Risk Of Intracerebral Hemorrhage In Patients Research Articles

Outcomes of patients with cerebral microbleeds undergoing percutaneous coronary intervention and dual antiplatelet therapy.

Cerebral microbleeds (CMBs) on brain magnetic resonance imaging (MRI) are predictive of intracerebral hemorrhage (ICH). However, the risk of ICH in patients with CMBs who undergo percutaneous coronary intervention (PCI) while receiving dual antiplatelet therapy (DAPT) is unclear. We conducted a study on 329 consecutive patients with coronary artery disease who underwent PCI and were evaluated using a 3T MRI scanner. Based on T2*-weighted imaging, patients were classified into three groups: no CMBs, < 5 CMBs, or ≥ 5 CMBs. We determined the occurrence of ICH during follow-up. At least 1 CMB was found in 109 (33%) patients. The mean number of CMBs per patient was 2.9 ± 3.6. Among the 109 patients with CMBs, 16 (15%) had ≥ 5 CMBs. Coronary stent implantation was performed in 321 patients (98%). DAPT was prescribed for 325 patients (99%). During a mean follow-up period of 2.3 years (interquartile range, 1.9-2.5 years), ICH occurred in one patient (1.1%) with four CMBs. There were no significant differences in the incidence of ICH (0% vs. 1.1% vs. 0%; p = 0.28). However, the rate of DAPT at 6 months of follow-up was significantly lower in patients with ≥ 5 CMBs than in patients with no CMBs or < 5 CMBs (89% vs. 91% vs. 66%, p = 0.026). Furthermore, there were no significant differences in systemic blood pressure during follow-up (123 ± 16 vs. 125 ± 16 vs. 118 ± 11 mmHg; p = 0.40). Although a substantial number of patients who underwent PCI had cerebral microbleeds, at approximately two years of follow-up, intracerebral hemorrhage was very rare in our study population.

Intracerebral Hemorrhage Risk in Patients with Primary Brain Tumors Taking Direct Oral Anticoagulants as Compared with Low Molecular Weight Heparin (P6-5.012)

Intracerebral Hemorrhage Risk in Patients with Primary Brain Tumors Taking Direct Oral Anticoagulants as Compared with Low Molecular Weight Heparin (P6-5.012)

APOE ε4 and Intracerebral Hemorrhage in Patients With Brain Arteriovenous Malformation

Intracerebral hemorrhage (ICH) is a serious complication of brain arteriovenous malformation (AVM). Apolipoprotein E (APOE) ε4 is a well-known genetic risk factor for ICH among persons without AVM, and cerebral amyloid angiopathy is a vasculopathy frequently observed in APOE ε4 carriers that may increase the risk of ICH. To assess whether APOE ε4 is associated with a higher risk of ICH in patients with a known AVM. This cross-sectional study including 412 participants was conducted in 2 stages (discovery and replication) using individual-level data from the UK Biobank (released March 2012 and last updated October 2023) and the All of Us Research Program (commenced on May 6, 2018, with its latest update provided in October 2023). The occurrence of AVM and ICH was ascertained at the time of enrollment using validated International Classification of Diseases, Ninth Revision and Tenth Revision, codes. Genotypic data on the APOE variants rs429358 and rs7412 were used to ascertain the ε status. For each study, the association between APOE ε4 variants and ICH risk was assessed among patients with a known AVM by using multivariable logistic regression. The discovery phase included 253 UK Biobank participants with known AVM (mean [SD] age, 56.6 [8.0] years, 119 [47.0%] female), of whom 63 (24.9%) sustained an ICH. In the multivariable analysis of 240 participants of European ancestry, APOE ε4 was associated with a higher risk of ICH (odds ratio, 4.58; 95% CI, 2.13-10.34; P < .001). The replication phase included 159 participants with known AVM enrolled in All of Us (mean [SD] age, 57.1 [15.9] years; 106 [66.7%] female), of whom 29 (18.2%) sustained an ICH. In multivariable analysis of 101 participants of European ancestry, APOE ε4 was associated with higher risk of ICH (odds ratio, 4.52; 95% CI, 1.18-19.38; P = .03). The results of this cross-sectional study of patients from the UK Biobank and All of Us suggest that information on APOE ε4 status may help identify patients with brain AVM who are at particularly high risk of ICH and that cerebral amyloid angiopathy should be evaluated as a possible mediating mechanism of the observed association.

Abstract TP279: Atrial Cardiopathy and Intracerebral Hemorrhage in Patients With Acute Ischemic Stroke

Background and Purpose: Atrial cardiopathy is recognized as a potential contributor to cardiovascular events. Whether atrial cardiopathy is associated with the risk of intracranial hemorrhage in acute ischemic stroke (AIS) remains uncertain. We aimed to investigate the relationship between atrial cardiopathy and intracerebral hemorrhage risk in patients with AIS. Methods: This single-center observational study included 631AIS patients (median age: 70 years [IQR] 61-78; 31.5% female). Atrial cardiopathy was defined as any presence of ≥1: left atrial diameter ≥ 52 mm (males) or ≥ 47 mm (females), elevated P-wave terminal force in V1 (PTFV1) &gt; 5000 μV·ms, or serum NT-proBNP &gt;250 pg/ml. Our primary outcomes included any intracranial hemorrhage (ICH) and symptomatic ICH (sICH) during follow-up. Our secondary outcome was ischemic stroke recurrence. The association between atrial cardiopathy and outcomes was analyzed using Cox hazards regression models. Results: During a median of 1.57 years follow-up, 67 (10.6%) AIS patients experienced any ICH, and 18 (2.9%) patients developed sICH. In Kaplan-Meier analysis, the rate of any ICH or sICH during follow-up was more frequent in patients with atrial cardiopathy compared to those without (log-rank test, p &lt; 0.001, respectively; Figure 1 ). After adjustment for CHA 2 DS 2 -VAS C , atrial cardiopathy was significantly associated with the risk of any ICH (HR 3.99, 95% CI 2.20-7.22, p &lt; 0.001) or sICH (HR 7.93, 95% CI 1.77-35.51, p = 0.007). There was no significant association of ischemic stroke recurrence with atrial cardiopathy. Conclusions: This investigation suggests a potential link between atrial cardiopathy and an increased risk of intracranial hemorrhage in patients with acute ischemic stroke.

March 2023 Stroke Highlights.

March 2023 Stroke Highlights.

Short-term air pollutants exposure has heterogeneous associations with intracerebral hemorrhage risk: A case-crossover study based on symptom onset time in Chengdu, China

BackgroundThe association between air pollutants and intracerebral hemorrhage (ICH) risk is inconsistent. Most previous research focuses on admission rather than symptom onset. In the present work, we used symptom onset time to explore the relationship between short-term air pollutants exposure and ICH risk in Chengdu, China. MethodsWe adopted a time-stratified case-crossover approach to study the association between six air pollutants exposure (PM2.5, PM10, SO2, NO2, CO & O3) and ICH risk in a teaching hospital, which covers a population of more than one million. Subgroup analysis was conducted and stratified by individual factors, including sex, age, and medical history. ResultsWe ultimately enrolled 1052 cases in this study. Overall, the daily concentration elevation of PM2.5, PM10, SO2, and CO in lag4 increased ICH risk. And the OR were 1.027 (95% CI 1.004 to 1.050), 1.017 (95% CI 1.003 to 1.031), 1.018 (95% CI 1.003 to 1.032), and 1.040 (95% CI 1.013 to 1.068), respectively. In subgroup analysis, increases of PM2.5 and PM10 promoted the ICH risk in patients <60 years old, and elevation of SO2 and NO2 upped the ICH risk in patients ≥60 years old. CO increased the ICH risk of male patients; NO2 was associated with reduced risk in female patients and increased risk in cases with non-smoking or non-drinking. PM2.5, PM10, SO2, and CO raised the ICH risk of patients with non-smoking, non-drinking, non-diabetes, or hypertension. The smoking or hypertension cases had greater OR after exposure to O3. ConclusionsShort-term air pollutants exposure has heterogeneous associations with ICH risk, and the connections are different in the overall cases and subgroups. Further studies are needed to clarify the biological association between specific pollutants and ICH risk.

Interaction Effect of Baseline Serum Glucose and Early Ischemic Water Uptake on the Risk of Secondary Hemorrhage After Ischemic Stroke.

Background and Purpose: Intracerebral hemorrhage (ICH) after mechanical thrombectomy (MT) for acute ischemic stroke (AIS) remains a major complication and its early prediction is of high relevance. Baseline serum glucose (BGL) is a known predictor of ICH, but its interaction with early ischemic changes remains uncertain. We hypothesized that BGL interacts with the effect of tissue water uptake on the occurrence of ICH.Methods: Three hundred and thirty-six patients with acute ischemic stroke treated with MT were retrospectively analyzed. ICH was diagnosed within 24 h on non-enhanced CT (NECT) and classified according to the Heidelberg Bleeding Classification. Early tissue water homeostasis has been assessed using quantitative lesion net water uptake (NWU) on admission CT. Multivariate logistic regression was used to identify predictors of ICH.Results: One hundred and seven patients fulfilled the inclusion criteria of which 37 (34.6%) were diagnosed with ICH. Patients with ICH had a significant higher BGL on admission (median 177 mg/dl, IQR: 127–221.75, P < 0.001). In patients with low BGL (<120 mg/dl), higher NWU was associated with 1.34-fold increased likelihood of ICH, while higher NWU was associated with a 2.08-fold increased likelihood of ICH in patients with a high BGL (>200 mg/dl). In multivariable logistic regression analysis, BGL (OR: 1.02, 95% CI: 1.00–1.04, P = 0.01) and NWU (OR: 2.32, 95% CI: 1.44–3.73, P < 0.001) were significantly and independently associated with ICH, showing a significant interaction (P = 0.04).Conclusion: A higher degree of early tissue water uptake and high admission BGL were both independent predictors of ICH. Higher BGL was significantly associated with accelerated effects of NWU on the likelihood of ICH. Although a clear causal relationship remains speculative, stricter BGL control and monitoring may be tested to reduce the risk of ICH in patients undergoing thrombectomy.

Intracerebral haemorrhage in patients with brain metastases receiving therapeutic anticoagulation

BackgroundVenous thromboembolism is common in patients with solid malignancies and brain metastases. Whether to anticoagulate such patients is controversial given the possibility of intracerebral haemorrhage (ICH). We evaluated the added...

CT-Visible Convexity Subarachnoid Hemorrhage is Associated With Cortical Superficial Siderosis and Predicts Recurrent ICH.

To investigate whether acute convexity subarachnoid hemorrhage (cSAH) detected on CT in lobar intracerebral hemorrhage (ICH) related to cerebral amyloid angiopathy (CAA) is associated with recurrent ICH. We analyzed data from a prospective cohort of consecutive acute lobar ICH survivors fulfilling the Boston criteria for possible or probable CAA who had both brain CT and MRI at index ICH. Presence of cSAH was assessed on CT blinded to MRI data. Cortical superficial siderosis (cSS), cerebral microbleeds, and white matter hyperintensities were evaluated on MRI. Cox proportional hazard models were used to assess the association between cSAH and the risk of recurrent symptomatic ICH during follow-up. A total of 244 ICH survivors (76.4 ± 8.7 years; 54.5% female) were included. cSAH was observed on baseline CT in 99 patients (40.5%). Presence of cSAH was independently associated with cSS, hematoma volume, and preexisting dementia. During a median follow-up of 2.66 years, 49 patients (20.0%) had recurrent symptomatic ICH. Presence of cSAH was associated with recurrent ICH (hazard ratio 2.64; 95% confidence interval 1.46-4.79; p = 0.001), after adjusting for age, antiplatelet use, warfarin use, and history of previous ICH. cSAH was detected on CT in 40.5% of patients with acute lobar ICH related to CAA and heralds an increased risk of recurrent ICH. This CT marker may be widely used to stratify the ICH risk in patients with CAA. This study provides Class II evidence that cSAH accurately predicts recurrent stroke in patients with CAA.

Risk factors for intracerebral hemorrhage in patients with COVID-19.

Intracerebral hemorrhage (ICH) can be a devastating complication of coronavirus disease (COVID-19). We aimed to assess risk factors associated with ICH in this population. We performed a retrospective cohort study of adult patients admitted to NYU Langone Health system between March 1 and April 27 2020 with a positive nasopharyngeal swab polymerase chain reaction test result and presence of primary nontraumatic intracranial hemorrhage or hemorrhagic conversion of ischemic stroke on neuroimaging. Patients with intracranial procedures, malignancy, or vascular malformation were excluded. We used regression models to estimate odds ratios and 95% confidence intervals (OR, 95% CI) of the association between ICH and covariates. We also used regression models to determine association between ICH and mortality. Among 3824 patients admitted with COVID-19, 755 patients had neuroimaging and 416 patients were identified after exclusion criteria were applied. The mean (standard deviation) age was 69.3 (16.2), 35.8% were women, and 34.9% were on therapeutic anticoagulation. ICH occurred in 33 (7.9%) patients. Older age, non-Caucasian race, respiratory failure requiring mechanical ventilation, and therapeutic anticoagulation were associated with ICH on univariate analysis (p < 0.01 for each variable). In adjusted regression models, anticoagulation use was associated with a five-fold increased risk of ICH (OR 5.26, 95% CI 2.33–12.24, p < 0.001). ICH was associated with increased mortality (adjusted OR 2.6, 95 % CI 1.2–5.9). Anticoagulation use is associated with increased risk of ICH in patients with COVID-19. Further investigation is required to elucidate underlying mechanisms and prevention strategies in this population.Electronic supplementary materialThe online version of this article (10.1007/s11239-020-02288-0) contains supplementary material, which is available to authorized users.

Utility of HAS-BLED and CHA2DS2-VASc Scores Among Patients With Atrial Fibrillation and Imaging Evidence of Cerebral Amyloid Angiopathy

ObjectiveTo determine the utility of the HAS-BLED (Hypertension, Abnormal renal/liver function, Stroke, Bleeding history or predisposition, Labile international normalized ratio, Elderly, Drugs/alcohol concomitantly) and CHA2DS2-VASc (Congestive heart failure, Hypertension, Age, Diabetes, previous Stroke/transient ischemic attack–VAScular disease) scores among patients on anticoagulation (AC) therapy for atrial fibrillation (AF) who have evidence of cerebral amyloid angiopathy (CAA). Patients and MethodsPatients older than 55 years with a diagnosis of AF who had a nontraumatic intracerebral hemorrhage (ICH) while on AC therapy between 1995 and 2016 were identified using the Rochester Epidemiology Project Database. Medical records were reviewed, including imaging of the brain, to identify baseline characteristics, AC use, and outcomes. ResultsA total of 65 patients were identified (mean age, 81.3 years); 35 (53.8%) had evidence of possible/probable CAA. Mean HAS-BLED score in the CAA group was significantly lower (2.1) than that of the non-CAA group (2.9; P<.001). Mortality after ICH, adjusted for HAS-BLED scores, was not significantly different among patients with and without CAA. Sixteen patients restarted on AC therapy after ICH; CHA2DS2-VASc scores were no different between this group and those who were not restarted. Among patients with CAA, the overall rate of ICH recurrence was 8.6% over 93.5 person-years of follow-up. Among patients with CAA, the rate of ICH recurrence was 3.2 per 100 patient-years, higher than their HAS-BLED scores would predict (1.9 bleeds/100 patient-years). ConclusionHAS-BLED scores were lower in patients who had evidence of CAA compared with those without, suggesting underestimation of ICH risk in patients with CAA. CHA2DS2-VASc scores did not affect resumption of AC therapy. ICH recurrence was higher in patients with CAA than their HAS-BLED scores predicted. Current risk assessment scoring systems do not accurately account for CAA in patients with AF on AC.

Effects of Statin Therapy on the Risk of Intracerebral Hemorrhage in Korean Patients with Hyperlipidemia.

Statins are widely used for primary and secondary prevention of cardiovascular and cerebrovascular disease. Several large randomized trials have suggested that statins might increase the risk of intracerebral hemorrhage (ICH); studies have also shown interethnic variability in responses to statins. This study aimed to determine the association between statin use and the risk of ICH in patients with hyperlipidemia among a Korean population. Population-based, retrospective cohort study. Korean National Health Insurance Service-National Sample Cohort database (2002-2015). A total of 313,368 patients, aged 40-85years, without a history of hemorrhagic stroke were included after being diagnosed with hyperlipidemia between January 2003 and December 2013 (for follow-up through December 2015). Of those, statin users were compared with nonusers by using propensity score matching in a 1:1 ratio (21,797 in each group). The study groups were matched for age, sex, Charlson Comorbidity Index score, follow-up duration, comorbidities, and concurrent medications. The primary endpoint was occurrence of an ICH event. Secondary endpoints were mortality (all-cause, major adverse cardiovascular and cerebrovascular event related, and stroke related) and outcomes after ICH (e.g., recurrent ICH and mortality after primary ICH event). The Cox proportional hazard model was used to evaluate the ICH risk of statins. Subgroup analyses were performed based on ICH-related risk factors. During a mean follow-up period of 6.4years, ICH occurred in 456 of the 43,594 patients (1.05%). Statin use was significantly associated with a decreased ICH risk (adjusted hazard ratio [aHR] 0.78, 95% confidence interval [CI] 0.65-0.94). Compared with nonusers, statin users showed significantly lower all-cause mortality (aHR 0.61, 95% CI 0.57-0.64), cardiovascular and cerebrovascular disease-related mortality (aHR 0.75, 95% CI 0.65-0.85), and stroke-related mortality (aHR 0.69, 95% CI 0.54-0.88). No significant differences in recurrence and mortality after an ICH event were noted between study groups. Statin therapy was associated with a decreased ICH risk and improvements in ischemic cardiovascular and cerebrovascular outcomes in Korean patients with hyperlipidemia. Further large-scale clinical studies are needed to clarify the impact of statins on the risk of developing ICH.

Intracerebral Hemorrhage in Multiple Sclerosis: A Retrospective Cohort Study

Background: To identify the vascular risk factors associated with the occurrence of intracerebral hemorrhage (ICH) in Multiple Sclerosis (MS) patients. MethodsThis is an observational, retrospective cohort study using the nationwide electronic medical records (EMR) database. Patients with the diagnosis of MS were extracted from inpatient and outpatient EMR using the international classification of diseases, ninth/tenth revisions, clinical modification codes. We excluded patients younger than 18 years, and those where gender was not specified. Patients were further stratified based on their demographics, risk factors, medications, and comorbidities. Tobacco, diabetes, hypertension, and alcohol were the predicting variables; antiplatelet medication, and anticoagulant agents were the primary exposures for the development of ICH. A validated diagnosis code algorithm defined the diagnosis of ICH. Multivariable logistic regression models were utilized to assess the risk of ICH in MS patients. ResultsOf the total 57,099 MS patients (women: 75%, n = 41,517), 107 (.19%) sustained an ICH. Age (OR = 2.74, CI = 1.13-6.62), use of anticoagulants (OR = 2.15, 95% CI = 1.30-3.56, P = .0028), and history of tobacco exposure (OR = 2.44, CI = 1.37-4.36, P = .0025) were associated with increased risk of ICH. Use of antiplatelet and disease-modifying drugs (DMDs) showed a protective trend against ICH. ConclusionsTobacco exposure and anticoagulant use were strongly associated with increased risk of ICH in patients with MS. There might be a protective effect that antiplatelet and DMDs have in the pathophysiology of this disease. Further prospective investigations are warranted to establish these associations.

Cerebral amyloid angiopathy: Review of clinico-radiological features and mimics.

Cerebral amyloid angiopathy (CAA) is an important cause of lobar intracerebral haemorrhage (ICH) in the elderly, but has other clinico-radiological manifestations. In the last two decades, certain magnetic resonance imaging (MRI) sequences, namely gradient-recalled echo imaging and the newer and more sensitive susceptibility-weighted imaging, have been utilised to detect susceptibility-sensitive lesions such as cerebral microbleeds and cortical superficial siderosis. These can be utilised sensitively and specifically by the Modified Boston Criteria to make a diagnosis of CAA without the need for 'gold-standard' histopathology from biopsy. However, recently, other promising MRI biomarkers of CAA have been described which may further increase precision of radiological diagnosis, namely chronic white matter ischaemia, cerebral microinfarcts and lobar lacunes, cortical atrophy, and increased dilated perivascular spaces in the centrum semiovale. However, the radiological manifestations of CAA, as well as their clinical correlates, may have other aetiologies and mimics. It is important for the radiologist to be aware of these clinico-radiological features and mimics to accurately diagnose CAA. This is increasingly important in a patient demographic that has a high prevalence for use of antiplatelet and antithrombotic medications for other comorbidities which inherently carries an increased risk of ICH in patients with CAA.

Statins and the Risk of Intracerebral Hemorrhage in Patients With Previous Ischemic Stroke or Transient Ischemic Attack

Although there is no overall association between statin use and intracerebral hemorrhage (ICH), whether there is an increased risk among those with a history of ischemic stroke (IS) or transient ischemic attack (TIA) remains controversial. We evaluated the relationship of preadmission statin use with the risk of ICH in patients with a history of IS or TIA in a population-based cohort. The Health Improvement Network primary care database in the United Kingdom was used to identify new users of low-dose aspirin and a matched comparison. Both cohorts were followed to identify incident cases of ICH, with validation by manual review of patient records and linkage to hospitalization data. In a nested case-control study, we compared the adjusted odds ratios (ORs) with 95% confidence intervals (CIs) for ICH based on statin use in the subgroup of individuals with history of IS/TIA. Last statin use within 1 year of ICH (OR, 0.92; 95% CI [confidence interval], 0.60-1.4), last use between 8 days and 1 year (OR, 1.81; 95% CI, 0.99-3.28), and statin use at the time of ICH (OR, 0.77; 95% CI, 0.49-1.21) were not associated with the overall ICH risk among 157 patients with ICH and 884 controls with a history of IS/TIA. There was also no difference in 30-day rates of fatal (OR, 0.82; 95% CI, 0.41-1.64) or nonfatal (OR, 0.90; 95% CI, 0.51-1.57) ICH. Statin use was not associated with an increased risk of ICH among patients with a previous history of IS/TIA.

Risk of intracerebral hemorrhage in HIV/AIDS: a systematic review and meta-analysis.

Evidence for the association and the increased risk of stroke with human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) is growing. Recent studies have reported on HIV infection as a potent risk factor for intracerebral hemorrhage (ICH). We used the pooled results from case-control studies to conduct a systematic review and a meta-analysis in order to evaluate the risk of ICH with HIV/AIDS. Our systematic review and meta-analysis was based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses algorithm of all available case-control studies that reported on the risk of ICH in patients with HIV/AIDS. Five eligible studies were identified, totaling 5,310,426 person-years studied over various periods that ranged from 1985 to 2010. There were a total of 724 cases of ICH, 138 with HIV/AIDS. HIV-infected ICH patients were in average younger. Pooled crude incidence rate ratio (IRR) for ICH in HIV/AIDS patients was 3.40 (95% confidence intervals [CI] 1.44-8.04; p = 0.005, random-effects model). Clinical AIDS was associated with a higher IRR of ICH (11.99, 95% CI 2.84-50.53; p = 0.0007) than HIV+ status without AIDS (1.73, 95% CI 1.39-2.16; p < 0.0001). Patients with CD4+ lymphocyte count <200cells/mm3 were similarly at a higher risk. Antiretroviral therapy did not seem to increase the risk of ICH. The available evidence suggests that HIV/AIDS is an important risk factor for ICH, particularly in younger HIV-infected patients and those with advanced disease.

Post-Thrombolysis Hemorrhage Risk of Unruptured Intracranial Aneurysms

Background/Aims: It has been questioned whether patients with unruptured intracranial aneurysms (IAs) are at a greater risk for the development of intracerebral hemorrhage (ICH) following thrombolytic therapy. We thus performed a meta-analysis to better quantify the risk of post-thrombolysis ICH in patients with acute ischemic stroke and incidental IAs. Methods: We searched PubMed, Web of Science and EMBASE for studies assessing ICH risk in patients with acute ischemic stroke treated with thrombolysis, in relation to the presence of pretreatment IAs. A fixed-effects model meta-analysis was performed. Results: We identified four studies totaling 707 participants receiving intravenous thrombolysis. The prevalence of unruptured IAs was 6.8%. Pooled analysis demonstrates relative risk (RR) for the presence of unruptured IAs and the development of any ICH to be 1.204 (95% CI 0.709-2.043; p = 0.492; I² = 0.0%). The RR for sICH is 1.645 (95% CI 0.453-5.970; p = 0.449; I² = 28.1%). Conclusion: Intravenous thrombolysis was safe among patients with acute ischemic stroke and incidental unruptured IAs. Future prospective studies with much larger sample sizes are required to clarify the significance of the association between pre-existing unruptured IAs and the development of post-thrombolysis ICH. i 2014 S. Karger AG, Basel

Association of genetic polymorphisms at beta-adrenergic receptor with risk of intracerebral hemorrhagic stroke in North Indian population: a case control study.

Stroke is a multifactorial, polygenic disorder, influenced by both environmental and genetic factors. The purpose of this study was to determine the association of beta-1 and beta-2 adrenergic receptor (AR) polymorphisms with intracerebral hemorrhagic stroke (ICH) in a North Indian population. One hundred and six patients with intracerebral hemorrhage (ICH) and 106 age- and sex- matched controls were recruited. Genotyping was performed by using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. RFLP results of three samples of each genotype were confirmed by DNA sequencing. Mean age of cases and controls were 53.47 ± 14 and 52.92 ± 13.4, respectively. Significant association between Ser49Gly polymorphism of beta-1 AR and ICH in patients who had onset of disease at a later stage of life (>50 years) under a dominant model of inheritance (OR, 3.6; 95% 1.4 to 9.7) was observed. Under the dominant model of inheritance, Gln27Glu polymorphism of beta-2 AR was associated with risk of ICH (OR, 3.2; 95% CI, 1.7 to 5.8) and significant association persisted even after adjustment for demographic and other risk factor variables (OR, 2.9; 95% CI, 1.04 to 8; P = 0.04). Age-stratified analysis showed an independent significant association of Gln27Glu polymorphism of beta-2 AR with risk of ICH in patients those had onset of disease at young age (<50 years) under a dominant model of inheritance (OR, 3.5; 95% CI, 1.1 to 11). The present study provides the first preliminary evidence that Gln27Glu polymorphism of beta-2 AR may contribute modest effect in increase in risk of ICH in North Indian Population. Large prospective studies with large sample size are required to confirm these findings.

Abstract TP301: Warfarin Increases Risk of Future Intracerebral Hemorrhage in Patients Presenting with Isolated Lobar Microbleeds on MRI

BACKGROUND/OBJECTIVES: Lobar microbleeds (LMB) are increasingly identified on brain MRI of older adults, suggesting a diagnosis of cerebral amyloid angiopathy (CAA) in the absence of intracerebral hemorrhage (ICH). Identifying the baseline characteristics and risk of future ICH of these subjects is important to understand their prognosis and safety of antithrombotic use in this setting. METHODS: Baseline characteristics (demographics, risk factors, APOE genotype), markers of CAA severity (LMB counts, white matter hyperintensity volume), and finally outcomes during a mean follow up of 4 years (incidence rate of ICH and case-fatality) were compared between 62 CAA patients without and 747 with ICH diagnosed using Boston criteria upon enrollment. The association between antithrombotic use and risk of incident ICH was explored in patients presenting with isolated LMBs after adjusting for covariates listed above. RESULTS: Female gender (52% vs. 37% p=0.023) and hypertension (67% vs. 53% p=0.025) were more common in patients presenting with ICH, other baseline characteristics did not differ. Patients presenting without ICH had more LMBs (median 10 vs. 1 p&lt;0.001), and higher white matter hyperintensity volume (38cc±32 vs. 27cc ±24 p=0.008) than patients with ICH even after correction for other covariates. Patients without ICH on enrollment had a lower but non-trivial incidence rate of ICH during follow-up (4.8 per 100 person-years vs. 9 per 100 person-years; RR: 0.56, 95%CI 0.27-0.97). The case-fatality rates were similar between these groups (p=0.5). In patients presenting without ICH, the use of Warfarin was an independent predictor of future ICH (p=0.02) in the multivariate model. Patients using either ASA 325mg/day OR Clopidogrel OR ASA/Dipyridamol had higher risk of future ICH (p=.049) but this association did not remain significant in multivariate model. Use of ASA 81mg daily was not a predictor of incident ICH risk. CONCLUSIONS: Patients presenting with LMBs on MRI have a clinical, genetic, and neuroimaging profile suggestive of severe CAA pathology. They have a considerable risk of incident ICH albeit lower than patients who had a prior lobar ICH. The use of warfarin increases the risk of future ICH in patients with isolated LMBs on MRI.

Risk of Intracerebral Hemorrhage in Patients With Cerebral Microbleeds Undergoing Endovascular Intervention

Cerebral microbleeds (CMBs) on MRI gradient echo images are hemosiderin deposits, which may predict intracerebral hemorrhage (ICH). The risk of ICH in patients with CMBs could be exacerbated by the use of antithrombotics. The purpose of our study is to prospectively evaluate the risk of ICH in patients with ischemic stroke who receive dual antiplatelet therapy for endovascular intervention. We analyzed MRI of 133 patients admitted consecutively for intra- and extracranial stenting for symptomatic large artery atherosclerosis who received aspirin and clopidogrel. Quantity and location of CMBs were recorded by neuroradiologists independent from the angioplasty team. The primary end point was symptomatic ICH as evident in CT of the brain within 12 weeks of procedure. CMBs were identified in 23 patients. Mean number of CMBs was 2.3 ± 1.6. Four patients had >5 CMBs. Forty-seven patients had intracranial stents, 84 patients had extracranial stents, and 2 patients had both intracranial and extracranial stents. There was no difference in risk of symptomatic ICH between those with (4.3%) and without CMBs (5.5%) patient with CMBs (P=1.000). The presence of a small number of CMBs does not cause a large increase in the short-term risk of symptomatic ICH in patients with ischemic stroke who undergo endovascular intervention with dual antiplatelet therapy. The risk of ICH in patients with ≥ 5 CMBs, however, remains unclear. Further studies with a larger sample size of patients with multiple CMBs are needed.