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)

Oral contraceptives users and control women sera were studied to determine the degree of incorporation of tritiated acetate into lipids by cultured human arterial smooth muscle cells and dermal fibroblasts. When the cells were exposed in vitro to oral contraceptive users serum, they showed a significant increase in synthesis of cholesterol above controls in both fibroblasts (increase of 25-26%) and smooth muscle cells (plus 28-42%) but no significant concomitant change in lecithin synthesis; this exposure also resulted in increased cholesterol/lecithin ratios in newly synthesized lipids much higher than controls in both fibroblasts (plus 50%) and smooth muscles (plus 30%). However, when steroid ingredients of the oral contraceptives were added in vitro to the growth medium containing control sera, no stimulation of lipogenesis by cells occurred. Tritiated mevalonate incorporation into cholesterol was no different with oral contraceptive user or control serum, indicating that the stimulation noted in cholesterol synthesis by oral contraceptive users serum was caused by an increased 3-hydroxy-3-methyl glutaryl-CoA reductase activity. This study suggests that increased sterol synthesis in arterial smooth muscle cells of oral contraceptive users may be a pathogenetic factor that affects the risk of atherosclerosis.
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PMID:Oral contraceptive steroids and atherosclerosis: lipogenesis in human arterial smooth muscle cells and dermal fibroblasts in presence of lipoprotein-deficient serum from oral contraceptive users. 743 43

Few data are available about the potential benefit of serum cholesterol reduction in the broad range of patients with coronary atherosclerosis and normal to moderately elevated serum cholesterol levels. REGRESS is a double-blind, placebo-controlled, multicenter study to assess the effect of a 2-year treatment with the 3-hydroxy-3-methylglutaryl co-enzyme A reductase inhibitor pravastatin on progression and regression of coronary atherosclerosis using quantitative coronary arteriography in 885 male patients with a total serum cholesterol value of 155-310 mg/dl (4-8 mmol/liter). Among symptomatic men with significant coronary atherosclerosis and normal to moderately raised levels of serum cholesterol, patients treated with pravastatin had less progression of coronary atherosclerosis and fewer new cardiovascular events than patients in the placebo group. Ultrasound examinations of carotid and femoral arteries were performed in 255 patients. Changes in intimal-medial thickness also showed a treatment effect from pravastatin; however, on a per patient basis, there was no correlation with the treatment effect in the coronary arteries.
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PMID:Effect of pravastatin on progression and regression of coronary atherosclerosis and vessel wall changes in carotid and femoral arteries: a report from the Regression Growth Evaluation Statin Study. 757 85

The 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors have proven to be more effective in reducing levels of low density lipoprotein (LDL) cholesterol and to be better tolerated than other lipid-lowering compounds. Most of the trials evaluating the effects of these new agents on progression of atherosclerosis have not included individuals asymptomatic for cardiovascular disease and who have LDL cholesterol levels at or below the limits established by the National Cholesterol Education Program for initiating treatment. The Asymptomatic Carotid Artery Progression Study (ACAPS) tested the effect of the HMG-CoA reductase inhibitor, lovastatin, on early-stage carotid atherosclerosis (as detected by B-mode ultrasonography) in 919 asymptomatic men and women, 40-79 years of age, who had LDL cholesterol levels between the 60th and 90th percentiles. Participants randomized into this double-blind, placebo-controlled, factorially designed study received lovastatin (20-40 mg/day) or lovastatin-placebo and warfarin (1 mg/day), or warfarin-placebo over a 3-year period. The progression of the mean maximum intimal-medial thickness (IMT) over 12 walls of both carotid arteries represented the primary outcome. Lovastatin treatment was associated with a reduction in progression of mean maximum IMT (p < 0.001). Levels of LDL cholesterol were reduced by 28% (43.5 mg/dl [11.25 mmol/liter]) in the lovastatin group within 6 months (p < 0.0001) and remained stable throughout the follow-up period, whereas these levels remained essentially unchanged in the lovastatin-placebo group. The difference in incidence of major cardiovascular events for patients in the lovastatin-placebo group was significant: 5 versus 14, respectively (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Results of the primary outcome measure and clinical events from the Asymptomatic Carotid Artery Progression Study. 757 86

The 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, or statins, are more efficacious than older lipid-lowering agents and therefore may be more effective in reducing the incidence of coronary events. The objective of this prespecified analysis was to examine in coronary patients the effect of the lipid-lowering agent pravastatin on 3-year rates of coronary event incidence, all-cause mortality, and nonfatal myocardial infarction (MI), and to determine whether any observed benefit was also evident in patients > or = 65 years of age. The design of this analysis was to pool the data from 2 concurrent 3-year placebo-controlled clinical trials of pravastatin monotherapy in coronary patients (Pravastatin Limitation of Atherosclerosis in the Coronary Arteries [PLAC I] and the Pravastatin, Lipids, and Atherosclerosis in the Carotid Arteries [PLAC II]). This pooled database included 559 coronary patients with moderately elevated levels of low density lipoprotein cholesterol (between the 60th and 90th percentiles for age and gender in the United States). Over the 3 years of follow-up, use of pravastatin was associated with a 55% reduction in coronary incidence (p = 0.014). Pravastatin was also associated with a 67% reduction in nonfatal MI (p = 0.006). Eleven placebo patients died over the 3 years of follow-up compared with 7 in the pravastatin groups (a 40% reduction). Among older patients (age > or = 65 years), pravastatin therapy was associated with a 79% reduction in coronary event incidence (95% confidence interval [CI] 33-100%) and with a 86% reduction in nonfatal myocardial infarction (CI, 35-100%).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Reduction in coronary events during treatment with pravastatin. PLAC I and PLAC II Investigators. Pravastatin Limitation of Atherosclerosis in the Coronary Arteries. 757 89

Although elevated plasma cholesterol levels represent a well-established and significant risk for developing atherosclerosis, there is a wide spectrum of cholesterol levels in patients with coronary artery disease (CAD). Most secondary prevention studies have generated convincing evidence that cholesterol reduction in patients with high cholesterol levels is associated with improved clinical outcome by reducing risk of further cardiovascular events. However, other risk factors may play a prominent role in the pathogenesis of coronary disease in the majority of patients with near-normal cholesterol values. The Cholesterol and Recurrent Events (CARE) study was designed to address whether the pharmacologic reduction of cholesterol levels with the 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor, pravastatin, would reduce the sum of fatal coronary artery disease (CAD) and nonfatal myocardial infarction (MI) in patients who have survived an MI yet have a total cholesterol value < 240 mg/dl (< 6.2 mmol/liter). The other inclusion criteria for this study were age 21-75 years, low density lipoprotein (LDL) cholesterol levels of 115-174 mg/dl (3.0-4.5 mmol/liter), and fasting serum triglyceride levels < 350 mg/dl (< 4.0 mmol/liter). A total of 4,159 eligible consenting patients without other study exclusions were then randomly assigned to receive either pravastatin 40 mg daily or matching placebo in addition to their individualized conventional therapy. The trial was designed to have a median follow-up of 5 years. Study endpoints will be evaluated with respect to predefined subgroups according to baseline lipid values, age, gender, prior cardiovascular risk factors, and history.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Cholesterol and Recurrent Events: a secondary prevention trial for normolipidemic patients. CARE Investigators. 757 95

The long-term efficacy and tolerability of simvastatin, a 3-hydroxy-3-methylglutaryl-co-enzyme A (HMG-CoA) reductase inhibitor, was assessed during a 24-month follow-up period in 168 elderly hypercholesterolemic patients. After completing a 4 week double blind dose ranging study with simvastatin, 47 males and 122 females over 62 years of age with type II hyperlipidemia, a total cholesterol level above 6.5 mmol/l and clinically manifest cardiovascular disease were included in this extended study. A total of 159 patients completed the 12-month follow-up period and 141 patients were monitored over the full 24 months. All patients were started on 10 mg simvastatin once daily and the dosage was increased until the target levels of low density lipoprotein (LDL) cholesterol between 2.3 mmol/l (90 mg/dl) and 3.6 mmol/l (140 mg/dl) were reached. Fifty percent of patients reached the targeted LDL cholesterol goal of < 3.6 mmol/l (140 mg/dl) during the study. At study completion, 65 patients (39%) were taking 40 mg simvastatin per day, 56 patients (33%) 20 mg, 42 patients (25%) 10 mg and 5 patients (3%) only used 5 mg per day. Sixteen patients (9%) received concomitant lipid lowering therapy. Over 2 years, the mean decrease in LDL cholesterol ranged from 36% to 38%, the median decrease in triglycerides was 12% to 19% and the mean increase in high density lipoprotein (HDL) cholesterol ranged from 9% to 10%, respectively. Seven patients discontinued simvastatin because of adverse clinical or laboratory events, but only in two (1.1%) was this considered to be drug-related. Side-effects were mild and most frequently gastrointestinal in nature. Mean changes in asparate aminotransferase (AST) were not significantly different from zero and mean changes in alanine aminotransferase (ALT) and creatine phosphokinase (CPK) showed a small increase. We conclude that simvastatin is an efficacious and well-tolerated treatment for hypercholesterolemia in elderly individuals for extended periods.
Atherosclerosis 1995 Aug
PMID:Long-term efficacy and tolerability of simvastatin in a large cohort of elderly hypercholesterolemic patients. 757 71

We examined whether serum cholesterol reduction alters the lesional composition of atherosclerotic plaques. To reduce serum cholesterol levels, we gave pravastatin sodium, a 3-hydroxy-3-methylglutaryl Coenzyme A reductase inhibitor, to mature Watanabe heritable hyperlipidemic rabbits, an LDL receptor-deficient animal model, for 48 weeks. Atherosclerotic lesions were immunohistochemically and conventionally stained and each lesional component area was measured by a color image analyzer. Compared with those of a placebo group, serum LDL cholesterol levels were reduced by 22% (P<.05). Data for atherosclerosis indicated a significant decrease in percent of surface lesion area (26% reduction) and in intimal thickening (30% reduction) in the abdominal aorta, as well as in coronary stenosis (29% reduction). Data for lesional composition indicated a significant decrease in the percent area of macrophage plus extracellular lipid deposits in aortic lesions (32% reduction) and coronary lesions (45% reduction). A significant increase was observed in the percent area of collagen in aortic lesions and in the percent area of smooth muscle cells in coronary lesions. The plaques seemed to become stable lesions as a result of pravastatin treatment. In conclusion, a long-term reduction of serum LDL cholesterol reduced lipid-related lesional components, in addition to suppressing the progression of established atherosclerosis.
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PMID:Reduction of serum cholesterol levels alters lesional composition of atherosclerotic plaques. Effect of pravastatin sodium on atherosclerosis in mature WHHL rabbits. 758 74

Hypercholesterolemia is common following renal transplantation and undoubtedly contributes to morbidity and mortality due to occlusive atherosclerosis in these patients. Although 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors are more tolerable as low density lipoprotein cholesterol (LDL-C)-lowering agents than other classes of drugs, their use in transplant patients has been limited due to potentially serious interactions with cyclosporine. Fluvastatin is the first wholly synthetic HMG-CoA reductase inhibitor. Because it has a shorter half-life and greater protein-binding capacity than other drugs of this class and has no active circulating metabolites, fluvastatin may be safer than other HMG-CoA reductase inhibitors in this group of patients. To study this question, 19 renal transplant recipients (age, 21-70 years) with hypercholesterolemia (LDL-C > 180 mg/dL; triglycerides < 400 mg/liter) were entered into a 14-week active-treatment period with fluvastatin at 20 mg/day following dietary stabilization and a 3-week placebo washout period. Changes in LDL-C levels were compared with those obtained in control hypercholesterolemic subjects treated in the same way. The lipid-lowering ability of fluvastatin was not imparied in these patients, indicating a lack of interaction with cyclosporine. Mean liver enzyme levels, creatine phosphokinase (CPK), and creatine did not change significantly from baseline. Two subjects experienced myalgias without CPK elevations, and another subject experienced an asymptomatic increase in CPK to > 10 times the upper limit of normal, related to exercise. In conclusion, fluvastatin safely and effectively lowers elevated LDL-C levels in renal transplant recipients.
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PMID:A preliminary report of the safety and efficacy of fluvastatin for hypercholesterolemia in renal transplant patients receiving cyclosporine. 760 82

The accelerated atherosclerosis in diseases associated with elevated remnant lipoprotein levels has directed interest toward the response of this lipoprotein species to lipid-lowering treatment. The effect of fluvastatin--a synthetic 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor--was compared with that of placebo on parameters of remnant metabolism in 57 patients with moderate hypercholesterolemia, but not heterozygous familial hypercholesterolemia, type III hyperlipidemia, or endogenous hypertriglyceridemia. Fluvastatin therapy resulted in decreases versus baseline in plasma total cholesterol, low density lipoprotein cholesterol (LDL-C) and LDL apolipoprotein (apo) B levels of 18%, 20%, and 18%, respectively (p < 0.01). Plasma parameters related to remnant metabolism were also significantly decreased: intermediate density lipoprotein by 43% and apo E by 22% (p < 0.01). The percent decrease in plasma intermediate density lipoprotein cholesterol level was twice that of LDL-C and 50% greater than the decrease seen in very low density lipoprotein cholesterol (VLDL-C), which was decreased by 28%. Total triglycerides were reduced by 11% and VLDL apo B by 24%, whereas high density lipoprotein cholesterol (HDL-C) rose significantly by 8%, HDL2-C by 24%, and HDL3-C by 3%. There were no increases in apo A-I levels compared with placebo nor any significant change in plasma lipoprotein(a) levels. The composition of LDL and VLDL particles did not appear to be altered by therapy, as assessed by the LDL-C:LDL-B, VLDL-C:VLDL-B, or triglyceride:VLDL-B ratios.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of fluvastatin on intermediate density lipoprotein (remnants) and other lipoprotein levels in hypercholesterolemia. 760 88

3-Hydroxy-3-methylglutaryl-CoA (HMG CoA) reductase inhibitors are the drugs most commonly prescribed in the US to lower blood cholesterol. Previous studies have shown their efficacy in reducing plasma low density lipoprotein (LDL) cholesterol. However, little is known about their effects on preventing diet induced atherosclerosis. We have investigated the changes in lipoprotein profiles and extent of atherogenesis in hamsters (F1B strain) consuming an atherogenic diet with and without lovastatin. Thirty-six animals were randomized into 3 groups of 12 animals each, with similar plasma cholesterol levels. One group of animals received a basal chow diet, and the other two groups a basal diet plus 10% (w/w) coconut oil and 0.05% cholesterol. After 2.5 weeks, one of the groups received the latter diet supplemented with lovastatin (25 mg/kg/day). A second study was carried out in which animals received the same diets, but lovastatin was given during the 10 week period at a dose of 12.5 mg/kg/day. At the end of the experimental period, animals were sacrificed and lipoprotein cholesterol, liver enzymes, and aortic foam cell development were determined. Animals fed the high fat diet plus lovastatin had significantly lower levels of non-high density lipoprotein (HDL) cholesterol than those fed the unsupplemented high fat diet. No differences were observed in mean levels of this parameter between animals fed the low fat diet and those receiving lovastatin. The amount of aortic lipid staining was significantly less in the lovastatin and low fat groups when compared to the unsupplemented high fat groups. These results indicate that lovastatin can prevent diet induced aortic lipid deposition in this animal model.
Atherosclerosis 1995 Apr 07
PMID:Lovastatin inhibits diet induced atherosclerosis in F1B golden Syrian hamsters. 760 73


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