Traditional Stroke Risk Factors Research Articles

Is adiponectin a risk factor for transient ischaemic attacks?

Adiponectin is an adipocytokine, and it plays a role in atherosclerosis. The role of adiponectin in the development of ischaemic stroke is controversial. Up to now, adiponectin was not evaluated in transient ischaemic stroke. In this study, we investigated the relationship between adiponectin and transient ischaemic attack. Forty patients with transient ischaemic attack were included into the study. In all patients, traditional risk factors of ischaemic stroke and intima-media thickness of carotid arteries were determined. Also, the relationship between these parameters and adiponectin levels were examined. No difference was found in terms of adiponectin levels between patients and healthy subjects. In addition, there was no association between adiponectin levels and traditional risk factors. Our results suggest that adiponectin may not be a predictive risk factor of transient ischaemic attack.

Abstract T P392: Optimal Combination Secondary Prevention Drug Treatment and Stroke Outcomes

Background: Over the last decade there has been a documented decline in the stroke incidence and mortality in several developed nations around the world, which is thought to be due mainly to better treatment of traditional risk factors for stroke. It has been suggested that optimal combination(s) of individually proven secondary prevention drug classes, could reduce recurrent vascular events. However, the effect of combining antihypertensive agents (AH), lipid modifiers (LM), and antithrombotic agents (AT) on outcomes after stroke has not previously been studied. Methods: We analyzed the database of a multicenter trial involving 3680 recent ischemic stroke patients aged ≥35 years and followed for 2 years. Patients were categorized by appropriateness level 0 to III depending on the number of the drugs prescribed divided by the number of the drugs potentially indicated for each patient (0=none of the indicated medications prescribed and III=all indicated medications prescribed). Independent associations of medication appropriateness level with recurrent stroke (primary outcome), stroke/coronary heart disease (CHD)/vascular death (secondary outcome), and all-cause death (tertiary outcome) were assessed. Results: The unadjusted rate of stroke declined with increasing medication appropriateness level (15.9% for level 0; 10.3% for level I; 8.6% for level II; and 7.3% for level III). Compared to level 0: the adjusted hazard ratio (AHR) of stroke for level I was (0.51, 95% CI, 0.21–1.25), level II 0.50 (0.23–1.09), and level III 0.39 (0.18–0.84); of stroke/CHD/vascular death for level I 0.60 (0.32-1.14), level II 0.45 (0.25–0.80), and level III 0.39 (0.22–0.69); of all-cause death for level I 0.89 (0.30-2.64), level II 0.71 (0.26-1.93), and level III 0.35 (0.13–0.96). Interpretation: Optimal combination prescription of secondary prevention medication was associated with an independent lower risk of stroke, stroke/CHD/vascular death, and all-cause death in recent stroke patients over a 2 year follow-up period. While future studies are certainly warranted to confirm/disconfirm our findings, clinicians may want to ensure that for eligible recent stroke patients, all appropriate secondary prevention drug classes are prescribed and maintained.

Abstract T MP43: Patient Characteristics and Outcomes in Pregnancy-Related Ischemic Stroke

Background: Ischemic Stroke (IS) is a rare but serious event during pregnancy or the postpartum period. We compared the characteristics and outcomes of pregnant vs. non-pregnant women diagnosed with IS in the Get With The Guidelines Stroke Registry. Methods: We identified 24641 female patients aged 18-44 with IS, based on medical history or ICD-9 codes, from 2008-2013. Patient and hospital categorical variables were compared by Chi-square and continuous variables by Wilcoxon Rank-Sum. Stratified logistic regression assessed the effect of pregnancy on outcomes conditional on age and adjusted for patient and hospital characteristics. Results: There were 338 (1.4%) pregnant IS patients. Compared to non-pregnant patients, pregnant patients had fewer traditional stroke risk factors, were less often black, and were more likely to be insured by Medicaid, in a healthcare setting at stroke onset, and admitted to a stroke center. Both groups had similar initial mild stroke severity and exam findings most notable for weakness (Table). Discharge outcomes of in-hospital death (aOR 0.70, 95% CI 0.33-1.50), discharge to home (aOR 1.04, 95% CI 0.81-1.34), independent ambulation (aOR 1.03, 95% CI 0.79-1.34) or length of stay >4 days (aOR 1.27, 95% CI 0.96-1.68) did not differ between groups. Of the 145 cases where pregnancy stage was coded, 76 (52.4%) occurred postpartum and 65 (44.8%) antepartum, with no difference in discharge outcomes. Women with postpartum compared with antepartum IS were more likely to have hypertension, use antihypertensives pre-stroke, and have higher median initial post-stroke blood pressure. Conclusions: Pregnancy-related IS is uncommon and occurs in women with few traditional stroke risk factors, often within 6 weeks postpartum. Despite these differences, short term outcomes after stroke are similar to non-pregnant women. Further research is needed to determine if pregnancy, itself, independently contributes to stroke risk.

Hypertensive disorders and pregnancy-related stroke: frequency, trends, risk factors, and outcomes.

To evaluate trends and associations of hypertensive disorders of pregnancy with stroke risk and test the hypothesis that hypertensive disorders of pregnancy-associated stroke results in higher rates of stroke-related complications than pregnancy-associated stroke without hypertensive disorders. A cross-sectional study was performed using 81,983,216 pregnancy hospitalizations from the 1994-2011 Nationwide Inpatient Sample. Rates of stroke hospitalizations with and without these hypertensive disorders were reported per 10,000 pregnancy hospitalizations. Using logistic regression, adjusted odds ratios (OR) with 95% confidence intervals were obtained. Between 1994-1995 and 2010-2011, the nationwide rate of stroke with hypertensive disorders of pregnancy increased from 0.8 to 1.6 per 10,000 pregnancy hospitalizations (103%), whereas the rate without these disorders increased from 2.2 to 3.2 per 10,000 pregnancy hospitalizations (47%). Women with hypertensive disorders of pregnancy were 5.2 times more likely to have a stroke than those without. Having traditional stroke risk factors (eg, congenital heart disease, atrial fibrillation, sickle cell anemia, congenital coagulation defects) substantially increased the stroke risk among hypertensive disorders of pregnancy hospitalizations: from adjusted OR 2.68 for congenital coagulation defects to adjusted OR 13.1 for congenital heart disease. Stroke-related complications were increased in stroke with hypertensive disorders of pregnancy compared with without (from adjusted OR 1.23 for nonroutine discharge to adjusted OR 1.93 for mechanical ventilation). Having traditional stroke risk factors substantially increased the stroke risk among hypertensive disorders of pregnancy hospitalizations. Stroke with hypertensive disorders in pregnancy had two distinctive characteristics: a greater increase in frequency since the mid-1990s and significantly higher stroke-related complication rates. III.

Protein kinase Cη polymorphism and the susceptibility to ischemic stroke in the Taiwan population.

Prior studies suggested that protein kinase Cη (PRKCH) 1425G/A polymorphism was associated with lacunar infarction. This study examined whether the association was independent of traditional risk factors in each of the stroke subtypes. This study included 206 ischemic stroke patients and 337 controls. Multivariable logistic regression was used for analyses. Co-variables of age, sex, hypertension, diabetes mellitus (DM), and smoking were included to delineate independency of associations. PRKCH 1425G/A was associated with ischemic stroke [odds ratio (OR) =1.5, 95% confidence interval (CI): 1.1-2.2, p = 0.024] when adjusted for age and sex. However, the significance of association became borderline when adjusted for co-variables (OR = 1.5, 95% CI: 1.004-2.3, p = 0.048). Of the infarction subtypes, PRKCH 1425G/A was associated with lacunar infarction (OR = 1.8, 95% CI: 1.1-2.9, p = 0.025), which remained significant when adjusted for co-variables (OR = 2.0, 95% CI: 1.1-3.5, p = 0.015). No association was found between the polymorphism and the other infarction subtypes. When stratified by age group, the magnitude of significance became stronger in patients >65 years old. Specifically, PRKCH 1425G/A was significantly associated with ischemic stroke in patients older than 65 years, when adjusted for all co-variables (OR = 2.0, 95% CI: 1.05-3.8, p = 0.036). Still, in patients older than 65 years, the association was only observed in lacunar infarction when adjusted for all co-variables (OR = 4.2, 95% CI: 1.7-10, p = 0.001). No association of PRKCH 1425G/A with stroke and any of the subtypes was identified in patients >65 years old. The association between PRKCH 1425G/A and lacunar infarction was independent of traditional stroke risk factors. PRKCH 1425G/A in stroke susceptibility differed between infarction subtypes and age groups.

Evidence for the prevention and treatment of stroke in dialysis patients.

The risks of both ischemic and hemorrhagic stroke are particularly high in dialysis patients of any age and outcomes are poor. It is therefore important to identify strategies that safely minimize stroke risk in this population. Observational studies have been unable to clarify the relative importance of traditional stroke risk factors such as blood pressure and cholesterol in those on dialysis, and are affected by biases that usually make them an inappropriate source of data on which to base therapeutic decisions. Well-conducted randomized trials are not susceptible to such biases and can reliably investigate the causal nature of the association between a potential risk factor and the outcome of interest. However, dialysis patients have been under-represented in the cardiovascular trials which have proven net benefit of commonly used preventative treatments (e.g., antihypertensive treatments, low-dose aspirin, carotid revascularization, and thromboprophylaxis for atrial fibrillation), and there remains uncertainty about safety and efficacy of many of these treatments in this high-risk population. Moreover, the efficacy of renal-specific therapies that might reduce cardiovascular risk, such as modulators of mineral and bone disorder, online hemodiafiltration, and daily (nocturnal) hemodialysis, have not been tested in adequately powered trials. Recent trials have also demonstrated how widespread current practices could be causing stroke. Therefore, it is important that reliable information on the prevention and treatment of stroke (and other cardiovascular disease) in dialysis patients is generated by performing large-scale randomized trials of many current and future treatments.

Abstract P220: Exposure to Secondhand Smoke and the Risk of Stroke

Background: Stroke is a leading cause of death worldwide, and is a major public health concern in terms of morbidity, mortality, economic costs, and loss of productivity. While exposure to secondhand smoke (SHS) is a risk factor for cardiovascular disease, associations of SHS with risk of stroke have been inconsistent. Hypothesis: We investigated the hypotheses that SHS exposure is associated with increased incidence of stroke and stroke subtypes (ischemic stroke and hemorrhagic stroke) among non-smokers, including never and former smokers. Methods: The Reasons for Geographic and Racial Differences in Stroke (REGARDS) study enrolled a U.S. population sample of 30,239 Caucasian and African-American men and women aged >=45 years in 2003-7 and is following them for stroke outcomes. We calculated the hazard ratio (HR) of stroke among non-smokers with SHS exposure using Cox proportional hazard models. Results: The cohort, without prevalent smoking, stroke and TIA (n=21,743), included 62% Caucasians and 38% African-Americans, with 55% females. Twenty-three percent reported SHS exposure the year prior to enrollment, and these individuals were more likely to be younger, African-American, male (all p<0.001), and have higher C-reactive protein (CRP) and white blood count (WBC) (p<0.05) compared to those not exposed. SHS exposure was associated with a 31% increased risk of any stroke event after adjustment for demographic, socioeconomic, and behavioral factors (Table 1). The association was seen only in ischemic, but not hemorrhagic stroke. Associations were slightly diminished after adjusting for traditional stroke risk factors, and markedly attenuated to the null after further addition of inflammation markers. Conclusions: SHS exposure was not related to stroke after accounting for inflammation markers. Further research is needed to confirm these findings.

Abstract P222: Serum fibroblast growth factor-23 and risk of incident stroke: The Atherosclerosis Risk in Communities Study (ARIC)

Background: Fibroblast growth factor-23 (FGF23), a hormone involved in phosphorous regulation and vitamin D metabolism, has been associated with risk of coronary heart disease and heart failure and is a potential target for intervention. FGF23 may influence stroke risk through several pathways: suboptimal vitamin D levels, impaired kidney function, endothelial dysfunction, and/or inflammation. We tested whether elevated FGF23 is associated with increased risk of incident stroke, independent of traditional stroke risk factors and kidney function. Methods: Biologically active intact FGF23 was measured in stored samples collected at baseline, in 1990-1992, from 12,432 stroke-free ARIC participants. Participants were followed through 2010. Incident stroke events (both ischemic and hemorrhagic) were identified during follow-up and adjudicated using medical chart review. Multivariable Cox proportional hazards regression models were used to evaluate the independent association of baseline serum FGF23 with risk of incident stroke. Results: Over a median follow-up of 19 years, 766 participants (median age 56, 24% black) developed incident stroke. A significant association of baseline FGF23 with incident stroke was only observed in the highest quintile of serum FGF23. Compared to those in the lowest quintile of FGF23, those in the highest quintile were at 37% greater risk of incident stroke (Table), after adjustment for demographics, behaviors, and body mass index. Additional adjustment for cardiovascular risk factors and eGFR categories completely attenuated the association. There was no evidence of interaction by age, sex, race, or eGFR category. Conclusions: Elevated levels of serum FGF23 were associated with modestly increased risk of incident stroke in this large, biracial, community-based cohort in minimally-adjusted models, however this association was not independent of cardiovascular risk factors and kidney function.

Transient Global Amnesia and the Risk of Ischemic Stroke

Whether transient global amnesia (TGA) represents an arterial insult that heralds ischemic stroke remains unclear. Therefore, we examined stroke risk after TGA in a population-based cohort. After performing chart review at our institution to validate the International Classification of Diseases, 9th Edition, Clinical Modification diagnosis code for TGA, we used administrative claims data to identify all patients discharged from nonfederal California emergency departments or acute care hospitals between 2005 and 2010 with a primary discharge diagnosis of TGA. Patients with a primary discharge diagnosis of migraine, seizure, or transient ischemic attack were included as controls. Kaplan-Meier statistics were used to calculate rates of ischemic stroke, and Cox proportional hazards analyses were used to compare stroke risk among the 4 exposure groups while controlling for traditional stroke risk factors. International Classification of Diseases, 9th Edition, Clinical Modification code 437.7 had a sensitivity of 86% and a specificity of 95% for TGA. The cumulative 1-year rate of stroke was 0.54% (95% confidence interval [CI], 0.36-0.81) after TGA, 0.22% (95% CI, 0.20-0.25) after migraine, 0.90% (95% CI, 0.83-0.97) after seizure, and 4.72% (95% CI, 4.60-4.85) after transient ischemic attack. After adjustment for demographic characteristics and stroke risk factors, TGA was not associated with stroke risk when compared with migraine (hazard ratio, 0.82; 95% CI, 0.61-1.10). The likelihood of stroke after TGA was lower than after seizure (hazard ratio, 0.57; 95% CI, 0.44-0.76) or transient ischemic attack (hazard ratio, 0.27; 95% CI, 0.20-0.35). Compared with patients diagnosed with migraine or seizure, patients diagnosed with TGA do not seem to face a heightened risk of stroke.

Long-term predictive value of the Framingham Risk Score for Stroke in HIV-positive vs HIV-negative men

To test the predictive accuracy of the Framingham Risk Score for Stroke (FRS-S) in HIV-infected (HIV+) vs HIV-uninfected (HIV-) men. The Multicenter AIDS Cohort Study (MACS) is an ongoing prospective study of HIV+ and HIV- men who have sex with men (MSM) enrolled in 4 US cities. We ascertained all reported stroke events during a recent 15-year timeframe (July 1, 1996 to June 30, 2011) among 3,945 participants (1,776 HIV+ and 2,169 HIV-). For those with strokes, FRS-S were calculated 10 years before the stroke event and assessed according to HIV status. A total of 114 stroke events occurred, including 57 HIV+ and 37 HIV- participants with first-ever strokes and 19 fatal strokes. The incidence of first-ever stroke was 1.7/1,000 person-years among HIV- and 3.3/1,000 person-years among HIV+ participants. Among those with strokes, HIV+ participants were younger than HIV- participants (median age 51.3 vs 61.8 years, p < 0.0001). For these men with stroke, the average 10-year risk of stroke was higher for HIV- MSM (6.6% [range 3%-26%] vs 4.9% for HIV+ MSM [range 0%-15%], p < 0.04). Traditional risk factors for stroke were similar among the Framingham cohort and the MACS HIV+ and HIV- participants. FRS-S prediction was systematically different in HIV+ vs HIV- men with stroke events. The FRS-S underestimates the long-term risk of stroke in HIV+ men.

Transient ischemic attack and stroke in systemic lupus erythematosus

Ischemic stroke is increased in systemic lupus erythematosus (SLE) patients. The differential diagnosis of stroke in SLE is complex. Transient ischemic attack and ischemic stroke share pathophysiologic mechanisms, but prognosis may vary depending on severity and cause, and definitions are dependent on the timing and extent of the diagnostic evaluation. In SLE patients with a history of transient ischemic attacks, stroke occurred in 57%. Cerebrovascular events account for 20% to 30% of deaths in patients with SLE. In SLE, both disease-specific and traditional stroke risk factors are important.

Serum Brain–Derived Neurotrophic Factor and Vascular Endothelial Growth Factor Levels Are Associated With Risk of Stroke and Vascular Brain Injury

Background and Purpose— Brain-derived neurotrophic factor (BDNF), a major neurotrophin and vascular endothelial growth factor (VEGF) have a documented role in neurogenesis, angiogenesis, and neuronal survival. In animal experiments, they impact infarct size and functional motor recovery after an ischemic brain lesion. We sought to examine the association of serum BDNF and VEGF with the risk of clinical stroke or subclinical vascular brain injury in a community-based sample. Methods— In 3440 Framingham Study participants (mean age, 65±11 years; 56% women) who were free of stroke/transient ischemic attack (TIA), we related baseline BDNF and logVEGF to risk of incident stroke/TIA. In a subsample with brain MRI and with neuropsychological tests available (n=1863 and 2104, respectively; mean age, 61±9 years, 55% women, in each), we related baseline BDNF and logVEGF to log-white matter hyperintensity volume on brain MRI, and to visuospatial memory and executive function tests. Results— During a median follow-up of 10 years, 193 participants experienced incident stroke/TIA. In multivariable analyses adjusted for age, sex, and traditional stroke risk factors, lower BDNF and higher logVEGF levels were associated with an increased risk of incident stroke/TIA (hazard ratio comparing BDNF Q1 versus Q2–Q4, 1.47; 95% confidence interval, 1.09–2.00; P =0.012 and hazard ratio/SD increase in logVEGF, 1.21; 95% confidence interval, 1.04–1.40; P =0.012). Persons with higher BDNF levels had less log-white matter hyperintensity volume (β±SE=−0.05±0.02; P =0.025), and better visual memory (β±SE=0.18±0.07; P =0.005). Conclusions— Lower serum BDNF and higher VEGF concentrations were associated with increased risk of incident stroke/TIA. Higher levels of BDNF were also associated with less white matter hyperintensity and better visual memory. Our findings suggest that circulating BDNF and VEGF levels modify risk of clinical and subclinical vascular brain injury.

Vascular Complications of Fungal Meningitis Attributed to Injections of Contaminated Methylprednisolone Acetate

Fungal meningitis due to injections of contaminated methylprednisolone acetate can present with vascular sequelae in immunocompetent individuals. This is particularly germane to neurologists because better recognition of the clinical characteristics of patients with fungal meningitis and ischemic stroke will provide more timely and efficient care. In a case series, 3 patients presented to Vanderbilt University Medical Center in Nashville, Tennessee, with acute ischemic stroke and later received a diagnosis of fungal meningitis attributed to epidural injections of contaminated methylprednisolone. Of these 3 patients, 2 were women, and the mean age for all 3 was 75.3 years. Their medical records and imaging scans were reviewed. All 3 patients presented with acute ischemic strokes and had a history of epidural spinal injections of methylprednisolone for low back pain. All 3 patients had 1 or more traditional risk factors for stroke. There were differing vascular patterns of presentation: 2 patients presented with small-vessel (lacunar) infarctions, whereas 1 patient presented with a large-vessel infarct. Of these 3 patients, 2 died and underwent an autopsy, which revealed Exserohilum rostratum as the presumed cause of death. For 2 cases, fever and meningeal signs were absent at presentation. Patients with fungal meningitis may present with ischemic stroke detected on initial imaging scans. A definitive diagnosis should not delay early antifungal treatment.

Physical Activity Frequency and Risk of Incident Stroke in a National US Study of Blacks and Whites

Regular physical activity (PA) is an important recommendation for stroke prevention. We compared the associations of self-reported PA with incident stroke in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study. REGARDS recruited 30 239 US blacks (42%) and whites, aged ≥45 years with follow-up every 6 months for stroke events. Excluding those with prior stroke, analysis involved 27 348 participants who reported their frequency of moderate to vigorous intensity PA at baseline according to 3 categories: none (physical inactivity), 1 to 3×, and ≥4× per week. Stroke and transient ischemic attack cases were identified during an average of 5.7 years of follow-up. Cox proportional hazards models were constructed to examine whether self-reported PA was associated with risk of incident stroke. Physical inactivity was reported by 33% of participants and was associated with a hazard ratio of 1.20 (95% confidence intervals, 1.02-1.42; P=0.035). Adjustment for demographic and socioeconomic factors did not affect hazard ratio, but further adjustment for traditional stroke risk factors (diabetes mellitus, hypertension, body mass index, alcohol use, and smoking) partially attenuated this risk (hazard ratio, 1.14 [0.95-1.37]; P=0.17). There was no significant association between PA frequency and risk of stroke by sex groups, although there was a trend toward increased risk for men reporting PA 0 to 3× a week compared with ≥4× a week. Self-reported low PA frequency is associated with increased risk of incident stroke. Any effect of PA is likely to be mediated through reducing traditional risk factors.

Report of stroke-like symptoms predicts incident cognitive impairment in a stroke-free cohort

The present study characterizes the relationship between report of stroke symptoms (SS) or TIA and incident cognitive impairment in the large biracial cohort of the Reasons for Geographic and Racial Differences in Stroke (REGARDS) Study. The REGARDS Study is a population-based, biracial, longitudinal cohort study that has enrolled 30,239 participants from the United States. Exclusion of those with baseline cognitive impairment, stroke before enrollment, or incomplete data resulted in a sample size of 23,830. Participants reported SS/TIA on the Questionnaire for Verifying Stroke-free Status at baseline and every 6 months during follow-up. Incident cognitive impairment was detected using the Six-item Screener, which was administered annually. Logistic regression found significant association between report of SS/TIA and subsequent incident cognitive impairment. Among white participants, the odds ratio for incident cognitive impairment was 2.08 (95% confidence interval: 1.81, 2.39) for those reporting at least one SS/TIA compared with those reporting no SS/TIA. Among black participants, the odds ratio was 1.66 (95% confidence interval: 1.45, 1.89) using the same modeling. The magnitude of impact was largest among those with fewer traditional stroke risk factors, particularly among white participants. Report of SS/TIA showed a strong association with incident cognitive impairment and supports the use of the Questionnaire for Verifying Stroke-free Status as a quick, low-cost instrument to screen for people at increased risk of cognitive decline.

Pregnancy and Puerperium-Related Strokes in Asian Women

Despite an increased risk of stroke in pregnancy and puerperium, the overall incidence of the condition in this population is low. Therefore, there is limited data pertaining to these patients particularly from Asian countries. Our objective was to describe the risk factors and outcomes of 110 pregnancy-related ischemic strokes from 5 Asian countries. Data were collected by retrospective chart review in most cases and prospectively in the rest. Inclusion criteria for this subanalysis were women, pregnant or within 1-month postpartum, presenting to the study center with acute ischemic stroke (arterial or venous) confirmed by neuroimaging. Intracranial hemorrhages other than the ones associated with cerebral venous thrombosis or hemorrhagic infarct were excluded. Risk factors were diagnosed based on already published criteria. Outcomes were measured using modified Rankin score. Statistical analysis was done using Statistical Package for Social Sciences version 19.0. In all, 110 women with mean age of 27.94 years presented with pregnancy-related ischemic strokes; 58.2% of the strokes occurred postpartum and 49.1% were secondary to cerebral venous thrombosis. Venous strokes were significantly more likely to occur postpartum compared with arterial strokes (P=.01), to have abnormal "hypercoagulable panel result on admission" (P<.001), less likely to have traditional stroke risk factors (P<.001), to have hemorrhagic conversion of stroke (P<.001), and to have lesser stroke severity and better functional outcome at 3 months (P<.001 for each). Cerebral venous thrombosis is a significant contributor to pregnancy-related strokes in Asian women. Both traditional and pregnancy-specific risk factors should be addressed to control ischemic stroke risk in these women.

Standard strategies for acute ischemic stroke within the rtPA therapeutic window.

The vision of thrombolysis for reversal of acute ischemic stroke (AIS) was launched in 1958,1 but it was not until 1995 that 2 landmark studies, one in Europe2 and the other in the United States,3 established IV administration of tissue plasminogen activator (tPA) as an effective treatment for AIS. The National Institute of Neurological Disorders and Stroke study, with a 3-hour treatment window from onset of symptoms to vein puncture, showed more efficacy and had fewer safety concerns than the original European Cooperative Acute Stroke Study (ECASS) trial that had designated 6 hours from symptom onset as the limit for IV infusion of tPA. Since 1995, the administration of IV tPA to reverse the ravages of AIS has become the standard and only validated form of treatment.4 So much has been published, discussed, commented, editorialized and publicly aired about IV tPA in AIS that one would assume that IV tPA is a universally available form of treatment. In a recent poster presentation at the 65th annual meeting of the American Academy of Neurology (AAN), a group of investigators from the United States5 reported the global use of IV tPA for AIS by country, income group, and country-level health expenditure per capita. The researchers conducted a systematic review in PubMed from 1997 to 2012. Each country's publications in any language were reviewed and the results were startling. Of 214 countries and independent territories, 54 (25%) reported use of IV tPA for AIS. In relation to income status, the study revealed IV tPA usage in 3% (1/36) of low-income countries, 13% (7/54) of lower-middle-income countries, 28% (15/54) of upper-middle-income countries, and 44% (31/70) of high-income countries. The authors concluded that IV tPA for AIS has limited use globally, is available to patients in only one-quarter of countries in the higher income brackets, and that barriers to IV tPA use for countries at different income levels must be understood to be overcome. Ironically, stroke incidence might be increasing in lower-income countries6 as traditional risk factors for stroke become increasingly prevalent in those countries.

Abstract 80: Amino-terminal Pro-B-type Natriuretic Peptide (NT-Pro-BNP) And Risk Of Stroke: The Reasons For Geographic And Racial Differences In Stroke (REGARDS) Cohort

Background: Higher NT-Pro-BNP is a biomarker of cardiac dysfunction associated with risk of future heart failure and atrial fibrillation, and as such may be a marker of stroke risk. Methods: REGARDS enrolled 30,239 US participants in 2003-07 (41% black, 59% white, 55% living in the southeastern stroke belt). With 5.4 years follow-up, baseline NT-Pro-BNP was measured in 610 subjects with first-time stroke and a 1017 person cohort random sample free from prebaseline stroke. Cox proportional hazards models were used to calculate hazard ratios (HR) of stroke by quartiles of NT-Pro-BNP. Net reclassification improvement (NRI) was calculated using the category free NRI statistic. Results: Baseline NT-Pro-BNP was higher with older age, in whites, women, and with diabetes, impaired kidney function, atrial fibrillation, prebaseline heart disease, lower body-mass index and left ventricular hypertrophy by ECG. Levels were higher in those who developed incident stroke. Adjusting for age, race and sex there was an increased HR of stroke with increasing quartiles of NT-Pro-BNP (Model 1 in table); subjects in the 4 th versus 1 st quartile had a 3.7-fold increased stroke risk. Adjustment for income, education and traditional stroke risk factors attenuated this HR to 3.0. There was minimal impact of added adjustment for kidney function, BMI and heart failure. Associations did not differ by age, sex, race or kidney disease status. Based on NRI, predicted stroke risk was more accurate in 27% of participants if NT-Pro-BNP was measured with traditional stroke risk factors (p&lt;0.001). Discussion: NT-Pro-BNP was a major risk marker for stroke and improved risk classification. By comparison, in this cohort the HRs of stroke were 1.5 for atrial fibrillation and 1.8 for hypertension. More work is needed to confirm that measuring NT-Pro-BNP improves clinical prediction scores for stroke.

Abstract WMP54: ABO Blood Type and Incident Stroke in the REasons for Geographic and Racial Differences in Stroke (REGARDS) Study

Background: Non-O blood type is associated with higher procoagulant proteins and potentially stroke. Prior studies may overestimate the association due to lack of control for race and stroke risk factors as there are known racial differences in blood type, conventional stroke risk factors, and stroke risk. Methods: REGARDS recruited 30,239 participants in their homes between 2003-07 from the continental US; 55% were female, 41% were black, and 56% lived in the southeast (by design). Using a case-cohort design, 553 participants with incident stroke and 991 participants without baseline stroke were genotyped to determine blood type. Cox proportional hazard models adjusting for race and Framingham or ARIC stroke risk factors were used to determine the association of blood type with incident stroke. Results: Blacks had a higher frequency of blood type B (17% vs. 10%) and AB (5% vs. 2%) and a lower frequency of blood type O (31% vs. 42%) than whites (p &lt;0.001) (Table). Except for diabetes (OR 4.1 95% CI 2.1, 7.9) and higher systolic blood pressure (7.5 mm hg higher, p = 0.01) for blood type AB vs. O, stroke risk factors did not differ by blood type. Over 4.5 years of follow-up, neither blood types A or B were associated with incident stroke accounting for race and traditional stroke risk factors (Table). Blood type AB was associated with a marginally increased risk of stroke after adjusting for race and Framingham (HR 1.8; 95% CI 1.0, 3.4) or ARIC (HR 1.8; 95% CI 1.0, 3.3) stroke risk factors (Table). Discussion: Blood type AB is associated with an increased risk of stroke which is not mediated by conventional stroke risk factors. This association could relate to increased factor VIII or von Willebrand factor in individuals with non-O blood type but this does not explain the unique association of blood type AB with stroke. Whether blood type should be incorporated into clinical stroke risk models is unknown.

Abstract 82: Serum VEGF Levels Alter Risk of Stroke: the Framingham Heart Study

Objective: To examine the association of serum VEGF levels with incident stroke and transient ischemic attack (TIA) in a large, community-based cohort. Background: VEGF, an endothelial growth factor promotes angiogenesis and neurogenesis and has demonstrated neuroprotective properties in animal experiments. However, high circulating VEGF levels have also been observed in patients with vascular risk factors, atherosclerosis and in small studies of acute stroke. There have been no studies examining the association of serum VEGF with the risk of stroke in a community-based sample. Methods: In 3440 stroke/TIA-free FHS participants (mean age 65+11yrs, 56%W), we related baseline VEGF (log-transformed) to risk of incident stroke/TIA. To examine the incremental utility of VEGF over age-, sex- and baseline Framingham Stroke Risk Profile (FSRP) in predicting stroke/TIA, we also calculated the net reclassification improvement (NRI). Results: During a median follow-up of 10 years, 193 participants experienced incident stroke/TIA (129 ischemic strokes). In multivariable analyses adjusted for age-, sex- and traditional stroke risk factors (as identified by the FSRP), higher logVEGF levels were associated with an increased risk of incident stroke/TIA (HR/1SD increase in logVEGF: 1.21, 95%CI: 1.04-1.40, p=0.012). This was also true for incident ischemic stroke events (HR/1SD increase in logVEGF: 1.21 95%CI: 1.01-1.44 p=0.04). In reclassification analyses, logVEGF, when added to a risk assessment model based on the FSRP resulted in significant improvement of risk prediction with NRI of 0.046 (p=0.036). Interpretation: After adjusting for traditional stroke risk factors, higher VEGF concentrations were associated with increased risk of incident stroke/TIA, suggesting that VEGF may serve as a novel risk marker for stroke/TIA and to improve risk stratification permitting more targeted preventive interventions.