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

The end-stage renal disease (ESRD) population experiences an excess morbidity and mortality due to arteriosclerotic cardiovascular disease (CVD) outcomes. Specifically, event rates for myocardial infarction and stroke are 5- to 10-fold in ESRD patients on maintenance dialysis than in the general population. Recently, there is controlled evidence that hyperhomocysteinemia occurs more commonly than any of the traditional CVD risk factors in ESRD patients. Prolonged exposure of endothelial cells to homocysteine impairs the production of nitric oxide and endothelium-dependent vasodilatation, they combine with low-density lipoprotein cholesterol to produce aggregates that are taken up by vascular macrophages in the arterial intima (foam cells), produce aggregatory effects on the platelets, and decrease endothelial antithrombotic activity due to changes in the thrombomodulin function. Current treatment regimens for ESRD hyperhomocysteinemia, which are based on the pharmacological doses of folic acid (5 to 15 mg/day), frequently result in suboptimal lowering of Hcy concentrations. Other potential therapeutic approaches (such as oral N-acetylcysteine at 1.2 g/day) merit controlled investigation.
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PMID:Hyperhomocysteinemia in end-stage renal failure. 1137 82

Stroke is a major cause of morbidity and mortality. Risk factors for stroke have been determined through prospective epidemiologic study. Control of risk factors has been demonstrated to reduce stroke incidence, either through controlled trials or inferred from observational studies. In the past few years, new approaches to the treatment of established risk factors have been discovered. These include aggressive control of hypertension in diabetes patients, prevention of type 2 diabetes through lifestyle modification, carotid endarterectomy for moderate symptomatic carotid stenosis, encouragement of a high level of physical activity, and control of abdominal obesity and elevated body mass index. In addition, new strategies for stroke prevention have been identified, including encouragement of a diet high in fruits, vegetables, whole grains, and omega-3 fatty acids, the use of vitamins B12, B6, and folic acid in hyperhomocysteinemia, and moderate alcohol consumption. Clinical trial data support the use of hydroxy-methyl-coenzyme A inhibitors in patients with coronary artery disease, and ramipril in high-risk patients with coronary artery disease and diabetes, for the primary prevention of stroke. New risk factors for stroke are being investigated, including the role of chronic inflammation and infection, and these may provide future strategies for stroke prevention.
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PMID:Prevention of strokes. 1138 98

Peripheral arterial disease affects approximately 8-10 million people in the United States. Approximately one-third to one-half of these individuals are symptomatic. The risk factors that contribute to peripheral arterial disease are similar to those associated with other forms of atherosclerosis, including diabetes mellitus, cigarette smoking, hypercholesterolemia, high blood pressure, and hyperhomocysteinemia. Of these, diabetes and cigarette smoking pose the greatest risk for developing peripheral arterial disease. The prognosis of patients with these risk factors is limited because of their greater risks for myocardial infarction, stroke, and cardiovascular death. Cardiovascular mortality correlates inversely with the ankle/brachial index, and the risk of death is greatest in those with the most severe peripheral arterial disease. Treatment regimens to reduce cardiovascular morbidity and mortality in patients with peripheral arterial disease should include risk factor modification and antiplatelet therapy. The cardinal symptoms of peripheral arterial disease include intermittent claudication and rest pain, with the latter being indicative of critical limb ischemia. Therapeutic strategies that focus on improving the patient's quality of life, reducing the severity of claudication, and improving limb viability include supervised exercise training, pharmacotherapy, and revascularization. Two drugs-pentoxifylline and cilostazol-currently are approved by the Food and Drug Administration for the treatment of patients with claudication. Meta-analyses have suggested that, compared with placebo, pentoxifylline improves maximal walking distance by approximately 20-25%. Cilostazol is a phosphodiesterase type 3 inhibitor. In clinical trials, cilostazol has consistently improved maximal walking distance as compared with placebo, with the range of improvement being approximately 40-60%. Drugs that are currently under investigation include propionyl-L-carnitine, vasodilator prostaglandins, L-arginine, and the angiogenic factors, vascular endothelial growth factor and basic fibroblast growth factors.
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PMID:Medical management of peripheral arterial disease. 1140 4

Effective and safe methods of preventing venous thromboembolism (VTE) are now widely available, but a significant proportion of patients develop VTE either because thromboprophylaxis has not been used or because the intensity of thromboprophylaxis is not matched to the level of risk. Thromboembolic risk varies widely according to the clinical setting and presence of underlying risk factors, but VTE may not be suspected even in high-risk patients. Clinical risk factors for VTE include recent surgery, cancer, stroke, previous VTE, immobilization, and advanced age. Recent attention has focused on the role of inherited and acquired molecular factors in determining overall thromboembolic risk. These factors include the classic thrombophilias-deficiencies of antithrombin III, protein C, and protein S-and several newly described molecular risk factors: factor V Leiden, the prothrombin 20210A gene mutation, and hyperhomocysteinemia. Based on emerging knowledge of risk factors, several risk assessment models (RAMs) have been devised that stratify patients according to overall VTE risk, allowing thromboprophylaxis to be tailored appropriately. Compared with older risk assessment formulas, current RAMs are simpler and include specific recommendations for thromboprophylaxis based on the available scientific evidence. Consensus documents on VTE prevention classify patients into low-, moderate-, and high-risk categories. More recently, a new risk group, very high risk, has been described. Very-high-risk patients are especially prone to thromboembolic complications and need intensive and in some cases prolonged thromboprophylaxis.
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PMID:Effective risk stratification of surgical and nonsurgical patients for venous thromboembolic disease. 1144 39

Large randomized, controlled trials of total homocysteine-lowering therapy for the potential reduction of cardiovascular disease outcomes are ongoing in the United States and Canada. These trials are the Vitamin Intervention for Stroke Prevention (VISP) trial, the Women's Antioxidant Cardiovascular Disease Study (WACS), and the Heart Outcomes Prevention Evaluation (HOPE-2). However, the dramatic effect of policies mandating fortification of cereal grain flour products with folic acid may reduce the statistical power of these trials. All three trials assume that the active treatment groups will achieve the same mean effects of total homocysteine-lowering therapy as those reported in the absence of folic acid-fortified cereal grain flour. This paper examines this assumption using data from studies of total homocysteine-lowering therapy in U.S. and Canadian patients with cardiovascular disease who were exposed to products made with folic acid-fortified cereal grain flour. These data showed that the VISP trial, HOPE-2, and WACS will probably achieve only approximately 20% to 25% of the projected treatment effects of mean total homocysteine-lowering therapy (1.0 to 1.5 micromol/L vs. 4.0 to 6.0 micromol/L). As a result, all three trials will be substantially underpowered to test the specific hypotheses of total homocysteine-lowering therapy identified a priori. In contrast, renal transplant recipients have a persistent excess prevalence of hyperhomocysteinemia in the era of fortification but remain very responsive to supraphysiologic doses of folic acid-based supplementation (mean reduction in total homocysteine level, 5.0 to 6.0 micromol/L). Therefore, unlike other populations with normal renal function that are at high risk for cardiovascular disease but are profoundly affected by fortification efforts, renal transplant recipients continue to merit serious consideration for a controlled trial of the "homocysteine hypothesis."
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PMID:Power Shortage: clinical trials testing the "homocysteine hypothesis" against a background of folic acid-fortified cereal grain flour. 1218 26

Hyperhomocysteinemia is known to be associated with an increased risk of myocardial infarction, stroke, peripheral arterial disease, and venous thrombosis. Gene polymorphisms in methylenetetrahydrofolate reductase (MTHFR) and methionine synthase (MS) may account for reduced enzyme activity and hyperhomocysteinemia. A recent study has documented evidence of polygenic regulation of plasma homocyteine. We report here on a case of occlusive stroke at young age and hyperhomocysteinemia with homozygous VN (677C to T) variant in the MTHFR gene as well as homozygous D/D (2756G to A) variant in the MS gene.
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PMID:Homozygous VN (677C to T) and d/D (2756G to A) variants in the methylenetetrahydrofolate and methionine synthase genes in a case of hyperhomocysteinemia with stroke at young age. 1146 Aug 81

Authors discussed the known risk factors of venous thromboembolism (VTE), which is complex disease with two manifestations: deep venous thrombosis (DVT) and pulmonary embolism (PE). Acquired risk factors of VTE are following: age over 40 years, bed rest, surgery, trauma, cancer, myocardial infarction, ischemic stroke, use of oral contraceptives, hormone-replacement therapy, pregnancy and puerperium, previous VTE, long lasting travel and presence of antiphospholipid antibodies. Group of genetic defects predisposing to thromboembolic events are called thrombophilia. The best known causes of thrombophilia are: resistance to activated protein C (factor V Leiden), the prothrombin 20210A, protein C deficiency, protein S deficiency, antithrombin deficiency, hyperhomocysteinemia and abnormality in the fibrinolytic system. Genetic predisposition to thrombosis may be detected in up to one-third of patients with VTER and more than 50% of patients with familial thrombosis. Detection of factor V Leiden is important for patients: with recurrent incidences of VTE, with other known causes of thrombophilia and in members of families with frequent occurrence of VTE. It is important also to detect deficiency of: protein C, protein S and especially of antithrombin in patient with previous VTE, because such patients have 8 to 10 fold increase risk of next incident of VTE. Chronic prevention of thrombosis should be used in all these cases.
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PMID:[Risk factors of venous thromboembolism]. 1155 14

Moderate hyperhomocysteinemia and endothelial dysfunction are consistent findings in uremic patients. Although an exceedingly high incidence of cardiovascular disease and stroke has been shown in dialysis patients, several traditional risk factors are relatively limited predictors. Hyperhomocysteinemia could be a principal candidate for endothelial dysfunction. Recent findings suggest that hyperhomocysteinemia may impair endothelial function by the generation of oxygen species and decreased nitric oxide (NO) bioavailability. However, the precise mechanisms underlying the link between hyperhomocysteinemia and impaired endothelial function in chronic renal failure remain unclear. Endothelial function was evaluated by the response to reactive hyperemia and donor of NO. We observed impairment in both endothelium-dependent and endothelium-independent vasodilation in dialysis patients. These data suggest that patients with chronic renal failure may have defective NO-mediated function in the endothelium and smooth muscle of vessels. Most reports have shown only impairment of endothelium-dependent vasodilation, whereas another report observed impaired smooth muscle function and intact endothelial function. Only a few previous observations included a full set of vascular function data, such as baseline vessel diameter, reactive hyperemia, and responses of endothelium to hyperemia and NO donor, although all these observations could be essential for comparison with other reports. Treatment with folic acid was reported to reduce plasma homocysteine levels, but not to normal levels, and failed to improve impaired endothelial function in patients in a predialysis phase and on maintenance dialysis therapy. Another investigation, directed at reducing homocysteine levels in earlier stages of renal failure, may be necessary to clarify the link between hyperhomocysteinemia and endothelial function.
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PMID:Association of endothelial dysfunction with sulfur amino acid metabolism in chronic renal failure. 1157 31

Hyperhomocysteinemia is the result of a disturbed methionine metabolism. It results from enzyme and/or vitamin deficiency. Epidemiological studies have proven, that hyperhomocysteinemia is a risk factor for atherosclerotic cardiovascular diseases, stroke, peripheral arterial occlusive disease and venous thrombosis. Conflicting results come from prospective studies. Trials which are now in progress may clarify the "causality" of high homocysteine concentrations and will assess the value of homocysteine-lowering therapy. The induction of the atherogenic process by hyperhomocysteinemia seems to be associated with an alteration of endothelial and smooth muscle cell function leading to an accelerated formation of reactive oxygen species. An increased endothelial expression of adhesion molecules will then lead to an enhanced deposition of oxidized LDL in the vessel wall with the formation of foam cells. Additionally, hyperhomocysteinemia interferes with the coagulation system and thus also has prothrombotic effects. There is a high prevalence of hyperhomocysteinemia as a sign of a vitamin deficiency in elderly subjects which strongly increases with age. Elderly people have a high frequency of vitamin B12 deficiency which can be diagnosed more reliably by the measurement of serum methylmalonic acid (MMA) level than by serum vitamin B12. Subjects following a strict vegetarian diet also have a high prevalence of hyperhomocysteinemia caused by functional vitamin B12 deficiency (increased MMA level). Last but not least, hyperhomocysteinemia is a factor in the pathogenesis of neural tube defects and pre-eclampsia. An early diagnosis of vitamin B12 deficiency is important for the prevention of neurological damages. Homocysteine should be measured in patients with a history of atherothrombotic vessel diseases, in patients with diabetes or hyperlipidemia, in renal patients, in obese subjects, in elderly people, in postmenopausal women, and in early pregnancy. A specific diagnosis of an underlying vitamin deficiency is important for adequate treatment. Individuals with homocysteine level >12 micromol/l should increase and/or supplement their dietary intake of vitamins.
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PMID:The importance of hyperhomocysteinemia as a risk factor for diseases: an overview. 1159 31

An inborn error of metabolism, homocystinuria due to cystathionine beta-synthase deficiency, results in markedly elevated levels of circulating homocysteine. Premature vascular events are the main life-threatening complication. Half of all untreated patients have a vascular event by 30 years of age. We performed a multicenter observational study to assess the effectiveness of long-term homocysteine-lowering treatment in reducing vascular risk in 158 patients. Vascular outcomes were analyzed and effectiveness of treatment in reducing vascular risk was evaluated by comparison of actual to predicted number of vascular events, with the use of historical controls from a landmark study of 629 untreated patients with cystathionine beta-synthase deficiency. The 158 patients had a mean (range) age of 29.4 (4.5 to 70) years; 57 (36%) were more than 30 years old, and 10 (6%) were older than 50 years. There were 2822 patient-years of treatment, with an average of 17.9 years per patient. Plasma homocysteine levels were markedly reduced from pretreatment levels but usually remained moderately elevated. There were 17 vascular events in 12 patients at a mean (range) age of 42.5 (18 to 67) years: pulmonary embolism (n=3), myocardial infarction (n=2), deep venous thrombosis (n=5), cerebrovascular accident (n=3), transient ischemic attack (n=1), sagittal sinus thrombosis (n=1), and abdominal aortic aneurysm (n=2). Without treatment, 112 vascular events would have been expected, for a relative risk of 0.09 (95% CI 0.036 to 0.228; P<0.0001). Treatment regimens designed to lower plasma homocysteine significantly reduce cardiovascular risk in cystathionine beta-synthase deficiency despite imperfect biochemical control. These findings may be relevant to the significance of mild hyperhomocysteinemia that is commonly found in patients with vascular disease.
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PMID:Vascular outcome in patients with homocystinuria due to cystathionine beta-synthase deficiency treated chronically: a multicenter observational study. 1174 88


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