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 multicenter, double-blind, placebo-controlled, dose-response study was conducted in patients with primary hypercholesterolemia to examine the effects of pravastatin, a selective inhibitor of HMG-CoA reductase, on plasma lipids and lipoproteins. A total of 306 patients on cholesterol-lowering diets received twice daily doses of 5 mg, 10 mg, 20 mg pravastatin, or placebo for 12 weeks. Marked reductions in low density lipoprotein (LDL) cholesterol and total cholesterol were observed after 1 week of treatment; maximum lipid-lowering effects occurred at 4 weeks and were sustained for the duration of the trial. At week 12, pravastatin treatment resulted in dose-dependent mean reductions from baseline in LDL cholesterol of 17.5%, 22.9%, and 30.8% for the 3 doses tested (P less than or equal to 0001 compared with baseline and placebo). The reduction in LDL cholesterol was log-linear with respect to dose; each doubling of dose reduced LDL cholesterol an additional 6.5%. Dose-dependent reductions in total cholesterol from 12.9% to 23.3% also occurred (P less than or equal to 0.001). Triglycerides decreased by as 15.4% (P less than or equal to 0.001) and high-density lipoprotein (HDL) cholesterol increased approximately 7% (P less than or equal to 0.01), but these effects were not dose-dependent. No patient receiving pravastatin was discontinued during the 12-week trial. Transient episodes of rash and headache occurred. Slight increases in mean serum levels of ASAT and ALAT occurred, and 2% of both placebo- and pravastatin-treated patients reported myalgia although there was no clinically significant elevation of creatine kinase. These data indicate that pravastatin favorably affects all lipid parameters and is well tolerated.
Atherosclerosis 1990 Nov
PMID:Efficacy and safety of pravastatin in patients with primary hypercholesterolemia. I. A dose-response study. 212 37

This 8-week multicenter, placebo-controlled trial compared the efficacy and safety of the HMG-CoA reductase inhibitor, pravastatin, when administered either as single doses of 40 mg in the morning (AM) or evening (PM) or 20 mg twice daily (bid) in 196 diet-stabilized outpatients with primary type II hypercholesterolemia. Mean reductions in total and low-density lipoprotein (LDL) cholesterol concentrations were observed in all pravastatin groups after 1 week and were sustained throughout the study (P less than or equal to 0.001 versus baseline and placebo). At week 8, mean reductions from baseline in the pravastatin treatment groups were 23-27% for total cholesterol and 30-34% for LDL cholesterol. LDL cholesterol was reduced greater than or equal to 15% by pravastatin in all patients in the group treated with 40 mg PM and in 88 and 96% in those receiving 20 mg bid and 40 mg AM, respectively. High density lipoprotein cholesterol was elevated (up to 8%) and triglycerides were reduced (up to 25%) by all pravastatin regimens (P less than or equal to 0.05). Pravastatin was well tolerated and was associated with a low incidence of adverse events. No patient withdrew from the study due to a pravastatin-related adverse event. Once-daily pravastatin is a safe and effective treatment for patients with primary hypercholesterolemia and has a favorable safety profile.
Atherosclerosis 1990 Dec
PMID:Efficacy and safety of pravastatin in patients with primary hypercholesterolemia. II. Once-daily versus twice-daily dosing. 212 19

The bile acid sequestrants, cholestyramine and colestipol, are the drugs of choice for the treatment of patients with hypercholesterolemia caused by increases in LDL-cholesterol levels without concurrent hypertriglyceridemia (type IIA and type IIB hyperlipoproteinemia). Longitudinal clinical studies with these drugs have shown their ability to slow the progression of atherosclerosis and to limit the consequences of the disease. Bile acid sequestrants can be used with other lipid-lowering drugs such as nicotinic acid or HMG CoA reductase inhibitors, to maximize the cholesterol-lowering effects. The side effect profile of the bile acid sequestrants is tolerable, with most complaints related to effects on the gastrointestinal tract and the bulkiness of the resins.
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PMID:Bile acid sequestrants. 217 78

The rationale of treatment to prevent or delay the onset of atherosclerotic disease is based upon recognition that a key process in atherogenesis is the uptake of certain lipoproteins by scavenger cells in the artery wall. These lipoproteins enter the artery wall from blood. Thus the risk of atherogenesis is linked to the concentrations of these lipoproteins in plasma. Although a number of processes involved in atherogenesis may ultimately yield to additional means of intervention, the current central strategy is to reduce levels of atherogenic lipoproteins in blood. This strategy draws support from several recent intervention trials, which have shown reduction of progression of coronary disease and, in one instance, reduced total mortality. Recent advances in therapy, including the advent of HMG CoA reductase inhibitors and the development of combined drug regimes of unprecedented effectiveness, now permit the reduction of plasma lipoprotein levels to the optimum in a majority of individuals. Rational selection of single-drug regimens and drug combinations is based on phenotypic characterization of lipoprotein disorders. The physician also needs to be aware of disease that can lead to secondary hyperlipoproteinemia so that the underlying disorders can be treated if possible. The treatment by diet of all individuals with hyperlipidemia or atherosclerotic disease is recommended. The decision to treat with drugs should involve consideration of risk factors such as the patient's sex, blood pressure, smoking habits, levels of HDL, and family history of atherosclerosis.
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PMID:Treatment of hyperlipidemia. 218 45

Coronary heart disease is the leading cause of death among patients with non-insulin-dependent diabetes mellitus (NIDDM). NIDDM patients have a high frequency of dyslipidemia, which along with obesity, hypertension, and hyperglycemia may contribute significantly to accelerated coronary atherosclerosis. Because risk factors for coronary heart disease are additive and perhaps multiplicative, even mild degrees of dyslipidemia may enhance coronary heart disease risk. Therefore, therapeutic strategies for management of NIDDM should give equal emphasis to controlling hyperglycemia and dyslipidemia. The National Cholesterol Education Program recently issued guidelines for treatment of hyperlipidemia in adults including diabetic patients. Because of the unique features of diabetic dyslipidemia, however, we suggest that certain modifications in these guidelines be made to meet specific needs of diabetic patients. For example, therapeutic goals for serum cholesterol reduction should be lower in diabetic patients than in nondiabetic subjects. Particular emphasis should be given to weight reduction in NIDDM patients. In some diabetic patients, monounsaturated fatty acids may be a better replacement for saturated fatty acids than carbohydrates. The target for cholesterol lowering should include both very-low-density lipoprotein and low-density lipoprotein (LDL) (non-high-density lipoprotein) rather than LDL alone. To obtain a substantial reduction of cholesterol levels, drug therapy may be required in many patients. However, first-line drugs for nondiabetic patients (nicotinic acid and bile acid sequestrants) may be less desirable in NIDDM patients than hydroxymethylglutaryl coenzyme A (HMG CoA) reductase inhibitors and even fibric acids. In fact, HMG CoA reductase inhibitors may be the drugs of choice for NIDDM patients with elevated LDL cholesterol and borderline hypertriglyceridemia, whereas gemfibrozil appears preferable for NIDDM patients with severe hypertriglyceridemia.
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PMID:Management of dyslipidemia in NIDDM. 219 Jul 70

As hypercholesterolemia is an essential risk factor of atherosclerosis, a strategy for diagnosis and treatment of hyperlipidemia is indispensable. Differences in mortality from coronary heart disease in different cultures seem to be due to environmental, not to genetic factors. Trials in Finland and the United States have shown that cholesterol levels and smoking can be reduced by information and education with an ensuing drop in cardiovascular mortality. This experience warrants national programmes for cholesterol-lowering in high risk countries. Programmes should be directed to doctors and health officials as well as legislators and the public. Within any given population individual differences of lipid levels are due to both nutritional habits and genetic variations concerning e.g. LDL-receptors and lipase activity. At present the only means of identifying subjects at risk is to measure their lipid levels and to scrutinize their family history. Measurements should be repeated to exclude biologic and laboratory variability. Drugs currently available include HMG CoA reductase inhibitors, bile acid binding resins, clofibrate derivatives and nicotinic acid. Formerly defined age groups with regard to therapeutic measures have meanwhile been abandoned.
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PMID:Strategy for diagnosis and treatment of hyperlipidemia. 219 53

The goals of treatment for patients with hyperlipoproteinemia are to reduce plasma concentrations of known atherogenic lipoproteins, thereby exerting a favorable effect upon lipid deposition in the arterial wall and, less commonly, to prevent the adverse sequelae of hyperchylomicronemia in patients with severe hypertriglyceridemia. Diet is the cornerstone of the therapy after the exclusion of secondary factors; the decision to begin drug therapy should be made only after an adequate trial of diet has failed to achieve satisfactory concentrations of plasma lipids and lipoproteins. For patients without evidence of atherosclerosis the goals is to reduce the plasma concentrations of low density lipoproteins to below 160 mg/dl (4.2 mM/L); for those individuals with atherosclerosis or the concurrent presence of two risk factors, a lower level of LDL is desirable (less than 130 mg/dl; 3.4 mM/L). For regression to occur the LDL level may need to be below 100 mg/dl (2.6 mM/L). The bile acid sequestrants (cholestyramine and colestipol), nicotinic acid, fenofibrate, and inhibitors of HMG CoA reductase (e.g., lovastatin or simvastatin) are the most effective drugs for use in patients with primary hypercholesterolemia and these agents reduce plasma concentrations of total and LDL cholesterol by 15-45%. For those patients with concurrent hypertriglyceridemia, nicotinic acid, lovastatin or simvastatin, or fenofibrate are the preferred drugs for initial use. Fibric acid derivatives (e.g., clofibrate, gemfibrozil, bezafibrate, or fenofibrate) are all effective in the therapy of patients with type III hyperlipoproteinemia, as is nicotinic acid or lovastatin.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Management of hyperlipidemia: goals for the prevention of atherosclerosis. 220 37

Hypercholesterolemia and increased concentrations of an apolipoprotein E (apoE)-containing HDL subclass, high density lipoprotein1 (HDL1) have been observed in streptozocin-alloxan diabetic dogs consuming normal amounts of dietary cholesterol. The aim of this study was to characterize the response of HDL1 and its targeting ligand, apoE, to insulin and HMG-CoA reductase inhibitor treatment in pancreatectomized diabetic dogs. Following induction of diabetes, plasma total cholesterol, HDL1, and apoE concentrations were all increased. Urinary mevalonate excretion, an index of cholesterol synthesis in humans, was 6-fold that of nondiabetic controls. Lipoprotein fractionation by Pevikon block electrophoresis and gel filtration chromatography showed that the increased cholesterol and apoE were associated with alpha 2-migrating particles corresponding to HDL1. Insulin treatment, resulting in near normal fasting blood glucose concentrations in the group as a whole (average 5.1 mM, 92 mg/dl), led to variable reductions in apoE, total plasma cholesterol, and HDL1. Uncorrected dyslipidemia during intensified insulin treatment appeared to be related to failure to achieve euglycemia. Despite unremitting hyperglycemia, treatment with lovastatin resulted in pronounced decreases in plasma cholesterol, HDL1 and apoE to concentrations below those observed in nondiabetic animals. Mevalonate excretion also fell, but remained twice normal. Thus neither modality corrected all of the abnormalities in canine diabetic dyslipidemia. Since apoE-containing HDL1 may mediate cholesterol traffic between the periphery and the liver (reverse cholesterol transport), the present observations suggest that increased cholesterol synthesis is accompanied by parallel abnormalities in cholesterol flux through the reverse transport pathway in the canine model.
Atherosclerosis 1990 Sep
PMID:Plasma apolipoprotein E, high density lipoprotein1 (HDL1) and urinary mevalonate excretion in pancreatectomized diabetic dogs: effects of insulin and lovastatin. 224 16

We evaluated the effect of cholesterol reduction on atherosclerotic coronary artery lesions using diet and simvastatin, a potent HMG CoA reductase inhibitor. Fifteen subjects aged 28-69 years (mean 44), each of whom demonstrated significant (greater than 50%) narrowing of a coronary artery and a baseline cholesterol level greater than 278 mg/dl, were studied. Coronary arteriography was performed prior to and after 20 +/- 2.5 months of therapy. A 42% reduction in total serum cholesterol, a 52% reduction in LDL cholesterol, and an 87% increase in the HDL/LDL cholesterol ratio (p less than 0.01) were achieved. Pretreatment and posttreatment angiograms were reviewed by three experienced angiographers with temporal order masked. Improvement in the overall status of coronary atherosclerotic lesions was demonstrated in two patients (13%), while deterioration occurred in one patient (7%). No overall change was found in the remaining 12 patients (80%). We conclude that a cholesterol-lowering regimen using a nonatherogenic diet and simvastatin therapy may at least stabilize coronary atherosclerosis.
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PMID:Effects of therapy with diet and simvastatin on atherosclerosis in hypercholesterolemic patients. 227 74

We examined the relationship between cholesterol synthesis and high affinity low density lipoprotein (LDL) catabolism in freshly isolated mononuclear leukocytes and plasma sterols and apolipoprotein concentrations in three homozygous and one heterozygous subject with sitosterolemia with xanthomatosis and in 12 control subjects. Observations in untreated subjects were compared during therapy with lovastatin or interruption of the enterohepatic circulation of bile acids. Plasma cholesterol, plant sterol, and apolipoprotein B concentrations declined more than 50% in the two homozygous sitosterolemic subjects after ileal bypass surgery. In contrast, plasma cholesterol, plant sterol, and apolipoprotein B concentrations remained constant in a homozygous sitosterolemic subject and declined only 7% in a heterozygous sitosterolemic subject during 20 weeks of lovastatin (40 mg/day) treatment compared to a 28% decrease in similarly treated control subjects. Lovastatin treatment decreased cholesterol synthesis more than 60% but did not increase high affinity catabolism of LDL further in the sitosterolemic cells, compared to a more than 20% rise in control mononuclear leukocytes. Conversely, bile acid malabsorption increased cholesterol synthesis 59%, total hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase activity 13%, and receptor-mediated LDL degradation 41% in control cells, but did not stimulate cholesterol synthesis or microsomal HMG-CoA reductase activity in sitosterolemic mononuclear leukocytes although receptor-mediated LDL catabolism rose an additional 26%. These results demonstrate a greater than expected decrease in plasma sterols and apolipoprotein B concentrations in sitosterolemic subjects after stimulation of bile acid synthesis because of the inability to up-regulate cholesterol production. We suggest that bile acid-sequestering drugs or ileal exclusion surgery may be more effective treatments to mobilize accumulated sterol deposits and prevent atherosclerosis in this disease.
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PMID:Unexpected failure of bile acid malabsorption to stimulate cholesterol synthesis in sitosterolemia with xanthomatosis. Comparison with lovastatin. 231 63


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