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 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Increased homocysteine levels are associated with increased risk of cardiovascular disease incidence and mortality in general population and with even greater risk in persons with diabetes mellitus. Among possible mechanisms of proatherogenic action of homocysteine increased procoagulant activity, increased oxidative stress and effect on proliferation of smooth muscle cells should be mentioned. However, the role of hyperhomocysteinemia in the development of microvascular complications is the subject of a few studies with controversial results. Some studies indicate the role of hyperhomocysteinemia in predicting micro- and macroalbuminuria and also retinopathy and neuropathy. Serum homocystine levels are dependent on age, renal function, and dietary intake of folic acid and B vitamins. The role of insulin in homocysteine metabolism is the subject of studies. Determination of the role of hyperhomocysteinemia in macrovascular and microvascular diabetes complications could be of importance in their prevention through dietary and pharmacological modifications of homocysteine levels.
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PMID:[Chronic complication of diabetes and homocysteine]. 1139 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

Cardiovascular disease is the leading cause of mortality in Mexico, as well as in other Western countries. Conventional risk factors for atherosclerosis, such as cigarette smoking, systemic hypertension, diabetes mellitus, and hypercholesterolemia, do not explain this association completely. Recently, it has been recognized that hyperhomocysteinemia contributes to the atherosclerotic process, promoting endothelial damage and oxidative stress in the vascular wall. Homocysteine, an amino acid generated under physiologic conditions after ingestion of protein-rich foods, is used in a variety of metabolic pathways. Elevated plasma levels of this amino acid (higher than 15 mmol/L or lower in the presence of other cardiovascular risk factors) promote the development of atherosclerosis. Folic acid and vitamin B6 and B12 supplements decrease plasma levels of homocysteine effectively and may play an important role in the prevention and treatment of atherosclerotic vascular disease.
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PMID:[Hyperhomocysteinemia. A new coronary risk factor]. 1151 57

The endothelium, a continuous cellular monolayer lining the blood vessels, has an enormous range of important homeostatic roles. It serves and participates in highly active metabolic and regulatory functions including control of primary hemostasis, blood coagulation and fibrinolysis, platelet and leukocyte interactions with the vessel wall, interaction with lipoprotein metabolism, presentation of histocompatibility antigens, regulation of vascular tone and growth and further of blood pressure. Many crucial vasoactive endogenous compounds like prostacyclin, thromboxane, nitric oxide, endothelin, angiotensin, endothelium derived hyperpolarizing factor, free radicals and bradykinin are formed in the endothelial cells to control the functions of vascular smooth muscle cells and of circulating blood cells. These versatile and complex systems and cellular interactions are extremely vulnerable. The balances may be disturbed by numerous endogenous and exogenous factors including psychological and physical stress, disease states characterized by vasospasm, inflammation, leukocyte and platelet adhesion and aggregation, thrombosis, abnormal vascular proliferation, atherosclerosis and hypertension. The endothelial cells are also the site of action of many drugs and exogenous toxic substances (e.g. smoking, alcohol). As markers and assays for endothelial dysfunction, direct measurement of nitric oxide, its metabolites from plasma and urine, functional measurement of vascular nitric oxide dependent responses and assay of different circulating markers have been used. In numerous pathological conditions (e.g. atherosclerosis, hypertension, congestive heart failure, hyperhomocysteinemia, diabetes, renal failure, transplantation, liver cirrhosis) endothelial dysfunction has been described to exist. Some of them, as well as hormonal and nutritional factors and drug treatment will be discussed in this short review.
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PMID:Clinically important factors influencing endothelial function. 1153 60

The erythrocyte concentrations of the body's chief physiologic methyl donor S-adenosylmethionine (SAM) and of its metabolite and inhibitor S-adenosylhomocysteine (SAH), the plasma concentrations of total homocysteine (tHcy), and the activity of N(5,10) methylenetetrahydrofolate reductase (MTHFR) in lymphocytes were determined in healthy subjects and patients with diabetes mellitus without complications and at various stages of diabetic nephropathy, categorized according to the degree of progression of the disease. These groups were as follows: 1, control; 2, diabetics with no complications; 3, patients with albuminuria; 4, patients with an elevated plasma creatinine; and 5, patients on dialysis. No parameter studied exhibited significant differences between the type 1 and the type 2 diabetics. In control subjects, the blood concentrations of SAM were proportional to the activity of MTHFR; in diabetics, it was not. Consistent with previous observations, progression of nephropathy was accompanied by increased concentrations of tHcy. Increased erythrocyte concentrations of SAH, decreased erythrocyte concentrations of SAM, SAM/SAH ratios, and lymphocyte MTHFR activity also accompanied disease progression. The blood concentrations of SAH paralleled those of tHcy, while the concentrations of SAM showed a bimodal relationship with those of tHcy. These results provide further evidence that alterations in the blood concentrations of SAM and related compounds are abnormal in patients with diabetes, particularly in those with nephropathy. The deficiency of SAM may lead to methyl deficiencies, which may contribute to the high morbidity and mortality in patients with diabetic nephropathy. We have also demonstrated a decrease in lymphocyte MTHFR activity in patients with advanced nephropathy, suggesting that hyperhomocysteinemia in these patients may be due to a generalized metabolic abnormality. Further studies are needed to determine the pathogenesis of these abnormalities and whether they are present in renal failure due to causes other than diabetes or whether they are specific to diabetic nephropathy.
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PMID:Blood S-adenosylmethionine concentrations and lymphocyte methylenetetrahydrofolate reductase activity in diabetes mellitus and diabetic nephropathy. 1155 31

Cardiovascular disease is the leading cause of morbidity and mortality in end-stage renal disease. Causes include those usually found in the general population, those related to the uremic status, and those related to dialytic treatment. Hypertension, hypotension, anemia, hypoalbuminemia, malnutrition, dyslipidemia, reactive C protein, calcium-phosphate product, dialysis modalities, and hyperhomocysteinemia are discussed extensively. Special emphasis is put on hyperparathyroidism as a traditional toxin. The emergent role of sleep apnea has been confirmed in animal models as well as in humans studied using polysomnography. There are difficulties in diagnosing coronary disease, because angiography is not risk-free, is expensive, and should be reserved for patients having symptoms of heart failure and/or patients having diabetes mellitus, and/or patients entering a transplantation list. This allows patients with coronary disease to undergo coronary artery bypass (preferably) or percutaneous transluminal angioplasty. Patients for whom surgery is not appropriate should be treated using more traditional medical procedures.
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PMID:The heart in uremia: role of hypertension, hypotension, and sleep apnea. 1157 20

Hyperhomocysteinemia is a well established risk factor for cardiovascular disease, and multiple factors likely lead to abnormal regulation of plasma homocysteine in patients with diabetes. To examine a possible role for insulin and glucose in homocysteine metabolism, we examined the activity of two important enzymes of homocysteine metabolism in hepatocytes. In various tissues of six mice, methylene tetrahydrofolate reductase (MTHFR) activity was present in all tissues tested and the highest concentration (per gram) was in the brain. In contrast, cystathionine beta-synthase (CBS) activity appeared to be present only in the liver and to a small extent in the kidney. Using HEP G2 cells in culture, MTHFR activity was 3.3+/-0.8 nmol/h when the glucose concentration in the medium was 100 mg/dl and fell to 2.3+/-0.3 nmol/h when glucose was increased to 300 mg/dl. MTHFR activity was 3.4+/-0.3 nmol/h when cells were exposed to an insulin concentration of 5 mU/ml and fell to 2.8+/-0.3 nmol/h when insulin concentration was increased to 200 mU/ml (P<0.01). In contrast CBS activity increased from 0.017 to 0.13 U/ml by increasing the glucose concentration in the medium (P<0.01), but decreased from 0.04 to 0.02 (P<0.01) when the insulin concentration was increased from 5 to 200 mU/ml, respectively. We conclude that CBS and MTHFR have different tissue distributions, with CBS being present predominantly in liver and kidney, and MTHFR found in many tissues. In addition, both insulin and glucose affect the activity of the two enzymes when added to hepatocytes in vitro. If such effects occur in humans with hyperglycemia and hyperinsulinemia, then alterations in homocysteine metabolism may contribute to the accelerated macrovascular disease associated with insulin resistance or type 2 diabetes.
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PMID:The effect of glucose and insulin on the activity of methylene tetrahydrofolate reductase and cystathionine-beta-synthase: studies in hepatocytes. 1158 7

The high incidence of cardiovascular disease after renal transplantation is related to a high prevalence and accumulation of risk factors before and after transplantation. Hypertension, posttransplantation diabetes, and hyperlipidemia are well-recognized risk factors for the development of cardiovascular events after renal transplantation and are strongly associated with immunosuppressive therapy. Hyperhomocysteinemia is a potential risk factor for cardiovascular disease in renal transplant recipients, but although a growing matter of study, a direct association with immunosuppressive agents is not yet proven. In addition to treatment intervention, risk management should also involve tailoring the immunosuppressive regimen to minimize the more indirect cardiovascular risk factors such as renal dysfunction and acute rejection.
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PMID:Graft function and other risk factors as predictors of cardiovascular disease outcome. 1158 39

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

A moderate increase in plasma total homocysteine (tHcy) is considered to be an independent risk factor for cardiovascular disease (CVD) in the general population. Almost all chronic renal failure (CRF) patients have plasma concentration of tHcy that is elevated 3 to 4 times above normal. The prevalence of CVD, diabetes mellitus, malnutrition and hypoalbuminemia is high in CRF patients. Previous investigations have focused on the role of vitamin status on plasma tHcy in CRF patients, but little information exists on the influence of nutritional status and hypoalbuminemia on plasma tHcy in CRF, although a substantial fraction of tHcy (>70%) is protein-bound, mainly to albumin. Our study in patients with end-stage renal disease showed that more than 90% of the patients had elevated plasma tHcy levels, which were higher in patients with normal nutritional status than in malnourished patients. Moreover, plasma tHcy was inversely correlated with subjective global nutritional assessment (high values denote malnutrition) and positively correlated with serum albumin and protein intake. Hence, it seems likely that serum-albumin is a strong determinant of plasma tHcy in CRF patients and this may contribute to the lower tHcy levels in malnourished patients. Patients with diabetes mellitus had lower serum-albumin and plasma tHcy than non-diabetic patients, irrespective whether they were malnourished or not. Patients with CVD had lower (although still elevated) plasma tHcy levels than those without CVD. An explanation may be that the prevalence of diabetes mellitus, malnutrition and hypoalbuminema, i.e. factors that decrease tHcy, was higher in patients with CVD, which may explain why they had less elevated values. Assuming that hyperhomocysteinemia carries an independent risk of CVD, this implies that almost all CRF patients are exposed to this risk. CRF patients with CVD had a higher prevalence of malnutrition, hypoalbuminemia and diabetes mellitus, which was associated with a lower plasma Hcy level. This may explain why plasma tHcy was lower (although still abnormally high) in patients with CVD than in patients without CVD. The lower tHcy levels in CVD patients do not contradict the assumption that hyperhomocysteinemia is a risk factor for CVD since almost all patients are exposed to this risk, and other factors might be present that confound the relationship between the absolute tHcy levels and CVD. Our findings imply that nutritional status and serum albumin, as well as the presence of diabetes mellitus, should be taken into consideration when evaluating tHcy as a risk factor for CVD in CRF patients.
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PMID:Hyperhomocysteinemia in chronic renal failure patients: relation to nutritional status and cardiovascular disease. 1159 43


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