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)

Liver disorders characterized by prolonged bile stasis are often associated with the accumulation of an abnormal lipoprotein, lipoprotein-X (LP-X), in plasma. LP-X is separated in the low-density lipoprotein (LDL) density range, but lacks apolipoprotein B and does not interact with the LDL receptor; LP-X can cause hyperlipidemia, cutaneous xanthomas, and worsening of arterial disease. We report the case of a patient with severe cholestasis, markedly elevated plasma cholesterol levels (26.8 to 31.5 mmol/L), mainly due to a massive accumulation of LP-X in plasma, and diffuse xanthomas. To reduce the elevated cholesterol levels, the patient was given extracorporeal treatment aimed at removing atherogenic lipoprotein (LDL-apheresis). LDL-apheresis was performed at weekly or bi-weekly intervals, either by a semi-selective technique using filters with a defined pore diameter (double filtration, DF) or by a more selective technique using dextran-sulfate-cellulose (DSC) columns able to bind LDL. The semi-selective DF technique proved more effective than DSC, removing 48% of total cholesterol (compared to 30% with DSC), and lowering cholesterol levels to 11.1 mmol/L in 6 weeks. DF removed both LDL and LP-X from plasma, whereas DSC selectively decreased the LDL content. The reduction of plasma cholesterol levels was associated with a complete regression of the xanthomas, supporting DF apheresis as a first-choice treatment for patients with massive LP-X accumulation due to cholestasis.
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PMID:Management of lipoprotein-X accumulation in severe cholestasis by semi-selective LDL-apheresis. 202 22

beta-Very low density lipoproteins (beta-VLDLs) are atherogenic, cholesterol-rich chylomicron and VLDL remnants that accumulate in the plasma of type III dysbetalipoproteinemic subjects. To evaluate the effect of fish oil supplementation on plasma beta-VLDL concentrations, we compared the lipid and lipoprotein responses in nine type III and nine type IV hyperlipidemic subjects. Each individual received 6 g/day omega-3 fatty acids for 12 weeks. Before treatment, the mean total cholesterol, total triglyceride, VLDL triglyceride, low density lipoprotein (LDL) cholesterol, and high density lipoprotein (HDL) cholesterol levels were not different between groups. Conversely, VLDL cholesterol, intermediate density lipoprotein (IDL) cholesterol, and IDL triglycerides were higher in type III than in type IV subjects. Fish oil supplementation was associated with significantly lower levels of cholesterol (-50%), triglycerides (-50%), and apolipoprotein B (-50%) in the d less than 1.006 g/ml ultracentrifugation plasma fraction in both groups, compatible with a reduction in VLDL in type III and type IV subjects, and in beta-VLDL in type III subjects. This finding was confirmed by analysis of the plasma zonal ultracentrifugation profile and the agarose gel electrophoretic pattern of lipoproteins, which showed a reduction in but not a disappearance of remnant particles, suggesting that not all beta-VLDL had been cleared after treatment. The levels of IDL cholesterol and IDL triglycerides (1.006 less than d less than 1.019 g/ml) were not affected in either group. Initially low LDL cholesterol (1.019 less than d less than 1.063 g/ml) and HDL cholesterol levels rose significantly in both groups. In type III hyperlipidemics, all LDL cholesterol values remained below 120 mg/dl, whereas they were higher than 150 mg/dl after treatment in two individuals with type IV hyperlipidemia.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Fish oil supplementation reduces beta-very low density lipoprotein in type III dysbetalipoproteinemia. 206 40

Although reduction in total plasma cholesterol has yet to be shown to have a beneficial effect on overall mortality, the weight of experimental and epidemiologic evidence supports efforts to lower total plasma cholesterol levels to reduce the risk of death from coronary heart disease (CHD). This is especially true in patients with heterozygous, type II-A hyperlipoproteinemia, whose total plasma cholesterol levels above the 90th percentile for age and sex place them at markedly increased risk of death from CHD. The lipid results of partial ileal bypass (PIB) were assessed in 110 patients with heterozygous, type II-A hyperlipoproteinemia in the Program on the Surgical Control of the Hyperlipidemias, a randomized, prospective clinical trial assessing the effects of cholesterol reduction on overall mortality and the course of CHD. Compared with dietary control (n = 52), PIB (n = 58) reduced total plasma cholesterol levels 24% +/- 2% (mean +/- SEM), reduced low-density lipoprotein (LDL) cholesterol levels 34% +/- 3%, and increased high-density lipoprotein (HDL) cholesterol levels 5% +/- 5% 5 years after surgery. Very low-density lipoprotein cholesterol levels were 28% +/- 21% higher and plasma triglyceride levels were 24% +/- 11% higher in the surgical group. The HDL cholesterol/total plasma cholesterol and HDL cholesterol/LDL cholesterol ratios were significantly higher after PIB. Apolipoprotein A-I and HDL subfraction 2 levels were significantly higher and apolipoprotein B-100 levels were significantly lower in the surgical group. PIB successfully lowered mean total plasma cholesterol and LDL cholesterol levels below the limits recommended by the National Cholesterol Education Program to minimize the risk of death from CHD. These results confirm the efficacy and support the role of PIB in the management of patients with marked hypercholesterolemia.
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PMID:Lipid results of partial ileal bypass in patients with heterozygous, type II-A hyperlipoproteinemia. Program on the Surgical Control of the Hyperlipidemias. 212 Jul 85

A detailed family history questionnaire collected from families of 35,000 sixteen year old high school students in Utah was used to identify population-bases sibships with two or more living adults affected with hypertension under age 60 or coronary artery disease before age 55. Detailed clinical and biochemical evaluations performed during a four-hour visit to a research clinic provided data to test for concordant abnormalities in siblings with either early hypertension or early coronary heart disease. A new syndrome, familial dyslipidemic hypertension (FDH), was found in 48% of the hypertensive sibships. In these FDH subjects, 68% had HDL-cholesterol below the 10th percentile, 49% had triglyceride level above the 90th percentile, and 27% had LDL levels above the 90th percentile. When compared to normolipidemic hypertensive subjects, persons with FDH had significantly elevated fasting plasma insulin levels, increased subscapular skinfold thickness, increased knee width and wrist circumference, and increased levels of VLDL cholesterol and apolipoprotein B. In coronary sibships, concordant abnormalities for lipids were consistent with familial combined hyperlipidemia in 30-40% of sibships, FDH in 15-45% of sibships, and low HDL-C (with normal cholesterol) in 10%. Concordant normal lipids were found in only 15% of sibships. These data suggest that inherited metabolic abnormalities likely explain some co-aggregation of hyperinsulinemia, obesity, hypertension, and early coronary heart disease. Current knowledge also suggests these metabolic abnormalities could be treated or prevented with appropriate modification in lifestyle factors such as diet and exercise as well as through the use of prescription medications.
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PMID:Concordant dyslipidemia, hypertension and early coronary disease in Utah families. 218 41

The study objective was to determine the effects of monotherapy with clonidine and atenolol versus placebo on serum lipids, apolipoproteins, and blood pressure in patients with mild primary hypertension. The protocol comprised a double blind, randomized, placebo-controlled 5-month prospective study carried out in an outpatient general internal medicine clinic in a university medical center. There were 92 patients ages 18 to 70, with mild primary hypertension (sitting diastolic blood pressure of greater than 90 mm Hg and less than 105 mm Hg) without significant cardiac, renal, cerebrovascular, hepatic, neoplastic, or hematologic disorders. Patients with severe hyperlipidemia or peripheral vascular disease were also excluded. All factors known to effect serum lipids were held constant throughout the study (i.e., diet, weight, exercise, caffeine, tobacco). Atenolol and clonidine significantly reduced blood pressure when compared with placebo. Atenolol caused significant increases in serum triglycerides and apolipoprotein B (p less than 0.05) and significant reductions in high-density lipoprotein-cholesterol, apolipoproteins A-I and A-II (p less than 0.05). Atenolol also induced a significant adverse effect on all lipid ratios, increasing total cholesterol/high density lipoprotein-cholesterol, low density lipoprotein-cholesterol/high density lipoprotein-cholesterol, apolipoprotein B/apolipoprotein A-I and apolipoprotein B/apolipoprotein A-II ratios and decreasing low density lipoprotein-cholesterol/apolipoprotein-B ratio (p less than 0.05). Clonidine caused significant reductions in high-density lipoprotein-cholesterol, apolipoproteins AI and AII (p less than 0.05 but was neutral on all other lipids, lipid subfractions, and apolipoproteins. Clonidine did not significantly alter any of the lipid ratios.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The effects of clonidine hydrochloride versus atenolol monotherapy on serum lipids, lipid subfractions, and apolipoproteins in mild hypertension. 219 93

To see whether there are any lipoprotein abnormalities in diabetic patients without hyperlipidemia, lipoprotein composition was examined in 75 strictly normolipidemic diabetic patients. Their plasma cholesterol (chol) and triglyceride (TG) were limited to less than 6.0 and less than 1.7 mM, respectively. Body-weight- and age-adjusted normolipidemic healthy subjects served as the control group. Plasma total chol and TG and low-density lipoprotein (LDL-) and high-density lipoprotein (HDL-) chol were identical in the diabetic and control subjects. Total apolipoprotein B (apoB) in the plasma of the diabetic subjects was significantly elevated. The chol-apoB ratio in the TG-rich (very-low-density + intermediate-density) lipoprotein fraction (Sf12-400) of the diabetic subjects was significantly higher than the control value, whereas LDL-apoB levels were increased and chol-apoB ratio in the LDL fraction was significantly suppressed in the diabetic subjects. Because each LDL particle contains only one apoB molecule, apoB and chol-apoB ratio in this fraction can represent particle number and chol loading of the LDL particles, respectively. Thus, these data suggest that LDL particle number is increased, and the particles are chol depleted in diabetic subjects even if they are normolipidemic.
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PMID:Abnormal lipoprotein composition in normolipidemic diabetic patients. 220 2

The inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase are highly effective in treating severe elevations of serum cholesterol, and are being widely used for this purpose. In our laboratory, these drugs have been used for the treatment of other forms of dyslipidemia including primary moderate hypercholesterolemia, primary mixed hyperlipidemia, diabetic dyslipidemia, hyperlipidemia of the nephrotic syndrome, and primary hypoalphalipoproteinemia. In these conditions, the HMG CoA reductase inhibitors proved effective in substantially decreasing levels of both low-density lipoproteins and very low density lipoproteins, as well as apolipoprotein B. In some patients, they may even increase levels of high-density lipoproteins. The primary mode of action of HMG CoA reductase inhibitors appears to be to increase the synthesis of hepatic receptors for lipoproteins containing apolipoprotein B, although a reduction in synthesis of these lipoproteins has not been ruled out with certainty. Regardless of mechanisms, drugs of this type appear to have the potential for effective therapy of various forms of dyslipidemia beyond primary severe hypercholesterolemia.
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PMID:Use of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors in various forms of dyslipidemia. 220 34

Clinical trials were conducted to assess the utility of HimegaR in the management of hyperlipidaemia. Himega is an ethyl ester concentrate from fish oil containing at least 50% n-3 fatty acid and minimal cholesterol. In Study 1, 13 subjects with primary hypertriglyceridaemia consumed Himega or a triglyceride-based fish oil in a randomised, double-blind crossover study for 12 weeks. Nine subjects took 2 g/day of n-3 fatty acid but four subjects with marked hypertriglyceridaemia took 4 g/day. Plasma triglycerides were reduced by approximately 50% with either product. There was a very similar effect on all lipid and lipoprotein parameters, including an 18% increase in LDL cholesterol and 23% increase in serum apolipoprotein B. In Study 2, nine subjects with primary hypercholesterolaemia took 2 g/day of n-3 fatty acid (Himega) or placebo (olive oil) in a randomised, double-blind crossover study for nine weeks. Plasma cholesterol was reduced by 6%, without significant change in LDL cholesterol. Fish oils in the form of ethyl esters or triglyceride are assimilated to a similar degree and lead to equivalent triglyceride-lowering in hypertriglyceridaemia, while simultaneously increasing LDL particle numbers. Himega does not reduce LDL levels in hypercholesteraemia, despite being a product with minimal cholesterol content.
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PMID:Effects of an ethyl ester preparation of fish oils (Himega) on lipids and lipoproteins in hyperlipidaemia. 228 85

Familial defective apolipoprotein B-100 (FDB) is a recently identified, dominantly inherited genetic disorder, which leads to increased serum concentration of low density lipoprotein (LDL) cholesterol with reduced affinity for the LDL receptor. This disorder is associated with a G to A mutation in exon 26 of the apolipoprotein B (apo B) gene which creates a substitution of glutamine for arginine in the codon for amino acid 3500. We have searched for this mutation in 374 unrelated individuals with hyperlipidaemia from the United Kingdom, and in 371 unrelated individuals with a primary clinical diagnosis of atherosclerosis from the United Kingdom and Scandinavia. Ten individuals, 9 from the U.K. and 1 from Denmark, were identified. The frequency of the mutation was 3% in individuals classified clinically as having familial hypercholesterolaemia (FH) and 3% in individuals with type IIa hyperlipidaemia without FH, and was not found in patients with types IIb and III hyperlipidaemia. The mutation was rare in individuals with a primary clinical diagnosis of atherosclerosis. Plasma lipid levels and clinical characteristics of the ten patients identified in the present study are similar to those reported for heterozygous FH. Thus, in our study, FDB is associated with moderate to severe hypercholesterolaemia, and appears to be a serious disorder causing premature cardiovascular disease. Individuals with this mutation can be identified unambiguously using routine molecular screening techniques.
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PMID:Familial defective apolipoprotein B-100: detection in the United Kingdom and Scandinavia, and clinical characteristics of ten cases. 231 Apr 29

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


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