Incident Intracerebral Hemorrhage Research Articles

Lacunar Infarcts and Intracerebral Hemorrhage Differences: A Nested Case-Control Analysis in the FHS (Framingham Heart Study).

Lacunar stroke (LS) and intracerebral hemorrhage (ICH) are 2 diverse manifestations of small vessel disease. What predisposes some patients to ischemic stroke and others to hemorrhage is not well understood. We performed a nested case-control study within the FHS (Framingham Heart Study) comparing people with incident ICH and lacunar ischemic stroke, to age- and sex-matched controls for baseline prevalence and levels of cardiovascular risk factors. We identified 118 LS (mean age 74 years, 51% male) and 108 ICH (75 years, 46% male) events. Hypertension, diabetes mellitus, smoking, and obesity were strongly associated with LS. Hypertension, but not diabetes mellitus, smoking, or cholesterol levels increased the odds of ICH. Contrary to LS, ICH cases had lower body mass index (BMI) than their controls (26 versus 27); BMI <20 was associated with 4-fold higher odds for ICH. In direct comparison, LS cases had higher BMI (28 versus 26) and obesity prevalence (odds ratio, 3.1); BMI <20 was associated with significantly lower odds of LS (odds ratio, 0.1). LS and ICH share hypertension, but not diabetes mellitus, as a common risk factor. ICH cases had lower BMI compared with not only LS but their controls as well; this finding is unexplained and merits further exploration.

Differential Effect of White-Matter Lesions and Covert Brain Infarcts on the Risk of Ischemic Stroke and Intracerebral Hemorrhage.

We examined the association of white-matter hyperintensity (WMH) volume and covert brain infarcts, which are the 2 major magnetic resonance imaging markers of covert cerebrovascular disease in older adults, with long-term risk of ischemic stroke and intracerebral hemorrhage (ICH) in the general population. Participants were 1731 individuals aged ≥65 years from the Three-City Dijon study. We studied the association of WMH volume and brain infarct, with incident ischemic stroke overall, and by subtype, and with incident ICH. High total, periventricular, and deep WMHs were associated with incident ICH. Extensive periventricular WMH volume was associated with increased risk of ischemic stroke (hazard ratio, 1.94; 95% confidence interval, 1.12-3.35), particularly cardioembolic stroke. Covert brain infarcts were associated with incident ICH but not with incident ischemic stroke or its subtypes. Although of ischemic nature, both WMH volume and covert brain infarcts portend a major risk of ICH. If confirmed in independent studies, these findings could have important implications for the clinical management of covert vascular brain lesions.

Midlife Alcohol Consumption and the Risk of Stroke in the Atherosclerosis Risk in Communities Study.

Alcohol consumption is common in the United States and may confer beneficial cardiovascular effects at light-to-moderate doses. The alcohol-stroke relationship remains debated. We estimated the relationship between midlife, self-reported alcohol consumption and ischemic stroke and intracerebral hemorrhage (ICH) in a biracial cohort. We examined 12,433 never and current drinkers in the Atherosclerosis Risk in Communities study, aged 45 to 64 years at baseline. Participants self-reported usual drinks per week of beer, wine, and liquor at baseline. We used multivariate Cox proportional hazards regression to assess the association of current alcohol consumption relative to lifetime abstention with incident ischemic stroke and ICH and modification by sex-race group. We modeled alcohol intake with quadratic splines to further assess dose-response relationships. One third of participants self-reported abstention, 39% and 24%, respectively, consumed ≤3 and 4 to 17 drinks/wk, and only 5% reported heavier drinking. There were 773 ischemic strokes and 81 ICH over follow-up (median≈22.6 years). For ischemic stroke, light and moderate alcohol consumption were not associated with incidence (hazard ratios, 0.98; 95% CI, 0.79-1.21; 1.06, 0.84-1.34), whereas heavier drinking was associated with a 31% increased rate relative to abstention (hazard ratios, 1.31; 95% CI, 0.92-1.86). For ICH, moderate-to-heavy (hazard ratios, 1.99; 95% CI, 1.07-3.70), but not light, consumption increased incidence. Self-reported light-to-moderate alcohol consumption at midlife was not associated with reduced stroke risk compared with abstention over 20 years of follow-up in the Atherosclerosis Risk in Communities study. Heavier consumption increased the risk for both outcomes as did moderate intake for ICH.

Statin therapy and the risk of intracerebral haemorrhage: a nationwide observational study.

The association between statin therapy and intracerebral haemorrhage is still unclear. The aim was to investigate whether prior use of statin was associated with risk of intracerebral haemorrhage. Between 2006 and 2009, we identified 7696 cases of intracerebral haemorrhage that were first-ever strokes in the Swedish Stroke Register and 14 670 stroke-free controls that were matched on age and gender in the Population Register. Drug therapy at the time of intracerebral haemorrhage was extracted from the Drug Prescription Register. The risk of intracerebral haemorrhage with statins was estimated by conditional logistic regression. In cases and controls, the median age was 73 years and 53% were men. Intracerebral haemorrhage cases had higher prevalence of antithrombotic therapy, hypertension, and diabetes than controls. Statins were used by 1276 (16·6%) of the intracerebral haemorrhage cases and by 2552 (17·4%) of the controls. The crude odds ratios of intracerebral haemorrhage did not differ significantly between patients with and without statins, but after adjustment for antithrombotic therapy, hypertension, and diabetes, patients with statins had a decreased risk of intracerebral haemorrhage (odds ratio = 0·68, 95% confidence interval, 0·63-0·74). The highest proportion (>20%) of antecedent statins was seen in the 70-84 age group, for both cases and controls. In this matched case-controlled study, statin therapy was associated with a decreased risk of incident intracerebral haemorrhage. Future studies on risk of stroke with statin therapy after intracerebral haemorrhage are needed.

Elevated rates of intracerebral hemorrhage in individuals from a US clinical care HIV cohort.

To compare rates of intracerebral hemorrhage (ICH) in HIV-infected and uninfected individuals in a large clinical care cohort and to assess risk factors associated with ICH. We identified incident ICH in HIV-infected and uninfected control cohorts from the Partners Health Care system using ICD-9-CM codes. We constructed Cox proportional hazards models to estimate adjusted hazard ratios for HIV infection and other predictors of ICH. The incidence rate of ICH was 2.29 per 1,000 person-years in HIV-infected individuals compared with 1.23 per 1,000 person-years in uninfected individuals, with an unadjusted incidence rate ratio of 1.85 (95% confidence interval 1.37-2.47, p < 0.001). In a multivariable model, HIV infection was independently associated with a higher hazard of ICH, although its effect diminished with increasing age. Female sex was associated with a lower hazard of ICH in the uninfected cohort but not in the HIV cohort. CD4 count <200 × 10(6) cells/L and anticoagulant use were predictive of ICH. HIV infection conferred an increased adjusted hazard of ICH, which was more pronounced in young patients and in women.

Racial differences in the association of insulin resistance with stroke risk: the REasons for Geographic And Racial Differences in Stroke (REGARDS) study.

Insulin resistance is associated with increased stroke risk, but the effect has not been adequately examined separately in white and black populations. The association of baseline insulin resistance with risk of cerebral infarction (CI) and intracerebral hemorrhage (ICH) was assessed in 12 366 white and 6782 black participants from the REasons for Geographic And Racial Differences in Stroke (REGARDS) cohort, recruited between 2003 and 2007 and followed for an average of 5.7 years. Insulin resistance was measured with the homeostasis model assessment-insulin resistance. There were 364 incident CI and 41 incident ICH events. The risk for CI increased with the log of insulin resistance in whites (hazards ratio [HR]ln(IR)=1.17; 95% confidence interval [CI], 1.00-1.38) but was largely attenuated by adjustment for stroke risk factors (HRln(IR)=1.05; 95% CI, 0.88-1.26). There was no association in blacks (HRln(IR)=1.01; 95% CI, 0.81-1.25). After adjustment for demographic factors and risk factors, there was a significant difference by race in the association of insulin resistance with risk of ICH (P=0.07), with a decrease in the risk of ICH in whites (HRln(IR)=0.61; 95% CI, 0.35-1.04) but a nonsignificant increase in blacks (HRln(IR)=1.20; 95% CI, 0.60-2.39). These data support the growing evidence that insulin resistance may play a more important role in stroke risk among white than black individuals and suggest a potentially discordant relationship of insulin resistance on CI and ICH among whites.

Incidence of symptomatic hemorrhage in patients with lobar microbleeds.

Lobar microbleeds suggestive of cerebral amyloid angiopathy (CAA) are often identified on MRI in the absence of lobar intracerebral hemorrhage (ICH). We compared the baseline characteristics and risk of subsequent ICH among such patients to those presenting with CAA-related lobar ICH. Clinical data (demographics, risk factors), apolipoprotein E genotype, neuroimaging markers of CAA severity (microbleed counts, leukoaraiosis volume), and clinical outcomes (incidence rates of ICH and death during a mean follow-up of 5.3±3.8 years) were compared between 63 patients enrolled because of incidentally found microbleeds and 316 with CAA-related ICH, in our prospectively enrolled cohort. Predictors of incident ICH were explored in the microbleed-only patients using multivariable Cox regression models. Microbleed-only patients shared similar demographic, apolipoprotein E, and vascular risk profiles with lobar ICH patients, but had more lobar microbleeds (median, 10 versus 2; P<0.001) and higher leukoaraiosis volumes (median, 31 versus 23 mL; P=0.02). Microbleed-only patients had a nontrivial incidence rate of ICH, not different from patients presenting with ICH (5 versus 8.9 per 100 person-years; adjusted hazard ratio, 0.58; 95% confidence interval, 0.31-1.06; P=0.08). Microbleed-only patients had a higher mortality rate (hazard ratio, 1.67; 95% confidence interval, 1.1-2.6) compared with ICH survivors. Warfarin use and increasing age were independent predictors of future ICH among microbleed-only patients after correction for other covariates. Patients presenting with isolated lobar microbleeds on MRI have a genetic, neuroimaging, and hemorrhagic risk profile suggestive of severe CAA pathology. They have a substantial risk of incident ICH, potentially affecting decisions regarding anticoagulation in clinical situations.

Abstract W MP87: Lack of Improvement in Incidence and Case-Fatality of First Time Hospital Admission With Intracerebral Hemorrhage in Denmark 2004-2012

Background: The mortality from ischemic stroke and other ischemic cardiovascular events have declined substantially in the last decades. Less is known about the epidemiology of intracerebral hemorrhage (ICH). However, the distribution of major modifiable risk factors, particularly hypertension, smoking, and use of antithrombotic medications changes rapidly in most populations, which underlines the need for updated data. Objectives: To examine trends in incidence of first hospitalization due to ICH and subsequent 30-day case-fatality in Denmark 2004-2012. Methods: We performed a nationwide population-based cohort study. Patients with a first hospitalization due to ICH were identified in the Danish Stroke Registry and followed using the Danish Civil Registration System to determine 30-days case-fatality. We calculated the standardized incidence rates of hospitalization for ICH. Using 2004 as reference, we used multivariable logistic regression with 95% confidence interval to estimate the odds ratio (OR) of death according to year of admission adjusting for age, gender, diabetes, atrial fibrillation, hypertension, previous myocardial infarction, diabetes, smoking, alcohol intake, and quality of in-hospital stroke care. Results: We identified 7850 patients with incident ICH (51.7 % men, median age 74 years). The overall standardized incidence rate (SIR) was 20.9 per 100.000 person years (95% CI: 19.5-22.3) and slightly higher among men compared with women. The SIR remained stable throughout the study period (2004: 20.7 (95% CI: 19.3-22.1) vs. 2012: 18.2 (95% CI: 16.9-19.5)). The average 30-day case-fatality was 31.2%. The adjusted OR for 30-day case-fatality was 1.24 (95% CI: 0.94-1.64) when comparing 2012 with 2004. Conclusions: The incidence rate of first hospitalization due to ICH and subsequent case-fatality have remained stable in Denmark in recent years despite increased focus on modifiable risk factors and improved early in-hospital stroke care.

Cerebral Microbleeds: A Review of Clinical, Genetic, and Neuroimaging Associations

Cerebral microbleeds (microbleeds) are small, punctuate hypointense lesions seen in T2* Gradient-Recall Echo (GRE) and Susceptibility-Weighted (SWI) Magnetic Resonance Imaging (MRI) sequences, corresponding to areas of hemosiderin breakdown products from prior microscopic hemorrhages. They occur in the setting of impaired small vessel integrity, commonly due to either hypertensive vasculopathy or cerebral amyloid angiopathy. Microbleeds are more prevalent in individuals with Alzheimer’s disease (AD) dementia and in those with both ischemic and hemorrhagic stroke. However they are also found in asymptomatic individuals, with increasing prevalence with age, particularly in carriers of the Apolipoprotein (APOE) ε4 allele. Other neuroimaging findings that have been linked with microbleeds include lacunar infarcts and white matter hyperintensities on MRI, and increased cerebral β-amyloid burden using 11C-PiB Positron Emission Tomography. The presence of microbleeds has been suggested to confer increased risk of incident intracerebral hemorrhage – particularly in the setting of anticoagulation – and of complications of immunotherapy for AD. Prospective data regarding the natural history and sequelae of microbleeds are currently limited, however there is a growing evidence base that will serve to inform clinical decision-making in the future.

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 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.

Total and differential leucocyte counts in relation to incidence of stroke subtypes and mortality: a prospective cohort study

Elevated levels of total leucocyte as well as leucocyte subtypes have been associated with increased risk of atherosclerotic disease. Atherosclerosis is an important cause of cerebral infarction, whereas its significance in intracerebral haemorrhage (ICH) is less clear. A small number of prospective studies have revealed the relationship between leucocyte counts and incident stroke, in particular incidence of stroke subtypes. We evaluated the associations between total leucocyte count (TLC) as well as leucocyte subtypes and the incidence of and mortality caused by different stroke subtypes. Of 28 449 participants from the Malmö Diet and Cancer Study, 26 927 stroke-free subjects (mean age at screening, 58 ± 8 years) were included in a prospective cohort study. The screening period was between 1991 and 1996. Incidence of stroke, 1-year mortality and 1-month case-fatality rate (CFR) were assessed by linkage to local and national registers. Cox regression analysis was used to assess stroke risk and 1-year mortality, and 1-month CFR was assessed by logistic regression analysis. During a follow-up period of 13.6 ± 3.3 years, 1515 participants had a first-ever stroke (cerebral infarction, n = 1314; ICH, n = 201). After adjustments for other risk factors, TLC and neutrophil count were significantly associated with increased incidence of cerebral infarction (hazards ratio (HR), 1.4; 95% confidence interval (CI), 1.2-1.7 and 1.3; 95% CI, 1.1-1.5, respectively). There was an inverse association between elevated TLC and incident ICH (HR, 0.7; 95% CI, 0.4-0.99). No associations were found between leucocyte counts and mortality for either stroke subtype. The results suggest that the relationships with inflammation for ischaemic stroke and ICH are different.

Elevated Admission Blood Pressure and Acute Ischemic Lesions in Spontaneous Intracerebral Hemorrhage

Concomitant acute ischemic lesions are detected in a subset of patients with intracerebral hemorrhage (ICH). In this study, our aim was to analyze the pattern of acute ischemic lesions detected by diffusion-weighted imaging (DWI) in patients with ICH, and to use this information, in combination with clinical characteristics of patients, to understand the underlying mechanisms of these lesions. We retrospectively analyzed patients with a diagnosis of ICH who underwent DWI within 14 days of symptom onset. We compared demographic, clinical, and imaging characteristics in patients with and without acute ischemic lesions. We also assessed the number, location, and topographic distribution of DWI bright lesions. Acute ischemic lesions were detected in 15 of 86 patients (17.4%); the lesions had a small, dot-like appearance in 13 patients (87%) and were located in an arterial territory separate from the incident ICH in 12 patients (80%). Patients with acute ischemic lesions had higher admission systolic, diastolic, and mean arterial blood pressure levels; greater periventricular leukoaraiosis burden; more microbleeds, and lower admission Glasgow Coma Scale score. In multivariate analyses, admission mean arterial blood pressure (P < .01) and Glasgow Coma Scale score (P =.03) remained as the only significant variables associated with DWI lesion positivity. Our findings highlight the role of elevated admission blood pressure in the development of concomitant acute ischemic lesions in patients with ICH. The pattern of DWI bright lesions, together with a trend toward an increased burden of leukoaraiosis and microbleeds in patients with acute ischemic lesions, suggest an underlying dysfunctional cerebral microvasculature in the etiology of these lesions.

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.

Triglycerides and risk of hemorrhagic stroke vs. ischemic vascular events: The Three-City Study

BackgroundFew studies have assessed the relationship between triglycerides and the risk of hemorrhagic stroke, which contrasts the considerable number of studies about triglycerides and ischemic vascular events. We analyzed the association pattern between triglycerides and incident intracerebral hemorrhage as compared with coronary events and ischemic stroke, in a large cohort of elderly. MethodsPopulation-based, prospective cohort study among 8393 men and women participating in the Three-City Study, aged ≥65 years at baseline. Fasting blood lipids, including triglycerides, were measured at baseline. Fatal and non-fatal strokes and coronary events were adjudicated and validated by scientific committees. Cox proportional hazards models were used to adjust for potential confounders. ResultsDuring a mean follow-up of 5.0 years, 36 hemorrhagic strokes, 143 ischemic strokes, and 393 coronary events occurred. An increased level of triglycerides was associated with an increased risk of ischemic vascular events. Conversely, a low level of triglycerides (≤0.94mmol/L) was associated with an increased risk of hemorrhagic stroke (adjusted hazard ratio 2.35; 95% confidence interval 1.18–4.70). The relationship with hemorrhagic stroke was mainly apparent in men, in individuals with high blood pressure, and in those with low levels of cholesterol. ConclusionsIn this large cohort of elderly men and women, low triglycerides levels were associated with an increased risk of hemorrhagic stroke and a decreased risk of ischemic vascular events. The association between triglycerides and hemorrhagic stroke was particularly strong in men, in subjects with high blood pressure and in those with low cholesterol levels.

Cerebral microbleeds are a risk factor for warfarin-related intracerebral hemorrhage

Cerebral microbleeds are known to be indicative of bleeding-prone microangiopathy and may predict incident intracerebral hemorrhage (ICH). In this study, we investigated whether microbleeds are associated with the incidence of warfarin-related ICH. Twenty-four patients with ICH while on outpatient treatment with warfarin were selected from a consecutive cohort. Control, warfarin-using subjects with no history of ICH were randomly selected during the same time period (n = 48). We compared demographic factors, vascular risk factors, laboratory findings, and radiologic findings including microbleeds between the groups. There were more cases of patients with microbleeds in the ICH than control group (79.2% vs 22.9%: p < 0.001), and the number of microbleeds was much higher for the ICH group (9.0 +/- 26.8 vs 0.5 +/- 1.03: p < 0.001). Moreover, the number of microbleeds was significantly correlated with the presence of warfarin-related ICH (r = 0.299; p < 0.001). Conditional logistic regression analysis showed that increased prothrombin time and the presence of microbleeds were independently related to the incidence of warfarin-related ICH (microbleeds: adjusted OR, 83.12). This study suggests that underlying microbleeds are independently associated with an incidence of warfarin-related intracerebral hemorrhage. Future research should focus on elucidating the risks and benefits of warfarin medication in patients with microbleeds.

Acute treatment costs of intracerebral hemorrhage and ischemic stroke in Argentina

Stroke is the third leading cause of death in Argentina, yet little information exists on the acute treatment provided for stroke or its costs. This study estimates the national costs of the acute treatment of first-ever intracerebral hemorrhage (ICH) and ischemic stroke (IS) in Argentina. Retrospective hospital-based inception study design using data on resource use and costs from high-volume stroke centers in Argentina, and published population-based incidence data. Treatment provided at two large urban hospitals were evaluated in all patients admitted with a first-ever stroke between 1 January 2004 and 31 August 2006, and costs were assigned using appropriate unit cost data for all resource use. Cost estimates in Argentinian pesos were converted to US dollars ($) using the 2005 purchasing power parity index. National costs of acute treatment for incident strokes were estimated by extrapolation of average costs estimates to national incidence data. Assumptions of the average cost of stroke treatment on a national scale were examined in sensitivity analysis. The acute care of 167 patients with stroke was thoroughly evaluated from hospital admission to hospital discharge. Mean length of hospital stay was 35.4 days for ICH and 13.0 days for IS. Ninety-one percent of the patients with ICH and 68% of the patients with IS were admitted to an ICU for a mean length of stay (LOS) of 12.9 +/- 20.3 and 3.6 +/- 5.9 days respectively. Mean total costs of initial hospitalization were $12,285 (SD +/-14,336) for ICH and $3888 (SD +/-4018) for IS. Costs differed significantly by Glasgow Coma Scale (GCS) score at admission, development of pneumonia and infections during hospitalization, and functional outcome at hospital discharge. Aggregate national healthcare expenditures for acute treatment of incident ICH were $194.2m (range 97.1-388.4) and $239.9m for IS (range 119.9-479.7). The direct hospital costs of incident ICH and IS in Argentina are substantial and primarily driven by stroke severity, in-hospital complications and clinical outcomes. With the expected increase in the incidence of stroke over the coming decades, these results emphasize the need for effective preventive and acute medical care.

Outcome after spontaneous and arteriovenous malformation-related intracerebral haemorrhage: population-based studies

Spontaneous (non-traumatic) intracerebral haemorrhage (ICH) has a high case-fatality and leaves many survivors disabled. Clinical characteristics and outcome seem to vary according to the cause of ICH, but population-based comparisons are scarce. We studied two prospective, population-based cohorts to determine differences in outcome [case-fatality and modified Rankin Scale (mRS)] after incident ICH due to brain arteriovenous malformations (AVM) [Scottish Intracranial Vascular Malformation Study (SIVMS), n = 90] and spontaneous ICH [Oxford Vascular Study (OXVASC), n = 60]. Patients with AVM-ICH were younger, had lower pre-stroke and admission blood pressure (BP), higher admission Glasgow Coma Scale (GCS) and were more likely to have an ICH in a lobar location than patients with spontaneous ICH (sICH). Case fatality throughout 2-year follow-up was greater following sICH than AVM-ICH [34/56 (61%) versus 11/90 (12%) at 1 year, odds ratio (OR) 11 (95% Confidence Interval (CI) 5-25)], as was death or dependence (mRS >or= 3) [40/48 (83%) versus 26/65 (40%) at 1 year, OR 8 (3-19)]. Differences in outcome persisted following stratification by age and sensitivity analyses. In multivariable analyses of 1 year outcome, independent predictors of death were sICH (OR 21, 4-104) and increasing ICH volume (OR 1.03, 1.01-1.05), and independent predictors of death or dependence were sICH (OR 11, 2-62) and GCS on admission (OR 0.79, 0.67-0.93). Outcome after AVM-ICH is better than after sICH, independent of patient age and other known predictors of ICH outcome.

Effect of Statins on Intracerebral Hemorrhage Outcome and Recurrence

3-Hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, or statins, have been associated with improved outcome after ischemic stroke and subarachnoid hemorrhage but an increased risk of incident intracerebral hemorrhage (ICH). We investigated (1) whether statin use before ICH was associated with functional independence at 90 days, and (2) whether survivors exposed to statins after ICH had an increased risk of recurrence. We analyzed 629 consecutive ICH patients with 90-day outcome data enrolled in a prospective cohort study between 1998 to 2005. Statin use was determined by patient interview at the time of ICH and supplemented by medical record review. Independent status was defined as Glasgow Outcome Scale 4 or 5. ICH survivors were followed by telephone interview every 6 months. Statins were used by 149/629 (24%) before ICH. There was no effect of pre-ICH statin use on the rates of functional independence (28% versus 29%, P=0.84) or mortality (46% versus 45%, P=0.93). Medical comorbidities and warfarin use were more common in statin users. Hematoma volumes were similar (median 28 cm(3) in pre-ICH statin users compared to 22 cm(3) in nonusers, P=0.18). The multivariable-adjusted odds ratio for independent status in pre-ICH statin users was 1.16 (95% CI 0.65 to 2.10, P=0.62). ICH survivors treated with statins after discharge did not have a higher risk of recurrence (adjusted HR 0.82, 95% CI 0.34 to 1.99, P=0.66). Pre-ICH statin use is not associated with improved ICH functional outcome or mortality. Post-ICH statin use is not associated with an increased risk of ICH recurrence.

APOE genotype, ethnicity, and the risk of cerebral hemorrhage

The apolipoprotein E (APOE) polymorphism is an established risk factor for intracerebral hemorrhage (ICH) that is related to cerebral amyloid angiopathy in the white population. Among Asian populations, although ICH represents up to one third of all strokes and has high rates of mortality and morbidity, the role of the APOE polymorphism has not been well studied. The Perindopril Protection Against Recurrent Stroke Study (PROGRESS) was a randomized, double-blind, placebo-controlled trial of a blood pressure lowering regimen in subjects with prior cerebrovascular disease. APOE status was determined for 5,671 patients, including 2,148 Asians (38%). During the 3.9 years of follow-up, ICH occurred in 99 patients. Overall, carrying an epsilon 2 or epsilon 4 allele of the APOE polymorphism was associated with an adjusted hazard ratio (HR(a)) of 1.85 (95% CI = 1.24 to 2.76). In Asian patients the risk of ICH for epsilon 2 or epsilon 4 carriers was 2.11 (95% CI = 1.28 to 3.47) and 1.48 (95% CI = 0.76 to 2.87) in Europeans. Carriers of the epsilon 2 or epsilon 4 allele had an increased risk of both incident and recurrent ICH, and both cortical and deep ICH, and most risk estimates were higher in Asians than in Europeans. For both ethnic groups and for subtypes of ICH active treatment more than halved the risk of ICH and the treatment effects were not different in carriers of the epsilon 2 or epsilon 4 allele and in those with the epsilon 3 epsilon 3 genotype. There is a strong association between APOE genotype and the risk of intracerebral hemorrhage (ICH). In Asian patients the role of APOE polymorphisms in ICH is much broader than was previously supposed.