Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This report describes the response of patients with severe coronary artery disease to a dynamic fat load test and monitors the change induced by fenofibrate therapy. The presence of disease was associated with prolonged and exaggerated hypertriglyceridemia following the meal and with lower basal HDL cholesterol and HDL subfraction masses. A further indicator of risk was the persistence of increased amounts of retinyl palmitate in the plasma of severely affected individuals 24 h after its ingestion with the meal. These observations are consistent with the proposal that the clearance of chylomicrons and their remnants is impaired in coronary atherosclerosis. Fenofibrate reduced alimentary lipemia following the fat load in both normo- and hypercholesterolemic subjects. This was associated with a 10% rise in plasma HDL cholesterol levels. The improvement in chylomicron catabolism probably derived from a 37% increase (P less than 0.001) in lipoprotein lipase activity induced by fenofibrate. Hepatic lipase on the other had was only slightly affected by treatment.
Atherosclerosis 1990 Dec
PMID:Postprandial lipemia, fenofibrate and coronary artery disease. 210 83

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

Hyperlipoproteinaemia may represent a high risk factor in the pathogenesis of atherosclerosis, especially for the coronary heart disease. This metabolic disorder should therefore be treated. Strict diet is the basis of the treatment. In case the lipoprotein level does not normalize by means of diet, medicamentous therapy ought to be applied in addition. A total of 269 individuals suffering from hyperlipoproteinaemia have been treated in this study. According to Fredrickson there were 35 with Type IIa, 134 with Type IIb, 32 with Type IV and 68 with Type V. All of them had been previously treated with diet for at least three months. Afterwards, they were treated with fenofibrate (Katalip) in a dosage of 100 mg, 2 capsules in the morning and 1 in the evening. Biochemical parameters were checked a month after start of therapy. Cholesterol (-20%, -17%, -114%, -224%), triglycerides (-31%, -37%, -47%, -704), LDL cholesterol (-23%, -19%, -11% no significant, -31%), VLDL cholesterol (-25%, -29%, -32%, -59%), atherosclerosis index (-27%, -28%, -28%, -55%), urea (-5% no significant, -21%, -22%, -28%), gamma GT (-23%, -25%, -15% no significant, -39%) of patients with Type IIa, IIb, IV and V have decreased significantly (P less than 0.05), whereas the value of HDL cholesterol increased (0% no significant, +20%, +12%, +29%). No statistically significant changes during the therapy were observed in alkaline phosphatase (-8%, -9%, -11%, -10%), SGOT (-3%, -8%, +5%, -15%), SGPT (-22%, +4%, -18%, -15%) and glucose (-17% significant, -5%, -7%, -10%). Fenofibrate decreases the risk of the development of atherosclerosis by lowering lipoproteins and uric acid level.
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PMID:[The effect of fenofibrate in various types of hyperlipoproteinemias]. 274 11

Fenofibrate (300 mg daily) was given to 9 subjects (7 men, 2 women) with dysbetalipoproteinemia type III. The treatment brought about important plasma level reductions in cholesterol (-35%), triglycerides (-56%), VLDL-cholesterol (-63%) and VLDL-triglycerides (-59%). The VLDL-C/TG ratio, which was 0.40 before treatment, was 0.30 after 4 weeks of fenofibrate, still suggestive of type III. LDL-C, when measured by conventional methods, was unchanged but isolation of the IDL (1.006-1.019 g/ml) fraction from the 1.006 g/ml infranatant revealed that true LDL-C levels actually increased in 6 individuals while IDL-C decreased considerably. The total HDL-C increase was mostly due to a 33% HDL3-C change. Apolipoprotein levels were considerably modified, notably apo B, C-III and E which were decreased, as well as the lipoprotein particles containing combinations of these apolipoproteins, namely LpE:B and LpC-III:B. Apo A-I was slightly modified as LpA-I: A-II particle levels increased and LpA-I decreased. There were marked compositional modifications of apo B-containing lipoproteins which corresponded to changes of the whole lipoprotein profile. Some abnormal classes of lipoproteins (e.g., beta-VLDL, dense LDL), characteristic of this disease, tended to disappear and were in some cases replaced by material of different size and density.
Atherosclerosis 1989 Aug
PMID:Lipoprotein composition changes induced by fenofibrate in dysbetalipoproteinemia type III. 278 1

To investigate the lipoprotein effect of fenofibrate in hypercholesterolemia or combined hyperlipidemia (types II A and II B hyperlipidemias, respectively), 240 patients were recruited and 227 randomized to a double-blind randomized trial lasting 24 weeks and 192 patients continued to participate in an open-label phase for another 24 weeks. A 100-mg dose of fenofibrate or a matching placebo was given three times daily. Fenofibrate side effects in excess of placebo affected 6 percent of fenofibrate users and were confined almost entirely to skin rashes. In 180 hypercholesterolemic patients randomly assigned to receive fenofibrate versus placebo, triglyceride and very low-density lipoprotein cholesterol levels decreased 38 percent, total cholesterol levels decreased 17.5 percent, and low-density lipoprotein cholesterol levels decreased 20.3 percent with fenofibrate treatment. High-density lipoprotein cholesterol levels increased 11.1 percent with a decrease in the low-density lipoprotein cholesterol: high-density lipoprotein cholesterol ratio of 27 percent. All differences were statistically significant (p less than 0.01). In combined hyperlipidemic (type II B) patients, triglyceride levels decreased by 45 percent, very low-density lipoprotein cholesterol levels decreased 52.7 percent, total cholesterol levels decreased 16 percent, low-density lipoprotein cholesterol levels decreased 6 percent, and high-density lipoprotein levels increased 15.3 percent for a low-density lipoprotein cholesterol: high-density lipoprotein cholesterol ratio decrease of 13 percent. All differences were again statistically significant (p less than 0.01). In both groups of patients, the onset of the drug effect was generally rapid, with maximal total and low-density lipoprotein cholesterol level lowering achieved within four weeks in hypercholesterolemic patients and maximal triglyceride and cholesterol level lowering in hypertriglyceridemic patients achieved in two weeks. Maximum high-density lipoprotein increases occurred after four weeks in type II A patients and 12 to 16 weeks in type II B patients. Fenofibrate is a well-tolerated drug in the fibric acid series and has putatively beneficial effects on triglyceride, very low-density lipoprotein, low-density lipoprotein, and high-density lipoprotein cholesterol concentrations in both type II A and type II B hyperlipidemic patients. If the lipid hypothesis of atherosclerosis applies to the lipoprotein changes induced by fenofibrate, reductions in cardiovascular disease risk in both type II A and II B hyperlipidemic patients should result from fenofibrate treatment.
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PMID:Effects of fenofibrate on plasma lipoproteins in hypercholesterolemia and combined hyperlipidemia. 331 54

Eight male, normolipidemic, non-obese subjects were given fenofibrate (F) (300 mg daily) for eight days (period F). After a wash-out period of four weeks, phenobarbital (P) (100 mg daily) was given for eight days (period P). At the end of this period, P was continued at the same dosage but F (300 mg daily) was added and both drugs were given simultaneously for a further eight-day period (period P + F). The plasma concentrations of lipids and the plasma activities of enzymes involved in the interconversion of plasma lipoproteins: lipoprotein lipase (LPL), hepatic lipase (HL) and lecithin: cholesterol acyltransferase (LCAT) were measured before and at the end of each period of treatment. Fenofibrate induced a decrease in the plasma concentration of triglycerides (TG), total cholesterol (TC), apoB and an increase in the plasma activities of LPL and LCAT. Phenobarbital induced a decrease in the plasma concentration of TC, HDL-C and LDL-C (with an unchanged HDL-C/LDL-C ratio) and in the plasma activity of LPL. Addition of P to F did not modify the hypolipidemic action of F but the increase of LPL activity during period P + F was found to be greater than that observed during period F. It is concluded that P does not modify the serum lipoprotein pattern in a way which can be considered as beneficial in terms of atherosclerosis. By measuring the serum concentration of unconjugated bilirubin, the plasma clearance of antipyrine and the urinary excretion of 6 beta-hydroxycortisol as parameters of hepatic microsomal induction, F appeared to be a slight inducer as compared with P. Thus, enzyme induction cannot explain the changes in serum lipoproteins induced by P and does not modify the hypolipidemic action of F.
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PMID:Changes in plasma activities of lipolytic enzymes and lipids of normolipidemic subjects given phenobarbital, a strong microsomal inducer, alone or in combination with fenofibrate. 341 May 96

This study investigates the influence of pharmacological doses of fenofibrate on HDL and LDL metabolism in 5 familial hypercholesterolemia heterozygotes. Fenofibrate lowered plasma low density lipoprotein cholesterol (20%, P less than 0.025), triglycerides (37%: P less than 0.005) and apolipoprotein B (14%: P less than 0.05) but increased apo A-I (20%; P = 0.01). Kinetic studies showed that the drug markedly increased the fractional catabolic rate of LDL-apo B by 59% and its synthetic rate by 36%. Fractional catabolic rate of apo A-I was also increased by 26% but accompanied by a much greater increase of its synthetic rate (49%). Thus the change in balance between catabolism and synthesis of both apoproteins affected by fenofibrate accounts for the observed plasma concentration changes, which may be considered as favourable with regard to the management of atherosclerosis.
Atherosclerosis 1985 May
PMID:Effects of fenofibrate on high and low density lipoprotein metabolism in heterozygous familial hypercholesterolemia. 392 68

A total of 28 hyperlipoproteinaemic patients (8 type IIA, 12 type IIB and 8 type IV) were studied. Each patient was put on a 'prudent' isocaloric diet (50% carbohydrate, 30% fat, 20% protein) following a 2-month period of wash-out. Fenofibrate (300 mg/day) was then given for 2 periods of 2 months, each separated by a 2-month period in which only the dietary treatment was continued. Fenofibrate induced a significantly beneficial effect on the abnormal plasma levels of lipids and apolipoproteins A-I and B in all three phenotypes. Total cholesterol significantly decreased in type IIA and IIB; total triglycerides decreased significantly in all three types. HDL-C increased in all the patients but significantly only in those presenting types IIB and IV. ApoB significantly decreased in the 3 groups while apoA-I increased. The ratio apoA/apoB increased significantly in the three groups. Enzymatic parameters did not vary during the drug treatment. However, 6 patients (16%) dropped out because of gastro-intestinal side effects.
Atherosclerosis 1983 Apr
PMID:Variations in lipids and proteins of lipoproteins by fenofibrate in some hyperlipoproteinaemic states. 687 Sep 93

Fenofibrate is an efficient serum lipid-lowering drug with few clinical side effects. The drug was further evaluated in a study comprising 56 patients, which combined a dose-response trial with a subsequent comparison between the optimal fenofibrate dose and a clofibrate dose of 2 g/day. When the fenofibrate dose was gradually increased (200-300-400 mg/day), a reduction of the elevated lipoproteins within each type of hyperlipoproteinaemia was found. During the dose-response part of the therapy a transient serum creatinine rise was observed, which disappeared at the 400 mg/day level. The highest dose, 400 mg/day, proved to have the best lipid-lower effects. On this therapy the elevated LDL-cholesterol fell by 28% in type IIA + B patients, and the elevated VLDL-TG by 65% in type IIB + IV patients. The HDL/VLDL + LDL-cholesterol ratio increased significantly in all groups, in particular in type IV patients (from 0.19 to 0.28, P less than 0.001). Fenofibrate and clofibrate were each given for 2 months in random order, and the effects on lipoproteins compared. Significant differences were: higher HDL-cholesterol in type IIA on clofibrate, lower LDL-cholesterol in type IIB on fenofibrate, lower TG and cholesterol in both VLDL an LDL in type IV on fenofibrate, combined with higher HDL-cholesterol on this drug. Thus, fenofibrate seems to be an efficient lipid lowering drug with 400 mg/day as an optimal dosage under our conditions.
Atherosclerosis
PMID:Fenofibrate therapy of hyperlipoproteinaemia. A dose-response study and a comparison with clofibrate. 722 66

Drug treatment against atherosclerosis has been evaluated recently in many epidemiological studies. Lipid Research Clinics Group convincingly reported in a large scale design that anion exchange resin effectively reduced blood cholesterol level and concomitantly decreased the events of coronary heart disease. Subsequently, anion exchange resin with or without combined administration of niacin or statin was found to inhibit the progression of coronary atherosclerotic lesions in FATS, SCOR, CLAS and STARS. Fenofibrate also successfully reduced the coronary artery narrowings. Based on these intervention studies, several hypocholesterolemic agents are definitely effective in the treatment of coronary atherosclerosis.
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PMID:[The treatment of atherosclerosis--drug therapy]. 841 78


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