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Introduction The risk of intracerebral haemorrhage (ICH) associated with hypertension (HTN) is well documented. While the prevalence of HTN increases with age, the greatest odds ratio (OR) for HTN as a risk for ischemic stroke is at an early age. We sought to evaluate if the risk for ICH from HTN was higher in the youngest patients of each race. Patients and methods The Ethnic/Racial Variations of ICH (ERICH) study is a prospective multicenter case-control study of ICH among whites, blacks, and Hispanics. Participants were divided into age groups based on race-specific quartiles. Cases in each race/age group were compared to controls using logistic regression (i.e., cases and controls unmatched). The probability of ICH among cases and controls for each race were compared against independent variables of HTN, quartile of age and interaction of quartile and age also using logistic regression. Results Overall, 2033 non-lobar ICH cases and 2060 controls, and 913 lobar ICH cases with 927 controls were included. ORs were highest in the youngest age quartile for non-lobar haemorrhage for blacks and Hispanics and highest in the youngest quartile for lobar haemorrhage for all races. The formal test of interaction between age and HTN was significant in all races for all locations with the exception of lobar ICH in whites (p = 0.2935). Discussion Hypertension is a strong independent risk factor for ICH irrespective of location among persons of younger age, consistent with the hypothesis that first exposure to HTN is a particularly sensitive time for all locations of ICH.

Background and Purpose— Selective serotonin reuptake inhibitors (SSRIs) have a well-established association with bleeding complications and conflicting reports on outcome after stroke. We sought to evaluate whether pre–intracerebral hemorrhage (ICH) SSRI use increased ICH risk and post-ICH SSRI use improved ICH outcome. Methods— Through post hoc analysis of the ERICH study (Ethnic/Racial Variations of Intracerebral Hemorrhage), SSRI use was categorized into no use, pre-ICH only, pre- and post-ICH use (termed “continuous”), and post-ICH only (termed “new”). Using multivariable modeling, associations were sought between pre-ICH SSRI use and ICH risk in the case-control set, and associations between post-ICH SSRI use and 3-month outcome were analyzed in the ICH case set. Exploratory analyses sought to assess influence of race/ethnicity in models. Results— The final study cohort consisted of 2287 ICH cases and 2895 controls. Pre-ICH SSRI use was not associated with ICH risk (odds ratio, 0.824 [95% CI, 0.632–1.074]) nor potentiation of ICH risk with anticoagulant or antiplatelet use. New post-ICH SSRI use was associated with unfavorable modified Rankin Scale score at 3 months after ICH (odds ratio, 1.673 [95% CI, 1.162–2.408]; P =0.006) in multivariable analyses. Additional propensity score analysis indicated a similar trend but did not reach statistical significance ( P =0.107). When stratified by race/ethnicity, multivariable modeling demonstrated reduced ICH risk with pre-ICH SSRI use in Hispanics (odds ratio, 0.513 [95% CI, 0.301–0.875]; P =0.014), but not non-Hispanic whites or blacks, and no associations between post-ICH SSRI use and 3-month outcome in any racial/ethnic group. Conclusions— In a large multiethnic cohort, pre-ICH SSRI use was not associated with increased ICH risk, but post-ICH SSRI use was associated with unfavorable 3-month neurological outcome after ICH. Registration— URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01202864.

Background: Intracerebral hemorrhage (ICH) patients may appear disabled despite intact cortical spinal tracts (CST). ICH lesions may also vary in volume and location relative to the CST with differential impacts on motor outcome. In this study, we evaluated whether diffusion tensor imaging (DTI) integrity of CST fiber tracking associates with mobility three months post ICH. Methods: The Recovery and Outcomes from StrokE (ROSE) Study is a prospective, multi-center study of ICH serially assessed with motor, cognitive, and functional outcomes and MRI/DTI. Outcome data were collected by hospital chart review and interview/exam. Acute MRI images were analyzed by a central neuroimaging core for ICH location, size, intraventricular hemorrhage, and fractional anisotropy (FA) derived from DTI of the CST. Mobility was assessed at 3-month follow-up using the Barthel Mobility Index. We computed single variable logistic regression analyses (outcome = Barthel mobility at 3 months). We also computed a stepwise logistic model, with and without age, sex, and race, including variables that met P Results: There were 76 ICH patients with DTI FA data available for analysis; 61 with complete data for the multivariate model. Poor mobility after ICH (N = 21; 27.6%) was associated with ICH volume, presence of IVH, Glasgow coma score, ipsilesional CST FA, ipsilesional CP FA and CP FA asymmetry index (Table 1). The multivariate model that adjusted for age, sex, and race identified ipsilesional CP FA, admission GCS and presence of IVH as associated with poor mobility at 3 months; notably, log ICH volume was not associated after controlling for CST injury (Table 1). Conclusions: The presence of IVH and the GCS score at baseline were associated with poor mobility. In addition, the CP FA asymmetry index was independently associated with poor mobility even after accounting for log ICH volume, suggesting that DTI is informative of outcome beyond classic ICH outcome predictors.

Key Points Question Does the prevalence and burden of risk factors for lobar and nonlobar intracerebral hemorrhage (ICH) differ among Black, Hispanic, and White populations? Findings In this case-control study of 3000 cases of ICH among Black, Hispanic, and White patients, the ɛ2 and ɛ4 alleles of APOE, the gene encoding apolipoprotein E, were associated with lobar ICH in White but not Black and Hispanic patients; hypertension was a risk factor for both lobar and nonlobar ICH in all groups; and the mean age for ICH among Black and Hispanic patients was more than 10 years younger than that of their White counterparts. Black and Hispanic patients had a higher attributable risk percentage for treated or untreated hypertension and lack of health insurance than White patients. Meaning These findings suggest that potentially modifiable risk factors and social determinants of health are important contributors to the disproportionate ICH burden experienced by Black and Hispanic populations., This case-control study examines the prevalence, odds, and population attributable risk for established and novel risk factors for intracerebral hemorrhage, stratified by intracerebral hemorrhage location and racial/ethnic group., Importance Black and Hispanic individuals have an increased risk of intracerebral hemorrhage (ICH) compared with their White counterparts, but no large studies of ICH have been conducted in these disproportionately affected populations. Objective To examine the prevalence, odds, and population attributable risk (PAR) percentage for established and novel risk factors for ICH, stratified by ICH location and racial/ethnic group. Design, Setting, and Participants The Ethnic/Racial Variations of Intracerebral Hemorrhage Study was a case-control study of ICH among 3000 Black, Hispanic, and White individuals who experienced spontaneous ICH (1000 cases in each group). Recruitment was conducted between September 2009 and July 2016 at 19 US sites comprising 42 hospitals. Control participants were identified through random digit dialing and were matched to case participants by age (±5 years), sex, race/ethnicity, and geographic area. Data analyses were conducted from January 2019 to May 2020. Main Outcomes and Measures Case and control participants underwent a standardized interview, physical measurement for body mass index, and genotyping for the ɛ2 and ɛ4 alleles of APOE, the gene encoding apolipoprotein E. Prevalence, multivariable adjusted odds ratio (OR), and PAR percentage were calculated for each risk factor in the entire ICH population and stratified by racial/ethnic group and by lobar or nonlobar location. Results There were 1000 Black patients (median [interquartile range (IQR)] age, 57 [50-65] years, 425 [42.5%] women), 1000 Hispanic patients (median [IQR] age, 58 [49-69] years; 373 [37.3%] women), and 1000 White patients (median [IQR] age, 71 [59-80] years; 437 [43.7%] women). The mean (SD) age of patients with ICH was significantly lower among Black and Hispanic patients compared with White patients (eg, lobar ICH: Black, 62.2 [15.2] years; Hispanic, 62.5 [15.7] years; White, 71.0 [13.3] years). More than half of all ICH in Black and Hispanic patients was associated with treated or untreated hypertension (PAR for treated hypertension, Black patients: 53.6%; 95% CI, 46.4%-59.8%; Hispanic patients: 46.5%; 95% CI, 40.6%-51.8%; untreated hypertension, Black patients: 45.5%; 95% CI, 39.%-51.1%; Hispanic patients: 42.7%; 95% CI, 37.6%-47.3%). Lack of health insurance also had a disproportionate association with the PAR percentage for ICH in Black and Hispanic patients (Black patients: 21.7%; 95% CI, 17.5%-25.7%; Hispanic patients: 30.2%; 95% CI, 26.1%-34.1%; White patients: 5.8%; 95% CI, 3.3%-8.2%). A high sleep apnea risk score was associated with both lobar (OR, 1.68; 95% CI, 1.36-2.06) and nonlobar (OR, 1.62; 95% CI, 1.37-1.91) ICH, and high cholesterol was inversely associated only with nonlobar ICH (OR, 0.60; 95% CI, 0.52-0.70); both had no interactions with race and ethnicity. In contrast to the association between the ɛ2 and ɛ4 alleles of APOE and ICH in White individuals (eg, presence of APOE ɛ2 allele: OR, 1.84; 95% CI, 1.34-2.52), APOE alleles were not associated with lobar ICH among Black or Hispanic individuals. Conclusions and Relevance This study found sleep apnea as a novel risk factor for ICH. The results suggest a strong contribution from inadequately treated hypertension and lack of health insurance to the disproportionate burden and earlier onset of ICH in Black and Hispanic populations. These findings emphasize the importance of addressing modifiable risk factors and the social determinants of health to reduce health disparities.

Background and Purpose: For survivors of oral anticoagulation therapy (OAT)–associated intracerebral hemorrhage (OAT-ICH) who are at high risk for thromboembolism, the benefits of OAT resumption must be weighed against increased risk of recurrent hemorrhagic stroke. The ε2/ε4 alleles of the apolipoprotein E ( APOE ) gene, MRI-defined cortical superficial siderosis, and cerebral microbleeds are the most potent risk factors for recurrent ICH. We sought to determine whether combining MRI markers and APOE genotype could have clinical impact by identifying ICH survivors in whom the risks of OAT resumption are highest. Methods: Joint analysis of data from 2 longitudinal cohort studies of OAT-ICH survivors: (1) MGH-ICH study (Massachusetts General Hospital ICH) and (2) longitudinal component of the ERICH study (Ethnic/Racial Variations of Intracerebral Hemorrhage). We evaluated whether MRI markers and APOE genotype predict ICH recurrence. We then developed and validated a combined APOE -MRI classification scheme to predict ICH recurrence, using Classification and Regression Tree analysis. Results: Cortical superficial siderosis, cerebral microbleed, and APOE ε2/ε4 variants were independently associated with ICH recurrence after OAT-ICH (all P APOE genotype and MRI data resulted in improved prediction of ICH recurrence (Harrell C: 0.79 versus 0.55 for clinical data alone, P =0.033). In the MGH (training) data set, CSS, cerebral microbleed, and APOE ε2/ε4 stratified likelihood of ICH recurrence into high-, medium-, and low-risk categories. In the ERICH (validation) data set, yearly ICH recurrence rates for high-, medium-, and low-risk individuals were 6.6%, 2.5%, and 0.9%, respectively, with overall area under the curve of 0.91 for prediction of recurrent ICH. Conclusions: Combining MRI and APOE genotype stratifies likelihood of ICH recurrence into high, medium, and low risk. If confirmed in prospective studies, this combined APOE -MRI classification scheme may prove useful for selecting individuals for OAT resumption after ICH.

Background: The risk of intracerebral hemorrhage (ICH) with hypertension (HTN) is well documented, with prior studies showing that HTN is the most important risk factor associated with ICH. Prior studies have shown that while the prevalence of HTN increases with age, the odds ratio (OR) of HTN for non-lobar ICH is greater earlier in life. We have previously found a lack of Apolipoprotein E allele association with lobar ICH in minority populations. Here we seek to determine if, similar to non-lobar ICH, the odds ratio of HTN for lobar ICH is greater at an earlier age. Methods: The Ethnic/Racial Variations of ICH (ERICH) study is a prospective multicenter case-control study of ICH among whites, blacks, and Hispanics. Cases were enrolled from 42 sites. Controls matched to cases 1:1 by age (±5 years), sex, ethnicity/race, and metropolitan area were identified by random-digit dialing. Participants were interviewed to determine history of HTN. Participants were divided into age groups based on ethnicity-specific quartiles. Cases in each ethnic/age group were compared to controls using logistic regression (i.e., cases and controls unmatched). ORs were calculated to show the risk of lobar ICH associated with HTN by quartile. Results: Overall, 917 lobar ICH cases and 932 controls were included. The Table shows the multivariable OR. ORs were highest in the youngest age quartile across all races (6.47 for blacks, 5.72 for Hispanics and 2.74 for whites). HTN produced a significant increase in risk for the youngest two quartiles in blacks and Hispanics, but only the youngest quartile in whites. However, the age of the lowest quartile in whites was equivalent to the bottom two quartiles in minorities. Discussion: Similar to non-lobar ICH, HTN earlier in life bears a greater risk of lobar ICH than later in life and this risk is across a greater range in disproportionately affected minorities. Research into how new onset or early life HTN leads to disproportionate risk compared to late life is needed.

Introduction: Anticoagulant therapy after intracerebral hemorrhage (ICH) in patients with atrial fibrillation or deep vein thrombosis has been associated with a marked reduction of death. Prevention of ischemic stroke could explain this reduction. We sought to describe the causes of death after discharge and beyond 30 days in a longitudinal follow-up of a multi-racial/ethnic cohort of ICH. We hypothesized that recurrent ICH and ischemic stroke are the most common cause of death after ICH. Methods: The Ethnic/Racial Variations of Intracerebral Hemorrhage (ERICH) Study was a prospective, multi-center, case-control study of ICH among whites, blacks, and Hispanics. Subjects previously in the ERICH study were approached for enrollment in the Longitudinal Follow-up of ICH Survivors (ERICH-L) study. A standardized research interview was completed over the phone and 959 contacts were made with participants and surrogates to capture outcomes of interest at 6-month intervals, including information on ICH recurrence, ischemic stroke, cognitive performance, and cause of death. The median follow-up was 4.3 years with an IQR of 3.2-5.4. The cause of death categories were ICH, cardiac, ischemic CVA, other, cancer, pulmonary, renal, endocrine, accidents, infection, dementia and unknown. Results: There were 180 deaths (18.8%) reported by surrogates contacted in the ERICH-L study. Of those, 63 causes of death were unknown or considered unverifiable. The most common cause of death reported was decline from the index ICH (32.7%). The next most common cause of death was cardiac (14%), other (12.1%), infection (11.2%), cancer (10.3%) and ischemic stroke (1.9%). Some examples reported as other are liver failure, old age, myelodysplastic syndrome, suicide and Parkinson’s Disease. Recurrent ICH occurred in 4 out of 107 known causes of death. By year 5, cardiac causes surpassed ICH as the cause of death. Conclusion: Cardiac causes of death were more common than either recurrent ICH or ischemic stroke, surpassed only by decline from the index ICH. Future efforts to prevent causes of death after ICH should address cardiac disease and risk factors. This finding may explain the effect of restarting anticoagulant or antiplatelet therapy and improved mortality.

BACKGROUND: Intraventricular hemorrhage (IVH) and white matter lesion (WML) severity are associated with higher rates of death and disability in intracerebral hemorrhage (ICH). A prior report identified an increased risk of IVH with greater WML burden but did not control for location of ICH. We sought to determine whether a higher degree of WML is associated with a higher risk of IVH after controlling for ICH location. METHODS: Utilizing the patient population from two large ICH studies; the Genetic and Environmental Risk Factors for Hemorrhagic Stroke (GERFHS III) Study and the Ethnic/Racial Variations of Intracerebral Hemorrhage (ERICH) Study, we graded WML using the Van Swieten Scale (0-1 for mild, 2 for moderate, and 3-4 for severe WML) and presence or absence of IVH in baseline CT scans. We used multivariable regression models to adjust for relevant covariates. RESULTS: Among 3023 ICH patients, 1260 (41.7%) had presence of IVH. In patients with IVH, the proportion of severe WML (28.6%) was higher compared with patients without IVH (21.8%) (p

Introduction: The National Institute of Health Stroke Scale (NIHSS) is the most widely used measure of neurological deficits in clinical trials. Using the placebo arm of the NINDS t-PA Stroke Trial, it has been demonstrated that the total volume of cerebral infarction in patients with similar NIHSS scores is greater for right compared to left hemisphere strokes. Our objective was to verify this finding in a non-clinical trial, independent data set of acute ischemic strokes. Methods: The Greater Cincinnati/Northern Kentucky Stroke Study (GCNKSS) is a population-based study that tracks the incidence of stroke. A convenient subsample from the 2010 GCNKSS ischemic stroke cohort (N= 368) underwent detailed imaging analysis. Research nurses abstracted patient reords to include baseline retrospective NIHSS score. The 24 hour infarct volume was segmented using manual tracing. NIHSS was compared between left and right brain using Wilcoxon rank sum test. Spearman rank correlation determined the association between the NIHSS score and infarct volume by hemisphere. Patients were stratified by NIHSS (0 to 5, 6 to 20, and greater than 20). Results: Among 368 ischemic stroke subjects with imaging data, excluded were 77 brainstem or cerebellar infarcts, 37 undetermined volume, 1 missing NIHSS, and 3 undetermined laterality. For the remaining 250 patients, 132 were left and 118 were right hemisphere strokes, and 210 had an MRI and 40 had CT. Median time from onset to imaging was 24 hours. Baseline NIHSS was similar by hemisphere and correlated with stroke volume (r=0.38, p Conclusion: The NIHSS score correlates with volume by hemisphere, but has a larger infarct volume for right hemisphere than left hemisphere for similar NIHSS. This likely reflects the different weighting of the NIHSS with regard to language. This finding confirms prior results in an independent dataset.

Introduction: Cryptogenic stroke is defined as not attributable to an identified source despite standard evaluation. The absence of small vessel or large artery disease in such evaluation suggests that cryptogenic stroke may be largely cardioembolic. We hypothesized that cryptogenic stroke would be similar to cardioembolic stroke in clinical and imaging characteristics. Methods: The Greater Cincinnati/Northern Kentucky Stroke Study (GCNKSS) is a population-based study that tracks the regional incidence of stroke. A convenient subsample from the 2010 GCNKSS ischemic stroke cohort (N= 368) was selected for detailed neuroimaging analysis. The study physician subtyped cases based on clinical, radiographic and laboratory findings (carotid ultrasound, echocardiography, vascular imaging). Subtypes included cryptogenic, cardioembolic, large-vessel, small-vessel, undetermined, and other. Three radiologists performed imaging analysis including number of acute infarcts, location and white matter hyperintensity (WMH). Infarct volume was segmented using manual tracing. Results: Of 368 ischemic stroke cases with imaging data, subtypes were 26.4% cryptogenic, 16.3% large vessel, 15.5% small vessel, 24.7% cardioembolic, 5.4% undetermined, and 11.7% other. Compared to cardioembolic, cryptogenic stroke patients were younger, had less hypertension, higher alcohol use, smaller infarct volume and differed in location of stroke. Cryptogenic stroke had more clinical and radiological features in common with large and small-vessel stroke (Table). Undetermined and other had no significant differences to cryptogenic. Conclusion: Contrary to our hypothesis, cryptogenic stroke was different from cardioembolic stroke and appeared more similar to large vessel stroke in clinical and radiological characteristics. Further testing on a larger sample size to evaluate the impact of cardiac event monitoring on subtype distribution is needed.