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

Despite the decline in coronary heart disease in many European countries, the disease remains an enormous public health problem. Although we know a great deal about environmental risk factors for coronary heart disease, a heritable component was recognized a long time ago. The earliest and best known examples of how our genetic constitution may determine cardiovascular risk relate to lipoprotein(a), familial hypercholesterolaemia and apolipoprotein E. In the past 20 years a fair number of polymorphisms assessed singly have shown strong associations with the disease but most are subject to poor repeatability. Twins constitute a compelling natural experiment to establish the genetic contribution to coronary heart disease and its risk factors. GenomEUtwin, a recently funded Framework 5 Programme of the European Community, affords the opportunity of comparing the heritability of risk factors in different European Twin Registries. As an illustration we present the heritabilities of systolic and diastolic blood pressure, based on data from over 4000 twin pairs from six different European countries and Australia. Heritabilities for systolic blood pressure are between 52 and 66% and for diastolic blood pressure between 44 and 66%. There is no evidence of sex differences in heritability estimates and very little to no evidence for a significant contribution of shared family environment. A non-twin based prospective case/cohort study of coronary heart disease and stroke (MORGAM) will allow hypotheses relating to cardiovascular disease, generated in the twin cohorts, to be tested prospectively in adult populations. Twin studies have also contributed to our understanding of the life course hypothesis, and GenomEUtwin has the potential to add to this.
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PMID:The genetics of coronary heart disease: the contribution of twin studies. 1462 27

The literature on the association between apolipoprotein E (ApoE) and mortality across ethnic and age groups has been inconsistent. No studies have looked at this association in developing countries. We used data from the Indianapolis-Ibadan Dementia study to examine this association between APOE and mortality in 354 African-Americans from Indianapolis and 968 Yoruba from Ibadan, Nigeria. Participants were followed up to 9.5 years for Indianapolis and 8.7 years for Ibadan. Subjects from both sites were divided into 2 groups based upon age at baseline. A Cox proportional hazards regression model adjusting for age at baseline, education, hypertension, smoking history and gender in addition to time-dependent covariates of cancer, diabetes, heart disease, stroke, and dementia was fit for each cohort and age group. Having ApoE epsilon4 alleles significantly increased mortality risk in Indianapolis subjects under age 75 (hazard ratio: 2.00; 95% CI: 1.19-3.35; p = 0.0089). No association was found in Indianapolis subjects 75 and older (hazard ratio: 0.71; 95% CI: 0.45-1.10; p = 0.1238), Ibadan subjects under 75 (hazard ratio: 1.04; 95% CI: 0.78 to 1.40; p = 0.7782), or Ibadan subjects over 75 (hazard ratio: 1.21; 95% CI: 0.83 to 1.75; p = 0.3274).
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PMID:Apolipoprotein E and mortality in African-Americans and Yoruba. 1464 29

A 74-year-old woman had a history over 25 years of endarterectomy of both renal arteries, iliac venous thrombosis, pulmonary embolism, left internal carotid artery endarterectomy, coronary angioplasty, aortocoronary bypass grafting, occlusion of the right axillary artery, lower-limb claudication due to common iliac artery aneurysm, external iliac artery stenosis, multiple femoral artery stenoses, bifurcational stent grafting, occlusion of the left brachial artery and the right external iliac artery, and stroke. Assessment of the risk-factor profile revealed an absence of classic risk factors but the presence of the factor V Leiden mutation, the methylenetetrahydrofolate reductase AI298C mutation, the HFE C282Y mutation, plasminogen activator inhibitor-1 gene mutation, the -455 G/A fibrinogen gene polymorphism, the epsilon3/epsilon4 apolipoprotein E -675 4G gene polymorphism, and hyperhomocysteinemia. This case shows that severe, generalized, occlusive vascular disease may be due to the combination of various genetic risk factors for atherosclerosis and venous thromboembolism.
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PMID:Risk-factor profile in severe, generalized, obliterating vascular disease. 1474 32

To explore the clinical effects of inflammation associated with vascular deposits of the amyloid beta peptide (A beta), we analyzed 42 consecutive patients with pathologically diagnosed cerebral amyloid angiopathy (CAA) for evidence of an inflammatory response. Inflammation with giant-cell reaction surrounding amyloid-laden vessels was identified in 7 of the 42 cases. The clinical symptoms in each of the seven were subacute cognitive decline or seizure rather than hemorrhagic stroke, the primary clinical presentation in 33 of 35 patients with noninflammatory CAA (p < 0.001). Inflammatory CAA also was associated with radiographic white matter abnormalities, significantly younger age at presentation, and a marked overrepresentation of the apolipoprotein E epsilon 4/epsilon 4 genotype (71% vs 4%, p < 0.001). Of the six inflammatory CAA patients with available follow-up information, five demonstrated clinical and radiographic improvement after immunosuppressive treatment. The syndrome of CAA-related perivascular inflammation appears to represent a subset of CAA with clinically distinct symptoms that may respond to immunosuppressive treatment. These data add to evidence that inflammation against A beta can cause vascular dysfunction, a potential mechanism for the toxic response recently observed in clinical trials of A beta immunization.
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PMID:Clinical manifestations of cerebral amyloid angiopathy-related inflammation. 1475 29

Fasting hyperinsulinemia is associated with an increased risk of atherosclerotic complications, namely heart attack and stroke, which has led to the concept that insulin may promote atherosclerosis despite the absence of any evidence that insulin is atherogenic either in humans or in experimental models. Recent evidence shows that insulin exerts vasodilatory, antiplatelet, and anti-inflammatory effects at the cellular level in vitro and in humans in vivo. Because atherosclerosis is an inflammatory process, insulin is probably antiatherosclerotic in the long-term. Recent data on experimental atherosclerosis in mice show that (a) insulin administration reduces the number and the size of atherosclerotic lesions in apolipoprotein E null mice; and (b) in insulin receptor substrate-2 null mice, the interruption in insulin signal transduction results in enhanced atherogenicity. The use of a low dose of insulin infusion in patients with acute myocardial infarction (AMI) has been shown to markedly improve clinical outcomes both in diabetic and nondiabetic patients. The authors' most recent data show that a low-dose infusion of insulin in patients with AMI induces a reduction in inflammation (C-reactive protein and serum amyloid A) and oxidative stress and may have a role in myocardial protection. The authors conclude that insulin is both anti-inflammatory and antiatherogenic and may be of use in the treatment of cardiovascular inflammatory conditions, including AMI.
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PMID:Insulin as an anti-inflammatory and antiatherosclerotic hormone. 1498 4

Activation of the 5-lipoxygenase (5-LO) pathway leads to the biosynthesis of proinflammatory leukotriene lipid mediators. Genetic studies have associated 5-LO and its accessory protein, 5-LO-activating protein, with cardiovascular disease, myocardial infarction and stroke. Here we show that 5-LO-positive macrophages localize to the adventitia of diseased mouse and human arteries in areas of neoangiogenesis and that these cells constitute a main component of aortic aneurysms induced by an atherogenic diet containing cholate in mice deficient in apolipoprotein E. 5-LO deficiency markedly attenuates the formation of these aneurysms and is associated with reduced matrix metalloproteinase-2 activity and diminished plasma macrophage inflammatory protein-1alpha (MIP-1alpha; also called CCL3), but only minimally affects the formation of lipid-rich lesions. The leukotriene LTD(4) strongly stimulates expression of MIP-1alpha in macrophages and MIP-2 (also called CXCL2) in endothelial cells. These data link the 5-LO pathway to hyperlipidemia-dependent inflammation of the arterial wall and to pathogenesis of aortic aneurysms through a potential chemokine intermediary route.
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PMID:The 5-lipoxygenase pathway promotes pathogenesis of hyperlipidemia-dependent aortic aneurysm. 1534 Apr 8

Cohort studies show that having a positive family history of stroke increases the odds of having a stroke by approximately 30%. The heritability of stroke appears to be heterogeneous across ischemic stroke subtypes, with cardioembolic stroke being least heritable. The relative influence of stroke risk attenuates with age, but genetics does not cease to be relevant in later adulthood. Recent family history and twin studies suggest that genetic factors remain relevant even beyond the seventh decade of life. One of the challenges of gene discovery in stroke relates to the complexities of phenotype. The complexities of phenotype can be addressed by focusing on individual ischemic stroke subtypes or by studying intermediate phenotypes like leukaraiosis, which has a heritability of approximately 70%. Although most stroke genetics research has focused on the identification of risk factor genes, an independent set of genes likely influences poststroke outcomes (for example, apolipoprotein E) and response to drug therapies (example, alpha-adducin and diuretic therapy).
Stroke 2004 Nov
PMID:Clinically translated ischemic stroke genomics. 1535 68

Human apolipoprotein E (apo E) alleles are polymorphic with significantly different frequencies among different ethnic groups and have been associated with increased risk of coronary heart disease, and postulated as a major genetic susceptibility locus for Alzheimer's disease. Studies undertaken in different populations have shown different association patterns between apo E genotype and stroke. The aim of this study was to determine the risk of apo E genotype in stroke patients living in the eastern part of Turkey. The apo E genotypes and allele frequencies of 229 individuals from the same geographic area were determined by polymerase chain reaction and restriction fragment length polymorphism, of which 103 were patients with a documented history of stroke without other apparent dementia and 126 age-matched healthy subjects as a control group. A reduced E3/4 genotype frequency was found in subjects with stroke and the E2/3 genotype frequency was elevated in patients with previous stroke. There was no association between apo E epsilon4 allele and stroke. The APOE alleles had divergent effects in this population. Association between APOE (the gene) alleles and stroke in this population may be altered due to interaction with other genetic effects. The effects of APOE alleles and genotypes require further study in different populations.
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PMID:Apolipoprotein E polymorphism and stroke in a population from eastern Turkey. 1537 Jan 97

Stroke is a common entity. It is the third leading cause of death and the leading cause of adult disability in the developed world. More than 110 heritable disorders, more than 175 genetic loci, and more than 2050 unique mutations predisposing to stroke are known. Although ischemic stroke can result from merely one gene defect (and a number of clearly defined mendelian hereditary disorders do lead to stroke), the interaction of unfavorable genetic factors such as the Leiden V, methylenetetrahydrofolate reductase (MTHFR) 677TT, apolipoprotein E (ApoE) 4, and angiotensin-converting enzyme (ACE) D/D genotypes, which alone are not major risk factors, can in specific patterns exert a synergistic effect on certain clinical risk factors. This chapter discusses how to evaluate these interactions and the interpretation of findings.
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PMID:Evaluation of the interactions of common genetic mutations in stroke. 1545 71

Ischemic stroke is thought to have a polygenic basis, but identification of stroke susceptibility genes and quantification of associated risks have been hampered by conflicting results from underpowered case-control studies. We performed a meta-analysis of all candidate gene association studies in ischemic stroke. Electronic databases were searched up until January 2003 for all case-control and nested case-control studies in English-language journals relating to the investigation of any candidate gene for ischemic stroke in humans. Cases were required to have neuroimaging evidence of the diagnosis. To maintain genetic homogeneity, only studies in white adults were included. Studies that evaluated quantitative traits or intermediate phenotypes were excluded. Data from 120 case-control studies were included. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) from random- and fixed-effects models were calculated. Of 32 genes studied, 15 polymorphisms were identified for which at least 3 studies had been conducted. Statistically significant associations with ischemic stroke were identified for factor V Leiden Arg506Gln (OR, 1.33; 95% CI, 1.12-1.58), methylenetetrahydrofolate reductase C677T (OR, 1.24; 95% CI, 1.08-1.42), prothrombin G20210A (OR, 1.44; 95% CI, 1.11-1.86), and angiotensin-converting enzyme insertion/deletion (OR, 1.21; 95% CI, 1.08-1.35). These were also the most investigated candidate genes, including 4588, 3387, 3028, and 2990 cases, respectively. No statistically significant association with ischemic stroke was detected for the 3 next most investigated genes (factor XIII, apolipoprotein E, and human platelet antigen type 1). There is a genetic component to common stroke. No single gene with major effect was identified; rather, common variants in several genes, each exerting a modest effect, contribute to the risk of stroke. These findings have important implications for the design of future genetic studies and for predictive genetic testing for stroke and other multifactorial diseases.
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PMID:Meta-analysis of genetic studies in ischemic stroke: thirty-two genes involving approximately 18,000 cases and 58,000 controls. 1553 75


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