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1.  [No title available] 
PMCID: PMC3609905  PMID: 23265781
2.  [No title available] 
PMCID: PMC3946730  PMID: 24119626
3.  [No title available] 
PMCID: PMC3946748  PMID: 24119622
4.  The Effect of Season and Temperature Variation on Hospital Admissions for Incident Stroke Events in Maputo, Mozambique 
Identifying locale-specific patterns regarding the variation in stroke incidence throughout the year and with atmospheric temperature may be useful to the organization of stroke care, especially in low-resource settings.
We aimed to describe the variation in the incidence of stroke hospitalizations across seasons and with short-term temperature variation, in Maputo, Mozambique.
Between August 1, 2005, and July 31, 2006, we identified 651 stroke events in Maputo dwellers, according to the World Health Organization's STEPwise approach. The day of symptom onset was defined as the index date. We computed crude and adjusted (humidity, precipitation and temperature) incidence rate ratios (IRRs) and 95% confidence intervals (CIs) with Poisson regression.
Stroke incidence did not vary significantly with season (dry versus wet: crude IRR 5 .98, 95% CI: .84-1.15), atmospheric temperature at the index date, or average atmospheric temperature in the preceding 2 weeks. The incidence rates of stroke were approximately 30% higher when in the previous 10 days there was a decline in the minimum temperature greater than or equal to 3°C between any 2 consecutive days (variation in minimum temperature −5.1 to −3.0 versus −2.3 to −.4, adjusted IRR = 1.31, 95% CI: 1.09-1.57). No significant associations were observed according to the variation in maximum temperatures.
Sudden declines in the minimum temperatures were associated with a higher incidence of stroke hospitalizations in Maputo. This provides important information for prediction of periods of higher hospital affluence because of stroke and to understand the mechanisms underlying the triggering of a stroke event.
PMCID: PMC4167826  PMID: 23523200
Stroke; Mozambique; temperature; seasons
5.  Clinical Use of CT Perfusion For Diagnosis and Prediction of Lesion Growth in Acute Ischemic Stroke 
Background and Purpose
CT perfusion (CTP) mapping in research centers correlates well with diffusion weighted imaging (DWI) lesions and may accurately differentiate the infarct core from ischemic penumbra. The value of CTP in real-world clinical practice has not been fully established. We investigated the yield of CTP– derived cerebral blood volume (CBV) and mean transient time (MTT) for the detection of cerebral ischemia and ischemic penumbra in a sample of acute ischemic stroke (AIS) patients.
We studied 165 patients with initial clinical symptoms suggestive of AIS. All patients had an initial non-contrast head CT, CT Perfusion (CTP), CT angiogram (CTA) and follow up brain MRI. The obtained perfusion images were used for image processing. CBV, MTT and DWI lesion volumes were visually estimated and manually traced. Statistical analysis was done using R-2.14.and SAS 9.1.
All normal DWI sequences had normal CBV and MTT studies (N=89). Seventy-three patients had acute DWI lesions. CBV was abnormal in 23.3% and MTT was abnormal in 42.5% of these patients. There was a high specificity (91.8%)but poor sensitivity (40.0%) for MTT maps predicting positive DWI. Spearman correlation was significant between MTT and DWI lesions (ρ=0.66, p>0.0001) only for abnormal MTT and DWI lesions>0cc. CBV lesions did not correlate with final DWI.
In real-world use, acute imaging with CTP did not predict stroke or DWI lesions with sufficient accuracy. Our findings argue against the use of CTP for screening AIS patients until real-world implementations match the accuracy reported from specialized research centers.
PMCID: PMC3608754  PMID: 23253533
Acute ischemic stroke; neuroimaging; Diffusion-Weighted Imaging; stroke diagnosis; ischemic penumbra; perfusion imaging; stroke outcomes
6.  Acute Kidney Injury is Associated with Increased Hospital Mortality after Stroke 
Acute kidney injury (AKI) is common and associates with poor clinical outcomes. Information about the incidence of AKI and effect on stroke outcomes is limited.
Data were analyzed from a registry of subjects with ischemic stroke and intracerebral hemorrhage (ICH) hospitalized at a single academic medical center. Admission creatinine was considered to be the baseline. AKI was defined as a creatinine increase of 0.3 mg/dL or a percentage increase of at least 50% from baseline, occurring during hospitalization. Multivariate logistic regression models were created for both stroke types, with hospital mortality as the outcome. Covariates included gender, race, age, admission creatinine, admission NIH Stroke Scale score, performance of contrast-enhanced CT scan of the head and neck, and medical co-morbidities.
There were 528 cases of ischemic stroke with 70 deaths (13%), and 829 cases of ICH with 268 deaths (32%). The mean age was 64 years, with 56% men and 71% whites. AKI complicated 14% of ischemic stroke and 21% of ICH hospitalizations. In multivariate analysis stratified by stroke type, AKI was associated with increased hospital mortality from ischemic stroke (odds ratio (OR) 3.08, 95% confidence interval (CI) [1.49–6.35]) but not ICH (OR 0.82, 95% CI [0.50–1.35]), except for those surviving at least two days (OR 2.11, 95% CI [1.18–3.77]).
AKI occurs frequently after stroke and is associated with increased hospital mortality. Further studies are needed to establish if the association is causal and if measures to prevent AKI would result in decreased mortality.
PMCID: PMC3507321  PMID: 22818389
7.  Acute decrease in serum magnesium level after ischemic stroke may not predict decrease in neurologic function 
Higher serum levels of magnesium (Mg(2+)) may contribute to improved outcome following ischemic stroke, and this may be related to vessel recanalization. Patients with low or normal serum magnesium levels during the acute phase of ischemic stroke may be more susceptible to neurologic deterioration and worse outcomes.
All patients who presented to our center within 48hrs of acute ischemic stroke (07/2008-12/2010) were retrospectively identified. Patient demographics, laboratory values, and multiple outcome measures, including neurologic deterioration (ND), were compared across admission serum Mg(2+) groups as well as change in Mg(2+) from baseline to 24hr groups.
Three hundred thirteen patients met inclusion criteria (mean age 64.8 years, 42.2% female, 64.0% black). Mg(2+) groups at baseline were not predictive of poor functional outcome, death or discharge disposition. Patients whose serum Mg(2+) decreased during the first 24hrs of admission were also not at greater odds of ND or poor outcome measures compared to patients with unchanging or increasing Mg(2+) levels.
Our results suggest that patients who have low Mg(2+) at baseline or a reduction in Mg(2+) 24hrs after admission are not at a higher risk of experiencing ND or poor short-term outcome. Ongoing prospective interventional trials will determine if hyperacute aggressive magnesium replacement affords neuroprotection in stroke.
PMCID: PMC3818504  PMID: 23830960
stroke; ischemia; magnesium; neurologic deterioration; neuroprotection
8.  APOE genotype modifies the relationship between midlife vascular risk factors and later cognitive decline 
Vascular risk factors have been associated with cognitive decline, however, it remains unclear whether apolipoprotein E (APOE) genotype modifies this relationship. We aimed to further elucidate these relationships and extend previous findings by examining data from a more comprehensive cognitive assessment than used in prior studies. 1,436 participants from the prospective Framingham Offspring Cohort Study underwent health examination from 1991-1995, followed by a baseline neuropsychological assessment (1999-2003) and a repeat neuropsychological assessment approximately eight years later (2004-2009). Multivariate linear regression analyses were performed to examine the relationship between midlife vascular risk factors, presence of the APOE ε4 allele, and cognitive change. APOE genotype significantly modified the associations between both midlife hypertension and cardiovascular disease and decline in language abilities as well as midlife diabetes and decline in verbal memory, attention, and visuospatial abilities. Associations between increased midlife vascular risk burden and greater cognitive decline were observed among APOE ε4 carriers but not non-carriers. The present findings revealed a subgroup at increased risk for cognitive decline (APOE ε4 carriers with midlife exposure to vascular risk factors) and suggest that treatment of vascular risk factors during midlife may reduce the risk of cognitive impairment later in life, particularly among APOE ε4 carriers.
PMCID: PMC3849195  PMID: 23601373
Apolipoprotein E; Cognition; Vascular Risk; Aging; Diabetes; Hypertension; Cardiovascular Disease
9.  Glycosylated Hemoglobin for Diagnosis of Prediabetes in Acute Ischemic Stroke Patients 
Prediabetes (PD) is an independent risk factor for stroke. The American Diabetes Association (ADA) has recently published new guidelines recommending glycosylated hemoglobin A1c (HbA1c) as a marker to diagnose diabetes and PD. Diagnosis of diabetes Mellitus (DM) is often made at the time of hospitalization for stroke. Less is known about identifying PD in acute ischemic stroke (AIS) patients. We aim to investigate the frequency of new-onset PD in the hospitalized AIS patients using the new ADA guidelines.
We retrospectively studied 362 AIS patients from our local database. Stroke risk factors, type of stroke, and white matter hyperintensities (WMHs) were all collected. Based on the 2010 ADA guidelines, patients were classified as prediabetics, with HbA1c levels of 5.7%–6.4%; diabetics, with HbA1c levels more than 6.5%; and normoglycemic, HbA1c levels less than 5.7%. We used SAS 9.3 for analysis.
On admission, 279 (78%) AIS patients had HbA1c values collected. Stratifying by HbA1c, 113 (31%) AIS patients were given the diagnosis of DM and 109 (30%) were given the diagnosis of PD. From the 166 patients with no DM history, 53% had PD and 15% had DM. Patients with DM and PD were more likely to have hypertension (P <.001) and hyperlipidemia (P =.05). The likelihood of new-onset PD increased with age (P <.01). No differences were found by the type of stroke or WMH.
Diabetes and PD are highly prevalent in the hospitalized ischemic stroke (IS) patients. Our results suggest a need for routine HbA1c testing in all patients with IS. Further larger studies need to confirm these findings.
PMCID: PMC3849229  PMID: 23871698
Acute ischemic stroke; diabetes; prediabetes; hospitalization
10.  Residential Proximity to High Traffic Roadways and Post-Stroke Mortality 
Living in areas with higher levels of ambient air pollution has been associated with a higher incidence of ischemic stroke and all-cause mortality, but less is known about the relationship between traffic related pollution and long term survival following stroke.
We identified consecutive patients admitted to Beth Israel Deaconess Medical Center with ischemic stroke between 1999 and 2008 and determined distance to the nearest roadway with an average daily traffic count >10,000 vehicles/day. Categories of residential proximity were defined as ≤100 meters (m), 100 to 200, 200 to ≤400 or > 400m from a busy roadway. We identified deaths through June 2012 using the Social Security Death Index and used Cox proportional hazards models adjusted for medical history, and socioeconomic factors to calculate hazard ratios for the association between residential proximity to a high traffic roadway and all-cause mortality.
Among 1683 stroke patients with complete data, there were 950 deaths [median follow-up = 4.6 years]. We observed higher post-stroke mortality among people living closer to high traffic roadways. Patients living ≤100m from high traffic roadways had a 20% (95% CI: 1%, 43%) higher rate of post-stroke mortality than patients living >400m away (p-trend=0.02).
In this study, living close to a high traffic roadway was associated with an elevated mortality rate. This relationship remained statistically significant after adjustment for individual and neighborhood- level factors, providing evidence that traffic-related pollution is associated with a higher mortality rate among stroke survivors.
PMCID: PMC4066388  PMID: 23721619
11.  Predictors of acute stroke mimics in 8,187 patients referred to a stroke service 
Some patients seen by a stroke team do not have cerebrovascular disease but a condition that mimics stroke. The purpose of this study was to determine the rate and predictors of stroke mimics in a large sample.
This is an analysis of data from consecutive patients seen by the NIH Stroke Program over 10 years. Data were collected prospectively as a quality improvement initiative. Patients with a cerebrovascular event or a stroke mimic were compared with the Student t or Pearson’s chi-square test as appropriate and logistic regression was done to identify independent predictors.
The analysis included 8,187 patients: 30% had a stroke mimic. Patients with a stroke mimic were younger and the proportion of patients with a stroke mimic was higher among women, patients without any risk factors, those seen as a code stroke or who arrived to the emergency department via personal vehicle, and those who had the onset of symptoms while inpatients. The proportion of patients with a stroke mimic was marginally higher among African Americans than Caucasians. Factors associated with the greatest odds of having a stroke mimic in the logistic regression were lack of a history of hypertension atrial fibrillation, or hyperlipidemia.
A third of the patients seen by a stroke team over 10 years had a stroke mimic. Factors associated with a stroke mimic may be ascertained by an emergency physician before calling the stroke team.
PMCID: PMC3812364  PMID: 23680681
Acute stroke; emergency medicine; stroke mimics
12.  Validation of the 12-Item Stroke-Specific Quality of Life Scale in a Bi-ethnic Stroke Population 
The 12-item Stroke-Specific Quality of Life Scale (SSQOL), a shortened version of the original SSQOL, was developed to be an efficient and valid outcome in stroke research. We aimed to assess the validity of this scale in a bi-ethnic ischemic stroke population.
From a population-based study, the Brain Attack Surveillance in Corpus Christi Project, validated ischemic stroke patients who completed the 49-item SSQOL at 90 days post-stroke were identified. Cronbach’s alpha was used to assess internal consistency of the scales. Intraclass correlation coefficient (ICC) and linear regression were used to assess agreement between the two scales.
Of the 45 ischemic stroke patients, mean age was 66.0 years (SD, 11.3). Fifty-six percent were female and 51% were Mexican American. The mean score of the 49-item scale was 3.33 (SD, 0.84) compared with 3.31 (SD, 0.95) from the 12-item scale. Internal consistency was 0.96 for the 49-item scale and 0.88 for the 12-item scale. The two scales were highly correlated (ICC= 0.98, R2 =0.97).
This study in ischemic stroke patients from diverse race-ethnic backgrounds found that the more efficient 12-item SSQOL is a valid alternative to the full scale for the assessment of health-related quality of life.
PMCID: PMC3552000  PMID: 22995379
Stroke; Quality of Life; Clinical Outcomes; Ischemia
13.  Interobserver Reproducibility of Signal Intensity Ratio on Magnetic Resonance Angiography for Hemodynamic Impact of Intracranial Atherosclerosis 
Changes of signal intensities (SIs) across intracranial atherosclerosis (ICAS) on magnetic resonance angiography (MRA) may reflect hemodynamic impact of the lesion. We evaluated the interobserver reproducibility of an index termed signal intensity ratio (SIR), developed in a previous study to represent the changes of SIs across ICAS on MRA.
Symptomatic ICAS on MRA were retrospectively recruited. Two observers respectively evaluated the images and calculated the SIR as follows, blinded to each other’s readings: SIR = (mean poststenotic SI − mean background SI)/(mean prestenotic SI − mean background SI). Statistical analyses were performed to evaluate the interobserver reproducibility of this index.
A total of 102 symptomatic ICASs were enrolled, with 36 (35.3%) lesions of 50%–69% MRA stenoses and others being 70%–99% stenoses or flow void on MRA. Overall, mean SIRs were not significantly different between the 2 observers (.92 ± .17 versus .93 ± .17; mean difference −.006 ±.09; P =.496 for paired t test). Pearson correlation coefficients were >.80 for all analyses, indicating strong linear correlations between SIRs by the 2 observers. Bland–Altman analysis for SIRs of all cases showed no systematic bias between the 2 observers. For different cut-points ranging from .75 to 1.00, the kappa statistics were mostly greater than .6 and interobserver agreements were all greater than 80%, implying substantial agreement between observers.
SIR was demonstrated to be highly reproducible between observers in the present study. Future studies are warranted to further explore the role of this index in comprehensive evaluation and risk stratification of symptomatic ICAS.
PMCID: PMC3873834  PMID: 24075586
Interobserver reproducibility; intracranial atherosclerosis; magnetic resonance angiography; signal intensity; hemodynamics
While the ambulatory setting is recognized as the best arena for optimizing antihypertensive drug treatment after a stroke, little is known about recent office-based antihypertensive drug treatment patterns in the United States. We assessed national trends in antihypertensive treatment of stroke patients in office-based medical practice.
Datafrom the 2000-2009 National Ambulatory Medical Care Surveys were analyzed comprising outpatient visits to physicians in office-based practice by patientsaged ≥ 40 yearswith a diagnosis of stroke(weighted estimate = 46,317,269). The main outcome measure was visits with a prescription of antihypertensive medication(s).
The proportion of total visits that included a prescription of antihypertensive medicationwas 35.6% in 2000-2002, 29.5% in 2003-2005, and 49.3% in 2006-2009 (p=0.002);50.9% were primary care physician (PCP) visits vs.26.2% neurologist-visits (<0.0001).Age-adjusted logistic regression analyses confirmed a higher prescription rate in 2006-2009 vs. 2000-2002 (1.81, 95% CI=1.10-2.96) and PCP vs. neurologists (2.82, 95% CI=1.86-4.27). Use of two or more agent classes was 31.6% in 2000-2002, 44.2% in 2003-2005, and 56.7% in 2006-2009 (p=0.014). Age-adjusted logistic regression analyses confirmed a higher prescription rate of ≥ 2 agent classesin 2006-2009 vs. 2000-2002 (2.96, 95% CI=1.40-6.24). There were no significant differences in agent class type or number between neurologists vs. PCPs.
Over the last decade, there was a significant rise in use of antihypertensive drugs and combination of agent classes for patients aged≥ 40 years seen in an ambulatory setting with a diagnosis of stroke. PCPs were more likely than neurologists to prescribe these agents.
PMCID: PMC4084703  PMID: 23871702
Comparative Effectiveness; Outcomes; Stroke, Ischemic; Blood Pressure; Hypertension; Prognosis; Health services; Antihypertensive therapy; Target goals; Intensive; Guidelines
15.  Mechanical Thrombectomy in Acute Stroke: Utilization Variances and Impact of Procedural Volume on Inpatient Mortality 
Background and Purpose
An increasing number of endovascular mechanical thrombectomy procedures are being performed for the treatment of acute ischemic stroke. This study examines variances in the allocation of these procedures in the United States at the hospital level. We investigate operative volume across centers performing mechanical revascularization and establish that procedural volume is independently associated with inpatient mortality.
Data was collected using the Nationwide Inpatient Sample database in the U.S. for 2008. Medical centers performing mechanical thrombectomy were identified using International Classification of Disease, 9th revision codes and procedural volumes were evaluated according to hospital size, location, control/ ownership, geographical characteristics and teaching status. Inpatient mortality was compared for hospitals performing ≥ 10 mechanical thrombectomy procedures versus those performing < 10 procedures yearly. After univariate analysis identified the factors that were significantly related to mortality, multivariable logistic regression was performed to compare mortality outcome by hospital procedure volume independent of covariates.
Significant allocation differences existed for mechanical thrombectomy procedures according to hospital size (p<0.001), location (p<0.0001), control/ ownership (p<0.0001), geography (p<0.05) and teaching status (p<0.0001). Substantial procedural volume was independently associated with decreased mortality (p=0.0002, OR = 0.49) when adjusting for demographic covariates.
The number of mechanical thrombectomy procedures performed nationally remains relatively low, with a disproportionate distribution of neurointerventional centers in high volume, urban teaching hospitals. Procedural volume is associated with mortality in facilities performing mechanical thrombectomy for acute ischemic stroke patients. These results suggest a potential benefit for treatment centralization to facilities with substantial operative volume.
PMCID: PMC4085991  PMID: 23017430
Acute stroke; Neurointerventional Procedures; Mortality; Thrombectomy
16.  DWI – FLAIR Mismatch in Nocturnal Strokes Patients with Unknown Time of Onset 
More than a quarter of ischemic strokes (IS) are excluded from thrombolysis due to unknown time of symptom onset. Recent evidence suggests that a mismatch between DWI and FLAIR imaging could be used as a surrogate for the time of stroke onset. We compared used the DWI–FLAIR mismatch and the FLAIR/DWI ratio to estimate the time of onset in a group of patients with nocturnal strokes and unknown time of onset.
We used a prospectively collected acute IS patient database with MRI as the initial imaging modality. Nineteen selected nocturnal stroke patients with unknown time of onset were compared with 22 patients who had an MRI within 6 hours from stroke onset (control A) and 19 patients who had an MRI between 6 and 12 hours (control B). DWI and FLAIR signal was rated as normal or abnormal. FLAIR/DWI ratio was calculated from independent DWI and FLAIR ischemic lesion volumes using semiautomatic software.
The DWI–FLAIR mismatch was different among groups (unknown 43.7%, control A 63.6%, control B 10.5%; FFH p=0.001). There were significant differences in FLAIR/DWI ratio among the 3 groups (unknown: 0.05±0.12, control A: 0.17±0.15, control B: 0.04±0.06; KW p<0.0001). Post-hoc pair wise comparisons showed that FLAIR/DWI ratio from the unknown group was significantly different from control B (p=0.0045), but not different from control A. DWI volumes were not different among the 3 groups.
A large proportion of nocturnal IS patients with unknown time of stroke initiation have a DWI-FLAIR mismatch suggesting a recent stroke onset.
PMCID: PMC3366022  PMID: 22325574
Acute ischemic stroke; Fluid Attenuated Inversion Recovery; Diffusion-Weighted Imaging; circadian pattern; sleep
17.  Predictors of Functional Outcome Among Stroke Patients in Lima, Peru 
Due to the aging population in low- and middle-income countries, cerebrovascular disease is expected to remain a leading cause of death. Little has been published about stroke in Peru.
We conducted a retrospective cohort study of hospitalized stroke patients at a referral center hospital in Lima, Peru to explore factors associated with functional outcome among stroke patients.
We identified 579 patients hospitalized for ischemic stroke or intracerebral hemorrhage stroke at the National Institute of Neurologic Sciences in Lima, Peru in 2008 and 2009. A favorable outcome was defined as a modified Rankin score of ≤2 at discharge.
The mean age was 63.3 years; 75.6% had ischemic stroke; the average length of stay was 17.3 days. At hospital discharge, 231 (39.9%) had a favorable outcome. The overall mortality rate was 5.2%. In multivariate models, the likelihood of having a favorable outcome decreased linearly with increasing age (p=0.02) and increasing NIHSS (p=0.02). Favorable outcome was also associated with male gender (relative risk [RR]=1.2; 95% confidence interval [CI]: 1.0, 1.5) and divorced status (RR=1.3, 95% CI: 1.1, 1.7). Patients on Salud Integral de Salud (public assistance-type insurance, SIS) (RR=0.7, 95% CI: 0.5,1.0) were also less likely to have a favorable outcome.
Favorable outcome after stroke was independently associated with younger age, lower NIHSS score, male gender, being divorced, and not being on SIS insurance. These findings suggest further study of worse functional outcomes in patients with SIS insurance and confirm the importance of risk adjustment for age, stroke severity (NIHSS) and other socioeconomic factors in outcomes studies. Future studies should preferentially assess outcome at 30-days and 6-months to provide more reliable comparisons and allow additional study of Peruvian end-of-life decision-making and care.
PMCID: PMC3659203  PMID: 23352681
18.  Identification of modifiable and non-modifiable risk factors for neurological deterioration following acute ischemic stroke 
Neurological deterioration (ND) following ischemic stroke has been shown to impact short-term functional outcome and is associated with in-hospital mortality.
Patients with acute ischemic stroke who presented between 07/08–12/10 were identified and excluded for in-hospital stroke, presentation >48hrs since last seen normal, or unknown time of last seen normal. Clinical and laboratory data, National Institutes of Health Stroke Scale (NIHSS) scores, and episodes of ND (increase in NIHSS score ≥2 within a 24hr period) were investigated.
Of the 596 patients screened, 366 were included (median age 65 y, 42.1% female, 65.3% black). Of these, 35.0% experienced ND. Patients with ND were older (69 vs. 62 y, p<0.0001), had more severe strokes (median admission NIHSS 12 vs. 5, p<0.0001), carotid artery stenosis (27.0% vs. 16.8%, p=0.0275), and coronary artery disease (26.0% vs. 16.4%, p=0.0282) compared to patients without ND. Patients with ND had higher serum glucose on admission than patients without ND (125.5 vs. 114 mg/dL, p=0.0036). After adjusting for crude variables associated with ND, age >65 and baseline NIHSS>14 remained significant independent predictors of ND. In a logistic regression analysis adjusting for age and serum glucose, each 1-point increase in admission NIHSS was associated with a 7% increase in the odds of ND (OR 1.07 95%CI 1.04-1.10, p<0.0001).
Older patients and patients with more severe strokes are more likely to experience ND. Initial stroke severity was the only significant, independent, and modifiable risk factor for ND, amenable to recanalization and reperfusion.
PMCID: PMC3690312  PMID: 23246190
Acute ischemic stroke; neurological deterioration; risk factors; outcome
19.  Impact of Gender and Blood Pressure on Post-Stroke Cognitive Decline among Older Latinos 
Post-stroke cognitive decline (PSCD) is an important consequence of stroke that may be more severe in women than men. The existence of any gender differences in PSCD among Mexican Americans, and their potential mechanisms, such as blood pressure (BP), remain unknown. We assessed PSCD stratified on gender in older Mexican Americans and explored the influence of pre-stroke and post-stroke systolic BP on PSCD.
Among 1,576 non-demented, stroke-free adults 60 years or older when recruited in 1998–99 in the Sacramento Area Latino Study on Aging (SALSA) cohort, we examined pre-stroke and post-stroke longitudinal changes in Spanish English Verbal Learning test scores (WL), a verbal memory test, and errors on the Modified Mini Mental State Exam (3MSE) scores, a global cognition test, stratified by gender, adjusting for baseline and time-varying covariates with linear mixed-effects models.
We identified 151 adults (mean age, 72 ± 8 years) with incident first-ever stroke during ten years of follow-up. After adjustment for age, education and time-varying depressive symptoms, 3MSE errors increased by 22%/year (95% CI, 6.8%–36.7%) in men and 13.2%/year (95% CI, 3.5%–22.9%) in women over the post-stroke period. Post-stroke WL scores improved by 0.05 words/year (95% CI, −0.24–0.33) in men and by 0.09 words/year (95% CI, −0.16–0.34) in women. Results persisted after adjustment for time-varying systolic BP.
Among this population of older Mexican Americans, PSCD did not differ by gender. We found no evidence that systolic BP influenced PSCD in women or men.
PMCID: PMC4030756  PMID: 22748715
[MeSH] Cerebrovascular disease/stroke; Cognition; Hispanic Americans; Sex; Epidemiology
20.  Cerebral white matter hyperintensity in African Americans and European Americans with type 2 diabetes 
Prior studies involving inner city populations detected higher cerebral white matter hyperintensity (WMH) scores in African Americans (AAs), relative to European Americans (EAs). This finding may be attributable to excess cardiovascular disease (CVD) risk factors in AAs and poorer access to healthcare. Despite racial differences in CVD risk factor profiles, AAs have paradoxically lower levels of subclinical CVD. We hypothesized that AAs with diabetes and access to healthcare would have comparable or lower levels of WMH as EAs.
Racial differences in the distribution of WMH were analyzed in 46 AAs and 156 EAs with type 2 diabetes (T2D) enrolled in the Diabetes Heart Study (DHS)-MIND, and replicated in a sample of 113 AAs and 61 EAs patients who had clinically-indicated cerebral MRIs. Wilcoxon two-sample tests and linear models were used to compare the distribution of WMH in AAs and EAs and test for association between WMH and race.
The unadjusted mean WMH score in AAs from DHS-MIND was 1.9, compared to 2.3 in EAs (p=0.3244). Among those with clinically-indicated MRIs, WMH scores were 2.9 in AAs and 3.9 in EAs (p=0.0503). Adjustment for age and gender showed no statistically significant differences in WMH score between AAs and EAs.
These independent datasets reveal comparable WMH scores between AAs and EAs. This result suggests that disparities in access to healthcare and environmental exposures likely underlie the previously reported excess burden of WMH in AAs.
PMCID: PMC3465633  PMID: 22608346
African American; cognitive performance; diabetes mellitus; MRI; race; white matter hyperintensity
21.  Pre-stroke dementia is associated with poor outcomes after reperfusion therapy among elderly stroke patients 
In elderly acute stroke patients, reperfusion therapy is often withheld. We sought to determine whether pre-stroke dementia contributed to poor outcomes after reperfusion therapy in these patients.
All consecutive patients ≥ 80 years who received IV or intra-arterial reperfusion therapy (IAT) were identified in our GWTG-S database. Vascular risk factors, presence of dementia, and outcomes were abstracted from the medical record. Dementia was recorded when listed in past history or when under medical treatment. Primary outcome was in-hospital mortality. Secondary outcome was discharge destination, “favorable” (home, rehabilitation facility) versus “unfavorable” (skilled nursing facility, hospice, death). Multivariate logistic regression models were used to assess outcomes.
Of 153 patients, 72% received IV tPA, 35% IAT, and 7% both. Mean age was 85.8 ± 4.6 years; 13.6% had pre-stroke dementia. In-hospital mortality rate was 35%. The likelihood of death increased with NIHSS (OR 1.14, 95%CI 1.07–1.21), IAT (OR 3.43, 95%CI 1.70–6.92) and dementia (OR 3.61, 95%CI 1.39–9.37), and decreased with IV tPA (OR 0.34, 95%CI 0.17–0.71). Increasing NIHSS (OR 0.90, 95%CI 0.85–0.95), symptomatic intracranial hemorrhage (OR 0.08, 95%CI 0.01–0.67), IAT (OR 0.43, 95%CI 0.22–0.84), and dementia (OR 0.37, 95%CI 0.14–0.97) decreased the likelihood of favorable discharge. In multivariate analysis, only NIHSS (OR 1.13, 95%CI 1.06–1.22) and dementia (OR 5.64, 95%CI 1.88–16.89) independently predicted death and unfavorable discharge destination.
Among the elderly, pre-stroke dementia is a powerful independent predictor of in-hospital mortality after acute reperfusion therapy for stroke. Future investigations of thrombolysis outcomes in the elderly are warranted.
PMCID: PMC3310930  PMID: 22182760
acute stroke; reperfusion therapy; tPA; dementia; outcome
22.  Validating Imaging Biomarkers of Cerebral Edema in Patients with Severe Ischemic Stroke 
Background and Purpose
There is no validated neuroimaging marker for quantifying brain edema. We sought to test whether MRI-based metrics would reliably change during the early subacute period in a manner consistent with edema and whether they would correlate with relevant clinical endpoints.
Serial MRI studies from patients in the EPITHET trial with initial diffusion weighted imaging (DWI) lesion volume >82 cm3 were analyzed. Two independent readers outlined the hemisphere and lateral ventricle on the involved side and calculated respective volumes at baseline and day 3 to 5. We assessed inter-rater agreement, volume change between scans and the association of volume change with early neurological deterioration (END: NIHSS score worsening ≥4 points), 90-day modified Rankin Scale (mRS) score 0–4 and mortality.
Of 12 patients who met study criteria, average baseline and follow-up DWI lesion size was 138 cm3 and 234 cm3, respectively. Mean time to follow-up MRI was 62 hours. Concordance correlation coefficients between readers were >0.90 for both hemisphere and ventricle volume assessment. Mean percent hemisphere volume increase was 16.2±8.3% (p<.0001), and mean percent ventricle volume decrease was 45.6±16.9% (p<0.001). Percent hemisphere growth predicted END (area under the curve [AUC]=0.92, p=0.0005) and 90-day mRS 0–4 (AUC 0.80, p=0.02).
In this exploratory analysis of severe ischemic stroke patients, statistically significant changes in hemisphere and ventricular volumes within the first week are consistent with expected changes of cerebral edema. MRI-based analysis of hemisphere growth appears to be a suitable biomarker for edema formation.
PMCID: PMC3529850  PMID: 22325573
Acute Ischemic Stroke; Cerebral Edema; Malignant Stroke; MRI; Biomarker
23.  Clinical Features and Racial/Ethnic Differences among the 3020 Participants in the Secondary Prevention of Small Subcortical Strokes (SPS3) Trial 
To describe the baseline characteristics, racial/ethnic differences, and geographic differences among participants in the Secondary Prevention of Small Subcortical Strokes (SPS3) study.
The SPS3 trial enrolled patients with a symptomatic small subcortical stroke (lacunar stroke) within the prior 6 months and an eligible lesion on MRI, who were randomized, in a factorial design, to antiplatelet therapy (aspirin 325 mg daily plus clopidogrel 75 mg daily vs. aspirin 325 mg daily plus placebo) and to one of two levels of systolic blood pressure targets (“intensive” (<130 mmHg) vs. “usual” (130–149 mmHg)).
Among the 3020 participants recruited from 81 clinical sites in 8 countries, the mean age was 63 years, 63% were men, 75% had a history of hypertension, and 37% were diabetic. Fifty-one percent were White, 30% Hispanic, and 16% Black. Black participants were younger (mean age 58 years vs. 64 years, p<0.001) and more often had hypertension (95% vs. 89%, p<0.001) than White participants. Hispanic and Black participants more often had diabetes than White participants (42%, 40% vs. 32% respectively, both p<0.001). Tobacco smoking at the time of qualifying stroke was much more frequent among Spanish participants (32%) than those from North America (22%) or Latin America (8%) (p<0.001); systolic blood pressure at study entry was 5 mmHg lower among Spanish vs. North American participants (p<0.01).
The SPS3 cohort is the largest MRI-defined series of patients with S3. Among the racially/ethnically diverse SPS3 participants, there are important differences in patient features and vascular risk factors could influence prognosis for recurrent stroke and response to interventions.
Clinical Trial Registration Information
The SPS3 study is registered on (NCT00059306).
PMCID: PMC3970545  PMID: 22516427
24.  Physical Activity Correlates with Arterial Stiffness in Community-dwelling Individuals with Stroke 
Physical inactivity contributes to atherosclerotic processes, which manifest as increased arterial stiffness. Arterial stiffness is associated with myocardial demand and coronary perfusion and is a risk factor for stroke and other adverse cardiac outcomes. Poststroke mobility limitations often lead to physical inactivity and sedentary behaviors. This exploratory study aimed to identify functional correlates, reflective of daily physical activity levels, with arterial stiffness in community-dwelling individuals >1 year poststroke.
Carotid–femoral pulse wave velocity (cfPWV) was measured in 35 participants (65% men; mean ± SD age 66.9 ± 6.9 years; median time poststroke 3.7 years). Multivariable regression analyses examined the relationships between cfPWV and factors associated with daily physical activity: aerobic capacity (VO2 peak), gait speed, and balance ability (Berg Balance Scale). Age and the use of antihypertensive medications, known to be associated with pulse wave velocity, were also included in the model.
Mean cfPWV was 11.2 ± 2.4 m/s. VO2 peak and age were correlated with cfPWV (r = −0.45 [P = .006] and r = 0.46 [P = .004], respectively). In the multivariable regression analyses, age and the use of antihypertensive medication accounted for 20.4% of the variance of cfPWV, and the addition of VO2 peak explained an additional 4.5% of the variance (R2 = 0.249).
We found that arterial stiffness is elevated in community-dwelling, ambulatory individuals with stroke relative to healthy people. Multivariable regression analysis suggests that aerobic capacity (VO2 peak) may contribute to the variance of cfPWV after accounting for the effects of age and medication use. Whether intense risk modification and augmented physical activity will improve arterial stiffness in this population remains to be determined.
PMCID: PMC3828171  PMID: 23473623 CAMSID: cams3234
Arterial stiffness; physical activity; stroke
25.  Bleeding complications associated with warfarin treatment in ischemic stroke patients with atrial fibrillation: a population-based cohort study 
Bleeding events are the major obstacle to the widespread use of warfarin for secondary stroke prevention. Previous studies have not examined the use of risk stratification scores to estimate lifetime bleeding risk associated with warfarin treatment in a population-based setting. The purpose of this study is to determine the lifetime risk of bleeding events in ischemic stroke patients with atrial fibrillation (AF) undergoing warfarin treatment in a population-based cohort and to evaluate the use of bleeding risk scores to identify patients at high-risk for lifetime bleeding events.
The resources of the Rochester Epidemiology Project Medical Linkage System were used to identify acute ischemic stroke patients with atrial fibrillation undergoing warfarin treatment for secondary stroke prevention from 1980 to 1994. Medical information for patients seen at Mayo Clinic and at Olmsted Medical Center were used to retrospectively risk-stratify stroke patients according to bleeding risk scores (including the HAS-BLED and HEMORR2HAGES scores) prior to warfarin initiation. These scores were reassessed one and five years later, and compared with lifetime bleeding events.
One hundred patients (mean age, 79.3 years; 68% women) were studied. Ninety-nine patients were followed to death. Major bleeding events occurred in 41 patients at a median of 19 months following warfarin initiation. Patients with a history of hemorrhage before warfarin treatment were more likely to develop major hemorrhage (15% vs 3%, p=0.04). Patients with baseline HAS-BLED scores ≥2 had a higher lifetime risk of major bleeding events compared with those with scores ≤1 (53% vs 7%, p<0.01), while those with HEMORR2HAGES score ≥2 had a higher life-time risk of major bleeding events compared with those with scores ≤1 (52% vs 16%, p=0.03). Patients with an increase in the HAS-BLED and HEMORR2HAGES scores during follow-up had a higher remaining lifetime risk of major bleeding events compared to those with no change.
Our findings indicate high lifetime bleeding risk associated with warfarin treatment for patients with ischemic stroke. Risk stratification scores are useful to identify patients at high-risk of developing bleeding complications and should be recalculated at regular intervals to evaluate the bleeding risk in anticoagulated patients with ischemic stroke.
PMCID: PMC4080718  PMID: 23499334
stroke; atrial fibrillation; warfarin; bleeding complications

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