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

Heterozygous familial hypercholesterolemia (FH) is an autosomal dominant disorder known to be associated with elevated cholesterol levels and increased risk of premature coronary heart disease. Since increased cholesterol levels lead to atherosclerosis, FH has also been proposed as a risk factor for peripheral vascular and ischemic cerebrovascular disease. Currently, the association between clinical FH and risk of stroke is unclear: Two studies conducted in the 1980s indicated an increased risk of stroke in FH subjects; however, two others found no higher risk, and all had methodological limitations. A recent prospective study of familial hypercholesterolemia by the United Kingdom-based Simon Broome Register Group did not find an excess risk of stroke mortality for subjects with clinical FH. By contrast, the prevalence of peripheral arterial disease is increased from five- to 10-fold in FH subjects compared with non-FH controls. In addition, the intima-media thickness of the carotid and/or femoral artery is increased in FH subjects. Better understanding of the association between FH and the incidence of ischemic stroke events could have a public health impact by improving the diagnosis, prognosis, and treatment of individuals with FH and their relatives and by elucidating the relation between cholesterol levels and ischemic cerebrovascular disease.
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PMID:Familial hypercholesterolemia, peripheral arterial disease, and stroke: a HuGE minireview. 1532 39

Atherosclerosis, the primary cause of coronary artery disease (CAD) and stroke, is a disorder with multiple genetic and environmental contributions. Genetic-epidemiologic studies have identified a surprisingly long list of genetic and nongenetic risk factors for CAD. However, such studies indicate that family history is the most significant independent risk factor (15, 52, 77). Many Mendelian disorders associated with atherosclerosis, such as familial hypercholesterolemia (FH), have been characterized, but they explain only a small percentage of disease susceptibility (although a substantial fraction of early CAD). Most cases of myocardial infarction (MI) and stroke result from the interactions of multiple genetic and environmental factors, none of which can cause disease by itself. Successful discovery of these genetic factors will require using complementary approaches with animal models, large-scale human genetic studies, and functional experiments. This review emphasizes the common, complex forms of CAD.
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PMID:Genetics of atherosclerosis. 1548 48

The reduction of circulating atherogenic lipoproteins through lifestyle modification and pharmacologic intervention is an important therapeutic goal in patients at risk for acute cardiovascular events. A large number of clinical trials have demonstrated that the reduction of low-density lipoprotein cholesterol (LDL-C) is associated with significant decreases in the incidence of all cause mortality, stroke, fatal and nonfatal myocardial infarction, and the need for revascularization with coronary artery bypass grafting and percutaneous transluminal coronary angioplasty. Therapy with 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase inhibitors (i.e., statins) are the agents of choice for treating a variety of dyslipidemias, particularly when LDL-C levels are elevated. The statins are highly efficacious; however, not all patients are able to tolerate the higher doses of these medications due to adverse side-effects such as hepatoxicity and myotoxicity. Moreover, many patients cannot achieve their various lipoprotein targets at even the highest doses of these medications. Ezetimibe is a novel cholesterol absorption inhibitor that blocks the translocation of dietary and biliary cholesterol from the gastrointestinal lumen into the intracellular space of jejunal enterocytes. Ezetimibe undergoes enterohepatic recirculation with minimal systemic exposure and not does not adversely impact the pharmacokinetic profile of statins. Ezetimibe significantly reduces serum LDL-C. It is safe when used as monotherapy or when used in combination with statins. Ezetimibe is indicated in the management of hyperlipidemia, familial hypercholesterolemia, and sitosterolemia and significantly increases the percentage of patients able to reach their lipid-lowering goals.
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PMID:Cholesterol absorption blockade with ezetimibe. 1650 65

Over 800 different missense mutations in the low density lipoprotein (LDL) receptor gene (LDLR) have been identified in patients with familial hypercholesterolaemia (FH). Only two of them, including the Alanine to Threonine change at position 370 (A370T), have been discovered in FH patients but do not cause FH. The frequency of the 370T allele has been reported worldwide to be between 0.022 and 0.070, with no clear association with high cholesterol levels or risk for coronary heart disease (CHD) and stroke. To explore this relationship in more detail we have determined this genotype in 2,659 healthy middle-aged (50-61 years) men participating in the prospective Second Northwick Park Heart Study, with 236 CHD and 67 stroke incident events. The genotype distribution was in Hardy-Weinberg equilibrium and in the no-event group the frequency of 370T was 0.046 (95% CI 0.040-0.052). Overall, there was no significant association of the 370T allele with any measured plasma lipid trait, and there was no difference in genotype distribution or allele frequency between the no-event and CHD (0.059; 95% CI 0.040-0.085) or stroke (0.037; 95% CI 0.012-0.085) groups ( p= 0.18 and 0.65, respectively). There was evidence for significant interaction ( p= 0.006) between body mass index (BMI) and genotype on CHD risk, with 370A homozygotes showing the expected higher CHD risk for those with higher BMI, whilst risk for 370T allele carriers was highest in men in the lowest tertile of BMI. The explanation for this association is unclear, and may simply be chance. Thus, these data confirm the absence of a significant impact of the A370T polymorphism on LDL receptor function, at least as measured by the effect on plasma lipid levels and CHD risk.
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PMID:The A370T variant (StuI polymorphism) in the LDL receptor gene is not associated with plasma lipid levels or cardiovascular risk in UK men. 1704 44

1. Recently, we reported that 4-hydroxyderricin, one of the major chalcones in Angelica keiskei extract (ethyl acetate extract from the yellow liquid of stems), exerted hypotensive and lipid regulatory actions in stroke-prone spontaneously hypertensive rats (SHRSP). In the present study, we isolated xanthoangelol, another major chalcone in A. keiskei extract, and examined the effect of dietary xanthoangelol on blood pressure and lipid metabolism in SHRSP. 2. Six-week-old male SHRSP were fed diets containing 0.02% or 0.1% xanthoangelol (0.02 and 0.10 Xan, respectively) for 7 weeks, with free access to the diet and water. There were no significant changes in daily food intake, bodyweight or systolic blood pressure throughout the experimental period. Serum total cholesterol levels tended to decrease in the two experimental groups (albeit not significantly), which was due to a dose-dependent decrease in the cholesterol content of the low-density lipoprotein (LDL) fraction. These results suggest that dietary xanthoangelol decreases serum LDL levels. 3. In the liver, significant dose-dependent decreases in relative liver liver weight and total triglyceride content were seen in the 0.02 and 0.10 Xan groups. In addition, a significant decrease in total cholesterol content was found in the 0.10 Xan group, which may be due to an elevation of faecal cholesterol excretion in addition to the decrease in liver weight. 4. Investigation of the hepatic mRNA expression of proteins involved in lipid metabolism indicated that there was a significant increase in peroxisome proliferator-activated receptor (PPAR) alpha mRNA expression associated with the tendency for increases in acyl-coenzyme A (CoA) synthetase and acyl-CoA oxidase mRNA expression in the 0.10 Xan group, which may be responsible, at least in part, for the decrease in hepatic triglyceride content in the xanthoangelol-treated rats. In addition, a significant increase in LDL receptor mRNA expression in the 0.10 Xan group may be responsible, at least in part, for the decrease in serum LDL levels in the xanthoangelol-treated rats. 5. In conclusion, dietary xanthoangelol results in a reduction of serum LDL levels and decreases in total cholesterol and triglyceride contents in the liver of SHRSP. These beneficial effects are more effective following consumption of diet containing 0.10% xanthoangelol.
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PMID:Beneficial effect of xanthoangelol, a chalcone compound from Angelica keiskei, on lipid metabolism in stroke-prone spontaneously hypertensive rats. 1725 Jun 45

It is becoming increasingly clear that suboptimal blood glucose control results in adverse effects on large blood vessels, thereby accelerating atherosclerosis and cardiovascular disease, manifested as myocardial infarction, stroke, and peripheral vascular disease. Cardiovascular disease is accelerated by both type 1 and type 2 diabetes. In type 1 diabetes, hyperglycemia generally occurs in the absence of elevated blood lipid levels, whereas type 2 diabetes is frequently associated with dyslipidemia. In this review article, we discuss hyperglycemia versus hyperlipidemia as culprits in diabetes-accelerated atherosclerosis and cardiovascular disease, with emphasis on studies in mouse models and isolated vascular cells. Recent studies on LDL receptor-deficient mice that are hyperglycemic, but exhibit no marked dyslipidemia compared with nondiabetic controls, show that diabetes in the absence of diabetes-induced hyperlipidemia is associated with an accelerated formation of atherosclerotic lesions, similar to what is seen in fat-fed nondiabetic mice. These effects of diabetes are masked in severely dyslipidemic mice, suggesting that the effects of glucose and lipids on lesion initiation might be mediated by similar mechanisms. Recent evidence from isolated endothelial cells demonstrates that glucose and lipids can induce endothelial dysfunction through similar intracellular mechanisms. Analogous effects of glucose and lipids are also seen in macrophages. Furthermore, glucose exerts many of its cellular effects through lipid mediators. We propose that diabetes without associated dyslipidemia accelerates atherosclerosis by mechanisms that can also be activated by hyperlipidemia.
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PMID:Do glucose and lipids exert independent effects on atherosclerotic lesion initiation or progression to advanced plaques? 1752 72

A major goal of the second International Workshop on "Brain Uptake and Utilization of Fatty Acids, Lipids and Lipoproteins: Application to Neurological Disorders" was the identification of important future research areas that would lead to accelerated and systematic progress in the field. Major themes identified for future research include the following: (1) Rigorous research protocols for fatty acid (FA) studies should be established to overcome errors introduced by small differences in chain length and degree of unsaturation. (2) Using cellular integration models consisting of endothelial cells, astrocytes, and neurons, investigation of functional lipidomics, cell-specific signaling by lipids, and nutritional considerations should be undertaken. (3) Educational programs should be undertaken for women of childbearing age on the health benefits of omega3 long chain (LC) polyunsaturated fatty acids (PUFA) from fish consumption vs risks of mercury in fish. (4) Studies of the "flip-flop" model of passive diffusion should be extended to include other quantitative measures, such as the sizes of different fatty acid pools. (5) Investigations to establish physiologic roles and concentrations of omega3 LC-PUFA in various compartments of the brain should be undertaken. (6) Further studies should be carried out to illuminate the role and behavior of tight junctions in the microvascular endothelium of the blood-brain barrier and astrocytes, with emphasis on developing new LC-PUFA and lipid-based carriers of biomolecules across this barrier. (7) Roles and localization of very low density lipoproteins, low density lipoprotein (LDL), and the LDL receptor in the brain and their interactions with omega3 LC-PUFA, cholesterol, apolipoprotein E1-4, and their derivatives in Alzheimer's disease (AD) should be assessed. (8) Investigation of intraneuronal synthesis of DHA and its effects on signal transduction, apoptosis, and neurite growth stimulation should be undertaken. (9) Nutrition-based behavioral affects of EPA and DHA, particularly with respect to the omega6:omega3 FA ratio, gene regulation, neurodevelopment, and conversion to bioactive molecules by cyclooxygenases (COX) and lipoxygenase, should be explored. (10) Further assessment of brain lipid metabolism and neurodevelopment should be performed in DHA-deficient rodent models, including the use of imaging techniques. (11) Potential toxic effects of COX overexpression and the possible consequences of DHA over-supplementation in various neurological and neurodevelopmental disorders should be characterized. (12) The relationship between LC-PUFA, stroke, and AD should be clarified, and neurogenetic metabolic diseases that could benefit from supplementation with omega3 LC-PUFA such as DHA should be identified.
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PMID:Brain uptake and utilization of fatty acids, lipids & lipoproteins: recommendations for future research. 1790 59

A certain family with a history of familial hypercholesterolemia (FH) in which several members suffered cerebral infarction (CI) for 3 successive generations is reported. The first case is a 54-year-old female who suffered from medial longitudinal fasciculus syndrome caused by a lesion on the pons. The second case is the son of the first case and is a 28-year-old male who suffered from left hemiparesis by a lesion on the corona radiata. The third case is the mother of the first case and is a 77-year-old female who suffered from dizziness as a result of cerebellar lacunae. All 3 patients showed a marked elevation of their serum cholesterol level without any apparent history of coronary heart disease (CHD). Our cases are peculiar and unique because the patients are of 3 successive generations who suffer from CI without any apparent history of CHD. Moreover, the latter generations are having CI at younger ages. The mechanism of CI was thought to be the occlusion of the arteriole by the increased viscosity associated with other risk factors rather than the apparent arteriosclerosis in our cases. Although FH is often associated with a high incidence of CHD, the information about the occurrence of CI has not always been available. The patients may suffer from CI more frequently than was previously thought. We hope to point out the need for such FH patients to be carefully monitored and to be treated as a high-risk group for CI as well as CHD.
J Stroke Cerebrovasc Dis
PMID:Familial hypercholesterolemia: a family who suffered cerebral infarction over three successive generations. 1790 64

Statin reduces cerebrovascular events independent of its cholesterol lowering effect. We hypothesized that statin inhibits early atherosclerotic change in common carotid artery (CCA), and investigated its effect on lectin-like oxidized-LDL receptor-1 (LOX-1) and monocyte chemoattractant protein-1 (MCP-1) expression, both of which are early atherosclerotic markers. Stroke-prone spontaneous hypertensive rats (SHR-SP) of 8 weeks old were orally treated with vehicle or simvastatin (20mg/kg) daily. After 4 weeks of simvastatin or vehicle treatment, or 2 weeks of vehicle and 2 weeks of simvastatin treatment, CCA was removed. LOX-1 and MCP-1 expression as well as macrophage infiltration were histologically investigated. Lipid deposition was also investigated by Sudan III staining. Simvastatin groups showed significantly smaller amount of lipid deposition and LOX-1 and MCP-1 expression, independent of serum lipid levels. Macrophage infiltration was also decreased. Reduction of cerebrovascular events by statins may be brought by the direct inhibition of atherosclerotic change.
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PMID:Macrophage infiltration, lectin-like oxidized-LDL receptor-1, and monocyte chemoattractant protein-1 are reduced by chronic HMG-CoA reductase inhibition. 1804 52

The association of genetic factors and cerebral infarction (CI) has long been established. A positive family history alone is a recognized risk factor for CI and vascular events in general. However, there are certain inherited conditions that further increase the risk of stroke. These conditions are generally metabolic and mitochondrial genetic defects that have variable modes of inheritance. This article reviews major inherited metabolic disorders that predispose an individual to CI. Ten main conditions will be discussed: Fabry's disease, cerebrotendinous xanthomatosis, tangier disease, familial hypercholesterolemia, homocystinuria, methylmalonic acidemia, glutaric aciduria type I, propionic acidemia, ornithine transcarbamylase deficiency and mitochondrial encephalopathy, lactic acidosis and stroke-like phenomenon.
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PMID:Inherited metabolic disorders and cerebral infarction. 1898 43


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