Risk Factor For Intracerebral Hemorrhage Research Articles

TIMP-1 polymorphisms in a Chinese Han population with intracerebral hemorrhage

Remodeling of extracellular matrix (ECM) and breakdown of blood–brain barrier (BBB) are crucial events in the pathogenesis of intracerebral hemorrhage (ICH). Matrix metalloproteinases (MMPs), particularly MMP-9 and MMP-2, are the most important degrading enzymes in the ECM and BBB. These proteolytic effects are controlled predominantly by tissue inhibitors of metalloproteinases (TIMPs). TIMP-1 is the main endogenous inhibitor of MMP-9. Two polymorphisms in the TIMP-1 gene (rs4898 and rs2070584) were selected through a literature review and successfully genotyped in a study sample of 410 ICH patients and 305 controls. Differences in genotype and allele frequencies of identified polymorphisms were determined. Furthermore, the serum levels of TIMP-1 were measured in a subgroup of 96 ICH patients on days 1 after ICH onset and 76 controls. Analyses showed that C allele of rs2070584 was significantly associated with the development of ICH in male subjects (p = 0.037, OR = 1.535, 95%CI 1.025–2.300). Multiple logistic regression analysis under three genetic models demonstrated both rs4898 and rs2070584 were not risk factors for ICH in female subjects. Furthermore, serum levels of TIMP-1 were significantly higher in ICH patients than those in normal controls. However, the serum levels of TIMP-1 showed a nonsignificant decrease, depending on the alleles and genotypes of rs2070584 both in male and female cases. In conclusion, this is the first association study of the TIMP-1 gene variants with ICH. Our data suggest that C allele of rs2070584 is a risk factor for ICH development in the Chinese male population. However, the precise function of this variant needs further investigation.

Prevalence of Hypertension in Deep and Lobar Intracerebral Hemorrhage in a Group of Iraqi Patients

Background: Non-traumatic Intracerebral Hemorrhage (ICH) results from rupture of blood vessels in the brain. ICH categories can also be considered as being either lobar in location or within the deep white matter. Although hypertension is a major risk factor for ICH in general[11], it is commonly considered to be associated more with patients having deep than with those having lobar haemorrhage.Objectives: We investigate the relationship between hypertension and deep versus lobar intracerebral hemorrhage (ICH).Methods: a retrospective review of records of 163 patients aged 18-89 years admitted to Al-Kadhimiya Teaching Hospital (January 2008 - October 2010) and diagnosed with ICH.Results: There was no significant relationship between hypertension in deep versus lobar intracerebral hemorrhage (p=0.814)Conclusions: Although the relation between hypertension and ICH was not found to be significant, our study suggests and recommends age-appropriate investigations for patients with ICH, as well as the need to promote patients’ education with regards to this disease and the importance of adherence to treatment of risk factors.

Hypercholesterolemia as one of the risk factors of intracerebral hemorrhage

Stroke is still a major cause of morbidity and mortality throughout the world, although better stratification and treatment modalities are being developed. As compared to ischemic stroke, intracerebral hemorrhage (ICH) possesses many unknown data and lacks guidelines for better prophylaxis. In this study, we aimed to investigate patients with ICH hospitalized in our neurology department within 5 years in terms of risk stratification. A total of 4,449 patients were hospitalized; 1,378 of patients (31%) were diagnosed as having cerebrovascular disease and of these 165 patients (3.7%) had ICH. The risk factors of patients with ICH were investigated and compared with age- and gender matched 75 healthy subjects. We observed that hypercholesterolemia (p = 0.002) was one of the most common risk factors in patients with ICH as compared to controls, together with hypertension (p = 0.010). On the other hand, hypolipidemia (LDL-cholesterol level < 50 mg/dl) was not present in any of the patients. As our purpose as neurologists is to reduce the occurrence and fatal outcome of cerebrovascular events, we aimed to emphasize the importance of risk factors to be well defined, for which every effort should be exhibited for both primary and secondary prevention.

Understanding racial differences in intracerebral haemorrhage

Race is a recognised risk factor for intracerebral haemorrhage (ICH). A new study reports that the incidence of ICH is higher in black individuals than white people in young populations. In elderly populations, however, ICH incidence is higher in white than black individuals, suggesting ethnicity-related variation in ICH aetiology.

Epidemiological and clinical characteristics of 266 cases of intracerebral hemorrhage in Hangzhou, China

Ethnicity and socioeconomic factors can influence disease susceptibility, clinical presentation, and outcome. We investigated the clinical characteristics (age, sex, seasonal variation, lesion site, symptoms, complications, prognosis, and sequelae) and risk factors for intracerebral hemorrhage (ICH) in 266 cases treated at our hospital in Hangzhou City, China, from January 2011 to December 2011. Risk of ICH increased dramatically with age; only 4.3% of cases were <30 years old, while 44.4% were >60 years of age. Men outnumbered women by 2:1 (67.3% vs. 32.7%). Single hemorrhage was most often located in the cerebral lobes (37.2% of cases), basal ganglia (34.2%), thalamus (8.3%), cerebellum (6.8%), ventricle (1.5%), and brainstem (1.1%), while 10.9% of cases exhibited hemorrhages at multiple sites. Hypertension was also a major risk factor for ICH, as 47% of all patients were hypertensive and the percentage increased with age. In hypertensive patients, the most common hemorrhage site was the basal ganglia and ICH was often associated with thrombopenia. In patients with leukemia (all forms), most hemorrhages were lobar. Warfarin- and encephalic operation-associated ICHs were all lobar. Headache was the major symptom of occipital, temporal, and frontal lobe hemorrhage. Dizziness, nausea, and vomiting were the major symptoms of cerebellum hemorrhage. Limb dysfunction was the major symptom of thalamic and basal ganglia hemorrhage. Disturbed level of consciousness was the major symptom in multisite, ventricular, parietal lobe, and brainstem hemorrhage. Hyperspasmia occurred most often in lobar hemorrhage and blurred vision in occipital lobe hemorrhage. Hospital mortality was 24.4% (n=65) with a mean delay from presentation to death of (10.5±18.5) d. The majority of fatalities were cerebral hernia cases (58.5%) and these patients also had the shortest time to death [(2.9±3.5) d]. Mortality was 100% in brainstem ICH and hemorrhagic conversion of cerebral infarct. Thrombopenia-associated ICH also had a high mortality rate (81.0%), while patients with cerebrovascular malformations and cerebral aneurysms demonstrated a much better prognosis (46.2% recovery).

Risk factors for intracerebral hemorrhage: the REasons for geographic and racial differences in stroke (REGARDS) study.

Risk factors for intracerebral hemorrhage (ICH) have been largely identified in case-control studies, with few longitudinal studies available. Predictors of incident ICH among 27 760 black and white participants from the REasons for Geographic And Racial Differences in Stroke (REGARDS) cohort study were assessed. There were 62 incident ICH events during an average follow-up of 5.7 years. The increase in risk with age differed substantially between blacks and whites (P=0.006), with a 2.25-fold (95% confidence interval, 1.63-3.12) increase per decade in whites, but no age association with ICH risk in blacks (hazard ratio=1.09; 95% confidence interval, 0.70-1.68). We observed increased risk among men, those with higher systolic blood pressure, and warfarin users. The racial differences in the impact of age contributed to a risk of ICH that was >5 times higher for blacks than whites at age 45, but only about one third as great by age 85. Confirming findings from other studies, men participants with elevated systolic blood pressure and warfarin users were also at greater risk. The contributors to the racial differences in ICH risk require additional investigation.

Abstract WP302: Racial Differences in Imaging Characteristics and Risk Factors for Primary Intracerebral Hemorrhage: Final Results from the DECIPHER Study

Background: Previous studies have reported racial differences in the incidence, location and risk factors for primary intracerebral hemorrhage (ICH). We now report differences in imaging characteristics and risk factors for ICH from the DiffErenCes in the Imaging of Primary Hemorrhage based on Ethnicity or Race (DECIPHER) study. Methods: DECIPHER is a longitudinal, multicenter, MRI-based, natural history study of racial differences in primary ICH. Inclusion criteria were: primary ICH, age ≥ 18, baseline and 1 year MRI scan obtained. Clinical and demographic data were collected on all subjects. Results: A total of 193 subjects of black or white race were enrolled. Subject characteristics overall and by race are provided in the table. Black subjects were younger, had a higher rate of hypertension, cocaine use, and were more frequently smokers. White subjects had a higher rate of hyperlipidemia. A lobar ICH location was more frequent in the white subjects, while infratentorial hemorrhages were more common in blacks. 60% of blacks had 1 or more microbleeds compared to 52% of whites (NS), and blacks tended to have more severe white matter disease. Conclusions: In the DECIPHER study, there were significant racial differences both in the risk factors for primary ICH and in the imaging characteristics. Compared to whites, blacks have a greater rate of hypertension, as well as cocaine and tobacco use. Imaging findings are indicative of a more severe underlying small vessel vasculopathy in the black cohort. The risk factor information may be used to enhance prevention programs tailored for black communities at risk of ICH, while imaging data may provide a useful biomarker to assess the impact of these interventions.

Abstract TMP82: Increased Intracerebral Hemorrhage During Acute and Chronic Hypertension in Alzheimer's Transgenic Mice

Hypertension is a major risk factor for intracerebral hemorrhage (ICH), and the accumulation of amyloid-beta (Aβ) in the cerebrovascular system, cerebral amyloid angiopathy (CAA), is also a significant risk factor for intracerebral hemorrhage ICH. Currently, there are no animal studies demonstrating a direct involvement of hypertension in the accumulation of Alzheimer’s disease-like pathology. To address this issue we have developed several mouse models that combine hypertension protocols with amyloid precursor protein (APP) transgenic mice (Tg2576), which accumulate significant CAA in the large cerebral vessels and the meninges by 18 months of age. The goal of this study was to determine the effect of acute and chronic hypertension on ICH in wildtype and a transgenic mouse model overexpressing a mutant human amyloid precursor protein (Tg2576 mice) associated with early onset AD and CAA. Fifteen-month-old Tg2576 mice and non-transgenic (nTg) littermates were treated with an angiotensin II (AngII) infusion (1000 ng/kg/min) and L-NAME (100 mg/kg/day) in drinking water to produce chronic hypertension. One week later, transient acute hypertension was induced by daily AngII injections (0.5 μg/g, s.c., twice daily) to produce ICH. A similar increase in mean blood pressure was observed in Tg2576 and nTg mice when evaluated 2 weeks after initiation of treatment. However Tg2576 mice had a higher incidence of signs of stroke compared with nTg littermates (P &gt; 0.05). These data suggest that the accumulation of Aβ in the brain has an important role in development of ICH. Moreover, there was robust glial activation and increase in CAA in the gray matter of Tg2576 mice showing that hypertension may affect gray as well as white matter in the brain. Further studies may provide insights into the hypertension-induced changes in the cerebral vascular system that initiated the increase in CAA. The accumulation of Aβ in the cerebrovascular system is a significant risk factor for intracerebral hemorrhage (ICH), and has been linked to endothelial transport failure and blockage of perivascular drainage. While management of hypertension and atherosclerosis can reduce the incidence of ICH, there are currently no approved therapies for attenuating CAA.

Abstract TMP47: Risk Factors for Intracerebral Hemorrhage and the Racial Differences in the Impact of Age on Risk: The REasons for Geographic And Racial Differences in Stroke (REGARDS) Study

Introduction: Because of low incidence rates, risk factors for intracerebral hemorrhage (ICH) have largely been estimated in case/control studies, very selected population cohorts, or by pooling of multiple longitudinal cohorts. Methods: REGARDS is a longitudinal cohort study of 30,239 African American (AA) and white community-dwelling participants aged 45 and over, recruited from the 48 contiguous US states. Physician-adjudicated incident stroke events in the REGARDS study were used to assess risk factors for ICH among those stroke-free at baseline. Results: A total of 62 ICH events occurred over an average 5.6 year follow-up among 27,760 participants stroke-free at baseline. In multivariable models, there was a significant (p = 0.0066) interaction between race and age; ICH risk dramatically increases with age for whites (HR = 2.03 per 10 year difference; 95% CI: 1.14 - 2.86), but there was little evidence of increasing risk with age in AAs (HR = 1.01 per 10 year difference; 95%: 0.65 - 1.58). This differential impact of age underlies a substantial excess in AA-to-white risk at age 45 (HR = 5.30; 95% CI: 1.41 - 19.91), but a marginally lower risk at age 85 (HR = 0.33; 95% CI: 0.10 - 1.05) (see figure). Risk of ICH was also significantly higher for men than women (HR = 2.60; 95% CI: 1.50 - 4.48), in those with higher systolic blood pressure (HR = 1.19 per 10 mmHg difference; 95% CI: 1.05 - 1.36), and for warfarin use to non-use (HR = 2.24; 95% CI: 1.01 - 5.00). Diabetes, chronic kidney disease, cholesterol components, smoking, alcohol use, and aspirin use were not related to ICH risk. Discussion: Additional research is needed to understand the striking AA-to-white differences in ICH risk across the age spectrum. In addition, higher systolic blood pressure, male sex, and warfarin were confirmed as substantial ICH risk factors in the general population. Other factors found to be significant in other studies were not confirmed in this single cohort, population-based, longitudinal cohort study.

Abstract TP293: Antithrombotic Therapy Does Not Increase Cerebral Microbleeding.

BACKGROUND: Antithrombotic drug users are at risk of intracerebral hemorrhage (ICH). Cerebral microbleeding (MB) is also a risk factor for ICH. Therefore, it is important to clarify the relationship between antithrombotic therapy (AT) and MB in order to prevent ICH. The incidence and number of MBs were evaluated in AT users and nonusers among consecutive acute ICH cases. We attempted to gain insights into the statistical“ black box” of hemorrhagic phenomena in which AT, MB, and ICH are mutually related. METHODS: T2*-weighted magnetic resonance imaging (1.5T MRI, 25 brain slices, 2-mm thick) was performed in 273 of 384 consecutive acute ICH (mean age 69.4yrs; M:F, 166:107) to evaluate the incidence and number of MBs, excluding the low-signal intensities associated with the hematoma lesions. RESULTS: Of the 273 cases , 86 (32%) cases were users and 187(68%) were nonusers, and MBs were detected in 60 (70%) users and 116 (62%) non-users. The incidence of MBs was comparable between users and nonusers (Chi-square independence test: χ2, 2.018 ; χ2(0.95)3.842; P = 0.155; odds ratio, 0.67129). The mean number of MBs was also not significantly different between users and nonusers [13.03 (median, 7) vs. 12.46 (median 7): t test: t -0.208; t (0.95) 1.653: P = 0.582]. CONCLUSION AT did not increase MB in this study patients, suggesting that this treatment does not contribute to vascular wall fragility. Complex phenomena leading to ICH were simply categorized into 3 steps: fragility of vascular wall, breakdown of vascular wall, and extension of hemorrhage. Antithrombotic therapy affects only the 3rd step and do not affect the 1st and the 2nd step, whereas hypertension affects all 3 steps. Therefore, in order to prevent hemorrhage extension and severe brain damage, stricter blood pressure control is required in antithrombotic drug users with MBs than in nonusers with MBs.

Cerebral Amyloid Angiopathy: Perspectives on Cerebrovascular Dysfunction

Cerebral amyloid angiopathy (CAA) occurs sporadically in elderly populations or in familial forms of Alzheimer’s disease (AD) and is characterized by insoluble deposition of amyloid-beta peptides (Aβ), within arterial vessels of the central nervous system. Amyloid precursor protein is processed by β- and γ-secretases generating Aβ1-40 and Aβ1-42 species that exist as soluble monomers, soluble oligomers (toxic intermediate species), and insoluble fibrils (principle component of CAA) [1]. Of interest, the co-morbidity and relationship between vascular compromise and neurodegenerative processes are not fully understood. CAA is an associated risk factor for intracerebral hemorrhage and ischemic stroke and also may contribute to the cognitive decline observed in aging, AD, or both [1]. Most AD cases feature early decreases in cerebral perfusion that may arise as a consequence of peripheral vascular disease (e.g., type II diabetes, hypertension) and/or loss of basalocortical cholinergic innervation that regulates cerebral blood flow (CBF) among other neurological functions [2]. Much remains to be understood concerning CAA-induced vasomotor impairment and its impact toward the occurrence and/or progression of impaired cognitive function within neurodegenerative disease.

Prevalence of Hypertension in Deep and Lobar Intracerebral Hemorrhage in a Group of Iraqi Patients

FIBMS Summary: Background: Non-traumatic Intracerebral Hemorrhage (ICH) results from rupture of blood vessels in the brain. ICH categories can also be considered as being either lobar in location or within the deep white matter. Although hypertension is a major risk factor for ICH in general[11], it is commonly considered to be associated more with patients having deep than with those having lobar haemorrhage. Objectives: We investigate the relationship between hypertension and deep versus lobar intracerebral hemorrhage (ICH). Methods: a retrospective review of records of 163 patients aged 18-89 years admitted to Al-Kadhimiya Teaching Hospital (January 2008 - October 2010) and diagnosed with ICH. Results: There was no significant relationship between hypertension in deep versus lobar intracerebral hemorrhage (p=0.814) Conclusions: Although the relation between hypertension and ICH was not found to be significant, our study suggests and recommends age-appropriate investigations for patients with ICH, as well as the need to promote patients’ education with regards to this disease and the importance of adherence to treatment of risk factors.

Risk factors for intracerebral hemorrhage differ according to hemorrhage location

Risk factors have been described for spontaneous intracerebral hemorrhage (ICH); their relative contribution to lobar vs nonlobar hemorrhage location is less clear. Our purpose here was to investigate risk factors by hemorrhage location. This case-control study prospectively enrolled subjects with first-ever spontaneous ICH and matched each with up to 3 controls by age, race, and gender. Conditional stepwise logistic regression modeling was used to determine significant independent risk factors for lobar and nonlobar ICH. From December 1997 through December 2006, 597 cases and 1,548 controls qualified for the analysis. Hypertension, warfarin use, first-degree relative with ICH, personal history of ischemic stroke, less than a high school education, and APOE ε2 or ε4 genotype were more common in ICH cases. Hypercholesterolemia and moderate alcohol consumption (≤ 2 drinks per day) were less common in ICH cases. The associations of hypertension and hypercholesterolemia were specific for nonlobar ICH. Conversely, the association of APOE ε2 or ε4 genotype was specific for lobar ICH. APOE ε2 or ε4 genotype was associated specifically with lobar ICH. Hypertension was associated specifically with nonlobar ICH. A protective association was seen between hypercholesterolemia and nonlobar ICH; no such association was identified for lobar ICH.

Gender Differences in Patients with Intracerebral Hemorrhage: A Hospital-Based Multicenter Prospective Study

Gender differences are well described for patients with ischemic stroke. Conversely, sex disparities in stroke presentation, risk factors, treatment, and outcomes for intracerebral hemorrhage (ICH) were not previously studied. Our objective was to compare the frequency of risk factors, management patterns, symptoms at presentation, complication rates, and outcomes between genders in patients with ICH in Fortaleza, Brazil. Methods: Data were prospectively collected from patients admitted to 19 hospitals in Fortaleza with a diagnosis of ICH by trained research coordinators from June 2009 to October 2010. Daily visits to the selected hospitals were performed, and all patients admitted with a diagnosis of ICH were prospectively evaluated. Results: We evaluated 364 patients, 47.5% of whom were women. Men were younger (59.3 ± 14.58 years vs. 66.3 ± 14.6 years, p < 0.001), more frequently smokers (33.1 vs. 16.6%, p < 0.01) and had a higher frequency of alcohol abuse (48.5 vs. 8.2%, p < 0.01) than women. Women had a trend to have more dyslipidemia (41.1 vs. 31.3%, p = 0.12). Clinical presentation was similar between genders including the presence of motor and sensory deficits, headache, and depressed level of consciousness at presentation. Men had more speech disturbances than women (63.6 vs. 52.7%, p = 0.04). The time interval from symptoms onset to hospital admission was longer in women (25.1 ± 82.4 h vs. 7.9 ± 50.3 h, p = 0.08). Complication rates including pneumonia and deep vein thrombosis were not different between genders. Mortality was similar in both sexes (females: 35.8% vs. males: 33%, p = 0.66). Men were more frequently independent at discharge when evaluated by the modified Rankin Scale (mRS) score (mRS ≤2: 19.7% in men and 8.1% in women, p < 0.01). In the multivariate logistic regression analysis, older age, pre-stroke disability, depressed consciousness at admission, and female gender were independent predictors of poor outcome at discharge. Conclusion: Overall risk factors for ICH in men and women were similar in our series. Men had a higher frequency of alcohol abuse and smoking. Women were older, had an increased time length from symptoms onset to hospital admission and had a worse prognosis at discharge. A better understanding of the gender disparities in patients with ICH will hopefully lead to better outcomes in both sexes in the future.

Intracranial Hemorrhage in a Cirrhotic Patient: Does Hyponatremia Correction Plays a Role?

Purpose: A 58-year-old male with decompensated Laennec's cirrhosis presented with lethargy and fatigue. His liver disease was complicated by ascites, prior spontaneous bacterial peritonitis; esophageal varices; and hepatic encephalopathy. No other medical comorbidities. His last alcohol consumption was 2 years prior to admission. His home medications included spironolactone, ciprofloxacin and rifaximin. Physical exam revealed normal vital signs, jaundice, ascites, lower extremity edema, asterixis and otherwise normal neurologic evaluation. Laboratory data upon presentation revealed platelet count of 68,000, sodium of 113, creatinine 0.6, bilirubin 8.8 and INR 2.12, MELD score 23, Child-Pugh class C. Hyponatremia was medically managed, and sodium rose to 119 within first 24 hours. 48 hours after admission, he developed right side weakness and global aphasia. GCS decreased from 15 to 9. Vital signs had remained normal. Sodium level 48 hours after admission was 129, INR 2.7, PTT 200, fibrinogen 72 and platelet count 43,000. Liver biochemistries remained unchanged, but hemoglobin dropped from 11.7 to 7.5. CT of the head showed a 4.5 × 4.0 × 6.5 cm left temporo-parietal intraparenchymal hemorrhage, with surrounding edema and midline shift. Multiple units of platelets, cryoprecipitate, fresh frozen plasma, recombinant factor VII and red blood cells were administered. However, GCS rapidly deteriorated and intracranial bleeding worsened. No neurosurgical intervention was performed and patient died 48 hours after the initial bleed. Intracerebral hemorrhage (ICH) is a catastrophic and potentially deadly disease. Heavy alcohol intake has also been identified as a major risk factor for ICH. The risk of ICH is increased in cirrhosis from both alcoholic and non-alcoholic etiology. Degree of liver dysfunction appears to correlate with patient outcomes but not with an increased incidence of ICH. This is the first report of an association of hyponatremia correction with ICH. Correction of hyponatremia has been linked to the development of central pontine myelinolysis (CPM). CPM usually occurs in association with alcoholism, malnutrition and liver disease. The temporal association of the hyponatremia correction with the development of ICH suggests a potential causative role for the first one.

Postthrombolysis Intracranial Hemorrhage Risk of Cerebral Microbleeds in Acute Stroke Patients: A Systematic Review and Meta-Analysis

It has been questioned whether patients with cerebral microbleeds are at a greater risk for the development of symptomatic intracerebral hemorrhage following thrombolytic therapy in the management of acute ischemic stroke. Thus far, observational studies have not shown a statistically significant increased risk; however, these have been limited by small sample size. The aim is to better quantify the risk of postthrombolysis intracerebral hemorrhage in patients with acute ischemic stroke and cerebral microbleeds on magnetic resonance imaging. A systematic review of controlled studies investigating the presence of microbleeds on magnetic resonance imaging as a risk factor for intracerebral hemorrhage following thrombolysis in acute stroke patients was conducted. A random effects model meta-analysis was performed. In pooled analysis of five studies totaling 790 participants, the prevalence of microbleeds was 17%. The presence of microbleeds revealed a trend toward an increased risk of postthrombolysis symptomatic intracerebral hemorrhage [odds ratio: 1·98 (95% confidence interval, 0·90 to 4·35; P = 0·09), I(2) = 0%]. Adjusted analysis minimizing potential bias resulted in an increased absolute risk of 4·6% for the development of symptomatic intracerebral hemorrhage in patients with cerebral microbleeds [odds ratio: 2·29 (95% confidence interval, 1·01 to 5·17), I(2) = 0%] reaching borderline significance (P = 0·05). A significant relationship between increasing microbleed burden and symptomatic intracerebral hemorrhage (P = 0·0015) was observed. Isolated analysis of studies using exclusively intravenous tissue plasminogen activator was insignificant. Our data suggest that patients with cerebral microbleeds are at increased risk for symptomatic intracerebral hemorrhage following thrombolysis for acute ischemic stroke. However, current data are insufficient to justify withholding thrombolytic therapy from acute ischemic stroke patients solely of the basis of cerebral microbleed presence.

Burden of Risk Alleles for Hypertension Increases Risk of Intracerebral Hemorrhage

Genetic variation influences risk of intracerebral hemorrhage (ICH). Hypertension (HTN) is a potent risk factor for ICH and several common genetic variants (single nucleotide polymorphisms [SNPs]) associated with blood pressure levels have been identified. We sought to determine whether the cumulative burden of blood pressure-related SNPs is associated with risk of ICH and pre-ICH diagnosis of HTN. We conducted a prospective multicenter case-control study in 2272 subjects of European ancestry (1025 cases and 1247 control subjects). Thirty-nine SNPs reported to be associated with blood pressure levels were identified from the National Human Genome Research Institute genomewide association study catalog. Single-SNP association analyses were performed for the outcomes ICH and pre-ICH HTN. Subsequently, weighted and unweighted genetic risk scores were constructed using these SNPs and entered as the independent variable in logistic regression models with ICH and pre-ICH HTN as the dependent variables. No single SNP was associated with either ICH or pre-ICH HTN. The blood pressure-based unweighted genetic risk score was associated with risk of ICH (OR, 1.11; 95% CI, 1.02-1.21; P=0.01) and the subset of ICH in deep regions (OR, 1.18; 95% CI, 1.07-1.30; P=0.001), but not with the subset of lobar ICH. The score was associated with a history of HTN among control subjects (OR, 1.17; 95% CI, 1.04-1.31; P=0.009) and ICH cases (OR, 1.15; 95% CI, 1.01-1.31; P=0.04). Similar results were obtained when using a weighted score. Increasing numbers of high blood pressure-related alleles are associated with increased risk of deep ICH as well as with clinically identified HTN.

Elevated Blood Pressure Causes Larger Hematoma in a Rat Model of Intracerebral Hemorrhage

Hypertension has been recognized as an independent risk factor for intracerebral hemorrhage (ICH). The objective of this study was to assess the effect of chronically elevated blood pressure on amount of hematoma in a rat model of ICH. A total of 46 rats were divided into two groups-normotensive group (n = 18) and spontaneously hypertensive group (n = 28). To induce ICH, we delivered 2μL of collagenase solution (0.1 U/1μL normal saline) into the striatum. Each animal's brain was removed 24h post-surgery for spectrophotometric hemoglobin assay. Equal or unequal variance t tests were performed to assess changes in variables between the hypertensive and normotensive groups. Tissue analysis revealed a statistically significant difference in optical density percent change at 540-nm wavelength for the hypertensive vs. the normotensive group (261.47 ± 103.68 and 133.33 ± 58.53, p < 0.0001, respectively). As compared to the normotensive rats, hypertensive rats exhibited a higher neurological deficit, loss of balance and coordination, and loss of motor function. Our results demonstrated that hypertensive rats had significantly higher amounts of hemorrhage in comparison to normotensive ones. These findings support the need for further adequately powered studies to investigate differences in amount of hematoma and corresponding functional impairments due to ICH among hypertensive vs. normotensive rats.

The Effect of Admission Blood Pressure on the Prognosis of Patients with Intracerebral Hemorrhage That Occurred during Treatment with Aspirin, Warfarin, or No Drugs

Background. Hypertension is the most important modifiable risk factor for intracerebral hemorrhage (ICH), but blood pressure (BP) management during the acute phase of ICH is still controversial. Approximately one-fourth of ICHs occur during treatment with warfarin or aspirin. Aim. This study was designed to determine the effect of admission BP on the early prognosis of ICH patients by dividing them into three groups (warfarin, aspirin, and no drugs). Methods. Three hundred and sixty-nine patients with supratentorial ICH were divided into three groups according to medication. Each group was evaluated in terms of prognosis and the risk for mortality based on the modified Rankin Scale (mRS) score at discharge (good prognosis: mRS ≤ 3; poor prognosis: mRS > 3). The effect of admission BP on prognosis was evaluated for each group. Results. The inhospital mortality rate was 72% for ICH patients treated with warfarin, 41.6% for ICH patients treated with aspirin, and 35% for ICH patients treated with no drugs. Admission mean arterial blood pressure (MABP) values were higher in patients with poor prognosis compared with patients with good prognosis for the aspirin (P = .002) and no-drug (P = .001) groups, but not in the warfarin (P = .067) group. Conclusion. A high MABP at admission was found to be an independent predictor of poor prognosis for ICH patients treated with aspirin or with no drugs, but not for ICH patients treated with warfarin.

Carotid Intima-Media Thickness, Electrocardiographic Left Ventricular Hypertrophy, and Incidence of Intracerebral Hemorrhage

Carotid intima-media thickness and electrocardiographic left ventricular hypertrophy are 2 subclinical cardiovascular disease measures associated with increased risk of total and ischemic strokes. Increased intima-media thickness and electrocardiographic left ventricular hypertrophy also may reflect end-organ hypertensive effects. Information is scant on the associations of these subclinical measures with intracerebral hemorrhage (ICH). We hypothesized that greater carotid intima-media thickness and the presence of electrocardiographic left ventricular hypertrophy would be independently associated with increased ICH incidence. Among 18,155 participants initially free of stroke in the Atherosclerosis Risk in Communities Study (ARIC) and the Cardiovascular Health Study (CHS), we assessed carotid intima-media thickness, carotid plaque, and electrocardiographic left ventricular hypertrophy. Over a median of 18 years of follow-up, 162 incident ICH events occurred. After adjustment for other ICH risk factors, carotid intima-media thickness was associated positively with incidence of ICH in both ARIC and CHS. The risk was lowest in study-specific Quartile 1, elevated 1.6- to 2.6-fold in Quartiles 2 to 3, and elevated 2.5 to 3.7-fold in Quartile 4 (P<0.05 for both studies). In CHS, having a carotid plaque was associated with a 2-fold (95% CI, 1.1-3.4) greater ICH risk than having no plaque, but only 1.2-fold (95% CI, 0.76-2.0) greater ICH risk in ARIC. Electrocardiographic left ventricular hypertrophy carried a hazard ratio of ICH of 1.7 (95% CI, 0.77-3.7) in CHS and 2.8 (95% CI, 1.2-6.4) in ARIC. Our data suggest that people with carotid atherosclerosis and possibly left ventricular hypertrophy are at increased risk not only of ischemic stroke, but also of ICH.