UMLS:C0020473 - FACTA Search

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)

The objectives of this study were (1) to determine the incidence of dominantly inherited hyperlipoproteinemia in children referred to our medical center because of hyperlipidemia associated with a family history of premature coronary artery disease and (2) to assess the degree of expression in childhood of the most common inherited hyperlipoproteinemia, familial combined hyperlipidemia. Among 129 families referred to us by area pediatricians, we identified a dominantly inherited hyperlipoproteinemia in 97 of them. Twenty had familial hypercholesterolemia, 65 familial combined hyperlipidemia, 11 hyperapobetalipoproteinemia, and one familial hypertriglyceridemia. As expected, almost half (9/20) of the siblings of probands with familial hypercholesterolemia were affected. Although we expected incomplete gene penetrance in the siblings of the probands with familial combined hyperlipidemia, we found 43 affected and 40 unaffected among the 83 siblings of the 65 probands. Our findings suggest that hyperlipidemia in children, caused by familial combined hyperlipidemia, occurs more than three times as frequently as familial hypercholesterolemia and that in families identified by a child proband, the penetrance is complete. Pediatricians should identify this primary hyperlipidemia in childhood and attempt to prevent the associated risk of premature coronary artery disease by prescribing appropriate diet and life-style modifications.
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PMID:Prevalence and expression of familial combined hyperlipidemia in childhood. 231 96

We investigated the metabolism of very low density lipoprotein (VLDL), intermediate density lipoprotein (IDL), and low density lipoprotein (LDL) apolipoprotein B (apoB) in seven patients with combined hyperlipidemia (CHL), using 125I-labeled VLDL and 131I-labeled LDL and compartmental modeling, before and during lovastatin treatment. Lovastatin therapy significantly reduced plasma levels of LDL cholesterol (142 vs 93 mg/dl, P less than 0.0005) and apoB (1328 vs 797 micrograms/ml, P less than 0.001). Before treatment, CHL patients had high production rates (PR) of LDL apoB. Three-fourths of this LDL apoB flux was derived from sources other than circulating VLDL and was, therefore, defined as "cold" LDL apoB flux. Compared to baseline, treatment with lovastatin was associated with a significant reduction in the total rate of entry of apoB-containing lipoproteins into plasma in all seven CHL subjects (40.7 vs. 25.7 mg/kg.day, P less than 0.003). This reduction was associated with a fall in total LDL apoB PR and in "cold" LDL apoB PR in six out of seven CHL subjects. VLDL apoB PR fell in five out of seven CHL subjects. Treatment with lovastatin did not significantly alter VLDL apoB conversion to LDL apoB or LDL apoB fractional catabolic rate (FCR) in CHL patients. In three patients with familial hypercholesterolemia who were studied for comparison, lovastatin treatment increased LDL apoB FCR but did not consistently alter LDL apoB PR. We conclude that lovastatin lowers LDL cholesterol and apoB concentrations in CHL patients by reducing the rate of entry of apoB-containing lipoproteins into plasma, either as VLDL or as directly secreted LDL.
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PMID:Lovastatin therapy reduces low density lipoprotein apoB levels in subjects with combined hyperlipidemia by reducing the production of apoB-containing lipoproteins: implications for the pathophysiology of apoB production. 235 67

The relationship between apolipoprotein E (Apo E) phenotypes and progression of coronary atherosclerosis was investigated in 125 patients with coronary artery disease (CAD) proven angiographically (101 males, 24 females). To elucidate the pure effect of Apo E phenotypes on lipoproteins and coronary atherosclerosis, patients with familial hypercholesterolemia were excluded from the subjects. As a control group, 129 normal healthy volunteers (84 males, 45 females) were studied. In the CAD group, VLDL and LDL levels increased and HDL level decreased regardless of Apo E phenotypes in both sexes. The incidence of E4 was higher and that of E2 was slightly lower in the CAD group than in the control group. Two patients with E5/3 who had high LDL-cholesterol levels were found in the male CAD group. LDL-cholesterol level in E3/2 was lower than in E4/3 and E3/3 in the male CAD group. VLDL-cholesterol/triglyceride and VLDL cholesterol/phospholipid ratios in E3/2 were significantly higher than in E4/3 and E3/3 in the male CAD group, but the difference was not so marked as found in typical type III hyperlipidemia. When the male patients with effort angina were examined, coronary score (index of the severity of CAD) was the lowest in E3/2. In addition, the mean age at the onset of CAD was significantly higher in E3/2 than in E4/3. In conclusion, E2 acts protectively against coronary atherosclerosis, while E4 promotes it through the modulation of LDL-cholesterol level.
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PMID:Apolipoprotein E phenotypes in patients with coronary artery disease. 235 52

Double-filtration plasmapheresis is a therapeutic procedure for the extracorporeal depuration of atherogenic lipoproteins, which does not require the administration to the patient of exogenous fluids. We have used it in two patients affected by hyperlipidemia with severe cardiovascular complications. Both patients presented a dramatic improvement of their symptoms (angina pectoris and claudicatio intermittens) shortly after the beginning of treatment. By the brisk reduction of circulating low-density lipoproteins, plasma-filtration may favor the removal of cholesterol from atheromatous plaques of vessel walls. Furthermore, this procedure may modify platelet aggregation and blood viscosity. Our observation suggests that plasma-filtration may be useful not only for delaying coronary heart disease in the rare cases of homozygous familial hypercholesterolemia, but also in the management of patients with other primary hyperlipoproteinemias and clinical manifestations of already established cardiovascular complications.
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PMID:[Double filtration plasmapheresis in the treatment of vascular complications of hyperlipidemia]. 237 5

The principal goal of dietary prevention and treatment of atherosclerotic coronary heart disease is the achievement of physiological levels of the plasma total and LDL cholesterol, triglyceride, and VLDL. These goals have been well delineated by the National Cholesterol Education Program of the National Heart, Lung and Blood Institute and the American Heart Association. Dietary treatment is first accomplished by enhancing LDL receptor activity and at the same time depressing liver synthesis of cholesterol and triglyceride. Both dietary cholesterol and saturated fat decrease LDL receptor activity and inhibit the removal of LDL from the plasma by the liver. Saturated fat decreases LDL receptor activity, especially when cholesterol is concurrently present in the diet. The total amount of dietary fat is of importance also. The greater the flux of chylomicron remnants is into the liver, the greater is the influx of cholesterol ester. In addition, factors that affect VLDL and LDL synthesis could be important. These include excessive calories (obesity), which enhance triglyceride and VLDL and hence LDL synthesis. Weight loss and omega-3 fatty acids from fish oil depress synthesis of both VLDL and triglyceride in the liver. The optimal diet for the treatment of children and adults to prevent coronary disease has the following characteristics: cholesterol (100 mg/day), total fat (20% of calories, 6% saturated with the balance from omega-3 and omega-6 polyunsaturated and monounsaturated fat), carbohydrate (65% of calories, two thirds from starch including 11 to 15 gm of soluble fiber), and protein (15% of calories). This low-fat, high-carbohydrate diet can lower the plasma cholesterol 18% to 21%. This diet is also an antithrombotic diet, thrombosis being another major consideration in preventing coronary heart disease. Dietary therapy is the mainstay of the prevention and treatment of coronary heart disease through the control of plasma lipid and lipoprotein levels. The exact place of the omega-3 fatty acids from fish and fish oil remains to be defined. However, this much seems certain. Fish provides an excellent substitute for meat in the diet. Fish is lower in fat, especially saturated fat, and contains the omega-3 fatty acids. Fish oil may have promise as a therapeutic agent in certain hyperlipidemic states, especially the chylomicronemia of type V hyperlipidemia. Fish oil has logical and well-defined antithrombotic and anti-atherosclerotic activities since it depresses thromboxane A2 production and inhibits cellular proliferation responsible for the progression of atherosclerosis.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Diet, atherosclerosis, and fish oil. 240 91

Hyperlipidemia, long recognized as a difficult and common problem following organ transplantation, may be the underlying cause of the accelerated atherosclerosis observed in heart transplant recipients and children with renal transplants. In addition, hyperlipidemia may play a role in late renal graft loss. The cause of post-transplant hyperlipidemia is unclear. In patients treated with azathioprine and prednisone, hypertriglyceridemia is the commonest finding and probably results from an increased consumption of calories from carbohydrate and fat following resolution of uremia, in conjunction with glucose intolerance secondary to steroid administration. In patients treated with cyclosporine, hypercholesterolemia is the most common form of hyperlipidemia. Cyclosporine is a lipophilic drug that is transported in the plasma, largely in association with lipoproteins, and may require the low-density lipoprotein (LDL) receptor for internalization into cells. Hypercholesterolemia may result from interference with the basic cholesterol feedback mechanism via the LDL receptor. In addition, cyclosporine affects bile acid synthesis and worsens glucose tolerance, both factors that may promote hyperlipidemia. The first therapeutic approach to hyperlipidemia in the transplant recipient is dietary calorie-fat restriction and supplementation with soluble fiber. Ongoing clinical trials of the available pharmacologic lipid-lowering agents are addressing the safety and efficacy of these agents in the setting of immunosuppression; until that time, they should be used cautiously and in low doses.
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PMID:Hyperlipidemia after organ transplantation. 248 50

In the United Kingdom, about 5% of patients with familial hypercholesterolemia (FH) have a detectable deletion or rearrangement of part of the LDL-receptor gene, which results in the detection of shorter or abnormally sized fragments of the LDL-receptor gene in a Southern blot hybridization. This gene deletion can be used for following the inheritance of the defective gene and for diagnosis in the families of these individuals. In the families of the remaining patients, diagnosis may be possible using linked restriction fragment length polymorphisms (RFLPs) detected with the LDL-receptor probe. There are now 10 common RFLPs of the LDL-receptor gene, with variable sites in the 3' half of the gene. Over 80% of patients are heterozygous for at least one of these RFLPs, and, therefore, RFLPs are potentially informative for DNA diagnosis. For a fetus at risk of homozygous FH, antenatal diagnosis may also be possible using these methods. However, family studies require samples to be available from affected or unaffected relatives of the patient, and this limits the applicability of the tests. For some mutations, the base-pair change causing the defect in the LDL receptor itself creates or destroys a site for a restriction enzyme. Such "mutation-specific" RFLPs could be used for population screening, but, so far, such use has only been reported for the FH mutation common in Lebanon. In the future, it may be possible to develop mutation-specific oligonucleotide probes for the diagnosis of FH. These would be appropriate for screening populations or patients with hyperlipidemia. This information may also be useful if different mutations require different therapeutic strategies.
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PMID:Gene probes in diagnosis of familial hypercholesterolemia. 256 21

A monoclonal antibody-based direct binding enzyme-linked immunosorbent assay (ELISA) for apoprotein (apo) B-100 has been developed for use as a reference method. The assay uses the two well-characterized monoclonal antibodies, MB24 and MB47. MB47, which recognizes an epitope at the low density lipoprotein (LDL) receptor-binding domain of apoB and is specific for apoB-100, is bound to the microtiter plate as the capture antibody. MB24, which binds an epitope in the amino terminal half of the apoB-100 and identifies both apoB-100 and apoB-48, is conjugated to horseradish peroxidase and is utilized as the indicating antibody. The assay was calibrated with LDL (d 1.030-1.050 g/ml) and the LDL protein was determined by a sodium dodecyl sulfate (SDS) Lowry procedure. The working range of the assay is 0.25-1.25 micrograms/ml. Optimal dilution of whole plasma was found to be 1:2000. In the assay, MB47 bound approximately 97% of the apoB in all low density lipoprotein, and greater than 90% of the apoB in the majority of very low density lipoprotein preparations. Small dense LDL from subjects with familial combined hyperlipidemia (FCHL) and large bouyant LDL from subjects with familial hypercholesterolemia (FH) exhibited binding properties similar to LDL from healthy normolipidemic subjects when tested in the reference ELISA. The intra- and interassay coefficients of variation averaged 2.5% and 6.0%, respectively. Plasma B-100 levels were not influenced by freezing and thawing or storage at 4 degrees C for up to 3 weeks or storage at -70 degrees C for up to 11 months. Excellent agreement was obtained between the reference ELISA and a polyclonal RIA which measures total apoB (r = 0.93, n = 105, mean ELISA B-100 value = 100 mg/dl, mean RIA value = 101 mg/dl, Sy = 9.6). Reference ELISA B-100 values of samples pretreated with bacterial lipase were not significantly increased in most samples with plasma triglyceride levels below 600 mg/dl. To help reduce the large among-laboratories variability of apoB measurements, we recommend that this candidate reference direct binding ELISA be used to assign apoB target values to apoB reference pools.
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PMID:Evaluation of a monoclonal antibody-based enzyme-linked immunosorbent assay as a candidate reference method for the measurement of apolipoprotein B-100. 260 May 45

This study was designed to examine the influence of combined therapy with bezafibrate and cholestyramine on plasma lipids and on the metabolism of low-density lipoprotein (LDL). Twenty-one type II hyperlipidemic subjects were treated with bezafibrate alone or in combination with cholestyramine. A 17% fall in plasma cholesterol was seen with bezafibrate, and addition of cholestyramine produced an additional 9% reduction in this lipid. The effectiveness of the combination therapy was mediated through a 47% decrement in very-low-density lipoprotein (VLDL) cholesterol, a 37% reduction in LDL cholesterol, and a 15% increase in the level of that lipid in high-density lipoprotein (HDL). Plasma triglyceride fell 43% when bezafibrate was given alone, and did not change further when cholestyramine was added. The metabolism of LDL was examined in nine individuals to determine the mechanism underlying these changes. No significant modification in LDL synthetic rate was incurred with either drug regimen, whereas the fractional catabolic rate of LDL via the receptor pathway rose by 66% with bezafibrate alone and by 79% (compared to baseline) following the addition of cholestyramine. Plasma HDL rose during bezafibrate therapy due to an increase in the HDL3 subfraction. Compositional analysis of LDL showed a reduction in cholesterol ester and an increase in triglyceride and phospholipid during combined drug therapy. These results demonstrate that combined therapy with bezafibrate and cholestyramine markedly improves the lipoprotein profile in type II hyperlipidemia. The drugs appear to be complementary in their actions upon the LDL receptor pathway.
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PMID:Effect of combined therapy with bezafibrate and cholestyramine on low-density lipoprotein metabolism in type IIa hypercholesterolemia. 264 51

Recent trials have investigated the usefulness of fenofibrate, alone and in combination with other lipid-lowering therapies, in the treatment of hyperlipidemia. Studies of fenofibrate + bile acid sequestrants demonstrate that these two therapies may have an additive effect in reducing total cholesterol, low-density lipoprotein (LDL) cholesterol, very-low-density lipoprotein (VLDL) cholesterol and triglyceride levels in patients with hyperlipoproteinemia or familial hypercholesterolemia. These lipoprotein changes have been associated with a regression of tendon xanthoma. Pharmacokinetic studies have shown that bile acid sequestrants do not alter the absorption or the plasma levels of fenofibrate. The combined use of fenofibrate with bile acid sequestrants has been found to be comparably effective with the new 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, synvinolin, with respect to the reduction of total cholesterol and LDL. Although synvinolin was more effective in lowering LDL, VLDL cholesterol and triglycerides were reduced to a greater extent with fenofibrate. Another notable difference was that fenofibrate + bile acids more markedly increased HDL levels. The combination of fenofibrate + nicotinic acid also appears to have a beneficial effect on lipoproteins. These preliminary results indicate that fenofibrate may be a useful addition to the present lipid-lowering drug armamentarium.
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PMID:Review of clinical studies of fenofibrate in combination with currently approved lipid-lowering drugs. 265 23

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