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)

A placebo-controlled, double-blind study was performed to assess the effect of 12 weeks treatment with acipimox (250 mg three times per day) on lipoproteins and glycaemic control in patients with Type 2 diabetes. All patients studied had persistent hyperlipidaemia despite acceptable glycaemic control on treatment with diet alone or diet and oral hypoglycaemic agents, achieving glycosylated haemoglobin (HbA1) of less than 10.5% but with fasting total triglycerides greater than 2.5 mmol l-1 or total cholesterol greater than 6.5 mmol l-1. Forty-eight patients were randomized to treatment, 21 to acipimox and 27 to placebo; 43 completed the trial. All patients had been diabetic for at least 1 year. Total cholesterol fell by 6% and total triglycerides by 19% following 12 weeks of acipimox, compared to rises in the placebo group of 1% and 16%, respectively (p less than 0.05). There were no significant differences between acipimox and placebo in the change in low density lipoprotein (LDL) cholesterol, high density lipoprotein (HDL) cholesterol, apolipoproteins AI, AII, or B, or in glycaemic control during the treatment period. Acipimox is effective in reducing fasting total cholesterol and total triglycerides in patients with Type 2 diabetes with acceptable blood glucose control but persistent hyperlipidaemia. Acipimox does not adversely affect glucose tolerance.
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PMID:The effect of acipimox in patients with type 2 diabetes and persistent hyperlipidaemia. 151 66

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

The first well-controlled studies of fenofibrate in the United States indicate that the drug is safe and effective for the treatment of type IIa and type IIb hyperlipidemia. Fenofibrate produced a marked reduction in triglyceride (TG) levels (p less than 0.01) as well as a uniform decrease in very-low-density lipoprotein (VLDL) cholesterol levels (p less than 0.01) and a rise in high-density lipoprotein (HDL) cholesterol levels (p less than 0.01) in 227 subjects with both type IIa and IIb hyperlipidemias. Low-density lipoprotein (LDL) cholesterol levels also fell: 20.3% in type IIa and 6% in type IIb subjects. Fenofibrate also affected the structure and composition of some of the major classes of lipoproteins: increases in apolipoproteins (apo) AI and AII and decreases in apo B and apo E were consistent with reductions in TG, VLDL, and LDL and increases in HDL. Tolerance of fenofibrate was excellent, with most side effects being transitory or reversible. Thus, based on the lipid hypothesis of atherosclerosis, therapy with fenofibrate can potentially lead to significant reductions in cardiovascular disease in type IIa and type IIb hyperlipoproteinemia.
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PMID:Review of the effects of fenofibrate on lipoproteins, apoproteins, and bile saturation: US studies. 265 21

Alcohol consumption is one of the most common causes of secondary hyperlipidaemia in man, but not all alcohol addicts display hyperlipidaemia. 10 healthy male controls were compared with three groups of patients. The first group consisted of 9 heavy drinkers exhibiting type V hyperlipidaemia under the influence of alcohol. The second group consisted of 7 patients who had displayed type V hyperlipidaemia during alcohol consumption in the past; at the time of investigation, however, they had ceased to drink alcohol at least 6 months previously and were normolipidaemic. The third group consisted of 7 heavy drinkers without hyperlipidaemia. Determinations of plasma lipids and lipoproteins (by means of rate zonal ultracentrifugation), as well as the major apolipoproteins (apo) of high-density lipoproteins2 (HDL2) and HDL3 (by means of polyacrylamide disc-gel electrophoresis) was carried out in all subjects. Two distinct findings were obtained: the one caused by alcohol abuse itself and the other possibly representing a primary trait consisting of an alteration in lipoproteins. In both groups of heavy drinkers the content of apo-CI in HDL2 was lower and the content of apo-AII was higher than in the controls and the abstinent group. In groups I and II with alcohol-dependent type V hyperlipidaemia, the percentage content of total protein in HDL2, as well as the content of apo-D was higher than in controls and in heavy drinkers without hyperlipidaemia. This increased content of apo-D in HDL2 is discussed as being a possible primary marker of alcohol-inducible hyperlipidaemia.
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PMID:[Alcohol-induced type V hyperlipidemia in relation to changes in the chemical composition of HDL2]. 399 40

The aim of the study was to investigate the atherosclerosis risk factors related to hyperlipidemia in renal transplanted children. Plasma cholesterol, triglycerides, apolipoproteins (Apo) AI, AII and B, and the major lipoprotein classes separated by gradient ultracentrifugation were compared in 30 renal transplanted patients and 14 healthy children. Hyperlipidemia was present in 66% of the transplanted children. 'Positive' risk factors for atherosclerosis (high plasma cholesterol and Apo B) were present in hypercholesterolemic and combined hyperlipidemic subgroups. All transplanted children, whether normo- or hyperlipidemic, presented essentially 'negative' risk factors for atherosclerosis, i.e. significantly higher levels of Apo AI and AII in plasma and in high-density lipoprotein HDL2 and higher Apo AI/Apo B and/or Apo AII/B ratios. Repeated evaluations (over a 12-month period) in transplanted children indicated relatively frequent individual changes in the lipid pattern, but not in Apo AI and AII content. These results suggest that the risks for accelerated atherosclerosis related to hyperlipidemia may be considered as moderate in transplanted children.
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PMID:Plasma lipids, lipoproteins and apolipoproteins AI, AII, and B in renal transplanted children: what risk for accelerated atherosclerosis? 643 14

In view of the evidence linking plasma high density lipoprotein (HDL)-cholesterol levels to a protective effect against coronary artery disease and the widespread use of fibrates in the treatment of hyperlipidemia, the goal of this study was to analyze the influence of fibrates on the expression of apolipoprotein (apo) A-II, a major protein constituent of HDL. Administration of fenofibrate (300 mg/d) to 16 patients with coronary artery disease resulted in a marked increase in plasma apo A-II concentrations (0.34 +/- 0.11 to 0.45 +/- 0.17 grams/liter; P < 0.01). This increase in plasma apo A-II was due to a direct effect on hepatic apo A-II production, since fenofibric acid induced apo A-II mRNA levels to 450 and 250% of control levels in primary cultures of human hepatocytes and in human hepatoblastoma HepG2 cells respectively. The induction in apo A-II mRNA levels was followed by an increase in apo A-II secretion in both cell culture systems. Transient transfection experiments of a reporter construct driven by the human apo A-II gene promoter indicated that fenofibrate induced apo A-II gene expression at the transcriptional level. Furthermore, several other peroxisome proliferators, such as the fibrate, Wy-14643, and the fatty acid, eicosatetraynoic acid (ETYA), also induced apo A-II gene transcription. Unilateral deletions and site-directed mutagenesis identified a sequence element located in the J-site of the apo A-II promoter mediating the responsiveness to fibrates and fatty acids. This element contains two imperfect half sites spaced by 1 oligonucleotide similar to a peroxisome proliferator responsive element (PPRE). Cotransfection assays showed that the peroxisome proliferator activated receptor (PPAR) transactivates the apo A-II promoter through this AII-PPRE. Gel retardation assays demonstrated that PPAR binds to the AII-PPRE with an affinity comparable to its binding affinity to the acyl coA oxidase (ACO)-PPRE. In conclusion, in humans fibrates increase plasma apo A-II concentrations by inducing hepatic apo A-II production. Apo A-II expression is regulated at the transcriptional level by fibrates and fatty acids via the interaction of PPAR with the AII-PPRE, thereby demonstrating the pivotal role of PPAR in controlling human lipoprotein metabolism.
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PMID:Fibrates increase human apolipoprotein A-II expression through activation of the peroxisome proliferator-activated receptor. 763 67

Alagille syndrome is frequently associated with hyperlipidemia and xanthoma. The aim of the study was to assess the lipid profile (plasma lipoproteins, apolipoproteins (apo)) and lecithin cholesterol acyl transferase (LCAT) activity, with and without treatment with cholestyramine in Alagille syndrome. Five children (mean age = 6 +/- 4 years) with Alagille syndrome were studied at two different times while receiving no treatment, and while receiving cholestyramine. They were compared with 12 normal controls, who were not different from patients for age and sex. In Alagille syndrome, total serum cholesterol, triglycerides and phospholipids were elevated compared with the controls (P < 0.008). VLDL-cholesterol, LDL-cholesterol, HDL-triglycerides, LDL-triglycerides and VLDL-phospholipids were higher, whereas HDL-cholesterol was lower than controls (P < 0.03). Apo B, CIII, E and lipoprotein particles Lp AI were higher (P < 0.001), whereas Lp AI:AII was lower than controls (P < 0.03). Lipoprotein-X was present in the 5 children with Alagille syndrome and explained in part the elevation of plasma cholesterol, phospholipids, and apo CIII. LCAT activity was decreased (P < 0.01) and might cause some abnormalities of HDL with lower cholesterol, higher triglycerides, apo E and apo CIII contents than controls, and abnormalities of VLDL and LDL with higher cholesterol, triglycerides, phospholipids and apo B contents than controls. Some of the risk factors of atherosclerosis were found in Alagille syndrome, namely high levels of plasma cholesterol, LDL cholesterol, apo B, apo B/apo AI. Treatment with cholestyramine resulted in a few modifications to the lipid profile, while lipoprotein-X and the decrease of LCAT activity persisted.
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PMID:Lipoprotein pattern and plasma lecithin cholesterol acyl transferase activity in children with Alagille syndrome. 766 82

The behavior of apolipoprotein-defined subpopulations LpAI and LpAI,AII within high density lipoprotein (HDL) subclasses 2 and 3 was analyzed in the postprandial phase after a fat load. For the whole group of subjects, increases in plasma concentrations of HDL, principally due to the influx of lipoprotein surface components, were largely confined to the HDL3 density range and involved LpAI,AII and LpAI. However, the degree of postprandial lipemia influenced the distribution of surface remnants between the subfractions. In subjects with a limited postprandial rise in triglycerides, increased HDL mass was predominantly associated with LpAI,AII, and equally distributed between HDL2 and HDL3. Conversely, subjects with exaggerated postprandial lipemia manifested increased mass primarily within the HDL3 density range, implicating both LpAI,AII and LpAI. Stepwise regression analysis identified a two-variable model, involving LpAI,AII within HDL2 and LpAI within HDL3, as best defining the relationship between postprandial lipemia and the increase in HDL mass. Postprandial increases in triglyceride content were observed for all HDL subfractions, whilst modifications to the core lipid mass ratios were significant only for LpAI,AII. Stepwise regression analysis revealed a significant correlation between postprandial lipemia and the increase in triglyceride concentration only of LpAI,AII within HDL3. The results suggest that postprandial lipemia differentially influences apolipoprotein-defined HDL subfractions. The extent of postprandial lipemia may determine the involvement of different HDL subfractions in postprandial lipoprotein metabolism.
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PMID:Postprandial lipemia differentially influences high density lipoprotein subpopulations LpAI and LpAI,AII. 780 72

Modification of dietary fat composition may influence hemostatic variables, which are associated with increased risk of coronary heart disease (CHD). To address this question, we performed a controlled feeding study on 26 healthy male nonsmoking subjects with diets of differing fat composition. For the first 3 weeks, the subjects were given a diet calculated to supply 30% energy as total fat: 8% as monounsaturated, 4% as polyunsaturated, and 16% energy as saturated fatty acids, respectively (saturated diet). This was followed immediately by two diets taken in random order, each of 3-week duration and separated by an 8-week washout period on the subject's usual diet. Both diets were calculated to supply 30% of energy as fat: 14% monounsaturated, 6% as polyunsaturated, and 8% energy as saturated fatty acids. They both provided 5 g (approximately 1.7% energy) more of polyunsaturated fatty acids than the saturated fat diet; in one diet as long-chain n-3 fatty acids (n-3 diet) and in the other as linoleic acid (n-6 diet). Fasting plasma lipids, lipoproteins, and hemostatic factors were measured on the final 3 days of each dietary period. In a subset of 9 subjects the postprandial responses to a test meal were studied on the penultimate day of each period, each meal having the fat composition of its parent diet. On the n-3 diet compared with the n-6 diet, plasma triglyceride, HDL3 cholesterol, apoprotein AII, and fibrinogen concentrations were lower and HDL2 cholesterol concentration was higher (P = .0001, P = .003, P = .0001, P = .004, and P = .001, respectively). On both the n-3 and n-6 diets compared with the saturated diet, fasting plasma total and LDL cholesterol, apoprotein B, beta-thromboglobulin concentrations, and platelet counts were lower (P < .0001, P < .0001, P < .001, P < .01, and P < .05 respectively) and plasma Lp(a) and von Willebrand factor concentrations were higher (P = .02 and P < .01, respectively). Fasting factor VII coagulant activity (VIIc) was increased and apoprotein AI concentration reduced following the n-3 diet (P = .004 and P = .01, respectively) compared with the saturated diet. Plasma fibrinogen concentration was significantly greater following the n-6 diet than on the saturated diet (P = .02). Postprandially, plasma triglyceridemia was greater on the n-6 diet and lowest on the n-3 diet (P < .001) with the saturated diet being intermediate. Plasma VIIc was increased at 4 hours following the standardized test meals on the n-3 and n-6 diets (both P < .05) but not on the saturated diet. An increased intake of long chain n-3 fatty acids decreases fasting plasma triglyceride and apoprotein AII concentrations and increases HDL2 cholesterol concentrations and results in less postprandial lipemia but leads to an increase in VIIc. An increased intake of linoleic acid may raise plasma fibrinogen concentration. Decreasing the intake of saturated fatty acids reduces plasma LDL cholesterol and apoprotein B without affecting HDL cholesterol concentration independent of the type of polyunsaturated fatty acids in the diet. When advice is given to reduce saturated fat intake, it is important to ensure an appropriate ratio of n-3/n-6 fatty acids in the diet.
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PMID:Influence of n-6 versus n-3 polyunsaturated fatty acids in diets low in saturated fatty acids on plasma lipoproteins and hemostatic factors. 943 92