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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.

ObjectiveTo estimate the incidence of hospitalization for reversible cerebral vasoconstriction syndrome (RCVS), we identified RCVS-related hospital admissions across 11 US states in 2016.MethodsWe tested the validity of ICD-10 code I67.841 in 79 patients with hospital admissions for RCVS or other cerebrovascular diseases at 1 academic and 1 community hospital. After determining that this code had a sensitivity of 100% (95% confidence interval [CI], 82%–100%) and a specificity of 90% (95% CI, 79%–96%), we applied it to administrative data from the Healthcare Cost and Utilization Project on all hospital admissions across 11 states. Age- and sex-standardized RCVS incidence was calculated using census data. Descriptive statistics were used to analyze associated diagnoses.ResultsAcross 5,067,250 hospital admissions in our administrative data, we identified 222 patients with a discharge diagnosis of RCVS in 2016. The estimated annual age- and sex-standardized incidence of RCVS hospitalization was 2.7 (95% CI, 2.4–3.1) cases per million adults. Many patients had concomitant neurologic diagnoses, including subarachnoid hemorrhage (37%), ischemic stroke (16%), and intracerebral hemorrhage (10%). In the 90 days before the index admission, 97 patients had an emergency department (ED) visit and 34 patients a hospital admission, most commonly for neurologic, psychiatric, and pregnancy-related diagnoses. Following discharge from the RCVS hospital admission, 58 patients had an ED visit and 31 had a hospital admission, most commonly for neurologic diagnoses.ConclusionsUsing population-wide data, we estimated the age- and sex-standardized incidence of hospitalization for RCVS in US adults as approximately 3 per million per year.

ObjectiveTo test the hypothesis that silent myocardial infarction (MI) is a risk factor for ischemic stroke, we evaluated the association between silent MI and subsequent ischemic stroke in the Cardiovascular Health Study.MethodsThe Cardiovascular Health Study prospectively enrolled community-dwelling individuals ≥65 years of age. We included participants without prevalent stroke or baseline evidence of MI. Our exposures were silent and clinically apparent, overt MI. Silent MI was defined as new evidence of Q-wave MI, without clinical symptoms of MI, on ECGs performed during annual study visits from 1989 to 1999. The primary outcome was incident ischemic stroke. Secondary outcomes were ischemic stroke subtypes: nonlacunar, lacunar, and other/unknown. Cox proportional hazards analysis was used to model the association between time-varying MI status (silent, overt, or no MI) and stroke after adjustment for baseline demographics and vascular risk factors.ResultsAmong 4,224 participants, 362 (8.6%) had an incident silent MI, 421 (10.0%) an incident overt MI, and 377 (8.9%) an incident ischemic stroke during a median follow-up of 9.8 years. After adjustment for demographics and comorbidities, silent MI was independently associated with subsequent ischemic stroke (hazard ratio [HR], 1.51; 95% confidence interval [CI], 1.03–2.21). Overt MI was associated with ischemic stroke both in the short term (HR, 80; 95% CI, 53–119) and long term (HR, 1.60; 95% CI, 1.04–2.44). In secondary analyses, the association between silent MI and stroke was limited to nonlacunar ischemic stroke (HR, 2.40; 95% CI, 1.36–4.22).ConclusionIn a community-based sample, we found an association between silent MI and ischemic stroke.

Cerebrovascular complications among critically ill patients with COVID-19 have yet to be fully characterized. In this retrospective case series from a single academic tertiary care referral center in New York City, we present 12 patients with ischemic or hemorrhagic strokes that were found on imaging after a period of prolonged sedation in the setting of COVID-19 pneumonia. This series demonstrates a pattern of cerebrovascular events clinically masked by deep sedation required for management of COVID-19 related acute respiratory distress syndrome (ARDS). Of the 12 patients included, 10 had ischemic stroke, 4 of which had hemorrhagic conversion, and 2 had primary intracerebral hemorrhage. Ten patients were on therapeutic anticoagulation prior to discovery of their stroke, and the remainder received intermediate dose anticoagulation (in a range between prophylactic and therapeutic levels). Additional studies are needed to further characterize the counterbalancing risks of ischemic and hemorrhagic stroke, as well as the optimal management of this patient population.

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.

ObjectiveTo evaluate the relationship between prior antiplatelet therapy (APT) and outcomes after primary intracerebral haemorrhage (ICH), and assess if it varies by haematoma location.MethodsWe pooled individual patient data from the Virtual International Stroke Trials Archive-ICH trials dataset, Clot Lysis: Evaluating Accelerated Resolution of Intraventricular Hemorrhage III trial and the Minimally Invasive Surgery Plus Alteplase for Intracerebral Hemorrhage Evacuation Phase III trial. The exposure was APT preceding ICH diagnosis. The primary outcome was haematoma expansion at 72 hours. Secondary outcomes were admission haematoma volume, all-cause mortality, death or major disability (modified Rankin Scale (mRS) score ≥4) and shift in mRS distribution. Mixed-effects models were used to assess the relationship between APT and outcomes. Secondary analyses were stratified by ICH location and study cohort.ResultsAmong 1420 patients with ICH, there were 782 (55.1%) lobar and 596 (42.0%) deep haemorrhages. APT was reported in 284 (20.0%) patients. In adjusted regression models, prior APT was not associated with haematoma expansion (OR, 0.97; 95% CI 0.60 to 1.57), major disability or death (OR, 1.05; 95% CI 0.61 to 1.63), all-cause mortality (OR, 0.89; 95% CI 0.47 to 1.85), admission haematoma volume (beta, −0.17; SE, 0.09; p=0.07) and shift in mRS (p=0.43). In secondary analyses, APT was associated with admission haematoma volume in lobar ICH (beta, 0.25; SE, 0.12; p=0.03), but there was no relationship with other ICH outcomes when stratified by haematoma location or study cohort.ConclusionsIn a large heterogeneous cohort of patients with ICH, prior APT was not associated with haematoma expansion or functional outcomes after ICH, regardless of haematoma location. APT was associated with admission haematoma volumes in lobar ICH.

Objective We wanted to determine whether pregnancy is associated with cervical artery dissection. Methods We performed a case-control study using claims data from all nonfederal emergency departments and acute care hospitals in New York and Florida between 2005 and 2015. Cases were women 12-42 years of age hospitalized with cervical artery dissection, defined using validated diagnosis codes for carotid/vertebral artery dissection. Controls were women 12-42 years of age with a primary diagnosis of renal colic. Cases and controls were matched 1:1 on age, race, insurance, income, state, and visit year. The exposure variable was pregnancy, defined as labor and delivery within 90 days before or 6 months after the index visit. Logistic regression was used to compare the odds of pregnancy between cases and controls. We performed a secondary cohort-crossover study comparing the risk of cervical artery dissection during pregnancy versus the same time period 1 year later. Results Pregnancy was twice as common among 826 women with cervical artery dissection compared with the 826 matched controls with renal colic (odds ratio, 2.5; 95% confidence interval [CI], 1.3-4.7). In our secondary analysis, pregnancy was associated with a higher risk of cervical artery dissection (incidence rate ratio [IRR], 2.2; 95% CI, 1.3-3.5), with the heightened risk limited to the postpartum period (IRR, 5.5; 95% CI, 2.6-11.7). Interpretation Pregnancy, specifically the postpartum period, was associated with hospitalization for cervical artery dissection. Although these findings might in part reflect ascertainment bias, our results suggest that arterial dissection is one mechanism by which pregnancy can lead to stroke. ANN NEUROL 2020;88:596-602.

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.

This cohort study evaluates the mortality and functional outcome in patients with spontaneous intracerebral hemorrhage who received intraventricular alteplase vs those who received saline., Key Points Question Is intraventricular thrombolysis in patients with spontaneous intracerebral hemorrhage (ICH) and intraventricular hemorrhage (IVH) associated with reduced parenchymal ICH volume? Findings In this cohort study of 454 patients with ICH and IVH who were enrolled in a randomized clinical trial, intraventricular alteplase use was associated with a small reduction in the parenchymal ICH volume. However, no association was found between a change in parenchymal ICH volume and death or major disability. Meaning Findings of this study suggest that further exploration of the role of intraventricular thrombolysis in reducing parenchymal ICH volumes and potentially improving outcomes is warranted in patients with a moderate to large ICH with IVH and those with a thalamic ICH., Importance Intraventricular thrombolysis reduces intraventricular hemorrhage (IVH) volume in patients with spontaneous intracerebral hemorrhage (ICH), but it is unclear if a similar association with parenchymal ICH volume exists. Objective To evaluate the association between intraventricular alteplase use and ICH volume as well as the association between a change in parenchymal ICH volume and long-term functional outcomes. Design, Setting, and Participants This cohort study was a post hoc exploratory analysis of data from the Clot Lysis: Evaluating Accelerated Resolution of Intraventricular Hemorrhage phase 3 randomized clinical trial with blinded outcome assessments. Between September 1, 2009, and January 31, 2015, patients with ICH and IVH were randomized to receive either intraventricular alteplase or normal saline via an external ventricular drain. Participants with primary IVH were excluded. Data analyses were performed between January 1 and June 30, 2021. Exposure Randomization to receive intraventricular alteplase. Main Outcomes and Measures The primary outcome was the change in parenchymal ICH volume between the hematoma stability and end-of-treatment computed tomography scans. Secondary outcomes were a modified Rankin Scale score higher than 3 and mortality, both of which were assessed at 6 months. The association between alteplase and change in parenchymal ICH volume was assessed using multiple linear regression, whereas the associations between change in parenchymal ICH volume and 6-month outcomes were assessed using multiple logistic regression. Prespecified subgroup analyses were performed for baseline IVH volume, admission ICH volume, and ICH location. Results A total of 454 patients (254 men [55.9%]; mean [SD] age, 59 [11] years) were included in the study. Of these patients, 230 (50.7%) were randomized to receive alteplase and 224 (49.3%) to receive normal saline. The alteplase group had a greater mean (SD) reduction in parenchymal ICH volume compared with the saline group (1.8 [0.2] mL vs 0.4 [0.1] mL; P

Introduction: 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. Objectives: The aim of this study was to evaluate the risk of ischemic stroke among survivors of SAH. Methods: We performed a retrospective cohort study using claims data from Medicare beneficiaries from 2008 to 2015. The exposure was a diagnosis of SAH, while the outcome was an acute ischemic stroke, both identified using previously validated ICD-9-CM diagnosis codes. We used Cox regression analysis adjusting for demographics and stroke risk factors to evaluate the association between SAH and long-term risk of ischemic stroke. Results: Among 1.7 million Medicare beneficiaries, 912 were hospitalized with non-traumatic SAH. During a median follow-up of 5.2 years (IQR, 2.7–6.7), the cumulative incidence of ischemic stroke was 22 per 1,000 patients per year among patients with SAH, and 7 per 1,000 patients per year in those without SAH. In adjusted Cox models, SAH was associated with an increased risk of ischemic stroke (HR, 2.0; 95% confidence interval, 1.4–2.8) as compared to beneficiaries without SAH. Similar results were obtained in sensitivity analyses, when treating death as a competing risk (sub HR, 3.0; 95% CI, 2.8–3.3) and after excluding ischemic stroke within 30 days of SAH discharge (HR, 1.5; 95% CI, 1.1–2.3). Conclusions: In a large, heterogeneous national cohort of elderly patients, survivors of SAH had double the long-term risk of ischemic stroke. SAH survivors should be closely monitored and risk stratified for ischemic stroke.

Background and Purpose: The impact of arterial ischemic events after intracerebral hemorrhage (ICH) on 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, a composite of acute ischemic stroke or myocardial infarction (MI), identified using validated ICD-9-CM diagnosis codes. The outcome was mortality. We used marginal structural models to analyze the risk of death among ICH patients with and without an arterial ischemic event, after adjusting for confounders as time-varying covariates. Results: Among 8,804 Medicare beneficiaries with ICH, 2,371 (26.9%) had an arterial ischemic event. During a median follow-up time of 1.9 years (interquartile range, 0.7-3.9), ICH patients with an arterial ischemic event had a mortality rate of 21.7 (95% confidence interval [CI], 20.4-23.0) per 100 person-years compared to a rate of 15.0 (95% CI, 14.4-15.6) per 100 person-years in those without. In the marginal structural model, an arterial ischemic event was associated with an increased risk of death (hazard ratio [HR], 1.8; 95% confidence interval [CI], 1.6-1.9). In secondary analyses, the mortality risk was elevated after an ischemic stroke (HR, 1.7; 95% CI, 1.5-1.8), and MI (HR, 3.0; 95% CI, 2.4-3.8). Conclusions: We found that elderly patients who survived an ICH had an increased risk of death after a subsequent ischemic stroke or MI.

Objective Atrial cardiopathy without atrial fibrillation (AF) may be a potential cardiac source of embolic strokes of undetermined source (ESUS). Atrial volume is a feature of atrial cardiopathy, but the relationship between atrial volume and ESUS remains unclear. Methods We compared left atrial volume among ischemic stroke subtypes in the Cornell Acute Stroke Academic Registry (CAESAR), which includes all patients with acute ischemic stroke at our hospital since 2011. Stroke subtype was determined by neurologists per the TOAST classification and consensus ESUS definition. Left atrial volume index (LAVI) was obtained directly from our echocardiography image system (Xcelera, Philips Healthcare). We used t‐tests and analysis of variance for unadjusted comparisons and targeted minimum loss‐based estimation for comparisons adjusted for demographics and comorbidities. Results Among 2116 patients in CAESAR from 2011 to 2016, 1293 had LAVI measurements. LAVI varied across subtypes (P

Background and Purpose: Data are lacking on the long-term risk of hip fracture among patients with ischemic stroke. A better understanding of the contemporary incidence of hip fracture after ischemic stroke could benefit patient care by promoting strategies to prevent this disabling complication in stroke survivors. Methods: We performed a retrospective cohort study using inpatient and outpatient claims between 2008 and 2015 from a nationally representative 5% sample of Medicare beneficiaries. We included patients ≥66 years of age who were hospitalized with acute ischemic stroke, defined through a validated diagnostic code algorithm. We excluded patients who had a prior or concurrent hip fracture diagnosis at the time of ischemic stroke. The primary outcome was hip fracture requiring hospitalization. Survival statistics were used to calculate crude incidence rates, and the Kaplan-Meier method was used to calculate cumulative rates. Results: Among the 1 772 550 beneficiaries in our sample, 60 099 were diagnosed with an acute ischemic stroke without prior or concomitant hip fracture. During 4.5 (±2.2) years of follow-up, the incidence of hip fracture was 1.6 (95% confidence interval [CI]: 1.5-1.6) per 100 person-years in patients with acute ischemic stroke versus 0.6 (95% CI: 0.6-0.6) per 100 person-years in patients without acute ischemic stroke. The cumulative 5-year rate of hip fracture was 7.6% (95% CI: 7.2%-8.0%) among patients with acute ischemic stroke versus 2.8% (95% CI: 2.8%-2.9%) among the remaining Medicare beneficiaries. Conclusion: We found that among elderly Medicare beneficiaries with acute ischemic stroke, nearly 1 in 12 developed a hip fracture over the next 5 years.

Background and Purpose:Many studies supporting the association between specific surgical procedure categories and postoperative stroke (POS) do not account for differences in patient-level characteristics between and within surgical categories. The risk of POS after high-risk procedure categories remains unknown after adjusting for such differences in patient-level characteristics.Methods:Using inpatients in the American College of Surgeons National Surgical Quality Initiative Program database, we conducted a retrospective cohort study between January 1, 2000, and December 31, 2010. Our primary outcome was POS within 30 days of surgery. We characterized the relationship between surgical- and individual patient-level factors and POS by using multivariable, multilevel logistic regression that accounted for clustering of patient-level factors with surgical categories.Results:We identified 729 886 patients, 2703 (0.3%) of whom developed POS. Dependent functional status (odds ratio [OR]: 4.11, 95% confidence interval [95% CI]: 3.60-4.69), history of stroke (OR: 2.35, 95%CI: 2.06-2.69) or transient ischemic attack (OR: 2.49 95%CI: 2.19-2.83), active smoking (OR: 1.20, 95%CI: 1.08-1.32), hypertension (OR: 2.11, 95%CI: 2.19-2.82), chronic obstructive pulmonary disease (OR: 1.39 95%CI: 1.21-1.59), and acute renal failure (OR: 2.35, 95%CI: 1.85-2.99) were significantly associated with POS. After adjusting for clustering, patients who underwent cardiac (OR: 11.25, 95%CI: 8.52-14.87), vascular (OR: 4.75, 95%CI: 3.88-5.82), neurological (OR: 4.60, 95%CI: 3.48-6.08), and general surgery (OR: 1.40, 95%CI: 1.15-1.70) had significantly greater odds of POS compared to patients undergoing other types of surgical procedures.Conclusions:Vascular, cardiac, and neurological surgery remained strongly associated with POS in an analysis accounting for the association between patient-level factors and surgical categories.

Background: The short-term risk of ischemic stroke in patients with left ventricular (LV) thrombus identified via delayed-enhancement cardiac magnetic resonance (DE-CMR) imaging is uncertain. Methods: We performed a retrospective cohort study of patients who underwent DE-CMR for evaluation of LV systolic dysfunction at NewYork-Presbyterian Hospital/Weill Cornell between 2007 and 2016. We identified all hospitalized patients who had DE-CMR evidence of LV thrombus, and as controls, all hospitalized patients who had no DE-CMR evidence of LV thrombus; 2 control patients were randomly selected for each patient with LV thrombus. Our primary outcome was ischemic stroke prior to hospital discharge. Additionally, we compared the risk of stroke among patients with: (1) no LV thrombus, (2) LV thrombus by DE-CMR but not by echocardiography, and (3) LV thrombus by both DE-CMR and echocardiography. Results: We identified 33 patients with LV thrombus and 66 patients without LV thrombus on DE-CMR. Of the 33 patients with LV thrombus on DE-CMR, 13 had echocardiographic evidence of thrombus. Ischemic stroke occurred in 3 of 33 (9.1%; 95% CI, 1.9%-24.3%) patients with LV thrombus on DE-CMR. Ischemic stroke occurred in 0 of 66 (0%; 95% CI, 0%-5.4%) patients without LV thrombus on DE-CMR, 1 of 20 (5.0%; 95% CI, .1%-24.9%) patients with thrombus on DE-CMR but not echocardiogram, and 2 of 13 (15.4%; 95% CI, 1.9%-45.4%) patients with thrombus on both DE-CMR and echocardiogram (P value for comparison among groups, .02). Conclusions: We found a 9% short-term risk of ischemic stroke in patients with LV thrombus detected on DE-CMR.

BackgroundThe aetiology of wall motion abnormalities (WMA) in patients with ischaemic stroke is unclear. We hypothesised that WMAs on transthoracic echocardiography (TTE) in the setting of ischaemic stroke mostly reflect pre-existing coronary heart disease rather than simply an isolated neurocardiogenic phenomenon.MethodsData were retrospectively abstracted from a prospective ischaemic stroke database over 18 months and included patients with ischaemic stroke who underwent a TTE. Coronary artery disease was defined as history of myocardial infarction (MI), coronary intervention or ECG evidence of prior MI. The presence (vs absence) of WMA was abstracted. Multivariable logistic regression was used to determine the association between coronary artery disease and WMA in models adjusting for potential confounders.ResultsWe identified 1044 patients who met inclusion criteria; 139 (13.3%, 95% CI 11.2% to 15.4%) had evidence of WMA of whom only 23 (16.6%, 95% CI 10.4% to 22.8%) had no history of heart disease or ECG evidence of prior MI. Among these 23 patients, 12 had a follow-up TTE after the stroke and WMA persisted in 92.7% (11/12) of patients. In fully adjusted models, factors associated with WMA were older age (OR per year increase 1.03, 95% 1.01 to 1.05, p=0.009), congestive heart failure (OR 4.44, 95% CI 2.39 to 8.33, pConclusionIn patients with ischaemic stroke, WMA on TTE may reflect underlying cardiac disease and further cardiac evaluation may be considered.

Background: In 2013, investigators from A Randomized Trial of Unruptured Brain Arteriovenous Malformations (AVM; ARUBA) reported that interventions to obliterate unruptured AVMs caused more morbidity and mortality than medical management. Objective: We sought to determine whether interventions for unruptured AVM decreased after publication of ARUBA results. Methods: We used the Nationwide Readmissions Database to assess trends in interventional AVM management in patients ≥18 years of age from 2010 through 2015. Unruptured brain AVMs were identified using International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM) code 747.81 and excluding any patient with a diagnosis of intracranial hemorrhage. Our primary outcome was interventional AVM treatment, identified using ICD-9-CM procedure codes for surgical resection, endovascular therapy, and stereotactic radiosurgery. Join-point regression was used to assess trends in the incidence of interventional AVM management among adults from 2010 through 2015. Results: There was no significant U.S. population level change in unruptured brain AVM intervention rates before versus after ARUBA (p = 0.59), with the incidence of AVM intervention ranging from 8.0 to 9.2 per 10 million U.S. residents before the trial publication to 7.7–8.3 per 10 million afterwards. Conclusions: In a nationally representative sample, we found no change in rates of interventional unruptured AVM management after publication of the ARUBA trial results.

Objective Cirrhosis has been associated with nontraumatic subarachnoid hemorrhage (SAH). We sought to evaluate the specific association between cirrhosis and aneurysmal SAH. Methods We performed a retrospective cohort study using a sample of Medicare claims data from 2008 to 2015. Cirrhosis was defined using a validated ICD‐9‐CM diagnosis code algorithm. Nontraumatic SAH was identified using a validated approach requiring an inpatient claim for its ICD‐9‐CM diagnosis code. Additionally, we required the presence of an ICD‐9‐CM procedure code reflecting treatment of a cerebral aneurysm during the same hospitalization to ensure ascertainment of aneurysmal SAH specifically. We used survival statistics to calculate incidence rates and Cox proportional hazards models to evaluate the association between cirrhosis and aneurysmal SAH after adjustment for demographics, stroke risk factors, and comorbidities. Results We identified 10,658 (0.6%) patients with cirrhosis from among the 1,778,604 beneficiaries in our sample. The mean age of patients with cirrhosis was 73.5 (±7.8) years, and 48% were female. Over a mean of 4.7 (±2.1) years of follow‐up, 4,272 patients were hospitalized with aneurysmal SAH. The annual incidence of aneurysmal SAH in patients with cirrhosis was 0.12% (95% confidence interval [CI], 0.08–0.17%) compared to 0.05% (95% CI, 0.05–0.05%) in patients without cirrhosis. In the adjusted model, cirrhosis was independently associated with aneurysmal SAH (hazard ratio, 2.2; 95% confidence interval, 1.5–3.4). Interpretation Cirrhosis was independently associated with an increased risk of aneurysmal SAH among older individuals. Confirmation of these findings may yield opportunities for risk stratification and prevention.

Cancer patients with acute ischemic stroke (AIS) are high-risk for recurrent thromboembolic events (RTE). Currently, no risk stratification model exists to predict RTE in this population. We tested the hypothesis that the Khorana score, a validated risk model for predicting venous thromboembolism in cancer patients, can effectively classify RTE risk in cancer patients with AIS. We retrospectively identified adults with active solid or hematological cancer diagnosed with AIS at a tertiary-care cancer center from 2005 to 2010. The Khorana score at the time of index stroke was calculated. The primary outcome was arterial or venous RTE. Cox regression was used to evaluate the association of the Khorana score and its individual components with RTE. Harrell’s c-statistic was used to calculate the score’s discriminatory ability. Among 263 AIS patients, median survival was 84 days (IQR 24–149 days) and 90 (34%) had RTE. The median Khorana score was 2 (IQR 1–2, range 0–5). Cumulative rate of RTE was 28% among patients who scored 0, 36% with scores of 1–2, and 32% with scores of 3–6. The overall Khorana score was marginally associated with RTE (HR, 1.14; 95% CI, 1.02–1.28). Of its individual components, only leukocytosis was associated with RTE (HR adjusted for other components, 1.45; 95% CI 1.11–1.90). The score’s c-statistic for predicting RTE was 0.57. In this study, the Khorana score had poor discriminatory ability for predicting RTE in cancer patients with AIS. Future research is needed to identify better methods for predicting RTE in this high-risk population.

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.

Introduction: Leukocyte telomere length (LTL) is a potential biomarker of aging and associated with several age-related diseases. Current research on an association between LTL and incident stroke has had inconclusive results. We hypothesized that LTL is associated with incident stroke among American Indians (AI) in the Strong Heart Family Study (SHFS). Methods: The SHFS is a population-based cohort study of cardiovascular disease (CVD) and its risk factors. Participants (n=2,769) recruited from regions in Arizona, Oklahoma and the Dakotas were assessed for LTL and CVD risk factors during a clinic visit between 2001 and 2003. Incident stroke events were identified through the end of 2018 (mean follow-up: 16.4 years). We assessed the association between LTL and incident stroke using frailty models based on the proportional hazards, accounting for family relatedness and established stroke risk factors that include sex, geographical location, education, smoking, atrial fibrillation, diabetes mellitus, and hypertension. Results: Among 2,769 participants, the mean age was 40.6±17.2 and 41.4% were male. During follow-up, there were 79 (2.9%) incident stroke cases. In the primary model, which adjusted for demographic variables (sex, location and education), the hazard ratios (HR) for stroke in participants in the first and second LTL quartiles were significantly higher than those in the highest (longest) LTL quartile, with HRs of 3.1 (95%CI: 1.4 - 6.6) and 3.5 (95%CI: 1.7 - 7.5), respectively. After adjusting for smoking, atrial fibrillation, diabetes mellitus, and hypertension, the association between LTL and stroke was attenuated, but remained significant when comparing the second shortest LTL quartile to the longest LTL quartile, HR: 2.3 (95% CI: 1.1 – 5.0). Conclusions: In summary, LTL was associated with incident stroke among SHFS participants. Those with shorter LTL have higher risk of stroke. Longer follow-up time may add more power to data analyses since the SHFS is relatively young, with an average baseline age of 40 years. If results are confirmed in other populations, LTL may serve as a biomarker identifying high risk individuals for the purpose of stroke prevention.

Importance It is uncertain whether coronavirus disease 2019 (COVID-19) is associated with a higher risk of ischemic stroke than would be expected from a viral respiratory infection. Objective To compare the rate of ischemic stroke between patients with COVID-19 and patients with influenza, a respiratory viral illness previously associated with stroke. Design, Setting, and Participants This retrospective cohort study was conducted at 2 academic hospitals in New York City, New York, and included adult patients with emergency department visits or hospitalizations with COVID-19 from March 4, 2020, through May 2, 2020. The comparison cohort included adults with emergency department visits or hospitalizations with influenza A/B from January 1, 2016, through May 31, 2018 (spanning moderate and severe influenza seasons). Exposures COVID-19 infection confirmed by evidence of severe acute respiratory syndrome coronavirus 2 in the nasopharynx by polymerase chain reaction and laboratory-confirmed influenza A/B. Main Outcomes and Measures A panel of neurologists adjudicated the primary outcome of acute ischemic stroke and its clinical characteristics, mechanisms, and outcomes. We used logistic regression to compare the proportion of patients with COVID-19 with ischemic stroke vs the proportion among patients with influenza. Results Among 1916 patients with emergency department visits or hospitalizations with COVID-19, 31 (1.6%; 95% CI, 1.1%-2.3%) had an acute ischemic stroke. The median age of patients with stroke was 69 years (interquartile range, 66-78 years); 18 (58%) were men. Stroke was the reason for hospital presentation in 8 cases (26%). In comparison, 3 of 1486 patients with influenza (0.2%; 95% CI, 0.0%-0.6%) had an acute ischemic stroke. After adjustment for age, sex, and race, the likelihood of stroke was higher with COVID-19 infection than with influenza infection (odds ratio, 7.6; 95% CI, 2.3-25.2). The association persisted across sensitivity analyses adjusting for vascular risk factors, viral symptomatology, and intensive care unit admission. Conclusions and Relevance In this retrospective cohort study from 2 New York City academic hospitals, approximately 1.6% of adults with COVID-19 who visited the emergency department or were hospitalized experienced ischemic stroke, a higher rate of stroke compared with a cohort of patients with influenza. Additional studies are needed to confirm these findings and to investigate possible thrombotic mechanisms associated with COVID-19.

Objective To report four patients with coronavirus disease 2019 (COVID-19) who developed posterior reversible encephalopathy syndrome (PRES). Methods Patient data was abstracted from medical records at Weill Cornell Medical Center. Results Four patients with SARS-CoV-2 infection and PRES were identified. The patients' ages ranged from 64 to 74 years, and two were women. All four patients were admitted to the hospital with acute respiratory distress syndrome requiring intensive care unit admission and mechanical ventilation. PRES was diagnosed after persistent confusion, lethargy, new focal neurological deficits, or seizures were noted, with evidence of seizures on electroencephalogram for two of the patients. Imaging confirmed the presence of cerebral vasogenic edema. All four patients had elevated blood pressure and renal injury in the days preceding PRES diagnosis, as well as evidence of systemic inflammation and systemic hypercoagulability. Symptoms of PRES improved with blood pressure control. Conclusions Our four cases demonstrate the occurrence of PRES in critically-ill patients with COVID-19. PRES should be considered in the differential for acute neurological deficits and seizures in this setting., Highlights • We report four patients with COVID-19 COVID 19 who developed posterior reversible encephalopathy syndrome (PRES). • PRES was diagnosed in the context of persistent confusion, lethargy, focal neurologic deficits and seizure. • All patients had acute hypertension, renal injury,evidence of systemic inflammation and hypercoagulability. • PRES should be considered in patients with neurological symptoms and COVID-19 to ensure early treatment.

Background and Purpose: One-fifth of ischemic strokes are embolic strokes of undetermined source (ESUS). Their theoretical causes can be classified as cardioembolic versus noncardioembolic. This distinction has important implications, but the categories’ proportions are unknown. Methods: Using data from the Cornell Acute Stroke Academic Registry, we trained a machine-learning algorithm to distinguish cardioembolic versus non-cardioembolic strokes, then applied the algorithm to ESUS cases to determine the predicted proportion with an occult cardioembolic source. A panel of neurologists adjudicated stroke etiologies using standard criteria. We trained a machine learning classifier using data on demographics, comorbidities, vitals, laboratory results, and echocardiograms. An ensemble predictive method including L1 regularization, gradient-boosted decision tree ensemble (XGBoost), random forests, and multivariate adaptive splines was used. Random search and cross-validation were used to tune hyperparameters. Model performance was assessed using cross-validation among cases of known etiology. We applied the final algorithm to an independent set of ESUS cases to determine the predicted mechanism (cardioembolic or not). To assess our classifier’s validity, we correlated the predicted probability of a cardioembolic source with the eventual post-ESUS diagnosis of atrial fibrillation. Results: Among 1083 strokes with known etiologies, our classifier distinguished cardioembolic versus noncardioembolic cases with excellent accuracy (area under the curve, 0.85). Applied to 580 ESUS cases, the classifier predicted that 44% (95% credibility interval, 39%–49%) resulted from cardiac embolism. Individual ESUS patients’ predicted likelihood of cardiac embolism was associated with eventual atrial fibrillation detection (OR per 10% increase, 1.27 [95% CI, 1.03–1.57]; c-statistic, 0.68 [95% CI, 0.58–0.78]). ESUS patients with high predicted probability of cardiac embolism were older and had more coronary and peripheral vascular disease, lower ejection fractions, larger left atria, lower blood pressures, and higher creatinine levels. Conclusions: A machine learning estimator that distinguished known cardioembolic versus noncardioembolic strokes indirectly estimated that 44% of ESUS cases were cardioembolic.

ObjectiveTo test the hypothesis that the prevalence of cervical artery dissection remains constant across age groups, we evaluated the relationship between age and cervical artery dissection in patients with stroke using a nationally representative sample from the United States.MethodsWe used inpatient claims data included in the 2012–2015 releases of the National Inpatient Sample (NIS). We used validated ICD-9-CM codes to identify adults hospitalized with ischemic stroke and a concomitant diagnosis of carotid or vertebral artery dissection. Survey weights provided by the NIS and population estimates from the US census were used to calculate nationally representative estimates. The χ2 test for trend was used to compare the prevalence of concomitant dissection among stroke hospitalizations across patient subgroups defined by age. Poisson regression and the Wald test for trend were used to evaluate whether the prevalence of hospitalizations for stroke and concomitant dissection per million person-years varied by age groups.ResultsThere were 17,320 (95% confidence interval [CI], 15,614–19,026) hospitalizations involving ischemic stroke and a concomitant dissection. The prevalence of dissection among stroke hospitalizations decreased across 10-year age groups from 7.2% (95% CI, 6.2%–8.1%) among persons younger than 30 years to 0.2% (95% CI, 0.1%–0.2%) among persons older than 80 years (p value for trend p value for trend ConclusionIn a nationally representative sample, the prevalence of hospitalizations for dissection-related stroke increased with age.

Purpose of review This article discusses the epidemiology, diagnosis, treatment, and prevention of neurologic complications of common and rare blood cell disorders. Recent findings A growing number of preventive treatment options are available for stroke in sickle cell disease. Paroxysmal nocturnal hemoglobinuria and immune thrombocytopenia can lead to stroke. Thrombotic thrombocytopenic purpura frequently causes neurologic symptoms and should be considered in the differential diagnosis of a patient with neurologic symptoms, thrombocytopenia, and hemolytic anemia. Polycythemia vera and essential thrombocythemia are rare causes of stroke. Summary This article discusses sickle cell disease and the most recent advances in stroke preventive therapy as well as neurologic complications of paroxysmal nocturnal hemoglobinuria, immune thrombocytopenia, thrombotic thrombocytopenic purpura, polycythemia vera, and essential thrombocythemia.

Key Points Question How does the risk of acute ischemic stroke compare between patients with Covid-19 and patients with influenza (a respiratory virus previously linked to stroke)? Findings In this large retrospective cohort study conducted at two academic hospitals in New York City, patients with emergency department visits and hospitalizations with Covid-19 were approximately seven times as likely to have an acute ischemic stroke as compared to patients with emergency department visits or hospitalizations with influenza. Meaning Patients with Covid-19 are at heightened risk for acute ischemic stroke as compared to patients with influenza. Importance Case series without control groups suggest that Covid-19 may cause ischemic stroke, but whether Covid-19 is associated with a higher risk of ischemic stroke than would be expected from a viral respiratory infection is uncertain. Objective To compare the rate of ischemic stroke between patients with Covid-19 and patients with influenza, a respiratory viral illness previously linked to stroke. Design A retrospective cohort study. Setting Two academic hospitals in New York City. Participants We included adult patients with emergency department visits or hospitalizations with Covid-19 from March 4, 2020 through May 2, 2020. Our comparison cohort included adult patients with emergency department visits or hospitalizations with influenza A or B from January 1, 2016 through May 31, 2018 (calendar years spanning moderate and severe influenza seasons). Exposures Covid-19 infection confirmed by evidence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the nasopharynx by polymerase chain reaction, and laboratory-confirmed influenza A or B. Main Outcomes and Measures A panel of neurologists adjudicated the primary outcome of acute ischemic stroke and its clinical characteristics, etiological mechanisms, and outcomes. We used logistic regression to compare the proportion of Covid-19 patients with ischemic stroke versus the proportion among patients with influenza. Results Among 2,132 patients with emergency department visits or hospitalizations with Covid-19, 31 patients (1.5%; 95% confidence interval [CI], 1.0%-2.1%) had an acute ischemic stroke. The median age of patients with stroke was 69 years (interquartile range, 66-78) and 58% were men. Stroke was the reason for hospital presentation in 8 (26%) cases. For our comparison cohort, we identified 1,516 patients with influenza, of whom 0.2% (95% CI, 0.0-0.6%) had an acute ischemic stroke. After adjustment for age, sex, and race, the likelihood of stroke was significantly higher with Covid-19 than with influenza infection (odds ratio, 7.5; 95% CI, 2.3-24.9). Conclusions and Relevance Approximately 1.5% of patients with emergency department visits or hospitalizations with Covid-19 experienced ischemic stroke, a rate 7.5-fold higher than in patients with influenza. Future studies should investigate the thrombotic mechanisms in Covid-19 in order to determine optimal strategies to prevent disabling complications like 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.

Background Sex differences have been found in stroke risk factors, incidence, treatment, and outcomes. There are conflicting data on whether diagnostic evaluation for stroke may differ between men and women. Methods and Results We performed a retrospective cohort study using inpatient and outpatient claims between 2008 and 2016 from a nationally representative 5% sample of Medicare beneficiaries. We included patients ≥65 years old and hospitalized with ischemic stroke, defined by International Classification of Diseases, Ninth Revision, Clinical Modification ( ICD ‐9‐ CM ) and ICD ‐10‐ CM diagnosis codes. Logistic regression was used to determine the association between female sex and the odds of diagnostic testing and specialist evaluation, adjusted for age, race, and number of Charlson comorbidities. Among 78 822 patients with acute ischemic stroke, 58.3% (95% CI , 57.9–58.6%) were women. Female sex was associated with decreased odds of intracranial vessel imaging (odds ratio [ OR ]: 0.94; 95% CI , 0.91–0.97), extracranial vessel imaging ( OR: 0.89; 95% CI , 0.86–0.92), heart‐rhythm monitoring ( OR: 0.92; 95% CI , 0.87–0.98), echocardiography ( OR: 0.92; 95% CI , 0.89–0.95), evaluation by a neurologist ( OR: 0.94; 95% CI , 0.91–0.97), and evaluation by a vascular neurologist ( OR: 0.94; 95% CI , 0.90–0.97), after adjustment for age, race, and comorbidities. These findings were unchanged in separate sensitivity analyses excluding patients who died during the index hospitalization or were discharged to hospice and excluding patients with atrial fibrillation diagnosed before their index stroke. Conclusions In a nationally representative cohort of Medicare beneficiaries, we found that women with acute ischemic stroke were less likely to be evaluated by stroke specialists and less likely to undergo standard diagnostic testing compared with men.

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.