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Reducing blood pressure (BP) is a highly effective strategy for long-term stroke prevention. Despite overwhelmingly clear evidence from randomized trials that antihypertensive therapy substantially reduces the risk of stroke in primary prevention, uncertainty still surrounds the issue of BP lowering after cerebrovascular events, and the risk of recurrent stroke, coronary events, and vascular death remains significant. Important questions in a secondary prevention setting include should everyone be treated regardless of their poststroke BP, how soon after a stroke should BP-lowering treatment be commenced, how intensively should BP be lowered, what drugs are best, and how should long-term BP control be optimized and monitored. We review the evidence on BP control after a transient ischemic attack or stroke to address these unanswered questions and draw attention to some recent developments that hold promise to improve management of BP in current practice.

Introduction: Pre-pregnancy hypertension (HTN), hypertensive disorders of pregnancy (HDP), and diabetes are linked to increased risk of post-pregnancy coronary heart disease (CHD) and all-cause mortality, but the cumulative impact of pre-pregnancy HTN, HDP, and diabetes has yet to be fully investigated. We aimed to examine associations between HDP and diabetes with CHD and mortality ≤5 years of delivery stratified by race/ethnicity. Methods: This retrospective cohort study included women aged 12-49 with ≥1 singleton, live birth in South Carolina (2004-2016). After exclusions, 431,839 women remained: non-Hispanic White [NHW; 58.8%], non-Hispanic Black [NHB; 31.7%], and Hispanic [9.5%]. Birth certificates defined pre-pregnancy HTN, HDP (preeclampsia, eclampsia, gestational hypertension), and diabetes (pre-pregnancy, gestational); hospitalization/ED visit data also defined pre-pregnancy HTN and HDP. Hospitalization/ED visit data and death certificates defined incident CHD and all-cause mortality. Cox proportional hazard models adjusted for covariates assessed associations by condition and race/ethnicity. Results: Incident CHD risk was increased ≤5 years of delivery for women with diabetes (HR=1.79, CI: 1.40-2.29), HDP (HR=2.91, CI: 1.98-2.65), diabetes and HDP (HR=3.95 CI:3.09-5.05), pre-pregnancy HTN and HDP (HR=3.94, CI: 3.11-5.00), and all three conditions (HR=5.78, CI: 4.41-8.06) compared to none. All-cause mortality risk was increased for HDP (HR=1.31, CI: 1.08-1.58), diabetes and HDP (HR=1.93, CI: 1.30-2.87), pre-pregnancy HTN and HDP (HR=2.20, CI: 1.54-3.15), and all three conditions (HR=2.88, CI: 1.61-5.16), but not with diabetes. The table shows overall and race/ethnic-specific event rates and model results. Discussion: Women with HDP (regardless of pre-pregnancy HTN) and/or diabetes experienced higher incident CHD and all-cause mortality risk ≤5 years of delivery. Event rates were highest for women with two or three conditions, with all event rates higher for NHB than NHW women.

The CASSISS trial (China Angioplasty & Stenting for Symptomatic Intracranial Severe Stenosis), recently published in JAMA , is the most recent of several randomized controlled trials that have failed to show a benefit of percutaneous angioplasty and stenting over medical therapy for the prevention of stroke due to intracranial atherosclerotic stenosis. Current practice guidelines recommended that percutaneous angioplasty and stenting should not be performed routinely as a treatment for stroke prevention in patients with intracranial atherosclerotic stenosis. The CASSISS trial reinforces those recommendations and will not change practice, but it may provide some important lessons for future trial design.

Objectives High-resolution magnetic resonance imaging has the potential of characterising arterial wall changes after endovascular mechanical thrombectomy. The purpose of this study is to evaluate high-resolution magnetic resonance imaging features of large intracranial arteries following mechanical thrombectomy. Methods Patients who presented with acute ischaemic stroke due to large vessel occlusion and underwent mechanical thrombectomy were prospectively recruited. Subjects underwent high-resolution magnetic resonance imaging within 24 hours of the procedure. Magnetic resonance imaging sequences included whole brain T1 pre and post-contrast black-blood imaging, three-dimensional T2, contrast-enhanced magnetic resonance angiography and susceptibility-weighted imaging. Arterial wall enhancement was objectively assessed after normalisation with the pituitary stalk. The contrast ratio of target vessels was compared with non-affected reference vessels. Results Twenty patients with 22 target vessels and 20 reference vessels were included in the study. Sixteen patients were treated with stentriever with or without aspiration, and four with contact aspiration only. Significantly higher arterial wall enhancement was identified on the target vessel when compared to the reference vessel (U = 22.5, P s = 0.098, P = 0.748). Conclusions This prospective pilot study used the objective quantification of arterial wall enhancement in determining arterial changes after mechanical thrombectomy. Preliminary data suggest that the use of stentrievers is associated with a higher enhancement as compared to reperfusion catheters.

Introduction: Hypertensive disorders of pregnancy (HDP) increase the risk of infant and maternal morbidity and mortality, disproportionately affecting racial and ethnic minority groups. Less is known about disparities in infant mortality by mother’s HDP status. We assessed the relationships between HDP and pre-pregnancy hypertension and other pregnancy and delivery characteristics with infant mortality. Methods: This retrospective cohort study included 667,359 live, singleton deliveries (mother’s race/ethnicity: non-Hispanic White [NHW; 56.5%], non-Hispanic Black [NHB; 32.2%)], Hispanic [9.0%], other race/ethnicity [2.2%]) in South Carolina (2004-2016) to women aged 12-49 years. HDP (pre-eclampsia, eclampsia, gestational hypertension) and pre-pregnancy hypertension were defined by hospitalization/emergency department (ED) visit data or birth certificates. Infant mortality within one year (n=2,431) was defined by death certificates. Logistic regression models controlled for covariates. Results: Deliveries to women with pre-pregnancy hypertension with superimposed HDP (2.1%), HDP (16.9%), pre-pregnancy hypertension without superimposed HDP (0.3%), and neither condition (80.6%) were described. Infant mortality was increased for women with HDP with and without pre-pregnancy hypertension. Also associated with higher odds of infant mortality were NHB mothers, with high school education or less, Medicaid, higher pre-pregnancy BMI, no prenatal care, increasing number of prior pregnancies, prior Cesarean section, prior preterm birth, and women smoking during pregnancy; with the odds lower for increasing maternal age, Hispanic mothers, and female sex of baby. Discussion: The odds of infant mortality were increased 48% in women with HDP and 83% in women with both HDP and pre-pregnancy hypertension than women with neither condition after adjusting for pregnancy and delivery characteristics. Future studies are needed to identify social or other factors contributing to differences.

The coronavirus disease 2019 pandemic has disrupted the lives of whole communities and nations. The multinational multicenter National Institute of Neurological Disorders and Stroke Carotid Revascularization and Medical Management for Asymptomatic Carotid Stenosis Trial stroke prevention trial rapidly experienced the effects of the pandemic and had to temporarily suspend new enrollments and shift patient follow-up activities from in-person clinic visits to telephone contacts. There is an ethical obligation to the patients to protect their health while taking every feasible step to ensure that the goals of the trial are successfully met. Here, we describe the effects of the pandemic on the trial and steps that are being taken to mitigate the effects of the pandemic so that trial objectives can be met.

Background and Purpose: Pattern of infarct due to ICAS (e.g. borderzone) may predict recurrent stroke risk. We sought to describe the patterns of index and recurrent infarcts in patients enrolled in the medical arm of the SAMMPRIS Trial (Stenting and Aggressive Medical Management for Preventing Recurrent Stroke in Intracranial Stenosis). Methods: - Patients enrolled in the medical management arm of the SAMMPRIS trial with infarct as the qualifying event who had CT or MRI, or those with a recurrent infarct in the territory of the symptomatic artery during follow up were included. Infarct pattern for both the index infarct and any recurrent infarct in the territory was determined using criteria defined in prior SAMMPRIS publications as borderzone, MCA artery core, and perforator for anterior circulation and cerebellar, perforator and distal for posterior circulation (see figure for examples). Infarct pattern was adjudicated independently by 2 reviewers, with a 3 rd reviewer as tiebreaker. Results: - Among the 142 patients who had index infarcts in the anterior circulation (n=101) and posterior (n=41) circulation, the patterns were: 53 (37.3%) borderzone, 24 (16.9%) MCA core, 35 (24.6%) perforator, 13 (9.2%) distal, and 17 (12%) cerebellar. Among the 31 who had recurrent infarct in the territory, the patterns were: 10 (32.3%) borderzone, 6 (19.4%) MCA core, 6 (19.4%) perforator, 4 (12.9%) distal, 1 (3.2%) cerebellar, and 4 (12.9%) were missing imaging. Of the recurrent infarcts in territory, 21 had both index infarct and recurrent infarct in territory adjudications, with 11 demonstrating the same pattern of infarct for both events (7 borderzone, 2 core, 2 perforator). Conclusions: - The majority of patients with stroke due to severe symptomatic intracranial stenosis demonstrated borderzone pattern of infarct for index and recurrent infarcts. Ongoing analyses of this dataset will determine the association between pattern of index stroke and risk of recurrent stroke.

BackgroundWhite matter hyperintensity (WMH) on brain MRI is associated with developing dementia or mild cognitive impairment (MCI), but WMH progression over time has not been fully investigated as an independent risk factor.MethodsWe performed a post hoc analysis of the Systolic Blood Pressure Intervention Trial - Memory and Cognition in Decreased Hypertension (SPRINT MIND) trial. The primary outcome was incident probable dementia or MCI (dementia/MCI) before the follow-up MRI at 48 months from enrolment. The primary predictor was WMH progression, defined as the Z score difference between the follow-up and baseline WMH volumes. The secondary predictor was a binary WMH progression threshold (≥1.4 mL vs ResultsAmong the 433 included patients, 33 (7.6%) developed dementia/MCI. There were 156 (36.0%) patients who met the WMH progression threshold of ≥1.4 mL, in whom the rate of dementia/MCI was 12.8% (20/156) vs 4.7% (13/277) of patients with ConclusionsIn this post hoc analysis of SPRINT MIND, WMH progression over 48 months was associated with the development of probable dementia or MCI.

Cilostazol is a PDE3 (phosphodiesterase III) inhibitor with a long track record of safety that is Food and Drug Administration and European Medicines Agency approved for the treatment of claudication in patients with peripheral arterial disease. In addition, cilostazol has been approved for secondary stroke prevention in several Asian countries based on trials that have demonstrated a reduction in stroke recurrence among patients with noncardioembolic stroke. The onset of benefit appears after 60 to 90 days of treatment, which is consistent with cilostazol’s pleiotropic effects on platelet aggregation, vascular remodeling, blood flow, and plasma lipids. Cilostazol appears safe and does not increase the risk of major bleeding when given alone or in combination with aspirin or clopidogrel. Adverse effects such as headache, gastrointestinal symptoms, and palpitations, however, contributed to a 6% increase in drug discontinuation among patients randomized to cilostazol in a large secondary stroke prevention trial ( CSPS.com [Cilostazol Stroke Prevention Study for Antiplatelet Combination]). Due to limitations of prior trials, such as open-label design, premature trial termination, large loss to follow-up, lack of functional or cognitive outcome data, and exclusive enrollment in Asia, the existing trials have not led to a change in clinical practice or guidelines in Western countries. These limitations could be addressed by a double-blind placebo-controlled randomized trial conducted in a broader population. If positive, it would increase the evidence in support of long-term treatment with cilostazol for secondary prevention in the millions of patients worldwide who have experienced a noncardioembolic ischemic stroke.

Background and ObjectivesTo review treatments for reducing the risk of recurrent stroke or death in patients with symptomatic intracranial atherosclerotic arterial stenosis (sICAS).MethodsThe development of this practice advisory followed the process outlined in the American Academy of Neurology Clinical Practice Guideline Process Manual, 2011 Edition, as amended. The systematic review included studies through November 2020. Recommendations were based on evidence, related evidence, principles of care, and inferences.Major RecommendationsClinicians should recommend aspirin 325 mg/d for long-term prevention of stroke and death and should recommend adding clopidogrel 75 mg/d to aspirin for up to 90 days to further reduce stroke risk in patients with severe (70%–99%) sICAS who have low risk of hemorrhagic transformation. Clinicians should recommend high-intensity statin therapy to achieve a goal low-density lipoprotein cholesterol level

Intracranial atherosclerotic stenosis (ICAS) is one of the most frequent causes of stroke worldwide and confers one of the greatest risks of recurrent stroke compared with other causes of stroke. Asymptomatic ICAS is increasingly recognised as a risk factor for silent brain infarctions and dementia, magnifying the global burden of ICAS. Although ICAS is a lumen-based diagnosis, newer diagnostic imaging techniques, such as high-resolution MRI, might help to identify high-risk population subgroups to test interventions that might reduce the risk of stroke recurrence. Secondary stroke prevention in patients with ICAS currently consists of intensive management of modifiable risk factors and dual antiplatelet therapy, which is subsequently reduced to aspirin alone. Despite these therapies, the risk of recurrent stroke in patients presenting with stroke related to 70-99% ICAS exceeds 20% at 1 year; as such, better therapies are urgently needed. The optimal duration and combination of dual antiplatelet therapy in patients with ICAS is uncertain and is being investigated in addition to low-dose anticoagulation and aspirin. Other ongoing or planned studies will provide high-quality observational data on the role of transluminal angioplasty and stenting, submaximal balloon angioplasty alone, direct or indirect arterial bypass, and ischaemic conditioning for prevention of stroke in patients with ICAS.

Background Symptomatic intracranial atherosclerotic disease (ICAD) is an important cause of stroke. Although the high periprocedural risk of intracranial stenting from recent randomized studies has dampened enthusiasm for such interventions, submaximal angioplasty without stenting may represent a safer endovascular treatment option. Objective To examine the periprocedural and long-term risks associated with submaximal angioplasty for ICAD based on the available literature. Methods All English language studies of intracranial angioplasty for ICAD were screened. Inclusion criteria were as follows: ≥ 5 patients, intervention with submaximal angioplasty alone, and identifiable periprocedural (30-d) outcomes. Analysis was co-nducted to identify the following: 1) periprocedural risk of any stroke (ischemic or hemorrh-agic) or death, and 2) stroke in the territory of the target vessel and fatal stroke beyond 30 d. Mixed effects logistic regression was used to summarize event rates. Funnel plot and rank correlation tests were employed to detect publication bias. The relative risk of periprocedural events from anterior vs posterior circulation disease intervention was also examined. Results A total of 9 studies with 408 interventions in 395 patients met inclusion criteria. Six of these studies included 113 posterior circulation interventions. The estimated pooled rate for 30-d stroke or death following submaximal angioplasty was 4.9% (95% CI: 3.2%-7.5%), whereas the estimated pooled rate beyond 30 d was 3.7% (95% CI: 2.2%-6.0%). There was no statistical difference in estimated pooled rate for 30-d stroke or death between patients with anterior (4.8%, 95% CI: 2.8%-7.9%) vs posterior (5.3%, 95% CI: 2.4%-11.3%) circulation disease (P > .99). Conclusion Submaximal angioplasty represents a potentially promising intervention for symptomatic ICAD.

Introduction: Hypertensive disorders of pregnancy (HDP) and pre-pregnancy hypertension are associated with increased maternal morbidity and mortality, and information on racial/ethnic disparities is lacking. The association of HDP and pre-pregnancy hypertension with incident maternal embolism was examined within five years of delivery and for the study period (≤14 years) overall and by race/ethnicity. Methods: Women with a live, singleton birth in South Carolina (2004-2016) aged 12-49 years were included in a retrospective cohort study (n=433,625; non-Hispanic white [NHW; 58.7%], non-Hispanic black [NHB; 31.8%)] and Hispanic [9.5%]). HDP were defined by hospitalization/emergency department (ED) visit data (pre-eclampsia, eclampsia, gestational hypertension) or birth certificates (gestational hypertension). Pre-pregnancy hypertension was also defined by these data sources. Hospitalization/ED visit data and death certificates defined fatal and non-fatal incident embolism. Cox proportional hazards models were used with covariate adjustment. Results: In women with ≥1 pregnancy, 81.6% never experienced pre-pregnancy hypertension or HDP, 0.4% had pre-pregnancy hypertension without superimposed HDP, 15.7% had HDP alone, and 2.3% had pre-pregnancy hypertension with superimposed HDP. Incident embolism risk was elevated ≤14 years after delivery for women with HDP alone (HR=1.21, 95% CI: 1.12-1.30) and with pre-pregnancy hypertension with superimposed HDP (HR=1.44, 95% CI: 1.26-1.65) compared to neither condition. Pre-pregnancy hypertension alone was not associated with incident embolism risk (HR=1.23, 95% CI: 0.84-1.80). The table shows the joint impact of racial/ethnicity and the exposure categories. Discussion: Fatal and non-fatal embolism up to 14 years after delivery was increased for HDP regardless of pre-pregnancy hypertension suggesting a long-term impact. Incident embolism event rates were highest for NHB women and lowest for Hispanic women across all HDP exposure categories.

Background Pre‐pregnancy hypertension and hypertensive disorders of pregnancy (HDP; preeclampsia, eclampsia, gestational hypertension) are major health risks for maternal morbidity and mortality. However, it is unknown if racial/ethnic differences exist. We aimed to determine the impact of HDP and pre‐pregnancy hypertension on maternal coronary heart disease, stroke, and mortality risk ≤1, 3, and 5 years post‐delivery and by race/ethnicity ≤5 years. Methods and Results This retrospective cohort study included women aged 12 to 49 years with a live, singleton birth between 2004 to 2016 (n=254 491 non‐Hispanic White; n=137 784 non‐Hispanic Black; n=41 155 Hispanic). Birth and death certificates and International Classification of Diseases, Ninth and Tenth Revision, Clinical Modification ( ICD‐9‐CM and ICD‐10‐CM ) diagnosis codes in hospitalization/emergency department visit data defined HDP, pre‐pregnancy hypertension, incident coronary heart disease and stroke, and all‐cause mortality. During at least 1 pregnancy of the 433 430 women, 2.3% had pre‐pregnancy hypertension with superimposed HDP, 15.7% had no pre‐pregnancy hypertension with HDP, and 0.4% had pre‐pregnancy hypertension without superimposed HDP, whereas 81.6% had neither condition. Maternal deaths from coronary heart disease, stroke, and all causes totaled 2136. Within 5 years of delivery, pre‐pregnancy hypertension, and HDP were associated with all‐cause mortality (hazard ratio [HR], 2.21; 95% CI, 1.61–3.03), incident coronary heart disease (HR, 3.79; 95% CI, 3.09–4.65), and incident stroke (HR, 3.10; 95% CI, 2.09–4.60). HDP alone was related to all outcomes. Race/ethnic differences were observed for non‐Hispanic Black and non‐Hispanic White women, respectively, in the associations of pre‐pregnancy hypertension and HDP with all‐cause mortality within 5 years of delivery (HR, 2.34 [95% CI, 1.58–3.47]; HR, 2.11 [95% CI, 1.23–3.65]; P interaction=0.001). Conclusions Maternal cardiovascular outcomes including mortality were increased ≤5 years post‐delivery in HDP, pre‐pregnancy hypertension, or pre‐pregnancy hypertension with superimposed HDP. The race/ethnic interaction for all‐cause mortality ≤5 years of delivery warrants further research.

BACKGROUND This article will serve as a comprehensive review of secondary prevention of ischemic stroke and central and branch retinal artery ischemia, which are closely linked pathologically and can be managed similarly to prevent further reoccurrence. EVIDENCE ACQUISITION We conducted a search in PubMed with a focus on reports involving secondary stroke prevention. RESULTS This review discusses the etiologies of stroke and addresses the evidence for optimal therapies for secondary stroke prevention. We review recent clinical trials that will serve as an aid to the neuro-ophthalmologist in practice to determine the best next step in management and when to consider further referral to a stroke specialist. CONCLUSIONS The optimal treatment to prevent stroke recurrence is determined by the etiology of stroke. After stroke workup, patients will typically be placed on proper medical therapy for the appropriate duration in addition to counseling on lifestyle modifications to reduce the risk of recurrent strokes. For complex patients, it is reasonable for providers to consider patient referral to stroke specialists for further aid in selection of appropriate medical therapy.

Background and Purpose: The CREST2 trial (Carotid Revascularization and Medical Management for Asymptomatic Carotid Stenosis) is comparing intensive medical management (IMM) alone to IMM plus revascularization with carotid endarterectomy or transfemoral carotid artery stenting for preventing stroke or death within 44 days after randomization or ipsilateral ischemic stroke thereafter. There are extensive clinical trial data on outcomes after revascularization of asymptomatic carotid stenosis, but not for IMM. As such, the experimental treatment in CREST2 is IMM, which is described in this article. Methods: IMM consists of aspirin 325 mg/day and intensive risk factor management, primarily targeting systolic blood pressure Results: The mean baseline LDL of 80.5 mg/dL improved to 66.7 mg/dL. The mean baseline systolic blood pressure of 139.7 mm Hg improved to 130.3 mm Hg. The proportion of patients in-target improved from 43% to 61% for systolic blood pressure P Conclusions: The rigorous multimodal approach to intensive stroke risk factor management in CREST2 has resulted in significant improvements in risk factor control that will enable a comparison of cutting-edge medical care to revascularization in patients with asymptomatic carotid stenosis. Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT02089217.

Introduction The COVID-19 pandemic has presented challenges to managing vascular risk factors with in-person follow-up of patients with asymptomatic carotid stenosis enrolled in the CREST2 trial. CREST2 is comparing intensive medical management alone versus intensive medical management plus revascularization with endarterectomy or stenting. We performed a study to evaluate the feasibility of a home-based program for testing blood pressure (BP) and low-density lipoprotein (LDL) in CREST2. Methods This study involved 45 patients at 10 sites in the CREST2 trial. The initial patients were identified by the Medical Management Core (MMC) as high-risk patients defined by stage 2 hypertension, LDL > 90 mg/dl, or both. If a patient at the site declined participation, another was substituted. All patients who agreed to participate were sent a BP monitoring device and a commercially available at-home lipid test kit that uses a self-performed finger-stick blood sample that was resulted to the patient. Training on the use of the equipment and obtaining the risk factor results was done by the study coordinator by telephone. Results Ten of the 130 currently active CREST2 sites participated, 8 in the LDL portion and 5 in the BP portion (3 sites did both). Twenty-six BP devices and 23 lipid tests were sent to patients. Of the 26 patients who obtained BP readings with the devices, 9 were out of the study target and adjustments in BP medications were made in 3. Of the 23 patients sent LDL tests, 13 were able to perform the test showing 7 were out of target, leading to adjustments in lipid medications in 4. Conclusion This study established the feasibility of at-home monitoring of BP and LDL in a clinical trial and identified implementation challenges prior to widespread use in the trial. (ClinicalTrials.gov number NCT02089217)

Background The safety and efficacy of dual antiplatelet use for symptomatic intracranial atherosclerosis beyond 90 days is unknown. Data from SAMMPRIS was used to determine if dual antiplatelet therapy (DAPT) beyond 90 days impacted the risk of ischemic stroke and hemorrhage. Methods This post hoc exploratory analysis from SAMMPRIS included patients who did not have a primary endpoint within 90 days after enrollment (n = 397). Patients in both the aggressive medical management (AMM) and percutaneous transluminal angioplasty and stenting (PTAS) arms were included. Baseline features and outcomes during follow-up were compared between patients who remained on DAPT beyond 90 days (on clopidogrel) and patients who discontinued clopidogrel and remained on aspirin alone at 90 days (off clopidogrel) using Fisher's exact tests. Results The stroke rate was numerically lower in the group on clopidogrel vs off clopidogrel among both the AMM alone arm (6.0% versus 10.8%, p = 0.31) and the PTAS arm (8.7% versus 9.8%; p = 0.82), but the difference was not significant. The major hemorrhage rates were numerically higher in the group on clopidogrel vs. off clopidogrel group among both the AMM alone arm (4.0% versus 2.5%; p = 0.67) and the PTAS arm (10.9% versus 3.5%; p = 0.08), but were not significant. Conclusion This exploratory analysis suggests that prolonged DAPT use may lower the risk of stroke in medically treated patients with intracranial stenosis but may increase the risk of major hemorrhage.

Background Atherosclerotic vertebrobasilar disease is a significant etiology of posterior circulation stroke. The prospective observational VER i TAS (Vertebrobasilar Flow Evaluation and Risk of Transient Ischemic Attack and Stroke) study demonstrated that distal hemodynamic status is a robust predictor of subsequent vertebrobasilar stroke risk. We sought to compare predictive models using thresholds for posterior circulation vessel flows standardized to age and vascular anatomy to optimize risk prediction. Methods and Results VER i TAS enrolled patients with recent vertebrobasilar transient ischemic attack or stroke and ≥50% atherosclerotic stenosis/occlusion in vertebral and/or basilar arteries. Quantitative magnetic resonance angiography measured large‐vessel vertebrobasilar territory flow, and patients were designated as low or normal flow based on a prespecified empiric algorithm considering distal territory regional flow and collateral capacity. For the present study, post hoc analysis was performed to generate additional predictive models using age‐specific normalized flow measurements. Sensitivity, specificity, and time‐to‐event analyses were compared between the algorithms. The original prespecified algorithm had 50% sensitivity and 79% specificity for future stroke risk prediction; using a predictive model based on age‐normalized flows in the basilar and posterior cerebral arteries, standardized to vascular anatomy, optimized flow status thresholds were identified. The optimized algorithm maintained sensitivity and increased specificity to 84%, while demonstrating a larger and more significant hazard ratio for stroke on time‐to‐event analysis. Conclusions These results indicate that flow remains a strong predictor of stroke across different predictive models, and suggest that prediction of future stroke risk can be optimized by use of vascular anatomy and age‐specific normalized flows.

Introduction: Hypertensive disorders of pregnancy (HDP) and pre-pregnancy hypertension are associated with increased morbidity and mortality for the mother, with potential long-term implications. We investigated the relationships between HDP and pre-pregnancy hypertension with fatal and nonfatal incident maternal heart failure (HF) within five years of delivery, and examined racial/ethnic differences. Methods: A retrospective population-based study was conducted among 433,636 women aged 13-49 (58.7% non-Hispanic white [NHW], 31.8% non-Hispanic black [NHB], 9.5% Hispanic) with a live, singleton birth in South Carolina between 2004-2016. HDP were defined as pre-eclampsia, eclampsia, or gestational hypertension based on hospitalization/emergency department (ED) visit data, or HDP on birth certificates. Pre-pregnancy hypertension was based on hospitalization/ED visit data or birth certificates. Incident HF was defined by hospital/ED visit and death certificate data. Cox proportional hazards models adjusted for sociodemographic, behavioral, and clinical characteristics. Results: Eighteen percent of women were diagnosed with HDP in ≥1 pregnancy (n=78,317; 53.5% NHW, 40.8% NHB, 5.7% Hispanic). Of the 433,636 women, 2.3% had pre-pregnancy hypertension with superimposed HDP, 15.7% had no pre-pregnancy hypertension with HDP, 0.4% had pre-pregnancy hypertension without superimposed HDP and 81.6% had neither condition. Compared to those without pre-pregnancy hypertension or HDP, incident HF risk was increased for women with: no pre-pregnancy hypertension with HDP (HR=4.35; 95% CI: 4.01-4.71), pre-pregnancy hypertension without superimposed HDP (HR=5.07; 95% CI: 3.52-7.29), and pre-pregnancy hypertension with superimposed HDP (HR=6.66; 95% CI: 5.91-7.51). The table shows race/ethnic specific estimates of incident HF risk. Discussion: Women with HDP and pre-pregnancy hypertension were at higher risk for HF or HF death within five years of delivery and the risk varied across racial/ethnic groups.

Introduction: While retrospective studies have shown that poor control of vascular risk factors is associated with progression of white matter hyperintensity (WMH), it has not been studied prospectively. Hypothesis: We hypothesize that higher systolic blood pressure (SBP) mean, LDL cholesterol, and Hgb A1c will be correlated with WMH progression in diabetics. Methods: This is a secondary analysis of the Memory in Diabetes (MIND) substudy of the Action to Control Cardiovascular Risk in Diabetes Follow-on Study (ACCORDION). The primary outcome was WMH progression, evaluated by fitting linear regression models to the WMH volume on the month 80 MRI and adjusting for the WMH volume on the baseline MRI. The primary predictors were the mean values of SBP, LDL, and A1c from baseline to month 80. We defined a good vascular risk factor profile as mean SBP and mean LDL Results: We included 292 patients, with a mean (SD) age of 62.6 (5.3) years and 55.8% male. The mean number of SBP, LDL, and A1c measurements per patient was 17, 5, and 12. We identified 86 (29.4%) patients with good vascular risk factor profile. In the linear regression models, mean SBP and LDL were associated with WMH progression and in a second fully adjusted model they both remained associated with WMH progression (Table). Those with a good vascular risk factor profile had less WMH progression (β Coefficient -0.80, 95% CI -1.42, -0.18, p=0.012). Conclusions: Our data reinforce prior research showing that higher SBP and LDL is associated with progression of WMH in diabetics, likely secondary to chronic microvascular ischemia, and suggest that control of these factors may have protective effects. This study has unique strengths, including prospective serial measurement of the exposures, validated algorithmic measurement methodology for WMH, and rigorous adjudication of study data. Clinical trials are needed to investigate the effect of vascular risk factor reduction on WMH progression.

Background: The Systolic Blood Pressure Intervention Trial (SPRINT) randomized patients to a goal SBP Methods: The primary outcome was a composite of stroke, MI, ACS, decompensated CHF, or CVD death. The secondary outcome was stroke. The WMHv was divided into quartiles. We fit Cox models to the outcomes and report adjusted hazard ratios for the quartiles of WMHv, and stratified by SPRINT treatment arm. Results: Among 719 included patients, the mean WMHv in the quartiles was 0.34, 1.09, 2.61, and 10.8 mL. The primary outcome occurred in 51/719 (7.1%) and the secondary outcome in 10/719 (1.4%). The WMHv was associated with both outcomes (Table 1, Figure 1). After stratifying by treatment arm, we found the association persisted in the standard, but not intensive, treatment arm (Table 2). However, the interaction term between WMHv and treatment arm was not significant. Conclusions: We observed that degree of WMH was associated with CVD and stroke risk in SPRINT MIND. The risk may be attenuated in patients randomized to intensive BP lowering. Trials are needed to determine if intensive BP lowering can prospectively reduce the high cardiovascular risk in patients with WMH.

Introduction: Retrospective and epidemiological studies have shown that white matter hyperintensity (WMH) is associated with vascular dementia, but WMH progression on serial MRIs has not been examined in a prospective study of diabetic patients, who have a higher risk of the adverse outcomes associated with WMH including dementia. Methods: This is a secondary analysis of the Memory in Diabetes (MIND) substudy of the Action to Control Cardiovascular Risk in Diabetes Follow-on Study (ACCORDION). The primary outcome was 4 cognitive tests measured at a baseline visit and month 80 follow-up visit, including Rey’s Auditory Verbal Learning Test (RAVLT), Mini Mental Status Examination (MMSE), Stroop test, and Digit Symbol Coding (DSC). The primary predictor was WMH progression, represented as the WMH volume on the month 80 MRI with the baseline WMH volume included in the model. We predicted change in the cognitive scores by modelling their association with WMH progression. Results: We included 262 patients, with a mean (SD) baseline age of 62.7 (5.3) years and 56.1% male. The mean (SD) WMH volume on the baseline and month 80 MRIs was 1.9 (3.0) and 4.3 (6.0) mL, respectively. The change in WMH was significantly associated with the change in RAVLT score in the linear regression model (β Coef -0.132, p=0.029). (Table). The mean (SD) RAVLT at baseline and month 80 was 8.0 (2.4) and 8.5 (2.8). Conclusions: WMH progression in diabetic patients is associated with worse performance on memory testing over an 80 month period. Though preliminary and not able to account for location of WMH, our results are consistent with the hypothesis that WMH progression is harmful to cognition in diabetics. The SPRINT MIND trial recently reported that intensive blood pressure control attenuates WMH progression and development of mild cognitive impairment, but excluded patients with diabetes. Against this backdrop, our data suggest that diabetics should be included in future trials to reduce WMH progression.

Background: Presence of atherosclerotic disease in more than one vascular bed (polyvascular disease) is associated with an increased risk of long-term vascular events. In the setting of asymptomatic carotid stenosis, the predictors of disease in other vascular beds is not well delineated. Objective: To identify the frequency and predictors of disease in other vascular beds the CREST 2 randomized trial population with hemodynamically significant stenosis. Methods: Recorded baseline characteristics among CREST 2 participants included: demographics, past medical history, lifestyle factors, and laboratory studies. Each variable was tested against three potential definitions of disease in other beds (cardiac, peripheral arterial disease (PAD) or disease in cardiac + PAD). Statistical analysis was done with Chi square and t tests as appropriate. Results: Data from 1447 patients were available for analysis. In these subjects with carotid disease, 51% also had cardiac disease, 24% also had PAD, and 16% had disease in in both cardiac and PAD. There was no relationship between age or race and presence of disease in other beds. Those with cardiac disease were more likely to be male. Diabetes, hypertension, hypercholesterolemia, and former history of smoking were all more common in those with either cardiac and PAD (TABLE). Elevated triglyceride and low HDL levels were also associated with all three definitions of disease in other beds. Those with either PAD or cardiac + PAD were more likely to be current smokers. Conclusions: Among CREST 2 participants, several medical conditions and lifestyle factors were associated with an increased frequency of disease in other vascular beds. Smoking, in particular, appears to be more common in those with PAD. Future analyses will address whether those with disease in other beds have higher rates of stroke or death.

Introduction: Studies have shown that the volume of white matter hyperintensity (WMH) is a risk factor for stroke, but there are scarce data exploring the relationship between WMH progression on serial MRIs and subsequent risk of stroke. Hypothesis: We hypothesize that WMH progression in the ACCORD trial increases the risk of subsequent incident stroke. Methods: The exposure period was from baseline to month 40, during which an MRI was performed at both baseline and month 40. The primary outcome was incident ischemic stroke after the month 40 MRI until study completion. We fit Cox models to the primary outcome and included both the baseline and month 40 WMH volume as covariates, with the hazard ratio for the month 40 WMH volume of primary interest because it represents WMH progression in this model. Results: We included 497 patients, of whom 53.3% were male and the mean (SD) age was 62.7 (5.7) years at enrollment. Mean (SD) follow-up after the month 40 MRI was 5.2 (1.8) years. Incident stroke occurred in 17 (3.4%) patients, in whom 2 were recurrent strokes and 15 were first-ever strokes. WMH progression was associated with subsequent stroke in the Cox model (HR 1.27, 95% CI 1.03-1.57, p=0.024) and remained significant after adjusting for patient age, history of prior stroke, and cigarette smoking (HR 1.33, 95% CI 1.07-1.65, p=0.010). Conclusions: Although this preliminary analysis is underpowered, WMH progression, independent of absolute WMH burden, may be a risk factor for future stroke in diabetic patients. This novel finding could have translational implications - specifically that interventions which reduce the progression of WMH could, in turn, reduce future risk of stroke.

BACKGROUND: Previous studies have reported that different locations of intracranial atherosclerosis (ICAS) are associated with different demographic features and vascular risk factors. We aimed to examine this observation in the Stenting and Aggressive Medical Management for Preventing Recurrent stroke in Intracranial Stenosis (SAMMPRIS) trial population. METHODS: SAMMPRIS was a randomized controlled trial that enrolled 451 patients with recent transient ischemic attack or stroke-related due to severe (70-99%) stenosis of a major intracranial artery. We compared the baseline demographic features and vascular risk factors between the symptomatic artery locations. Wilcoxon test was used to compare continuous variables, and chi-square test was used for categorical variables. RESULTS: Of 449 patients included in the analysis; 289 (64.4%) had ICAS in the anterior circulation and 160 (35.6%) in the posterior circulation. Features that were significantly different between patients with anterior versus posterior ICAS were: median age (58.3 years vs. 64.0 years, P

Background Lifestyle modification programs have improved the achievement of risk factor targets in a variety of clinical settings, including patients who have previously suffered a stroke or transient ischemic attack and those with multiple risk factors. Stenting Aggressive Medical Management for Prevention of Recurrent Stroke in Intracranial Stenosis (SAMMPRIS) was the first vascular disease prevention trial to provide a commercially available lifestyle modification program to enhance risk factor control. We sought to determine the relationship between compliance with this program and risk factor control in SAMMPRIS. Methods SAMMPRIS aggressive medical management included a telephonic lifestyle modification program provided free of charge to all subjects (n = 451) during their participation in the study. Subjects with fewer than 3 expected lifestyle-coaching calls were excluded from these analyses. Compliant subjects (n = 201) had greater than or equal to 78.5% of calls (median % of completed/expected calls). Noncompliant subjects (n = 200) had less than 78.5% of calls or refused to participate. Mean risk factor values or % in-target for each risk factor was compared between compliant versus noncompliant subjects, using t tests and chi-square tests. Risk factor changes from baseline to follow-up were compared between the groups to account for baseline differences. Results Compliant subjects had better risk factor control throughout follow-up for low-density lipoprotein, systolic blood pressure (SBP), hemoglobin A1c (HgA1c), non–high-density lipoprotein, nonsmoking, and exercise than noncompliant subjects, but there was no difference for body mass index. After adjusting for baseline differences between the groups, compliant subjects had a greater change from baseline than noncompliant subjects for SBP did at 24 months and HgA1c at 6 months. Conclusion SAMMPRIS subjects who were compliant with the lifestyle modification program had better risk factor control during the study for almost all risk factors.

BACKGROUND: The Systolic Blood Pressure Intervention Trial (SPRINT) randomized patients to a goal systolic blood pressure (SBP)

Introduction Heparin-induced thrombocytopenia (HIT) is an immune-mediated complication of heparin exposure. A limited number of studies have reported cerebral venous sinus thrombosis (CVST) as the presenting thrombotic event induced by HIT, only one of which occurred with exposure to low-molecular-weight heparin (LMWH), with death as outcome. Here, we present a unique case of LMWH-induced HIT leading to CVST but resulting in good clinical outcome. Case report A 52-year-old woman received subcutaneous LMWH for deep vein thrombosis prophylaxis while in rehabilitation following kyphoplasty for spinal fracture related to recent trauma. On postoperative day 15, she developed acute onset altered mental status with significant agitation and nonsensical speech and was found to have brain imaging findings suggestive of CVST. Work-up revealed a drop in platelets associated with HIT, which did not improve off heparin products and with steroids, requiring intravenous immunoglobulin therapy, likely due to an overlapping immune thrombocytopenic purpura. Patient was managed on an argatroban drip until platelet count normalized and was able to transition to warfarin. Her clinical outcome was very favorable with near-normal neurological exam except for subtle cognitive changes. Conclusions This unique case of LMWH-induced HIT leading to CVST but resulting in good clinical outcome highlights the importance of linking CVST with HIT and of establishing the need for early alternative antithrombotic therapeutic strategies.

Background and Purpose— The purpose of this study was to investigate the frequency of symptomatic in-stent restenosis (ISR) and its contribution to nonprocedural symptomatic infarction in the SAMMPRIS trial (Stenting and Aggressive Medical Management for the Prevention of Recurrent Stroke in Intracranial Stenosis). Methods— Patients without a periprocedural primary end point were followed up to determine the occurrence of any of the following events: ischemic stroke, cerebral infarct with temporary signs, or transient ischemic attack in the territory of the stented artery. Vascular imaging performed after these events was reviewed for ISR. Annual rates for symptomatic ISR were calculated using Kaplan–Meier estimates. Results— Of 183 patients in the stenting group without a periprocedural primary end point, 27 (14.8%) had a symptomatic infarction (stroke or cerebral infarct with temporary signs) and 16 (8.7%) had transient ischemic attack alone in the territory during a median follow-up of 35.0 months. Of the 27 patients with infarctions, 17 (9.3%) had an ischemic stroke and 10 (5.5%) had a cerebral infarct with temporary signs alone. Adequate vascular imaging to evaluate ISR was available in 24 patients with infarctions (showing ISR in 16 [66.7%]) and in 10 patients with transient ischemic attack alone (showing ISR in 8 [80%]). The 1-, 2-, and 3-year rates (with 95% confidence limits) for symptomatic ISR in the SAMMPRIS stent cohort were 9.6% (6.1%–14.9%), 11.3% (7.5%–17.0%), and 14.0% (9.6%–20.2%), respectively. Conclusions— Symptomatic ISR occurred in at least 1 of 7 patients in SAMMPRIS by 3 years of follow-up and was likely responsible for the majority of nonprocedural cerebral infarctions. Clinical Trial Registration— URL: https://clinicaltrials.gov . Unique identifier: NCT00576693.

Background and purposeCurrently, there is neither a standard protocol for vessel wall MR imaging of intracranial atherosclerotic disease (ICAD) nor a gold standard phantom to compare MR sequences. In this study, a plaque phantom is developed and characterized that provides a platform for establishing a uniform imaging approach for ICAD.Materials and methodsA patient specific injection mold was 3D printed to construct a geometrically accurate ICAD phantom. Polyvinyl alcohol hydrogel was infused into the core shell mold to form the stenotic artery. The ICAD phantom incorporated materials mimicking a stenotic vessel and plaque components, including fibrous cap and lipid core. Two phantoms were scanned using high resolution cone beam CT and compared with four different 3 T MRI systems across eight different sites over a period of 18 months. Inter-phantom variability was assessed by lumen dimensions and contrast to noise ratio (CNR).ResultsQuantitative evaluation of the minimum lumen radius in the stenosis showed that the radius was on average 0.80 mm (95% CI 0.77 to 0.82 mm) in model 1 and 0.77 mm (95% CI 0.74 to 0.81 mm) in model 2. The highest CNRs were observed for comparisons between lipid and vessel wall. To evaluate manufacturing reproducibility, the CNR variability between the two models had an average absolute difference of 4.31 (95% CI 3.82 to 5.78). Variation in CNR between the images from the same scanner separated by 7 months was 2.5–6.2, showing reproducible phantom durability.ConclusionsA plaque phantom composed of a stenotic vessel wall and plaque components was successfully constructed for multicenter high resolution MRI standardization.

Background Oxidized low-density lipoprotein (OxLDL) is a contributor to atherosclerosis development. OxLDL formation increases in the postprandial state due to oxidative stress in subjects with coronary artery disease (CAD) and diabetes, but has not been studied in patients with atherosclerotic stroke. We aimed to determine differences in postprandial OxLDL in patients with atherosclerotic stroke compared to stroke from other causes. Methods Patients with ischemic stroke but no history of CAD (n = 42) were enrolled and categorized by stroke subtype as extracranial atherosclerosis (EC), n = 12; intracranial atherosclerosis (IC), n = 16; or other cause, n = 14. After fasting overnight, subjects consumed a standardized fat meal. OxLDL levels were measured at t = 0 and t = 4 hours postprandial using enzyme-linked immunosorbent assay. Comparisons between the mean changes in OxLDL between the groups were performed using the analysis of variance procedure. Results The IC group had the highest mean baseline level of OxLDL and the greatest decline during the postprandial period. There was a trend toward a difference in the mean change in OxLDL between the 3 groups (P = .0553). Subjects with atherosclerotic stroke (EC and IC groups) had higher fasting OxLDL and had a significant decline in OxLDL compared to those with stroke from other causes (P = .0164). Conclusions Subjects with stroke due to atherosclerosis, particularly intracranially, demonstrated high fasting OxLDL and a decline in OxLDL during the postprandial period. This decline in OxLDL may indicate an accelerated clearance of OxLDL resulting from meal-induced oxidative stress.

Despite concerns regarding hypoperfusion in patients with large-artery occlusive disease, strict blood pressure (BP) control has become adopted as a safe strategy for risk reduction of stroke. We examined the relationship between BP control, blood flow, and risk of subsequent stroke in the prospective Vertebrobasilar Flow Evaluation and Risk of Transient Ischemic Attack and Stroke (VERiTAS) study.The VERiTAS study enrolled patients with recent vertebrobasilar (VB) transient ischemic attack or stroke and ≥50% atherosclerotic stenosis or occlusion of vertebral or basilar arteries. Hemodynamic status was designated as low or normal based on quantitative magnetic resonance angiography. Patients underwent standard medical management and follow-up for primary outcome event of VB territory stroke. Mean BP during follow-up (140/90 versus ≥140/90 mm Hg) and flow status were examined relative to subsequent stroke risk using Cox proportional hazards analysis.The 72 subjects had an average of 3.8 ± 1.2 BP recordings over 20 ± 8 months of follow-up; 39 (54%) had mean BP of140/90 mm Hg. The BP groups were largely comparable for baseline demographics, risk factors, and stenosis severity. Comparing subgroups stratified by BP and hemodynamic status, we found that patients with both low flow and BP140/90 mm Hg (n = 10) had the highest risk of subsequent stroke, with hazard ratio of 4.5 (confidence interval 1.3-16.0, P = .02), compared with the other subgroups combined.Among a subgroup of patients with VB disease and low flow, strict BP control (BP140/90) may increase the risk of subsequent stroke.

An American Heart Association/American Stroke Association (AHA/ASA) writing committee has recently recommended that tissue evidence of cerebral infarction associated with temporary symptoms (CITS) lasting24 hours should be considered a stroke. We analyzed the impact of considering CITS as equivalent to stroke on the results of the Stenting and Aggressive Medical Management for Preventing Recurrent Stroke in Intracranial Stenosis (SAMMPRIS) trial.We compared outcomes in the medical (n = 227) and stenting (n = 224) groups in SAMMPRIS using the following primary end point (new components in bold): any stroke, CITS, or death within 30 days after enrollment or within 30 days after a revascularization procedure for the qualifying lesion during follow-up; or ischemic stroke or CITS in the territory of the qualifying artery beyond 30 days. We also compared the use of brain magnetic resonance imaging (MRI) after transient ischemic attacks (TIAs) in both treatment groups.By considering CITS as equivalent to stroke, the number of primary end points increased from 34 to 43 in the medical group and from 52 to 66 in the stenting group of SAMMPRIS. The Kaplan-Meier curves for the primary end points in the 2 groups were significantly different (P = .009). The percentage of patients with reported TIAs who underwent brain MRI was 69% in the medical group and 61% in the stenting group (P = .40).Using the AHA/ASA definition of stroke resulted in a substantially higher primary end point rate in both treatment groups and an even higher benefit from medical therapy over stenting than originally shown in SAMMPRIS. The higher rate of CITS in the stenting group was not due to ascertainment bias.

Transcatheter closure of patent foramen ovale (PFO) has been demonstrated in clinical trials and meta-analyses to reduce the risk of subsequent stroke in patients who present with cryptogenic strokes [(1)][1]. In the REDUCE trial, PFO closure with the septal occluders (W.L. Gore, Newark, Delaware)

Background: White matter hyperintensity (WMH) is a common manifestation of chronic ischemic microvascular disease that heralds greater risk of functional disability, stroke, and dementia. SPRINT MIND recently reported that intensive blood pressure reduction resulted in lower rates of mild cognitive impairment and WMH progression, suggesting that medical interventions could have a measurable impact on WMH. We conducted an anonymous survey of providers in the NINDS StrokeNet to better understand neurologist attitudes about asymptomatic WMH. Methods: We sent a 7-question survey to the 29 Regional Coordinating Centers of the StrokeNet, whose coordinators disseminated the survey to providers “involved in the care of a patient after their stroke.” Results: We received 136 responses. For stroke prevention therapies, including aspirin and statin therapy and blood pressure target, there was substantial equipoise, with no single option receiving >50% endorsement and between 15-32% of respondents choosing the option of “not sure.” 83% of respondents indicated high or moderate enthusiasm for a trial targeting this patient population. The clinical outcomes of reduction in ischemic stroke, cognitive impairment, or dementia were high importance (>70% endorsement), while the remaining radiographic, safety, and clinical endpoints all failed to reach 50% endorsement. Conclusions: Our survey establishes meaningful neurologist attitudes that can inform future WMH research. There is considerable equipoise regarding optimal medical treatment for patients with asymptomatic WMH and providers in StrokeNet, who would be a vital stakeholder in WMH research in the United States, enthusiastically support a clinical trial to resolve open questions on optimal medical management.

Background: The importance of physical activity in preventing major vascular events has received increased attention in the past decade. Due to the inclusion of the INTERVENT lifestyle modification program, the CREST2 trial provides a unique opportunity to study physical activity profiles in patients with severe asymptomatic extracranial carotid stenosis. Hypothesis: Based on data from a trial of intracranial stenosis patients, we aimed to evaluate the hypothesis that Methods: We analyzed 1087 CREST2 participants with baseline data on physical activity. The Physician-based Assessment and Counseling for Exercise (PACE) score is recorded for each patient and dichotomized as “in target” (4-8 points) or “out of target” ( Results: The mean age of the study population is 69.5±7.8 years (60% male). The median PACE score at baseline is 4.0 (mean 3.8±2.1; IQR 2 to 6). The Table shows baseline characteristics of patients by mean PACE score. Being male, not having diabetes mellitus, having a body mass index Conclusions: We have defined several patient groups with asymptomatic carotid stenosis that have suboptimal physical activity. These results provide opportunities for targeted efforts to improve primary stroke prevention. These baseline data will also allow investigators to determine if trial involvement and the INTERVENT program leads to improvement in the level of physical activity.

Background and Purpose— Although aggressive medical therapy was superior to stenting in the SAMMPRIS trial (Stenting and Aggressive Medical Management for Preventing Recurrent Stroke in Intracranial Stenosis), the stroke rate in the medical arm was still high. The aim of this study was to determine the association between hemodynamic markers (borderzone infarct pattern and impaired collateral flow on baseline imaging) and rates of recurrent stroke in patients treated medically in SAMMPRIS. Methods— This was a post hoc analysis of patients whose qualifying event for SAMMPRIS was an infarct in the territory of a stenotic middle cerebral artery or intracranial carotid artery. Infarcts were adjudicated as involving primarily internal or cortical borderzone territories, the core middle cerebral artery territory, or perforator territories, and collateral flow was assessed according to a standard scale (American Society of Interventional and Therapeutic Neuroradiology/Society of Interventional Radiology). Log-rank tests and χ 2 tests were performed to assess associations of infarct patterns and collateral flow with rates of recurrent stroke. Results— Of 101 patients who qualified, 14 of 53 (26.4%) with borderzone infarcts, 2 of 24 (8.3%) with core middle cerebral artery infarcts, and 3 of 24 (12.5%) with perforator infarcts had a recurrent stroke in the territory ( P =0.14 for comparing the 3 groups, P =0.052 for borderzone versus nonborderzone). Of 82 patients with collateral flow assessment, 30 of 43 (70%) with borderzone infarcts, 7 of 19 (37%) with core middle cerebral artery infarcts, and 11 of 20 (55%) with perforator infarcts had impaired collateral flow distal to the stenosis ( P =0.049). Patients with borderzone infarcts and impaired collateral flow had the highest risk of recurrent stroke (37%). Conclusions— Borderzone infarcts and impaired collateral flow identify a subgroup of patients with intracranial stenosis who are at particularly high risk of recurrent stroke on medical treatment. Clinical Trial Registration— URL: https://www.clinicaltrials.gov . Unique identifier: NCT00576693.

Author(s): Writing Group Members; Mozaffarian, Dariush; Benjamin, Emelia J; Go, Alan S; Arnett, Donna K; Blaha, Michael J; Cushman, Mary; Das, Sandeep R; de Ferranti, Sarah; Despres, Jean-Pierre; Fullerton, Heather J; Howard, Virginia J; Huffman, Mark D; Isasi, Carmen R; Jimenez, Monik C; Judd, Suzanne E; Kissela, Brett M; Lichtman, Judith H; Lisabeth, Lynda D; Liu, Simin; Mackey, Rachel H; Magid, David J; McGuire, Darren K; Mohler, Emile R; Moy, Claudia S; Muntner, Paul; Mussolino, Michael E; Nasir, Khurram; Neumar, Robert W; Nichol, Graham; Palaniappan, Latha; Pandey, Dilip K; Reeves, Mathew J; Rodriguez, Carlos J; Rosamond, Wayne; Sorlie, Paul D; Stein, Joel; Towfighi, Amytis; Turan, Tanya N; Virani, Salim S; Woo, Daniel; Yeh, Robert W; Turner, Melanie B; American Heart Association Statistics Committee; Stroke Statistics Subcommittee

Background: In CREST2, intensive medical management of subjects’ vascular risk factors is overseen by the site Principal Investigator (PI) and implemented by a designated Medical Management Physician (MMP) and coordinator. These physicians have different specialties and experience with risk factor management. We sought to determine the relationship between risk factor control and PI and MMP specialty. Methods: Data on 613 patients with at least 1 follow-up visit from 105 CREST2 sites were used for these analyses. CREST2 sites were categorized based on both PI specialty and MMP specialty. Specialty of the site-designated primary MMP was used for sites with more than one MMP. We compared the percentage of patients in target at last follow-up visit for the primary risk factors, LDL < 70 mg/dL and SBP Results: The table shows the number of patients by PI and MMP specialty, as well as their control of SBP and LDL. There were no significant differences in control of SBP or LDL by PI specialty. There was a trend toward an association between LDL control and MMP specialty, with higher rates of LDL control at sites with Internal Medicine MMP specialists and lower rates of control with Vascular Surgery MMPs. SBP control rates were not significantly different across MMP specialties. Conclusions: In this early analysis of risk factor control in the CREST2 study, site PI and MMP specialty did not have a significant effect on LDL and SBP during follow-up. This suggests that protocol care pathways are generalizable to diverse physicians.