups for a composite lower extremity strength score, walking speed (level-walking and stair-walking) and health-related quality of life measure (36-Item Short Form Health Survey [SF-36]).
Both the experimental and control groups increased their strength and walking speed postintervention; however, there were no differences in the changes in walking speed between the groups. There was a trend (P = .06) toward greater strength improvement in the experimental group compared with the control group. No changes in SF-36 scores were found in either group.
Intervention aimed at increasing strength did not result in improvements in walking. The results of this study stress the importance of controlled clinical trials in determining the effect of specific treatment approaches. Strength training in conjunction with other task-related training may be indicated.
PMID: 17903837 CAMSID: cams2187
Gait; strength; stroke management
Higher plasma total homocysteine (tHcy) is an established risk factor for cardiovascular disease. The relation between tHcy and carotid artery intima-media thickness (IMT) at the internal carotid artery (ICA)/bulb-IMT and common carotid artery (CCA)-IMT has not been systematically examined. Since the ICA/bulb segment is more prone to plaque formation than the CCA segment, differential associations with tHcy at these sites might suggest mechanisms of tHcy action.
We examined the cross-sectional segment-specific relations of tHcy to ICA/bulb-IMT and CCA-IMT in 2,499 participants from the Framingham Offspring Study, free of cardiovascular disease.
In multivariable linear regression analysis, ICA/bulb-IMT was significantly higher in the fourth tHcy quartile category compared to the other quartile categories, in both the age- and sex-adjusted and in the multivariable-adjusted model (P for trend <0.0001 and <0.01, respectively). We observed a significant age by tHcy interaction for ICA/bulb-IMT (P=0.03) and therefore stratified the analyses by median age (58 years). There was a significant positive trend between tHcy and ICA/bulb-IMT in individuals 58 years of age or older (P-trend <0.01), but not in the younger individuals (P-trend=0.24). For CCA-IMT, no significant trends were observed in any of the analyses.
The segment-specific association between elevated tHcy levels and ICA/bulb-IMT suggests an association between tHcy and plaque formation.
carotid artery; intima-media thickness; homocysteine; atherosclerosis; Framingham Offspring Study
Background and Purpose
Stroke of the right MCA is common. Such strokes often have consequences for emotional experience, but these can be subtle. In such cases diagnosis is difficult because emotional awareness (limiting reporting of emotional changes) may be affected. The present study sought to clarify the mechanisms of altered emotion experience after right MCA stroke. It was predicted that after right MCA stroke the anterior cingulate cortex (ACC), a brain region concerned with emotional awareness, would show reduced neural activity.
Brain activity during presentation of emotional stimuli was measured in six patients with stable stroke, and in 12 age and gender matched non-lesion comparisons using positron emission tomography and the [15O]H2O autoradiographic method.
MCA stroke was associated with weaker pleasant experience and decreased activity ipsilaterally in the ACC. Other regions involved in emotional processing including thalamus, dorsal and medial prefrontal cortex showed reduced activity ipsilaterally. Dorsal and medial prefrontal cortex, association visual cortex and cerebellum showed reduced activity contralaterally. Experience from unpleasant stimuli was unaltered and was associated with decreased activity only in the left midbrain.
Right MCA stroke may reduce experience of pleasant emotions by altering brain activity in limbic and paralimbic regions distant from the area of direct damage, in addition to changes due to direct tissue damage to insula and basal ganglia. The knowledge acquired in this study begins to explain the mechanisms underlying emotional changes following right MCA stroke. Recognizing these changes may improve diagnoses, management and rehabilitation of right MCA stroke victims.
Stroke; neuroimaging; alexithymia; depression; nondysphoric depression; positron emission tomography; middle cerebral artery
This study investigated the influence of age, National Institutes of Health Stroke Scale (NIHSS) score, time from stroke onset, infarct location and volume in predicting placement of a percutaneous endoscopic gastrostomy (PEG) tube in patients with severe dysphagia from an acute-subacute hemispheric infarction. We performed a retrospective analysis of a hospital-based patient cohort to analyze the effect of the aforementioned variables on the decision of whether or not to place a PEG tube. Consecutive patients were identified using International Classification of Diseases, Ninth Revision (ICD-9) codes for acute ischemic stroke, Current Procedural Terminology (CPT)-4 codes for a formal swallowing evaluation by a speech pathologist, and procedure codes for PEG placement over a 5-year period from existing medical records at our institution. Only patients with severe dysphagia were enrolled. A total of 77 patients met inclusion criteria; 20 of them underwent PEG placement. The relationship between age (dichotomized; < and ≥75 years), time from stroke onset (days), NIHSS score, acute infarct lesion volume (dichotomized; < and ≥100 cc), and infarct location (ie, insula, anterior insula, periventricular white matter, inferior frontal gyrus, motor cortex, or bilateral hemispheres) with PEG tube placement were analyzed using logistic regression analysis. In univariate analysis, NIHSS score (P =.005), lesion volume (P =.022), and presence of bihemispheric infarction (P =.005) were found to be the main predictors of interest. After multivariate adjustment, only NIHSS score (odds ratio [OR], 1.15; 90% confidence interval [CI], 1.02–1.29; P = .04) and presence of bihemispheric infarcts (OR, 4.67; 90% CI, 1.58–13.75; P =.018) remained significant. Our data indicates that baseline NIHSS score and the presence of bihemispheric infarcts predict PEG placement during hospitalization from an acute-subacute hemispheric infarction in patients with severe dysphagia. These results require further validation in future studies.
Stroke; swallowing recovery; NIHSS score
Our objective was to outline the relationship between age and length of stay (LOS), hospital costs and discharge disposition following carotid endarterectomy (CEA).
Materials and Methods
We identified discharge records from the 2006 Nationwide Inpatient Sample (NIS). The primary outcome was LOS from the surgical procedure to discharge. We examined LOS from procedure to discharge because the time from procedure to discharge may better reflect hospital stay due to the procedure itself for subjects with symptomatic carotid artery disease rather than including days hospitalized for stroke recovery. Secondary endpoints included total LOS, discharge disposition and hospital costs.
There were 118,218 discharge records for CEA and >90% were for asymptomatic carotid disease. The LOS from procedure to discharge and total LOS increased per decade starting with the age range of 70–79 years. Age per decade increased the likelihood of requiring a LOS from procedure to discharge of >1 day. The same trend was seen for requiring a >2 day post-operative stay. Those age ≥80 years required longer post-operative LOS compared to younger ages (OR=1.45 for >1 day and OR=1.45 for >2 days, both p<0.001). Total hospital costs averaged $10,965 for all discharges. For age dichotomized at 80 years, the average cost increased by $845. Also, age ≥80 years was independently associated with discharge to a skilled nursing facility (OR=2.4, 95% CI=2.09–2.76).
Increased hospital LOS and costs were required following CEA as age increased. Morbidity following CEA should be discussed with subjects considering revascularization for asymptomatic disease.
Endarterectomy and angioplasty with stenting have emerged as two alternative treatments for carotid artery stenosis. This study’s objective is to determine cost-effectiveness of carotid artery stenting compared to carotid endarterectomy in symptomatic subjects who are suitable for either intervention.
A Markov analysis of these two revascularization procedures was conducted using direct Medicare costs (2007$ USD) and characteristics of a symptomatic 70-year-old cohort over a lifetime.
In the base case analysis, carotid stenting produced 8.97 quality adjusted life years compared to 9.64 quality adjusted life years for carotid endarterectomy. The incremental cost of stenting was $17,700 and thus, stenting was dominated by endarterectomy. Sensitivity analyses show that the long-term probabilities of major stroke or mortality influenced the results.
In the base case analysis, carotid endarterectomy for patients with symptomatic stenosis has a greater benefit than angioplasty with stenting with lower direct costs. With a 59% probability, CEA will be the optimal intervention when all of the model assumptions are varied simultaneously.
carotid arteries; stenosis; cost-benefit analysis; stroke
Sex-related disparities in stroke have been previously reported. However, the influence of sex on the outcome of recurrent stroke in blacks is less clear. Our objective is to investigate the effect of sex on the outcome of recurrent non-fatal stroke in the African American Antiplatelet Stroke Prevention Study (AAASPS)
The AAASPS is a double-blind, randomized, controlled trial of recurrent stroke. Participants -967 black women and 842 black men- with non-cardioembolic ischemic stroke were assigned to receive ticlopidine or aspirin and followed for up to two years. The NIH Stroke Scale (NIHSS), modified Barthel score (mBS), and the Glasgow Outcome Scale (GOS) were determined at enrollment, at pre-specified times thereafter and at the time of recurrent stroke. Survival analysis was used to test for a significant difference in the time to recurrent stroke between women and men.
Of the total 1,809 subjects enrolled in AAASPS, 186 subjects (89 women and 97 men) suffered recurrent non-fatal stroke. At enrollment, the NIHSS (2.87 for women and 3.00 for men; p=0.73), the mBS (18.26 for women and 18.52 for men; p=0.47) and the GOS (1.49 for women and 1.51 for men; p=0.86) were not significantly different. In follow-up and at the time of stroke recurrence, the NIHSS, mBS, and GOS were similar for both groups, except for the mBS at the 6-month visit, which was lower in women (18.49) than in men (19.37) (p=0.02). In the survival analysis, no significant difference in the time to recurrent stroke was found between women and men (p=0.69).
Although sex-related stroke disparities have been reported, in the AAASPS cohort outcomes for recurrent non-fatal non-cardioembolic ischemic stroke for women were not significantly different than for men. Differences in study populations and methodologies may explain discrepancies in results from the various studies.
African Americans; Ischemic stroke; Advances in Stroke; Database; Gender; Sex
To determine if the presence of the apoE4 allele, a known risk factor for Alzheimer’s disease, interacts with cerebrovascular risk factors to produce a disproportionate impairment in neuropsychological performance and alterations in structural morphometry as measured by magnetic resonance imaging.
1,995 participants from the community based Framingham Offspring Cohort participants (mean age 61; 1,063 women) underwent neuropsychological testing and structural magnetic resonance imaging in 1999-2002.
Multivariate linear regression was used to estimate the relationships between Framingham Stroke Risk Profile scores, neuropsychological variables and magnetic resonance imaging measures; interaction terms were included to examine modification of these relationships by the presence of the apoE4 allele. All analyses were cross sectional.
We found significant interactions between the presence of the apoE4 allele and the top sex-specific quartile of the Stroke Risk Profile and their effects on verbal memory (p=<0.001), verbal organization (p=<0.001), non-verbal memory (p=0.015), as well as set shifting and complex attention (p=0.005). Systolic blood pressure was the only individual risk factor significantly linked to these cognitive measures. With the exception of lateral ventricular volume, there were no significant interactions between presence of apoE4, the top sex-specific quartile of the Stroke Risk Profile and any of the magnetic resonance imaging variables.
The apoE4 allele exacerbates the effects of cerebrovascular risk factors on neuropsychological function. This relationship appears to be driven by systolic blood pressure, suggesting that treatment of high systolic blood pressure could potentially reduce risk of cognitive impairment among those already at increased risk for Alzheimer’s disease.
In 1995 two studies by the NINDS showed that intravenous t-PA was superior to placebo in stroke patients when given less than 3 hours from stroke onset. The recently published ECASS III study introduced new patient selection criteria and treatment between 3 and 4.5 hours. Using these criteria, t-PA was shown effective at the later time window. Both analyses used the 3 month mRS as main primary outcome. We sought to study the effect of applying the ECASS III selection criteria to the original NINDS cohort.
We analyzed the subgroup of patients from NINDS sample who matched the ECASSS III study criteria and examined 3-month outcomes adjusted and unadjusted for confounding factors.
The NINDS t-PA study included 624 patients. Two hundred in the t-PA treated and 199 in the placebo group were selected after applying ECASS III criteria. Of these selected patients, 52% in the t-PA group versus 31% had an mRS of 0 or 1 at 3 months (p<0.001). The unadjusted OR for t-PA treatment versus placebo on day 90 mRS 0–1 versus 2–6 was 2.45 (95% CI: 1.63–3.69) When adjusted for baseline NIHSS, smoking status, time to treatment and history of hypertension the OR was 2.14 (95% CI: 1.34–3.41) (p<0.001).
Using the ECASS III patient selection in patient treated in less than 3 hours, 52% of t-PA treated patient had a favorable outcome at 3 months.
Inflammatory and hemostasis-related biomarkers may identify women at risk of stroke.
Hormones and Biomarkers Predicting Stroke is a study of ischemic stroke among postmenopausal women participating in the Women’s Health Initiative Observational Study (n = 972 case-control pairs). A Biomarker Risk Score was derived from levels of seven inflammatory and hemostasis-related biomarkers that appeared individually to predict risk of ischemic stroke: C-reactive protein, interleukin-6, tissue plasminogen activator, D-dimer, white blood cell count, neopterin, and homocysteine. The c index was used to evaluate discrimination.
Of all the individual biomarkers examined, C-reactive protein emerged as the only independent single predictor of ischemic stroke (adjusted odds ratio comparing Q4 versus Q1 = 1.64, 95% confidence interval: 1.15–2.32, p = 0.01) after adjustment for other biomarkers and standard stroke risk factors. The Biomarker Risk Score identified a gradient of increasing stroke risk with a greater number of elevated inflammatory/hemostasis biomarkers, and improved the c index significantly compared with standard stroke risk factors (p = 0.02). Among the subset of individuals who met current criteria for “high risk” levels of C-reactive protein (> 3.0 mg/L), the Biomarker Risk Score defined an approximately two-fold gradient of risk. We found no evidence for a relationship between stroke and levels of E-selectin, fibrinogen, tumor necrosis factor-alpha, vascular cell adhesion molecule-1, prothrombin fragment 1+2, Factor VIIC, or plasminogen activator inhibitor-1 antigen (p >0.15).
The findings support the further exploration of multiple-biomarker panels to develop approaches for stratifying an individual’s risk of stroke.
stroke; epidemiology; women
Carotid intima-media thickness (IMT) is a sub-clinical marker of atherosclerosis and a strong predictor of stroke. Pericardial fat (PF), the fat depot around the heart, has been associated with several atherosclerosis risk factors. We sought to examine the association between carotid IMT and PF, and to examine whether such an association is independent from common atherosclerosis risk factors including measures of overall adiposity.
Unadjusted and multivariable adjusted linear regression analysis was used to examine associations between common (CCA-IMT) and internal (ICA-IMT) carotid IMT with PF in a random sample of 996 participants from the Multi-Ethnic Study of Atherosclerosis (MESA) who underwent carotid ultrasound and chest CT at baseline examination.
A significant positive correlation was observed between PF and CCA-IMT (r =0.27, P<0.0001) and ICA-IMT (r =0.17, P<0.0001). In an unadjusted sex-specific linear regression analysis, there was a significant association between PF (1-SD difference) and CCA-IMT (mm) in both women (β coefficient (95% CI): 0.06 (0.04, 0.08), P<0.0001) and men (0.03 (0.01, 0.05), P<0.0002), an association that persisted after further adjusting for age and ethnicity (0.02 (+0.00, 0.04), P=0.0120 for women, and 0.02 (+0.00, 0.03), P=0.0208 for men). However, after additional adjustment for atherosclerosis risk factors and either BMI or waist circumference, these relations were no longer significant in either sex. In similar analyses, PF was significantly associated with ICA-IMT in both men (0.11 (0.06, 0.15), P<0.0001) and women (0.08 (0.02, 0.13), P=041). These relations were no longer significant in women in multivariable adjusted models, but persisted in men in all models except after adjusting for age, ethnicity and waist circumference.
In the general population PF is associated with carotid IMT, an association that possibly not independent from markers of overall adiposity or common atherosclerosis risk factors.
One quarter of ischemic strokes occur during sleep and they are excluded from thrombolytic therapy due to an unknown time of stroke onset. It has been suggested that early ischemic changes in CT are similar between acute stroke patients and patients who recently awoke with stroke. We compared head CT scans using the Alberta Stroke Program Early CT Score (ASPECTS) in patients who were likely to suffer their stroke during sleep (AWOKE) to a control group of patients with stroke of known onset time.
Patients were recruited from a prospectively collected acute stroke database. The “AWOKE” group was defined as all ischemic stroke patients who were “last seen normal” more than 4 hours ago, arrived between 4AM and 10AM and had a head CT within 15 hours from last seen normal. The control group was randomly selected using patients who had a head CT within 4 hours from stroke onset. The ASPECTS evaluations were performed blinded to patient group and time of onset. In 15 AWOKE and 46 control patients a mRS at 90 days after stroke was available.
Twenty-eight AWOKE and 68 control patients had suitable imaging for the ASPECTS. Baseline demographics and risk factors were similar in both groups. The dichotomized ASPECTS analysis (≤7 versus 8–10) showed no significant differences between groups. In the AWOKE group 89.3% had an ASPECTS of 8–10, while for controls 95.6% scored 8–10 (p= 0.353). There was a trend toward better 90 day mRS (0–1) in the AWOKE group (73%) versus control (45%) p=0.079.
Initial ASPECTS were similar between patients with wake-up strokes and those with documented onset within 4 hours of symptoms.
To evaluate whether comprehensive post-discharge care management for stroke survivors is superior to organized acute stroke unit care with enhanced discharge planning in improving a profile of health and well-being.
This was a randomized trial of a comprehensive post-discharge care management intervention for ischemic stroke patients with NIH Stroke Scale scores ≥1 discharged from an acute stroke unit. An Advanced Practice Nurse (APN) performed an in-home assessment for the intervention group from which an Interdisciplinary Team developed patient-specific care plans. The APN worked with the primary care physician (PCP) and patient to implement the plan over the next 6 months.
Main outcome measures
The intervention and usual care groups were compared using a global and closed hypothesis testing strategy. Outcomes fell into 5 domains: 1) Neuromotor Function, 2) Institution Time or Death, 3) Quality of Life, 4) Management of Risk, and 5) Stroke Knowledge and Lifestyle.
Treatment effect was near zero standard deviations for all but the stroke knowledge and lifestyle domain which showed a significant effect of the intervention (p=0.0003).
Post discharge care management was not more effective than organized stroke unit care with enhanced discharge planning in most domains in this population. The intervention did, however, fill a post-discharge knowledge gap.
Background and purpose
Data on the association between alcohol consumption and ischemic stroke have been inconsistent. It is not known whether allele E4 of the apolipoprotein E (apoE) gene modifies the alcohol-stroke association. We sought to examine whether E4 allele of the apoE gene influences the association between alcohol consumption and ischemic stroke or high-density lipoprotein (HDL) cholesterol.
Cohort of 7,676 person-observations of the Framingham Heart Study. Incident stroke was ascertained by standardized methods. We used Cox proportional hazard model to estimate hazard ratios of ischemic stroke.
The average age at baseline was 63 years and 55% of the participants were women. During a mean follow up of 7.4 years, 222 new cases of ischemic stroke occurred (56 embolic and 166 atherothrombotic events). Comparing current drinkers with nondrinkers, multivariable adjusted hazard ratio (95% CI) for ischemic stroke were 0.50 (0.24–1.07) in the absence of E4 allele and 0.70 (0.24–2.05) in the presence of E4 allele (p for interaction 0.64) for subjects aged <65 years. Similarly, we did not observe a statistically significant interaction between E4 allele and alcohol consumption on the risk of stroke among people 65 years and older (p for interaction 0.17). Alcohol consumption was positively associated with HDL cholesterol independent of E4 allele and age.
Our data do not provide evidence for an interaction between E4 allele and alcohol consumption on the risk of ischemic stroke in this population. Furthermore, ApoE polymorphism did no influence the alcohol-HDL relation.
Alcohol drinking; ischemic stroke; apolipoprotein E gene; lipids