Jennifer Osborne

The Ethnic/Racial Variations of Intracerebral Hemorrhage (ERICH) Study Protocol

Background and Purpose— Epidemiological studies of intracerebral hemorrhage (ICH) have consistently demonstrated variation in incidence, location, age at presentation, and outcomes among non-Hispanic white, black, and Hispanic populations. We report here the design and methods for this large, prospective, multi-center case–control study of ICH. Methods— The Ethnic/Racial Variations of Intracerebral Hemorrhage (ERICH) study is a multi-center, prospective case–control study of ICH. Cases are identified by hot-pursuit and enrolled using standard phenotype and risk factor information and include neuroimaging and blood sample collection. Controls are centrally identified by random digit dialing to match cases by age (±5 years), race, ethnicity, sex, and metropolitan region. Results— As of March 22, 2013, 1655 cases of ICH had been recruited into the study, which is 101.5% of the target for that date, and 851 controls had been recruited, which is 67.2% of the target for that date (1267 controls) for a total of 2506 subjects, which is 86.5% of the target for that date (2897 subjects). Of the 1655 cases enrolled, 1640 cases had the case interview entered into the database, of which 628 (38%) were non-Hispanic black, 458 (28%) were non-Hispanic white, and 554 (34%) were Hispanic. Of the 1197 cases with imaging submitted, 876 (73.2%) had a 24 hour follow-up CT available. In addition to CT imaging, 607 cases have had MRI evaluation. Conclusions— The ERICH study is a large, case–control study of ICH with particular emphasis on recruitment of minority populations for the identification of genetic and epidemiological risk factors for ICH and outcomes after ICH.

Infection After Intracerebral Hemorrhage: Risk Factors and Association With Outcomes in the Ethnic/Racial Variations of Intracerebral Hemorrhage Study

Background and Purpose— Risk factors for infections after intracerebral hemorrhage (ICH) and their association with outcomes are unknown. We hypothesized there are predictors of poststroke infection and infections drive worse outcomes. Methods— We determined prevalence of infections in a multicenter, triethnic study of ICH. We performed univariate and multivariate analyses to determine the association of infection with admission characteristics and hospital complications. We performed logistic regression on association of infection with outcomes after controlling for known determinants of prognosis after ICH (volume, age, infratentorial location, intraventricular hemorrhage, and Glasgow Coma Scale). Results— Among 800 patients, infections occurred in 245 (31%). Admission characteristics associated with infection in multivariable models were ICH volume (odds ratio [OR], 1.02/mL; 95% confidence interval [CI], 1.01–1.03), lower Glasgow Coma Scale (OR, 0.91 per point; 95% CI, 0.87–0.95), deep location (reference lobar: OR, 1.90; 95% CI, 1.28–2.88), and black race (reference white: OR, 1.53; 95% CI, 1.01–2.32). In a logistic regression of admission and hospital factors, infections were associated with intubation (OR, 3.1; 95% CI, 2.1–4.5), dysphagia (with percutaneous endoscopic gastrostomy: OR, 3.19; 95% CI, 2.03–5.05 and without percutaneous endoscopic gastrostomy: OR, 2.11; 95% CI, 1.04–4.23), pulmonary edema (OR, 3.71; 95% CI, 1.29–12.33), and deep vein thrombosis (OR, 5.6; 95% CI, 1.86–21.02), but not ICH volume or Glasgow Coma Scale. Infected patients had higher discharge mortality (16% versus 8%; P=0.001) and worse 3-month outcomes (modified Rankin Scale ≥3; 80% versus 51%; P<0.001). Infection was an independent predictor of poor 3-month outcome (OR, 2.6; 95% CI, 1.8–3.9). Conclusions— There are identifiable risk factors for infection after ICH, and infections predict poor outcomes.Background and Purpose Risk factors for infections after intracerebral hemorrhage (ICH) and their association with outcomes are unknown. We hypothesized there are predictors of post-stroke infection and infections drive worse outcomes.

Monocyte Count and 30-Day Case Fatality in Intracerebral Hemorrhage

Background and Purpose— Monocytes may contribute to secondary injury after intracerebral hemorrhage (ICH). We tested the association of absolute monocyte count with 30-day ICH case fatality in a multiethnic cohort. Methods— Ethnic/Racial Variations of Intracerebral Hemorrhage (ERICH) study is a prospective, multicenter, case–control study of ICH among white, black, and Hispanic patients. In 240 adults with nontraumatic ICH within 24 hours of symptom onset, we evaluated the influence of ICH score and complete blood count components on 30-day case fatality using generalized linear models. Results— Mean age was 62.8 years (SD, 14 years); 61.7% were men, 33.3% black, and 29.6% Hispanic. Median ICH volume was 9.9 mL (interquartile range, 4.4–26.7). After adjusting for patient age and initial hemoglobin, higher total white blood cell count (P=0.0011), driven by higher absolute neutrophil count (P=0.002), was associated with larger ICH volume, whereas absolute monocyte count was not (P=0.15). After adjusting for age, Glasgow Coma Scale, ICH volume, location, and the presence or absence of intraventricular hemorrhage, baseline absolute monocyte count was independently associated with higher 30-day case-fatality (odds ratio, 5.39; 95% confidence interval, 1.87–15.49; P=0.0018), whereas absolute neutrophil count (odds ratio, 1.04; 0.46–2.32; P=0.93) and white blood cell count (odds ratio, 1.62; 0.58–4.54; P=0.36) were not. Conclusions— These data support an independent association between higher admission absolute monocyte count and 30-day case-fatality in ICH. Inquiry into monocyte-mediated pathways of inflammation and apoptosis may elucidate the basis for the observed association and may be targets for ICH neuroprotection.

Prophylactic Antiepileptic Drug Use and Outcome in the Ethnic/Racial Variations of Intracerebral Hemorrhage Study

Background and Purpose— The role of antiepileptic drug (AED) prophylaxis after intracerebral hemorrhage (ICH) remains unclear. This analysis describes prevalence of prophylactic AED use, as directed by treating clinicians, in a prospective ICH cohort and tests the hypothesis that it is associated with poor outcome. Methods— Analysis included 744 patients with ICH enrolled in the Ethnic/Racial Variations of Intracerebral Hemorrhage (ERICH) study before November 2012. Baseline clinical characteristics and AED use were recorded in standardized fashion. ICH location and volume were recorded from baseline neuroimaging. We analyzed differences in patient characteristics by AED prophylaxis, and we used logistic regression to test whether AED prophylaxis was associated with poor outcome. The primary outcome was 3-month modified Rankin Scale score, with 4 to 6 considered poor outcome. Results— AEDs were used for prophylaxis in 289 (39%) of the 744 subjects; of these, levetiracetam was used in 89%. Patients with lobar ICH, craniotomy, or larger hematomas were more likely to receive prophlyaxis. Although prophylactic AED use was associated with poor outcome in an unadjusted model (odds ratio, 1.40; 95% confidence interval, 1.04–1.88; P=0.03), this association was no longer significant after adjusting for clinical and demographic characteristics (odds ratio, 1.11; 95% confidence interval, 0.74–1.65; P=0.62). Conclusions— We found no evidence that AED use (predominantly levetiracetam) is independently associated with poor outcome. A prospective study is required to assess for a more modest effect of AED use on outcome after ICH.

Ischemic lesions, blood pressure dysregulation, and poor outcomes in intracerebral hemorrhage

Objective: To evaluate the associations among diffusion-weighted imaging (DWI) lesions, blood pressure (BP) dysregulation, MRI markers of small vessel disease, and poor outcome in a large, prospective study of primary intracerebral hemorrhage (ICH). Methods: The Ethnic/Racial Variations of Intracerebral Hemorrhage (ERICH) study is a multicenter, observational study of ICH among white, black, and Hispanic patients. Results: Of 600 patients, mean (±SD) age was 60.8 ± 13.6 years, median (interquartile range) ICH volume was 9.1 mL (3.5–20.8), and 79.6% had hypertension. Overall, 26.5% of cases had DWI lesions, and this frequency differed by race/ethnicity (black 33.8%, Hispanic 24.9%, white 20.2%, overall p = 0.006). A logistic regression model of variables associated with DWI lesions included lower age (odds ratio [OR] 0.721, p = 0.002), higher first recorded systolic BP (10-unit OR 1.12, p = 0.002), greater change in mean arterial pressure (MAP) prior to the MRI (10-unit OR 1.10, p = 0.037), microbleeds (OR 1.99, p = 0.008), and higher white matter hyperintensity (WMH) score (1-unit OR 1.16, p = 0.002) after controlling for race/ethnicity, leukocyte count, and acute in-hospital antihypertensive treatment. A second model of variables associated with poor 90-day functional outcome (modified Rankin Scale scores 4–6) included DWI lesion count (OR 1.085, p = 0.034) as well as age, ICH volume, intraventricular hemorrhage, Glasgow Coma Scale score, WMH score, race/ethnicity, acute in-hospital antihypertensive treatment, and ICH location. Conclusions: These results support the hypotheses that acute BP dysregulation is associated with the development of DWI lesions in primary ICH and that DWI lesions are, in turn, associated with poor outcomes.

Untreated Hypertension: A Powerful Risk Factor for Lobar and Non-Lobar Intracerebral Hemorrhage in Whites, Blacks, and Hispanics

Background: Hypertension is a significant risk factor for intracerebral hemorrhage (ICH). Although ethnic/racial disparities related to hypertension and ICH have been reported, these previous studies were limited by a lack of Hispanics and inadequate power to analyze by ICH location. In the current study, while overcoming these prior limitations, we investigated whether there was variation by ethnicity/race of treated and untreated hypertension as risk factors for ICH. Methods: The ERICH study (Ethnic/Racial Variations of Intracerebral Hemorrhage) is a prospective, multicenter, case-control study of ICH among whites, blacks, and Hispanics. Cases were enrolled from 42 recruitment sites. Controls matched to cases 1:1 by age (±5 years), sex, ethnicity/race, and metropolitan area were identified by random-digit dialing. Subjects were interviewed to determine history of hypertension and use of antihypertensive medications. Cases and controls within ethnic groups were compared by using conditional logistic regression. Multivariable conditional logistic regression models were computed for ICH as an overall group and separately for the location subcategories deep, lobar, and infratentorial (brainstem/cerebellar). Results: Nine hundred fifty-eight white, 880 black, and 766 Hispanic ICH patients were enrolled. For ICH cases, untreated hypertension was higher in blacks (43.6%, P<0.0001) and Hispanics (46.9%, P<0.0001) versus whites (32.7%). In multivariable analyses adjusted for alcohol use, anticoagulation, hypercholesterolemia, education, and medical insurance status, treated hypertension was a significant risk factor across all locations of ICH in whites (odds ratio [OR], 1.57; 95% confidence interval [CI], 1.24–1.98; P<0.0001), blacks (OR, 3.02; 95% CI, 2.16–4.22; P<0.0001), and Hispanics (OR, 2.50; 95% CI, 1.73–3.62; P<0.0001). Untreated hypertension was a substantially greater risk factor for all 3 racial/ethnic groups across all locations of ICH: whites (OR, 8.79; 95% CI, 5.66–13.66; P<0.0001), blacks (OR, 12.46; 95% CI, 8.08–19.20; P<0.0001), and Hispanics (OR, 10.95; 95% CI, 6.58–18.23; P<0.0001). There was an interaction between race/ethnicity and ICH risk (P<0.0001). Conclusions: Untreated hypertension confers a greater ICH risk in blacks and Hispanics relative to whites across all anatomic locations of ICH. Accelerated research efforts are needed to improve overall hypertension treatment rates and to monitor the impact of such efforts on racial/ethnic disparities in stroke. Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01202864.Background: Hypertension is a significant risk factor for intracerebral hemorrhage (ICH). Although ethnic/racial disparities related to hypertension and ICH have been reported, these previous studies were limited by a lack of Hispanics and inadequate power to analyze by ICH location. In the current study, while overcoming these prior limitations, we investigated whether there was variation by ethnicity/race of treated and untreated hypertension as risk factors for ICH. Methods: The ERICH study (Ethnic/Racial Variations of Intracerebral Hemorrhage) is a prospective, multicenter, case-control study of ICH among whites, blacks, and Hispanics. Cases were enrolled from 42 recruitment sites. Controls matched to cases 1:1 by age (±5 years), sex, ethnicity/race, and metropolitan area were identified by random-digit dialing. Subjects were interviewed to determine history of hypertension and use of antihypertensive medications. Cases and controls within ethnic groups were compared by using conditional logistic regression. Multivariable conditional logistic regression models were computed for ICH as an overall group and separately for the location subcategories deep, lobar, and infratentorial (brainstem/cerebellar). Results: Nine hundred fifty-eight white, 880 black, and 766 Hispanic ICH patients were enrolled. For ICH cases, untreated hypertension was higher in blacks (43.6%, P <0.0001) and Hispanics (46.9%, P <0.0001) versus whites (32.7%). In multivariable analyses adjusted for alcohol use, anticoagulation, hypercholesterolemia, education, and medical insurance status, treated hypertension was a significant risk factor across all locations of ICH in whites (odds ratio [OR], 1.57; 95% confidence interval [CI], 1.24–1.98; P <0.0001), blacks (OR, 3.02; 95% CI, 2.16–4.22; P <0.0001), and Hispanics (OR, 2.50; 95% CI, 1.73–3.62; P <0.0001). Untreated hypertension was a substantially greater risk factor for all 3 racial/ethnic groups across all locations of ICH: whites (OR, 8.79; 95% CI, 5.66–13.66; P <0.0001), blacks (OR, 12.46; 95% CI, 8.08–19.20; P <0.0001), and Hispanics (OR, 10.95; 95% CI, 6.58–18.23; P <0.0001). There was an interaction between race/ethnicity and ICH risk ( P <0.0001). Conclusions: Untreated hypertension confers a greater ICH risk in blacks and Hispanics relative to whites across all anatomic locations of ICH. Accelerated research efforts are needed to improve overall hypertension treatment rates and to monitor the impact of such efforts on racial/ethnic disparities in stroke. Clinical Trial Registration: URL: . Unique identifier: [NCT01202864][1]. # Clinical Perspective {#article-title-31} [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT01202864&atom=%2Fcirculationaha%2F134%2F19%2F1444.atom

Alcohol use and risk of intracerebral hemorrhage

Objective: To analyze the dose–risk relationship for alcohol consumption and intracerebral hemorrhage (ICH) in the Ethnic/Racial Variations of Intracerebral Hemorrhage (ERICH) study. Methods: ERICH is a multicenter, prospective, case-control study, designed to recruit 1,000 non-Hispanic white patients, 1,000 non-Hispanic black patients, and 1,000 Hispanic patients with ICH. Cases were matched 1:1 to ICH-free controls by age, sex, race/ethnicity, and geographic area. Comprehensive interviews included questions regarding alcohol consumption. Patterns of alcohol consumption were categorized as none, rare (<1 drink per month), moderate (≥1 drink per month and ≤2 drinks per day), intermediate (>2 drinks per day and <5 drinks per day), and heavy (≥5 drinks per day). ICH risk was calculated using the no-alcohol use category as the reference group. Results: Multivariable analyses demonstrated an ordinal trend for alcohol consumption: rare (odds ratio [OR] 0.57, p < 0.0001), moderate (OR 0.65, p < 0.0001), intermediate (OR 0.82, p = 0.2666), and heavy alcohol consumption (OR 1.77, p = 0.0003). Subgroup analyses demonstrated an association of rare and moderate alcohol consumption with decreased risk of both lobar and nonlobar ICH. Heavy alcohol consumption demonstrated a strong association with increased nonlobar ICH risk (OR 2.04, p = 0.0003). Heavy alcohol consumption was associated with significant increase in nonlobar ICH risk in black (OR 2.34, p = 0.0140) and Hispanic participants (OR 12.32, p < 0.0001). A similar association was not found in white participants. Conclusions: This study demonstrated potential protective effects of rare and moderate alcohol consumption on ICH risk. Heavy alcohol consumption was associated with increased ICH risk. Race/ethnicity was a significant factor in alcohol-associated ICH risk; heavy alcohol consumption in black and Hispanic participants poses significant nonlobar ICH risk.

Racial-ethnic disparities in acute blood pressure after intracerebral hemorrhage

Objective: To assess race-ethnic differences in acute blood pressure (BP) following intracerebral hemorrhage (ICH) and the contribution to disparities in ICH outcome. Methods: BPs in the field (emergency medical services [EMS]), emergency department (ED), and at 24 hours were compared and adjusted for group differences between non-Hispanic black (black), non-Hispanic white (white), and Hispanic participants in the Ethnic Racial Variations of Intracerebral Hemorrhage case-control study. Outcome was obtained by modified Rankin Scale (mRS) score at 3 months. We analyzed race-ethnic differences in good outcome (mRS ≤ 2) and mortality after adjusting for baseline differences and included BP recordings in this model. Results: Of 2,069 ICH cases enrolled, 30% were white, 37% black, and 33% Hispanic. Black and Hispanic patients had higher EMS and ED systolic and diastolic BPs compared with white patients (p = 0.0001). Although attenuated, at 24 hours after admission, black patients had higher systolic and diastolic BPs. After adjusting for baseline differences, significant race/ethnic differences persisted for EMS systolic, ED systolic and diastolic, and 24-hours diastolic BP. Only ED systolic and diastolic BP was associated with poor functional outcome, and no BP predicted mortality. We found no race-ethnic differences in 3-month functional outcome or mortality after adjusting for group differences, including acute BPs. Conclusions: Although black and Hispanic patients had higher BPs than white patients at presentation, we did not find race-ethnic disparities in 3-month functional outcome or mortality. ED systolic and diastolic BP was associated with poor functional outcome, but not mortality, in this race-ethnically diverse population.

Use of Statins and Outcomes in Intracerebral Hemorrhage Patients

Background and Purpose— Statin use may be associated with improved outcome in intracerebral hemorrhage patients. However, the topic remains controversial. Our analysis examined the effect of prior, continued, or new statin use on intracerebral hemorrhage outcomes using the ERICH (Ethnic/Racial Variations of Intracerebral Hemorrhage) data set. Methods— We analyzed ERICH (a multicenter study designed to examine ethnic variations in the risk, presentation, and outcomes of intracerebral hemorrhage) to explore the association of statin use and hematoma growth, mortality, and 3-month disability. We computed subset analyses with respect to 3 statin categories (prior, continued, or new use). Results— Two thousand four hundred and fifty-seven enrolled cases (mean age, 62 years; 42% females) had complete data on mortality and 3-month disability (modified Rankin Scale). Among those, 1093 cases were on statins (prior, n=268; continued, n=423; new, n=402). Overall, statin use was associated with reduced mortality and disability without any effect on hematoma growth. This association was primarily driven by continued/new statin use. A multivariate analysis adjusted for age and major predictors for poor outcome showed that continued/new statins users had good outcomes compared with prior users. However, statins may have been continued/started more frequently among less severe patients. When a propensity score was developed based on factors that could influence a physician’s decision in prescribing statins and used as a covariate, continued/new statin use was no longer a significant predictor of good outcome. Conclusions— Although statin use, especially continued/new use, was associated with improved intracerebral hemorrhage outcomes, this effect may merely reflect the physician’s view of a patient’s prognosis rather than a predictor of survival.

Incontinence and gait disturbance after intraventricular extension of intracerebral hemorrhage

Objective: We tested the hypothesis that intraventricular hemorrhage (IVH) is associated with incontinence and gait disturbance among survivors of intracerebral hemorrhage (ICH) at 3-month follow-ups. Methods: The Genetic and Environmental Risk Factors for Hemorrhagic Stroke study was used as the discovery set. The Ethnic/Racial Variations of Intracerebral Hemorrhage study served as a replication set. Both studies performed prospective hot-pursuit recruitment of ICH cases with 3-month follow-up. Multivariable logistic regression analyses were computed to identify risk factors for incontinence and gait dysmobility at 3 months after ICH. Results: The study population consisted of 307 ICH cases in the discovery set and 1,374 cases in the replication set. In the discovery set, we found that increasing IVH volume was associated with incontinence (odds ratio [OR] 1.50; 95% confidence interval [CI] 1.10–2.06) and dysmobility (OR 1.58; 95% CI 1.17–2.15) after controlling for ICH location, initial ICH volume, age, baseline modified Rankin Scale score, sex, and admission Glasgow Coma Scale score. In the replication set, increasing IVH volume was also associated with both incontinence (OR 1.42; 95% CI 1.27–1.60) and dysmobility (OR 1.40; 95% CI 1.24–1.57) after controlling for the same variables. Conclusion: ICH subjects with IVH extension are at an increased risk for developing incontinence and dysmobility after controlling for factors associated with severity and disability. This finding suggests a potential target to prevent or treat long-term disability after ICH with IVH.