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)

A 40-year-old male with heterozygous familial hypercholesterolaemia was resistant to combined drug treatment with cholestyramine and nicotinic acid in adequate doses. He had angina pectoris and evidence of three vessel disease in the coronary angiogram. Repeated plasma exchange at intervals of 1-3 weeks simultaneously with combined drug treatment decreased the plasma cholesterol levels by nearly 40%. There were also signs of regression of xanthomata and some improvement of his angina pectoris. No progression of atherosclerosis was seen angiographically after two years treatment. Plasma exchange may be a therapeutic alternative in drug-resistant familial hypercholesterolaemia.
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PMID:Plasma exchange in a patient with heterozygous familial hypercholesterolaemia resistant to drug therapy. 359 71

Xenalipin (4'-trifluoromethyl-2-biphenylcarboxylic acid) is a chemically novel compound which has been found to be an effective hypolipidemic agent in two animal species. Significant reductions in serum cholesterol and triglycerides were observed in cholesterol-cholic acid-fed rats following oral doses of 10-30 mg/kg/day. Xenalipin was considerably more potent than clofibrate, nicotinic acid, and cholestyramine in the same model. Lipoprotein analysis showed that xenalipin reduced cholesterol and protein content in very low density lipoprotein (VLDL), intermediate density lipoprotein (IDL), and low density lipoprotein (LDL). Triglycerides were reduced in VLDL and IDL. Xenalipin was also effective in reducing serum cholesterol and triglyceride concentrations in normocholesterolemic rats. In diet-induced hypercholesterolemic African green monkeys, xenalipin at oral doses of 15-60 mg/kg b.i.d. reduced serum LDL-cholesterol concentrations. These results suggest that xenalipin has a profile of activity which would be beneficial in therapy for hyperlipidemia.
Atherosclerosis 1987 Mar
PMID:Evaluation of the hypolipidemic activity of xenalipin in experimental animals. 368 93

Two types of end-point measurement are presently available in clinical trials of the effect of treatment of hyperlipidaemia on cardiovascular disease; these are the incidence of clinical events and the arteriographic assessment of progression or regression of atherosclerosis. These approaches are briefly reviewed. In the present trial, 25 hyperlipidaemic men with symptomatic femoral atherosclerosis underwent biplanar femoral arteriography at baseline. They were then randomised into treatment and usual-care groups; treatment was individualized, comprising a lipid-lowering diet with cholestyramine, nicotinic acid or clofibrate as appropriate for the lipoprotein disorder. Mean cholesterol and triglyceride levels were 19% and 37% lower in the treatment group. Arteriography was repeated after a mean period of 19 months. With attention to blinding of observers, changes in arteriograms were quantitated using computerised image analysis and visual methods, and expressed both by patient and by arterial segment. All end-points were in conformity and showed a lower rate of progression of arterial disease in the treatment group, and a higher frequency of segmental regression in treated patients. In this small trial of patients with functionally-significant atherosclerosis, effective treatment of hyperlipidaemia favourably affected the course of the arterial disease.
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PMID:Randomised controlled trial of the treatment of hyperlipidaemia on progression of atherosclerosis. 390 95

Acipimox, an analogue of nicotinic acid, is a hypolipidemic drug with antilipolytic activity. Ten patients with type III and 10 with type IV hyperlipoproteinemia participated in a comparative open cross-over study of the effect of acipimox (750 mg/day) and clofibrate (2 g/day) on lipoproteins, apoliproproteins and postheparin lipase activities during 6 weeks. During acipimox treatment 2 type III patients complained of flushing, resulting in one drop-out. In the type III patients serum cholesterol decreased 30% (P less than 0.01) during treatment with acipimox and 24% (P less than 0.01) with clofibrate, and serum triglycerides 48% (P less than 0.01) and 34% (P less than 0.01), respectively. In the type IV patients serum cholesterol remained unchanged and serum triglycerides decreased 34% (P less than 0.05) and 35% (P less than 0.01), respectively. HDL cholesterol increased during treatment with both drugs in both groups between 6 and 15% (P less than 0.05) mainly due to a rise in HDL3 cholesterol (d greater than 1.100 g/ml). LDL cholesterol increased significantly during treatment with clofibrate, but not with acipimox. There were no or slight changes in the apoproteins A and B. Postheparin lipoprotein lipase increased during clofibrate treatment and hepatic lipase decreased during acipimox treatment. We concluded that acipimox in a dose of 750 mg/day has a similar hypolipidemic effect as 2 g clofibrate daily in type III and IV hyperlipoproteinemia.
Atherosclerosis 1985 Apr
PMID:A comparative study of the effects of acipimox and clofibrate in type III and type IV hyperlipoproteinemia. 392 65

Nicotinic acid treatment thus induces several beneficial effects on serum lipoproteins and on hemodynamic factors related to the risk for development of atherosclerosis. It effectively reduces the atherogenic lipoproteins VLDL and LDL and also increases the anti-atherogenic HDL, mainly the HDL2 fraction. The drug seems to be active not only in decreasing the synthesis of various lipoproteins but also to enhance the removal into peripheral tissues, thereby speeding up the catabolic events of serum lipoproteins. The mode of action of NAc in adipose and muscle tissue needs further evaluation to better understand the complex interplay between free fatty acid and glucose and insulin metabolism. The recent findings of a stimulation of prostacyclin formation as well as a reduction in platelet aggregation are newly discovered favorable effects of the drug that needs to be further examined. Although the drug seems to induce some undesirable side effects (reversible), its several favorable anti-atherosclerotic properties should stimulate both experimental and clinical research with this drug. Hopefully newer derivatives with even better tolerance may be developed.
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PMID:Effects of nicotinic acid and its derivatives on lipid metabolism and other metabolic factors related to atherosclerosis. 403 1

Repeated plasma exchange is an effective treatment for young patients with familial hypercholesterolemia. We treated 2 homozygous and 1 heterozygous patient with very high cholesterol levels with continuous plasma exchange using human albumin solution as exchange medium. The treatment was repeated every 2 weeks in 2 patients and weekly in the third. Treatment periods of plasma exchange alone and of plasma exchange with concomitant drug therapy were compared. For drug treatment beta-pyridylcarbinol, the alcohol corresponding to nicotinic acid (0.9 g/day equivalent to 3 g of nicotinic acid) and cholestyramine (16 g/day) were used. Plasma exchange alone resulted in a decrease of all lipids by 55% and of apolipoproteins by 50-60% as compared to the plasma levels before exchange. Subsequently all lipoproteins rose again to reach pre-exchange levels within about 2 weeks. There was no difference between the homozygous and the heterozygous patients. Beta-pyridylcarbinol or cholestyramine given concomitantly did not alter the post-exchange increase of total, LDL, HDL cholesterol nor of the corresponding apolipoproteins except of apolipoprotein B.
Atherosclerosis 1985 Nov
PMID:Effect of plasma exchange with and without concomitant drug treatment on lipids and lipoproteins in patients with familial hypercholesterolemia confirmed by tissue culture. 408 56

Thriteen patients with heterozygous familial hypercholesterolaemia (FH) were sequentially treated with: a low-cholesterol, fat-restricted diet; diet and colestipol; and diet and colestipol and nicotinic acid. Concentrations of plasma cholesterol decreased from 415 +/- 69 mg/dl on diet alone to 327 +/- 54 mg/dl on colestipol and fell to 246 +/- 49 mg/dl on the combined drug regimen. Plasma concentrations of LDL cholesterol declined 24% on colestipol; the subsequent addition of nicotinic acid resulted in a further 31% fall so that values on the combined drug regimen were 47% below those seen on diet alone. HDL cholesterol levels were similar on both the diet (40 mg/dl) and colestipol (43 mg/dl) treatment periods but increased to 53 mg/dl on the combined drug regimen. Treatment resulted in significant decreases in the LDL:HDL ratio which fell from 8.4 on diet to 3.3 on the colestipol plus nicotinic acid regimen. In most patients with heterozygous FH, combined use of a bile acid sequestrant and nicotinic acid affords the opportunity to maintain a normal lipid profile. Prolonged use of this regimen may reduce the incidence of premature coronary atherosclerosis which naturally occurs in these patients.
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PMID:Colestipol plus nicotinic acid in treatment of heterozygous familial hypercholesterolaemia. 610 40

The effect of plasma lipid reduction on the progression of femoral atherosclerosis was studied in hyperlipidaemic patients with stable intermittent claudication. 24 patients were randomly assigned to treatment and usual-care groups, the former receiving dietary advice and cholestyramine, nicotinic acid, or clofibrate depending on their lipoprotein phenotype. Biplanar arteriography was performed when the study began and after a mean period of 19 months. Angiograms were assessed visually, with blinding, and by computerised image analysis. Therapy reduced mean plasma total cholesterol by 25%, mean low density lipoprotein (LDL) cholesterol by 28%, and mean plasma triglycerides by 45%. Significantly fewer arterial segments showed detectable progression of atherosclerosis in the treatment group. The mean increase in plaque area (mm2/segment/year) in the treatment group was only one third of that in the usual-care group. The mean increase in edge irregularity index (a measure of the severity of disease) in the treatment group was only 40% of that in the usual care group. Twice as many arterial segments showed improvement in the treatment group. In both groups changes in edge irregularity index were directly related to plasma LDL cholesterol concentration. This study, the first randomised controlled trial of its type, provides evidence that effective treatment of hyperlipidaemia favourably influences the natural history of symptomatic peripheral atherosclerosis.
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PMID:Treatment of hyperlipidaemia retards progression of symptomatic femoral atherosclerosis. A randomised controlled trial. 613 93

Glunicate is evaluated compared to nicotinic acid for effects on aortic atheromatous lesions, lipid parameters and factors involved in thrombosis and haemostasis in rabbits kept on a high-cholesterol diet for 12 weeks, using 2 doses of glunicate (0.17 and 0.69 g/day) and 1 of nicotinic acid (0.6 g/day). Glunicate afforded dose-dependent protection of the arterial wall from atheromatous lesions and from cholesterol and collagen accumulation, while nicotinic acid hardly had any effect. These effects were completely independent of plasma lipid-lowering action, the plasma levels of all lipids being indistinguishable in all cholesterol-fed groups. In addition to inducing the expected changes in the lipid pattern, the atherogenic diet increased platelet aggregation in response to collagen but not to ADP, prolonged the APTT and lowered the plasma fibrinogen levels. Both glunicate and nicotinic acid counteracted the effects of the diet on platelet aggregation and on APTT, but only glunicate normalised the fibrinogen levels. There was no change in PT or in prostacyclin-like activity release from the mesenteric artery after the diet or diet plus drugs.
Atherosclerosis 1984 Oct
PMID:Glunicate (LG 13979) protects the arterial wall from cholesterol-induced atherosclerotic changes in the rabbit without affecting plasma lipids. 623 1

The progression of coronary atherosclerosis was assessed by repeat angiography in 28 patients and 20 controls with hyperlipidaemia (serum cholesterol concentration greater than 7.2 mmol/l (278 mg/100 ml) or serum triglyceride concentration greater than 2.0 mmol/l (177 mg/100 ml), or both) and symptomatic coronary artery disease of two or three vessels. Twenty eight patients (26 men and two women) were treated with diet and drugs (clofibrate or nicotinic acid, or both) to lower lipid concentrations. Twenty men taking part in a simultaneous study served as non-randomised controls. They received medical treatment for coronary artery disease but no treatment to reduce lipid concentrations. The initial levels of coronary risk factors and the angiographic state were comparable in the two groups. In the 28 patients total cholesterol, total triglyceride, and low density lipoprotein cholesterol concentrations were reduced by an average 18%, 38%, and 19% respectively by treatment for hyperlipidaemia and high density lipoprotein cholesterol concentration was increased on average by 10%. The treatment maintained these concentrations during a follow up of seven years. By all criteria coronary lesions progressed significantly less in the patients than the controls: the angiographic state remained completely unchanged in nine (32%) of the patients compared with only one (8%) of the surviving controls; of the arterial segments at risk, 46 (16.5%) progressed in the patients compared with 50 (38.2%) in the controls (p less than 0.001); and the coronary obstruction increased less in patients than in controls (p less than 0.05). Cardiac survival was 89% in seven years in the patients compared with 65% in five years in the controls (p less than 0.01). The anginal symptoms diminished or remained stable in 16 of the 24 patients who survived until the end of the study. The progression of coronary atheromatosis was significantly greater in those patients who during the seven years of treatment had an average total cholesterol concentration, VLDL plus LDL cholesterol concentration, or ratio of LDL to HDL cholesterol concentration above the respective median value than in those with the corresponding values below median. On the other hand, the patients with HDL cholesterol concentrations above the median during treatment showed less progression than those with lower HDL cholesterol concentrations. The increase in coronary obstruction was inversely related to the average HDL cholesterol concentration during treatment. The progression was not, however, related to LDL cholesterol concentration during treatment.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Prevention of progression of coronary atherosclerosis by treatment of hyperlipidaemia: a seven year prospective angiographic study. 643 Apr 14


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