Risk factors for intracerebral hemorrhage differ according to hemorrhage location.

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 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. CONCLUSIONS: 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.

The effects of study participation in the Familial Intracranial Aneurysm Study on cigarette smoking.

BACKGROUND: Cigarette smoking is the most modifiable risk factor for the formation and rupture of intracranial aneurysm (IA). This study examined the impact of participation in the Familial IA study on smoking behavior. METHODS: On entry into the study, a baseline smoking history was obtained. At follow-up visits, subjects were surveyed concerning their current smoking status. Risk reduction education was site specific and the study did not include a standard approach. RESULTS: Of participants, 66% had a history of cigarette smoking, with 33.1% being current smokers. There was a significant reduction in the proportion of current smokers by the third yearly follow-up visit (26.7%, P < .001). There was a significant reduction in the daily amount of cigarettes smoked (17.7-11.5, P < .001), with the most significant reduction at the first follow-up visit. Current smokers given the diagnosis of an IA before entry or during the course of the study were more likely to decrease their smoking (19.4-9.8 cigarettes/day, P < .001) than those not given a diagnosis of an IA (16.0-13.3, P = .002). Individuals older then 51 years had a greater reduction in the amount of cigarettes smoked per day compared with those younger than 51 years (2.3 cigarettes/day reduction v 1.5, P = .002). CONCLUSION: Subjects who entered into the Familial IA study had a significant decrease in their smoking by the end of 3 years. Factors associated with decreased smoking were diagnosis of IA and older age.

Primary stroke prevention.

The best way to prevent a first-time stroke is to identify at-risk patients and control as many risk factors as possible. Some risk factors, such as smoking, can be eliminated; others, such as hypertension and carotid artery stenosis, can be controlled or treated to reduce the risk of stroke. Nurses are encouraged to work with patients to identify all risk factors in order to reduce the prevalence of this medical condition that costs billions of dollars annually and results in significant disability.

Gene expression in blood changes rapidly in neutrophils and monocytes after ischemic stroke in humans: a microarray study.

Ischemic brain and peripheral white blood cells release cytokines, chemokines and other molecules that activate the peripheral white blood cells after stroke. To assess gene expression in these peripheral white blood cells, whole blood was examined using oligonucleotide microarrays in 15 patients at 2.4+/-0.5, 5 and 24 h after onset of ischemic stroke and compared with control blood samples. The 2.4-h blood samples were drawn before patients were treated either with tissue-type plasminogen activator (tPA) alone or with tPA plus Eptifibatide (the Combination approach to Lysis utilizing Eptifibatide And Recombinant tPA trial). Most genes induced in whole blood at 2 to 3 h were also induced at 5 and 24 h. Separate studies showed that the genes induced at 2 to 24 h after stroke were expressed mainly by polymorphonuclear leukocytes and to a lesser degree by monocytes. These genes included: matrix metalloproteinase 9; S100 calcium-binding proteins P, A12 and A9; coagulation factor V; arginase I; carbonic anhydrase IV; lymphocyte antigen 96 (cluster of differentiation (CD)96); monocarboxylic acid transporter (6); ets-2 (erythroblastosis virus E26 oncogene homolog 2); homeobox gene Hox 1.11; cytoskeleton-associated protein 4; N-formylpeptide receptor; ribonuclease-2; N-acetylneuraminate pyruvate lyase; BCL6; glycogen phosphorylase. The fold change of these genes varied from 1.6 to 6.8 and these 18 genes correctly classified 10/15 patients at 2.4 h, 13/15 patients at 5 h and 15/15 patients at 24 h after stroke. These data provide insights into the inflammatory responses after stroke in humans, and should be helpful in diagnosis, understanding etiology and pathogenesis, and guiding acute treatment and development of new treatments for stroke.

The Familial Intracranial Aneurysm (FIA) study protocol.

BACKGROUND: Subarachnoid hemorrhage (SAH) due to ruptured intracranial aneurysms (IAs) occurs in about 20,000 people per year in the U.S. annually and nearly half of the affected persons are dead within the first 30 days. Survivors of ruptured IAs are often left with substantial disability. Thus, primary prevention of aneurysm formation and rupture is of paramount importance. Prior studies indicate that genetic factors are important in the formation and rupture of IAs. The long-term goal of the Familial Intracranial Aneurysm (FIA) Study is to identify genes that underlie the development and rupture of intracranial aneurysms (IA). METHODS/DESIGN: The FIA Study includes 26 clinical centers which have extensive experience in the clinical management and imaging of intracerebral aneurysms. 475 families with affected sib pairs or with multiple affected relatives will be enrolled through retrospective and prospective screening of potential subjects with an IA. After giving informed consent, the proband or their spokesperson invites other family members to participate. Each participant is interviewed using a standardized questionnaire which covers medical history, social history and demographic information. In addition blood is drawn from each participant for DNA isolation and immortalization of lymphocytes. High- risk family members without a previously diagnosed IA undergo magnetic resonance angiography (MRA) to identify asymptomatic unruptured aneurysms. A 10 cM genome screen will be performed to identify FIA susceptibility loci. Due to the significant mortality of affected individuals, novel approaches are employed to reconstruct the genotype of critical deceased individuals. These include the intensive recruitment of the spouse and children of deceased, affected individuals. DISCUSSION: A successful, adequately-powered genetic linkage study of IA is challenging given the very high, early mortality of ruptured IA. Design features in the FIA Study that address this challenge include recruitment at a large number of highly active clinical centers, comprehensive screening and recruitment techniques, non-invasive vascular imaging of high-risk subjects, genome reconstruction of dead affected individuals using marker data from closely related family members, and inclusion of environmental covariates in the statistical analysis.

Smoking cessation after stroke: education and its effect on behavior.

Smoking is an independent risk factor for stroke. The purpose of this prospective study was to determine whether significant changes in smoking behavior occurred in a cohort of stroke patients who were educated about risk reduction during their initial recovery period. Participants or their proxies were then contacted at 3 months for a follow-up interview, during which their current location, smoking status, and functional outcome were recorded. Of 405 participants interviewed, 112 were current smokers at the time of stroke. Participants younger than 65 years and Blacks were more likely to be smokers. At 3 months, 48 (43%) of the baseline smokers had quit smoking compared with an estimated rate of 28% previously reported in the literature. The number of participants who smoked > 20 cigarettes per day was 31 at baseline versus 7 at 3 months. This change of behavior was independent of baseline characteristics and the level of poststroke disability. Risk-reduction education provides stroke survivors with the information needed to change their lifestyles. Further research is needed to determine whether this behavior continues beyond 3 months and to determine why some stroke survivors continue to smoke.

Genetic epidemiology of intracerebral hemorrhage.

We have previously reported that family history of intracerebral hemorrhage (ICH) was associated with both lobar and nonlobar ICH. We sought to further examine this finding by analyzing differences by age and by apolipoprotein E (Apo E) genotype. All cases of hemorrhagic stroke in the greater Cincinnati area were identified through retrospective screening, and a subset was invited to undergo a direct interview and genetic testing. Interviewed subjects were matched to 2 controls by age, race, and sex. Conditional stepwise logistic regression modeling was used to determine whether having a first-degree relative with an ICH (FHICH) was an independent risk factor for ICH. Between May 1997 and December 2002, we recruited 333 cases of ICH. FHICH was found to be an independent risk factor for both lobar ICH (odds ratio [OR] = 3.9; P = .04) and nonlobar ICH (OR ratio = 5.4; P = .01) after controlling for the presence of numerous variables. Among nonlobar ICH cases, the risk appeared to be predominately in those age < 70 years. The presence of Apo E4 was associated with lobar ICH at age >/= 70 years but not at age < 70 years. Family history of ICH appears to be a significant risk factor for nonlobar ICH at age < 70 years. The presence of Apo E4 appears to be a risk factor for lobar ICH at age >/= 70 years but not at age < 70 years. Family history of ICH is a risk factor for lobar ICH after controlling for the presence of Apo E4.

Hypercholesterolemia, HMG-CoA reductase inhibitors, and risk of intracerebral hemorrhage: a case-control study.

BACKGROUND AND PURPOSE: Several studies have demonstrated an association between hypocholesterolemia and intracerebral hemorrhage (ICH). We tested the hypothesis that hypercholesterolemia or use of HMG-CoA reductase inhibitors (statin) agents, or both, are associated with ICH. METHODS: This study was part of the preplanned midway analysis of an ongoing, population-based, case-control study of the genetic and environmental risk factors of hemorrhagic stroke. Conditional stepwise logistic regression modeling was used to determine if self-reported hypercholesterolemia or statin use, or both, were independent risk factors for ICH. RESULTS: Between December 1, 1997, and June 30, 2000, 188 cases of ICH and 366 age-, race-, and gender-matched controls were enrolled. Hypercholesterolemia and statin use were less common among cases than controls: 25% versus 38% (P=0.003) and 9% versus 17% (P=0.03), respectively. Hypercholesterolemia with statin use was associated with less risk of ICH (OR=0.30; P=0.0008) in multivariable analysis after controlling for alcohol use, hypertension, previous stroke, first-degree relative with ICH, education level, and apolipoprotein E alleles. CONCLUSIONS: Hypercholesterolemia was associated with a lower risk of ICH. We have not found an increased risk of ICH with the widespread use of statins in our population. Given the lack of cholesterol levels in the current study, further studies are needed to determine if lower cholesterol levels secondary to statin use bear the same risk as low cholesterol levels for ICH.

Genetic and environmental risk factors for intracerebral hemorrhage: preliminary results of a population-based study.

BACKGROUND AND PURPOSE: Intracerebral hemorrhage (ICH) has a 30-day mortality rate of 40% to 50% and lacks a proven treatment. We report a preplanned, midpoint analysis of the first population-based, case-control study that examines both genetic and environmental risk factors of ICH. METHODS: We prospectively identified cases of hemorrhagic stroke at all 16 hospitals in the Greater Cincinnati/Northern Kentucky region. All cases underwent medical record and neuroimaging review. Cases enrolled in the direct interview and genetic sampling arm of the study were matched to population-based control subjects by age, race, and sex. Multivariable logistic regression was performed to identify significant independent risk factors. RESULTS: We enrolled 188 cases of ICH (67 lobar, 121 nonlobar) and 366 control subjects in the direct interview arm of the study. Significant independent risk factors for lobar ICH included the presence of an apolipoprotein E2 or E4 allele, frequent alcohol use, prior stroke, and first-degree relative with ICH. Significant independent risk factors for nonlobar ICH were hypertension, prior stroke, and first-degree relative with ICH. An increasing level of education was associated with a decreased risk of nonlobar ICH. The attributable risk of apolipoprotein E2 or E4 for lobar ICH was 29%, and the attributable risk of hypertension for nonlobar ICH was 54%. CONCLUSIONS: There is significant epidemiological evidence that the pathophysiology of ICH varies by location. We estimate that a third of all cases of lobar ICH are attributable to possession of an apolipoprotein E4 or E2 allele and that half of all cases of nonlobar ICH are attributable to hypertension.