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Background: Cerebral Amyloid Angiopathy (CAA) disease course is highly variable even in hereditary forms. Sex may be a possible modifying factor. We investigated biological sex differences in clinical disease course and magnetic resonance imaging-markers in sporadic (sCAA) and Dutch-type hereditary CAA (D-CAA). Methods: Patients with D-CAA and sCAA were included from hospital and research databases of the Leiden University Medical Center (2012–2020) and Massachusetts General Hospital (1994–2012). Key outcomes were: sex differences in symptomatic intracerebral hemorrhage (sICH) onset, recurrence and survival (analyzed using Kaplan Meier survival and regression analyses), and sex differences in magnetic resonance imaging-markers in D-CAA (explored using scatterplots), and in sCAA (investigated using regression analysis). Results: We included 136 patients with D-CAA (mean age 57 years, 56% women, 64% with previous sICH) and 370 patients with sCAA (mean age 76 years, 51% women, all with previous sICH). Men and women with D-CAA did not differ for sICH onset (median age 54 in men and 56 in women [ P =0.13]). Men with D-CAA had a slightly higher number of sICH compared with women (median 2 versus 1; adjusted RR, 1.5 [95% CI, 1.1–1.9]) and a shorter interval between the first and second sICH (median 1.8 years for men and 3.1 years for women, P =0.02). Men with sCAA had their first sICH at an earlier age (median 75 versus 78 years, respectively, P =0.003) and more lobar microbleeds (median 1 versus 0, P =0.022) compared with women with sCAA. No substantial differences were found in the other magnetic resonance imaging markers. Survival after first sICH was comparable between sexes for D-CAA ( P =0.12) and sCAA ( P =0.23). Conclusions: Men with CAA seem to have an earlier onset (sCAA) and more hemorrhagic disease course (sCAA and D-CAA) compared with women. Future studies are necessary to confirm these findings and determine the underlying role of sex-related factors.

Background: Blood pressure (BP) control represents a crucial intervention to improve long-term outcomes following spontaneous intracerebral hemorrhage (ICH). However, fewer than half of ICH survivors achieve target treatment goals. ICH survivors are also at very high risk for poststroke depression, which may contribute to inadequate BP control. We, therefore, sought to determine whether depressive symptoms after ICH are associated with inadequate BP control. We also investigated whether associations between depression after ICH and BP measurements were mediated by treatment with selective serotonin reuptake inhibitors or norepinephrine-serotonin reuptake inhibitors antidepressants. Methods: We leveraged data from a single-center longitudinal study of ICH conducted at Massachusetts General Hospital (Boston, MA) between 2006 and 2018. We collected data from semiautomated review of electronic health records, baseline and follow-up interviews, and computed tomography imaging. Information on BP measurements, depression diagnoses, antidepressants medication use, and medical visits were collected longitudinally and analyzed using mixed effects models. Primary outcomes included systolic and diastolic BP measurements during long-term follow-up after ICH. Results: We included 1243 consecutive ICH patients without pre-stroke depression history. Of these, 721 (58%) were diagnosed with incident depression over a median follow-up time of 52.8 months (interquartile range, 42.1–60.5). Depression onset was associated with subsequent increase in systolic (+8.3 mm Hg, SE, 2.4 mm Hg, P =0.012) and diastolic (+4.4 mm Hg, SE, 1.2 mm Hg) BP measurements. Resolution of depressive symptoms was associated with subsequent decrease in systolic (−5.9 mm Hg, SE, 1.4 mm Hg, P =0.031) and diastolic (−3.4 mm Hg, SE, 1.1 mm Hg, P =0.041) BP measurements. We also found associations between higher systolic BP measurements and use of selective serotonin reuptake inhibitor and noradrenaline-serotonin reuptake inhibitor antidepressants, independent of whether depression symptoms were active or not (all P Conclusions: ICH survivors displayed increasing BP values after receiving a diagnosis of depression, followed by decreasing values among those experiencing resolution of depressive symptoms. Use of selective serotonin reuptake inhibitor and noradrenaline-serotonin reuptake inhibitor antidepressants was independently associated with higher systolic BP measurements. Clinicians ought to closely monitor BP for ICH survivors being treated for depression, especially using selective serotonin reuptake inhibitor and noradrenaline-serotonin reuptake inhibitor. Future studies will also be required to investigate the mechanisms underlying these associations.

Background: Intracerebral hemorrhage (ICH) survivors are at high risk for recurrent stroke and cardiovascular events. Blood pressure (BP) control represents the most potent intervention to lower these risks, but optimal treatment targets in this patient population remain unknown. We sought to determine whether survivors of ICH achieving more intensive BP control than current guideline recommendations (systolic BP Methods: We analyzed data for 1828 survivors of spontaneous ICH from 2 cohort studies. Follow-up BP measurements were recorded 3 and 6 months after ICH, and every 6 months thereafter. Outcomes of interest were major adverse cardiovascular and cerebrovascular events (recurrent ICH, incident ischemic stroke, myocardial infarction), vascular mortality (defined as mortality attributed to recurrent ICH, ischemic stroke, or myocardial infarction), and all-cause mortality. Results: During a median follow-up of 46.2 months, we observed 166 recurrent ICH, 68 ischemic strokes, 69 myocardial infarction, and 429 deaths. Compared with survivors of ICH with systolic BP 120 to 129 mmHg, participants who achieved systolic BP 75 years or with modified Rankin Scale score 4 to 5, systolic BP Conclusions: Targeting systolic BP

Background: Uncontrolled blood pressure (BP) in intracerebral hemorrhage (ICH) survivors is common and associated with adverse clinical outcomes. We investigated whether characteristics of the ICH itself were associated with uncontrolled BP at follow-up. Methods: Subjects were consecutive patients aged ⩾18 years with primary ICH enrolled in the prospective longitudinal ICH study at Massachusetts General Hospital between 1994 and 2015. We assessed the prevalence of uncontrolled BP (mean BP ⩾140/90 mmHg) 6 months after index event. We used multivariable logistic regression models to assess the effect of hematoma location, volume, and event year on uncontrolled BP. Results: Among 1492 survivors, ICH was lobar in 624 (42%), deep in 749 (50%), cerebellar in 119 (8%). Lobar ICH location was associated with increased risk for uncontrolled BP after 6 months (OR 1.35; 95% CI [1.08–1.69]). On average, lobar ICH survivors were treated with fewer antihypertensive drugs compared to the rest of the cohort: 2.1 ± 1.1 vs 2.5 ± 1.2 ( p Conclusions: ICH survivors with lobar hemorrhage were more likely to have uncontrolled BP after 6 months follow-up. This appears to be a result of being prescribed fewer antihypertensive medications. Future treatment strategies should focus on aggressive BP control after ICH independent of hemorrhage location.

Background and Purpose: Intracerebral hemorrhage (ICH) is an acute manifestation of cerebral small vessel disease (CSVD), usually cerebral amyloid angiopathy or hypertensive arteriopathy. CSVD-related imaging findings are associated with increased depression incidence in the general population. Neuroimaging may, therefore, provide insight on depression risk among ICH survivors. We sought to determine whether CSVD CT and magnetic resonance imaging markers are associated with depression risk (before and after ICH), depression remission, and effectiveness of antidepressant treatment. Methods: We analyzed data from the single-center longitudinal ICH study conducted at Massachusetts General Hospital. Participants underwent CT and magnetic resonance imaging imaging and were followed longitudinally. We extracted information for neuroimaging markers of CSVD subtype and severity. Outcomes of interest included pre-ICH depression, new-onset depression after ICH, resolution of depressive symptoms, and response to antidepressant treatment. Results: We followed 612 ICH survivors for a median of 47.2 months. Multiple CSVD-related markers were associated with depression risk. Survivors of cerebral amyloid angiopathy-related lobar ICH were more likely to be diagnosed with depression before ICH (odds ratio, 1.68 [95% CI, 1.14–2.48]) and after ICH (sub-hazard ratio, 1.52 [95% CI, 1.12–2.07]), less likely to achieve remission of depressive symptoms (sub-hazard ratio, 0.69 [95% CI, 0.51–0.94]), and to benefit from antidepressant therapy ( P =0.041). Cerebral amyloid angiopathy disease burden on magnetic resonance imaging was associated with depression incidence and treatment resistance (interaction P =0.037), whereas hypertensive arteriopathy disease burden was only associated with depression incidence after ICH. Conclusions: CSVD severity is associated with depression diagnosis, both before and after ICH. Cerebral amyloid angiopathy-related ICH survivors are more likely to experience depression (both before and after ICH) than patients diagnosed with hypertensive arteriopathy-related ICH, and more likely to report persistent depressive symptoms and display resistance to antidepressant treatment.

Background and ObjectivesAlthough blood pressure (BP) control is considered the most effective measure to prevent functional decline after intracerebral hemorrhage (ICH), fewer than half of survivors achieve treatment goals. We hypothesized that long-term (i.e., prehemorrhage) hypertension severity may be a crucial factor in explaining poor BP control after ICH. We investigated changes in hypertension severity after vs before ICH using latent class analysis (LCA) and identified patient characteristics predictive of individuals' BP trajectories.MethodsWe analyzed data for ICH survivors enrolled in a study conducted at Massachusetts General Hospital (MGH) from 2002 to 2019 in Boston, a high-resource setting with near-universal medical insurance coverage. We captured BP measurements in the 12 months preceding and following the acute ICH hospitalization. Using LCA, we identified patient groups (classes) based on changes in hypertension severity over time in an unbiased manner. We then created multinomial logistic regression models to identify patient factors associated with these classes.ResultsAmong 336 participants, the average age was 74.4 years, 166 (49%) were male, and 288 (86%) self-reported White race/ethnicity. LCA identified 3 patient classes, corresponding to minimal (n = 114, 34%), intermediate (n = 128, 38%), and substantial (n = 94, 28%) improvement in hypertension severity after vs before ICH. Survivors with undertreated (relative risk ratio [RRR] 0.05, 95% CI 0.01–0.23) or resistant (RRR 0.03, 95% CI 0.01–0.06) hypertension before ICH were less likely to experience substantial improvement afterwards. Residents of high-income neighborhoods were more likely to experience substantial improvement (RRR 1.14 per $10,000, 95% CI 1.02–1.28). Black, Hispanic, and Asian participants with uncontrolled hypertension before ICH were more likely to experience minimal improvement after hemorrhagic stroke (interaction p < 0.001).DiscussionMost ICH survivors do not display consistent improvement in hypertension severity after hemorrhagic stroke. BP control after ICH is profoundly influenced by patient characteristics predating the hemorrhage, chiefly prestroke hypertension severity and socioeconomic status. Neighborhood income was associated with hypertension severity after ICH in a high-resource setting with near-universal health care coverage. These findings likely contribute to previously documented racial/ethnic disparities in BP control and clinical outcomes following ICH.

Background Survivors of intracerebral hemorrhage (ICH) are at high risk for recurrent stroke, which is associated with blood pressure control. Because most recurrent stroke events occur within 12 to 18 months of the index ICH, rapid blood pressure control is likely to be crucial. We investigated the frequency and prognostic impact of uncontrolled short‐term hypertension after ICH. Methods and Results We analyzed data from Massachusetts General Hospital (n=1305) and the University of Hong Kong (n=523). We classified hypertension as controlled, undertreated, or treatment resistant at 3 months after ICH and determined the following: (1) the risk factors for uncontrolled hypertension and (2) whether hypertension control at 3 months is associated with stroke recurrence and mortality. We followed 1828 survivors of ICH for a median of 46.2 months. Only 9 of 234 (4%) recurrent strokes occurred before 3 months after ICH. At 3 months, 713 participants (39%) had controlled hypertension, 755 (41%) had undertreated hypertension, and 360 (20%) had treatment‐resistant hypertension. Black, Hispanic, and Asian race/ethnicity and higher blood pressure at time of ICH increased the risk of uncontrolled hypertension at 3 months (all P P Conclusions Among survivors of ICH, >60% had uncontrolled hypertension at 3 months, with undertreatment accounting for the majority of cases. The 3‐month blood pressure measurements were associated with higher recurrent stroke risk and mortality. Black, Hispanic, and Asian survivors of ICH and those presenting with severe acute hypertensive response were at highest risk for uncontrolled hypertension.

ObjectiveBlack 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.MethodsWe 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.ResultsWe 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).ConclusionsWe 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.

Introduction: Survivors of Intracerebral Hemorrhage (ICH) are at high risk of recurrent stroke. This risk is inversely proportional to average Blood Pressure (BP) after ICH. Racial/ethnic minority ICH survivors in the US demonstrate greater hypertension severity after ICH and are at higher risk of recurrent cerebral bleeding. Since most recurrent strokes occur within 12-18 months of index ICH, rapidly achieving BP control is likely to be crucial. We investigated the frequency, prognostic impact, and racial/ethnic disparities in uncontrolled short-term hypertension (HTN) after ICH. Methods: We analyzed data from prospective ICH cohort studies at Massachusetts General Hospital (MGH-ICH, n=1305) and the University of Hong Kong (HK-ICH, n=523). We classified HTN as controlled, uncontrolled or treatment-resistant and determined: 1) risk factors for uncontrolled and treatment-resistant HTN; and 2) whether HTN control at 3 months is associated with long-term BP control, stroke recurrence and mortality across self-reported race/ethnicity groups. Results: We followed 1828 ICH survivors (1128 White, 565 Asian, 59 Hispanic, 49 Black, 27 other) for a median of 46.2 months. Only 9 of 172 (5%) recurrent strokes occurred before 3 months after ICH. At 3 months, 713 participants (39%) had controlled HTN, 755 (41%) had undertreated HTN, and 360 (20%) had treatment-resistant HTN. BP measurements at 3 months were highly correlated with measurements during follow-up (p Conclusions: Most ICH survivors have inadequate HTN control 3 months after ICH, with under-treatment accounting for the majority of cases. Three-month BP measurements are associated with inadequate long-term HTN control, higher recurrent stroke risk and mortality. ICH survivors self-reporting as Black, Hispanic or Asian appear to be at highest risk for uncontrolled HTN. Optimizing HTN control at 3 months is a unique opportunity to address racial/ethnic disparities in quality of care among survivors of primary ICH.

Introduction: Intracerebral Hemorrhage (ICH) is an acute manifestation of underlying Cerebral Small Vessel Disease (CSVD), usually Cerebral Amyloid Angiopathy (CAA) or Hypertensive Arteriopathy (HTNA). CSVD-related imaging and histopathology findings were previously associated with increased depression incidence in the general population. CSVD evaluation via neuroimaging may therefore provide insight on depression risk among ICH survivors. We sought to determine whether hematoma location and CSVD MRI markers are associated with depression risk (before and after ICH) and resistance to treatment. Methods: We analyzed data from the single-center longitudinal ICH study conducted at Massachusetts General Hospital (MGH-ICH) since 1994 and currently ongoing. All participants underwent CT and MRI imaging, and were then followed longitudinally via a combination of semi-automated review of Electronic Medical Records (EMR) and phone-based research interviews. We extracted information for hematoma location and MRI neuroimaging markers of CSVD subtype and severity. We conducted univariable and multivariable analyses of depression prevalence before ICH, new-onset of depression after ICH, and resolution of depressive symptoms during follow-up. Results: We enrolled 612 ICH survivors, and followed them for a median of 46.3 months (Inter-Quartile Range: 35.5-58.7). Multiple CSVD-related markers were associated with depression outcomes of interest. Survivors of CAA-related lobar ICH were at highest risk for depression (before and after ICH), as well as treatment resistance (all p Conclusions: CSVD severity on neuroimaging is associated with depression prevalence and treatment-resistance among ICH survivors. CAA-related ICH survivors are at higher risk for depression (both before and after ICH) than patients diagnosed with HTNA-related ICH. The potential role of CSVD evaluation in guiding care of ICH survivors with -or at high risk for- depression warrants additional investigative efforts

Introduction: Genome-wide association studies (GWAS) have identified genetic associations for many common diseases and traits. However, incorporating genetic information into disease risk prediction has been challenging because any single collection of variants explains a small proportion of risk. We explored whether combining genetic information from related traits could improve our ability to predict ICH. Methods: We constructed an ICH meta-Genetic Risk Score (metaGRS) using 21 polygenic risk scores (PRSs) from GWASs of traits associated with ICH risk: systolic/diastolic blood pressure, pulse pressure, diabetes, hemoglobin A1c, total cholesterol, high/low-density lipoprotein, triglycerides, body mass index, waist-hip ratio, urine albumin-creatinine ratio, kidney disease, eGFR, white matter hyperintensities, small vessel stroke, insomnia, sleep duration, education attainment, alcohol use and smoking. Each PRS contained common, independent variants at p≤5x10 -4 with each trait. PRSs were calculated in 1,867 ICH cases/1,722 controls, using 1,019 cases/928 controls as a training dataset to derive logORs of the PRSs with ICH status, and a validation dataset of 848 cases/794 controls to construct the metaGRS as a weighted average. Results: Patients in higher metaGRS percentiles had higher odds of ICH (Table) , and a one standard deviation increase in metaGRS was associated with odds of ICH (OR 1.42; 95% CI: 1.28-1.57; p=1.6x10 -11 ). Compared to patients in the middle decile of the metaGRS distribution, patients in the top 10% and 5% had increased odds of ICH (OR 1.87; 95% CI: 1.07-3.30; p=0.03, OR 2.72; 95% CI: 1.54-4.92; p=7.4x10 -4 respectively). Conclusions: A metaGRS identified individuals at high risk for ICH with an odds ratio comparable to traditional risk factors, such as hypertension (OR ~1.6). Further studies are needed to investigate the role of incorporating genetic information into clinical care.

Introduction: Although elevated blood pressure (BP) is an established risk factor for intracerebral hemorrhage (ICH), the impact of acute BP fluctuations on ICH outcomes remains unclear. In this study, we sought to investigate the effect of acute BP variability (BPV) on mortality and functional outcome in ICH survivors. Methods: Subjects were consecutive ICH patients ≥ 18 years with available inpatient BP data, who survived hospitalization. Four measures of systolic BPV were calculated: standard deviation (SD), coefficient of variation (CoV), average real variability (ARV), and successive variation (SV). Our outcomes were (1) death and (2) poor functional outcome, defined as a modified Rankin Score (mRS) of 3-6 in a period between 60-120 days after discharge. We assessed the effect of hyperacute (ICH event-72 hours) and acute/subacute (72 hours-discharge) BPV on outcomes. We constructed Cox proportional hazards and logistic regression models to investigate the associations of BPV (per 10 mmHg increase) with mortality and poor functional outcome, respectively, after adjustment for potential confounders. Results: We included 345 patients, 120 of whom had available mRS data. 151 (43.8%) patients were female and 280 (81.2%) were white; mean age was 71 (±13) years. SBP ARV and SBP SV were the strongest predictors of mortality (HR 2.53-2.91 per 10 mmHg increase), while SBP SD, CoV, and SV were the strongest predictors of poor functional outcome (OR 2.89-5.14 per 10 mmHg increase) (Table) . These associations remained significant when analyzing both hyperacute as well as acute/subacute BPV. Compared to hyperacute BPV, acute/subacute BPV was more strongly associated with both mortality and poor functional outcome. Conclusion: Inpatient blood pressure variability is an important determinant of mortality and poor functional outcome in ICH survivors. Further studies are needed to investigate the role of addressing BPV as a potential target for intervention.