Risk Of Recurrent Intracerebral Hemorrhage Research Articles

Abstract TMP70: Intracortical type of lobar cerebral microbleed predicts risk of recurrent intracerebral hemorrhage in spontaneous intracerebral hemorrhage survivors

Introduction and Objective: Lobar cerebral microbleed (CMB) is frequently found in patients with spontaneous intracerebral hemorrhage (ICH) and is closely linked to cerebral amyloid angiopathy (CAA) and risk of recurrent ICH. Lobar CMB could be further topographically categorized into intracortical type or subcortical white matter (WM) type, and our previous study showed that CAA is more related to the intracortical lobar CMB. The current study aimed to determine if the types of lobar CMB can predict risks ofrecurrent ICH and long-term vascular outcomes in patients with spontaneous ICH. Methods: A total of 587 patients with spontaneous ICH were included. Clinical data, neuroimaging markers, and 2-year follow-up outcomes (recurrent ICH, incident ischemic stroke, vascular mortality and composite outcome) were collected. We categorized patients into 4 different groups based on their lobar CMB types: Type 1 (strictly intracortical type, n=52), Type 2 (strictly subcortical WM type, n=127), Type 3 (mixed intracortical and subcortical WM type, n=86), and Type 4 (no lobar CMB, n=277). The associations between lobar CMB type and follow-up outcomes were assessed using multivariable Cox regression models with adjustment of age, sex, hypertension, diabetes mellitus and hyperlipidemia. We also examined the dose-relationship between intracortical lobar CMB number and ICH recurrence risk. Results: Compared to patients without lobar CMB (Type 4), patients with strictly intracortical lobar CMB type (Type 1) had higher ICH recurrence rate (HR 3.90[1.30-11.75], p=0.015) and composite outcomes (HR 2.55[1.26-5.17], p=0.009], p<0.001), while patients with strictly subcortical WM lobar CMB type (Type 2) was associated with high risk of composite outcomes (HR 2.22[1.31-3.79], p=0.003) and a trend toward risk of incident ischemic stroke (HR 2.12 (0.89-5.05), p=0.091) but not ICH (HR 1.66 [0.66-4.19], p=0.282). Mixed type (Type 3) was not associated with follow-up vascular events. For patients with at least one lobar CMB, three or more intracortical CMBs significantly elevated ICH recurrence risk (HR 2.85 [1.18-6.88], p=0.020). Conclusions: Topographical type of lobar CMB may have clinical significance in predicting ICH recurrence risks and vascular outcomes in ICH survivors. Patients with lobar CMBs restricted in the intracortical region, or with multiple number of intracortical lobar CMBs, are predisposed to higher ICH recurrence rate.

Subarachnoid hemorrhage and finger-like projection predict recurrence in patients with lobar intracerebral hemorrhage

Background and purposeLobar intracerebral hemorrhage (ICH) is associated with a high risk of recurrence, particularly in elderly patients, where cerebral amyloid angiopathy (CAA) is often the primary cause. Diagnostic markers of CAA-related ICH, including subarachnoid hemorrhage (SAH) and finger-like projection (FLP), have recently been developed. Here, we aimed to explore the associations between SAH, FLP and the risk of ICH recurrence in lobar ICH patients.MethodsWe analyzed data from consecutive lobar ICH patients using the method of cohort study. We divided them into 4 groups on the basis of the presence or absence of SAH and FLP on CT imaging. The Cox regression model and competing risk model were used to analyze the associations of SAH and FLP with the risk of ICH recurrence at 1 year.ResultsIn total, 353 patients with lobar ICH (median age 74 [62, 81] years, 57.2% male) were included in our study. During follow-up, recurrence occurred in 34 patients (10.6%), and 90 patients (28.1%) died. The competing risk model revealed that patients in the SAH + FLP- (HR 2.88, 95% CI 1.12–7.44, p = 0.03) and SAH + FLP + (HR 8.38, 95% CI 3.40–20.66, p < 0.001) groups had higher risks of ICH recurrence within 1 year than did those in the SAH-FLP- group.ConclusionSAH is an important predictor of ICH recurrence, and this predictive ability is further enhanced when FLP is present. These findings suggest that SAH, especially with FLP, can be a valuable tool for assessing prognosis in lobar ICH patients.

Intracranial carotid arteriosclerosis and their prognosis in intracerebral hemorrhage

Background: Intracerebral hemorrhage (ICH) is a manifestations of sporadic cerebral small vessel disease, and the survivors are predisposed to higher long-term risks of vascular events. Intracranial carotid artery calcification (ICAC), a potential marker for arteriosclerosis, is a risk factor for stroke but their roles in ICH is unknown. We aimed to investigate the prevalence and morphological subtypes of ICAC and their associations with long-term vascular events in ICH survivors. Materials and methods: Survivors of spontaneous ICH treated at a single center in Taiwan were included. ICAC was assessed by non-contrast CT; morphology was evaluated and categorized as intimal, internal elastic lamina (IEL), or mixed subtype. Patients were followed up for two years. Associations between calcification subtypes and follow-up events (stroke, cardiovascular event, death) were explored using multivariable Cox regression models. Results: Overall, 462 (80.1%) survivors of ICH had ICAC—223 (38.6%) were categorized as IEL calcification, 216 (37.4%) as intimal calcification, and 23 (4.0%) as mixed type calcification—and 115 patients (19.9%) had no calcification. Patients with IEL calcification were older than patients with intimal or no calcification ( p &lt; 0.001). Age ( p &lt; 0.001), diabetes ( p = 0.010), and reduced renal function ( p = 0.001) were independently associated with IEL calcification. During 2-years of follow-up, IEL calcification was not associated with a significant difference in the risk of recurrent ICH (HR=2.8 [0.8‒9.7]), but was associated with higher risks of incident ischemic stroke (HR = 9.0 [1.0‒77.4]), vascular mortality (HR = 13.6 [1.7‒1772.4], and all-cause mortality (HR = 13.9 [1.8‒105.8]). Conclusions: ICAC is common among ICH survivors and the subtype of IEL calcification may potentially have prognostic value for long-term vascular events.

Risk and benefit of reinitiating antiplatelet therapy after spontaneous intracerebral hemorrhage: a systematic review and meta-analysis.

This study aimed to assess the risks and benefits of reinitiating antiplatelet therapy after spontaneous intracerebral hemorrhage (ICH) through a systematic review and meta-analysis. The reinitiation of antiplatelet therapy is commonly used to reduce major vascular events in patients with occlusive vascular diseases, but its use in ICH patients may increase the risk of bleeding. A comprehensive search was conducted on databases including MEDLINE, Embase, Cochrane Library, clinicaltrials.gov, and the International Standard Randomized Controlled Trial Number Register (ISRCTN). Randomized controlled trials and cohort studies that investigated the use of reinitiation of antiplatelet therapy after hemorrhagic stroke were included. Data on ICH recurrence, major bleeding events, major occlusive cerebrovascular events, ischemic stroke, and all-cause mortality were extracted and analyzed using R software. The study included a total of 10 studies with 6,340 participants. The control group consisted of 2,964 patients who did not receive antiplatelet therapy, while the study group included 1,285 patients who received antiplatelet therapy without restrictions on the specific drug type. The meta-analysis showed that antiplatelet therapy significantly reduced the risk of ICH recurrence (RR=0.72, 95% CI: 0.59, 0.87), had no significant impact on the risk of severe bleeding events (RR=0.93, 95% CI: 0.80, 1.08), significantly lowered the risk of major occlusive cerebrovascular events (RR=0.59, 95% CI: 0.46, 0.77), had no significant effect on the risk of ischemic stroke (RR=0.77, 95% CI: 0.53, 1.12), and did not significantly influence the risk of all-cause mortality (RR=0.75, 95% CI: 0.45, 1.15). Based on the findings, reinitiating antiplatelet therapy after spontaneous ICH appears to be generally safe. However, the benefits in terms of reducing the risk of all-cause mortality are not evident and require confirmation through large-scale, long-term, prospective, randomized controlled trials.

Association of LDL-cholesterol

Recent intensive low-density lipoprotein cholesterol (LDL-C) lowering trials, including FOURIER, ODYSSEY OUTCOMES, and Treat Stroke to Target (TST) trials, have mostly refuted the concern surrounding statin use, LDL-C lowering, and intracerebral hemorrhage (ICH) risk. However, the results from these trials may not be fully applied to ICH survivors, as the populations studied were mainly patients without prior ICH, in whom the inherent ICH risk is more than 10 times lower than that of ICH survivors. Although available literature on statin use after ICH has demonstrated no excess risk of recurrent ICH, other potential factors that may modify ICH risk, especially hypertension control and ICH etiology, have not generally been considered. Notably, data on LDL-C levels following ICH are lacking. We aim to investigate the association between LDL-C levels and statin use with ICH risk among ICH survivors, and to determine whether the risk differed with patients' characteristics, especially ICH etiology. Follow-up data of consecutive spontaneous ICH survivors enrolled in the University of Hong Kong prospective stroke registry from 2011 to 2019 were retrospectively analyzed. ICH etiology was classified as cerebral amyloid angiopathy (CAA) using the modified Boston criteria or hypertensive arteriopathy, while the mean follow-up LDL-C value was categorized as <1.8 or ⩾1.8 mmol/L. The primary endpoint was recurrent ICH. The association of LDL-C level and statin use with recurrent ICH was determined using multivariable Cox regression. Pre-specified subgroup analyses were performed, including based on ICH etiology and statin prescription. Follow-up blood pressure was included in all the regression models. In 502 ICH survivors (mean age = 64.2 ± 13.5 years, mean follow-up LDL-C = 2.2 ± 0.6 mmol/L, 28% with LDL-C <1.8 mmol/L), 44 had ICH recurrence during a mean follow-up of 5.9 ± 2.8 years. Statin use after ICH was not associated with recurrent ICH (adjusted hazard ratio (AHR) = 1.07, 95% confidence interval (CI) = 0.57-2.00). The risk of ICH recurrence was increased for follow-up LDL-C <1.8 mmol/L (AHR = 1.99, 95% CI = 1.06-3.73). This association was predominantly observed in ICH attributable to CAA (AHR = 2.52, 95% CI = 1.06-5.99) and non-statin users (AHR = 2.91, 95% CI = 1.08-7.86). The association between post-ICH LDL-C <1.8 mmol/L and recurrent ICH was predominantly observed in CAA patients and those with intrinsically low LDL-C (non-statin users). While statins can be safely prescribed in ICH survivors, LDL-C targets should be individualized and caution must be exercised in CAA patients.

Rationale and Design of the Statin Use in Intracerebral Hemorrhage Patients (SATURN) Trial

Introduction: The benefits and risks of HMG-CoA reductase inhibitor (statin) drugs in survivors of intracerebral hemorrhage (ICH) are unclear. Observational studies suggest an association between statin use and increased risk of lobar ICH, particularly in patients with apolipoprotein-E (APOE) ε2 and ε4 genotypes. There are no randomized controlled trials addressing the effects of statins after ICH leading to uncertainty as to whether statins should be used in patients with lobar ICH who are at high risk for ICH recurrence. The SATURN trial aims to evaluate the effects of continuation versus discontinuation of statin on the risk of ICH recurrence and ischemic major adverse cerebro-cardio-vascular events (MACCEs) in patients with lobar ICH. Secondary aims include the assessment of whether the APOE genotype modifies the effects of statins on ICH recurrence, functional and cognitive outcomes, and quality of life. Methods: The SATURN trial is a multi-center, pragmatic, prospective, randomized, open-label, phase III clinical trial with blinded end-point assessment. A planned total of 1,456 patients with lobar ICH will be recruited from 140 sites in the USA, Canada, and Spain. Patients presenting within 7 days of a spontaneous lobar ICH that occurred while taking a statin will be randomized (1:1) to continuation (control) versus discontinuation (intervention) of the same statin drug and dose that they were using at ICH onset. The primary outcome is the time to recurrent symptomatic ICH within a 2-year follow-up period. The primary safety outcome is the occurrence of ischemic MACCE. Conclusion: The results will help to determine the best strategy for statin use in survivors of lobar ICH and may help to identify if there is a subset of patients who would benefit from or be harmed by statins.

Abstract WP158: Cortical Superficial Siderosis is Associated With Ischemia After Intracerebral Hemorrhage

Background: Ischemia on diffusion weighted imaging (DWI) after intracerebral hemorrhage (ICH) increases the risk of future ischemic stroke. Radiographic markers of small vessel disease, including cerebral microbleeds (CMB), are associated with DWI lesions. Though cortical superficial siderosis (cSS) is also a hemorrhagic small vessel disease subtype, it is unclear if cSS similarly relates to DWI lesions. We hypothesized that cSS would represent a more severe phenotype of small vessel disease and would associate with DWI lesions after ICH independent to other small vessel disease markers. Methods: Using the Intracerebral Hemorrhage Outcomes Project (ICHOP), we included all cases of spontaneous ICH who underwent DWI and susceptibility imaging/gradient echo. DWI hyperintensities were identified if &gt;10mm from the hematoma with decreased ADC signal. cSS were identified as subarachnoid hemosiderin deposition without acute subarachnoid hemorrhage. The relationship of cSS with DWI lesion presence as the outcome was assessed with logistic regression adjusted for ICH score, blood pressure change within 24 hours, and small vessel disease markers (CMB and white matter hyperintensity). Sensitivity analyses were performed to adjust for demographics and ICH location. A secondary analysis using linear regression assessed the association with the number of DWI lesions adjusted for similar covariates. Results: Of 198 patients analyzed, DWI lesions were observed in 31.3% and cSS in 10.6%. The presence of cSS was associated with DWI lesions (adjusted OR 3.72, CI: 1.29-10.72), independent of other small vessel disease markers. Separate sensitivity analyses adjusting for sex, race, and ICH location did not change the association of cSS with DWI lesions. In secondary analyses, cSS was not associated with greater number of DWI lesions counts (b 0.213, CI -0.53-0.63). Discussion: cSS is associated with the presence of DWI lesions, independent to other small vessel disease markers. cSS may represent a severe phenotype of small vessel disease with a risk of ICH recurrence and ischemia. Further work is required to investigate underlying mechanisms and optimal strategies to mitigate competing risks of future hemorrhage and ischemic events in these patients.

Effect of statin therapy patterns on readmission and mortality in patients with intracerebral hemorrhage.

There is limited and inconsistent evidence for the association of statin therapy and statin treatment patterns with the risk of recurrent intracerebral hemorrhage (ICH) in patients with prior ICH. To assess the association of statin therapy and its intensity, type, initiation time, and discontinuation with the risk of recurrent ICH and mortality in Chinese patients with ICH. Patients with newly diagnosed ICH in the Beijing Employee Medical Claims Data database from 2010 to 2017 were included. Post-ICH statin users (post-diagnosis only) and nonusers (never), statin discontinuers (pre-diagnosis only) and continuers (pre- and post-diagnosis) were matched on a 1:1 propensity score, respectively. Adjusted Cox proportional risk models were used to estimate the risk ratios for ICH readmission and mortality under various statin patterns. A total of 2668 post-ICH statin users and 2668 nonusers without a history of statin use were enrolled. Post-ICH statin users had a lower risk of ICH readmission (HR, 0.57; 95% CI 0.48, 0.69) and all-cause death (0.56: 0.49, 0.63) than nonusers. Low/moderate-intensity treatment was associated with a 63% lower risk of recurrent ICH compared with nonusers (0.37: 0.29, 0.46), whereas high-intensity treatment did not reduce the risk (0.93: 0.74, 1.16). Both low/moderate-intensity (0.42: 0.36, 0.48) and high-intensity statins (0.57: 0.48, 0.69) were associated with a lower risk of all-cause mortality. The risk of ICH readmission was 53% (0.47: 0.30, 0.74) lower with adherence to rosuvastatin than with atorvastatin. Only starting medication within 30days of the first diagnosis of ICH reduced the risk of ICH readmission (0.49: 0.40, 0.60). Among patients with a history of statin use, 1807 discontinuing and 1,807 continuing users of statins were included. The risk of ICH readmission (4.00: 3.32, 4.80) and the risk of all-cause death (4.01: 3.57, 4.50) were substantially increased in statin discontinuation compared with continued statin use. Statin therapy after ICH was associated with lower risks for ICH readmission and all-cause mortality compared with non-statin therapy, especially at low/moderate intensity and early initiation of statins after ICH. Adherence to rosuvastatin was associated with a lower risk of recurrence of ICH than atorvastatin. Among patients with a statin history prior to ICH, discontinuation of statins after ICH was associated with increased risk of ICH recurrence and death.

Clinical Characteristics, Neuroimaging Markers, and Outcomes in Patients with Cerebral Amyloid Angiopathy: A Prospective Cohort Study.

Background and purpose: Sporadic cerebral amyloid angiopathy (CAA) is a small vessel disease, resulting from progressive amyloid-β deposition in the media/adventitia of cortical and leptomeningeal arterioles. We sought to assess the prevalence of baseline characteristics, clinical and radiological findings, as well as outcomes among patients with CAA, in the largest study to date conducted in Greece. Methods: Sixty-eight patients fulfilling the Boston Criteria v1.5 for probable/possible CAA were enrolled and followed for at least twelve months. Magnetic Resonance Imaging was used to assess specific neuroimaging markers. Data regarding cerebrospinal fluid biomarker profile and Apolipoprotein-E genotype were collected. Multiple logistic regression analyses were performed to identify predictors of clinical phenotypes. Cox-proportional hazard regression models were used to calculate associations with the risk of recurrent intracerebral hemorrhage (ICH). Results: Focal neurological deficits (75%), cognitive decline (57%), and transient focal neurological episodes (TFNEs; 21%) were the most common clinical manifestations. Hemorrhagic lesions, including lobar cerebral microbleeds (CMBs; 93%), cortical superficial siderosis (cSS; 48%), and lobar ICH (43%) were the most prevalent neuroimaging findings. cSS was independently associated with the likelihood of TFNEs at presentation (OR: 4.504, 95%CI:1.258-19.088), while multiple (>10) lobar CMBs were independently associated with cognitive decline at presentation (OR:5.418, 95%CI:1.316-28.497). cSS emerged as the only risk factor of recurrent ICH (HR:4.238, 95%CI:1.509-11.900) during a median follow-up of 20 months. Conclusions: cSS was independently associated with TFNEs at presentation and ICH recurrence at follow-up, while a higher burden of lobar CMBs with cognitive decline at baseline. These findings highlight the prognostic value of neuroimaging markers, which may influence clinical decision-making.

Impact of previous statin use on first intracerebral hemorrhage in cerebral amyloid angiopathy

ObjectivesStatins have been associated with an increased risk of spontaneous intracerebral hemorrhage (ICH), but without dedicated study in cerebral amyloid angiopathy (CAA). We aimed to evaluate the association between previous statin treatment and radiological hemorrhagic lesions in a CAA population during a first lobar ICH event. Materials and methodsWe retrospectively included all patients meeting the modified Boston criteria for probable CAA and admitted for a first lobar ICH between 2010 and 2021 at Rouen University Hospital. Patients were classified as having previous statin treatment or not. We compared the ICH volume, the number of associated cerebral microbleeds (CMBs), and cortical superficial siderosis (CSS) according to previous statin treatment or not. We also compared functional outcomes and ICH recurrence during the follow-up period between the two groups. ResultsWe included 99 patients, 27 of whom had statin treatment prior to their ICH. The ICH volume and the number of CMBs did not differ between groups. Disseminated CSS was initially more frequent in the statin group (88% versus 57%; P=0.019), but this was no longer significant after adjustment for antiplatelet treatment (P=0.13). The long-term outcome was similar between the two groups with no increased risk of ICH recurrence in the statin-treated group (29.63% versus 23.61%, P=0.54). ConclusionsPrevious statin treatment was not associated with more severe hemorrhagic lesions in CAA in terms of ICH volume or number of microbleeds, but a trend for increased disseminated CSS was highlighted, which will require further larger studies.

Comparison of Stroke Recurrence, Cardiovascular Events, and Death Among Patients With Pregnancy-Associated vs Non–Pregnancy-Associated Stroke

Women with pregnancy-associated stroke might have different risks of stroke recurrence, including during subsequent pregnancies, and other cardiovascular events due to pregnancy-specific stroke risk factors, such as gestational hypertension, preeclampsia, or gestational diabetes. To estimate the rate of stroke recurrence, cardiovascular hospitalization, and death in women with pregnancy-associated stroke compared with women with non-pregnancy-associated stroke. This cohort study included all women aged 15 to 49 years in France who were affiliated with the general scheme of French health care insurance (94% of women) and had a first hospitalization for stroke between January 1, 2010, and December 31, 2018. Women were followed up until December 31, 2020, with the registration of stroke recurrence, hospitalization for cardiovascular conditions, and death. Data were from the French health care database Système National des Données de Santé. Statistical analyses were conducted between December 2021 and September 2022. Pregnancy status at the time of stroke. Poisson regressions were used to estimate incidence rates of these events with 95% CIs. We used Cox proportional hazards regression models to estimate the hazard ratios (HRs) of each event during the follow-up for women with a pregnancy-associated stroke vs women with a non-pregnancy-associated stroke. Among women aged between 15 and 49 years between 2010 and 2018 and living in France, 1204 had a pregnancy-associated stroke at a mean (SD) age of 31.5 (5.8) years, and 31 697 had a non-pregnancy-associated stroke at a mean age of 39.6 (8.2) years. Among the 1204 women with a pregnancy-associated stroke, the incidence rate was 11.4 (95% CI, 9.0-14.3) per 1000 person-years, with 2 recurrent events during a subsequent pregnancy. Compared with women with non-pregnancy-associated stroke, women with pregnancy-associated stroke had lower risks of ischemic stroke (adjusted HR, 0.53; 95% CI, 0.36-0.77), cardiovascular events (adjusted HR, 0.58; 95% CI, 0.49-0.69), and death (adjusted HR, 0.42; 95% CI, 0.22-0.79). In contrast, the risk of recurrent intracerebral hemorrhage and cerebral venous thrombosis did not differ significantly, whereas the risks of venous thromboembolism (HR, 2.02; 95% CI, 1.14-3.58) and acute coronary syndrome with ST-segment elevation (HR, 3.93; 95% CI, 1.10-14.0) were increased. In this cohort study, although the risks of ischemic stroke, overall cardiovascular events, and mortality were lower after a pregnancy-associated stroke than after a non-pregnancy-associated stroke, the risks of venous thromboembolism and acute coronary syndrome with ST-segment elevation were higher. Recurrent stroke during a subsequent pregnancy remained rare.

Comparison of Boston Criteria v2.0/v1.5 for Cerebral Amyloid Angiopathy to Predict Recurrent Intracerebral Hemorrhage.

Intracerebral hemorrhage (ICH) caused by cerebral amyloid angiopathy (CAA) has a high recurrence risk. The Boston criteria, while not designed to predict recurrence, are commonly used for in vivo diagnosis of CAA and have recently been revised to the version 2.0 (v2.0), introducing nonhemorrhagic white matter features. We investigated whether the new v2.0 criteria change ICH recurrence risk in patients with probable CAA. We assessed ICH recurrence risk in consecutive patients with ICH and available brain magnetic resonance imaging. Patients with macrovascular or structural causes were excluded. Recurrent ICH was determined using electronic health records and confirmed by neuroimaging. We compared ICH recurrence risk for Boston criteria v2.0 versus v1.5 for probable CAA using survival analysis. Fifty-nine of 443 patients (13.3%) had recurrent ICH over a median follow-up of 5.7 years (2682 patient-years). Thirty-seven out of one hundred two patients (36.3%) with probable CAA according to the Boston criteria v2.0 had recurrent ICH compared with 36/82 patients (43.9%) according to the v1.5 criteria. Patients with probable CAA according to the Boston v1.5 criteria had a higher ICH recurrence rate (10.9 per 100 person-years [95% CI, 7.8-15.1]) compared with those diagnosed by the v2.0 criteria (8.5 per 100 person-years [95% CI, 6.1-11.7]). The 20 patients defined as probable CAA only by the v2.0 criteria had a very low recurrence rate (0.9 per 100 person-years [95% CI, 0.1-6.7]), lower than those diagnosed using the v1.5 criteria (P<0.001). Our findings suggest a wide spectrum of ICH recurrence risk in patients with probable CAA. Patients with ICH diagnosed with CAA based only on the nonhemorrhagic white matter markers introduced in the Boston v2.0 criteria had a much lower risk of recurrence than those diagnosed with the previous Boston criteria v1.5, comparable to that of patients with ICH not fulfilling any probable CAA criteria.

Colchicine pre-treatment and post-treatment does not worsen bleeding or functional outcome after collagenase-induced intracerebral hemorrhage.

Patients with intracerebral hemorrhage (ICH) are at increased risk for major ischemic cardiovascular and cerebrovascular events. However, the use of preventative antithrombotic therapy can increase the risk of ICH recurrence and worsen ICH-related outcomes. Colchicine, an anti-inflammatory agent, has the potential to mitigate inflammation-related atherothrombosis and reduce the risk of ischemic vascular events. Here we investigated the safety and efficacy of colchicine when used both before and acutely after ICH. We predicted that daily colchicine administration would not impact our safety measures but would reduce brain injury and improve functional outcomes associated with inflammation reduction. To test this, 0.05 mg/kg colchicine was given orally once daily to rats either before or after they were given a collagenase-induced striatal ICH. We assessed neurological impairments, intra-parenchymal bleeding, Perls positive cells, and brain injury to gauge the therapeutic impact of colchicine on brain injury. Colchicine did not significantly affect bleeding (average = 40.7 μL) at 48 hrs, lesion volume (average = 24.5 mm3) at 14 days, or functional outcome (median neurological deficit scale score at 2 days post-ICH = 4, i.e., modest deficits) from 1-14 days after ICH. Colchicine reduced the volume of Perls positive cells in the perihematomal zone, indicating a reduction in inflammation. Safety measures (body weight, food consumption, water consumption, hydration, body temperature, activity, and pain) were not affected by colchicine. Although colchicine did not confer neuroprotection or functional benefit, it was able to reduce perihematomal inflammation after ICH without increasing bleeding. Thus, our findings suggest that colchicine treatment is safe, unlikely to worsen bleeding, and is unlikely but may reduce secondary injury after an ICH if initiated early post ICH to reduce the risk of ischemic vascular events. These results are informative for the ongoing CoVasc-ICH phase II randomized trial (NCT05159219).

Cardiovascular Events After Intracerebral Hemorrhage.

Cardiovascular events after primary intracerebral hemorrhage (ICH) have emerged as a leading cause of poor functional outcomes and mortality during the long-term recovery after an ICH. These events encompass arterial ischemic events such as ischemic stroke and myocardial infarction, arterial hemorrhagic events that include recurrent ICH, and venous thrombotic events such as venous thromboembolism. The purpose of this review is to summarize the cardiovascular complications after ICH, epidemiology and associated risk factors, and their impact on ICH outcomes. Additionally, we will highlight possible pathophysiological mechanisms to explain the short- and long-term increased risks of ischemic and hemorrhagic events after ICH. Finally, we will highlight potential secondary stroke and venous thrombotic prevention strategies often not considered after ICH, balanced against the risk of ICH recurrence.

Abstract WP136: Recurrent Intracerebral Hemorrhage In Patients With Cerebral Amyloid Angiopathy

Background: Studies suggest an increased risk of recurrent intracerebral hemorrhage (ICH) in patients with cerebral amyloid angiopathy (CAA). In this study, we sought to compare the rates of recurrent cerebrovascular events in patients admitted for ICH with and without CAA. Methods: We utilized the National Readmissions Database 2016-2018 to identify hospitalizations with the primary discharge diagnosis of ICH with and without a concomitant diagnosis of CAA. Hospitalizations with age &gt;55 years, survival to discharge, and known discharge disposition were included for further analysis. Propensity score matching was used to match for the differences in demographics, comorbidities, and disease severity between the CAA and no CAA groups. Survival analysis was performed to evaluate the rates of recurrent ICH, subarachnoid hemorrhage (SAH), and acute ischemic stroke (AIS) in the propensity-matched groups. Results: A total of 194,290 patients with ICH met the study inclusion criteria; 8,247 with CAA and 186,043 without CAA. After propensity score matching, we identified 7,857 hospitalizations with CAA and 7,874 without CAA. Patients with CAA were more likely to be readmitted due to ICH [hazards ratio (HR): 3.4, 95% confidence interval (CI): 2.6-4.6, P &lt;0.001] and SAH (HR: 2.5, 95% CI: 1.2-5.4, P 0.007) during the mean follow-up period of 6 months. However, there was no statistically significant difference in readmissions due to AIS (HR: 0.7, 95% CI: 0.5-1.0, P 0.061) [Figure 1]. Age (HR: 0.96 per year increase in age, 95% CI: 0.95-0.98, P &lt;0.001) and Medicare payer (HR: 3.23; 95% CI: 1.92-5.41, P &lt;0.001) were independently associated with readmissions due to ICH. Conclusions: Patients admitted for ICH with a secondary diagnosis of CAA are three times more likely to have readmissions for recurrent ICH compared to patients without CAA.

Time in therapeutic range of anticoagulation among patients with atrial fibrillation and cerebral amyloid angiopathy

Atrial fibrillation (AF) and cerebral amyloid angiopathy (CAA) present risks of ischemic stroke and intracerebral hemorrhage (ICH). Vitamin K antagonist use is associated with fluctuations in international normalized ratio (INR), which predispose to a higher bleeding risk. Patients with a diagnosis of AF and ICH while on a vitamin K antagonist were identified using the Rochester Epidemiology Project. Sixty patients were identified (mean age 81.3 years; 24 men). Thirty-three (55%) exhibited characteristics consistent with possible (n = 25) or probable (n = 8) CAA. Mean time in therapeutic range in the 30 days preceding ICH was 55.4%, with no difference between CAA and non-CAA patients. Mean time spent above therapeutic range (INR > 3.0) was 17.7%, with no difference between CAA and non-CAA patients. Following ICH, 21 (35%) died within 30 days, with total mortality at 76.7% after 176.4 person-years of follow-up (mean 2.9 years). Time in therapeutic range in the 30 days prior to ICH had no significant impact on 7-day mortality, nor risk of recurrent ICH or ischemic stroke. Patients with warfarin-related ICH were often outside of the therapeutic range within the month preceding hemorrhage but more frequently were subtherapeutic. Even with careful avoidance of supratherapeutic INR, vitamin K antagonist use in CAA patients is unlikely to have a major effect in preventing ICH and must be used with caution.

Risk of cerebrovascular events in intracerebral haemorrhage survivors with atrial fibrillation: the Danish Stroke Registry

Abstract Background In patients with atrial fibrillation (AF), who have suffered an intracerebral haemorrhage (ICH), the optimal stroke prevention strategy is unclear. The PRESTIGE-AF trial is a multinational randomized controlled trial designed to investigate the optimal stroke prevention strategy in patients with AF who have recently suffered an ICH. Until the results of the PRESTIGE-AF trial becomes available, data on the risk of future cerebrovascular events in AF patient surviving an ICH are important to gain knowledge on the risk in this patient group and to support the clinician in this challenging situation. Purpose To investigate the risk of cerebrovascular events in a study population of ICH survivors with AF resembling the expected trial population of the PRESTIGE-AF trial. Methods We used the Danish nationwide registries to identify all patients presenting with incident ICH and prevalent AF between 2003–2018. To resemble the expected trial population of the PRESTIGE-AF trial, key inclusion and exclusion criteria of the PRESTIGE-AF trial were applied [Flowchart]. Patients were followed for up to one year in the Danish Stroke Registry, and outcomes (recurrent ICH, cerebrovascular ischaemic event, and all-cause death) were reported according to initiation/resumption of oral anticoagulant therapy (OAC) during follow-up. Results A total of 1,885 patients were included in the study. At one year after the incident ICH, we observed 40 recurrent ICH, 63 cerebrovascular ischaemic events, 88 all strokes, and 650 all-cause deaths [Figure]. When splitting the follow-up period according to initiation/resumption of OAC during follow-up, 526 patients initiated/resumed OAC during follow-up. The median time to initiation/resumption of OAC was 5.3 months (IQR: 1.1–12.0). For the subpopulation of patients not initiating/resuming OAC during follow-up, we observed a 2.6% risk of cerebrovascular ischaemic events, a 1.5% risk of recurrent ICH, and a 30.3% risk of all-cause death at one year after the incident ICH. For the subpopulation of patients initiating/resuming OAC during follow-up, we observed a 2.8% risk of recurrent ICH, a 3.2% risk of cerebrovascular ischaemic events, and a 22.0% risk of all-cause death at one year after the incident ICH. Conclusion In this observational cohort study, we identified a population of ICH survivors with concomitant AF mirroring the expected PRESTIGE-AF trial population. One year after the incident ICH, we observed more cerebrovascular ischaemic events than recurrent ICH events, which was also evident for the subpopulation of patients initiating/resuming OAC during follow-up. The results of the PRESTIGE-AF trial are warranted to determine optimal stroke prevention among ICH survivors with concomitant AF. Funding Acknowledgement Type of funding sources: Public grant(s) – EU funding. Main funding source(s): This study has received funding from the European Union's Horizon 2020 research and innovation programme. FlowchartFigure

Acute intracerebral haemorrhage and diffusion-weighted imaging lesions: A meta-analysis.

Diffusion-weighted imaging lesions in intracerebral haemorrhage are related to a higher risk of recurrent intracerebral haemorrhage, cognitive damage, and mortality. However, it has been reported that the relationship between the risk of diffusion-weighted imaging lesions and intracerebral haemorrhage subtype or the risk factors for diffusion-weighted imaging lesions is variable. This meta-analysis was performed to evaluate this relationship. A systematic literature search up-to August 2020 was performed and 12 studies included 2815 subjects at the baseline with intracerebral haemorrhage. They were reporting relationships between the diffusion-weighted imaging lesions and intracerebral haemorrhage subtype or investigated the risk factors for diffusion-weighted imaging lesions. Odds ratio (OR) with 95% confidence intervals (CIs) was calculated to evaluate the prognostic role of diffusion-weighted imaging lesions and intracerebral haemorrhage subtype and investigated the risk factors for diffusion-weighted imaging lesions using the dichotomous and continuous method with a random or fixed-effect model. Lobar intracerebral haemorrhage was not significantly related to a higher rate of diffusion-weighted imaging lesions (OR, 1.01; 95% CI, 0.75-1.36, P=.94) compared to the non-lobar intracerebral haemorrhage. Also, history of diabetes mellitus (OR, 1.15; 95% CI, 0.83-1.60, P=.39); history of smoking (OR, 0.95; 95% CI, 0.68-1.33, P=.76); history of hypercholesterolaemia (OR, 1.04; 95% CI, 0.73-1.48, P=.83) and history of ischaemic stroke (OR, 1.63; 95% CI, 0.57-4.66, P=.36) were not significantly related to higher rate of diffusion-weighted imaging lesions compared to no history of those factors. However, the history of hypertension was significantly related to a higher rate of diffusion-weighted imaging lesions (OR, 1.33; 95% CI, 1.04-1.70, P=.02) compared to no history of hypertension. Also, Subjects with diffusion-weighted imaging lesions had a greater decrease in systolic pressure in the acute phase of the intracerebral haemorrhage (OR, 10.23; 95% CI, 7.41-13.06, P<.001) compared to without diffusion-weighted imaging lesions. Based on this meta-analysis, the history of hypertension may have an independent risk relationship with a higher rate of diffusion-weighted imaging lesions. Also, subjects with diffusion-weighted imaging lesions had a greater decrease in systolic pressure in the acute phase of the intracerebral haemorrhage compared to those without diffusion-weighted imaging lesions. This relationship forces us to recommend that identification of diffusion-weighted imaging lesions might add appreciated evidence to evaluate the progression of the underlying micro-angiopathy especially in subjects with a history of hypertension. Though further studies are needed to define the mechanisms by which these lesions may lead to cognitive damage and stroke reappearance.

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.

The relation between acute intracerebral hemorrhage and diffusion-weighted imaging lesions: a meta-analysis.

Diffusion-weighted imaging lesions in intracerebral hemorrhage are related to a higher risk of recurrent intracerebral hemorrhage, cognitive damage, and mortality. However, it has been reported that the relationship between the risk of diffusion-weighted imaging lesions and intracerebral hemorrhage subtype or the possible risk factors for diffusion-weighted imaging lesions is variable. This meta-analysis was performed to evaluate this relationship. A systematic literature search up-to August 2020 was performed and 12 studies included 2815 subjects at the baseline with intracerebral hemorrhage. Odds ratio (OR) or mean difference (MD) with 95% confidence intervals (CIs) was calculated to evaluate the prognostic role of diffusion-weighted imaging lesions and intracerebral hemorrhage subtype and investigated the possible risk factors for diffusion-weighted imaging lesions using the dichotomous and continuous methods with a random or fixed-effect model. Lobar intracerebral hemorrhage was not significantly related to a higher rate of diffusion-weighted imaging lesions (OR, 1.01; 95% CI, 0.75-1.36, p = 0.94) compared to the non-lobar intracerebral hemorrhage. Also, history of diabetes mellitus (OR, 1.15; 95% CI, 0.83-1.60, p = 0.39); history of smoking (OR, 0.95; 95% CI, 0.68-1.33, p = 0.76); history of hypercholesterolemia (OR, 1.04; 95% CI, 0.73-1.48, p = 0.83); and history of ischemic stroke (OR, 1.63; 95% CI, 0.57-4.66, p = 0.36) were not significantly related to higher rate of diffusion-weighted imaging lesions compared to no history of those factors. However, the history of hypertension was significantly related to a higher rate of diffusion-weighted imaging lesions (OR, 1.33; 95% CI, 1.04-1.70, p = 0.02) compared to no history of hypertension. Also, Subjects with diffusion-weighted imaging lesions had a greater decrease in systolic pressure in the acute phase of the intracerebral hemorrhage (MD, 10.23; 95% CI, 7.41-13.06, p < 0.001) compared to without diffusion-weighted imaging lesions. Based on this meta-analysis, the history of hypertension may have an independent risk relationship with a higher rate of diffusion-weighted imaging lesions. Also, subjects with diffusion-weighted imaging lesions had a greater decrease in systolic pressure in the acute phase of the intracerebral hemorrhage compared to those without diffusion-weighted imaging lesions. This relationship forces us to recommend that identification of diffusion-weighted imaging lesions might add appreciated evidence to evaluate the progression of the underlying micro-angiopathy especially in subjects with a history of hypertension. Though further studies are needed to define the mechanisms by which these lesions may lead to cognitive damage and stroke reappearance.