Large Artery Disease Research Articles

Abstract 34: Improvement In Etiological Identification In Tia And Minor Stroke Using The Causative Classification Of Stroke.

Background: classification of Transient Ischemic attacks (TIA) and minor stroke is challenging, as there is no classification systems developed specifically for the TIA and minor stroke patient population. Hypothesis: We hypothesize that the newly developed Causative Classification System (CCS) and the Atherosclerosis Small Vessel Disease Cardiac Source Other Source (ASCO) classification would reduce the proportion of patients classified as cause undetermined compared with The Trial of ORG 10172 in Acute Stroke Treatment (TOAST) classification in a large prospectively evaluated TIA and Minor stroke population. Methods: Using published algorithms for TOAST, CCS, and ASCO, a single rater classified the etiology in patients presenting with a high-risk TIA (weakness or speech disturbance lasting ≥ 5minutes) or minor ischemic stroke (National Institute of Health Stroke Scale score ≤ 3) who underwent CT/CTA and subsequent MRI as part of the CATCH study. Results: 419 patients with TIA or Minor stroke were classified using TOAST, CCS, and ASCO. The proportion of patients with an undetermined etiology was 51.3% (215/419) with TOAST. This was significantly reduced by both CCS 36% (151/419, p< 0.001) and ASCO 41% (172/419, p< 0.001). CCS was also less likely to have an undetermined etiology as compared to ASCO (36% versus 41%, p = 0.024). When compared with TOAST, there was a 23.9% (95%CI:18.1- 29.7, P< 0.001) and 17.4% (10.1- 24.7, P< 0.001) reduction in the proportion of patients assigned to the undetermined group using CCS and ASCO respectively. The 8.5 % reduction in the undetermined group between CCS and ASCO was also statistically different P=0.031). Compared with ASCO1, CCS increased the assignment of patients to large artery disease (relative increase 7.4% {4.3-10.4}, P< 0.001) and Cardio-embolism/cardio-aortic categories (relative increase 8.1% {4.6-11.5}, P< 0.001). Conclusions: Both CCS and ASCO were superior to TOAST in assigning fewer patients to an undetermined etiology category. CCS was superior to ASCO at reducing the proportion of patients with undetermined etiology. This was largely driven by increased assignment in the large artery and Cardio-aorto embolic categories.

Effect of Vildagliptin on Atherosclerosis Progression in High Cholesterol–Fed Male Rabbits

Background: Atherosclerosis is a progressive disease of large and medium-sized arteries characterized by the accumulation of lipids and fibrous elements in the large arteries. Aim of the study: This study was undertaken to assess the effect of vildagliptin on the progression of atherosclerosis via interfering with inflammatory and oxidative pathways. Materials and Methods: 18 local domestic male rabbits were included in this study. The animals were randomly divided into three groups (6 rabbits for each group): Group I rabbits fed normal chow (oxiod) diet for 12 weeks. Group II rabbits fed 1% cholesterol enriched diet for 12 weeks. Group III rabbits fed with cholesterol enriched diet for 6 weeks, and then continued on cholesterol-enriched diet and treated with vildaglipin 50 mg/kg/day orally for the next 6 weeks. Blood samples were collected at the start of the study, at 6weeks of the study and then at the end of treatment course to measure Serum lipids profile [(TC), (TG), (HDL)], hsCRP and TNFα. At the end of the study the aorta were removed for measurement of aortic MDA, glutathione, sectioning for histopathology and measuring aortic intima- media thickness. Results: Treatment of rabbits with vildagliptin for 6 weeks results in a significant reduction (P<0.05) in serum level of TC, TG, hsCRP and TNFα and a significant increase (P<0.05) in serum HDL level. There was a significant reduction (P<0.05) in aortic MDA and intima-media thickness, in comparison to the rabbits in the induced untreated control group. vildagliptin treatment cause significant increment (P<0.05) in aortic GSH in comparison to induced untreated group. Regarding the histopathological results, vildagliptin treatment for 6 weeks results in a significant reduction (P<0.05) in atherosclerotic lesions in comparison to the induced untreated group and significant reduction in aortic intima- media thickness (P<0.05). Conclusions: Vildagliptin reduced atherosclerosis progression in hyperlipidemic rabbit via its effect on lipid parameters and interfering with inflammatory and oxidative stress pathway.

MRSを用いた症候性脳主幹動脈閉塞性病変の脳代謝の検討

MRSを用いた症候性脳主幹動脈閉塞性病変の脳代謝の検討

In this Issue: Nef, A Lingering Problem; Are There Better Immunoglobulins for Human Use; and Takayasu Arteritis, Still a Mystery

The current issue of the International Reviews of Immunology brings the latest in three different areas of basic and clinical immunology. First, there is the lingering question of residual HIV-related pathology in patients on chronic antiretroviral therapy. The specific role of Nef in the macrophage-mediated disease manifested through lymphoma, metabolic disease and neurological disorder, is extensively discussed. A second topic is a clinical immunology one, a critical perspective on the efficacy and safety profile of various preparations of immunoglobulin products currently prescribed for a range of immunodeficiencies. Surprisingly, the authors showed that while the available preparations are equivalent from efficacy standpoint, they differ from the standpoint of toxicity. The third subject is again, in the arena of clinical immunology and deals with a relatively rare yet extremely puzzling disease –Takayasu arteritis –with a pathogenesis that needs elucidation and a dire need for better treatments. The authors provide a state of the art in terms of genetic association, other factors possibly involved in the onset and progression of this unusual inflammatory disease of large arteries, and provide a perspective on current standard of care and potential usefulness of TNF-α blockade as therapy for Takayasu arteritis.

Characteristics of stroke mechanisms in patients with medullary infarction

Few studies have focused on the mechanisms underlying medullary infarctions. Our aim in this study was to investigate stroke mechanisms in patients with medullary infarctions and to determine the clinical, radiological and laboratory characteristics of these patients with different underlying stroke etiologies. Consecutive patients with medullary infarction were analysed. Stroke mechanisms were classified as large artery disease (LAD), cardiogenic embolism (CE), small vessel disease (SVD), arterial dissection or undetermined etiology. Clinical, radiological and laboratory factors were analysed according to the location of the lesion and stroke mechanisms. A total of 77 patients were enrolled in this study. Amongst them, 53 (68.8%) patients had lateral medullary infarction (LMI), 22 (28.6%) had medial medullary infarction (MMI), and the remaining 2 (2.6%) had hemimedullary infarction. In both LMI and MMI patients, LAD was the most frequently encountered stroke mechanism. Arterial dissection was the second most common cause followed by SVD and CE in patients with LMI, whereas SVD was more frequently observed (P<0.001) and dissection and CE were less prevalent (P<0.001 and P=0.024, respectively) in MMI than in LMI. Regarding differences amongst stroke etiologies, patients with dissection were younger and had a significantly lower incidence of metabolic syndrome (P=0.002 and P=0.009, respectively) than patients with LAD and SVD. Patients in the LAD (19/34, 60%) and dissection groups (12/14, 75%) had abnormal perfusion-weighted MRI (PWI) findings, whereas all patients with SVD (9/9) had normal PWI findings (P<0.001). Stroke mechanisms in medullary infarction differ between LMI and MMI. Clinical and radiological characteristics, especially PWI features, are helpful in discriminating the etiologies of stroke in these patients.

Clinical and Radiological Features of Stroke Patients with Poor Outcomes Who Do Not Receive Intravenous Thrombolysis because of Mild Symptoms

Background and Aims: A substantial proportion of patients who did not receive intravenous thrombolysis with recombinant tissue plasminogen activator (rtPA), solely because of mild symptoms, can show poor outcome. The aim of our study was to analyze clinical and radiological features of the patients. Methods: We enrolled 72 patients between 2007 and 2009 who presented to our hospital within 3 h after stroke onset and who did not receive rtPA therapy solely because of mild symptoms (NIHSS score of ≤4 at rtPA decision), and examined detailed characteristics of patients with poor outcomes. Poor outcome was defined as a modified Rankin Scale score of ≥2 at 3 months after the stroke. Results: Eleven of 72 patients (15%) had poor outcomes. Major vessel occlusion was observed in 7 of the 11 patients. Neurological deterioration after admission was main reason for poor outcome. Infarct expansion in 6 patients (2 large artery diseases and 4 small vessel diseases) and distal embolism by clot migration in 3 patients led to neurological deterioration. Conclusions: Clinical and radiological features of mild stroke patients with poor outcomes, who did not receive rtPA therapy, were identified. In such patients, intravenous thrombolysis may be justified.

Rates and predictors of risk of stroke and its subtypes in diabetes: a prospective observational study

BackgroundSmall vessel disease is reported to be a more common cause of ischaemic stroke in people with diabetes than in others. However, population based studies have shown no difference between...

Lipoprotein(a), type 2 diabetes and nephropathy; the mystery continues

Lipoprotein(a), type 2 diabetes and nephropathy; the mystery continues

What Is Certain When the Stroke Etiology Is Uncertain?

See related article, p 2948. > “Medicine is a science of uncertainty and an art of probability.” > > —William Osler (1849–1919) The great majority of ischemic strokes are due to cardioembolism, largeartery atherosclerotic disease, smallvessel occlusive disease, or other unusual mechanisms (eg, cervical dissection, thrombophilia, etc).1 Nevertheless, in approximately 20% to 40% of patients with stroke, the underlying etiology is not established (called “cryptogenic,” “uncertain,” or “undetermined” stroke).2,3 Limited information is available on longterm outcomes in this specific subgroup. Clinicians wonder about the risk of recurrence and whether death and/or disability in patients with cryptogenic stroke are better or worse compared with those with a determined etiology. In the present study, Nam et al studied 3278 patients with an ischemic stroke with a median followup of 3.4 years.4 Overall, 37% were classified as “undetermined.” Two thirds of patients had a mild stroke (National Institutes of Health Stroke Scale <6) with an overall median National Institutes of Health Stroke Scale of 4. Nearly 40% were exposed to smoking and 31% had diabetes. Interestingly, the authors broke down the undetermined strokes into …

Dynamic T cell–APC interactions sustain chronic inflammation in atherosclerosis

Atherosclerosis is a chronic inflammatory disease of large and medium-sized arteries characterized by leukocyte accumulation in the vessel wall. Both innate and adaptive immune responses contribute to atherogenesis, but the identity of atherosclerosis-relevant antigens and the role of antigen presentation in this disease remain poorly characterized. We developed live-cell imaging of explanted aortas to compare the behavior and role of APCs in normal and atherosclerotic mice. We found that CD4+ T cells were capable of interacting with fluorescently labeled (CD11c-YFP+) APCs in the aortic wall in the presence, but not the absence, of cognate antigen. In atherosclerosis-prone Apoe-/-CD11c-YFP+ mice, APCs extensively interacted with CD4+ T cells in the aorta, leading to cell activation and proliferation as well as secretion of IFN-γ and TNF-α. These cytokines enhanced uptake of oxidized and minimally modified LDL by macrophages. We conclude that antigen presentation by APCs to CD4+ T cells in the arterial wall causes local T cell activation and production of proinflammatory cytokines, which promote atherosclerosis by maintaining chronic inflammation and inducing foam cell formation.

The Effectiveness of Dual Antiplatelet Treatment in Acute Ischemic Stroke Patients with Intracranial Arterial Stenosis: A Subgroup Analysis of CLAIR Study

Dual antiplatelet therapy with clopidogrel and aspirin reduces the presence and number of microembolic signals in patients with large artery disease. However, whether it is effective in patients with intracranial disease alone remains uncertain. We performed a subgroup analysis of the The CLopidogrel plus Aspirin for Infarction Reduction (CLAIR in acute stroke or transient ischemic attack patients with large artery stenosis and microembolic signals) study of only patients with intracranial occlusive disease, excluding those with extra cranial disease. CLAIR was a randomized-controlled, open-label, multicenter clinical trial with blinded outcome evaluation, which recruited patients with symptoms of ischemic stroke or transient ischemic attack within seven-days of onset, with large artery stenosis verified by transcranial Doppler and carotid ultrasound, and with microembolic signals detected by transcranial Doppler recording. All patients were randomized to receive clopidogrel plus aspirin daily for seven-days (dual treatment), or aspirin alone for seven-days (monotherapy). Repeated transcranial Doppler recordings for microembolic signals were made on day one, two, and seven. This subgroup study only analyzed the patients with purely intracranial large artery disease and excluded those with extra cranial stenosis. There were 70 patients recruited with purely intracranial stenosis, 34 in the dual treatment group and 36 in the monotherapy group. The proportion of the patients with positive emboli at day seven in the dual treatment group was significantly lower than that in the monotherapy group (relative risk reduction 56·5%, 95% confidence interval 2·5-80·6; P = 0·029). The number of emboli in the dual treatment group decreased significantly at day two (P = 0·043) and day seven (P = 0·018) compared with the monotherapy group. After adjustment for the number of emboli at day one, the effect of dual treatment was still significant for the reduction of presence (relative risk reduction 56·0%; 95% confidence interval 5·4-79·6; P = 0·036) and number (adjusted mean difference -0·9; 95% confidence interval -1·5 to -0·3; P = 0·004) of positive emboli at day seven. Dual treatment with clopidogrel and aspirin for seven-days is more effective than aspirin alone to reduce microembolic signals in patients with intracranial arterial stenosis.

Improving the Prediction of Stroke or Death After Transient Ischemic Attack (TIA) by Adding Diffusion-weighted Imaging Lesions and TIA Etiology to the ABCD2 Score

The present study investigated the addition of transient ischemic attack (TIA) etiology and diffusion-weighted imaging (DWI) to the ABCD2 score, creating the ABCDE+ score, to improve the predictive ability of stroke risk or death at 6 months after TIA. We performed a cohort study of 150 consecutive patients with TIA. All patients underwent DWI and all had an etiologic workup and were followed up for 6 months. The area under the receiver operating characteristic curve (AUC) was used to compare the scores' ability to predict the outcome of stroke or death. Multivariate Cox regression analysis was performed to evaluate the association between the measured variables and subsequent stroke or death. Thirty patients (20%) experienced future stroke, and 12 patients (8%) died within the 6-month follow-up. A comparison of AUCs demonstrated the superiority of the ABCDE+ score over the ABCD2 score for predicting stroke (0.64 vs 0.60) and for predicting death (0.62 vs 0.56). ABCD2 score >4, ABCDE+ score >6, large-artery disease, and lesions detected on DWI were found to be independent predictors of future stroke, and ABCDE+ score >6, age, and heart disease were independent predictors of death. We conclude that incorporating DWI positivity and etiology of TIA into the ABCD2 score can improve the ability to predict stroke and death within 6 months after TIA.

Combination Oral Antiplatelet Therapy may Increase the Risk of Hemorrhagic Complications in Patients With Acute Ischemic Stroke Caused by Large Artery Disease

The incidence of hemorrhagic complications is likely increased in patients with acute ischemic stroke secondary to large artery disease who are treated with combination antiplatelet therapy.

Associations of ankle-brachial index (ABI) with cerebral arterial disease and vascular events following ischemic stroke

ObjectivesLow ankle-brachial index (ABI), indicative of peripheral arterial disease (PAD), is a risk factor for stroke. ABI has been shown to be associated with cerebral arterial disease and prognosis following stroke. We studied the associations of the degree of ABI lowering with extracranial carotid disease (ECD), intracranial large artery disease (ICLAD), and subsequent vascular events in a prospective cohort of acute ischemic stroke patients. MethodsABI, extracranial and intracranial cerebral arteries were assessed in a blinded manner. ABI was categorized into 0.9–1.3 (normal), 0.8–0.89 (mildly lowered) and <0.8 (severely lowered). Follow-up data at 1 year were obtained from standardized telephone interviews and verified with medical records. ResultsAmong the 1311 patients, 73% had normal ABI, 13% had ABI 0.8–0.89 and 13% had ABI <0.8. Compared to patients with normal ABI, those with ABI<0.8 had higher prevalence of severe ECD (15% vs. 5%, p = 0.006) and ICLAD (72% vs. 48%, p = 0.003), even after adjustment for age, gender, hypertension, diabetes, hyperlipidemia, smoking, ischemic heart disease and atrial fibrillation (severe ECD p < 0.001, ICLAD p < 0.001). At 1 year, patients with ABI <0.8 had a higher incidence of composite vascular events (19% vs. 11%, p = 0.02), stroke (15% vs. 10%, p = 0.06) and myocardial infarction (4% vs. 2%, p = 0.07) than patients with normal ABI. ConclusionAmong ischemic stroke patients, large cerebral arterial disease and incidence of subsequent vascular events at 1 year were associated with severe ABI lowering <0.8, but not with mild ABI lowering (0.8–0.89).

Hemodynamic alterations in vertebrobasilar large artery disease assessed by arterial spin-labeling MR imaging.

VB artery stenosis is associated with a high risk of recurrent ischemic events, and knowledge about the hemodynamic relevance of VB stenosis is important for clinical decision making. In this study, multiple inflow pulsed ASL MR imaging was assessed for its ability to measure CBF and ATT in patients with VB disease. ASL was performed on a 3T MR imaging scanner in 41 participants. Twenty-one patients had a history of ischemic events in the VB circulation (14 men, 7 women, age 66 ± 11 years). Clinical data and CE-MRA were used to classify VB disease severity. Twenty age-matched adults were controls. Group and within-VB analyses were performed. Mean CBF and ATT values in the ROIs were adjusted by excluding voxels that did not produce a reliable ASL estimate. CBF was reduced (P < .003) in patients compared with controls, which was significant after excluding voxels with a poor fit. Differences in ATT between patients and controls were not significant after voxel correction. There was a strong correlation between CBF and ATT among patients. Finally, ATT was significantly correlated with VB disease severity (P = .026). Multiple inflow ASL distinguished patients with VB disease from age matched-controls. VB disease rating was associated with prolonged ATT downstream. ASL may have diagnostic potential among patients in whom risk of intervention is high.

Riesenzellarteriitis

Giant cell arteritis is a potentially systemic disease of medium-sized and large caliber arteries, showing a preferential manifestation in the extracranial branches of the carotid artery. The diagnosis is oriented to clinical and histomorphological criteria which will be critically reviewed. Particular emphasis is placed on the differentiation from normal aging processes and from healing stages under steroid therapy. In addition, the advances in our understanding of the disease pathomechanism during the last 10 years will be briefly presented as the basis for the hitherto empiric steroid treatment.

Abstract 114: Pomegranate Regressed Atheroma in Carotid and Coronary Arteries: Fiction or Fact?

Background: Atherosclerosis is a disease of large and medium-sized muscular arteries and is characterized by endothelial dysfunction, vascular inflammation, and the buildup of lipids, cholesterol, calcium, and cellular debris within the intima of the vessel wall, oxidized low-density lipoprotein (LDL) can reduce the expression of nitric oxide synthase, the enzyme that produces nitric oxide. Nitric oxide reduces injury to the vessel walls, which also helps prevent the development of atherosclerosis Recently, they discovered that pomegranate juice enhances the bioactivity of nitric oxide synthase in endothelial cells. Furthermore, pomegranate’s antioxidant properties protect nitric oxide from oxidative destruction, thus augmenting its biological actions. Therefore the objective of present study was to assess the effect of pomegranateon atherosclerosis regression via interfering with inflammatory and oxidative pathways. Methods: 60 local domestic rabbits were assigned to three groups: Group I (n = 30) fed normal diet,Group II ( n = 30) Rabbit fed high cholesterol-diet (induced untreated group), Group III ( n = 30) high cholesterol-diet for 12 weeks but adding oral pomegranate juice at 6 weeks .Blood samples were collected at (0 time ), after 6 and 12 weeks for measurement of serum triglycerides (TG), total cholesterol (TC), HDL-C and serum high sensitive C-Reactive Protein (hsCRP), serum IL-6 and serum TNF-a. At the end of 12 weeks,both carotid and right coronary arteries was removed, part of it for histopathology to assess the atherosclerotic change according to AmericanHeart Association classification of atherosclerosis phases and for aortic intema-media thickness also part of it homogenized for malondialdehyde (MDA) and reduced glutathione (GSH). Results: Compared with the control, levels of TC, TG, LDL-C, VLDL-C, atherogenic index, hsCRP, IL-6, TNF-a and arterial MDA were increased and arterial GSH and serum HDL-C were decreased in the animals with a high-choleterole diet ( P &lt; 0.01). Histologically all induced-untreated rabbit showed significant atherosclerosis lesions in both arteries ( P &lt; 0.01) all occurred at 6 and 12 weeks. While in pomegranate treated group at 12 weeks, levels of TC, TG, LDL-C, VLDL-C, atherogenic index, hsCRP, IL-6, TNF-a and arterial tissue of MDA were decreased and coronary and carotid GSH and serum HDL-C were increased relatively ( P &lt; 0.01).Low power microscopic morphologic analysis revealed that pomegranate treated group markedly regressed ( P &lt; 0.01) the atherosclerotic lesion in form of decrease intima-media thickness in histomorphometric measurements in the studied arteries at 12 weeks compared with rabbits on a high-fat diet at same period. In conclusion pomegranate juiceregressed atherosclerosis in carotid and coronary arteries in hypercholesterolemic rabbit via inhibition of inflammatory, oxidative pathways, reduced level of lipid parameters and decreased aortic intima-media thickness.

Posterior circulation ischemic stroke-clinical characteristics, risk factors, and subtypes in a north Indian population: a prospective study.

Posterior circulation stroke accounts for approximately 20% of all strokes with varied clinical presentation, which differ from strokes in anterior circulation, with reference to etiology, clinical features, and prognosis. Short penetrating and circumferential branches in the posterior circulation supply the brain stem, thalamus, cerebellum, occipital, and medial temporal lobes. We prospectively analyzed 80 participants of posterior circulation ischemic stroke from a registry of 944 participants attending a tertiary care referral university hospital. Patients were analyzed for demographics, stroke risk factors, clinical characteristics, neuroimaging, and stroke subtypes. Posterior circulation ischemic stroke accounted for 80 (8.5%) of 944 of all strokes and 80 (10.45%) of 765 of ischemic stroke. Sixty-three were males with mean age 51.7 ± 14.4 years. Twenty-one participants were young (defined as age less than 45 years). Hypertension was found to be the most common risk factor (63.75%). Vertigo was the most common clinical symptom reported in 45 (56.25%) cases. Sixty-eight (85%) patients had large artery disease, 8 (10%) had documented cardioembolic source, 3 (3.75%) small artery disease, and 2 (2.5%) vasculitis. Posterior cerebral artery was most commonly involved. Topographically distal intracranial involvement was most frequent (66.25%) followed by proximal (30%) and middle intracranial territory (3.75%). Our study demonatrated the occurrence of posterior circulation stroke in relatively younger age group compared to the Western world. We also found higher percentage of large artery disease, while cardioembolism as a less frequent cause of posterior circulation ischemic stroke in North Indian population. Distal territory involvement was most common in our study.

Stroke prevention: an update

Stroke is a personal, familial, and social disaster. It is the third cause of death worldwide, the first cause of acquired disability, the second cause of dementia, and its cost is astronomic. The burden of stroke is likely to increase given the aging of the population and the growing incidence of many vascular risk factors. Prevention of stroke includes--as for all other diseases--a "mass approach" aiming at decreasing the risk at the society level and an individual approach, aiming at reducing the risk in a given subject. The mass approach is primarily based on the identification and treatment of vascular risk factors and, if possible, in the implementation of protective factors. These measures are the basis of primary prevention but most of them have now been shown to be also effective in secondary prevention. The individual approach combines a vascular risk factor modification and various treatments addressing the specific subtypes of stroke, such as antiplatelet drugs for the prevention of cerebral infarction in large and small artery diseases of the brain, carotid endarterectomy or stenting for tight carotid artery stenosis, and oral anticoagulants for the prevention of cardiac emboli. There is a growing awareness of the huge evidence-to-practice gap that exists in stroke prevention largely due to socio-economic factors. Recent approaches include low cost intervention packages to reduce blood pressure and cheap "polypills" combining in a single tablet aspirin and several drugs to lower blood pressure and cholesterol. Polypill intake should however not lead to abandon the healthy life-style measures which remain the mainstay of stroke prevention.

Abstract 189: Analysis of Hypertension Associated Genetic Variants in Stroke Cases and Controls

BACKGROUND: Recent genome-wide association studies (GWAS) have identified a number of novel SNPs associated with blood pressure and hypertension-related traits although studies were very large (approaching 80K participants) and effect sizes were modest with per allele effect sizes as small variants as a single millimeter of mercury difference in blood pressure. However, because hypertension is the most potent modifiable risk factor for ischemic stroke, lowering blood pressure by a few mm Hg can translate into measurable decrease in stroke risk. METHODS: We investigated 22 hypertension (HTN) associated SNPs in a case-control analysis of ischemic stroke in multiple stroke studies including the Siblings With Ischemic Stroke Study (SWISS), the Ischemic Stroke Genetics Study (ISGS), the Bio-Repository of DNA in Stroke (BRAINS), the Vitamin Intervention for Stroke Prevention (VISP) trial, and the Women's Health Initiative (WHI). SWISS/ISGS/BRAINS were analyzed together and included subtype information. Genotyping was funded through the individual studies, the Genomics and Randomized Trials Network (GARNET) consortium, and the SHARe (SNP Health Association Resource). All studies had both raw and imputed GWAS data. Analyses included the following phenotypes: all ischemic stroke, stroke subtypes, and age-at-stroke-onset and were stratified by race. Analyses were minimally adjusted for age, sex and principal components 1 &amp; 2. Alpha was set at 0.05. RESULTS: Eleven of the SNPs from the HTN GWAS were associated with ischemic stroke in European ancestry from one or more of the study populations. Two SNPs on chromosome 12 and one on chromosome 21 were associated in multiple European ancestry cohorts. No SNP was associated in all studies. A SNP previously associated with HTN in African ancestry populations was associated with stroke in African-Americans. Analysis of subtypes found associations with small vessel disease and cardioembolic stroke but not large artery disease. The case-only age-at-stroke-onset analysis also found associations for the two SNPs on chromosome 12. CONCLUSION: These data suggest that candidate SNPs from a HTN GWAS may be associated with ischemic stroke and warrant further investigation. Racial differences were observed. Replication in populations from the other SiGN (Stroke Genetics Network), GENEVA (Gene Environment Association Studies) consortium, and the ISGC (International Stroke Genetics Consortium) studies are underway.