Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018799 (heart disease)
 34,133 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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

Epidemiologic evidence has linked elevation of serum homocysteine to an increased risk of coronary artery disease, stroke, and dementia. An increase in homocysteine levels in Parkinson disease (PD) recently has been discovered. Although B vitamin status and genetic factors are important modifying influences determining the degree of this elevation, the main cause appears to be therapy with L-dopa. It has been suggested that breakdown of L-dopa by catechol-O-methyltransferase results in increased homocysteine formation. Therefore, there are reasons to suggest that management of PD may render patients at increased risk of stroke, heart disease, dementia, and even accelerated nigral degeneration. At present, no controlled prospective studies have evaluated this phenomenon, although they are ongoing.
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PMID:Homocysteine and levodopa: should Parkinson disease patients receive preventative therapy? 1536 41

A growing body of literature has documented that job stress is associated with the development of cardiovascular disease. Nevertheless, the pathophysiological mechanism of this association remains unclear. The purpose of this study is to elucidate the relationship between job stress, heart rate variability, and metabolic syndrome. The study design was cross-sectional, and a total of 169 industrial workers were recruited. A structured-questionnaire was used to assess the general characteristics and job characteristics (work demand, decision latitude). Heart rate variability (HRV) was recorded using SA-2000 (medi-core), and was assessed by time-domain and by frequency-domain analyses. Time domain analysis was performed using SDNN (Standard Deviation of normal to normal interval), and spectral analysis using low-frequency (LF), high-frequency (HF), and total frequency power. Metabolic syndrome was defined on the basis of risk factors being clustered when three or more of the following cardiovascular risk factors were included in the fifth quintile: glucose, systolic blood pressure, high-density lipoprotein cholesterol (bottom quintile), triglyceride, and waist-hip ratio. The results showed that job characteristics were not associated with cardiovascular risk factors. Compared to the lower strain group (low strain+passive+active group), the high strain group had a less favorable cardiovascular risk profile with higher levels of blood pressure, glucose, homocysteine, and clotting factor, but the difference was not statistically significant. The SDNN of HRV was significantly lower in the high strain group than in the low strain group. The prevalence of metabolic syndrome in the lower strain group and high strain group was 13.2% and 23.8%, respectively. In the high strain group, the metabolic syndrome was significantly related to a decreased SDNN. However, we could not find a significant association in LF/HF ratio. This result suggests that decreased HRV found in the high-strain group are not a direct indicator of disease. However, it can induce cardiovascular abnormalities or dysfunctions related to the onset of heart disease among high risk groups.
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PMID:Association between job stress on heart rate variability and metabolic syndrome in shipyard male workers. 1551 94

Four classes of agents capable of producing human illness have been identified: toxicity, heredity, infection and deficiency. The leading paradigm for the etiology and pathophysiology of ischemic heart disease in the 20th century was that of intoxication by too much of the wrong kind of dietary fat. This overemphasis on lipid metabolism persists because important data are neglected and because of inattention to details. For example, heart disease risk does not correlate with fat intake within nations in contrast to between nations. Also development of ischemic heart disease involves inter alia arterial spasm, cardiac rhythm, metabolism of connective tissue, glucose and homocysteine, plus paraoxonase activity and thrombus formation which generally are unaffected by dietary fat. Homocysteine thiolactone accumulates when homocysteine is high. This lactone specifically inhibits lysyl oxidase which depends on copper to catalyze cross linking of collagen and elastin in arteries and bone. The lactone is hydrolyzed by paraoxonase, activity of which can be decreased by copper deficiency. Just as cholesterol was an important focus for heart disease as intoxication, homocysteine can become an excellent focus for a paradigm shift to heart disease as deficiency because supplementation with several nutrients can alter homocysteine metabolism and decrease its plasma concentration. These supplements include betaine, copper, folate, pyridoxine and vitamin B-12. Opportunities for research on ischemic heart disease as deficiency disease are plentiful.
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PMID:Ischemic heart disease as deficiency disease. 1570 51

The role of folic acid and homocysteine in pregnancy is becoming clearer. The efforts of many countries to prevent neural tube defects through public awareness of folic acid have been disappointing, but evidence is now emerging that the food fortification programs in the United States and Canada are effective in reducing the numbers of neural tube defects, and there may be additional benefits in terms of other congenital defects such as oral-facial clefts and congenital heart disease. Homocysteine has a significant association with vascular disease in later life, is elevated in preeclampsia, and has been associated with other pregnancy complications such as early pregnancy loss. The data from cohorts of women with a history of preeclampsia during pregnancy indicate that they are at increased risk for cardiovascular and cerebrovascular disease in later life. Elevated homocysteine concentrations may be a common link that accounts for these associations.
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PMID:Homocysteine and folic acid: implications for pregnancy. 1604 71

Congenital heart disease will be the next frontier for prevention by periconceptional management of homocysteine and its metabolites by folate supplementation. Evidence for the connection between maternal and fetal folate metabolism and congenital malformations of the cardiovascular system is reviewed including possible applications to the large population of patients at risk for a child with congenital heart disease.
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PMID:Homocysteine, folate, and congenital heart defects. 1624 51

Cystathionine beta-synthase plays a key role in the intracellular disposal of homocysteine and is the single most common locus of mutations associated with homocystinuria. Elevated levels of homocysteine are correlated with heart disease, Alzheimer's and Parkinson's diseases, and neural tube defects. Cystathionine beta-synthase is modular and subjected to complex regulation, but insights into the structural basis of this regulation are lacking. We have employed hydrogen exchange mass spectrometry to map peptides whose motions are correlated with transmission of intrasteric inhibition and allosteric activation. The mass spectrometric data provide an excellent correlation between kinetically and conformationally distinguishable states of the enzyme. We also demonstrate that a pathogenic regulatory domain mutant, D444N, is conformationally locked in one of two states sampled by the wild type enzyme. Our hydrogen exchange data identify surfaces that are potentially involved in the juxtaposition of the regulatory and catalytic domains and form the basis of a docked structural model for the full-length enzyme.
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PMID:Mapping peptides correlated with transmission of intrasteric inhibition and allosteric activation in human cystathionine beta-synthase. 1624 37

Basic research has demonstrated that homocysteine enhances both arteriosclerosis and thrombosis - the principal cause of CVD. Although studies demonstrate that patients with elevated homocysteine levels have small to moderate increased risk of CVD it remains unclear whether lowering plasma homocysteine levels will decrease risks of CVD. The study was aimed to detect reliability of homocysteine lowering on risk of CVD. We studied 256 patients (56 stenocardia; 96 myocardial infarction; 104 post infarction period). Besides we investigated the influence of blood homocysteine concentration on coronary vessels of patients suffering ischemic heart disease, acute heart disease and those in post infarct period. The majority of coronary vessels demonstrated occlusion and stenosis. The investigation showed the connection between body reactivity and homocysteine level. The higher body reactivity was associated with the higher homocysteine concentration in the blood. It stimulated the development of the mild form of ischemic heart disease -- stenocardia. The increase of homocysteine concentration up to the normal top level points to the danger of development of acute ischemic myocardial disease rather than stenocardia. The investigation showed that the homocysteine blood levels are among the reliable diagnostic markers of CVD. The results of the investigation would permit rational clinical decision making for individual patients and policy decisions for the health of the general population.
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PMID:[Homocysteine as risk marker of cardiovascular disease]. 1630 48

Risk factors for cardiovascular disease, including high cholesterol, high homocysteine, hypertension and inflammation, increase the risk of dementia, including its most common form, Alzheimer's disease (AD). High cholesterol is also associated with elevated beta-amyloid (Abeta), the hallmark of AD. Oxidative damage is a major factor in cardiovascular disease and dementia, diseases whose risk increases with age. Garlic, extracted and aged to form antioxidant-rich aged garlic extract (AGE or Kyolic), may help reduce the risk of these diseases. AGE scavenges oxidants, increases superoxide dismutase, catalase, glutathione peroxidase, and glutathione levels, and inhibits lipid peroxidation and inflammatory prostaglandins. AGE reduces cholesterol synthesis by inhibiting 3-hydroxy-3-methylglutaryl-CoA reductase and is additive with statins in its action. Inhibition of cholesterol, LDL oxidation, and platelet aggregation by AGE, inhibits arterial plaque formation; AGE decreases homocysteine, lowers blood pressure, and increases microcirculation, which is important in diabetes, where microvascular changes increase heart disease and dementia risks. AGE also may help prevent cognitive decline by protecting neurons from Abeta neurotoxicity and apoptosis, thereby preventing ischemia- or reperfusion-related neuronal death and improving learning and memory retention. Although additional observations are warranted in humans, compelling evidence supports the beneficial health effects attributed to AGE in helping prevent cardiovascular and cerebrovascular diseases and lowering the risk of dementia and AD.
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PMID:Garlic reduces dementia and heart-disease risk. 1648 70

Elevated homocysteine is associated with increased risk of heart disease, stroke, and dementia. Therapy of Parkinson disease (PD) with levodopa elevates homocysteine. The authors conducted a 6-week, multicenter, randomized, double-blind, placebo-controlled trial to test whether folate 1 mg/vitamin B(12) 500 microg or entacapone reduced serum homocysteine in 35 levodopa-treated PD patients. Levodopa initiation caused a small elevation in homocysteine. Vitamin therapy, but not entacapone, resulted in a decrease in homocysteine compared to placebo.
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PMID:Vitamins and entacapone in levodopa-induced hyperhomocysteinemia: a randomized controlled study. 1745 98


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