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Query: UMLS:C0038454 (stroke)
 147,016 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To investigate whether mortality risk is influenced by apolipoprotein E (APOE) genotype and whether the risk differs by ethnicity, we compared the mortality risk in 2,112 individuals > or = 65 years of age residing in northern Manhattan in New York. Mortality risks associated with the APOE genotype, adjusted for sex, high-density lipoprotein (HDL), low-density lipoprotein (LDL), and triglycerides, differed significantly by ethnic group. Among Caucasian and Hispanics, the E2/E3 genotype was associated with the lowest mortality risk in the multivariate Cox proportional hazards modeling, adjusted for lipid levels, whereas mortality risk did not differ substantially between the E4/E3 and E3/E3 genotypes. Among African-Americans, the E2/E3 genotype was not associated with the lowest mortality risk, but the E4/E3 genotype was. Adjustment for heart disease, diabetes, and stroke reduced mortality risk associated with each genotype by about 50% for all ethnic groups, but the patterns remained the same. Although we cannot rule out the possibility of a healthy survival bias, our analyses designed to examine healthy survival by comparing risk of mortality in groups who were younger or older at entry do not support this possibility. Our findings suggest that the APOE genotype is associated with mortality and that the genotypic risks differ by ethnic group. Nearly 50% of the mortality risk associated with the APOE genotype appears to act through major chronic diseases, but those diseases only partially explain the mechanism by which the genotypic risk acts. To better understand the observed ethnic differences in mortality risk by genotype, a detailed prospective study is needed to examine the relationships among APOE, other candidate genes, health conditions, and eventual death.
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PMID:Mortality and apolipoprotein E in Hispanic, African-American, and Caucasian elders. 1156 17

Clearance of infarct tissue would be an important process for tissue repair after a stroke. Delayed clearance may hamper reconstitution of the blood-brain barrier and glial boundary formation. Recent growing evidence has indicated that apolipoprotein E (APOE), a major apoprotein, plays an important role in lipid transport and homeostasis in the brain. The tissue in the infarction contains abundant lipids must be removed for tissue clearance. In the current study, the authors investigated APOE expression after focal ischemia and the functional role of APOE in tissue clearance using APOE-knockout mice. Expression of APOE was delayed, but marked, in immunohistochemistry and immunoblotting 7 days after permanent focal ischemia. Macrophages were found to express APOE in the infarct center. Infarct size was similar after focal ischemia between wild-type and APOE-knockout mice, although there was no APOE protein expression in knockout mice. However, clearance of infarct tissue 2 weeks after ischemia was significantly delayed in APOE-knockout mice compared with wild-type mice. The current study supports current thinking that APOE is a key molecule for tissue remodeling in the brain. Clearance of damaged tissue may be one of the important functions of APOE in the brain.
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PMID:Delayed, but marked, expression of apolipoprotein E is involved in tissue clearance after cerebral infarction. 1159 97

Cerebral amyloid angiopathy (CAA) due to the accumulation of amyloid beta-protein (Abeta) occurs in up to half of elderly individuals and in most cases of Alzheimer's disease (AD). Following identification of the apolipoprotein E (APOE) epsilon4 allele as a risk factor for AD, APOE epsilon4 was also found to be associated with asymptomatic CAA. The major clinical manifestation of CAA is stroke due to a lobar hemorrhage. A complex relationship between APOE epsilon4, APOE epsilon2 and hemorrhage associated with CAA (CAAH) is emerging. Pathological studies have demonstrated that APOE epsilon2 is over-represented among patients with CAAH. This remains the case for patients with co-existing Alzheimer's disease, who otherwise have a very low epsilon2 allele frequency. Other forms of intracranial hemorrhage do not share the same association, indicating that APOE epsilon2 has a specific association with CAAH. Patients with the epsilon2 allele and CAAH are more likely to have taken anticoagulant or antiplatelet medication, had hypertension or had minor head trauma than non-epsilon2 carriers. In addition, the epsilon2 allele is specifically associated with CAA-associated microangiopathic changes such as fibrinoid necrosis and concentric splitting of the vessel wall.
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PMID:APOE gene polymorphism as a risk factor for cerebral amyloid angiopathy-related hemorrhage. 1167 91

Determining the effectiveness of candidate treatments for preventing hemorrhagic strokes caused by cerebral amyloid angiopathy will require clinical drug trials. This article explores tvo potential outcome markers for such trials: (1) clinical recurrence of hemorrhagic stroke, and (2) the appearance of small, clinically silent hemorrhagic lesions on gradient-echo MRI. Using pilot data from our cohort of survivors of lobar hemorrhage, we estimated the sample sizes required to demonstrate efficacy with each of these outcome markers as the study endpoint. A study with recurrent hemorrhagic stroke as the endpoint was estimated to require 145 patients per treatment arm to demonstrate a 50% reduction in the recurrence rate over a 24-month follow-up period, while a study using new hemorrhagic lesions on MRI was estimated to require 70 patients per arm for a 17-month follow-up interval. The required sample sizes could be further reduced (to 105 and 52 patients, respectively) by limiting the analysis to those at highest risk of recurrence, defined according to apolipoprotein E genotype or the presence of more than one hemorrhagic lesion at study entry. This analysis suggests that radiographic detection of small hemorrhages may be an efficient surrogate endpoint for pilot trials of promising therapeutic approaches to cerebral amyloid angiopathy.
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PMID:Outcome markers for clinical trials in cerebral amyloid angiopathy. 1167 92

In 1992, the twelve-item Brief Smell Identification Test((R)) and, in 1992 and 1996, a variety of measures of verbal learning and memory, executive control, and global function were administered to a total of 359 individuals (286 men and 73 women; mean age in 1992 74.3 years). Individuals with a history of stroke or impaired cognition at baseline were excluded from analyses. Impaired olfactory function (present or absent) was related to a greater 4.5-year decline on several indices of verbal memory, but not to a decline on measures of executive control or of global functioning after adjustment for baseline cognitive performance, age, education, gender, and history of smell difficulties. Olfactory loss remained associated with a decline in components of verbal memory, independently of the apolipoprotein E epsilon4 status. The predictive utility of impaired smell identification in older adults appears to be specific to a decline in components of verbal memory.
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PMID:Impaired olfaction predicts cognitive decline in nondemented older adults. 1190 Dec 74

Variation in lipid levels has been associated with atherosclerotic vascular disease, including stroke. Genes contributing to interindividual variation in lipid levels may play a role in the etiology of stroke, either through their effects on lipid synthesis and metabolism or through separate pathways. For this reason, we sought to examine the association between polymorphisms in the lipoprotein lipase (LPL) and apolipoprotein E (APOE) genes and subclinical and clinical stroke in the Atherosclerosis Risk in Communities (ARIC) Study. Subclinical stroke was determined by cerebral magnetic resonance imaging (MRI). Subclinical cerebral infarct cases (n = 197) were compared to a stratified random sample identified from individuals participating in the MRI examination (n = 200). Incidence of clinical ischemic stroke was determined by following the ARIC cohort for an average of 7.5 years for potential cerebrovascular events; 218 validated clinical ischemic strokes were identified. A stratified random sample of the ARIC cohort (CRS, n = 964) was used as the comparison group for clinical cases. The LPL S291-carrying genotypes and APOE epsilon2- and epsilon4-carrying genotypes were not significantly associated with subclinical or clinical stroke. The LPL X447-containing genotypes were significantly associated with subclinical (odds ratio [OR], 4.32; 95% confidence interval [CI], 1.23-15.15; P = 0.020) and clinical stroke (hazard rate ratio [HRR], 2.57; 95% CI, 1.24-5.34; P = 0.01) in men, both by themselves and after adjustment for multiple stroke risk factors. The LPL S447X polymorphism is significantly associated with subclinical cerebral infarction and incident clinical ischemic stroke in men from a middle-aged American population. This association does not appear to be mediated by triglyceride, high-density lipoprotein (HDL)- and low-density lipoprotein (LDL)-cholesterol levels, or additional stroke risk factors.
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PMID:LPL polymorphism predicts stroke risk in men. 1192 Oct 83

One of the goals of modern medicine is to foster successful aging. In order to age successfully, one must accomplish two things: first, survive; and second, survive with good health and a sharp mind. In this discussion of apolipoproteins and aging, the focus will be on apolipoprotein E (apoE), a protein with three common isoforms, which has a large impact on longevity and successful aging. One variant of apoE (E4) is associated with increased risk for heart disease, stroke and Alzheimer's disease (AD). In addition, some of the potential mechanisms for the observed effects of apoE on aging will be discussed.
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PMID:Apolipoproteins and aging: emerging mechanisms. 1206 91

The association between apolipoprotein E (apo E) polymorphism and stroke has been controversial. So far there are no studies reported on the polymorphism of apolipoprotein E in cerebrovascular diseases in the Asian Indians. A blinded case-control study was therefore undertaken and the apo E genotypes and lipid profile of a total of 120 subjects (63 stroke patients and 57 healthy controls) were done. The frequency distribution of apo E alleles and genotypes were assessed and their relation with the occurrence of stroke in Asian Indian subjects was determined. A significantly high frequency of apo epsilon4 allele (30%) was observed in the stroke patients than the controls (11%) (p < 0.005), and patients with epsilon4 allele had a fourfold higher odds to develop stroke OR (95%CI) 4.2 (1.8-10.1) (p < 0.005). On multivariate analysis, after adjusting for age, triglycerides and hypertension, the association of epsilon4 allele with stroke was found to be no longer statistically significant, OR (95%CI) 1.2 (0.4-4.5) (p = NS). On multiple logistic regression analysis age, OR (95%CI) 1.1 (1.1-1.2) (p < 0.001), and hypertension OR (95%CI) 15.1 (2.6-89.1) (p < 0.005) were found to be independent risk factors for development of stroke. This is the first report to have examined the association of apo E gene polymorphism with stroke in the Asian Indians. This study suggests that apo epsilon4 allele, triglycerides, age and hypertension are the predictors for stroke development.
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PMID:Apolipoprotein E gene polymorphism in cerebrovascular disease: a case-control study. 1212 86

A prospective analysis of risk factors for Alzheimer's disease was a major objective of the Canadian Study of Health and Aging, a nationwide, population-based study. Of 6,434 eligible subjects aged 65 years or older in 1991, 4,615 were alive in 1996 and participated in the follow-up study. All participants were cognitively normal in 1991 when they completed a risk factor questionnaire. Their cognitive status was reassessed 5 years later by using a similar two-phase procedure, including a screening interview, followed by a clinical examination when indicated. The analysis included 194 Alzheimer's disease cases and 3,894 cognitively normal controls. Increasing age, fewer years of education, and the apolipoprotein E epsilon4 allele were significantly associated with increased risk of Alzheimer's disease. Use of nonsteroidal anti-inflammatory drugs, wine consumption, coffee consumption, and regular physical activity were associated with a reduced risk of Alzheimer's disease. No statistically significant association was found for family history of dementia, sex, history of depression, estrogen replacement therapy, head trauma, antiperspirant or antacid use, smoking, high blood pressure, heart disease, or stroke. The protective associations warrant further study. In particular, regular physical activity could be an important component of a preventive strategy against Alzheimer's disease and many other conditions.
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PMID:Risk factors for Alzheimer's disease: a prospective analysis from the Canadian Study of Health and Aging. 1219 14

Potential cerebrospinal fluid (CSF) markers for Alzheimer's disease (AD) include tau protein, the 42 amino-acid form of amyloid beta (amyloid beta(1-42)) and apolipoprotein E (apoE). To study new aspects of these protein markers, we examined consecutive CSF samples from 26 patients with acute ischemic stroke. CSF samples were taken on day 0-1, day 2-3, day 7-9, 3 weeks and 3-5 months after the stroke. CSF-tau showed a marked increase day 2-3, which peaked after 1 week and returned to normal after 3-5 months. CSF-tau also showed correlation (r=0.95; p<0.01) with the size of the infarct. In contrast, CSF-amyloid beta(1-42) and CSF-apoE showed no significant changes during the period. The marked increase in CSF-tau levels after acute ischemic stroke indicate that CSF-tau reflect the degree of neuronal damage. The reason for unchanged levels of CSF-amyloid beta(1-42) and CSF-apoE after ischemic stroke remains unclear.
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PMID:Cerebrospinal fluid markers for Alzheimer's disease evaluated after acute ischemic stroke. 1221 84


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