Ethnic/Racial Variations Of Intracerebral Hemorrhage Research Articles

Association of Chronic Kidney Disease With Risk of Intracerebral Hemorrhage

The evidence linking chronic kidney disease (CKD) to spontaneous intracerebral hemorrhage (ICH) is inconclusive owing to possible confounding by comorbidities that frequently coexist in patients with these 2 diseases. To determine whether there is an association between CKD and ICH risk. A 3-stage study that combined observational and genetic analyses was conducted. First, the association between CKD and ICH risk was tested in the Ethnic/Racial Variations of Intracerebral Hemorrhage (ERICH) study, a multicenter case-control study in the US. All participants with available data on CKD from ERICH were included. Second, this analysis was replicated in the UK Biobank (UKB), an ongoing population study in the UK. All participants in the UKB were included in this study. Third, mendelian randomization analyses were implemented in the UKB using 27 CKD-related genetic variants to test for genetic associations. ERICH was conducted from August 1, 2010, to August 1, 2017, and observed participants for 1 year. The UKB enrolled participants between 2006 and 2010 and will continue to observe them for 30 years. Data analysis was performed from November 11, 2019, to May 10, 2022. CKD stages 1 to 5. The outcome of interest was ICH, ascertained in ERICH via expert review of neuroimages and in the UKB via a combination of self-reported data and International Statistical Classification of Diseases, Tenth Revision, codes. In the ERICH study, a total of 2914 participants with ICH and 2954 controls who had available data on CKD were evaluated (mean [SD] age, 61.6 [14.0] years; 2433 female participants [41.5%]; 3435 male participants [58.5%]); CKD was found to be independently associated with higher risk of ICH (odds ratio [OR], 1.95; 95% CI, 1.35-2.89; P < .001). This association was not modified by race and ethnicity. Replication in the UKB with 1341 participants with ICH and 501 195 controls (mean [SD] age, 56.5 [8.1] years; 273 402 female participants [54.4%]; 229 134 male participants [45.6%]) confirmed this association (OR, 1.28; 95% CI, 1.01-1.62; P = .04). Mendelian randomization analyses indicated that genetically determined CKD was associated with ICH risk (OR, 1.56; 95% CI, 1.13-2.16; P = .007). In this 3-stage study that combined observational and genetic analyses among study participants enrolled in 2 large observational studies with different characteristics and study designs, CKD was consistently associated with higher risk of ICH. Mendelian randomization analyses suggest that this association was causal. Further studies are needed to identify the specific biological pathways that mediate this association.

Risk Factors Associated With Mortality and Neurologic Disability After Intracerebral Hemorrhage in a Racially and Ethnically Diverse Cohort

Intracerebral hemorrhage (ICH) is the most severe subtype of stroke. Its mortality rate is high, and most survivors experience significant disability. To assess primary patient risk factors associated with mortality and neurologic disability 3 months after ICH in a large, racially and ethnically balanced cohort. This cohort study included participants from the Ethnic/Racial Variations of Intracerebral Hemorrhage (ERICH) study, which prospectively recruited 1000 non-Hispanic White, 1000 non-Hispanic Black, and 1000 Hispanic patients with spontaneous ICH to study the epidemiological characteristics and genomics associated with ICH. Participants included those with uniform data collection and phenotype definitions, centralized neuroimaging review, and telephone follow-up at 3 months. Analyses were completed in November 2021. Patient demographic and clinical characteristics as well as hospital event and imaging variables were examined, with characteristics meeting P < .20 considered candidates for a multivariate model. Elements included in the ICH score were specifically analyzed. Individual characteristics were screened for association with 3-month outcome of neurologic disability or mortality, as assessed by a modified Rankin Scale (mRS) score of 4 or greater vs 3 or less under a logistic regression model. A total of 25 characteristics were tested in the final model, which minimized the Akaike information criterion. Analyses were repeated removing individuals who had withdrawal of care. A total of 2568 patients (mean [SD] age, 62.4 [14.7] years; 1069 [41.6%] women and 1499 [58.4%] men) had a 3-month outcome determination available, including death. The final logistic model had a significantly higher area under the receiver operating characteristics curve (C = 0.88) compared with ICH score alone (C = 0.76; P < .001). Among characteristics associated with neurologic disability and mortality were larger log ICH volume (OR, 2.74; 95% CI, 2.36-3.19; P < .001), older age (OR per 1-year increase, 1.04; 95% CI, 1.02-1.05; P < .001), pre-ICH mRS score (OR, 1.62; 95% CI, 1.41-1.87; P < .001), lobar location (OR, 0.22; 95% CI, 0.16-0.30; P < .001), and presence of infection (OR, 1.85; 95% CI, 1.42-2.41; P < .001). The findings of this cohort study validate ICH score elements and suggest additional baseline and interim patient characteristics were associated with variation in 3-month outcome.

Abstract WMP79: Elevated Cardiac Troponin Levels In Patients With Non-traumatic Intracerebral Hemorrhage

Background: Elevated cardiac troponin (cTn) levels are frequently encountered after intracerebral hemorrhage (ICH). In small cohorts, increased cTn was associated with in-hospital mortality. This study investigated the factors associated with elevated cTn in ICH cases and its relationship with outcome. Methods: We examined maximum cTn levels within 48 hours of hospital arrival in subjects enrolled in the Ethnic Racial Variations of Intracerebral Hemorrhage (ERICH) study. ERICH is a multi-center prospective study designed to examine ethnic variations in the risk, presentation, and outcomes of ICH. Elevated troponins were defined as cTn&gt;0.1 mg/dL. Poor outcome was defined as modified Rankin Scale (mRS)≥3 at 3 months. We used logistic regression analysis with backward elimination to identify factors associated with elevated cTn levels and their relationship with poor outcome. The model included baseline demographics and clinical characteristics with at least weak association at baseline (p&lt;0.2). Results are presented as odds ratios (OR) with their correspondent 95% confidence intervals (CI). Results: Of the 2061 included in the analysis, 39% were females and 177 (9.4%) had elevated cTn levels. The sample was 31% white, 33% Hispanic, and 36% black. In univariate analysis, blacks, prior use of opioids or marijuana, low Glasgow coma scale (GCS) on admission, and presence of intraventricular hemorrhage (IVH) were associated with elevated cTn (p&lt;0.05 of all). In the multivariate model, blacks (OR=1.60, 95% CI 1.06-2.41), previous use of opiates (OR=2.27, 95% CI 1.23-4.21) or marijuana (OR=2.07, 95% CI 1.23-3.50), GCS on presentation (OR=0.90, 95% CI 0.87-0.94), presence of IVH (OR=1.42, 95% CI 1.01-2.00), and first measured systolic blood pressure (SBP) (OR=1.01, 95% CI 1.00-1.01) were associated with elevated cTn. Elevated cTn was associated with mRS&gt;3 at 3 months (OR=2.17, 95% CI 1.43-3.30). Conclusion: Elevated cardiac troponin was associated with worse 3 month outcome independent of ICH severity. Surprisingly, sympathomimetic drug use was not associated with peak troponin while opiate and marijuana use were. Our results suggest the need to understand why blacks may have a greater susceptibility to myocardial injury after ICH.

Abstract TP133: Diabetes/hyperglycemia Is Associated With Poor Six-month Functional Outcomes, But Is Not Associated With The Development Of Microvascular Ischemic Lesions After Intracerebral Hemorrhage

Introduction: Ischemic lesions seen on diffusion weighted imaging (DWI) are associated with worsened outcomes after intracerebral hemorrhage (ICH) and are thought to arise due to microvascular damage. While hyperglycemia and diabetes mellitus contribute to small vessel disease, it is not known if these factors contribute to the development of DWI lesions and associated outcomes after ICH. Hypothesis: Indicators of diabetes/hyperglycemia will be associated with the development of DWI lesions and poor outcomes after ICH Methods: 1123 patients with MRI data from the Ethnic/Racial Variations of Intracerebral Hemorrhage (ERICH) study were included. Predictors with p&lt;0.15 in univariate analyses were included in initial multivariable logistic regression models. Least absolute shrinkage and selection operator (LASSO) regression was used to identify final models. Results: In univariate analysis, no measure of diabetes or hyperglycemia (medical history of diabetes, insulin or non-insulin antidiabetic medication use, blood glucose obtained by emergency medical services, blood glucose on admission, fasting blood glucose, or hemoglobin A1c) was associated with the development of DWI lesions (p&gt;0.05). Blood glucose on admission was incorporated into the initial multivariable model (p&lt;0.15). Univariate analysis for poor six-month functional outcome (modified Rankin Score &gt;3) showed that history of diabetes (p&lt;0.001), blood glucose on admission (p=0.002), fasting blood glucose (p=0.049), and use of non-insulin antidiabetic medications (p=0.036) were associated with poor outcomes. Final multivariable logistic regression analyses are shown in Tables 1 and 2. Conclusions: While diabetes and hyperglycemia are associated with worsened outcomes after ICH, this relationship is unexpectedly not mediated by microinfarcts despite their association with cerebral small vessel disease.

Contribution of Racial and Ethnic Differences in Cerebral Small Vessel Disease Subtype and Burden to Risk of Cerebral Hemorrhage Recurrence.

Black and Hispanic survivors of intracerebral hemorrhage (ICH) are at higher risk of recurrent intracranial bleeding. MRI-based markers of chronic cerebral small vessel disease (CSVD) are consistently associated with recurrent ICH. We therefore sought to investigate whether racial/ethnic differences in MRI-defined CSVD subtype and severity contribute to disparities in ICH recurrence risk. We analyzed data from the Massachusetts General Hospital ICH study (n = 593) and the Ethnic/Racial Variations of Intracerebral Hemorrhage (ERICH) study (n = 329). Using CSVD markers derived from MRIs obtained within 90 days of index ICH, we classified ICH cases as cerebral amyloid angiopathy (CAA)-related, hypertensive arteriopathy (HTNA)-related, and mixed etiology. We quantified CSVD burden using validated global, CAA-specific, and HTNA-specific scores. We compared CSVD subtype and severity among White, Black, and Hispanic ICH survivors and investigated its association with ICH recurrence risk. We analyzed data for 922 ICH survivors (655 White, 130 Black, 137 Hispanic). Minority ICH survivors had greater global CSVD (p = 0.011) and HTNA burden (p = 0.021) on MRI. Furthermore, minority survivors of HTNA-related and mixed-etiology ICH demonstrated higher HTNA burden, resulting in increased ICH recurrence risk (all p < 0.05). We uncovered significant differences in CSVD subtypes and severity among White and minority survivors of primary ICH, with direct implication for known disparities in ICH recurrence risk. Future studies of racial/ethnic disparities in ICH outcomes will benefit from including detailed MRI-based assessment of CSVD subtypes and severity and investigating social determinants of health.

Impact of Preexisting Cognitive Impairment and Race/Ethnicity on Functional Outcomes Following Intracerebral Hemorrhage.

In intracerebral hemorrhage (ICH), preexisting cognitive impairment has been identified as a risk factor for increased mortality and morbidity. However, previous studies examined predominantly White populations; therefore, the prevalence and effect of preICH cognitive impairment has not been studied in a multiethnic cohort. This limits the generalizability of previous findings. We sought to investigate the role of preexisting cognitive impairment in a multiethnic population on short-term mortality and functional outcomes after ICH. Patients with ICH were prospectively enrolled as cases for the GERFHS III (Genetic and Environmental Risk Factors for Hemorrhagic Stroke) Study and the Ethnic/Racial Variations of ICH (ERICH) Study. Cognitive impairment before ICH was defined as positive history of dementia or treatment with donepezil, galantamine, memantine, or rivastigmine on chart abstraction or baseline interview. Specific outcomes-modified Rankin Scale score at 3 months (0-2 versus ≥3), Barthel Index score (<100 versus 100) at 3 months, and withdrawal of care-were analyzed using multivariable logistic regression. Propensity score matching and analysis was done because of imbalances between cognitively impaired and cognitively intact groups. Of the 3537 cases of ICH, 304 patients had cognitive impairment predating ICH. Cognitively impaired subjects were more likely to experience withdrawal of care during hospitalization, and for survivors, greater disability (modified Rankin Scale score of ≥3) and lower Barthel scores after ICH. After propensity score matching, preexisting cognitive impairment was associated with a lower modified Rankin Scale at 3 months in the White, Black, and Hispanic subgroups. Preexisting cognitive impairment was associated with loss of independence 3-month post-ICH, when matching for risk factors of cognitive impairment, in the White, Black, and Hispanic subgroups. This suggests that preexisting cognitive impairment has a negative effect in obtaining functional independence following ICH, irrespective of race/ethnicity.

Hematoma expansion is more frequent in deep than lobar intracerebral hemorrhage.

To test the hypothesis that patients with deep intracerebral hemorrhage (ICH) would encounter hematoma expansion (HE) more frequently compared to patients with lobar ICH. Patients with ICH with neuroimaging to calculate HE were analyzed from the multicenter Ethnic/Racial Variations of Intracerebral Hemorrhage (ERICH) cohort. Patients with laboratory coagulopathy or preceding anticoagulant use were excluded to assess relationships of ICH location alone (deep vs lobar) with HE, defined as >33% relative growth. Odds ratios (ORs) and 95% confidence intervals (CIs) for these relationships were estimated with logistic regression. Sensitivity and specificity determined HE thresholds best associated with poor 3-month outcomes (modified Rankin score 4-6) stratified by location. There were 1,049 patients with deep and 408 patients with lobar ICH analyzed. Deep ICH locations were more likely to have HE (adjusted OR 1.57, 95% CI 1.08-2.29) after adjustment for age, sex, race, baseline hematoma size, and intraventricular hemorrhage. However, this difference was nonsignificant (adjusted OR 1.35, 95% CI 0.81-2.24) after controlling for time from symptom onset to admission CT in a subgroup analysis of 729 patients with these data. Yet, the threshold of HE best associated with poor outcomes was smaller in deep (30%) compared to lobar (50%) ICH. While HE was more frequent in deep than lobar ICH, this could be due to differences in symptom onset to admission CT times in our cohort. However, patients with deep ICH appear particularly vulnerable to the deleterious effects of small volumes of HE. Further studies should clarify whether ICH location needs to be considered in HE treatment paradigms.

Abstract TP347: Obstructive Sleep Apnea Frequency in Intracerebral Hemorrhage

Introduction: Obstructive sleep apnea (OSA) is a treatable condition and well-established risk factor for ischemic stroke, but the prevalence in ICH is unknown. We aim to characterize the frequency of OSA in spontaneous intracerebral hemorrhage (ICH). Methods: The Ethnic/Racial Variations of Intracerebral Hemorrhage (ERICH) study is a prospective observational study evaluating risk factors for ICH among whites, blacks, and Hispanics. OSA status was determined using two different strategies: (1) the Berlin Questionnaire, a validated screening tool to identify those with a high likelihood of OSA where “high risk” is defined as &gt; 1 point in at least 2 of 3 categories assessing snoring, fatigue, and hypertension, and (2) self-reported history of diagnosed sleep apnea. Results: We evaluated 3000 ICH cases. Within this group, 2896 (96.5%) completed the Berlin questionnaire, with 2064 (71%) patients being high risk for OSA. Compared to patients with low risk of OSA, those at high risk were more likely to be male (61% versus 53%, p&lt;0.001) with hypertension (93% versus 65%, p&lt;0.001), diabetes (32% versus 20%, p&lt;0.001), hyperlipidemia (49% versus 38%, p&lt;0.001), and higher BMI (29.8 +/- 8.1 versus 26.8 +/- 6.5, p&lt;0.001), and less likely to have lobar ICH location (29% versus 35%, p&lt;0.001). Self-reported history of prior sleep apnea diagnosis was present in only 175 (9.5%) of ICH cases. Conclusions: OSA is highly prevalent and underdiagnosed in our cohort of ICH patients. Given the effective treatments available for OSA, which have been shown to improve morbidity and mortality in patients with ischemic stroke, further studies are needed to assess the role of OSA as both a determinant of both risk and outcome in ICH.

Abstract WP408: Risk of Lobar Intracerebral Hemorrhage From Hypertension is Greatest at an Early Age

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.

Determinants of Poor Outcome after Intracerebral Hemorrhage: Ethnic/Racial Variations of Intracerebral Hemorrhage (ERICH) Study

Introduction: Intracerebral hemorrhage (ICH) is the most severe subtype of stroke. Its mortality rate is high, and the majority of survivors suffer significant disability. The Ethnic/Racial Variations of Intracerebral Hemorrhage (ERICH) study prospectively recruited 1000 non-Hispanic white, 1000 non-Hispanic black, and 1000 Hispanic spontaneous ICH cases to study the epidemiology and genomics of ICH. Herein, we report the primary determinants of 3-month outcome after ICH in a large, multi-ethnic cohort. Methods: Between 2010 and 2015, cases were prospectively recruited with uniform data collection and phenotype definitions, centralized neuroimaging review, and telephone follow-up at 3 months. Individual characteristics were screened for association with 3-month outcome of modified Rankin Scale (mRS) ≥4 versus ≤3 under a logistic regression model, and those meeting P<0.2 were candidates for a multivariate model, in which the final model minimized the Akaike information criterion. Analyses were repeated removing individuals that had withdrawal of care. ICH Score elements were specifically analyzed. Results: Of the 3000 cases, 2568 had a 3-month outcome determination available (including death). Of the 76 characteristics examined univariately, 51 met the P<0.2 criteria, and 25 were retained in the final model. This logistic model had a significantly higher (P=6.2x1022) area under the receiver operating characteristics curve (C = 0.88) compared with ICH score alone (C=0.76). Among the characteristics with the strongest association with poor outcome were log increased ICH volume (OR=2.7), age (OR=1.03) and pre-ICH mRS (OR=1.6), lobar location (OR=0.21), and presence of infection (OR=1.9). Conclusion: ICH score elements were validated as important determinants of 3-month outcome. However, additional patient characteristics that significantly increase our model's predictive ability were also identified and should be considered in future studies. Funding: The study was supported by the National Institute of Neurological Diseases and Stroke (NINDS U01NS069763). Declaration of Interest: CEH received subcontract support under NINDS U01NS069763 from The University of Cincinnati during the life of the Study, and subcontract support under NINDS 1R34NF056638-01 Clear III from Johns Hopkins and subcontract support under NINDS 2P50NS044203-06 STOP-IT from The University of Cincinnati during portions of the life of the trial. CDA receives sponsored research support from the National Institutes of Health of the United States (R01NS103924), the American Heart Association Atrial Fibrillation Strategically Focused Research Network, Massachusetts General Hospital, and Bayer AG, and has consulted for ApoPharma, Inc. No other related conflicts to report. Ethical Approval: IRB approval was obtained at all participating centers, and informed consent was obtained from all cases or their legally authorized representative.

Intracranial pressure monitoring in patients with spontaneous intracerebral hemorrhage.

The utility of ICP monitoring and its benefit with respect to outcomes after ICH is unknown. The aim of this study was to compare intracerebral hemorrhage (ICH) outcomes in patients who underwent intracranial pressure (ICP) monitoring to those who were managed by care-guided imaging and/or clinical examination alone. This was a retrospective analysis of data from the Ethnic/Racial variations of Intracerebral Hemorrhage (ERICH) study between 2010 and 2015. ICH patients who underwent ICP monitoring were propensity-score matched, in a 1:1 ratio, to those who did not undergo ICP monitoring. The primary outcome was 90-day mortality. Secondary outcomes were in-hospital mortality, hyperosmolar therapy use, ICH evacuation, length of hospital stay, and 90-day modified Rankin Scale (mRS) score, excellent outcome (mRS score 0-1), good outcome (mRS score 0-2), Barthel Index, and health-related quality of life (HRQoL; measured by EQ-5D and EQ-5D visual analog scale [VAS] scores). A secondary analysis for patients without intraventricular hemorrhage was performed. The ICP and no ICP monitoring cohorts comprised 566 and 2434 patients, respectively. The matched cohorts comprised 420 patients each. The 90-day and in-hospital mortality rates were similar between the matched cohorts. Shift analysis of 90-day mRS favored no ICP monitoring (p < 0.001). The rates of excellent (p < 0.001) and good (p < 0.001) outcome, Barthel Index (p < 0.001), EQ-5D score (p = 0.026), and EQ-5D VAS score (p = 0.004) at 90 days were lower in the matched ICP monitoring cohort. Rates of mannitol use (p < 0.001), hypertonic saline use (p < 0.001), ICH evacuation (p < 0.001), and infection (p = 0.001) were higher, and length of hospital stay (p < 0.001) was longer in the matched ICP monitoring cohort. In the secondary analysis, the matched cohorts comprised 111 patients each. ICP monitoring had a lower rate of 90-day mortality (p = 0.041). Shift analysis of 90-day mRS, Barthel Index, and HRQoL metrics were comparable between the matched cohorts. The findings of this study do not support the routine utilization of ICP monitoring in patients with ICH.

Abstract WP442: Cause of Death After Intracerebral Hemorrhage in the Longitudinal Follow-up of ICH Survivors in ERICH (ERICH-L) Study

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.

Abstract TP446: Predictors of Surgical Intervention in Patients With Spontaneous Intracerebral Hemorrhage

Objective: Despite no clear evidence from randomized trials, surgical intervention of spontaneous intracerebral hemorrhage (ICH) still occurs. We sought to describe the characteristics of patients undergoing surgical intervention in ICH. Methods: Data from the Ethnic/Racial Variations of Intracerebral Hemorrhage (ERICH) study were analyzed, and ICH patients were categorized into surgical intervention or nonoperative management groups. Patients with primary intraventricular hemorrhage (IVH) and those without data regarding the use of surgical intervention data were excluded. Multivariable models were developed to identify predictors of surgical intervention. Results: The study cohort comprised 2,947 patients, and surgical intervention was performed in 289 (10%). Younger age (p&lt;0.001), lower baseline modified Rankin Scale score (mRS; p&lt;0.001), higher admission Glasgow Coma Scale (GCS; p=0.007), larger ICH volume (p&lt;0.001), infratentorial ICH location (p&lt;0.001), lobar ICH location (p&lt;0.001), lack of IVH (p=0.001), ICP monitoring (p&lt;0.001), and mannitol use (p&lt;0.001) were independent predictors of surgical intervention. Younger age (p&lt;0.001), lower baseline mRS score (p=0.002), larger ICH volume (p&lt;0.001), lobar ICH location (p&lt;0.001), ICP monitoring (p&lt;0.001), and mannitol use (p&lt;0.001) were independent predictors of surgical interventions in supratentorial ICHs. Larger ICH volume (p&lt;0.001), ICP monitoring (p&lt;0.001), and mannitol use (p=0.005) were independent predictors of surgical interventions in infratentorial ICHs. Conclusion: We identified multiple factors associated with surgical intervention for patients with ICH. Younger age, good neurological function at baseline, large ICH volume on presentation, and lobar or infratentorial hematomas were independently associated with surgical intervention in ICH patients. Additional studies are necessary to determine the risk to benefit profile of ICH surgery.

Abstract 75: Predictors of Poor Outcome After Intracerebral Hemorrhage: Ethnic/Racial Variations of Intracerebral Hemorrhage (ERICH) Study

Introduction: Intracerebral hemorrhage (ICH) is the most severe subtype of stroke with a high mortality rate and majority of survivors suffering significant disability. The Ethnic/Racial Variations of Intracerebral Hemorrhage (ERICH) study prospectively recruited 1000 white, 1000 black and 1000 Hispanic spontaneous ICH cases. Herein, we report the main results of the predictors of 3 month outcome after ICH. Hypothesis: We hypothesized that ICH Score variables of age, ICH volume, ICH location, presence of intraventricular hemorrhage (IVH), and presenting Glasgow Coma Scale would predict long-term disability in addition to prior validation of mortality. Methods: Between 2010-2015, cases were prospectively recruited with uniform phenotype definitions, centralized neuroimaging review and with telephone follow-up at 3 months. Apolipoprotein E genotyping was performed centrally. Individual characteristics were screened for association under a logistic regression model, 90-day mRS ≥ 4 versus 0-3, and those meeting P&lt;0.2 were entered into multivariate model building where the final model was determined by minimum AIC score. Analyses were repeated removing subjects with withdrawal of care. Results: The Table presents the prevalence/average of each variable entering the final multivariate model for association with poor (mRS 4-6) compared to good (mRS 0-3) outcome at 3 months. When analyses were repeated excluding withdrawal of care, overall Graeb (IVH) score fell out of the model (with presence of IVH replacing it) but the remaining variables were retained and in the same direction of effect. C-statistic for the multivariate model = 0.884 compared to 0.763 for ICH score alone (p=1.7E-22). Conclusion: ICH score elements were validated as predictive of 3 month outcome. Novel baseline characteristics such as white matter hyperintensity as well as subsequent clinical events that may affect outcomes were identified. Location specific results to be presented.

Abstract TP438: Cigarette Smoking History and Functional Outcomes After Spontaneous Intracerebral Hemorrhage

Objective: While cigarette use may be a risk for intracerebral hemorrhage (ICH), animal models suggest that nicotine has a potential neuroprotective effect. The aim of this multicenter study is to determine the effect of smoking on outcome in ICH patients. Methods: We analyzed prospectively collected data from the Ethnic/Racial Variations of Intracerebral Hemorrhage (ERICH) study, and included patients with smoking status data in the analysis. Patients were dichotomized into non-smokers versus ever-smokers, and the latter group was further categorized as former (&gt;30 days before ICH) or current (≤30 days before ICH) smokers. The primary outcome was 90-day modified Rankin Scale (mRS) score shift analysis. Secondary outcomes were in-hospital mortality and mortality, Barthel Index, and self-reported health status measures at 90 days. Results: The overall study cohort comprised 1,509 non-smokers and 1,423 ever-smokers (841 former, 577 current, 5 unknown). No difference in primary outcome was observed between non-smokers versus ever-smokers (aOR=1.041 [0.904-1.199], p=0.577). No differences in primary outcome were observed between former (aOR=0.932 [0.791-1.178], p=0.399) or current smokers (aOR=1.178 [0.970-1.431], p=0.098) versus non-smokers. Subgroup analyses by race/ethnicity demonstrated no differences in primary outcome when former and current smokers were compared to non-smokers. Former, but not current, smokers had a lower in-hospital mortality rate (aOR=0.695 [0.500-0.968], p=0.031), which was only observed in Hispanics (aOR=0.533 [0.309-0.921], p=0.024). Differences in self-reported health status measures were only observed in whites. Conclusion: Cigarette smoking history does not appear to provide a beneficial effect on 90-day functional outcome in patients with ICH.

Minority Patients are Less Likely to Undergo Withdrawal of Care After Spontaneous Intracerebral Hemorrhage.

Prior studies of patients in the intensive care unit have suggested racial/ethnic variation in end-of-life decision making. We sought to evaluate whether race/ethnicity modifies the implementation of comfort measures only status (CMOs) in patients with spontaneous, non-traumatic intracerebral hemorrhage (ICH). We analyzed data from the Ethnic/Racial Variations of Intracerebral Hemorrhage (ERICH) study, a prospective cohort study specifically designed to enroll equal numbers of white, black, and Hispanic subjects. ICH patients aged ≥ 18years were enrolled in ERICH at 42 hospitals in the USA from 2010 to 2015. Univariate and multivariate logistic regression analyses were implemented to evaluate the association between race/ethnicity and CMOs after adjustment for potential confounders. A total of 2705 ICH cases (912 black, 893 Hispanic, 900 white) were included in this study (mean age 62 [SD 14], female sex 1119 [41%]). CMOs patients comprised 276 (10%) of the entire cohort; of these, 64 (7%) were black, 79 (9%) Hispanic, and 133 (15%) white (univariate p < 0.001). In multivariate analysis, compared to whites, blacks were half as likely to be made CMOs (OR 0.50, 95% CI 0.34-0.75; p = 0.001), and no statistically significant difference was observed for Hispanics. All three racial/ethnic groups had similar mortality rates at discharge (whites 12%, blacks 9%, and Hispanics 10%; p = 0.108). Other factors independently associated with CMOs included age (p < 0.001), premorbid modified Rankin Scale (p < 0.001), dementia (p = 0.008), admission Glasgow Coma Scale (p = 0.009), hematoma volume (p < 0.001), intraventricular hematoma volume (p < 0.001), lobar (p = 0.032) and brainstem (p < 0.001) location and endotracheal intubation (p < 0.001). In ICH, black patients are less likely than white patients to have CMOs. However, in-hospital mortality is similar across all racial/ethnic groups. Further investigation is warranted to better understand the causes and implications of racial disparities in CMO decisions.

Hypertension and intracerebral hemorrhage recurrence among white, black, and Hispanic individuals.

To clarify whether recurrence risk for intracerebral hemorrhage (ICH) is higher among black and Hispanic individuals and whether this disparity is attributable to differences in blood pressure (BP) measurements and their variability. We analyzed data from survivors of primary ICH enrolled in 2 separate studies: (1) the longitudinal study conducted at Massachusetts General Hospital (n = 759), and (2) the ERICH (Ethnic/Racial Variations of Intracerebral Hemorrhage) study (n = 1,532). Participants underwent structured interview at enrollment (including self-report of race/ethnicity) and were followed longitudinally via phone calls and review of medical records. We captured systolic BP (SBP) and diastolic BP measurements, and quantified variability as SBP and diastolic BP variation coefficients. We used multivariable (Cox regression) survival analysis to identify risk factors for ICH recurrence. We followed 2,291 ICH survivors (1,121 white, 529 black, 605 Hispanic, and 36 of other race/ethnicity). Both black and Hispanic patients displayed higher SBP during follow-up (p < 0.05). Black participants also displayed greater SBP variability during follow-up (p = 0.032). In univariable analyses, black and Hispanic patients were at higher ICH recurrence risk (p < 0.05). After adjusting for BP measurements and their variability, both Hispanic (hazard ratio = 1.51, 95% confidence interval 1.14-2.00, p = 0.004) and black (hazard ratio = 1.98, 95% confidence interval 1.36-2.86, p < 0.001) patients remained at higher risk of ICH recurrence. Black and Hispanic patients are at higher risk of ICH recurrence; hypertension severity (average BP and its variability) does not fully account for this finding. Additional studies will be required to further elucidate determinants for this health disparity.

Restarting antiplatelet therapy after spontaneous intracerebral hemorrhage: Functional outcomes.

To compare the functional outcomes and health-related quality of life metrics of restarting vs not restarting antiplatelet therapy (APT) in patients presenting with intracerebral hemorrhage (ICH) in the ERICH (Ethnic/Racial Variations of Intracerebral Hemorrhage) study. Adult patients aged 18 years and older who were on APT before ICH and were alive at hospital discharge were included. Patients were dichotomized based on whether or not APT was restarted after hospital discharge. The primary outcome was a modified Rankin Scale score of 0-2 at 90 days. Secondary outcomes were excellent outcome (modified Rankin Scale score 0-1), mortality, Barthel Index, and health status (EuroQol-5 dimensions [EQ-5D] and EQ-5D visual analog scale scores) at 90 days. The APT and no APT cohorts comprised 127 and 732 patients, respectively. Restarting APT was associated with lower rates of good functional outcome (36.5% vs 40.8%; p = 0.021) and lower Barthel Index scores at 90 days (p = 0.041). The 2 cohorts were then matched in a 1:1 ratio, and the matched cohorts each comprised 107 patients. No difference in primary outcome was observed between restarting vs not restarting APT (35.5% vs 43.9%; p = 0.105). There were also no differences between the secondary outcomes of the 2 cohorts. Restarting APT in patients with ICH of mild to moderate severity after acute hospitalization is not associated with worse functional outcomes or health-related quality of life at 90 days. In patients with significant cardiovascular risk factors who experience an ICH, restarting APT remains the decision of the treating practitioner.

Abstract WMP107: Efficacy of Intraventricular Administration of Alteplase for Intraventricular Hemorrhage

Introduction: The efficacy of extraventricular drain (EVD) alone was compared to EVD with intraventricular alteplase injection for the treatment of intraventricular hemorrhage (IVH) in the Ethnic/Racial Variations of Intracerebral Hemorrhage (ERICH) cohort. Methods: ERICH study subjects with IVH and EVD placement were dichotomized by alteplase administration. Propensity score modeling was used to adjust for significant differences in baseline variables and included age, gender, race/ethnicity, initial Glasgow Coma Scale (GCS) score, ICH location, initial ICH volume, primary IVH, and initial IVH volume (Table 1). Outcome measures included 3, 6, and 12-month modified Rankin scale (mRS) as well as IVH volume change on follow-up head CT within 24 hours. Good outcome was defined as a mRS &lt;=3. Mann-Whitney U and Chi-squared tests were utilized for statistical analyses. Results: Follow-up mRS scores at 3, 6, and 12 months were not significantly different between the two groups. Compared to the initial head CT on presentation, a significant reduction of IVH volume was seen on the subsequent head CT (Table 2). Conclusion: For ERICH subjects with IVH and EVD placement, the administration of intraventricular alteplase resulted in significant IVH volume reduction. The sample size, however, was likely insufficient to detect a difference between mRS outcomes. Our findings in this non-randomized IVH cohort highlight real world clinical practice outcomes and are consistent with the results of CLEAR III.

Abstract 132: Utility of Prophylactic Antiepileptic Drug Administration on Seizure Prevention and Disability Following Intracerebral Hemorrhage in the Ethnic/Racial Variations of Intracerebral Hemorrhage Study

Background &amp; Purpose: Intracerebral hemorrhage (ICH) has the highest morbidity and mortality rate of any stroke subtype and clinicians often administer prophylactic anti-epileptic drugs (AEDs) as a means of preventing post-stroke seizures, particularly following lobar hemorrhage (LH). However, evidence for AED efficacy in preventing seizures and reducing disability is lacking given difficulty executing randomized prospective trials. We report an analysis of data from a large prospective observational study of ICH that evaluates the effect of prophylactic AED administration on seizure occurrence and disability following ICH. Methods: Primary analysis was performed on 1636 patients with ICH enrolled in the Ethnic/Racial Variations of Intracerebral Hemorrhage (ERICH) study with subset analysis completed in patients with primary LH (n=562). A propensity score for administration of prophylactic AED was based on age, gender, race, ICH volume, location, presence of intraventricular hemorrhage, ventriculostomy, surgery, GCS, history of ischemic stroke, diabetes, sepsis, dementia, alcohol use and illicit drug use; patients were matched by the closest propensity score (difference &lt;0.1). McNemar’s test was used to compare the occurrence of seizure and disability, defined by Modified Rankin Score (mRS) ≥ 3 at 3 months post ICH, in the treated and untreated groups. Similarly, analysis was performed on patients with LH by matching 281 treated patients with 281 untreated patients. Results: Of the 818 matched pairs of patients who were treated with prophylactic AEDs, there was no significant difference in seizure occurrence (p=0.6799) or disability (p=0.6521). Subset analysis of 281 matched pairs of patients with LH revealed no significant difference in seizure occurrence (p=0.1161) or disability (p=0.9146) between those treated with prophylactic AED and untreated patients. Conclusions: While prophylactic AED treatment of ICH is not recommended by current guidelines, clinical use remains widespread. Data from the large prospective ERICH study clearly reveal lack of efficacy in administering AEDs for prevention of seizures and reduction of disability following ICH, thus providing strong evidence to influence clinical practice and patient care.