Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0038454 (stroke)
 147,016 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The primary objectives of claudication treatment are to reduce cardiovascular mortality and improve walking ability. Patients with claudication have 60% mortality over 10 years, with most deaths due to myocardial infarction and stroke. Aggressive risk-factor modification is required in all these patients, particularly smoking cessation, lipid modification, and treatment of hypertension, diabetes and elevated homocysteine levels. Aspirin, ticlopidine and clopidogrel are all effective in reducing the risk of myocardial infarction, stroke and vascular death, and thus antiplatelet therapy should be considered in all claudicants. Patients with disabling claudication should be considered for therapies that relieve claudication pain and improve exercise performance, the most effective being exercise training and smoking cessation. Pentoxifylline, the only approved claudication drug in the United States, has modest efficacy in improving treadmill exercise performance. Other drugs shown to be of some benefit in patients with claudication include propionyl-L-carnitine, cilostazol and possibly prostaglandin derivatives. Several antiplatelet agents and angiogenic growth factors are also being evaluated for the treatment of claudication.
 ...
PMID:Current and future drug therapies for claudication. 954 77

A polymorphism associated with a thermolabile variant (C677T) of the enzyme methylenetetrahydrofolate reductase has been associated with both elevated total homocysteine (tHcy) levels and risk for cardiovascular disease. Data from the Stroke Prevention in Young Women Study were used to determine the prevalence of the C677T genotype and to assess whether environmental factors modified the association between genotype and tHcy concentration. The C677T genotype prevalence was 80% -/-, 20% +/-, and 0% +/+ among 46 African-American women; and 39% -/-, 53% +/-, and 8% +/+ among 77 white women (P < 0.01). There was a trend toward higher tHcy levels in African-American women with the +/- genotype when compared with the -/- genotype (6.9 mumol/L vs 5.3 mumol/L respectively, p = 0.10); no association was found among the white women (6.0 mumol/L, -/-; 4.5 mumol/L, +/-; and 6.2 mumol/L, +/+; p = 0.67). Among African American women, those who smoked and were +/- genotype had the highest tHcy levels (8.0 mumol/L); while among white women, those who smoked and were -/- had the highest tHcy levels (8.1 mumol/L). Despite being hampered by a limited sample size, the thermolabile allele is significantly less common among African-American than white women. The association between genotype and tHcy concentration is influenced by smoking and multivitamin use.
 ...
PMID:Thermolabile methylenetetrahydrofolate reductase polymorphism (C677T) and total homocysteine concentration among African-American and white women. 968 Dec 81

Hyperhomocysteinemia is a condition which, in the absence of kidney disease, indicates a disrupted sulfur amino acid metabolism, either because of vitamin deficiency (folate, B12 and B6) or a genetic defect. Epidemiologic evidence suggests that mild hyperhomocysteinemia is associated with increased risk of arteriosclerotic disease and stroke. The relationship between hyperhomocysteinemia and thrombosis has been investigated in 10 studies involving a total of 1200 patients and 1200 controls. Eight of these studies demonstrated positive association with odds ratios that ranged from two to 13. This association was enhanced by including a methionine loading test. There is some evidence which suggests that hyperhomocysteinemia and activated protein C resistance have synergistic effect on the onset of thrombotic disease. Recent studies with animal models for mild hyperhomocysteinemia provided encouraging results in the understanding of the mechanism that underlies this relationship between mild elevations of plasma homocysteine and vascular disease. These animal models pointed to the possibility that the effect of elevated homocysteine is multifactorial, affecting both the vascular wall structure and the blood coagulation system.
 ...
PMID:Relationship between homocysteine and thrombotic disease. 970 66

Hyperhomocyst(e)inemia has been identified as an independent risk factor for atherosclerotic and thromboembolic diseases such as coronary artery disease, cerebral artery disease, and venous thrombosis. Recently, the alanine/valine (A/V) gene polymorphism of 5,10-methylenetetrahydrofolate reductase (MTHFR), one of the key enzymes that catalyzes the remethylation of homocysteine, was reported. The VV genotype is correlated with increased plasma homocyst(e)ine levels as a result of the reduced activity and increased thermolability of this enzyme. In this study, we examined the association between the V allele of the MTHFR gene and ischemic stroke in an elderly Japanese population. The diagnosis of cerebral infarction of all study patients was confirmed by CT of the brain. The MTHFR genotype was analyzed by polymerase chain reaction followed by HinfI digestion. In 256 stroke patients and 325 control subjects, the frequencies of the V allele were 0.45 and 0.32, respectively. The odds ratios and 95% confidence intervals adjusted for the other risk factors were, respectively, 1.51 (1.02 to 2.23) for the AV genotype and 3.35 (1.94 to 5.77) for the VV genotype compared with the AA genotype. Both of these effects were statistically significant (P=0.041 and P<0.001, respectively). In patients with multiple infarcts in particular, the allele frequency of the V mutation was 0.56, and the association between the V allele and stroke was highly significant. Plasma homocyst(e)ine levels were significantly higher in patients with the VV genotype than in patients with the AA or AV genotype, especially those with low plasma folate levels. The V allele of the MTHFR gene was significantly associated with cerebral infarction in an elderly Japanese population in a codominant manner. The VV genotype may contribute to risk for ischemic stroke through a predisposition to increased plasma homocyst(e)ine levels, and dietary folate supplementation may be of benefit, particularly to patients with this genotype.
 ...
PMID:Methylenetetrahydrofolate reductase gene polymorphism and ischemic stroke in Japanese. 974 36

The authors report the occurrence of vascular occlusion due to hyperhomocysteinemia without significant underlying atherosclerotic disease. This unique observation supports the potential of hyperhomocysteinemia to induce thrombosis and the independence of the thrombosis from hyperhomocysteinemia's associated atherosclerosis. The case demonstrates the clinical relevance of the effects of hyperhomocysteinemia on the coagulation cascade. A 42-year-old woman who lacked signs of classic homocystinuria developed disseminated thrombosis with a 24-hour urine homocysteine concentration of 384 mg, twelve times the upper limit of normal. Thrombosis was present in the aortic arch and its major branches and in the mesenteric arteries and veins. A fatal stroke resulted from the thrombosis. Autopsy revealed minimal atherosclerotic disease and no complicated plaques. This case demonstrates an expanded role of hyperhomocysteinemia in clinically significant vascular occlusion. Serum homocysteine concentration determination may be a factor in the evaluation of a hypercoagulable state. Hyperhomocysteinemia should be considered when evaluating arterial or venous thrombosis in a young person regardless of whether atherosclerosis or other signs of abnormal homocysteine metabolism are present.
 ...
PMID:Homocysteine associated hypercoagulability and disseminated thrombosis--a case report. 975 29

Hyperhomocysteinemia is now recognized as a common risk factor for thrombotic vascular events such as stroke, myocardial infarction, and venous thrombosis. Studies of cultured cells in vitro indicate that homocysteine has prothrombotic effects on the endothelium and vascular smooth muscle. An association between moderate hyperhomocysteinemia and vascular dysfunction was confirmed in recent studies in animals and humans. Current models propose that dysregulation of homocysteine metabolism may impair vascular function through mechanisms involving oxidant stress or altered cellular methylation. Although moderate hyperhomocysteinemia can be treated effectively by administration of folic acid and other B vitamins, the clinical benefit of this therapeutic approach has not been proven in patients with thrombosis.
 ...
PMID:Mechanisms of thrombosis in hyperhomocysteinemia. 977 14

Fasting hyperhomocysteinemia is an independent risk factor for coronary artery disease, stroke, peripheral vascular atherosclerosis, and for arterial and venous thromboembolism. The risk for cardiovascular disease with homocysteine is similar to conventional risk factors. The interaction of hyperhomocysteinemia with hypertension and smoking is strong and the combined effect is more than multiplicative. The combined effect of homocysteine and cholesterol is additive. Homocysteine produces atherosclerosis, thromboembolism, and vascular endothelial cell injury. Vascular dysfunction produced by homocysteine may be due to endothelial cell damage. Homocysteinemia-induced atherosclerosis is probably due to various factors including endothelial cell injury, inability to sustain S-nitroso-homocysteine formation because of imbalance between production of nitric oxide by dysfunctional endothelium and homocysteine, smooth muscle cell proliferation, and thromboembolism. There is strong evidence that endothelial cell injury is associated with oxidative stress produced by homocysteine. Hyperhomocysteinemia is associated with numerous conditions, including coronary disease, stroke, peripheral vascular disease (carotid artery and cerebrovascular atherosclerosis), venous thrombosis, renal disease, diabetes mellitus, and organ transplant. Folic acid, vitamin B12 and B6 have been shown to be beneficial in reducing plasma homocysteine levels. Folic acid is specifically very effective, safe and inexpensive.
 ...
PMID:Homocysteine, a Risk Factor for Cardiovascular Disease. 982 15

Peripheral arterial disease has received less attention from epidemiologists than coronary and cerebrovascular disease. Prevalence and incidence data typically show that peripheral arterial disease increases with age, is more common in men than women, and that symptomatic disease is only the tip of the iceberg. Studies concerning the prevalence of peripheral arterial disease rely mainly on the Rose questionnaire, which is used to screen for intermittent claudication, and on the ankle/brachial index, used to detect asymptomatic disease. Although there is a certain parallel between the 2 sets of data, the figures for asymptomatic disease consistently surpass those for clinical disease, and there is a wide variation between frequencies obtained in individual studies. In general, the prevalence of peripheral arterial disease is estimated to be under 2% for men aged less than 50 years, increasing to over 5% in those aged more than 70 years. Women reach these rates almost 10 years after men, although this gender difference decreases with increasing age. Figures for incidence follow a similar trend. The incidence of chronic critical ischaemia is estimated to be between 0.05% and 0.1% of the population. Asymptomatic disease detected with noninvasive tests is 3 to 4 times more frequent than intermittent claudication: its prevalence increases from under 5% for individuals aged less than 50 years to over 20% for individuals aged more than 70 years. The classical risk factors for atherosclerosis also apply to peripheral arterial disease, although their order of importance may be different from that for coronary and carotid disease. Several studies have shown that peripheral arterial disease correlates most strongly with cigarette smoking. Smoking is also the single greatest predictor of the progression of peripheral arterial disease. Other risk factors include hypertension, raised lipid levels (cholesterol and triglycerides for severe disease), diabetes, increased plasma viscosity, fibrinogen and homocysteine levels. Divergent views have been expressed in individual epidemiological studies with regard to the respective contribution of these risk factors to the development and progression of peripheral arterial disease. The natural history of peripheral arterial disease is characterised by a relatively benign local evolution. It can be estimated that, in general, 3 of 4 men presenting with intermittent claudication will never have a serious problem necessitating vascular intervention, and that no more than 5% are ever likely to require a major amputation. However, the underlying atherosclerotic pathology progresses with time: nondiseased arteries become obliterated and disease with an initially unilateral pattern frequently progresses to become bilateral. In addition, the few patients who do progress to critical ischaemia are at a significantly higher risk of amputation. The general prognosis for patients with peripheral arterial disease is particularly negative. There is a high prevalence of coronary heart disease and cerebrovascular disease in such patients, although the exact percentages depend on the patient population selected and on the method used for their evaluation. Coronary heart disease is detected in 40 to 60% of patients through a medical history combined with electrocardiography, while systematic coronary angiography detects coronary heart disease in 90% of those undergoing surgery. Although few patients with peripheral arterial disease have a history of stroke, in studies of surgical patients almost 30% appear to have significant extracranial disease. Patients with peripheral arterial disease have a poor life expectancy: the mortality rate is 3 to 5% per year in those with intermittent claudication and 20% per year in those with critical ischaemia. Coronary heart disease accounts for half of the total mortality, while vascular disease in general accounts for almost two-thirds.
 ...
PMID:[Epidemiology and prognosis of peripheral obliterative arteriopathy]. 984 97

Hyperhomocysteinemia is an independent risk factor for atherosclerotic disease in the middle-aged. We investigated whether a high serum homocysteine level is a risk factor for vascular disease in 878 elderly men (mean age at baseline, 71.5 years; range, 64 to 84 years) in a population-based, representative cohort followed up for 10 years in Zutphen, the Netherlands. Thirty-one percent had nonfasting homocysteine levels >/=17 micromol/L. After adjustment for other major risk factors, high homocysteine levels at baseline (the third compared with the first tertile) were associated with an increased baseline prevalence of myocardial infarction (odds ratio [OR], 1.81; 95% confidence interval [CI], 1.07 to 3.08; P for trend, 0.03) and with a marginally significant increase in the risk of dying of coronary heart disease (relative risk [RR], 1.58; 95% CI, 0.93 to 2.69; P for trend, 0.09) but not with an increased risk of first-ever myocardial infarction. In addition, high homocysteine levels at baseline were associated with an increased baseline prevalence of stroke (OR, 4.61; 95% CI, 1.79 to 11.89; P for trend, 0.002) and with an increased risk of dying of cerebrovascular disease in subjects without hypertension (RR, 6.18; 95% CI, 2.28 to 16.76) but not in those with hypertension. High homocysteine levels were associated with an increased risk of first-ever stroke among normotensive subjects that was not statistically significant (RR, 1. 77 [95% CI, 0.83 to 3.75; P for trend, 0.14]). In a general population of elderly men, a high homocysteine level is common and is strongly associated with the prevalence of coronary heart disease and cerebrovascular disease. It is a strong predictive factor for fatal cerebrovascular disease in men without hypertension but less so for coronary heart disease.
 ...
PMID:Serum homocysteine and risk of coronary heart disease and cerebrovascular disease in elderly men: a 10-year follow-up. 984 81

The authors report the case of a young woman (47 yrs old) who underwent cardiac evaluation for recurrent unexplained cerebral transient ischemic attacks. In the search for a source of embolization, a transesophageal echocardiography was performed and this revealed an atherosclerotic complex plaque of the ascending aorta as the sole potential source of cerebral embolism, while the remaining aortic wall was normal. The atheroma showed a calcific portion inserted on the aortic wall and a mobile hypoechogenic portion protruding into the aortic lumen. Furthermore, we found increased levels of cholesterol, fibrinogen and plasmatic homocysteine after methionine loading. Atherosclerotic lesions of the aortic arch are a rare cause of embolism in young patients with stroke, but they can lead to important complications such as thrombosis and embolism, similar to atherosclerotic lesions in elderly patients. The mechanisms that predispose for atherosclerosis of the aorta in young patients are still unknown. It was recently reported that not only hypercholesterolemia but also elevated levels of fibrinogen and homocysteine are independent risk factors for cerebrovascular disease. It is possible that these factors may be important predictors of atherosclerosis of the thoracic aorta in young patients, but more clinical data are still necessary. This case report confirms the importance of performing a TEE study and examining the cholesterol, fibrinogen and homocysteine plasmatic concentrations in all of young patients with unexplained stroke or transient ischemic attacks.
 ...
PMID:[Complicated atherosclerosis of the ascending aorta as a cause of recurrent cerebral embolisms in young adulthood]. 988 98


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>