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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hyperhomocysteinemia is associated with ischemic cardiovascular disease (ICD) and venous thromboembolism (VTE). We tested the hypothesis that methylenetetrahydrofolate reductase (MTHFR) C677T homozygosity with hyperhomocysteinemia is associated with ICD and VTE. First, 9238 randomly selected whites from the general population were followed for 23 years. Second, 2125 whites with ischemic heart disease and 836 whites with ischemic cerebrovascular disease were compared with 7568 controls from the general population. Plasma homocysteine was elevated 25% in homozygotes versus noncarriers (P < .001) and 19% in ICD/VTE cases versus controls (P < .001). In prospective studies adjusted hazard ratios for ICD and VTE for homozygotes versus noncarriers did not differ from 1.0. Furthermore, MTHFR C677T homozygosity was not associated with increased risk of ICD or VTE in subgroups after stratification for sex, age, cholesterol, high-density lipoprotein cholesterol, lipoprotein(a), fibrinogen, triglycerides, body mass index, smoking, diabetes mellitus, hypertension, and factor V Leiden genotype. Finally, in case-control studies odds ratios for ischemic heart disease and ischemic cerebrovascular disease in homozygotes versus noncarriers did not differ from 1.0. In conclusion, MTHFR C677T homozygosity with hyperhomocysteinemia is not associated with ICD or VTE; however, ICD/VTE is associated with hyperhomocysteinemia. Therefore, ICD and VTE may cause hyperhomocysteinemia, rather than vice versa.
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PMID:Methylenetetrahydrofolate reductase polymorphism (C677T), hyperhomocysteinemia, and risk of ischemic cardiovascular disease and venous thromboembolism: prospective and case-control studies from the Copenhagen City Heart Study. 1580 48

Stroke, particularly ischemic stroke, has a major impact on public health due to its high incidence, prevalence and rate of subsequent disability in Italy as in most industrialised countries. Apart from age, many modifiable factors, such as hypertension, smoking, diabetes, dyslipidemia, obesity, physical inactivity, alcohol abuse and hyperhomocysteinemia, have been recognised as playing a role in the pathogenesis of this disease. While appropriate pharmacological therapy has proven effective in the prevention of stroke in particular categories of patients, most of the above mentioned predisposing conditions are amenable to be affected by nutrition. Unequivocal demonstration of a protective or adverse role of single foods and nutrients against the risk of stroke has been however difficult to achieve due to confounding by biological variability, methodological inadequacies in the assessment of individual nutritional habits and difficulty to carry out long-term randomised controlled trials in the nutritional area. Notwithstanding, in several cases, causal relationships could be inferred from case-control and cohort studies in the presence of plausible and reproducible associations, evidence of dose-dependent effects and consistency in the results of different studies. The aim of this paper was to review present knowledge and highlight limitations and future perspectives about the role of nutrition in the prevention of ischemic stroke.
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PMID:Nutrition and prevention of ischemic stroke: present knowledge, limitations and future perspectives. 1524 43

Background: Stroke mainly affects the older population, although it has also been reported in younger patients. In this study, we focused on patients 65 years of age or younger with stroke. Methods: The files of three patient populations were studied: 93 patients aged 65 years or younger with stroke (group A), 93 patients older than 65 with stroke (group B), and 604 patients without stroke representing the general population of patients admitted to our service during January 2000 (group C). We reviewed the patient files and compared patient characteristics, epidemiological features, clinical picture,imaging findings, and coagulation tests. Results: Overall, 318 patients were studied. The mean age of group A was 55 years compared to 77 years in group B and 71 years in group C. In both stroke groups (A and B), the male: female ratio was 2:1, in contrast with a balanced ratio in group C. Most of the patients in group A (63%) were of Sephardic origin compared to 39% in group B (P=0.002) and 30% in group C. The clinical picture in both stroke groups (A and B) was similar. The risk factor smoking was reported by 45% in group A and by only 29% in group B (P=0.034). Hypertension, diabetes mellitus, and hyperlipidemia were evenly prevalent in both stroke groups. The coagulation system was studied in the "young" patients (group A): hyperhomocysteinemia was found in 37%, high titers of anticardiolipin antibodies in 35%, low levels of antithrombin III in 13%, protein C deficiency in 5%, and activated protein C resistance (APCR) in 4%. Overall, 49% of the patients from group A were found to have coagulation abnormalities. Conclusions: We found in our study that the younger patient with stroke tends to be a Sephardic male with the classical risk factors as well as a history of smoking and coagulopathy. These findings suggest strict medical supervision and primary prophylaxis. This work also lays the basis for a prospective, interventional trial with younger patients.
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PMID:Clinical and ethnic characteristics of stroke in an Israeli population: a study in a community hospital population. 1524 19

About half of all deaths are due to cardiovascular disease and its complications. The economic burden on society and the healthcare system from cardiovascular disability, complications, and treatments is huge and becoming larger in the rapidly aging populations of developed countries. As conventional risk factors fail to account for part of the cases, homocysteine, a "new" risk factor, is being viewed with mounting interest. Homocysteine is a sulfur-containing intermediate product in the normal metabolism of methionine, an essential amino acid. Folic acid, vitamin B(12), and vitamin B(6) deficiency and reduced enzyme activities inhibit the breakdown of homocysteine, thus increasing the intracellular homocysteine concentration. Numerous retrospective and prospective studies have consistently found an independent relationship between mild hyperhomocysteinemia and cardiovascular disease or all-cause mortality. Starting at a plasma homocysteine concentration of approximately 10 micromol/l, the risk increase follows a linear dose-response relationship with no specific threshold level. Hyperhomocysteinemia as an independent risk factor for cardiovascular disease is thought to be responsible for about 10 percent of total risk. Elevated plasma homocysteine levels (> 12 micromol/l; moderate hyperhomocysteinemia) are considered cytotoxic and are found in 5 to 10 percent of the general population and in up to 40 percent of patients with vascular disease. Additional risk factors (smoking, arterial hypertension, diabetes, and hyperlipidemia) may additively or, by interacting with homocysteine, synergistically (and hence overproportionally) increase overall risk. Hyperhomocysteinemia is associated with alterations in vascular morphology, loss of endothelial antithrombotic function, and induction of a procoagulant environment. Most known forms of damage or injury are due to homocysteine-mediated oxidative stresses. Especially when acting as direct or indirect antagonists of cofactors and enzyme activities, numerous agents, drugs, diseases, and life style factors have an impact on homocysteine metabolism. Folic acid deficiency is considered the most common cause of hyperhomocysteinemia. An adequate intake of at least 400 microg of folate per day is difficult to maintain even with a balanced diet, and high-risk groups often find it impossible to meet these folate requirements. Based on the available evidence, there is an increasing call for the diagnosis and treatment of elevated homocysteine levels in high-risk individuals in general and patients with manifest vascular disease in particular. Subjects of both populations should first have a baseline homocysteine assay. Except where manifestations are already present, intervention, if any, should be guided by the severity of hyperhomocysteinemia. Consistent with other working parties and consensus groups, we recommend a target plasma homocysteine level of < 10 micromol/l. Based on various calculation models, reduction of elevated plasma homocysteine concentrations may theoretically prevent up to 25 percent of cardiovascular events. Supplementation is inexpensive, potentially effective, and devoid of adverse effects and, therefore, has an exceptionally favorable benefit/risk ratio. The results of ongoing randomized controlled intervention trials must be available before screening for and treatment of hyperhomocysteinemia can be recommended for the apparently healthy general population.
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PMID:Clinical use and rational management of homocysteine, folic acid, and B vitamins in cardiovascular and thrombotic diseases. 1525 38

Endothelial dysfunction is characterized by a shift of the actions of the endothelium toward reduced vasodilation, a proinflammatory state, and prothrombic properties. It is associated with most forms of cardiovascular disease, such as hypertension, coronary artery disease, chronic heart failure, peripheral artery disease, diabetes, and chronic renal failure. Mechanisms that participate in the reduced vasodilatory responses in endothelial dysfunction include reduced nitric oxide generation, oxidative excess, and reduced production of hyperpolarizing factor. Upregulation of adhesion molecules, generation of chemokines such as macrophage chemoattractant peptide-1, and production of plasminogen activator inhibitor-1 participate in the inflammatory response and contribute to a prothrombic state. Vasoactive peptides such as angiotensin II and endothelin-1; the accumulation of asymmetric dimethylarginine, an endogenous nitric oxide inhibitor; hypercholesterolemia; hyperhomocysteinemia; altered insulin signaling; and hyperglycemia can contribute to these different mechanisms. Detachment and apoptosis of endothelial cells (anoikis) are associated phenomena. Endothelial dysfunction is an important early event in the pathogenesis of atherosclerosis, contributing to plaque initiation and progression. Reductions in circulating endothelial progenitor cells that participate in regeneration of the endothelium participate in endothelial pathophysiology. The severity of endothelial dysfunction has been shown to have prognostic value for cardiovascular events. Correction of endothelial dysfunction may be associated with reduced cardiovascular risk. Circulating endothelial progenitor cells may represent a potential therapeutic approach for endothelial dysfunction.
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PMID:Endothelial dysfunction. 1528 84

Homocysteine is an intermediate product in the methionine metabolism, which is catalysed by several enzymes with B2, B6, B12 vitamins and folic acid as cofactors. Moderate hyperhomocysteinemia, defined as total homocysteine concentration between 12 to 30 micromol/l, represents an independent risk factor for heart disease, vascular brain disease, phlebothrombosis and thromboembolic complications. It is related to placental abruptions, spina bifida and some neuropsychiatric disorders. Hyperhomocysteinemia is a metabolic syndrome based on interaction between genetic factors (most frequently 677C/T polymorphism of methylentetrahydrofolate reductase), diseases and demographic factors (smoking, aging, hormonal and nutritional factors). Moderate hyperhomocysteinemia occurs in about 20 to 30% of patients with clinical complications of atherosclerosis. Prospective and genetic studies have shown, that moderate hyperhomocysteinemia in healthy persons is only a weak predictor of cardiovascular diseases. Contrary to it, in patients with ischaemic heart disease, renal failure or diabetes mellitus and in thromboembolic disease, hyperhomocysteinemia represents a strong predictor of vascular morbidity and mortality. Toxic effects of hyperhomocysteinemia on the vascular wall can be explained by a chemical modification of lipoproteins and vascular structure, oxidative stress, endothelial dysfunction, inadequate endothelial cell regeneration, smooth muscle cell proliferation or by an accumulation of functionally non sufficient connective tissue. Also thrombogenic effects or an increased expression of cholesterol level controlling proteins and fatty acids in the liver can be considered. Treatment of hyperhomocysteinemia is based on the administration of pharmacological doses of folic acid, B6 and B12 vitamins, which can decrease total homocysteine concentration by 25 to 30%. Such decrease, which is in average 3 micromol/l, results in the decrease of relative risk of ischaemic heart disease by 11 to 16%, phlebothrombose by 25% and vascular brain diseases by 19 to 24%.
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PMID:[Consequences of moderate hyperhomocysteinemia in internal medicine]. 1530 62

Endothelial dysfunction is one of the earliest events in atherogenesis. A consequence of endothelial damage is a lower availability of nitric oxide (NO), the most potent endogenous vasodilator. NO inhibits platelet aggregation, smooth muscle cell proliferation and adhesion of monocytes to endothelial cells. Endothelial dysfunction is present in patients with cardiovascular disease and/or coronary risk factors, such as hypertension, dyslipidemia, diabetes, smoking or hyperhomocysteinemia. At present, soluble markers and high resolution ultrasound of the brachial artery, have provided simple tools for the study of endothelial function and the effects of several interventions. It has been demonstrated that dietary factors may induce significant changes on vascular reactivity. Nutrients, such as fish oil, antioxidants, L-arginine, folic acid and soy protein have shown an improvement in endothelial function that can mediate, at least partially, the cardioprotective effects of these substances. Attention has been focused on dietary patterns in populations with lower prevalence of cardiovascular disease. There is some evidence suggesting that Mediterranean diet characterized by high consumption of vegetables, fish, olive oil and moderate wine consumption may have a positive effect on endothelial function. These results give us evidence on the significant role of diet on endothelial function and its impact on the pathogenesis of atherosclerosis.
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PMID:Diet and endothelial function. 1545 51

A great number of epidemiologic and experimental results of scientific research led to the conclusion, that hyperhomocysteinemia could be possible risk factor for the cardiovascular diseases development in patients suffering from the homocysteinuria and in all the population, because of homocysteine's ability to the activation of the thrombogenesis processes and to the creation of the atherosclerotic changes. Furthermore, the elevated homocysteine concentration exacerbates the effects of the other atherosclerogenous factors, such as tobacco smoking or arterial hypertension. The increased mortality caused by the cardiovascular diseases was observed in patients with the homocysteine concentration elevated above 15 micromol/l on an empty stomach and 38 micromol/l after the methionine intake (the mortality was twice higher). The concentration aimed 10 to 15 micromol/l is assumed to be the normal high concentration. There were no screening researches led on the population for the showing the number of people with the increased homocysteine concentration, however such kind of investigation could be recommended in patients with diabetes, kidney diseases, family history with reported cardiovascular diseases, heart and other organs transplantation, and in patients with the constant intake medicaments increasing the homocysteine concentration. We have no results of prospective research conducted on the numerous patient group, which could document the profits resulted by the treatment of the hyperhomocysteinemia in the primary and secondary prophylactic of the cardiovascular disease.
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PMID:[Homocysteine as the factor of atherosclerosis risk]. 1551 33

Hyperhomocysteinemia is associated with an enhanced risk for cardiovascular disease. Patients with peripheral arterial disease (PAD) show an increased prevalence of hyperhomocysteinemia. A decreased biological activity of nitric oxide (NO) may contribute to homocysteine-associated endothelial dysfunction. This study was designed to investigate whether elevated levels of the endogenous NO synthase inhibitor asymmetric dimethylarginine (ADMA) are involved in endothelial dysfunction in patients with chronic hyperhomocysteinemia and PAD. A total of 76 patients (58 males and 18 females; mean age 65.2 +/- 2.0 years) with PAD were included in the analysis and characterized according to demographic variables and cardiovascular risk factors. Flow-dependent vasodilation (FDD) was determined by high-resolution ultrasound in the radial artery. Total plasma homocysteine (plasma tHcy) and ADMA levels were measured by HPLC. Urinary nitrate was quantified using gas chromatography-mass spectrometry. Patients with plasma tHcy in the highest tertile (n = 27; i.e. > 10.6 micromol/l) had a mean plasma level of 14.4 +/- 1.21 mol/l compared with 9.9 +/- 0.1 micromol/l in those patients in the middle tertile (n = 22; p < 0.05) and 9.4 +/- 0.1 micromol/l in those in the lowest tertile (n = 27; i.e. <9.6 micromol/l; p < 0.05). The hyperhomocysteinemic individuals (highest tertile) had a significantly decreased FDD compared with healthy age-matched controls (n = 15) (7.6 +/- 1.0 vs 13.0 +/- 0.4%; p < 0.05), higher plasma ADMA concentrations (4.0 +/- 0.3 vs 2.6 +/- 0.3 micromol/l; p < 0.05), and a lower urinary nitrate excretion rate (89.5 +/- 13.4 vs 131.3 +/- 17.9 micromol/mmol creatinine; p < 0.05) compared with patients with plasma tHcy in the lowest tertile. Multivariate regression analysis including plasma tHcy, ADMA, total cholesterol, diabetes mellitus, smoking, and systolic blood pressure revealed ADMA as the only significant factor determining FDD (p < 0.05). In conclusion, we demonstrated a stronger relationship between impaired endothelial function and elevated ADMA levels in comparison with plasma tHcy concentrations in patients with PAD and chronic hyperhomocysteinemia. This may raise the question of whether different therapeutical options that interact indirectly with plasma tHcy, i.e. treatment with ACE inhibitors and AT1-receptor blockers to reduce ADMA plasma concentrations or L-arginine, could be a beneficial tool for treating patients with hyperhomocysteinemia.
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PMID:Endothelial dysfunction in patients with peripheral arterial disease and chronic hyperhomocysteinemia: potential role of ADMA. 1552 98

Hyperhomocysteinemia is thought to have an important role in the pathogenesis of ischemic cerebral infarction. When associated with diabetes mellitus, it might worsen the neurologic course. The aim of the study was to clarify the relation between plasma homocysteine (Hcy) concentrations and silent brain infarction (SBI) in patients with type 2 diabetes mellitus. Total plasma Hcy levels were prospectively studied in 46 patients with type 2 diabetes and SBI (group I), mean age 56+/-5.4 years, as compared to 38 diabetic patients without SBI (group II) and with 31 controls (group III). Homocysteine concentrations were determined using a high-performance liquid chromatography assay. The results were compared using the Student's t test. The mean level of Hcy was 22.6+/-2.4 micromol/l in group I, 19.7+/-1.6 micromol/l in group II and 11.4+/-1.4 micromol/l in group III; between group I and group II p < or = 0.001. These data are consistent with increased Hcy levels in type 2 diabetic patients, contributing to the onset of SBI in some patients. The phenomenon should be considered in any future strategy for the therapy of hyperhomocyst(e)inemia (HHcy).
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PMID:Study of total homocyst(e)ine levels in type 2 diabetic patients with silent brain infarction. 1552 24


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