Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020473 (hyperlipidemia)
 15,891 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Early onset vascular disease unexplained until today by usual risk factors (hyperlipidemia, hypertension, tobacco, stress), can now find an explanation in sulfur amino acid metabolism defect. By transsulfuration, alimentary methionine leads to homocysteine, which is itself turn into cysteine, or remethylated into methionine. Several abnormalities of these different pathways lead to plasma accumulation of homocysteine, which will be responsible of arterial or venous occlusive lesions, concerning peripheral or deep vessels. Homocysteine stays in plasma upon several forms: 75% being linked by disulfide bounds to proteins, 22% as disulfide, homocystine (homocysteine-homocysteine) or mixed-disulfide (homocysteine-cysteine), and less than 3% as free reduced homocysteine. Plasma reduction allows total homocysteine evaluation with amino acid autoanalyzer. The basal plasma homocysteine level is less than 14 microMl. However, levels near this basal value can be found in patients with latent abnormality, which needs to be revealed by a methionine loading test. This study concerns two methodologies and their application to the exploration of a patient with unidentified neurologic disorders. The first one describes a new galenic oral form of methionine. Other authors use the methionine load of 100 mg/kg dissolving it in a fruit juice glass. In order to obtain a complete dissolution of this weakly soluble substance and to ensure its total absorbtion by the patient, we prepare a granular form aimed to give in water a perfect flavoured suspension. The second methodology concerns methionine loading test and amino acid analysis. After 10 hours fasting, a 100 mg/kg peroral methionine load is realized performing 5 EDTA blood samples before and 4, 8, 12 and 24 hours after loading.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[The homocysteinemia vascular risk factor. Methodologies and application to a clinical case]. 179 72

Homocysteine (Hcy) represents a branching point between the transsulfuration and transmethylation pathway of methionine. A large increase of plasma concentration of Hcy is observed in patients with inherited hyperhomocysteinemia. A moderated increase (above 10 microM) is also observed in various pathological conditions, such as arterial occlusion, hypertension, hyperlipidemia and chronic renal failure. While amino acids were largely studied using capillary electrophoresis with UV or laser-induced fluorescence detection (LIF), thiol-amino acids were not. In this work we present a new approach for testing homocysteine in human plasma using CE-LIF and fluorescein isothiocyanate. The low fluorescence yield of the fluorescein thiocarbamyl (FTC) thiol-amino acids limits, probably, the sensitivity of the detection to 8 x 10(-10) M (instead of 10(-12) M for FTC-arginine).
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PMID:Quantitation of homocysteine in human plasma by capillary electrophoresis and laser-induced fluorescence detection. 976 92

Favourable effects of n-3 fatty acids on the atherogenic risk profile were recently demonstrated in subjects with combined (type IIb) hyperlipidaemia, not responding to a therapeutic diet. Re-examination of a previous patient material was performed to assess the influence of n-3 fatty acids on homocysteine and several coagulation factors. Subjects were randomly allocated to receive either a concentrated compound of 85% eicosapentaenoic acid (EPA)/docosahexaenoic acid (DHA) (n = 28), or corn oil (n = 29), in a daily dose of 4g for 12 weeks. The intervention was double-blind. Homocysteine remained unchanged in both groups after 12-week treatment. N-3 fatty acids supplementation did not affect the levels of fibrinogen, coagulation factor VII or tissue factor pathway inhibitor (TFPI), while plasminogen activator inhibitor (PAI) increased significantly (Student's t-test; p <0.05). Total blood platelets were significantly reduced in subjects receiving n-3 fatty acids (Student's t-test; p <0.05), whereas bleeding times increased non-significantly.
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PMID:Atherothrombogenic risk modulation by n-3 fatty acids was not associated with changes in homocysteine in subjects with combined hyperlipidaemia. 1023 39

Several studies have reported that moderate hyperhomocysteinemia is related to an increased risk for atherosclerosis, but few data are available with regard to any other thiol compound having a potential vascular toxicity. Therefore, we measured both total cysteine and homocysteine plasma levels in patients with hyperlipidemia (242 males and 147 females, 41-65 years old). Homocysteine was higher in males than in females, 13.2+/-4.1 versus 11.1+/-3.4 micromol/l (P<0.0001). The mean cysteine level was 243.3+/-45.7 micromol/l in the whole study population. The subjects were split in two groups, symptomatic patients with cardiovascular disease (n = 106) and asymptomatic subjects (n = 283). Blood pressure, smoking status, total cholesterol, LDL-cholesterol and triglycerides did not statistically differ between groups, but the mean HDL-cholesterol level was lower in symptomatic patients (1.24+/-0.38 versus 1.42+/-0.41, P<0.0001). Cysteine levels were higher in patients with cardiovascular disease than in asymptomatic patients, respectively 254.7+/-47.7 versus 239.1+/-44.3 micromol/l (P = 0.003). A similar result was found for homocysteine, respectively 13.1+/-4.3 versus 12.2+/-3.9 micromol/l (P = 0.05). To analyse whether cysteine levels were related to atherosclerosis independently of age, adjusted levels were compared between asymptomatic patients with normal carotid arteries (n = 176), carotid atherosclerosis (n = 107) and symptomatic patients (n = 106). Age adjusted cysteine levels differed significantly between groups (P = 0.027) while the P-value was of borderline significance for homocysteine (P = 0.09). Odds ratios for having symptomatic cardiovascular disease were 1.81 (95% CI, 1.02-3.21) and 2.05 (95% CI, 1.16-3.60) for the mid and highest tertiles of cysteine using the lowest as the reference. After adjustment in a multivariate model including age, sex, and creatinine, the odds ratio for disease remained significant between the highest tertile versus the lowest (OR = 1.89). Adjusted odds ratios were found to be weaker when homocysteine tertiles were compared. Our data suggest that plasma total cysteine is a risk factor for atherosclerosis in hyperlipidemic patients.
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PMID:Cysteine is a cardiovascular risk factor in hyperlipidemic patients. 1048 86

Over the last 10 years, there has been an explosion of interest in homocysteine, a sulfur-containing amino acid that occupies a central location in the metabolic pathways of thiol compounds. This interest is primarily because of the realization that hyperhomocysteinemia is an important risk factor for vascular disease, including stroke, independent of long-recognized factors such as hyperlipidemia, hypertension, diabetes mellitus, and smoking. Since elevated homocysteine levels can often be normalized by supplementing the diet with folic acid (folate), pyridoxine hydrochloride (vitamin B(6)), and cyanocobalamin (vitamin B(12)), these observations raise the exciting possibility that this inexpensive and well-tolerated therapy may be effective in decreasing the incidence of vascular disease. In addition to its association with cerebrovascular disease, homocysteine may play a role in neurodegenerative disorders, even if only as a marker of functional vitamin B(12) deficiency. Homocysteine is also important to neurologists since most anticonvulsants raise homocysteine levels, an effect that may explain the teratogenic effects of these drugs. Practical knowledge concerning some details of homocysteine metabolism, the diagnosis of hyperhomocysteinemia, and the use of polyvitamin therapy to lower homocysteine levels will be increasingly important in the treatment of patients with neurologic disease. Arch Neurol. 2000;57:1422-1428
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PMID:Homocysteine and neurologic disease. 1103 Jul 93

Various lifestyle factors have been associated with increasing the risk of stroke. These include lack of exercise, alcohol, diet, obesity, smoking, drug use, and stress. Guidelines endorsed by the Centers for Disease Control and Prevention and the National Institutes of Health recommend that Americans should exercise for at least 30 minutes of moderately intense physical activity on most, and preferably all, days of the week. Recent epidemiologic studies have shown a U-shaped curve for alcohol consumption and coronary heart disease mortality, with low-to-moderate alcohol consumption associated with lower overall mortality. High daily dietary intake of fat is associated with obesity and may act as an independent risk factor or may affect other stroke risk factors such as hypertension, diabetes, hyperlipidemia, and cardiac disease. Homocysteine is another important dietary component associated with stroke risk, while other dietary stroke risk factors are thought to be mediated through the daily intake of several vitamins and antioxidants. Smoking, especially current smoking, is a crucial and extremely modifiable independent determinant of stroke. Despite the obstacles to the modification of lifestyle factors, health professionals should be encouraged to continue to identify such factors and help improve our ability to prevent stroke.
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PMID:Lifestyle factors and stroke risk: exercise, alcohol, diet, obesity, smoking, drug use, and stress. 1112 40

The effect of fenofibrate (FEN), compared with placebo (PL), on total plasma homocysteine (tHcy) levels in the fasted and fed states has been examined. Twenty men with established coronary artery disease (CAD) or with at least two cardiovascular risk factors, who had elevated plasma triglyceride levels (> 2.3 mmol/l) and reduced HDL-C levels (< 0.91 mmol/l), and in whom a fibric acid derivative was clinically indicated were studied. The study was a randomized, PL controlled, double-blind study designed to test the effect of micronized FEN on postprandial lipemia. Plasma tHcy levels were investigated as a post-hoc analysis. After a 4-week dietary stabilization period, patients were randomized to PL or FEN (200 mg/day) for 8 weeks, followed by an 8-h postprandial study, consisting of 1 g fat/kg body weight (35% cream). The methionine content of cream was approximately 0.53 mg/ml. A 5-week washout period was then followed by a second 8-week treatment period (FEN or PL), at the end of which a second postprandial study was undertaken. Blood was sampled in the fasted state (0 h) and postprandially at 2, 4, 6 and 8 h. Plasma was stored at -80 degrees C for homocysteine, vitamins B(6), B(12) and folate measurements. FEN caused a marked decrease in all triglyceride-rich lipoprotein parameters, no change in LDL-C, and an increase in HDL-C levels. Fen treatment was associated with an increase in fasting tHcy (PL: 10.3+/-3.3 micromol/l to FEN: 14.1+/-3.8 micromol/l, 40.4+/-20.5%, P < 0.001) and fed tHcy levels 6 h post-fat load (PL: 11.6+/-3.3 micromol/l vs. FEN: 17.1+/-5.4 micromol/l, P < 0.001). Homocysteine levels were increased by the fat load; PL: 14% (P < 0.001) and FEN: 21%, P < 0.001 at the 2, 4, 6 and 8 h time points. Change in tHcy level on FEN was not associated with changes in plasma levels of folate, vitamins B(6) or B(12) or creatinine. Amino acid analysis revealed that methionine and cysteine were significantly increased on FEN (P < 0.005). The incidence of hyperhomocysteinemia (defined as tHcy level >14 micromol/l) was PL: 2/20 (10%) and FEN: 9/20 (45%) (chi(2) = 4.51, P = 0.034). There was no correlation between changes in plasma triglyceride levels and tHcy levels. Since tHcy is considered an emerging cardiovascular risk factor, the ability of FEN to increase plasma tHcy levels could potentially mitigate the potential of this drug to protect against cardiovascular disease.
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PMID:Fenofibrate raises plasma homocysteine levels in the fasted and fed states. 1125 17

This study was performed to assess the significance of association between coronary artery disease (CAD) and circulating homocysteine concentrations. 100 consecutive CAD patients (78 men and 22 women, aged 31 to 79 years) qualified for PTCA were investigated. At the time of PTCA, the risk factors for CAD and plasma for homocysteine and vitamins were obtained. The controls were without clinical evidence of coronary artery disease and hypertension (90 men and 30 women aged 32 to 81 years). Homocysteine was assayed using ELISA test. Red cell folate and plasma vitamin B12 were assayed by immunofluoroscency (Delphia test). Homocysteine concentrations were higher in patients than in controls (13.61 +/- 4.5 vs 10.99 +/- 4.49 mumol/L, p < 0.001, adjusted for age). Male patients had nonsignificantly higher homocysteine levels than females (13.94 +/- 5.21 vs 11.46 +/- 5.16 mumol/L, p = 0.05, adjusted for age). Elevated homocysteine level--defined as one in the top fifth of the control distribution > or = 12.83 mumol/L--was seen in 46% of the patients compared with 20% of the control group (p = 0.001). The odds ratio (OR) for CAD in persons with elevated homocysteine level was 3.1 (95% Cl 1.6-5.8, p < 0.001, adjusted for age). The OR for CAD of 5 mumol/L increment in homocysteine level was 2.1 (95% Cl 1.4-3.1 p < 0.001, adjusted for age). After adjustment for conventional risk factors (age, smoking, hypertension, family history of CAD, hyperlipidemia), elevated homocysteine level remained independent risk factor for CAD (OR 2.88, 95% Cl 1.1-7.8, p < 0.05). We observed inverse correlation between homocysteine and folate level (r = -0.32, p = 0.005) and between homocysteine and vitamin B12 concentrations (r = -0.24, p = 0.03), especially in men. Patients with elevated homocysteine level had lower levels of folate (629.6 +/- 241.2 nmol/L vs 735.1 +/- 252.4 nmol/L, p < 0.05), and vitamin B12 (213.6 +/- 64.4 pmol/L vs 246.6 +/- 62.3 pmol/L, p < 0.05) than patients with normal level of homocysteine. Elevated plasma homocysteine level is a strong risk factor for coronary artery disease. A 5 mumol/L increment in total homocysteine level may be associated with twofold increase of risk for the disease.
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PMID:[Elevated levels of homocysteine in plasma as a risk factor for coronary artery disease]. 1130 24

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

Homocysteine is considered to be an independent risk factor for atherosclerosis. Experimental animal models of hyperhomocysteinemia show aortic calcification, suggesting that this disorder is associated with aortic calcification in humans. A total of 28 patients with hyperlipidemia were enrolled into this study. The degree of aortic calcification at the level of the bifurcation and 1 cm proximal to the bifurcation was assessed by computed tomography of the aorta and the association between calcification of the aorta and the plasma level of homocysteine was then analyzed. The mean plasma homocysteine level in 28 patients was 8.7 microM. They were divided into 2 groups, high homocysteine level group (HHL; homocysteine level >8.7 microM) and low homocysteine level group (LHL; homocysteine level < = 8.7 microM). The degree of aortic calcification at the level of the bifurcation differed significantly between the two groups (19.1% vs. 10.5%; p < 0.01). We found that mild hyperhomocysteinemia was associated with aortic calcification, which suggests that interventions to reduce the plasma level of homocysteine may also reduce the severity of aortic calcification.
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PMID:Association of mild hyperhomocysteinemia with aortic calcification in hypercholesterolemic patients. 1186 36


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