Search

Background: Posterior reversible encephalopathy syndrome (PRES) can cause short-term cerebrovascular complications, such as brain infarction and hemorrhage. We hypothesized that PRES is also associated with an increased long-term risk of stroke. Methods: We performed a retrospective cohort study in the United States using statewide all-payer claims data from 2016 to 2018 on all admissions to nonfederal hospitals in 11 states. Adults with PRES were compared with adults with renal colic (negative control) and transient ischemic attack (TIA; positive control). Any stroke and the secondary outcomes of ischemic and hemorrhagic stroke were ascertained using International Classification of Diseases, Tenth Revision, Clinical Modification codes . We excluded prevalent stroke. We used time-to-event statistics to calculate incidence rates and Cox proportional hazards analyses to evaluate the association between PRES and stroke, adjusting for demographics and stroke risk factors. In a sensitivity analysis, outcomes within 2 weeks of index admission were excluded. Results: We identified 1606 patients with PRES, 1192 with renal colic, and 38 216 with TIA. Patients with PRES had a mean age of 56±17 years; 72% were women. Over a median follow-up of 0.9 years, the stroke incidence per 100 person-years was 6.1 (95% CI, 5.0–7.4) after PRES, 1.0 (95% CI, 0.62–1.8) after renal colic, and 9.7 (95% CI, 9.4–10.0) after TIA. After statistical adjustment for patient characteristics and risk factors, patients with PRES had an elevated risk of stroke compared with renal colic (hazard ratio [HR], 2.3 [95% CI, 1.7–3.0]), but lower risk than patients with TIA (HR, 0.67 [95% CI, 0.54–0.82]). In secondary analyses, compared with TIA, PRES was associated with hemorrhagic stroke (HR, 2.0 [95% CI, 1.4–2.9]). PRES was associated with ischemic stroke when compared with renal colic (HR, 1.9 [95% CI, 1.4–2.7]) but not when compared with TIA (HR, 0.49 [95% CI, 0.38–0.63]). Results were similar with 2-week washout. Conclusions: Patients with PRES had an elevated risk of incident stroke.

Background: In patients with intracerebral hemorrhage (ICH), it is unclear whether early neurological deterioration, hematoma expansion (HE), and outcome vary by supratentorial ICH location (deep versus lobar). Herein, we assessed these relationships in a clinical trial cohort that underwent brain imaging early after symptom onset. We hypothesized that HE would occur more frequently, and outcome would be worse in patients with deep ICH. Methods: We performed a post hoc analysis of the FAST (Factor-VII-for-Acute-Hemorrhagic-Stroke-Treatment) trial including all patients with supratentorial hemorrhage. Enrolled patients underwent brain imaging within 3 hours of symptom onset and 24 hours after randomization. Multivariable regression was used to test the association between ICH location and 3 outcomes: HE (increase of ≥33% or 6mL), early neurological deterioration (decrease in Glasgow Coma Scale score ≥2 points or increase in National Institutes of Health Stroke Scale ≥4 points within 24 hours of admission), and 90-day outcome (modified Rankin Scale). Results: Of 841 FAST trial patients, we included 728 (mean age 64 years, 38% women) with supratentorial hemorrhages (deep n=623, lobar n=105). HE (44 versus 27%, P =0.001) and early neurological deterioration (31 versus 17%, P =0.001) were more common in lobar hemorrhages. Deep hemorrhages were smaller than lobar hemorrhages at baseline (12 versus 35mL, P P P =0.03). However, when adjusting for variables included in the ICH score including ICH volume, deep location was associated with worse and lobar location with better outcome (odds ratio lobar location, 0.58 [95% CI, 0.38–0.89]; P =0.01). Conclusions: In this secondary analysis of randomized trial patients, lobar ICH location was associated with larger ICH volume, more HE and early neurological deterioration, and worse outcome than deep ICH. After adjustment for prognostic variables, however, deep ICH was associated with worse outcome, likely due to their proximity to eloquent brain structures.

Background: Continued smoking after stroke is associated with a high risk of stroke recurrence and other cardiovascular disease. We sought to comprehensively understand the epidemiology of smoking cessation in stroke survivors in the United States. Furthermore, we compared smoking cessation in stroke and cancer survivors because cancer is another smoking-related condition in which smoking cessation is prioritized. Methods: We performed a cross-sectional analysis of data from the Centers for Disease Control and Prevention Behavioral Risk Factor Surveillance System, an annual, nationally representative health survey. Using pooled data from 2013 to 2019, we identified stroke and cancer survivors with a history of smoking. We used survey procedures to estimate frequencies and summarize quit ratios with attention to demographic and geographic (state-wise and rural-urban) factors for stroke survivors. The quit ratio is conventionally defined as the proportion of ever smokers who have quit. Then, we used multivariable logistic regression to compare quit ratios in stroke and cancer survivors while adjusting for demographics and smoking-related comorbidities. Results: Among 4 434 604 Americans with a history of stroke and smoking, the median age was 68 years (interquartile range, 59–76), and 45.4% were women. The overall quit ratio was 60.8% (95% CI, 60.1%–61.6%). Quit ratios varied by age group, sex, race and ethnicity, and several geographic factors. There was marked geographic variation in quit ratios, ranging from 48.3% in Kentucky to 71.5% in California. Furthermore, compared with cancer survivors, stroke survivors were less likely to have quit smoking (odds ratio, 0.72 [95% CI, 0.67–0.79]) after accounting for differences in demographics and smoking-related comorbidities. Conclusions: There were considerable demographic and geographic disparities in smoking quit ratios in stroke survivors, who were less likely to have quit smoking than cancer survivors. A targeted initiative is needed to improve smoking cessation for stroke survivors.

Introduction: While well-established risk factors for cervical artery dissection include trauma and connective tissue disorders, many cases are considered “spontaneous.” Although the incidence of cervical artery dissection is greatest in the young, the prevalence increases with age, suggesting a potential role of vascular disease. In this study, we hypothesized that atherosclerosis may be a risk factor for cervical artery dissection. Methods: We performed a retrospective cohort study using administrative claims data from a 5% sample of Medicare beneficiaries between 2008 and 2018. The exposures of interest were vascular risk factors potentially associated with atherosclerosis including coronary artery disease, hyperlipidemia, hypertension, diabetes mellitus, heart failure, chronic kidney disease, chronic obstructive pulmonary disease, valvular heart disease, atrial fibrillation, tobacco use, and alcohol abuse. The primary outcome was a new diagnosis of cervical artery dissection. Marginal structural Cox models were used to characterize the association between the exposures and outcomes, adjusted for time-dependent confounding, age, sex, race/ethnicity, and prior stroke. Results: Among 2,256,826 eligible Medicare beneficiaries, 1,527 (0.07%) developed cervical artery dissection, with a mean age of 70.8, compared to 71.5 in those without cervical artery dissection. The following exposures were found to be significantly associated with the development of cervical artery dissection: coronary artery disease (1.81 [1.63-2.01]), hyperlipidemia (1.84 [1.61-2.11]), hypertension (2.04 [1.76-2.37]), diabetes mellitus (1.34 [1.21-1.49]), heart failure (1.44 [1.25-1.67]), chronic kidney disease (1.38 [1.20-1.59]), chronic obstructive pulmonary disease (1.3 [1.16-1.46]), valvular heart disease (1.81 [1.60-2.04]), atrial fibrillation (HR 1.75 [95% CI 1.54-1.98]), tobacco use (1.84 [1.57-2.15]), and alcohol abuse (1.84 [1.56-2.16]). Conclusion: In a large population-based cohort of older people, atherosclerotic risk factors were associated with subsequent cervical artery dissection. Further studies exploring the role of atherosclerosis in the development of cervical artery dissection are required.

Introduction: Anticoagulation in patients with acute intracranial hemorrhage (ICH) and mechanical heart valves (MHV) is often held to mitigate the risk of ICH expansion or recurrence; however there exists a competing risk of acute ischemic stroke (AIS). Optimal timing to resume anticoagulation after ICH remains uncertain. Methods: We retrospectively studied ICH patients with MHV at two academic hospitals from April, 2000-August, 2018. The primary outcome was a composite endpoint of symptomatic hematoma expansion or new ICH, AIS, and intracardiac thrombus up to 30 days post-ICH. The exposure was timing of re-initiation of anticoagulation classified as early if therapeutic anticoagulation was resumed up to 7 days after ICH; late if ≥7 and up to 30 days after ICH; and never if not resumed or resumed after 30-days post-ICH. Cox proportional hazard models were built adjusted for age, sex, and covariates significantly different in univariate analysis at a pre-specified p-value threshold of 0.05. Results: We identified 184 patients with ICH and MHV (65 anticoagulated early, 100 resumed late, 19 not resumed by day 30 post-ICH). We observed 12 AIS, 16 new ICH, and 6 intracardiac thromboses. The mean time from ICH to anticoagulation in the cohort was 12.7 days. Patients resumed early versus late were more likely to have atrial fibrillation (62% versus 42%), and less likely to be reversed (75% versus 94%), to undergo hematoma evacuation (23% versus 43%), have midline shift (27% versus 52.9%), and to have intracerebral involvement (26% versus 49%). There was no significant difference in the hazard of AIS, new or symptomatic ICH expansion, or the composite outcome among those resumed early versus late. Patients not resumed within 30 days post-ICH had a significantly higher risk of AIS compared to those resumed within 30 days (HR 15.9; 95% C.I.1.9-129.7, p=0.0098). Discussion: In this study of ICH patients with MHV, there was no difference in the 30-day thrombotic and hemorrhagic brain-related outcomes in patients anticoagulated within 7 days versus 7-30 days. Withholding anticoagulation within the first 30 days was associated with a significantly higher risk of AIS. Our findings provide a discrete time window to guide resumption of anticoagulation in MHV patients with ICH.

Background: Intracerebral hemorrhage (ICH) is associated with an increased risk of ischemic stroke. Whether there are racial and ethnic disparities in the risk of ischemic stroke after ICH is poorly understood. Hypothesis: Non-Hispanic Black and Hispanic ICH patients have a higher risk of ischemic stroke compared to White ICH patients. Methods: We retrospectively analyzed data from the Healthcare Cost and Utilization Project on all hospitalizations at all nonfederal hospitals in Florida from 2005 to 2018 and New York from 2006 to 2016. We included patients with an ICH, and without a prior or concomitant diagnosis of ischemic stroke. ICH and ischemic stroke were ascertained using validated ICD-9-CM and ICD-10-CM codes. Using Cox proportional hazard models, we studied the relationship between race and risk of ischemic stroke, after adjustment of demographics and comorbidities. Results: We included 55,582 patients with ICH- 66% Non-Hispanic White, 19% Non-Hispanic Black, and 13% Hispanic. Black and Hispanic patients were younger and had a higher prevalence of cardiovascular comorbidities; however, atrial fibrillation was more prevalent among White patients. During a median follow up period of 3.6 years (IQR 0.7-7.2), an incident ischemic stroke occurred in 3,361 (9%) Non-Hispanic White, 1,308 (12%) Non-Hispanic Black, and 858 (12%) Hispanic patients (p Conclusions: Among patients with ICH, Non-Hispanic Black and Hispanic patients had a significantly higher risk of ischemic stroke compared to Non-Hispanic White patients.

Introduction: Serum neutrophil-lymphocyte ratio (NLR) is a surrogate marker for the inflammatory response after intracerebral hemorrhage (ICH), and is associated with perihematomal edema and long-term functional outcomes. Whether NLR is associated with short-term ICH complications is poorly understood. Hypothesis: NLR is associated with 30-day infection and thrombotic events after ICH. Methods: We performed a post hoc exploratory analysis of the Clot Lysis: Evaluating Accelerated Resolution of Intraventricular Hemorrhage (CLEAR) III trial. The study exposure was the serum NLR obtained at baseline, and on days 3 and 5. The co-primary outcomes, ascertained at 30 days, were any infection and a thrombotic event, defined as composite of cerebral infarction, myocardial infarction, or venous thromboembolism; both infection and thrombotic event were determined via adjudicated adverse event reporting. Binary logistic regression was used to study the relationship between NLR and outcomes, after adjustment for demographics, ICH severity and location, and treatment randomization. Results: Among the 500 patients enrolled in CLEAR III, we included 228 (45.6%) with no missing data on daily NLR in the first week. There were no differences in demographics, comorbidities, or ICH severity between patients with and without data on NLR. In adjusted logistic regression models, NLR at day 3 was associated with infection (OR, 1.2; 95% CI, 1.01-1.26), but not with thrombotic events (OR, 0.96; 95% CI, 0.85-1.10). Conversely, NLR at day 5 was associated with thrombotic events (OR, 1.2, 95% CI, 1.01-1.26), but not with infections (OR, 1.03; 95% CI, 0.94-1.14). NLR at baseline was not associated with either outcome. Conclusions: Serum NLR ascertained between days 3 and 5 was associated with 30-day infection and thrombotic events after ICH, suggesting that NLR could be a potential early biomarker for ICH-related complications.

Introduction: Chronic hypertension is an established long-term risk factor for stroke. However, little is known about short-term stroke risk after an episode of acute severe hypertension without evidence of target organ damage (i.e., hypertensive urgency [HU]). We evaluated the short-term risk of stroke after an ED visit with HU resulting in discharge home (treat-and-release). Methods: We performed a case-crossover study using deidentified administrative claims from all nonfederal EDs and hospitals across 11 states. The study cohort comprised patients diagnosed with any stroke (ischemic stroke, intracerebral hemorrhage, or subarachnoid hemorrhage), defined using validated ICD-10 codes, between 2016-2018. We tabulated and compared incident ED visits for HU during case periods (2-week intervals from 0-24 weeks before the index stroke) to control periods (equivalent time periods exactly 1 year earlier). ED visits with HU were ascertained using the ICD-10 code I16.0, which we validated through detailed chart review of 50 patients at our center resulting in a code sensitivity and specificity of 100% and 96%, respectively. We used McNemar’s test for matched data to calculate risk ratios (RRs) for an ED HU visit occurring before stroke. Results: Among 45,063 patients with stroke, 22,417 (50%) were female and 37,577 (83%) had a prior diagnosis of hypertension. There were 201 patients with stroke who had at least one ED visit for HU during the preceding 24 weeks. An ED visit for HU was significantly more common in the 2 weeks before stroke compared to the 2-week control period 1 year earlier (RR, 5.1; 95% CI, 2.4-12.7; p Conclusion: Treat-and-release ED visits for HU are associated with a significantly increased short-term risk of stroke.

Introduction: Syndromes of cerebrovascular dysregulation such as posterior reversible encephalopathy syndrome (PRES) and reversible cerebral vasoconstriction syndrome (RCVS) can be challenging to diagnose given their rarity and the need for advanced neuroimaging to diagnose them. We sought to measure the rate of potential PRES/RCVS misdiagnosis in the ED and identify features associated with misdiagnosis. Methods: We conducted a retrospective cohort study of patients with PRES/RCVS using deidentified administrative claims data from all nonfederal EDs and hospitals across 11 states from 2016-2018. To identify patients with PRES/RCVS, we used the previously validated ICD-10-CM codes I67.841 and I67.83. We defined patients with a probable misdiagnosis of PRES/RCVS as those with an ED visit resulting in discharge to home that occurred within the 14 days prior to their PRES/RCVS hospitalization. Only preceding ED visits where a non-specific neurological condition (e.g., headache, dizziness, numbness) was diagnosed were considered instances of probable ED misdiagnosis. Standard tests of comparison between patients with versus without probable misdiagnosis were used to identify patient-level and ED facility-level features associated with misdiagnosis. Results: We identified 4,633 patients hospitalized for PRES/RCVS; the majority (4,169; 90.0%) had PRES. A total of 210 patients (4.5%, 95% CI: 3.95-5.17) had at least one preceding ED visit with a probable misdiagnosis; these patients were younger (mean age 47.7 vs. 53.8 years; P Conclusion: Probable ED misdiagnosis occurred in nearly 1 of 20 cases of PRES/RCVS in a large, multistate cohort.

Background and Purpose: Recent studies suggest that alteration of the normal gut microbiome contributes to atherosclerotic burden and cardiovascular disease. While many gastrointestinal diseases are known to cause disruption of the normal gut microbiome in humans, the clinical impact of gastrointestinal diseases on subsequent cerebrovascular disease remains unknown. We conducted an exploratory analysis evaluating the relationship between gastrointestinal diseases and ischemic stroke. Methods: We performed a retrospective cohort study using claims between 2008 and 2015 from a nationally representative 5% sample of Medicare beneficiaries. We included only beneficiaries ≥66 years of age. We used previously validated diagnosis codes to ascertain our primary outcome of ischemic stroke. In an exploratory manner, we categorized gastrointestinal disorders by anatomic location, disease chronicity, and disease mechanism. We used Cox proportional hazards models to examine associations of gastrointestinal disorder categories and ischemic stroke with adjustment for demographics and established vascular risk factors. Results: Among a mean of 1 725 246 beneficiaries in each analysis, several categories of gastrointestinal disorders were associated with an increased risk of ischemic stroke after adjustment for established stroke risk factors. The most notable positive associations included disorders of the stomach (hazard ratio, 1.17 [95% CI, 1.15–1.19]) and functional (1.16 [95% CI, 1.15–1.17]), inflammatory (1.13 [95% CI, 1.12–1.15]), and infectious gastrointestinal disorders (1.13 [95% CI, 1.12–1.15]). In contrast, we found no associations with stroke for diseases of the anus and rectum (0.97 [95% CI, 0.94–1.00]) or neoplastic gastrointestinal disorders (0.97 [95% CI, 0.94–1.00]). Conclusions: In exploratory analyses, several categories of gastrointestinal disorders were associated with an increased risk of future ischemic stroke after adjustment for demographics and established stroke risk factors.

Introduction: When a stroke hospitalization follows soon after an Emergency Department (ED) treat-and-release visit for non-specific neurological complaints, a diagnostic error may have occurred. In this study, we sought to evaluate potential stroke misdiagnoses after ED treat-and-release headache visits. Methods: We conducted a retrospective cohort study using state-wide administrative claims data for all ED visits and admissions at nonfederal hospitals in Florida 2005-2018 and New York 2005-2016. Using standard ICD codes, we identified adult patients discharged home from the ED with a benign headache diagnosis (cohort of interest) as well as those with a diagnosis of back pain or renal colic (negative control cohorts). The primary study outcome was hospitalization within 30 days for stroke (ischemic or hemorrhagic), defined using validated ICD codes. We used Cox proportional hazards modeling to assess the relationship between the index ED visit reason and stroke hospitalization adjusting for demographics and vascular risk factors. Results: We identified 1,458,904 patients with an ED treat-and-release headache visit; mean age was 41 (SD: 17) and 70% were female. A total of 2,636 (0.18%) headache patients were hospitalized for stroke within 30 days. Stroke risk was higher among headache patients compared to patients diagnosed with renal colic (HR: 2.7; 95% CI, 2.3-3.1) or back pain (HR: 3.8; 95% CI, 3.6-4.1; Figure). Among patients Conclusion: Approximately 1 in 500 patients discharged home from the ED with a headache diagnosis had a stroke in the following month. Stroke risk was 3-4 times higher after an ED visit for headache compared to back pain or renal colic. There may be opportunities to reduce diagnostic error among patients with ED visits for headache, particularly for those

Introduction: Posterior reversible encephalopathy syndrome (PRES) can cause brain infarction and hemorrhage in the acute phase. We hypothesized that PRES is also associated with an increased long-term risk of stroke. Methods: We performed a retrospective cohort study using statewide all-payer claims data from 2016-2018 for all admissions to nonfederal hospitals in 11 states. Adult patients with PRES were compared to patients with TIA (positive control) and renal colic (negative control), as done in prior studies. The primary outcome was any stroke, and secondary outcomes were ischemic and hemorrhagic stroke. Diagnoses were ascertained using ICD-10-CM codes. We excluded patients with stroke before and during index admissions for PRES and controls. We used Cox proportional hazards analyses to evaluate associations between PRES and stroke, adjusting for demographics, stroke risk factors, and factors associated with PRES (cancer, kidney disease, rheumatological disease). In a sensitivity analysis, stroke events within 4 weeks of index admissions were excluded. Results: We identified 3,086 patients with PRES, 85,189 with TIA, and 3,094 with renal colic. Patients with PRES (55±17 years) and renal colic (54±18 years) were younger than those with TIA (72±14 years). Median follow-up was 1.1 years and similar between groups. Stroke incidence was 3.2 per 100 person-years after PRES, 3.8 per 100 person-years after TIA, and 0.4 per 100 person-years after renal colic (Figure). After adjustment, patients with PRES had a similar stroke risk as patients with TIA (HR, 0.9; 95% CI, 0.8-1.2), and a higher stroke risk than patients with renal colic (HR, 2.6; 95% CI, 2.0-3.5). Compared to TIA, PRES had a higher risk of hemorrhagic stroke (HR, 2.9; 95% CI, 2.2-3.9) and a lower risk of ischemic stroke (HR, 0.7; 95% CI, 0.6-0.9). Results were similar with a 4-week washout period. Conclusions: PRES is associated with an increased risk of future stroke, specifically hemorrhagic stroke.

Introduction: Coronavirus Disease 2019 (COVID-19) is associated with an increased risk of stroke and worse stroke outcomes. A clinical score that can identify high-risk patients could enable closer monitoring and targeted preventative strategies. Methods: We used data from the AHA’s COVID-19 CVD Registry to create a clinical score to predict the risk of stroke among patients hospitalized with COVID-19. We included patients aged >18 years who were hospitalized with COVID-19 at 122 centers from March 2020-March 2021. To build our score, we used demographics, preexisting comorbidities, home medications, and vital sign and lab values at admission. The outcome was a cerebrovascular event, defined as any ischemic or hemorrhagic stroke, TIA, or cerebral vein thrombosis. We used two separate analytical approaches to build the score. First, we used Cox regression with cross validation techniques to identify factors associated with the outcome in both univariable (p Results: Among 21,420 patients hospitalized with COVID-19 (mean age 61 years, 54% men), 312 (1.5%) had a cerebrovascular event. Using traditional Cox regression, we created and internally validated a risk stratification score (CANDLE) (Fig) with a C-statistic of 0.66 (95% CI, 0.60-0.72). The machine learning estimator had similar discriminatory performance, with a C-statistic of 0.69 (95% CI, 0.65-0.72). For ischemic stroke or TIA, CANDLE’s C-statistic was 0.67 (95% 0.59-0.76). Conclusion: We developed an easy-to-use clinical score, with similar performance to a machine learning estimator, to help stratify stroke risk among patients hospitalized with COVID-19.

Introduction: Isolated amyloid deposition in the brain is associated with intracranial hemorrhage. Whether systemic amyloidosis also increases the risk of intracranial hemorrhage is unclear. Methods: We evaluated the association between systemic amyloidosis and intracranial hemorrhage using claims data from a 5% national sample of Medicare beneficiaries from 2008-2015. The primary outcome was non-traumatic intracranial hemorrhage, defined as a composite of intracerebral hemorrhage, subarachnoid hemorrhage, and subdural hemorrhage. Secondary outcome were each hemorrhage type assessed separately. The exposure and outcomes were identified using previously validated ICD-9-CM diagnosis codes. We used Cox regression analysis adjusting for demographics and vascular risk factors to evaluate the association between systemic amyloidosis and intracranial hemorrhage. We also examined the risk of hip fracture (negative control). In sensitivity analyses, we excluded patients with cardiac amyloidosis, a subset most likely to be on antithrombotic therapy. Results: Among 1.8 million Medicare beneficiaries, 924 were diagnosed with systemic amyloidosis. During a median follow-up of 5.3 years (IQR, 2.8- 6.7), the cumulative incidence of intracranial hemorrhage was 19 per 1,000 patients per year among patients with amyloidosis, and 2 per 1,000 patients per year in those without amyloidosis. In adjusted Cox models, systemic amyloidosis was associated with an increased risk of intracranial hemorrhage (HR, 4.3; 95% CI, 2.9-6.3). The association persisted in a sensitivity analysis after excluding beneficiaries with cardiac amyloidosis (HR, 8.0; 95% CI, 5.0-12.7). In secondary analyses, systemic amyloidosis was associated with intracerebral hemorrhage (HR, 5.6; 95% CI, 3.6-8.7), subarachnoid hemorrhage (HR, 14.7; 95% 9.0-24.0), and subdural hemorrhage (HR, 3.6; 95% 2.0-6.2). There was no association between systemic amyloidosis and hip fracture (HR, 0.9; 95% CI, 0.6-1.4). Conclusions: In a large, heterogeneous national cohort of elderly patients, a diagnosis of systemic amyloidosis was associated with a 4-fold increased risk of intracranial hemorrhage, including intracerebral, subarachnoid, and subdural hemorrhages.

Objective: To assess rates of postoperative stroke after elective noncardiac surgery in patients with atrial fibrillation (AF). Methods: We conducted a retrospective cohort study using all-payer administrative claims data on all non-federal hospitalizations and emergency department visits in 11 states between 2016 and 2018. We included patients hospitalized for elective noncardiac surgery, as defined by a surgical diagnosis related group and major diagnostic category codes. The exposure variable was preoperative AF. The outcome variable was ischemic stroke within 30 days of surgery. We performed survival analyses using Kaplan-Meier cumulative rates and Cox proportional hazards models. We stratified AF patients by their CHA 2 DS 2 -VASc score and tested its discrimination using the c-statistic. Results: We identified 1,301,709 patients undergoing elective noncardiac surgery, of whom 94,363 (7.3%) had preoperative AF. Patients with AF were older (mean age, 73 versus 62 years) and had higher CHA 2 DS 2 -VASc scores (mean score, 3.2 vs 2.2). We identified 2,893 patients with postoperative stroke. The cumulative rate of postoperative stroke was 0.65% (95% CI, 0.60-0.70%) in patients with AF vs 0.19% (95% CI, 0.18-0.20%) in patients without AF. After adjustment for demographics and vascular risk factors, AF was associated with a higher risk of postoperative stroke (HR, 1.7; 95% CI, 1.5-1.8). Among AF patients, the CHA 2 DS 2 -VASc score was a good predictor of postoperative stroke (AUC, 0.81; 95% CI, 0.79-0.83). Rates of postoperative stroke among AF patients ranged from 2 DS 2 -VASc score of 0-2 to 14% in those with a score of 8 (Figure). Conclusions: Patients with AF faced a heightened risk of postoperative stroke and this risk varied in proportion to the CHA 2 DS 2 -VASc score.

Introduction: Transthoracic echocardiography (TTE) is valuable in evaluating stroke etiology. A left ventricular (LV) thrombus, the identification of which can immediately impact clinical management, is rarely seen unless the ejection fraction (EF) is less than 50%. A clinical prediction score to identify stroke patients with EF less than 50% may help guide the timing of TTE after stroke. Methods: The CAESAR registry includes all patients with ischemic stroke at our medical center. We derived a clinical prediction score using CAESAR data from calendar years 2011-2016. We included all patients who underwent TTE and had a quantitative EF measurement. We selected clinical factors, laboratory values, and vital signs based on biological plausibility and the results of multiple logistical regression with backward selection. Results: Of 2,116 patients with ischemic stroke from 2011-2016, 1,045 patients had an EF measurement. The mean age was 63 (SD, 15), 49% were women, and the mean EF was 63% (SD, 14%). Reduced EF was identified in 171 patients (16%). Our final model comprised historical variables (coronary disease, heart failure, and chronic kidney disease) and clinical parameters from the time of admission (NIHSS score, heart rate, serum potassium, and serum creatinine). The model AUC was 0.80 (95% CI, 0.76-0.85) and model calibration was good (Figure). At a predicted probability threshold of 0.1, the score’s sensitivity for reduced EF was 80% with a specificity of 62%. In a sensitivity analysis excluding patients with atrial fibrillation, the AUC was 0.77 (95% CI 0.70-0.83) and calibration remained good. Conclusions: We derived a clinical score with good performance for predicting reduced EF in acute ischemic stroke patients. If externally validated, such a score may help identify which patients are most likely to benefit from an expedited inpatient TTE.

Background: The postpartum state is associated with a heightened risk of thrombosis. The duration of heightened risk for postpartum cerebral venous thrombosis (CVT) is uncertain. Methods: Using claims data from the Healthcare Cost and Utilization Project (HCUP) from all emergency departments and acute care hospitalizations in Florida from 2005-2015 and New York from 2006-2015, we identified women aged ≥18 years old who were hospitalized for labor and delivery. CVT was ascertained using previously validated International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM), diagnosis codes. For women with multiple labor-related hospitalizations during a single 40-week period, we excluded cases of false labor by identifying delivery as the latest hospitalization during that time. Patients with claims for CVT before their first recorded delivery, and women with a second delivery during the follow-up period were also excluded. We compared the likelihood of a first-ever recorded CVT during postpartum days 0-41 compared with the same period 1 year later. We repeated this crossover-cohort analysis for consecutive 6-weeks periods after delivery, as compared with the corresponding 6-week period 1 year later. We used McNemar's to calculate odds ratios for each 6-week interval. Results: Among the 1,406,447 women with a first recorded delivery, the risk of CVT was markedly higher within the 6 weeks after delivery than in the same period 1 year later (22 versus 3 CVTs per million deliveries). This corresponded to an absolute risk difference of 19 events per million (95% confidence interval [CI], 11-27) and an odds ratio of 10.0 (95% CI, 3.1-51.2). There was no significant increase in the risk of CVT during the period of 7 to 12 weeks after delivery as compared with the same period 1 year later with an absolute risk difference of 6.0 events (95% CI, 0-11) per million deliveries and an odds ratio of 3.0 (95% CI, 0.9-12.8). Conclusion: There appears to be a heightened risk of CVT for 6 weeks after delivery.

Introduction: There is a known risk of ischemic stroke (IS) and mortality among patients with heart failure with reduced ejection fraction (HFrEF) and sinus rhythm. We identify predictors of IS and all-cause death in patients with left ventricular ejection fraction (LVEF) < 35% and sinus rhythm by a machine-learning approach. Methods: We performed a post-hoc analysis of the WARCEF trial which randomized patients with LVEF < 35% and sinus rhythm to either aspirin or warfarin. We built two Random Forest for Survival, Longitudinal, and Multivariate (RF-SLAM) algorithms to model the outcomes of IS and all-cause death separately using all baseline variables with missingness < 10%. The training data set was comprised of 70% of observations and the testing set of the remaining 30%. To assess variable importance in outcome prediction, Mean Decrease Accuracy was computed for each variable over all out-of-bag cross-validated predictions. Results: In 2,298 participants (median age 61.5 years [IQR 54.3-69.6], 20% female) during a mean follow-up of 3.5 years (SD 1.8 years), 84 (3.7%) patients had an ischemic stroke and 547 (23.8%) died. Patient-specific characteristics contributing most to ischemic stroke prediction with variable Mean Decrease Accuracies ≥ 2.5 were prior transient ischemic attack, CHA 2 DS 2 -VASc score, age, prior stroke, glucose, and blood urea nitrogen (model accuracy 0.95; 95% C.I. 0.93-0.97). Age, hemoglobin, glucose, INR, platelet count, BUN, and systolic blood pressure were the most important patient-specific predictors of all-cause death with variable Mean Decrease Accuracies ≥ 2.5 (model accuracy 0.76; 95% C.I. 0.72-0.79). Conclusions: Clinical and serologic characteristics identified by the RF-SLAM algorithm predict IS and all-cause death risks in patients with HFrEF and sinus rhythm. Future studies are needed to assess the impact of these factors on treatment effects in heart failure trials evaluating outcomes which include stroke.

Background and Purpose— Patients who continue to smoke after a stroke face a higher risk of recurrent stroke. While several effective drugs for smoking cessation became available over the past 2 decades, whether active smoking has decreased among stroke survivors is unknown. We, therefore, evaluated trends in active smoking among stroke survivors during this period. Methods— We performed trends analyses using cross-sectional data collected every 1 to 2 years from 2 US health surveys spanning 1999 to 2018. In the National Health and Nutrition Examination Survey (NHANES) and the Behavioral Risk Factor Surveillance System (BRFSS) survey, participants were asked about prior stroke and active tobacco smoking. In NHANES, serum cotinine levels were available as a secondary measure of active smoking. We used multivariable logistic regression models for survey data to assess trends in active smoking among participants with and without prior stroke. Results— Among 49 375 participants in NHANES during 1999 to 2016 and 3 621 741 participants in BRFSS during 2011 to 2018, the prevalence of stroke was ≈3%. The overall prevalence of active smoking among stroke survivors was 24% in NHANES and 23% in BRFSS. Among individuals without prior stroke, the odds of smoking decreased over time in both NHANES (odds ratio, 0.95 per 2 years [95% CI, 0.93–0.96]) and BRFSS (odds ratio, 0.96 per year [95% CI, 0.96–0.96]). In contrast, there was no decrease in smoking among stroke survivors in NHANES (odds ratio, 1.00 [95% CI, 0.93–1.07]) or BRFSS (odds ratio, 0.99 [95% CI, 0.98–1.004]). Results were consistent in secondary analysis using biochemical ascertainment of active smoking in NHANES and in sensitivity analyses accounting for potential demographic changes in stroke epidemiology. Conclusions— In contrast to the general population, the prevalence of active smoking among stroke survivors has not decreased during the past 2 decades.

Background and Purpose— The risk of arterial ischemic events after subdural hemorrhage (SDH) is poorly understood. This study aimed to evaluate the risk of acute ischemic stroke and myocardial infarction among patients with and without nontraumatic SDH. Methods— We performed a retrospective cohort study using claims data from 2008 through 2014 from a nationally representative sample of Medicare beneficiaries. The exposure was nontraumatic SDH. Our primary outcome was an arterial ischemic event, a composite of acute ischemic stroke and acute myocardial infarction. Secondary outcomes were ischemic stroke alone and myocardial infarction alone. We used validated International Classification of Diseases , Ninth Revision , Clinical Modification diagnosis codes to identify our predictor and outcomes. Using Cox regression and corresponding survival probabilities, adjusted for demographics and vascular comorbidities, we computed the hazard ratio in 4-week intervals after SDH discharge. We performed secondary analyses stratified by strong indications for antithrombotic therapy (composite of atrial fibrillation, peripheral vascular disease, valvular heart disease, and venous thromboembolism). Results— Among 1.7 million Medicare beneficiaries, 2939 were diagnosed with SDH. In the 4 weeks after SDH, patients’ risk of an arterial ischemic event was substantially increased (hazard ratio, 3.6 [95% CI, 1.9–5.5]). There was no association between SDH diagnosis and arterial ischemic events beyond 4 weeks. In secondary analysis, during the 4 weeks after SDH, patients’ risk of ischemic stroke was increased (hazard ratio, 4.2 [95% CI, 2.1–7.3]) but their risk of myocardial infarction was not (hazard ratio, 0.8 [95% CI, 0.2–1.7]). Patients with strong indications for antithrombotic therapy had increased risks for arterial ischemic events similar to patients in the primary analysis, but those without such indications did not demonstrate an increased risk for arterial ischemic events. Conclusions— Among Medicare beneficiaries, we found a heightened risk of arterial ischemic events driven by an increased risk of ischemic stroke, in the 4 weeks after nontraumatic SDH. This increased risk may be due to interruption of antithrombotic therapy after SDH diagnosis.

Background and Purpose— The risk of arterial ischemic events after intracerebral hemorrhage (ICH) is poorly understood given the lack of a control group in prior studies. This study aimed to evaluate the risk of acute ischemic stroke and myocardial infarction (MI) among patients with and without ICH. Methods— We performed a retrospective cohort study using claims data from Medicare beneficiaries from 2008 to 2014. Our exposure was acute ICH, identified using validated International Classification of Diseases, Ninth Revision, Clinical Modification diagnosis codes. Our primary outcome was a composite of acute ischemic stroke and MI, whereas secondary outcomes were ischemic stroke alone and MI alone. We used Cox regression analysis to compute hazard ratios during 1-month intervals after ICH. Sensitivity analyses entailed exclusion of patients with atrial fibrillation and valvular heart disease. Results— Among 1 760 439 Medicare beneficiaries, 5924 had ICH. The 1-year cumulative incidence of an arterial ischemic event was 5.7% (95% CI, 4.8–6.8) in patients with ICH and 1.8% (95% CI, 1.7–1.9) in patients without ICH. After adjusting for potential confounders, the risk of an arterial ischemic event remained significantly increased for the first 6 months after ICH and was especially high in the first month (hazard ratio, 6.7 [95% CI, 5.0–8.6]). In secondary analysis, the risk of ischemic stroke was increased in the first 6 months after ICH (hazard ratio, 6.1 [95% CI, 3.5–9.3]) but the risk of MI was not (hazard ratio, 1.6 [95% CI, 0.3–2.9]). In sensitivity analyses excluding patients with atrial fibrillation and valvular heart disease, the association between ICH and arterial ischemic events was similar to that of the primary analysis. Conclusions— In a large population-based cohort, we found that elderly patients with ICH had a substantially increased risk of ischemic stroke in the first 6 months after diagnosis. Further exploration of this risk is needed to determine optimal secondary prevention strategies for these patients.

Introduction: Influenza-like illness (ILI) is associated with an increased short-term risk of ischemic stroke. Whether ILI is associated with an increased short-term risk of hemorrhagic stroke remains uncertain. Hypothesis: We hypothesized that ILI would be associated with a heightened risk of hemorrhagic stroke. Methods: We performed a case-crossover analysis utilizing administrative claims data from all emergency department visits and acute care hospitalizations from 2006-2015 in NY and 2005-2015 in FL. We used previously validated International Classification of Disease, Ninth Revision, Clinical Modification codes (ICD-9-CM) to identify patients with ILI and hemorrhagic stroke. Hemorrhagic stroke was defined as the composite of nontraumatic intracranial hemorrhage, nontraumatic subarachnoid hemorrhage, and nontraumatic subdural hemorrhage. We compared the risk of hemorrhagic stroke in successive 30-day periods after ILI versus the corresponding 30-day period one year earlier. We used McNemar test for matched data to calculate the absolute risk increases. Results: We identified 2,838,178 patients with ILI. The absolute increase in hemorrhagic stroke risk was 0.02% (95% confidene interval [CI], 0.02-0.03%) in the thirty days post ILI compared with the same period one year earlier (OR, 3.7; 95% CI, 3.2-4.3). The absolute increase in hemorrhagic stroke risk decreased over successive 30-day periods after ILI and was no longer significant after 180 days post ILI (Figure). Our results were similar when we evaluated the risk of hemorrhagic stroke subtypes separately. Conclusions: ILI is associated with a heightened short-term risk of hemorrhagic stroke. Further studies are warranted to evaluate mechanisms of how infection and/or inflammation lead to a heightened risk of hemorrhagic stroke.

Introduction: Elevations in troponin (cTn) are common in patients with acute ischemic stroke, yet their significance remains uncertain. Hypothesis: Elevated cTn at the time of acute ischemic stroke is associated with ischemic stroke recurrence. Methods: We included all adult patients with acute ischemic stroke who were residents of the Greater Cincinnati/Northern Kentucky region and who presented to an emergency department (ED) in 2015 and who had a cTn measured within 24 hours of ED arrival. Our exposure variable was an elevated cTn, defined as a value exceeding the laboratory’s 99 th percentile. Our primary outcome was ischemic stroke recurrence, defined as a new ischemic stroke with radiographic confirmation in the 3 years following the index ischemic stroke event. Cox proportional hazards model was used to evaluate the association between elevated cTn and ischemic stroke recurrence while adjusting for demographics, vascular risk factors, and stroke severity. In a secondary analysis, we excluded patients with a concomitant adjudicated myocardial infarction (MI) at the time of the index ischemic stroke. Results: Among 2,334 patients with acute ischemic stroke, 1,992 (85%) had a cTn assay within 24 hours of ED arrival and were included in the analysis. 402 (20%) patients had an elevated cTn and 259 (13%) patients had a recurrent ischemic stroke. 66 (3%) patients had an elevated cTn and a concomitant acute MI and 336 (17%) patients had an elevated cTn without a concomitant acute MI. After adjustment for demographics, vascular risk factors, and stroke severity, we found an association between elevated cTn and recurrent ischemic stroke (hazards ratio [HR], 1.5; 95% CI, 1.1-2.0). Our results were unchanged after excluding patients with a concomitant adjudicated MI (HR 1.4; 95% CI, 1.03-2.0). Conclusions: Among patients with acute ischemic stroke, elevated cTn even in the absence of concomitant adjudicated MI, was associated with ischemic stroke recurrence. Further mechanistic studies are necessary to explore the underlying etiology of hypertroponinemia among patients with acute ischemic stroke in order to guide targeted therapies to reduce stroke recurrence.

Introduction: Aortic stenosis (AS) is known to cause mechanical degradation of von Willebrand factor, resulting in an increased risk of gastrointestinal bleeding, also known as Heyde syndrome. We hypothesized that AS is also associated with an increased risk of nontraumatic intracerebral hemorrhage (ICH). Methods: We performed a retrospective cohort study of Medicare beneficiaries using a 5% sample of inpatient and outpatient claims from1/1/2008-9/30/2015. Based on prior validation, we ascertained AS based on at least one inpatient or two outpatient claims with ICD-9-CM diagnosis code 395.0 in any position. ICH was identified through a validated ICD-9-CM diagnosis code algorithm. We used survival statistics to determine incidence rates and Cox proportional hazard analyses to examine associations. In prespecified models, we controlled for age, gender, race, bleeding risk (HAS-BLED and ATRIA scores), and common indications for antithrombotic treatment (atrial fibrillation, coronary artery disease, peripheral vascular disease, venous thromboembolism). Results: Among 1,785,836 Medicare beneficiaries, the mean age was 73.5 years (SD, 7.7) and 57.0% were women. AS was diagnosed in 6,157 (0.34%) patients. During a mean of 4.7 years (SD, 2.2) of follow-up, 28,309 (1.6%) were hospitalized with ICH. The incidence of ICH was 5.9 (95% CI, 4.9-7.2) per 1,000 person-years in those with AS compared to 3.4 (95% CI, 3.4-3.4) per 1,000 person-years in those without. After adjustment for demographics, AS was associated with an increased risk of ICH (HR, 1.31; 95% CI, 1.09-1.59). This association was not statistically significant after adjusting additionally for HAS-BLED score components (HR 1.15, 95% CI 0.95-1.39) or ATRIA score components (HR 1.18, 95% CI 0.98-1.43). Effect sizes were further attenuated after adjusting for indications for antithrombotic drugs in addition to the HAS-BLED score (HR, 0.90; 95% CI, 0.74-1.09) and ATRIA score (HR, 0.90; 95% CI, 0.73-1.08). Conclusions: Medicare beneficiaries with AS faced an elevated risk of ICH. However, comorbid conditions that require the use of antithrombotic drugs accounted for the observed association, making an independent association between AS and ICH unlikely.

Introduction: Patients with acute ischemic stroke (AIS) are generally vulnerable to subsequent infection, but there are few population-based data on the risk of herpes zoster infection after AIS. We tested the hypothesis that AIS is associated with an increased risk of zoster. Methods: We performed a retrospective cohort study using statewide administrative claims data from all emergency department (ED) visits and admissions at nonfederal hospitals in Florida from 2005 to 2015 and New York from 2006 to 2015. These Healthcare Cost and Utilization Project data are well suited for longitudinal analyses of acute care utilization. The primary exposure was AIS, and the outcome was subsequent zoster; diagnoses were ascertained using validated ICD-9-CM codes. We excluded people with zoster before AIS. Survival statistics were used to calculate incidence rates, and Cox proportional hazards analysis was used to determine the association between AIS and subsequent ED visit or admission with zoster. In addition to demographics and comorbidities, models were adjusted for conditions associated with zoster (cancer and HIV/AIDS). In a secondary analysis, we limited the population to people under 50 years old, because current guidelines recommend zoster vaccination for only those at least 50 years old. Results: Among 19,675,854 beneficiaries, 421,940 (2.1%) had AIS; their mean age was 70.8 (SD, 14.5) years. Follow-up duration was a mean of 4.1 (SD, 3.0) years. The incidence of zoster was 4.1 per 1000 patient-years in those with AIS and 2.1 per 1000 patient-years in those without. After AIS, the median time to zoster was 1.7 years (IQR, 0.4-4.1). In unadjusted models, patients with AIS had a two-fold higher risk of zoster (HR, 2.1; 95% CI, 2.0-2.1). AIS remained associated with zoster after adjusting for cardiopulmonary comorbidities and risk factors, medical comorbidities, tobacco and alcohol use, cancer, and HIV/AIDS (HR, 1.34; 95% CI, 1.30-1.39). This association was also observed in people under 50 years old (HR, 1.55; 95% CI, 1.31-1.84). Conclusions: AIS is associated with an increased risk of subsequent ED and inpatient visit with zoster infection. Preventive strategies, including with currently available vaccinations, should be investigated.

Background and Purpose: Emerging data suggest an increased risk of arterial ischemic events after intracerebral hemorrhage (ICH), but their impact on ICH outcomes is unclear. This study aimed to evaluate the risk of death among ICH survivors with and without an incident arterial ischemic event. Methods: We performed a retrospective cohort study using claims data from Medicare beneficiaries with a non-traumatic ICH from January 2008 to October 2015. Our exposure was an arterial ischemic event, defined as a composite of acute ischemic stroke or myocardial infarction (MI), identified using validated ICD-9-CM diagnosis codes. The outcome was death. After excluding ischemic events and deaths in the first 30 days after ICH discharge to prevent carryover of diagnosis codes from the initial hospitalization, we used marginal structural models to analyze the risk of death among ICH patients with and without an arterial ischemic event, after adjusting for demographics and vascular comorbidities as time-varying covariates. In secondary analyses, we studied the mortality risk separately after an ischemic stroke and MI. Results: Among 8,222 Medicare beneficiaries with an ICH, 2,371 (28.8%) had an arterial ischemic event. During a median follow up time of 2.0 years (interquartile range, 0.8-3.8), the cumulative mortality rate was 7.0% (95% confidence interval [CI], 6.5-7.5%) in patients with an arterial ischemic event and 4.0% (95% CI, 3.8-4.2%) in patients without an arterial ischemic event. In the marginal structural model, the occurrence of an arterial ischemic event was associated with an increased risk of death (hazard ratio [HR], 1.6; 95% confidence interval [CI], 1.5- 1.7). In secondary analyses, the mortality risk was elevated after both an ischemic stroke (HR, 1.5; 95% CI, 1.4-1.6), and a MI (HR, 2.6; 95% CI, 2.1-3.2). Conclusions: In a large population-based cohort, we found that elderly patients who survived an ICH had an increased risk of death after a subsequent ischemic stroke or MI. Careful exploration of secondary cardiovascular and stroke prevention strategies may be warranted in these patients.

Background and Purpose: Non-traumatic subarachnoid hemorrhage (SAH) is associated with poor long-term functional outcomes, but the risk of ischemic stroke among SAH survivors is poorly understood. Methods: We performed a retrospective cohort study using claims data from Medicare beneficiaries from 2008-2015. The exposure was a diagnosis of SAH, while the outcome was an acute ischemic stroke. The exposure and outcomes were identified using previously validated ICD-9-CM diagnosis codes. We excluded patients with prevalent ischemic stroke at the time of SAH diagnosis and those which occurred in the first 90 days after SAH discharge to avoid inclusion of stroke occurring as a medical or procedural complication of SAH. We used Cox regression adjusting for demographics and stroke risk factors to evaluate the association between SAH and long-term risk of ischemic stroke. Results: Among 1.3 million Medicare beneficiaries, 3,171 (0.18%) were diagnosed with non-traumatic SAH. During a median follow-up of 5.3 years (interquartile range [IQR], 2.7- 6.7), the cumulative incidence of ischemic stroke was 92 per 1,000 patients per year among patients with SAH, and 21 per 1,000 patients per year in those without SAH. In multivariable Cox regression analysis, SAH was associated with an increased risk of ischemic stroke (hazard ratio, 2.6; 95% confidence interval, 2.4-2.8) as compared to beneficiaries without SAH. Conclusions: In a large, heterogeneous national cohort of elderly patients, we found that survivors of SAH had more than double the long-term risk of ischemic stroke as compared to those without SAH. SAH survivors should be closely monitored and risk stratified for ischemic stroke.

Introduction: Patients with stroke face an increased risk of contracting influenza and herpes zoster. We compared vaccination rates in stroke survivors versus the general United States population. Methods: We performed a cross-sectional analysis of data from the Centers for Disease Control and Prevention (CDC) Behavioral Risk Factor Surveillance System, which is an annual, nationally representative, health survey. Respondents are asked about medical conditions and care. We used the most recent years with complete data for influenza (2018) and zoster (2017). We utilized survey procedures to estimate CDC-recommended vaccination rates for influenza (annual vaccination for all) and zoster (one-time vaccination for those at least 50 years old). Multiple logistic regression was used to compare the odds of vaccination in those with and without prior stroke, while adjusting for demographics (including income and health insurance) and comorbidities that may influence vaccination rates (obesity, diabetes, heart disease, cancer, pulmonary disease, and smoking). Results: In 2018, 8,254,136 (3.4%; 95% CI, 3.3-3.5) Americans were stroke survivors. The influenza vaccination rate was 44.4% (95% CI, 42.8-46.2) in stroke survivors and 32.8% (95% CI, 32.5-33.1) otherwise. In unadjusted models, stroke survivors were more likely to have had an influenza vaccination in the past year than those without stroke (OR, 1.6; 95% CI, 1.5-1.8). In 2017, 5,839,186 (5.7%; 95% CI, 5.5-5.9) Americans over 50 years old (i.e., eligible for zoster vaccination) were stroke survivors. The zoster vaccination rate was 30.3% (95% CI, 28.8-32.0) in stroke survivors and 27.6% (95% CI, 27.3-28.0) in those without prior stroke. Stroke survivors were more likely to have had zoster vaccination than those without stroke (OR, 1.14; 95% CI, 1.06-1.23). However, after accounting for demographics and comorbidities, stroke survivors were not more likely to be vaccinated for influenza (OR, 1.01; 95% CI, 0.93-1.10) or zoster (OR, 1.00; 95% CI, 0.90-1.12). Conclusion: Stroke survivors were not vaccinated at higher rates than expected based on demographics and comorbidities, and absolute vaccination rates were low, especially for zoster. Efforts to increase vaccination after stroke may be needed.

Introduction: Arterial dissections often have no known identifiable risk factor. Whether infection/inflammation may play a role in the development of arterial dissection is uncertain. Hypothesis: Influenza-like illness (ILI) is associated with a heightened risk of arterial dissection. Methods: We performed a case-crossover analysis using administrative claims data on emergency department visits and acute care hospitalizations from 2006 to 2015 in NY and 2005-2015 in FL. We used previously validated International Classification of Diseases, Ninth Revision, Clinical Modification codes to identify patients with ILI and arterial dissection. Arterial dissection included the composite of cervical artery dissection (carotid and vertebral), coronary artery dissection, and aortic dissection. We compared the risk of arterial dissection in successive 30-day periods after ILI versus the corresponding 30-day periods one year earlier. We used McNemar test for matched data to calculate the absolute risk increases. Results: We identified 2,838,178 patients with ILI. The absolute increase in arterial dissection was 0.005% (95% CI, 0.004-0.006%) in the thirty days post ILI compared with the same period one year earlier (OR 3.3, 95% CI, 2.5-4.4). The absolute increase in arterial dissection attenuated over successive 30-day periods after ILI and was no longer significant after 120 days post ILI (Figure). Our results were similar in secondary analyses evaluating cervical, coronary, and aortic dissections separately. Conclusions: ILI is associated with a heightened short-term risk of arterial dissection. Further studies are warranted to evaluate mechanisms of how ILI and/or related inflammation leads to a heightened risk of systemic and cerebrovascular dissections.

Background: Cervical artery dissection (CAD) often affects young, otherwise healthy people. Few data exist on whether patients with CAD face an increased vulnerability to aortic dissection. Herein we tested the hypothesis that CAD is associated with an increased risk of aortic dissection. Methods: We performed a retrospective cohort study using statewide administrative claims data from all Emergency Department visits and admissions at nonfederal hospitals in Florida from 2005 to 2015 and New York from 2006 to 2015. We used previously validated International Classification of Disease, Ninth Revision, Clinical Modification codes (ICD-9-CM) to identify patients with CAD and aortic dissection. Patients with prevalent aortic dissection were excluded. Our exposure variable was CAD and the outcome was incident aortic dissection after discharge from CAD hospitalization. Survival statistics were used to calculate incidence rates and Cox proportional hazards analysis was used to determine the association between CAD and aortic dissection while adjusting for demographics and vascular risk factors. In a secondary analysis, we excluded patients who had a traumatic CAD, defined as having concomitant ICD-9-CM codes for head or neck trauma at the time of CAD. Results: Among 19,715,114 patients, 4,537 (0.02%) had a CAD. The mean age of patients with CAD was 52.3±16.4 years. During 4.2±3.1 years of follow up, 16,571 patients were diagnosed with an aortic dissection (0.08%). The incidence of aortic dissection was 2.5 (95% CI, 1.7-3.7) per 1,000 patients per year in those with CAD versus 0.2 (95% CI, 0.2-0.2) per 1,000 patients per year in those without CAD. After adjustment for demographics and vascular risk factors, we found that CAD was associated with subsequent aortic dissection (HR 3.0, 95% CI, 2.1-4.5). Our results were similar in a secondary analysis excluding patients with traumatic CAD (HR 3.3, 95% CI, 2.2-4.8). Conclusions: In a large population-based cohort, we found that CAD was associated with a 3-fold increased risk of aortic dissection. Future studies should evaluate the utility of performing screening aortic imaging in patients with CAD.

Introduction: About 21% of acute ischemic stroke (AIS) patients present to medical attention with an elevated cardiac troponin (cTn). Previously, we described that elevated cTn is associated with an increased case-fatality at 1 year. However, it is not clear if there is a dose-dependent relationship between cTn and case-fatality, or if this effect is related to causes of death. Methods: Within a catchment area of 1.3 million we screened local hospital admissions using ICD-9/10 codes 430-436/I60-I68, G45-46 in 2014/2015, and ascertained all physician-confirmed AIS cases by retrospective chart review. Positive cTn was defined by the standard 99th percentile. To account for by hospital variance in cTn results in machine brands and normal ranges, cTn values were log-transformed and centered. Case fatality at 1 year and cause of death was obtained from the National Death Index database. Logistic regression evaluated the impact of cTn on case fatality, and included demographic and clinical risk factors in the model. The percentage with all-cause and cardiac/non-cardiac case-fatality was computed by quartiles of centered cTn levels and compared using the chi-square test. Results: In 2014/2015, there were 2989 AIS cases ascertained, which were 53% female, 30% black, with a mean age of 70 (SD 14). 441 patients with hypertropinemia were included in the analysis. See Table for case fatality at 1 year by quartile of centered cTn levels. There was no association between cTN and non-cardiac case-fatality. After adjustment for demographic and clinical characteristics, every 0.5 point increase in the centered cTn level increased the cardiac case-fatality by OR 1.19 (1.09, 1.31), p Discussion: We found that the impact of hypertropinemia on case fatality after AIS appears to be a dose-dependent association: as cTn increases, so does the cardiac case-fatality. This suggests that the degree of cTn elevation is likely an important prognostic marker for cardiac death in AIS patients.

Background and Purpose: Cardiac amyloidosis is increasingly recognized as an important cause of heart failure. Given the paucity of data on cerebrovascular complications of cardiac amyloidosis, we evaluated whether cardiac amyloidosis is associated with ischemic stroke. Methods: We performed a retrospective cohort study of Medicare beneficiaries using a 5% sample of inpatient and outpatient claims from January 1, 2008 through October 1, 2015. We identified patients with cardiac amyloidosis using International Classification of Diseases, 9th Revision, Clinical Modification ( ICD-9-CM ) code 277.3x in combination with a diagnosis code for heart failure or cardiomyopathy. The primary outcome was ischemic stroke, identified by a previously validated ICD-9-CM code algorithm. We used survival statistics to determine incidence rates. Cox proportional hazard analysis, adjusted for demographics, vascular risk factors, and the Elixhauser comorbidity index, was used to study the risk of ischemic stroke. Results: Among 1.8 million beneficiaries with mean follow-up of 4.6 years (standard deviation ±2.2), 454 (0.03%) had a diagnosis of cardiac amyloidosis. Patients with cardiac amyloidosis were older (78.1±7.4 versus 73.4±7.7 years) and had a greater comorbidity burden than those without the diagnosis. A total of 63,627 (3.6%) developed an ischemic stroke in the entire cohort. The incidence of ischemic stroke was 47 per 1,000 patients per year in those with cardiac amyloidosis compared to 7.8 per 1,000 patients per year in those without cardiac amyloidosis. In the adjusted Cox regression analysis, cardiac amyloidosis was associated with an increased risk of ischemic stroke (HR, 2.4; 95% confidence interval, 1.6-3.6). Conclusions: In a large heterogenous cohort of elderly patients, cardiac amyloidosis was associated with a 2.5-fold heightened risk of ischemic stroke.

Background and Purpose— Cervicocephalic artery dissection is an important cause of stroke. The clinical presentation of dissection can resemble that of benign neurological conditions leading to delayed or missed diagnosis. Methods— We performed a retrospective cohort study using statewide administrative claims data from all Emergency Department visits and admissions at nonfederal hospitals in Florida from 2005 to 2015 and New York from 2006 to 2015. Using validated International Classification of Diseases, Ninth Revision, CM codes , we identified adult patients hospitalized for cervicocephalic artery dissection. We defined probable misdiagnosis of dissection as having an Emergency Department treat-and-release visit for symptoms or signs of dissection, including headache, neck pain, and focal neurological deficits in the 14 days before dissection diagnosis. Multivariable logistic regression was used to compare adverse clinical outcomes in patients with and without probable misdiagnosis. Results— Among 7090 patients diagnosed with a dissection (mean age 52.7 years, 44.9% women), 218 (3.1% [95% CI, 2.7%–3.5%]) had a preceding probable Emergency Department misdiagnosis. After adjustment for demographics and vascular risk factors, there were no differences in rates of stroke (odds ratio, 0.82 [95% CI, 0.62–1.09]) or in-hospital death (odds ratio, 0.26 [95% CI, 0.07–1.08]) between dissection patients with and without a probable misdiagnosis at index hospitalization. Conclusions— We found that ≈1 in 30 dissection patients was probably misdiagnosed in the 2 weeks before their diagnosis.

Introduction: Myocardial infarction (MI) is associated with cerebral infarction. We assessed whether MI size and location is related to the risk of cerebral infarction. Methods: We performed a cross-sectional study of patients evaluated between 2014-2017 at New York-Presbyterian Hospital/Weill Cornell Medicine. We included all adults who underwent both brain MRI and delayed-enhancement cardiac MRI (DE-CMR) within 365 days of each other and had evidence of MI on DE-CMR. We evaluated associations between MI size and any cerebral infarction, apical MI and any cerebral infarction, and between MI size/location and cortical versus subcortical cerebral infarction. We used multiple logistic regression models adjusted for age, sex, race, and the total number of vascular risk factors. Results: We identified 234 patients who underwent DE-CMR and brain MRI within 365 days, among whom 76 had evidence of MI on DE-CMR. Of these 76 patients, 51 (67.1%) had evidence of cerebral infarction. There was no association between the size of MI (global MI burden) and any cerebral infarction (OR per 1% increase in MI size, 1.02; 95% CI, 1.0-1.1; P = 0.43), but there was an association between MI size and cortical cerebral infarction (OR per 1% increase in MI size, 1.05; 95% CI, 1.0-1.1; P = 0.047). We found no association between apical MI location and any cerebral infarction (OR 3.2, 95% CI, 0.9-12.2, P = 0.08), but there was an association between apical MI location and cortical cerebral infarction (OR, 3.7; 95% CI, 1.2-11.3; P = 0.02). Conclusion: Among patients with MI on cardiac imaging, MI size and apical MI location were associated with cortical cerebral infarction. Our results may help stratify cardioembolic risk and lead to improved antithrombotic treatment algorithms among patients with MI.

Background and Purpose: Pregnancy is a risk factor for stroke. The mechanisms of stroke in pregnancy have not been well established. Cervical artery dissection may be one such mechanism, but it is unclear whether pregnancy is a risk factor for cervical artery dissection. Methods: We performed a cohort-crossover analysis using administrative claims data from all hospitalizations and emergency department visits involving nonfederal acute care hospitals in NY and FL between 2005-2015. We identified women ≥12 years old who were hospitalized for labor and delivery. Our outcome was cervical artery dissection, defined as carotid or vertebral artery dissection. We defined the period of risk as 6 months antepartum through 3 months postpartum. We compared each patient’s risk of dissection during this time period versus the corresponding 270-day period exactly 1 year later. Conditional Poisson models with robust standard errors were used to calculate incidence risk ratios (IRRs). Results: We identified 4,193,417 pregnancies among 3,061,413 women during our study period. There were 52 cases of cervical artery dissection during the peripartum period and 24 cases during the control period 1 year later. The incidence of cervical artery dissection was 12 (95% CI, 10-17) per million pregnancies versus 6 (95% CI, 4-9) per million patients during the control period 1 year later (IRR, 2.2; 95% CI, 1.3-3.5). Our findings were similar when we limited our outcome to cervical artery dissections complicated by ischemic stroke (IRR, 2.3; 95% CI, 1.1-5.1). Secondary analyses suggested that the heightened risk occurred in the peripartum and postpartum period (IRR,5.5; 95% CI, 2.6-11.7), not the antepartum period (IRR, 0.5; 95% CI, 0.2-1.2). Conclusions: In a large, population-based sample of women, pregnancy was associated with an increased risk of cervical artery dissection. This increased risk appeared to be limited to the peripartum and postpartum period.

Background: Liver disease has been associated with cardiac structural abnormalities and atrial fibrillation. We hypothesized that advanced liver fibrosis - commonly subclinical in the general population - is associated with cardioembolic stroke subtype. Secondarily, we hypothesized an association with cryptogenic stroke, based on its suspected embolic etiology. Methods: Among patients prospectively enrolled in the Cornell AcutE Stroke Academic Registry (CAESAR) from 2011-2016, we selected patients who had liver function tests within 7 days of admission. We calculated each patient’s Fibrosis-4 score, a validated, non-invasive liver fibrosis score derived from age, transaminase values, and platelet count. The primary exposure was advanced liver fibrosis, defined using a validated threshold of > 3.25; these patients were compared to patients without liver fibrosis. The primary outcome was cardioembolic stroke subtype, adjudicated using TOAST classification. The secondary outcome was cryptogenic subtype. We used logistic regression to separately evaluate the association between advanced liver fibrosis and these stroke subtypes, as compared to non-cardioembolic stroke. Models were adjusted for demographics, atrial fibrillation, hypertension, diabetes, dyslipidemia, coronary artery disease, congestive heart failure, peripheral vascular disease, and chronic kidney disease. Results: Among 1,586 ischemic stroke patients in our study, the mean age was 71 (SD, 15) years, and 50% were women. Overall, 18% had liver fibrosis; 34% and 27% of strokes were cardioembolic and cryptogenic, respectively. Advanced liver fibrosis was associated with cardioembolic stroke after adjusting for demographics and vascular risk factors (odds ratio [OR], 3.8; 95% confidence interval [CI], 2.1-6.9) compared to patients without liver fibrosis. There was a significant, albeit attenuated, association with cryptogenic stroke (OR, 1.9; 95% CI, 1.0-3.4). Conclusion: Advanced liver fibrosis is associated with cardioembolic stroke and, to a lesser degree, cryptogenic stroke. Whether liver fibrosis is a marker or independent causal factor of cardioembolism is to be determined.

Introduction: The insular cortex controls several aspects of vital function including autonomic regulation, and strokes affecting the insula have been associated with dysautonomia, cardiac dysfunction, and arrhythmias. Previous studies have shown an association between insular strokes, elevated troponin levels, and atrial fibrillation (AF). In this study, we aim to determine the association between cardiac biomarkers and insular involvement of the infarct and hypothesize that insular involvement implicates a cardioembolic source. Methods: We abstracted data from a prospective comprehensive stroke center registry of consecutive patients with a discharge diagnosis of acute ischemic stroke who underwent brain imaging (CT or MRI) and work up to determine stroke mechanism. Data included demographics, clinical baseline variables, laboratory tests (including admission troponin level), and transthoracic echocardiographic variables (regional wall motion abnormalities, ejection fraction, and left atrial volume index), and stroke subtype. Multivariable logistic regression models were built to determine associations between AF, and cardiac biomarkers and insular infarcts. Results: We identified 1224 patients who met the inclusion criteria; 397 (32.4%) had insular involvement of the infarct. In multivariable models, insular infarcts were associated with AF (adjusted OR 1.73, 95% CI 1.23-2.43, p = 0.001) and left atrial volume index (adjusted OR per standard deviation increase 1.30, 95% CI 1.13-1.49, p = 0.001). There was a trend for association between insular involvement and positive troponin level (adjusted OR 1.45 95% CI 0.91-2.33, p = 0.122) but not with regional wall motion abnormalities (adjusted OR 1.13, 95% CI 0.69-1.84, p = 0.627). Insular involvement was associated with cardioembolic stroke subtype (45.8% vs. 26.7%, p Conclusion: The insular cortex is commonly involved in patients with atrial fibrillation and/or atrial dilation and maybe a neuroimaging biomarker of cardioembolic stroke. Larger studies are needed to confirm this association and test anticoagulation therapy in patients with insular infarcts.

Introduction: Thrombophilias are a known cause of acute ischemic stroke (AIS) in the young. We hypothesized that thrombophilias would be associated with an increased burden of chronic cerebrovascular disease in these patients. Methods: We included patients enrolled in the prospective Cornell AcutE Stroke Academic Registry (CAESAR) who were 18-65 years of age, diagnosed with AIS by brain MRI between 2011-2015, and had thrombophilia testing within 6 months of their stroke. The exposure variable was thrombophilia, defined as at least one positive thrombophilia test according to standard criteria. The primary outcome was the total Age-Related White Matter Changes (ARWMC) score (0-15). Secondary outcomes were the Fazekas score (0-3) and the number of chronic small vessel (subcortical) cerebral infarcts. Outcomes were determined by a single radiologist blinded to thrombophilia status using clinically-performed brain MRIs at the time of index stroke. Doubly robust estimator analyses were used to test the association between an underlying thrombophilia and outcomes. Models were adjusted for age, gender, race, and vascular risk factors. Results: Among 177 patients meeting eligibility criteria, mean age was 47 (SD, 10) years and 50% were women. Thrombophilia was detected in 77 patients (44%). The mean total ARWMC score, Fazekas score, and number of chronic small vessel infarcts were 1.90 (SD, 1.74), 0.91 (SD, 0.69), and 0.16 (SD, 0.63) in patients with thrombophilia and 2.16 (SD, 1.64), 1.07 (SD, 0.69) and 0.35 (SD, 0.81) in patients without thrombophilia. In multivariable analyses, there was no difference in the total ARWMC score (mean difference -0.05, 95% CI -0.43 to 0.33, p=0.80) or Fazekas score (mean difference -0.05, 95% CI -0.21 to 0.11, p=0.52) between patients with thrombophilia and those without. However, in multivariable analyses, the number of chronic infarcts (mean difference -0.22, 95% CI -0.42 to -0.01, p=0.01) was lower in patients with thrombophilia than in those without. Conclusions: In a single-center study of young adults with AIS, underlying thrombophilia was not associated with white matter disease burden. However, contrary to our hypothesis, it was inversely associated with the number of chronic small vessel infarcts.

Background and Purpose: While studies have stratified cardioembolic (CE) stroke risk by qualitative left atrial appendage (LAA) morphology and biomarkers of atrial dysfunction, the quantitative properties that underlie these observations are not well established. Accordingly, we hypothesized that LAA volume and contrast density (attenuation) on computerized tomography (CT) may capture the structural and hemodynamic processes that underlie CE stroke risk. Methods: Data were collected from a single center prospective ischemic stroke database over 18 months and included all patients with ischemic stroke who previously underwent routine, non-gated, contrast enhanced thin-slice (≤2.5 mm) chest CT. Stroke subtype was determined based on the inpatient diagnostic evaluation. LAA volume and attenuation were determined from CT studies performed for various clinically appropriate indications. Univariate and multivariable analyses were performed to determine factors associated with ischemic stroke subtype, including known risk factors and biomarkers, as well as LAA density and morphologic measures. Results: We identified 311 patients with a qualifying chest CT (119 CE subtype, 109 ESUS, and 83 non-CE). In unadjusted models, there was an association between CE (vs. non-CE) stroke subtype and LAA volume (OR per mL increase 1.15, 95% CI 1.07-1.24, pth quartile vs. 1 st quartile; OR 2.95, 95% CI 1.28-6.80, p=0.011), but not with ESUS (vs. non-CE) subtype. In adjusted models, only the association between LAA density and CE stroke subtype persisted (adjusted OR 3.71, 95% CI 1.37-10.08, p=0.010). Conclusion: The LAA volume and density values on chest CT are associated with CE stroke subtype but not ESUS subtype. Patients with ESUS and increased LAA volume or attenuation may be a subgroup where the mechanism is cardioembolic and anticoagulation can be tested for secondary stroke prevention.

Introduction: To study the risk of arterial ischemic events after non-traumatic subdural hemorrhage (SDH). Methods: We performed a retrospective cohort study using inpatient and outpatient claims data from 2008-2015 from a nationally representative 5% sample of Medicare beneficiaries. The exposure was diagnosis of SDH. Our primary outcome was an arterial ischemic event defined as a composite of acute ischemic stroke and acute myocardial infarction (MI). Secondary outcomes were ischemic stroke alone and MI alone. We used validated ICD-9-CM diagnosis codes to identify our predictor and outcomes. We excluded patients who had an arterial ischemic event prior to SDH diagnosis. Using Cox regression and corresponding survival probabilities, adjusted for demographics and vascular comorbidities, we computed the hazard ratio (HR) in each 4-week interval after discharge for SDH. We performed secondary analyses stratified by strong indications for antithrombotic therapy (composite of atrial fibrillation, peripheral vascular disease, valvular heart disease and venous thromboembolism). Results: Among 1.7 million Medicare beneficiaries, 2,939 were diagnosed with SDH. Compared to patients without SDH, those with SDH were more often older, male, and had more vascular risk factors. In the 4 weeks after SDH, patients’ risk of an arterial ischemic event was substantially increased (HR, 4.2; 95% CI, 2.2-6.7). There was no association between SDH diagnosis and arterial ischemic event risk beyond 4 weeks. In secondary analysis, during the 4 weeks after SDH, patients’ risk of ischemic stroke was increased (HR, 5.6; 95% CI, 3.6-9.7) but not their risk of MI (HR, 0.8, 95% CI, 0.2-1.7). Patients with strong indications for antithrombotic therapy had similarly increased risks for arterial ischemic events as compared to patients in the primary analysis; patients without strong indications for antithrombotic did not demonstrate an increased risk for arterial ischemic events. Conclusions: Among Medicare beneficiaries, we found a heightened risk of arterial ischemic events, particularly ischemic stroke, in the four weeks after SDH. This increased risk may be driven by withholding of antithrombotic therapy after SDH diagnosis.

Introduction: Previous studies have shown an elevated risk of MI (MI) in patients with symptomatic intracranial atherosclerotic disease (sICAD), but the mediators of increased risk of MI or death in these patients remain uncertain. We aim to determine risk factors associated with MI or death in patients with symptomatic ICAD. Methods: Patients enrolled in SAMMPRIS had sICAD and were randomized to aggressive medical management (AMM) vs. stenting and AMM. The primary outcome of this post-hoc analysis is MI or vascular death within 2 years of follow-up. We excluded patients who were lost to follow up, had a stroke during follow up, had non-vascular death or death within 30 days of stenting. Patients meeting the inclusion criteria were divided into two groups: those with vs. those without the primary outcome. We used binary logistic regression to determine predictors of incident MI or death within 2 years. Results: Of the 451 patients enrolled in SAMMPRIS, 350 patients met the inclusion criteria (reasons for exclusion: 4 deaths occurring within 30 days of stenting, 63 with ischemic stroke, 6 with symptomatic hemorrhage, 7 patients with non-cardiovascular death within 2 years, and 21 lost to follow up). At 2 years, 17 patients (4.9%) had MI/death; 10 patients had MI and 7 had cardiovascular deaths. In a multivariable model, factors associated with MI/death were: history of coronary artery disease (adjusted OR 3.19, 95% CI 1.14 - 8.93, p = 0.027) and systolic blood pressure (adjusted OR per 10 mm increase 1.20, 95% CI 0.98 - 1.44, p = 0.080). This risk was abut 24% with both predictors present and 2.8% with them absent (Figure). Conclusion: Higher systolic blood pressure and pre-existing cardiovascular disease were independently associated with incident MI or vascular death in patients with sICAD, despite medical management. Further studies are needed to confirm this association and test interventions to reduce this risk.

Background: Active smoking after stroke is associated with worse outcomes. Since several smoking cessation drugs have become available during the last two decades, we sought to determine whether the rate of active smoking among stroke survivors has decreased. Methods: We performed a trends analysis using cross-sectional data from all nine available consecutive cycles of the continuous phase of the National Health and Nutrition Examination Survey from 1999 to 2016. Participants in each cycle were asked about their medical history and health-related behaviors. We included participants 20 years of age and older who answered questions regarding smoking. Patients with prior stroke were identified based on self-report, which has been validated against expert chart review. Active smoking was defined based on self-report. We used multivariable logistic regression methods for survey data to assess for trends in active smoking among all participants and those with prior stroke. Models were adjusted for demographics. Results: We included 49,440 participants in our analysis, of whom 1,921 (2.7%) reported a prior stroke. The mean age of stroke survivors was 64.8 (standard error, 0.5) years, and 57% were women. The average prevalence of active smoking over 1999-2016 was 22.2% for the whole sample and 24.3% among stroke survivors. In the overall population, the adjusted prevalence of active smoking decreased over the study period (odds ratio [OR] per cycle, 0.96; 95% confidence interval [CI], 0.94-0.97). The rate did not decrease among stroke survivors (OR, 1.01; 95% CI, 0.93-1.09) (Fig). Conclusion: Despite the availability of several effective smoking cessation therapies, the rate of active smoking among stroke survivors has not decreased in the past two decades. Effective strategies for smoking cessation for secondary stroke prevention are needed.

Introduction: Reversible cerebral vasoconstriction syndrome (RCVS) is a syndrome of recurrent thunderclap headaches with transient cerebral vasoconstriction which can cause stroke. There are few population-based data on the incidence of RCVS as well as associated risk factors and complications. Methods: We performed a retrospective cohort study using administrative claims data from all nonfederal emergency department (ED) visits and hospitalizations in 11 U.S. states during 2016. Using ICD-10 diagnosis code I67.841, we identified adult patients hospitalized with RCVS and evaluated associated diagnoses during prior, concurrent, and subsequent ED visits and hospitalizations. We used U.S. census data to estimate the age- and sex-standardized incidence of RCVS in the U.S. adult population. In a validation study, we reviewed the records of patients with a discharge diagnosis of RCVS and a random sample of patients with other cerebrovascular diagnoses at our medical center to estimate the sensitivity and specificity of the RCVS diagnosis code, and calculated the RCVS 2 score of patients with RCVS. Results: In our validation study, the sensitivity of the RCVS ICD-10 code was 100% (95% CI, 66-100%) and the specificity 90% (95% CI, 74-98%); the median RCVS 2 score among patients diagnosed with RCVS was 6, supporting that the diagnosis code generally identified true cases of RCVS. In our statewide analysis, we identified 222 patients diagnosed with RCVS in 2016, equating to a U.S. incidence of 2.7 (95% CI, 2.4-3.1) per million adults per year. The mean age was 46.8 (±14.3) years, 63.5% of patients were white, and 77.5% were female. There were 17 ED visits (22% of all ED visits) for headache in the 3 months before RCVS diagnosis. During the RCVS hospitalization, the most common complications were subarachnoid hemorrhage (33.5%), followed by ischemic stroke (14.9%), intracerebral hemorrhage (9.3%), and seizures (9.3%). Most patients were discharged home after admission for RCVS (76.6%). Conclusions: Hospitalization with a recognized case of RCVS occurs in about 3 per million adults in the U.S. per year. Although majority of patients hospitalized with RCVS were discharged home, a substantial proportion had serious cerebrovascular complications.

Background and Purpose— Carotid artery plaque with Methods— We included patients enrolled in the Cornell Acute Stroke Academic Registry from 2011 to 2015 who had anterior circulation infarction, magnetic resonance imaging of the brain, and magnetic resonance angiography of the neck. High-risk plaque was identified by intraplaque hemorrhage ascertained from routine neck magnetic resonance angiography studies using validated methods. Infarct location was determined from diffusion-weighted imaging. Intraplaque hemorrhage and infarct location were assessed separately in a blinded fashion by a neuroradiologist. We used the McNemar test for matched data to compare the prevalence of intraplaque hemorrhage ipsilateral versus contralateral to brain infarction. We reclassified stroke subtypes by including large-artery atherosclerosis as a cause if there was intraplaque hemorrhage ipsilateral to brain infarction, regardless of the degree of stenosis. Results— Among the 1721 acute ischemic stroke patients registered in the Cornell Acute Stroke Academic Registry from 2011 to 2015, 579 were eligible for this analysis. High-risk plaque was more common ipsilateral versus contralateral to brain infarction in large-artery atherosclerotic (risk ratio [RR], 3.7 [95% CI, 2.2–6.1]), cryptogenic (RR, 2.1 [95% CI, 1.4–3.1]), and cardioembolic strokes (RR, 1.7 [95% CI, 1.1–2.4]). There were nonsignificant ipsilateral-contralateral differences in high-risk plaque among lacunar strokes (RR, 1.2 [95% CI, 0.4–3.5]) and strokes of other determined cause (RR, 1.5 [95% CI, 0.7–3.3]). After accounting for ipsilateral high-risk plaque, 88 (15.2%) patients were reclassified: 38 (22.6%) cardioembolic to multiple potential etiologies, 6 (8.5%) lacunar to multiple, 3 (15.8%) other determined cause to multiple, and 41 (20.8%) cryptogenic to large-artery atherosclerosis. Conclusions— High-risk carotid plaque was more prevalent ipsilateral to brain infarction across several ischemic stroke subtypes. Accounting for such plaques may reclassify the etiologies of up to 15% of cases in our sample.

Background and Purpose— We sought to determine the long-term risk of seizures after stroke according to age, sex, race, and stroke subtype. Methods— We performed a retrospective cohort study using administrative claims from 2 complementary patient data sets. First, we analyzed data from all emergency department visits and hospitalizations in California, Florida, and New York from 2005 to 2013. Second, we evaluated inpatient and outpatient claims from a nationally representative 5% random sample of Medicare beneficiaries. Our cohort consisted of all adults at the time of acute stroke hospitalization without a prior history of seizures. Our outcome was seizure occurring after hospital discharge for stroke. Poisson regression and demographic data were used to calculate age-, sex-, and race-standardized incidence rate ratios (IRR). Results— Among 777 276 patients in the multistate cohort, the annual incidence of seizures was 1.68% (95% confidence interval [CI], 1.67%–1.70%) after stroke versus 0.15% (95% CI, 0.15%–0.15%) among the general population (IRR, 7.3; 95% CI, 7.3–7.4). By 8 years, the cumulative rate of any emergency department visit or hospitalization for seizure was 9.27% (95% CI, 9.16%–9.38%) after stroke versus 1.21% (95% CI, 1.21%–1.22%) in the general population. Stroke was more strongly associated with a subsequent seizure among patients Conclusions— Almost 10% of patients with stroke will develop seizures within a decade. Hemorrhagic stroke, nonwhite race, and younger age seem to confer the greatest risk of developing seizures.

Background and Purpose— We sought to model the effects of interhospital transfer network design on endovascular therapy eligibility and clinical outcomes of stroke because of large-vessel occlusion for the residents of a large city. Methods— We modeled 3 transfer network designs for New York City. In model A, patients were transferred from spoke hospitals to the closest hub hospitals with endovascular capabilities irrespective of hospital affiliation. In model B, which was considered the base case, patients were transferred to the closest affiliated hub hospitals. In model C, patients were transferred to the closest affiliated hospitals, and transfer times were adjusted to reflect full implementation of streamlined transfer protocols. Using Monte Carlo methods, we simulated the distributions of endovascular therapy eligibility and good functional outcomes (modified Rankin Scale score, 0–2) in these models. Results— In our models, 200 patients (interquartile range [IQR], 168–227) with a stroke amenable to endovascular therapy present to New York City spoke hospitals each year. Transferring patients to the closest hub hospital irrespective of affiliation (model A) resulted in 4 (IQR, 1–9) additional patients being eligible for endovascular therapy and an additional 1 (IQR, 0–2) patient achieving functional independence. Transferring patients only to affiliated hospitals while simulating full implementation of streamlined transfer protocols (model C) resulted in 17 (IQR, 3–41) additional patients being eligible for endovascular therapy and 3 (IQR, 1–8) additional patients achieving functional independence. Conclusions— Optimizing acute stroke transfer networks resulted in clinically small changes in population-level stroke outcomes in a dense, urban area.

Background and Purpose— Elevated cardiac troponin is a marker of cardiac disease and has been recently shown to be associated with embolic stroke risk. We hypothesize that early elevated troponin levels in the acute stroke setting are more prevalent in patients with embolic stroke subtypes (cardioembolic and embolic stroke of unknown source) as opposed to noncardioembolic subtypes (large-vessel disease, small-vessel disease, and other). Methods— We abstracted data from our prospective ischemic stroke database and included all patients with ischemic stroke during an 18-month period. Per our laboratory, we defined positive troponin as ≥0.1 ng/mL and intermediate as ≥0.06 ng/mL and Results— We identified 1234 patients, of whom 1129 had admission troponin levels available; 10.0% (113/1129) of these had a positive troponin. In fully adjusted models, there was an association between troponin positivity and embolic stroke of unknown source subtype (adjusted odds ratio, 4.46; 95% confidence interval, 1.03–7.97; P =0.003) and cardioembolic stroke subtype (odds ratio, 5.00; 95% confidence interval, 1.83–13.63; P =0.002). Conclusions— We found that early positive troponin after ischemic stroke may be independently associated with a cardiac embolic source. Future studies are needed to confirm our findings using high-sensitivity troponin assays and to test optimal secondary prevention strategies in patients with embolic stroke of unknown source and positive troponin.