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Background and Purpose: We investigated the prevalence, awareness, and control of vascular risk factors (VRFs) and the use of antithrombotic and statin agents in HCHS (Hispanic Community Health Study)/SOL (Study of Latinos) participants with self-reported history of stroke or transient ischemic attack. Methods: Sociodemographic characteristics, medications, and prevalence of different VRFs were recorded. VRF diagnoses and goals were based on the recommendations of professional organizations. Factors associated with optimal VRF control and use of antithrombotic and statin agents were investigated using multivariate logistic regression. Results: The analysis included 404 participants (39% men). The prevalences of hypertension, dyslipidemia, and diabetes were 59%, 65%, and 39%, respectively. Among those who met the diagnostic criteria for these diagnoses, the frequencies of awareness were 90%, 75%, and 83%, respectively. In participants who were aware of their VRFs, the prevalences of controlled hypertension, dyslipidemia, and diabetes were 46%, 32%, and 54%. Approximately 46% of the participants were on antithrombotics, 39% on statins, and 26% on both. Only 38% of those with atrial fibrillation received anticoagulation. In multivariate analyses adjusted for baseline sociodemographic characteristics, older age was associated with uncontrolled hypertension and diabetes. Residing in the United States for ≥10 years and born in the United States were associated with uncontrolled diabetes, female sex with uncontrolled dyslipidemia, and lack of health insurance with decreased use of statins and hyperlipidemia. Conclusions: Hispanic/Latino adults in the United States have high prevalence and awareness of VRFs but low adherence to secondary stroke prevention strategies. Older adults, women, and uninsured people are vulnerable groups that may benefit from targeted interventions. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02060344.

Hydrogenation of substituted styrenes and unactivated aliphatic alkenes by molecular hydrogen has been achieved using a Mn catalyst with a non‐pincer, picolylphosphine ligand. This is the second reported example of alkene hydrogenation catalyzed by a Mn complex. Mechanistic studies showed that a Mn hydride formed by H2 activation in the presence of a base is the catalytically active species. Based on experimental and DFT studies, H2 splitting is proposed to occur via a metal‐ligand cooperative pathway involving deprotonation of the CH2 arm of the ligand, leading to pyridine dearomatization.

Introduction: Prior evidence suggests that treatment outcomes after ischemic stroke differ based on racial background. For example, two studies that queried the National Inpatient Sample (NIS) found that White patients were more likely to be discharged home compared to non-White patients after treatment with mechanical thrombectomy or IV tPA. Although these database studies provide the advantage of substantial patient numbers, the NIS is an inpatient administrative dataset lacking stroke-specific outcomes such as modified Rankin Score (mRS) and follow-up data. Nevertheless, a relationship between race and clinical outcome after thrombectomy is suggested. Methods: We utilized the NeuroVascular Quality Initiative-Quality Outcomes Database (NVQI-QOD) to collect demographic data, clinical information, and outcome measures on ischemic stroke patients treated with mechanical thrombectomy. Univariate and multivariate analysis was conducted to evaluate the relationship between race and outcomes such as mRS at discharge (0-2 vs. 3-6), discharge disposition, and 90-day mRS (0-2 vs. 3-6). Race was included in multivariate modeling as it was our predictor variable of interest. P Results: A total of 3,597 patients were included. Of the entire cohort, 15.8% of patients were Black. On univariate analysis, Black race was significantly associated with younger age at treatment, CHF, hypertension, diabetes, prior stroke, being a current smoker, and higher baseline NIHSS (16.4 for Black compared to 15.8 for non-Black, p=0.044). Non-Black race was significantly associated with atrial fibrillation and hyperlipidemia at baseline. On both univariate and multivariate analysis, Black race was not significantly associated with discharge mRS, discharge to home, or 90-day mRS (p>0.3 for all). Conclusions: In conclusion, though Black race seems to be associated with several comorbidities prior to ischemic stroke, we did not find a significant association between Black race and clinical outcome after mechanical thrombectomy.

BACKGROUND Delayed cerebral vasospasm is a feared complication of aneurysmal subarachnoid hemorrhage (SAH). OBJECTIVE To investigate the relationship of systemic inflammation, measured using the systemic immune-inflammation (SII) index, with delayed angiographic or sonographic vasospasm. We hypothesize that early elevations in SII index serve as an independent predictor of vasospasm. METHODS We retrospectively reviewed the medical records of 289 SAH patients for angiographic or sonographic evidence of delayed cerebral vasospasm. SII index [(neutrophils × platelets/lymphocytes)/1000] was calculated from laboratory data at admission and dichotomized based on whether or not the patient developed vasospasm. Multivariable logistic regression and receiver operating characteristic (ROC) analysis were performed to determine the ability of SII index to predict the development of vasospasm. RESULTS A total of 246 patients were included in our study, of which 166 (67.5%) developed angiographic or sonographic evidence of cerebral vasospasm. Admission SII index was elevated for SAH in patients with vasospasm compared to those without (P

OBJECTIVE To assess depressive symptom outcomes in a pooled sample of epilepsy self-management randomized controlled trials (RCTs) from the Managing Epilepsy Well (MEW) Network integrated research database (MEW DB). METHODS Five prospective RCTs involving 453 adults with epilepsy compared self-management intervention (n = 232) versus treatment as usual or wait-list control outcomes (n = 221). Depression was assessed with the nine-item Patient Health Questionnaire. Other variables included age, gender, race, ethnicity, education, income, marital status, seizure frequency, and quality of life. Follow-up assessments were collapsed into a visit 2 and a visit 3; these were conducted postbaseline. RESULTS Mean age was 43.5 years (SD = 12.6), nearly two-thirds were women, and nearly one-third were African American. Baseline sample characteristics were mostly similar in the self-management intervention group versus controls. At follow-up, the self-management group had a significantly greater reduction in depression compared to controls at visit 2 (P

A mild and efficient nickel-catalyzed method for the chemo and regioselective coupling of unactivated alkyl chlorides with the C–H bond of indoles and pyrroles at 60 °C is described., A mild and efficient nickel-catalyzed method for the coupling of unactivated primary and secondary alkyl chlorides with the C–H bond of indoles and pyrroles is described which demonstrates a high level of chemo and regioselectivity. The reaction tolerates numerous functionalities, such as halide, alkenyl, alkynyl, ether, thioether, furanyl, pyrrolyl, indolyl and carbazolyl groups including acyclic and cyclic alkyls under the reaction conditions. Mechanistic investigation highlights that the alkylation proceeds through a single-electron transfer (SET) process with Ni(i)-species being the active catalyst. Overall, the alkylation follows a Ni(i)/Ni(iii) pathway involving the rate-influencing two-step single-electron oxidative addition of alkyl chlorides.

Background and Purpose: The role of regional hypoperfusion as a contributor to stroke risk in atherosclerotic vertebrobasilar disease has recently been confirmed by the observational VERiTAS (Vertebrobasilar Flow Evaluation and Risk of Transient Ischemic Attack and Stroke) Study. We examined the stability of hemodynamic status over time and its relationship to stroke risk in patients from this prospective cohort. Methods: VERiTAS enrolled patients with recently symptomatic ≥50% atherosclerotic stenosis/occlusion of vertebral and/or basilar arteries. Large vessel flow in the vertebrobasilar territory was assessed using quantitative magnetic resonance angiography, and patients were designated as low or normal flow based on distal territory regional flow, incorporating collateral capacity. Patients underwent standard medical management and follow-up for primary outcome event of vertebrobasilar territory stroke. Quantitative magnetic resonance angiography imaging was repeated at 6, 12, and 24 months. Flow status over time was examined relative to baseline and relative to subsequent stroke risk using a cause-specific proportional hazard model, with flow status treated as a time-varying covariate. Mean blood pressure was examined to assess for association with changes in flow status. Results: Over 19±8 months of follow-up, 132 follow-up quantitative magnetic resonance angiography studies were performed in 58 of the 72 enrolled patients. Of the 13 patients with serial imaging who had low flow at baseline, 7 (54%) had improvement to normal flow at the last follow-up. Of the 45 patients who had normal flow at baseline, 3 (7%) converted to low flow at the last follow-up. The mean blood pressure did not differ in patients with or without changes in flow status. The time-varying flow status remained a strong predictor of subsequent stroke (hazard ratio, 10.3 [95% CI, 2.2–48.7]). Conclusions: There is potential both for improvement and worsening of hemodynamics in patients with atherosclerotic vertebrobasilar disease. Flow status, both at baseline and over time, is a risk factor for subsequent stroke, thus serving as an important prognostic marker. Registration: URL: https://clinicaltrials.gov . Unique identifier: NCT00590980.

Purpose People with epilepsy (PWE) come from a wide variety of social backgrounds and educational skillsets, making self-management (SM) education for improving their condition challenging. Here, we evaluated whether a mobile technology-based personalized epilepsy SM education intervention, PAUSE to Learn Your Epilepsy (PAUSE), improves SM measures such as self-efficacy, epilepsy SM behaviors, epilepsy outcome expectations, quality of life (QOL), and personal impact of epilepsy in adults with epilepsy. Methods Recruitment for the PAUSE study occurred from October 2015 to March 2019. Ninety-one PWE were educated using an Internet-enabled computer tablet application that downloads custom, patient-specific educational programs from Epilepsy.com. Validated self-reported questionnaires were used for outcome measures. Participants were assessed at baseline (T0), the first follow-up at completion of the PWE-paced 8–12-week SM education intervention (T1), and the second follow-up at least 3 months after the first follow-up (T2). Multiple linear regression was used to assess within-subject significant changes in outcome measures between these time points. Results The study population was diverse and included individuals with a wide variety of SM educational needs and abilities. The median time for the first follow-up assessment (T1) was approximately 4 months following the baseline (T0) and 8 months following baseline for the second follow-up assessment (T2). Participants showed significant improvement in all SM behaviors, self-efficacy, outcome expectancy, QOL, and personal impact of epilepsy measures from T0 to T1. Participants who scored lower at baseline tended to show greater improvement at T1. Similarly, results showed that participant improvement was sustained in the majority of SM measures from T1 to T2. Conclusion This study demonstrated that a mobile technology-based personalized SM intervention is feasible to implement. The results provide evidence that epilepsy SM behavior and practices, QOL, outcome expectation for epilepsy treatment and management, self-efficacy, and outcome expectation and impact of epilepsy significantly improve following a personalized SM education intervention. This underscores a greater need for a pragmatic trial to test the effectiveness of personalized SM education, such as PAUSE to Learn Your Epilepsy, in broader settings specifically for the unique needs of the hard-to-reach and hard-to-treat population of PWE., Highlights • PAUSE is a personalized epilepsy self-management (SM) education program. • PAUSE was implemented in diverse and mostly underserved adults with epilepsy. • Self-efficacy, frequency of SM behaviors, and QOL significantly improved over time. • Personal negative impact of epilepsy significantly reduced over time. • Greater improvement was seen in those with lower scores at baseline.

Background and Purpose— The VERiTAS (Vertebrobasilar Flow Evaluation and Risk of Transient Ischemic Attack and Stroke) study demonstrated posterior circulation distal flow status, determined by quantitative magnetic resonance angiography, is a robust predictor of vertebrobasilar stroke risk in patients with symptomatic atherosclerotic vertebrobasilar disease. Flow-compromised high-risk patients may benefit from flow-restoring endovascular procedures, such as submaximal angioplasty. In this study, we examine the cost-effectiveness of quantitative magnetic resonance angiography screening to identify patients who may benefit from submaximal angioplasty to restore vertebrobasilar flow. Methods— A Markov model was created comparing a no screening strategy with standard medical management alone and a screening strategy involving quantitative magnetic resonance angiography imaging and submaximal angioplasty for treatable patients with low vertebrobasilar flow for a 30-year time horizon. Outcomes included quality-adjusted life years (QALY) and lifetime costs. Rates of stroke and death were obtained from VERiTAS data, and disability rates and costs were derived from VERiTAS and the literature. A sensitivity analysis was performed with periprocedural stroke rate from angioplasty the primary variable of interest. Results— At a 6% periprocedural stroke risk, the screening strategy saved an average of 0.364 QALYs per patient and a lifetime cost savings of $7312 versus the no screening strategy. Among patients with low flow suitable for intervention, the benefit was substantially higher, averaging 1.485 QALYs saved and lifetime cost savings of $21 294. Across the entire cohort, QALY savings were observed at the end of the first year and economic savings at year 6. The benefit of screening declined at higher periprocedural risk. Conclusions— Quantitative magnetic resonance angiography screening and submaximal angioplasty with 6% periprocedural risk in suitable patients are cost effective both in terms of QALY and lifetime costs for patients with symptomatic vertebrobasilar occlusive disease. With potential health and economic savings, a clinical trial examining the periprocedural risk of submaximal angioplasty is warranted. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00590980.

The quinolinyl-based pincer nickel complex, κN,κN,κN-{C9H6N-(μ-N)-C6H4–NMe2}NiCl [(QNNNMe2)NiCl; (1)] has recently been demonstrated to be an efficient and robust catalyst for the alkylation of azoles with alkyl halides under copper-free conditions. Herein, we report the detailed mechanistic investigation for the alkylation of azoles catalyzed by (QNNNMe2)NiCl (1), which highlights an iodine-atom transfer (IAT) mechanism for the reaction involving a NiII/NiIII process. Deuterium labeling experiments indicate reversible cleavage of the benzothiazole C–H bond, and kinetic studies underline a fractional negative rate order with the substrate benzothiazole. The involvement of an alkyl radical during the alkylation is validated by radical clock and external additive experiments. An active intermediate species (QNNNMe2)Ni(benzothiazolyl) (5a) has been isolated and structurally characterized. The complex (QNNNMe2)Ni(benzothiazolyl) (5a) is found to be the resting state of catalyst 1. Kinetic analysis of electron...

Background and Purpose— Cerebral hypoperfusion symptoms (defined as symptoms related to change in position, effort or exertion, or recent change in antihypertensive medication) have been used in stroke studies as a surrogate for detecting hemodynamic compromise. However, the validity of these symptoms in identifying flow compromise in patients has not been well established. We examined whether hypoperfusion symptoms correlated with quantitative measurements of flow compromise in the prospective, observational VERiTAS study (Vertebrobasilar Flow Evaluation and Risk of Transient Ischemic Attack and Stroke). Methods— VERiTAS enrolled patients with recent vertebrobasilar transient ischemic attack or stroke and ≥50% atherosclerotic stenosis or occlusion in vertebral or basilar arteries. Hemodynamic status using vertebrobasilar large vessel flow was measured using quantitative magnetic resonance angiography, and patients were designated as low, borderline, or normal flow based on distal territory regional flow, incorporating collateral capacity. The presence of qualifying event hypoperfusion symptoms was assessed relative to the quantitatively determined flow status (normal versus borderline/low) and also examined as a predictor of subsequent stroke risk. Results— Of the 72 enrolled subjects, 66 had data on hypoperfusion symptoms available. On initial quantitative magnetic resonance angiography designation, 43 subjects were designated as normal flow versus 23 subjects designated as low flow (n=16) or borderline flow (n=7). Of these, 5 (11.6%) normal flow and 3 (13.0%) low/borderline flow subjects reported at least one qualifying event hypoperfusion symptom ( P =0.99, Fisher exact test). Hypoperfusion symptoms had a positive predictive value of 37.5% and negative predictive value of 65.5% for low/borderline flow status. Compared with flow status, which strongly predicted subsequent stroke risk, hypoperfusion symptoms were not associated with stroke outcome ( P =0.87, log-rank test). Conclusions— These results suggest that hypoperfusion symptoms alone correlate poorly with actual hemodynamic compromise as assessed by quantitative magnetic resonance angiography and subsequent stroke risk in vertebrobasilar disease, and are not a reliable surrogate for flow measurement. Clinical Trial Registration— URL: https://www.clinicaltrials.gov . Unique identifier: NCT00590980.

Epilepsy, a complex spectrum of disorders, affects about 2.9 million people in the U.S. Similar to other chronic disorders, people with epilepsy face challenges related to management of the disorder, its treatment, co-occurring depression, disability, social disadvantages, and stigma. Two national conferences on public health and epilepsy (1997, 2003) and a 2012 IOM report on the public health dimensions of epilepsy highlighted important knowledge gaps and emphasized the need for evidence-based, scalable epilepsy self-management programs. The Centers for Disease Control and Prevention translated recommendations on self-management research and dissemination into an applied research program through the Prevention Research Centers Managing Epilepsy Well (MEW) Network. MEW Network objectives are to advance epilepsy self-management research by developing effective interventions that can be broadly disseminated for use in people's homes, healthcare providers' offices, or in community settings. The aim of this report is to provide an update on the MEW Network research pipeline, which spans efficacy, effectiveness, and dissemination. Many of the interventions use e-health strategies to eliminate barriers to care (e.g., lack of transportation, functional limitations, and stigma). Strengths of this mature research network are the culture of collaboration, community-based partnerships, e-health methods, and its portfolio of prevention activities, which range from efficacy studies engaging hard-to-reach groups, to initiatives focused on provider training and knowledge translation. The MEW Network works with organizations across the country to expand its capacity, help leverage funding and other resources, and enhance the development, dissemination, and sustainability of MEW Network programs and tools. Guided by national initiatives targeting chronic disease or epilepsy burden since 2007, the MEW Network has been responsible for more than 43 scientific journal articles, two study reports, seven book chapters, and 62 presentations and posters. To date, two programs have been adopted and disseminated by the national Epilepsy Foundation, state Epilepsy Foundation affiliates, and other stakeholders. Recent expansion of the MEW Network membership will help to extend future reach and public health impact.

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.

INTRODUCTION Ulnar neuropathy at the elbow (UNE) is the second most common entrapment neuropathy. Our goal was to create and analyze a grading system for UNE electrodiagnostic severity. METHODS We retrospectively analyzed EMG reports with UNE. We then classified 112 limbs as having mild, moderate, or severe grade UNE based on electrodiagnostic findings. The association between presenting symptoms and signs, EMG findings, treatment type, and electrodiagnostic grade was statistically analyzed. RESULTS Seventeen limbs (15.2%) had mild, 80 (71.4%) had moderate, and 15 (13.4%) had severe UNE. Symptoms (P = .016), exam findings (P

Purpose People with epilepsy (PWE) from underserved populations face significant barriers to epilepsy management and therefore may lack knowledge about epilepsy and self-management (SM) of epilepsy. This paper evaluates SM practices, self-efficacy, outcome expectancy, quality of life, and personal impact of epilepsy in PWE from underserved populations as compared with all PWE. Methods Recruitment for the Managing Epilepsy Well (MEW) Network PAUSE to Learn Your Epilepsy study occurred from October 2015 to March 2019. Participants were assessed at baseline; after SM education intervention; and 6-, 9-, and 15-month postbaseline assessment. Baseline data from 112 PWE were analyzed for this report. Results Study population was diverse: 63% were women, 47.3% were non-Hispanic black, 24.1% were Hispanic, and 57.4% had public healthcare coverage. Participants on average had epilepsy for 14 years, and 49.1% reported at least one seizure within the past month, but only 27% reported having used a seizure diary or calendar for seizure tracking. Self-management practices & behaviors were significantly lower among PWE from underserved populations than all PWE, though self-efficacy among PWE from underserved populations was significantly higher. Conclusion This study identifies the unique epilepsy SM needs of PWE from underserved populations. We discuss the need for a personalized approach for developing SM skills and behaviors among these PWE.

Introduction: Distal territory blood flow is independently associated with subsequent strokes in symptomatic vertebrobasilar atherosclerotic disease. We aimed to assess infarct patterns in relation to hemodynamic status in the prospective Vertebrobasilar Flow Evaluation and Risk of Transient Ischemic Attack and Stroke (VERiTAS) study. Methods: Distal territory blood flow was measured using quantitative magnetic resonance angiography (MRA) in 72 patients with symptomatic atherosclerotic vertebrobasilar disease, and then dichotomized into normal (n = 54) and low (n = 18) flow. Patients were followed longitudinally on standard medical management. Two observers blinded to flow status independently reviewed the imaging performed at the time of subsequent strokes, in order to adjudicate the likely mechanism based on infarct patterns. The frequency of stroke mechanisms was qualitatively compared based on flow status. Results: During a median follow-up period of 23 months, 10/72 patients had a subsequent stroke; 5 of these had low distal flow. Infarct patterns were adjudicated to be consistent with hemodynamic (n = 2), embolic (n = 4), and junctional plaque/perforator (n = 4) infarcts. Hemodynamic infarcts were seen in 40% (2/5) low-flow patients, in comparison to 0% (0/5) normal-flow patients. Conclusion: In contrast to normal-flow patients, those with low distal flow seem to be uniquely susceptible to hemodynamic infarctions, although other patterns of infarction can also be seen in these hemodynamically impaired patients.

Background: Population studies showed that Hispanic/Latino adults have elevated rates of uncontrolled cardiovascular risk factors (CVRFs) with noticeable sex-specific variations . We investigated prevalence of CVRFs and the use of American Heart Association (AHA) secondary stroke prevention strategies in Hispanics/Latinos in the United States. Methods: Data from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) were used to examine sociodemographic characteristics, use of antithrombotic agents and statins, and treatment of CVRFs in persons with a history of stroke or transient ischemic attack (TIA). CVRFs were categorized as “controlled” if the CVRF met the goals defined by the AHA irrespective of whether the subject was on treatment for it or not; and “unaware” if the participant denied having a CVRF but met the diagnostic criteria for it. Differences between men and women were tested using ANOVA test and Pearson’s χ 2 . Factors associated with adherence to AHA recommendations were investigated using logistic regression. Results: These analyses included 404 individuals with history of stroke/TIA (men=159; women=245). Women were slightly older than men (55.1±1.5 vs. 54.1±1.6 years; p10 years in the US were associated with uncontrolled HC and DM, respectively. Conclusion: Hispanics/Latinos with stroke have elevated rates of awareness but suboptimal use of AHA secondary stroke prevention strategies. Older persons and women are vulnerable groups that may benefit from targeted interventions.

The quinoline-based pincer nickel(II) complexes κN,κN,κN-{R2N-C6H4-(μ-N)-C9H6N}NiX ((R2NNNQ)NiCl: R = Me, 2a; R = Et, 2b) were synthesized by the reaction of the ligand precursors (R2NNNQ)H (R = Me, 1a; R = Et, 1b) with (DME)NiCl2 in the presence of Et3N. Similarly, the pincer nickel(II) derivatives (R2NNNQ)NiX (R = Me, X = Br, 3a; R = Et, X = Br, 3b; R = Me, X = OAc, 4a) were obtained by treatment of the ligands (R2NNNQ)H with the nickel precursor (THF)2NiBr2 or Ni(OAc)2. All of these complexes were characterized by 1H and 13C NMR spectroscopy as well as by elemental analysis. Further, the molecular structures of 2a and 3a,b were elucidated by X-ray crystallography. Complex 2a is found to be an efficient catalyst for the direct C–H bond alkylation of substituted benzothiazoles and oxazoles with various unactivated alkyl halides containing β-hydrogens under mild reaction conditions. The catalyst 2a is very robust and was recycled and reused five times for the alkylation reaction without a decrease in its ...

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

Intracranial endovascular interventions provide effective and minimally invasive treatment of a broad spectrum of diseases. This area of expertise has continued to gain both wider application and greater depth as new and better techniques are developed and as landmark clinical studies are performed to guide their use. Some of the greatest advances since the last American Heart Association scientific statement on this topic have been made in the treatment of ischemic stroke from large intracranial vessel occlusion, with more effective devices and large randomized clinical trials showing striking therapeutic benefit. The treatment of cerebral aneurysms has also seen substantial evolution, increasing the number of aneurysms that can be treated successfully with minimally invasive therapy. Endovascular therapies for such other diseases as arteriovenous malformations, dural arteriovenous fistulas, idiopathic intracranial hypertension, venous thrombosis, and neoplasms continue to improve. The purpose of the present document is to review current information on the efficacy and safety of procedures used for intracranial endovascular interventional treatment of cerebrovascular diseases and to summarize key aspects of best practice.

Each chapter listed in the Table of Contents (see next page) is a hyperlink to that chapter. The reader clicks the chapter name to access that chapter. Each chapter listed here is a hyperlink. Click on the chapter name to be taken to that chapter. Each year, the American Heart Association (AHA), in conjunction with the Centers for Disease Control and Prevention, the National Institutes of Health, and other government agencies, brings together in a single document the most up-to-date statistics related to heart disease, stroke, and the cardiovascular risk factors listed in the AHA’s My Life Check - Life’s Simple 7 (Figure1), which include core health behaviors (smoking, physical activity, diet, and weight) and health factors (cholesterol, blood pressure [BP], and glucose control) that contribute to cardiovascular health. The Statistical Update represents …

Introduction: Hypoperfusion symptoms, defined as symptoms related to change in position (i.e. supine to seated), effort or exertion, or recent change in antihypertensive medication have been used in stroke studies as a surrogate for detecting hemodynamic compromise. However, the validity of these symptoms in identifying flow compromise in patients has not been well established. We examined whether hypoperfusion symptoms correlated with quantitative evaluation of flow compromise in the prospective observational Vertebrobasilar Flow Evaluation and Risk of Transient Ischemic Attack and Stroke (VERiTAS) study. Methods: VERiTAS enrolled patients with recent vertebrobasilar TIA or stroke and ≥50% atherosclerotic stenosis or occlusion in vertebral and/or basilar arteries. Hemodynamic status using large vessel flow in the vertebrobasilar territory was measured using quantitative magnetic resonance angiography (QMRA), and patients were designated as low, borderline or normal flow based on distal territory regional flow, incorporating collateral capacity, as previously reported. The presence of qualifying event hypoperfusion symptoms was assessed relative to the quantitatively determined flow status (normal vs borderline/low), and also examined as a predictor of subsequent stroke risk. Results: Of the 72 enrolled subjects, 66 had data on hypoperfusion symptoms available. On initial QMRA designation, 43 subjects were designated as normal flow vs. 23 subjects designated as low flow (n=16) or borderline (n=7). Of these, 5 (11.6%) normal flow and 3 (13.0%) low/borderline flow subjects reported at least one qualifying event hypoperfusion symptom (p=0.99, Fisher’s exact test). Hypoperfusion symptoms had a positive predictive value of 37.5% and negative predictive value of 65.5% for low/borderline flow status. Compared to flow status, which strongly predicted subsequent stroke risk, hypoperfusion symptoms were not associated with stroke outcome (p=0.87, log rank test). Conclusions: These results suggest that hypoperfusion symptoms alone correlate poorly with actual hemodynamic compromise, and subsequent stroke risk in vertebrobasilar disease, and are not a reliable surrogate for flow measurement.

The pathogenesis of venous intimal hyperplasia and venous outflow stenosis associated with cerebral arteriovenous malformation (AVM) draining veins is poorly understood. We sought to determine the relationship between venous stenosis and age.All patients with an AVM seen at our institution between 1990 and 2016 who underwent a diagnostic cerebral angiogram were retrospectively reviewed. Draining vein stenosis was measured from angiograms before any treatment. The relationship between venous stenosis and age was assessed.We included 281 patients (mean age 39 years, age range 3-83 years, 55% male). Venous stenosis measuring ≥50% was present in 59 patients (21% of cohort). Peak age at presentation was 25-29 years, whereas peak frequency of venous stenosis ≥50% was 50-54 years. Venous stenosis was present in a significantly higher proportion of patients ≥50 years versus50 years (P = 0.03). Mean percentage stenosis was significantly higher in patients ≥50 years versus50 years (32% vs. 22%, P = 0.001).Clinically significant cerebral AVM draining vein stenosis appears to be associated with older age, suggesting that venous stenosis is a progressive disease that occurs by the same process that leads to intimal hyperplasia. These results should be confirmed with a population-based longitudinal study.

Stroke is a global health problem. However, very little is known about stroke care in low- to middle-income countries. Obtaining country-specific information could enable us to develop targeted programs to improve stroke care. We surveyed neurologists from 12 countries (Chile, Georgia, Nigeria, Qatar, India, Lithuania, Kazakhstan, Indonesia, Denmark, Brazil, Belgium, and Bangladesh) using a web-based survey tool. Data were analyzed both for individual countries and by income classification (low income, lower middle income, upper middle income, and high income). Six percent (n = 200) of 3123 targeted physicians completed the survey. There was a significant correlation between income classification and access and affordability of head computed tomography scan (ρ = .215, P = .002), transthoracic echocardiogram (ρ = .181, P = .012), extracranial carotid Doppler ultrasound (ρ = .312, P ≤ .000), cardiac telemetry (ρ = .353, P ≤ .000), and stroke treatments such as intravenous thrombolysis (ρ = .276, P ≤ .001), and carotid endarterectomy (ρ = .214, P ≤ .004); stroke quality measures such as venous thromboembolism prophylaxis during hospital stay (ρ = .163, P ≤ .022), discharge from hospital on antithrombotic therapy (ρ = .266, P ≤ .000), consideration for acute thrombolytic therapy (ρ = .358, P ≤ .000), and antithrombotic therapy prescribed by end of hospital day 2 (ρ = .334, P ≤ .000). However, there was no significant correlation between income classification and the access and affordability of antiplatelet agents, vitamin K antagonists and statins, anticoagulation for atrial fibrillation/flutter, statin medication, stroke education, and assessment for rehabilitation. Our study shows that it is possible to get an overview of stroke treatment measures in different countries by conducting an internet-based survey. The generalizability of the findings may be limited by the low survey response rate.

Author(s): Mozaffarian, Dariush; Benjamin, Emelia J; Go, Alan S; Arnett, Donna K; Blaha, Michael J; Cushman, Mary; de Ferranti, Sarah; Despres, Jean-Pierre; Fullerton, Heather J; Howard, Virginia J; Huffman, Mark D; Judd, Suzanne E; Kissela, Brett M; Lackland, Daniel T; Lichtman, Judith H; Lisabeth, Lynda D; Liu, Simin; Mackey, Rachel H; Matchar, David B; McGuire, Darren K; III, 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; Sorlie, Paul D; Stein, Joel; Towfighi, Amytis; Turan, Tanya N; Virani, Salim S; Willey, Joshua Z; Woo, Daniel; Yeh, Robert W; Turner, Melanie B; Comm, Amer Heart Assoc Stat; Subcomm, Stroke Stat

Regioselective C–H bond palladation of the hybrid pincer-type ligands, 3-R2PO-C6H4-1-CH2NiPr2 [R2POCNiPr2–H; R = Ph (1a), R = Et2N (1b)] has been described to accomplish mono- and binuclear palladacycles. The reactions of the ligands R2POCNiPr2–H (1a, 1b) with Pd(COD)Cl2 in the presence of K3PO4 afforded the mononuclear pincer complexes {κP,κC,κN-2-(R2PO)-C6H3-6-(CH2NiPr2)}PdCl (R2POCNiPr2)PdCl [R = Ph (2a), R = Et2N (2b)], whereas similar reactions in the presence of Et3N produced the chloro-bridged binuclear palladacycles [{κP,κC-2-(R2PO)-C6H3-4-(CH2NiPr2)}(μ-Cl)Pd]2 {R = Ph (4a), R = Et2N (4b)} via the regioselective ligands C(2)–H and C(4)–H bond activation, respectively. Similarly, the reaction of a previously reported ligand iPr2POCNiPr2–H (1c) with Pd(COD)Cl2 in the presence of Et3N affords a chloro-bridged binuclear complex [{κP,κC-2-(iPr2PO)-C6H3-4-(CH2NiPr2)}(μ-Cl)Pd]2 (4c) via the regioselective C(4)–H bond palladation. On the contrary, using Pd(OAc)2 instead of Pd(COD)Cl2 in the palladation reaction of 1a, in the presence or absence of base, leads to the exclusive formation of the acetate-bridged binuclear palladacycle [{κP,κC-2-(Ph2PO)-C6H3-4-(CH2NiPr2)}(μ-OAc)Pd]2 (5a). Mechanistic detail for this regioselective C–H bond activation to achieve mono- and binuclear palladacycles has been demonstrated, which highlights that the coordinating ability of the external base, sterics between the coordinated base and N-arm of the POCN ligand as well as the electrophilicity of the palladium center are crucial to the regioselective palladation. The palladium complex 4c was shown to be the active catalyst for the direct arylation of azoles with aryl iodides under mild reaction conditions.

Measurement of volume flow rates in major cerebral vessels can be used to evaluate the hemodynamic effects of cerebrovascular disease. However, both age and vascular anatomy can affect flow rates independent of disease. We prospectively evaluated 325 healthy adult volunteers using phase contrast quantitative magnetic resonance angiography to characterize these effects on cerebral vessel flow rates and establish clinically useful normative reference values. Flows were measured in the major intracranial and extracranial vessels. The cohort ranged from 18 to 84 years old, with 157 (48%) females. All individual vessel flows and total cerebral blood flow (TCBF) declined with age, at 2.6 mL/minute per year for TCBF. Basilar artery (BA) flow was significantly decreased in individuals with one or both fetal posterior cerebral arteries (PCAs). Internal carotid artery flows were significantly higher with a fetal PCA and decreased with a hypoplastic anterior cerebral artery. Indexing vessel flows to TCBF neutralized the age effect, but anatomic variations continued to impact indexed flow in the BA and internal carotid artery. Variability in normative flow ranges were reduced in distal vessels and by examining regional flows. Cerebral vessel flows are affected by age and cerebrovascular anatomy, which has important implications for interpretation of flows in the disease state.

Objectives: Patients with symptomatic atherosclerotic vertebrobasilar disease are at high risk for recurrent stroke and we have demonstrated that distal flow status is independently associated with this risk. Our aim was to assess the mechanism of recurrent strokes in these patients related to their distal flow status. Methods: Patients with symptomatic atherosclerotic vertebrobasilar disease were enrolled in a prospective longitudinal cohort study (VERiTAS) with a median follow-up of 23 months. Large-vessel flow in the posterior circulation distal to the stenosis and/or occlusion was measured on quantitative MR angiography and dichotomized into normal or low flow. Three observers, who were blinded to the distal flow status, independently reviewed the imaging done at the time of the recurrent stroke to classify the most likely stroke mechanism. Results: Ten out of 72 enrolled patients had a recurrent stroke in the posterior circulation. Four patients were determined to have embolic infarcts, four patients had infarcts caused by plaques that occluded a branch or perforating artery (junctional plaques), and two patients had imaging that suggested hemodynamic infarction. Five of the ten patients with recurrent strokes had low distal flow. Of these, two patients had hemodynamic infarcts, one patient had an embolic infarct, and two patients had a junctional plaque. None of the five patients with normal flow had hemodynamic infarcts, three patients had embolic infarcts, and two patients had a junctional plaque. Conclusion: Despite the small numbers, there seems to be a higher risk of hemodynamic infarction in patients with low flow distal to symptomatic vertebrobasilar disease than in the presence of normal distal flow. This would confirm the hypothesis that in addition to embolic strokes and those related to junctional plaque, patients with low distal flow are at risk for hemodynamic infarction. Further studies are required to determine whether flow measurements could be used to select patients who may benefit from endovascular treatment of atherosclerotic vertebrobasilar disease.

OBJECTIVES The combined sensory index (CSI), a sensitive composite score of 3 median sensory comparison studies, may still be underutilized in diagnosing mild cases of carpal tunnel syndrome (CTS). Our goal was to compare the effectiveness of the "standard" median digit 2 (D2) sensory study to a CSI algorithm in diagnosing mild CTS. METHODS We retrospectively identified patients with typical CTS symptoms and signs. Electrodiagnostically normal patients and those having mild CTS diagnosed by D2 or CSI algorithm were separated into groups. RESULTS Seventy-four patients were included, and 51 (68.9%) were diagnosed with mild CTS. Of the 51, 31 (60.8%) were diagnosed using the CSI algorithm, and 20 (39.2%) were diagnosed using D2 (P < 0.001). CONCLUSIONS Our data suggest that the CSI algorithm is significantly more effective than the D2 to diagnose mild CTS. If mild CTS is diagnosed earlier, treatment can be initiated sooner and morbidity can likely prevented.

Author(s): Go, Alan S; Mozaffarian, Dariush; Roger, Veronique L; Benjamin, Emelia J; Berry, Jarett D; Blaha, Michael J; Dai, Shifan; Ford, Earl S; Fox, Caroline S; Franco, Sheila; Fullerton, Heather J; Gillespie, Cathleen; Hailpern, Susan M; Heit, John A; Howard, Virginia J; Huffman, Mark D; Judd, Suzanne E; Kissela, Brett M; Kittner, Steven J; Lackland, Daniel T; Lichtman, Judith H; Lisabeth, Lynda D; Mackey, Rachel H; Magid, David J; Marcus, Gregory M; Marelli, Ariane; Matchar, David B; McGuire, Darren K; Mohler, Emile R; Moy, Claudia S; Mussolino, Michael E; Neumar, Robert W; Nichol, Graham; Pandey, Dilip K; Paynter, Nina P; Reeves, Matthew J; Sorlie, Paul D; Stein, Joel; Towfighi, Amytis; Turan, Tanya N; Virani, Salim S; Wong, Nathan D; Woo, Daniel; Turner, Melanie B; American Heart Association Statistics Committee and Stroke Statistics Subcommittee

Thienopyridine-derivatives (ticlopidine, clopidogrel, and prasugrel) are the primary antiplatelet agents. Thrombotic thrombocytopenic purpura (TTP) is a rare drug-associated syndrome, with the thienopyridines being the most common drugs implicated in this syndrome. We reviewed 20 years of information on clinical, epidemiologic, and laboratory findings for thienopyridine-associated TTP. Four, 11, and 11 cases of thienopyridine-associated TTP were reported in the first year of marketing of ticlopidine (1989), clopidogrel (1998), and prasugrel (2010), respectively. As of 2011, the FDA received reports of 97 ticlopidine-, 197 clopidogrel-, and 14 prasugrel-associated TTP cases. Severe deficiency of ADAMTS-13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13) was present in 80% and antibodies to 100% of these TTP patients on ticlopidine, 0% of the patients with clopidogrel-associated TTP (p < 0.05), and an unknown percentage of patients with prasugrel-associated TTP. TTP is associated with use of each of the three thienopyridines, although the mechanistic pathways may differ.

Introduction: Prior studies have demonstrated superiority of the combined sensory index (CSI) algorithm in diagnosing mild carpal tunnel syndrome (CTS) and have compared presenting symptoms to CTS grade. However, CTS symptoms, signs, and outcomes, including CSI-diagnosed cases, have not been compared with CTS grade. Methods: We retrospectively studied 294 CTS hands from 2010 to 2013; stratified them into mild, moderate, and severe grades; and analyzed the association between CTS grade and presenting symptoms/signs and outcomes. Results: Sensorimotor symptoms (P = 0.017) and signs (P < 0.001) were significantly associated with CTS grade. Regardless of CTS grade, 94% of hands improved with surgery compared with 42% with conservative treatment (P < 0.001). Even in mild CTS, 100% improved with surgery vs. 33% with conservative management (P = 0.011). Discussion: These results corroborate prior studies that compared symptoms to CTS grade and suggest that more objective signs associate even better. CTS grades associate with outcomes, but additional studies are required. Muscle Nerve 57: 45–48, 2018

Background: Fractional flow across an atherosclerotic lesion measured with TOF-MRA signal intensity ratio (SIR) may be used to gauge hemodynamic severity and to predict subsequent stroke. The degree of flow impairment may also be ascertained by quantitative MRA (QMRA). We analyzed performance of these noninvasive imaging parameters to estimate risk of subsequent posterior circulation events in VERiTAS. Methods: TOF-MRA data and QMRA were simultaneously acquired in VERiTAS. SIR were derived from TOF source images and normalized for analysis with volume flow ratios (VFR) on QMRA at standard anatomical landmarks and across the maximal stenosis. Statistics analyzed the correlation between SIR and VFR, and the ability of each to predict clinical events. Results: 72 subjects (mean age 65.6±10.3 years, 32 (44%) women) with posterior circulation atherosclerosis were enrolled in VERiTAS. Posterior communicating artery (PCOMM) flow to the posterior circulation was detected in 85% on the right, in 86% on the left, with bilateral PCOMM flow in 78%. Fractional flow measures or SIR across the maximal stenotic lesion evident on TOF MRA was reduced in 43%, increased in 16%, with no change in 40%. SIR from the proximal to distal basilar artery segments increased in 62%, was unchanged in 33% and decreased in 4% of cases. SI and VFR exhibited limited correlation at corresponding arterial segments. QMRA VFR indicative of low distal flow status predicted subsequent clinical events, unlike SIR. Conclusions: Evaluation of hemodynamics in posterior circulation atherosclerosis reveals superiority of QMRA to SIR in prospectively predicting recurrent ischemia. Collateral circulation, tandem disease and unique aspects of vertebrobasilar atherosclerosis likely influence the utility of SIR on TOF MRA.

Introduction: Despite theoretical concerns regarding hypoperfusion in patients with large artery occlusive disease, strict blood pressure (BP) control has become adopted as a safe strategy for stroke risk reduction. We examined the relationship between BP control, flow, and risk of subsequent stroke in the prospective Vertebrobasilar Flow Evaluation and Risk of Transient Ischemic Attack and Stroke (VERiTAS) Study. Hypothesis: Strict BP control may be less efficacious and safe in flow compromised patients with symptomatic vertebrobasilar (VB) disease. Methods: VERiTAS enrolled patients with recent VB TIA or stroke and ≥50% atherosclerotic stenosis or occlusion of vertebral or basilar arteries. Hemodynamic status using large vessel flow in the VB territory was designated as low or normal flow using quantitative MRA. Patients underwent standard medical management and follow-up for primary outcome event of VB territory stroke. Mean SBP during follow-up ( Results: The 72 enrolled subjects had an average of 3.8±1.2 BP recordings over the 20 ±8 months of follow-up; 40 (56%) had mean SBP of Conclusion: Among a subgroup of patients with VB disease and low flow, strict BP control (SBP

Introduction: The role of regional hypoperfusion as an important contributor to stroke risk in atherosclerotic vertebrobasilar (VB) disease has recently been confirmed by the observational Vertebrobasilar Flow Evaluation and Risk of Transient Ischemic Attack and Stroke (VERiTAS) Study. We examined the stability of hemodynamic status over time and relationship to stroke risk in patients followed in this prospective cohort. Methods: VERiTAS enrolled patients with recent VB TIA or stroke and ≥50% atherosclerotic stenosis or occlusion of vertebral and/or basilar arteries. Large vessel flow in the vertebrobasilar territory was assessed using quantitative MRA, and patients were designated as low flow or normal flow based on distal territory regional flow, incorporating collateral capacity. Patients underwent standard medical management and follow-up for primary outcome event of VB territory stroke. QMRA imaging was repeated at 6, 12 and 24 months. Flow status over time was examined relative to baseline, and relative to subsequent stroke risk using survival analysis. Results: Of 72 enrolled subjects, 50, 45 and 28 had follow-up QMRA at 6, 12 and 24 months respectively. 18 (25%) were characterized as low flow at baseline, 10% at 6 m, 20 % at 12m and 11% at 24m. Over 18±7months of follow-up, 7 of the 12 low flow patients (58%) with follow-up imaging had improved their flow status (low to normal) while only 3 of 44 normal flow patients (7%) had worsened. Baseline flow status has previously been demonstrated to be an independent stroke risk predictor; flow status at latest follow-up and prior to event remained a strong predictor of subsequent stroke (HR 4.9, CI 1.4 to16.9, p=0.01). Conclusions: There is potential both for improvement and worsening of hemodynamics in patients with atherosclerotic VB disease; improvement, likely attributable to development of collateral supply, was evident more frequently than worsening, presumably due to progression of disease. Flow status, both at baseline and over time, remains a robust risk factor for subsequent stroke, thus serving as an important prognostic marker.

Life expectancy at birth has increased from 74 years in 1980 to 78 years in 2006. Older adults (aged 65 years and older) are living longer with cardiovascular conditions, which are leading causes of death and disability and thus an important public health concern. We describe several major issues, including the impact of comorbidities, the role of cognitive health, prevention and intervention approaches, and opportunities for collaboration to strengthen the public health system. Prevention can be effective at any age, including for older adults. Public health models focusing on policy, systems, and environmental change approaches have the goal of providing social and physical environments and promoting healthy choices.

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

The process of atherosclerosis may begin in youth and continue for decades, leading to both nonfatal and fatal cardiovascular events, including myocardial infarction, stroke, and sudden death. With primordial and primary prevention, cardiovascular disease is largely preventable. Clinical trial evidence has shown convincingly that pharmacological treatment of risk factors can prevent events. The data are less definitive but also highly suggestive that appropriate public policy and lifestyle interventions aimed at eliminating tobacco use, limiting salt consumption, encouraging physical exercise, and improving diet can prevent events. There has been concern about whether efforts aimed at primordial and primary prevention provide value (ie, whether such interventions are worth what we pay for them). Although questions about the value of therapeutics for acute disease may be addressed by cost-effectiveness analysis, the long time frames involved in evaluating preventive interventions make cost-effectiveness analysis difficult and necessarily flawed. Nonetheless, cost-effectiveness analyses reviewed in this policy statement largely suggest that public policy, community efforts, and pharmacological intervention are all likely to be cost-effective and often cost saving compared with common benchmarks. The high direct medical care and indirect costs of cardiovascular disease—approaching $450 billion a year in 2010 and projected to rise to over $1 trillion a year by 2030—make this a critical medical and societal issue. Prevention of cardiovascular disease will also provide great value in developing a healthier, more productive society.

Hypertension has long been recognized as a major risk factor for stroke, and lowering blood pressure has been shown to be effective in preventing first-time strokes. However, it is only over the past decade or so that lowering blood pressure has been shown to also be effective in preventing recurrent strokes. Large recent studies have quantified the effect of blood pressure lowering on stroke prevention, and increasing attention is being paid to variability of blood pressure rather than usual blood pressure values in determining stroke risk and explaining some of the class differences between various antihypertensives in stroke prevention. On the flip side, however, large trials aimed at showing a benefit of angiotensin receptor blockers on stroke prevention, above and beyond blood pressure lowering, have not yielded positive results. Many important questions such as the optimal time to initiate antihypertensive treatment after a stroke, the choice of the antihypertensive agent, and the optimal blood pressure goal after a stroke remain to be determined.

Thrombotic thrombocytopenic purpura (TTP) is a fulminant disease characterized by platelet aggregates, thrombocytopenia, renal insufficiency, neurologic changes, and mechanical injury to erythrocytes. Most idiopathic cases of TTP are characterized by a deficiency of ADAMTS13 (a disintegrin and metalloprotease, with thrombospondin-1-like domains) metalloprotease activity. Ironically, use of anti-platelet agents, the thienopyridine derivates clopidogrel and ticlopidine, is associated with drug induced TTP. Data were abstracted from a systematic review of English-language literature for thienopyridine-associated TTP identified in MEDLINE, EMBASE, the public website of the Food and Drug Administration, and abstracts from national scientific conferences from 1991 to April 2008. Ticlopidine and clopidogrel are the two most common drugs associated with TTP in FDA safety databases. Epidemiological studies identify recent initiation of anti-platelet agents as the most common risk factor associated with risks of developing TTP. Laboratory studies indicate that most cases of thienopyridine-associated TTP involve an antibody to ADAMTS13 metalloprotease, present with severe thrombocytopenia, and respond to therapeutic plasma exchange (TPE); a minority of thienopyridine-associated TTP presents with severe renal insufficiency, involves direct endothelial cell damage, and is less responsive to TPE. The evaluation of this potentially fatal drug toxicity can serve as a template for future efforts to comprehensively characterize other severe adverse drug reactions.

The epidemiology of ischemic and hemorrhagic stroke is an ongoing exploration to identify risk factors that continue to expand with the advent of technological advancements and preventative medical practices. Identification of risk factors that can or cannot be modified is a crucial step in determining stroke risk. Many of the modifiable risk factors are well established, and specific interventions to reduce stroke risk have been established. Some risk factors are less established, and intervention to reduce risk is yet to be determined by evidence-based medicine. Data from ongoing randomized clinical trials continue to enhance our ability to prevent a first stroke.