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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 Survivors of intracranial hemorrhage (ICH) are at increased risk for major adverse cardiovascular and cerebrovascular events (MACCE), in the form of recurrent stroke and myocardial Infarction. We investigated whether long‐term blood pressure (BP) variability represents a risk factor for MACCE after ICH, independent of average BP. Methods and Results We analyzed data from prospective ICH cohort studies at Massachusetts General Hospital and the University of Hong Kong. We captured long‐term (ie, visit‐to‐visit) BP variability, quantified as individual participants’ variation coefficient. We explored determinants of systolic and diastolic BP variability and generated survival analyses models to explore their association with MACCE. Among 1828 survivors of ICH followed for a median of 46.2 months we identified 166 with recurrent ICH, 68 with ischemic strokes, and 69 with myocardial infarction. Black (coefficient +3.8, SE 1.3) and Asian (coefficient +2.2, SE 0.4) participants displayed higher BP variability. Long‐term systolic BP variability was independently associated with recurrent ICH (subhazard ratio [SHR], 1.82; 95% CI, 1.19–2.79), ischemic stroke (SHR, 1.62; 95% CI, 1.06–2.47), and myocardial infarction (SHR, 1.54; 95% CI, 1.05–2.24). Average BP during follow‐up did not modify the association between long‐term systolic BP variability and MACCE. Conclusions Long‐term BP variability is a potent risk factor for recurrent hemorrhage, ischemic stroke, and myocardial infarction after ICH, even among survivors with well‐controlled hypertension. Our findings support the hypothesis that combined control of average BP and its variability after ICH is required to minimize incidence of MACCE.

Background Cognitive impairment and depressive symptoms are highly prevalent after Intracerebral Hemorrhage (ICH). We leveraged Latent Profile Analysis (LPA) to identify profiles for cognitive decline and depression onset after ICH. We also investigated differences in clinical, genetic and neuroimaging characteristics across patients’ profiles. Methods We analyzed data from the ICH study conducted at Massachusetts General Hospital between January 1998 and December 2019. We collected information from electronical health records, follow-up interviews, CT and MRI imaging, and APOE genotype. We conducted LPA and multinomial logistic regression analyses to: 1) identify distinct profiles for cognitive decline and depression onset after ICH; 2) identify clinical, neuroimaging and genetic factors predicting individuals’ likelihood to express a specific profile. Results We followed 784 ICH survivors for a median of 45.8 months. We identified four distinct profiles in cognitive and depressive symptoms after ICH: low depression and dementia risk, early-onset depression and dementia, late-onset depression and dementia, high depression with low dementia risk. Cerebral small vessel disease severity and APOE genotype were specifically associated with the late-onset profile (both p < 0.05). Acute hematoma characteristics (size, intraventricular extension) and functional disability were specifically associated with the early-onset profile (all p < 0.05). Conclusion We identified four distinct profiles for cognitive and depressive symptoms after ICH, each displaying specific associations with individual patients’ clinical, genetic and neuroimaging data. These associations reflect separate biological mechanisms influencing dementia and depression risk after ICH. Our findings support employing LPA in future ICH studies, and is likely applicable to stroke survivors at large.

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

OBJECTIVE Outcome prognostication unbiased by early care limitations (ECL) is essential for guiding treatment in patients presenting with intracerebral hemorrhage (ICH). The aim of this study was to determine whether the max-ICH (maximally treated ICH) Score provides improved and clinically useful prognostic estimation of functional long-term outcomes after ICH. METHODS This multicenter validation study compared the prognostication of the max-ICH Score versus the ICH Score regarding diagnostic accuracy (discrimination and calibration) and clinical utility using decision curve analysis. We performed a joint investigation of individual participant data of consecutive spontaneous ICH patients (n = 4,677) from 2 retrospective German-wide studies (RETRACE I + II; anticoagulation-associated ICH only) conducted at 22 participating centers, one German prospective single-center study (UKER-ICH; nonanticoagulation-associated ICH only), and 1 US-based prospective longitudinal single-center study (MGH; both anticoagulation- and nonanticoagulation-associated ICH), treated between January 2006 and December 2015. RESULTS Of 4,677 included ICH patients, 1,017 (21.7%) were affected by ECL (German cohort: 15.6% [440 of 2,377]; MGH: 31.0% [577 of 1,283]). Validation of long-term functional outcome prognostication by the max-ICH Score provided good and superior discrimination in patients without ECL compared with the ICH Score (area under the receiver operating curve [AUROC], German cohort: 0.81 [0.78-0.83] vs 0.74 [0.72-0.77], p

Background Black and Hispanic survivors of Intracerebral Hemorrhage (ICH) are at higher risk of recurrent intracranial bleeding when compared to their white counterparts. While established differences in hypertension severity after ICH play a role, they do not fully account for this health disparity. MRI-based markers of chronic Cerebral Small Vessel Disease (CSVD) are consistently associated with increased risk of recurrent ICH. We therefore sought to investigate whether differences in CSVD subtype and/or severity exist among self-reported race/ethnicity groups. Methods We utilized data from the MGH-ICH study and the ERICH-L study. We collected baseline patient information and MRI-based CSVD markers, in the form of cerebral microbleeds (CMBs). We conducted univariable and multivariable analyses for presence and burden of CMBs, differentiating on the basis of two primary CSVD subtypes: Cerebral Amyloid Angiopathy (CAA) and Arteriolo-Sclerosis (AS). Results We analyzed data for a total of 2192 ICH survivors (MGH-ICH study: 991 and ERICH-L: 1201). Of these, 1245 self-identified as white, 460 as black, 392 as Hispanic, and 67 as other race/ethnicity. We found that minority ICH survivors were more likely to have CMBs on MRI scan at time of ICH compared to white participants (54% vs. 41%, p Conclusion Minority ICH survivors presented with greater CSVD burden on MRI scan at time of stroke, especially as it pertains to the AS-subtype. Given the known association between AS and hypertension, our findings may reflect disparities in primary stroke prevention long pre-dating ICH. Future studies will be required to clarify the impact of our findings on ICH recurrence risk.