The incidence of anticoagulant-associated intracerebral hemorrhage quintupled in our population during the 1990s. The majority of this change can be explained by increasing warfarin use. Anticoagulant-associated intracerebral hemorrhage now occurs at a frequency comparable to subarachnoid hemorrhage.

Intracerebral hemorrhage (ICH) is the stroke subtype with the worst prognosis and has no established acute treatment. ICH is classified as lobar or nonlobar based on the location of ruptured blood vessels within the brain. These different locations also signal different underlying vascular pathologies. Heritability estimates indicate a substantial genetic contribution to risk of ICH in both locations. We report a genome-wide association study of this condition that meta-analyzed data from six studies that enrolled individuals of European ancestry. Case subjects were ascertained by neurologists blinded to genotype data and classified as lobar or nonlobar based on brain computed tomography. ICH-free control subjects were sampled from ambulatory clinics or random digit dialing. Replication of signals identified in the discovery cohort with p < 1 × 10(-6) was pursued in an independent multiethnic sample utilizing both direct and genome-wide genotyping. The discovery phase included a case cohort of 1,545 individuals (664 lobar and 881 nonlobar cases) and a control cohort of 1,481 individuals and identified two susceptibility loci: for lobar ICH, chromosomal region 12q21.1 (rs11179580, odds ratio [OR] = 1.56, p = 7.0 × 10(-8)); and for nonlobar ICH, chromosomal region 1q22 (rs2984613, OR = 1.44, p = 1.6 × 10(-8)). The replication included a case cohort of 1,681 individuals (484 lobar and 1,194 nonlobar cases) and a control cohort of 2,261 individuals and corroborated the association for 1q22 (p = 6.5 × 10(-4); meta-analysis p = 2.2 × 10(-10)) but not for 12q21.1 (p = 0.55; meta-analysis p = 2.6 × 10(-5)). These results demonstrate biological heterogeneity across ICH subtypes and highlight the importance of ascertaining ICH cases accordingly.

Intracerebral hemorrhage (ICH) mortality did not improve significantly between study periods. Operation for ICH became less frequent, whereas anticoagulant-associated ICH became more common.

Background and Purpose-Risk factors for intracerebral hemorrhage (ICH) vary by location. Incidence rates of ICH are known to be higher in American blacks than whites, but how rates may differ by hemorrhage location is unknown. We sought to define incidence rates for different ICH locations in a biracial population. Methods-All hospitalized patients age Ն20 years with spontaneous ICH were identified in the Greater Cincinnati/ Northern Kentucky metropolitan area from May 1998 to July 2001 and August 2002 to April 2003. Incidence rates per 100 000 persons were age, sex, and race adjusted as appropriate to the 2000 US population. Risk ratios (RRs) with 95% CIs were calculated from unadjusted incidence rates. Results-There were 1038 qualifying ICHs. Annual incidence rates per 100 000 persons Ն20 years of age were 48.9 for blacks and 26.6 for whites. Annual incidence rates per 100 000 blacks in lobar, deep cerebral, brain stem, and cerebellar locations were 15.2, 25.7, 5.1, and 2.9, respectively. Annual incidence rates per 100 000 whites in the same locations were 9.4, 13.0, 1.3, and 2.9. The greatest excess risk of ICH in blacks compared with whites was found among young to middle-aged (35 to 54 years) persons with brain stem (RR, 9.8; 95% CI, 4.2 to 23.0) and deep cerebral (RR, 4.5; 3.0 to 6.8) hemorrhage. Conclusions-The

Background Among patients with intracerebral hemorrhage (ICH) warfarin use prior to onset leads to greater mortality. In a retrospective study we sought to determine if warfarin use is associated with larger initial hematoma volume, one determinant of mortality after ICH. Methods We identified all patients hospitalized with ICH in the Greater Cincinnati region from 1/05–12/05. ICH volumes were measured on the first available brain scan using the abc/2 method. Univariable analyses and a multivariable generalized linear model were used to determine whether international normalized ratio (INR) influenced initial ICH volume after adjusting for other factors including age, race, gender, antiplatelet use, hemorrhage location, and time from stroke onset to scan. Results There were 258 patients with ICH including 51 patients taking warfarin. In univariable comparison, when INR was stratified there was a trend toward a difference in hematoma volume by INR category (INR < 1.2 = 13.4 cc, INR 1.2–2.0 = 9.3 cc, INR 2.1–3.0 = 14.0 cc, INR > 3.0 = 33.2 cc, p = 0.10). In the model, compared to patients with INR < 1.2, there was no difference in hematoma size for patients with INR 1.2–2.0 (p=0.25) or INR 2.1–3.0 (p=0.36), but patients with INR > 3.0 had greater hematoma volume (p=0.02). Other predictors of larger hematoma size were ICH location (lobar compared to deep cerebral, p=0.02) and shorter time from stroke onset to scan (p<0.001). Conclusion Warfarin use was associated with larger initial ICH volume, but this effect was only observed for INR values >3.0. Larger ICH volume among warfarin users likely accounts for part of the excess mortality in this group.

Objectives: 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.Methods: 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.Results: 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 e2 or e4 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 e2 or e4 genotype was specific for lobar ICH.Conclusions: APOE e2 or e4 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. Intracerebral hemorrhage (ICH) accounts for approximately 20% of strokes worldwide, with 30-day mortality estimates of 32%-50%. [1][2][3][4] Of patients who survive, only 28%-35% are independent at 3 months. 5,6 Prior reports from our group and others support the hypothesis that risk factors for ICH vary according to hemorrhage location.7-10 The Genetic and Environmental Risk Factors in Hemorrhagic Stroke (GERFHS) Study is designed to examine the genetic and environmental variables associated with hemorrhagic stroke in the biracial population of the Greater Cincinnati/Northern Kentucky (GCNK) region (population 1.3 million, 16% black). In 2002, our preplanned interim analysis examined the hypothesis that risk factors for ICH varied according to hemorrhage location. Hypertension had the highest attributable risk for nonlobar ICH (e.g., basal ganglia, thalamus, brainstem, cerebellum, or periventricular white matter), whereas APOE alleles e2 and e4 had the highest attributable risk for lobar ICH 7 -findings that have been replicated in other studies. [8][9][10] That report had a limited sample size and therefore limited ability to differentiate risk factors by subgroup. The current report, with over 3 times the sample size of our interim report, re-examines the hypothesis that risk factors for ICH vary in prevalence and attributable risk for lobar vs nonlobar ICH.METHODS Study design. GERFHS is a case-control study of hemorrhagic stroke that used population-based case ascertainment.

Background and Purpose-Stroke is the third leading cause of death and the leading cause of disability in the UnitedStates. Intracerebral hemorrhage and subarachnoid hemorrhage represent Ϸ20% of all stroke cases and have a mortality rate of 40% to 50%. Hypertension is an important risk factor for these subtypes of stroke. We sought to determine whether untreated hypertension carries a different risk from treated hypertension for hemorrhagic stroke. Methods-Cases of hemorrhagic stroke in the greater Cincinnati region were identified by screening all area hospital emergency rooms, radiology reports, and International Classification of Diseases 9 codes. Medical records were reviewed for risk factors and medication use. Cases of hemorrhagic stroke were approached for enrollment into the genetic sampling and interview arm. If subjects agreed, the case was matched by age, race, and gender to population-based controls. Results-Between May 1997 and December 2002, we recruited 549 cases of hemorrhagic stroke, of which 322 were intracerebral hemorrhage and 227 were subarachnoid hemorrhage. Untreated hypertension was found to be a significant risk factor for hemorrhagic stroke (odds ratio [OR]ϭ3.5 [2.3 to 5.2]; PϽ0.0001) as was treated hypertension (ORϭ1.4 [1.0 to 1.9]; Pϭ0.03). Insurance status of "self-pay" or Medicaid was a significant risk factor for untreated hypertension (ORϭ2.7 [1.6 to 4.4]). We estimate that 17% to 28% of hemorrhagic strokes among hypertensive patients would have been prevented if they had been on hypertension treatment. Conclusion-Untreated hypertension is highly prevalent and an important risk factor for hemorrhagic stroke. We estimate that among hypertensive subjects, approximately one fourth of hemorrhagic strokes would be prevented if all hypertensive subjects received treatment.

Background-Nonaneurysmal perimesencephalic subarachnoid hemorrhage (PMSAH) appears to have an etiology and natural history distinct from aneurysm rupture. Referral-based studies suggest that 15% of SAH patients have no discernable cause of bleeding, but the incidence of PMSAH is unknown. We describe the first population-based study of PMSAH and place it in the context of all non-traumatic SAH, with presentation of incidence rates, patient demographics, and clinical outcomes.