Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0151744 (myocardial ischemia)
 31,282 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cardiomyopathy in chronic uremia results from pressure and volume overload. The former causes concentric left ventricular [LV] hypertrophy, results from hypertension and aortic stenosis, and is also associated with diabetes mellitus and anemia. Volume overload causes LV dilatation, results from arteriovenous shunting, salt and water overload, and anemia, and is also associated with ischemic heart disease, hypertension, and hypoalbuminemia. Decreased major arterial compliance and an early return of arterial wave reflections are also associated with the extent of LV hypertrophy. Cardiomyopathy predisposes to diastolic and systolic dysfunction. The latter results from myocyte death, and predisposing factors include ischemic heart disease and the uremic environment. Ischemic heart disease may be atherosclerotic or nonatherosclerotic in origin. Multiple factors contribute to the vascular pathology of chronic uremia, including injury to the vessel wall, dyslipidemia, prothrombotic factors, increased oxidant stress, and hyperhomocysteinemia. Ischemic risk factors include hypertension, LV hypertrophy, hypoalbuminemia, and perhaps hyperparathyroidism. The clinical consequences of cardiomyopathy include heart failure, ischemic heart disease, dialysis hypotension, and arrhythmias. The adverse impact of ischemic heart disease is probably mediated through the development of cardiac failure.
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PMID:Cardiac disease in chronic uremia: pathogenesis. 923 25

Hyperhomocysteinemia is reported to be associated with an increase in the incidence of ischemic heart disease and cerebrovascular disease. Genetic aberrations in methylenetetrahydrofolate reductase (MTHFR) may account for reduced enzyme activity and elevated plasma homocysteine level. A recent report revealed that a common mutation (677C to T; Ala to Val) in the MTHFR gene is associated with decreased specific MTHFR activity and with increased risk for coronary artery disease in the homozygous state (Val/Val). In the present study, we investigated whether the MTHFR gene is a genetic risk factor for cerebrovascular disease (CVD). To undertake a case-control study, we selected the patients with cerebral infarction (n = 48) or cerebral hemorrhage (n = 35) and examined the association between MTHFR gene polymorphism and CVD. The genotype distribution of the MTHFR gene was not significantly different between cases and controls. Because the possibility of matching the morbidity of the effects of hypertension, the lack of association could not be excluded in the first study; however, we also examined whether the MTHFR mutation was associated with any clinical risk factor for CVD or with hypertension. It turned out that the subjects with the Val allele of the MTHFR gene had significantly lower blood pressure than the subjects with other genotypes in the general population (P = .02), and that the frequency of the Val/Val genotype in hypertensive subjects (n = 173) was significantly lower than in control subjects (n = 184) (P = .03). From these results, we conclude that the Val/Val homozygous state of the MTHFR gene increased the risk of thrombosis, but reduced the blood pressure, which resulted in the lack of increased risk for CVD.
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PMID:Methylenetetrahydrofolate reductase gene polymorphism: relation to blood pressure and cerebrovascular disease. 971 96

Many cross-sectional and prospective studies have shown that raised serum/plasma levels of total homocysteine increase the risk of coronary, cerebral, and peripheral artery disease. The risk associated with hyperhomocysteinemia appears to be concentration-dependent and not attributable to traditional risk factors. The odds ratio for ischemic heart disease has been estimated to be 1.4 for every 5 mumol/l increase of total plasma homocysteine. Median fasting total plasma homocysteine in adult males is approximately 10 mumol/l. Mild hyperhomocysteinemia is estimated to occur in 5-10% of the general population. Plasma concentrations are increased as a result of age, male gender, impaired renal function, low vitamin B intake, and genetically-determined defects of the enzymes involved in homocysteine metabolism. Folate supplements can reduce total homocysteine levels by approximately 25%. Studies in vitro and in vivo indicate that homocysteine can impair endothelial function. Despite increasing recognition of hyperhomocysteinemia as a risk factor for arterial occlusive disease, irrefutable proof that mild hyperhomocysteinemia contributes directly to the pathogenesis of atherothrombosis will come if interventions to lower total homocysteine reduce cardiovascular events. Family studies may also provide evidence of causality if genetic causes of hyperhomocysteinemia are found to segregate with disease.
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PMID:Homocysteine and arterial occlusive disease: a concise review. 1037 85

TNF-alpha (so-called cachectin), IL-1 and 6 are important regulating agents in the homeostasis of energy in the organism, as among others they control processes of apoptosis and thus also the volume of adipose and muscular tissues. They are produced not only in immunocompetent cells but also in adipocytes and muscle cells. The cytokine system is then activated not only in tumours and infections but elevated values were found also in obesity, NIDDM, in myocardial infarction and in advanced decompensated cardiac patients. By acting on phosphorylation of IRS-1 and PI-3 kinase TNF-alpha promotes significantly insulin resistance, causes deterioration of diabetes, as well as elevated body temperature, sleepiness and anorexia. In a group of 65 patients, mostly with android obesity, in hyperleptinaemic and insulin resistant probands with coronarographically confirmed microvascular angina pectoris (n = 22) or IHD, mostly after a myocardial infarction (n = 43) with one or more significant stenoses on the epicardial coronary arteries in half the patients positive or elevated TNF-alpha was found and in 28% also IL-6. This increase did not correlate however with BMI, the percentage of body fat, IRI and C peptide levels nor with cortisol and leptin levels. Insulin resistant subjects had more frequently elevated homocysteine and Lp(a) values which are further two independent risk factors of atherothrombogenesis. Hyperhomocysteinaemia can be favourably influenced by vitamin fortification of the diet or by administration of folate and pyridoxine (1 tablet per day) involving negligible financial costs.
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PMID:[Relation between cytokines (TNF-alpha, IL-1 and 6) and homocysteine in android obesity and the phenomenon of insulin resistance syndromes]. 1042 20

This pictorial introduction to homocysteine illustrates at a glance the nature of homocysteine and its role in cardiovascular disease by means of eight simple figures and an essential bibliography. Homocysteine is a sulfur-containing metabolite of methionine. Conversion back to methionine or transsulfuration to cysteine are the two major metabolic pathways that reduce total homocysteine (tHcy) concentrations in cells and blood. B vitamins are essential cofactors in homocysteine metabolism. Median fasting total homocysteine levels in adult males are approximately 10 micromol/L. Increased plasma tHcy concentrations are found with methionine-rich diets, low vitamin B intake, male gender, age, impaired renal function, and genetically determined defects of the enzymes involved in homocysteine metabolism. An inverse relation exists between plasma tHcy and circulating folate or vitamin B(6) concentrations, and folic acid supplements of 0.5 mg/d can reduce tHcy levels by approximately 25%. Homocystinuric patients, who have severe hyperhomocysteinemia, die prematurely of atherothrombotic disease. Many (but not all) cross-sectional and prospective studies indicate, on average, that plasma tHcy levels <.10 micromol/L are associated with, or predict the development of, coronary, cerebral, and peripheral vascular disease. The risk conferred by hyperhomocysteinemia is graded and is independent of traditional risk factors, with an estimated odds ratio for ischemic heart disease of 1.4 for every 5 micromol/L increase in plasma tHcy. In vitro and in vivo, tHcy has been found to impair endothelial function. It is now well established that tHcy represents a marker of current or subsequent ischemic vascular disease. However, irrefutable proof that hyperhomocysteinemia actually causes atherothrombosis will come only if interventions to lower plasma tHcy will produce concomitant reductions in cardiovascular events.
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PMID:Homocysteine and risk of cardiovascular disease. 1059 Jan 84

In France, a diet high in saturated fat and cholesterol is associated with low coronary artery disease mortality and it may be that drinking wine is protective against ischemic heart disease. Recent studies suggest that high plasma homocysteine concentrations are an independent risk factor for coronary, cerebral and peripheral arterial occlusive diseases. One of several routes for metabolism of homocysteine involves methylation using betaine as the methyl donor. Betaine is often added to less expensive wine when beet sugar is used to increase alcohol content. We found that many commercial wines contain betaine; an average glass of wine contains approximately 3 mg betaine. This small amount is less than the dose used to lower homocysteine in patients with genetic forms of hyperhomocysteinemia, but we do not know whether humans with modest elevations of homocysteine would be influenced by this dose.
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PMID:Betaine in wine: answer to the French paradox? 1061 37

Hyperhomocysteinemia is currently regarded as an independent and modifiable risk factor for ischemic vascular diseases and thrombosis. We measured fasting plasma total homocysteine levels by HPLC with fluorescence detection in 30 patients presenting with acute coronary syndromes and 30 age and sex-matched control subjects. Demographic data, classical risk factors (systolic blood pressure, diabetes mellitus, smoking, ethanol intake, family history of ischaemic heart disease) and life-style habits were recorded. Lipid fractions including total cholesterol, triglycerides, HDL-cholesterol, total cholesterol/HDL-cholesterol ratio, serum creatinine, LDL-cholesterol and vitamins involved in the metabolism of homocysteine, folic acid and vitamin B12 were also assessed. Total fasting homocysteine concentrations were significantly higher in the patient group (12.2 +/- 1.01 micromol/l) than in the control subjects (7.05 +/- 0.36 micromol/l; p < 0.0001). Homocysteine correlated positively with age (r = 0.617; p < 0.01) and serum creatinine (r = 0.457; p < 0.01) in the patient group. Hyperhomocysteinemia was not associated with vitamin B12 or folate deficiency states. Vitamin B12 concentration was 273 +/- 16.4 ng/l in the control group and 284.3 +/- 32.2 ng/l in the patient group (p = NS). Serum folate concentration also was not significantly different between controls and patients; 7.57 +/- 0.58 microg/l and 8.05 +/- 0.72 microg/l, respectively. Since no significant difference was observed in the lipid parameters between patients and controls, the hyperhomocysteinemia in the patient group supports the view that homocysteine is an independent risk factor for cardiovascular diseases. Our results strongly suggest that elevated homocysteine levels are among the interacting factors in the complex, multifactorial pathophysiology of ischemic heart disease.
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PMID:Plasma homocysteine levels in acute coronary syndromes. 1073 56

Folic acid supplementation may help prevent the following three common and important disorders: neural tube defect pregnancies, ischemic heart disease and strokes, and possibly colon cancer. Several studies have irrefutably established that folic acid supplementation in proper doses reduces neural tube defect pregnancies. Fortified food would be the most reliable way to address this health issue. Several epidemiologic reports have established a close link between hyperhomocysteinemia and ischemic heart disease. This is supported by evidence obtained from genetic defects leading to elevated plasma levels of homocysteine. There is reasonable evidence to conclude that hyperhomocysteinemia is the actual cause of excessive cardiac diseases. Again, folic acid supplementation in proper doses could potentially reduce ischemic heart disease by 40% There is also some evidence to suggest that folic acid treatment reduces the incidence of colon cancer. The reduction in all three health problems is dependent upon the dose of folic acid administered. The levels needed are rarely supplied by the daily food intake, even under ideal conditions, although breakfast cereals address this problem at least in part. It is proposed that flour be fortified because it is a food product heavily used by most people, and that governmental agencies should oversee such programs because they are responsible for setting public health policies.
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PMID:Fortifying food with folic acid. 1101 53

Ischemic heart disease and other complications of atherosclerosis are the usual cause of death in patients with chronic renal failure. Important factors associated with early onset of atherosclerosis in these patients are hyperhomocysteinemia, hyperfibrinogenemia, and elevated levels of lipoprotein(a) (Lp(a)). Folic acid (15 mg/d), pyridoxine (150 mg/d), and cyanocobalamin (1 mg/wk) were administered for 4 weeks in 21 patients receiving dialysis, and a simultaneous, statistically significant reduction in the concentration of homocysteine, fibrinogen, and Lp(a) was found. A positive correlation between decreasing homocysteine and fibrinogen levels was also noted. The parameters studied approached presupplementation values 6 months after vitamins were discontinued. The results suggest that vitamin supplementation has a favorable effect on risk factors of atherosclerosis in patients with renal failure and that interactions may exist between homocysteine, fibrinogen, and Lp(a).
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PMID:Homocysteine, fibrinogen, and lipoprotein(a) levels are simultaneously reduced in patients with chronic renal failure treated with folic acid, pyridoxine, and cyanocobalamin. 1122 18

Due to its multifarious biological activity the renin-angiotensin system occupies a special position among risk factors of ischemic heart disease. The discovery of I/D polymorphism of the ACE gene led to a better understanding of genetic control of this enzyme. Hyperhomocysteinemia is an independent risk factor of ischemic heart disease. Elevated plasma levels of homocysteine may be due to improper diet (e.g. shortage of folic acid) and/or genetic influence. Methylenetetrahydrofolate reductase (MTHFR) is a key enzyme in the metabolism of homocysteine. The present study was performed in 100 patients (14 women and 86 men, mean age 54.2 +/- 9.2 years) with a history of myocardial infarction. The control group included 100 patients (10 women and 90 men, mean age 52.3 +/- 10 years) without such history. PCR was used to detect I/D ACE and C677T MTHFR polymorphisms. Genomic DNA was isolated from peripheral blood nuclear cells and amplified by PCR with two pairs of primers flanking the polymorphic regions. The restriction enzyme Hinf I was used to identify genotypes of the MTHFR polymorphism. No difference between both groups was found concerning the distribution of I/D ACE genotypes (31% II, 51% ID, 18% DD in the study group; 30% II, 57% ID, 13% DD in the control group; Tab. 1) or the distribution of C677T MTHFR genotypes (46% CC, 45% CT, 9% TT in the study group; 39% CC, 50% CT, 11% TT in the control group; Tab. 2). There was a significant effect of I/D genotype on ACE activity (IU/L) in the study (II = 18.2 +/- 17.9; ID = 33.5 +/- 19.9; DD = 68.9 +/- 21.9) and in the control group (II = 24.2 +/- 18.1; ID = 31.5 +/- 20.9; DD = 51.4 +/- 19.5; Tab. 3). No correlation was confirmed between ACE or MTHFR genotypes and age at infarction or left ventricular mass (Tabs. 4, 5, 6). The results indicate that neither the I/D ACE nor the C677T MTHFR polymorphisms are associated with risk of myocardial infarction in the Polish population.
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PMID:[Polymorphism of genes coding for angiotensin I converting enzyme and methylenetetrahydrofolate reductase in patients with ischemic heart disease]. 1171 21


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