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

In 482 patients sequentially referred for diagnosis and therapy of hyperlipidemia, our specific aim was to determine the prevalence of homocysteinemia, to assess whether it was independently associated with atherosclerotic vascular disease, and to determine how effectively high homocysteine could be treated with folic acid and pyridoxine. Of the 482 patients, 18 (3.7%) had high homocysteine (> or = 16.2 mumol/L, median = 19), 31 had high cystathionine (> or = 342 nmol/L) with normal homocysteine (median = 12), and 433 had normal cystathionine and homocysteine (median = 9). Of the 18 patients with high homocysteine, 13 (72%) had atherosclerotic vascular disease, much higher than the 44% (192 of 433 patients) with normal homocysteine (chi-square = 5.4, p = 0.02). In the 18 kindreds with a homocysteinemic proband, 14 (78%) had > or = 1 first-degree relatives with atherosclerotic vascular disease before age 65, compared with 50% (215 of 433) of the families where the proband had normal homocysteine (chi-square = 5.5, p = 0.02). In the 482 patients already at high risk for atherosclerotic vascular disease by virtue of hyperlipidemia, when assessed by logistic regression, homocysteine was an independent positive predictor of atherosclerotic vascular disease (p = 0.007); relative risk for atherosclerotic events was 2.8 times higher (p = 0.0004) in patients with top (> or = 11.4 mumol/L) than with bottom (< 6.9 mumol/L) quintile homocysteine. After 15 weeks of folic acid (5 mg/day) and pyridoxine (100 mg/day) therapy in 10 patients with high homocysteine, median homocysteine normalized, decreasing from 18 to 11 mumol/L (p = 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Evidence that homocysteine is an independent risk factor for atherosclerosis in hyperlipidemic patients. 781 Apr 87

Vascular damage in systemic lupus erythematosus (SLE) occurs through vasculitis, premature atherosclerosis, and hypercoagulability (predominantly due to the antiphospholipid antibody syndrome). In the Hopkins Lupus Cohort, a prospective cohort study, the incidence of thrombosis is 2 per 100 person-years of follow-up. Markers of immune-complex mediated injury (high anti-dsDNA and low C3), atherosclerosis (hypertension, hyperlipidemia, homocysteine) and antiphospholipid antibodies (lupus anticoagulant or anticardiolipin) are independent predictors of thrombosis. Hydroxychloroquine use is protective against future thrombosis.
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PMID:Thrombosis and systemic lupus erythematosus: the Hopkins Lupus Cohort perspective. 879 94

A common mutation (C677-->T) in methylenetetrahydrofolate (MTHFR) gene, involved in the metabolism of homocysteine, has been suggested to play a role in increasing cardiovascular disease risk. We determined the frequency of C677-->T genotypes and alleles in 155 Caucasian patients with angiographically documented coronary artery disease (CAD) and in 155 age and sex matched normal Caucasian individuals. DNA was extracted from the blood and genotypes were determined by polymerase chain reaction, restriction mapping with HinfI and gel electrophoresis. The distribution of MTHFR C677-->T genotypes followed the Hardy-Weinberg equilibrium. The distribution of MTHFR genotypes and the frequency of alleles were similar in cases and controls. The TT genotype was present in 8% of controls as compared to 6% of cases (P = 0.50, OR = 0.82; 95% CI: 0.34-1.96). The frequency of T allele was also similar in patients with CAD compared with controls (0.29 vs. 0.33; P = 0.29). There was also no significant association between C677-->T genotypes and the risk of myocardial infarction. In a subgroup of 44 cases and 89 controls who had no conventional risk factors for CAD (hyperlipidemia, hypertension, diabetes mellitus, and smoking), the frequency of TT genotype was similar (11% vs. 8%, respectively, P = 0.71, OR: 0.67, 95% CI: 0.20-2.23). Thus, the MTHFR TT genotype is not a major genetic risk factor for predisposition to CAD and its thrombotic complications in this population.
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PMID:A common mutation in methylenetetrahydrofolate reductase gene is not a major risk of coronary artery disease or myocardial infarction. 905 Dec 3

Our specific aim was to examine the interface between risk factors for atherosclerosis, thrombosis, and hypofibrinolysis in a previously healthy 35-year-old male who had sustained a recent myocardial infarction. By angiography, the right, left main, and left anterior descending coronary arteries were smooth-walled, widely patent, and free of significant obstruction; the circumflex exhibited total, probably thrombotic occlusion of the distal large second marginal branch. The patient was found to have prothrombotic high homocysteine (46.4 mumol/L), prothrombotic resistance to activated protein C (ratio, 1.47), and hypofibrinolytic high plasminogen activator inhibitor (PAI-Fx) activity (54 U/mL). He was homozygous for the 677C-->T; A-->V mutation in the methylenetetrahydrofolate reductase (MTHFR) gene causing homocysteinemia, heterozygous for the mutant factor V Leiden gene causing resistance to activated protein C, and heterozygous for the 4G/5G polymorphism in the PAI-1 promoter gene causing high PAI-Fx. Other major risk factors for coronary artery disease included previously undiagnosed adult-onset diabetes, high triglycerides (291 mg/dL), and low high-density lipoprotein (HDL) cholesterol (26 mg/dL). The patient's prothrombotic status (homocysteinemia and resistance to activated protein C) and hypofibrinolysis (high PAI-Fx) apparently facilitated occlusive coronary artery thrombus formation and retention. Prothrombotic factors and hypofibrinolysis appear to play important pathogenetic roles in premature myocardial infarction. In patients with severe premature coronary artery disease, we suggest that interactions between prothrombotic factors, hypofibrinolysis, and hyperlipidemia-atherosclerosis be regularly evaluated, since such interactions may have ramifications for the outcome of short- and long-term secondary prevention. Moreover, in patients with heritable prothrombotic factors or hypofibrinolysis, it should be important to optimize lipid and lipoprotein cholesterol levels with the goal of stabilizing coronary plaques to reduce the likelihood of plaque rupture and thrombosis.
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PMID:Myocardial infarction in a 35-year-old man with homocysteinemia, high plasminogen activator inhibitor activity, and resistance to activated protein C. 943 45

The study sought to define the relation of plasma total homocysteine to biological and clinical variables and to serum vitamin concentrations in patients with primary hyperlipidaemia. Fasting plasma total homocysteine was measured in 219 men and 159 women; vitamin concentrations were available for about 60% of the sample. Men had significantly higher plasma total homocysteine than women [median (25th, 75th percentiles) 9.4 (8.2, 11.5) mumol L-1 vs. 8.5 (7.0, 10.2) mumol L-1; P = 0.0001]. Plasma total homocysteine was lower in women taking lipid-lowering drugs than in women who were not taking drugs. Serum folate and vitamin B12 concentrations were normal for all but one and four subjects respectively. Correlations (P < or = 0.06) were found between plasma total homocysteine and age, triglyceride concentration in women, uric acid concentration in men, serum folate, vitamin B12 and creatinine concentrations. In multiple regression analysis, the association between plasma total homocysteine and sex and between plasma total homocysteine and use of lipid-lowering drugs disappeared when creatinine concentration was entered into the analysis. This study shows that plasma total homocysteine is related to vitamin concentrations within the normal range, suggesting that plasma total homocysteine may be modifiable by diet in hyperlipidaemic subjects with normal vitamin nutrition. Sex-related differences appear to be related to men's higher creatinine concentration. Whether lipid-lowering drugs interact with total homocysteine concentration requires further study.
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PMID:Correlates of plasma total homocysteine in patients with hyperlipidaemia. 946 31

Mild hyperhomocysteinemia has been associated with an increased risk to develop premature coronary heart disease. Recently, the homocysteine concentration has been positively correlated with several main cardiovascular risk factors. We addressed the issue as to whether patients with coronary heart disease and a low cardiovascular risk profile also have a higher prevalence of hyperhomocysteinemia than matched controls. Ninety-five patients (aged 50.5 +/- 6.6 years) and 34 controls (50.0 +/- 6.7 years) less than 60 years of age were selected from a sample of patients after coronary angiography. Subjects with hypertension, diabetes, and moderate or severe hyperlipidemia were excluded. We determined plasma aminothiols (total homocysteine, cysteine, and glutathione), lipoprotein fractions, fibrinogen, and uric acid, the body mass index (weight in kilograms divided by height in meters squared), and the waist to hip ratio. Furthermore, 37 healthy subjects aged 30.8 +/- 7.5 years underwent aminothiol determinations. Patients and controls were similar with regard to age and primary cardiovascular risk factors. Total homocysteine concentrations in the patient group (9.2 +/- 2.4 micromol/L) were significantly higher than in the healthy subjects (8.0 +/- 2.0 micromol/L). However, they did not differ from the levels in the age-matched controls (9.3 +/- 3.0 micromol/L). Neither total cysteine nor glutathione concentrations were significantly different between patients and controls. Male patients (n = 85) had higher mean very-low-density lipoprotein (VLDL) triglycerides (1.36 +/- 0.90 mmol/L) and lower high-density lipoprotein 3 (HDL3) cholesterol (0.75 +/- 0.21 mmol/L) than male controls (n = 28; 1.01 +/- 0.62 and 0.88 +/- 0.26 mmol/L, respectively). Female patients did not have any significant differences in lipoprotein concentrations versus the controls. Among further cardiovascular risk factors, we found a higher prevalence of central obesity in male patients. In conclusion, there was not a higher incidence of hyperhomocysteinemia among patients with premature coronary heart disease and a low cardiovascular risk profile. The higher prevalence of hyperhomocysteinemia found in other studies may be related to the primary risk factors seen in these populations, and may therefore be an indicator of the global cardiovascular risk.
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PMID:Plasma total homocysteine levels in patients with early-onset coronary heart disease and a low cardiovascular risk profile. 950 May 62

Epidemiologic data obtained over the past 30 years suggest that a number of new biologic markers are associated with increased risk for cardiovascular disease. These include indices related to (1) altered glucose metabolism, particularly insulin resistance; (2) hyperlipidemia; (3) elevated levels of lipoprotein(a) and homocysteine; (4) increased levels of molecules reflecting decreased fibrinolysis and increased activation of the coagulation cascade; (5) elevations in cell adhesion molecules and other markers of endothelial function; and (6) elevations in molecules associated with infection, inflammation, and vascular remodeling. Changes in molecules associated with increased risk usually occur in clusters. This clustering suggests that effective treatment of one marker may have positive effects on multiple markers. Indeed, several studies have demonstrated that therapies designed to reduce hyperlipidemia may also lower the plasma levels of factors associated with increased coagulation and reduced fibrinolysis. Thus, careful assessment of patient risk factors, and the development of therapies directed toward chains of markers associated with increased risk, may significantly alter the course of cardiovascular disease.
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PMID:Biologic markers as predictors of cardiovascular disease. 968 48

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

Stroke is the third leading cause of death and the leading cause of chronic disability in the United States. In the past several decades, case series, case-control studies, and prospective cohort studies have successfully identified nonmodifiable risk markers for stroke, such as age, gender, race, ethnicity, heredity and several well-established modifiable risk factors for ischemic stroke. Hypertension, atrial fibrillation, other cardiac diseases, hyperlipidemia, diabetes, cigarette smoking, physical inactivity, carotid stenosis, and transient ischemic attack (TIA) are all potentially treatable conditions that predispose to stroke. Research on other putative stroke risk factors-including antiphospholipid antibodies, elevated homocysteine, alcohol, inflammation, and infection-is ongoing. Controlled trials have shown that stroke risk can be reduced by blood-pressure control, lipid-lowering agents, surgery for carotid stenosis, warfarin for atrial fibrillation, and antiplatelet agents. It is hoped that an improved understanding of stroke risk factors will reduce the future burden of stroke.
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PMID:Stroke risk factors and stroke prevention. 993 14


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