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Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Important novel developments in the pharmacotherapy of cardiovascular diseases are briefly summarized. New results with lipid lowering statins in secondary prevention of atherosclerosis are mentionned. Atorvastatin, introduced recently, is compared to the other statins. The extended possibilities for inhibition of platelet-aggregation in coronary disease and after interventional coronary therapy with ticlopidine, clopidogrel and specific antagonists of platelet integrin IIb/IIIa receptors (abciximab, tirofibrane) as well as fibrinolysis with reteplase are covered. Among modern trends in pharmacotherapy of heart failure studies with angiotensin-II-receptor inhibition (losartane and related compounds) or betablockers (carvedilol) are worth mentioning.
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PMID:[New cardiovascular drugs: expanded therapeutic possibilities in coronary heart disease and in heart failure]. 1040 78

Male Hartley guinea pigs were fed a hypercholesterolemic diet rich in lauric and myristic acids with 0, 10, or 20 mg/kg of simvastatin or atorvastatin for 21 days. Atorvastatin and simvastatin resulted in a lowering of plasma low-density lipoprotein (LDL) cholesterol in a dose-dependent manner by an average of 48 and 61% with 10 and 20 mg/kg, respectively. Both statins were equally effective in lowering plasma LDL cholesterol and apolipoprotein B (apo-B) levels. Atorvastatin and simvastatin treatments yielded LDL particles that differed in composition from the control. Due to the relevance of LDL oxidation and cholesteryl ester transfer in plasma to the progression of atherosclerosis, these parameters were analyzed after statin treatment. Atorvastatin and simvastatin treatment decreased the susceptibility of LDL particles to oxidation by 95% as determined by the formation of thiobarbituric acid reactive substances. An 80% decrease in the transfer of cholesteryl ester between high-density lipoprotein (HDL) and the apo-B-containing lipoproteins was observed after simvastatin and atorvastatin treatment. In addition, statin effects on plasma LDL transport were studied. Simvastatin- and atorvastatin-treated guinea pigs exhibited 125 and 175% faster LDL fractional catabolic rates, respectively, compared with control animals. No change in LDL apo-B flux was induced by either treatment; however, LDL apo-B pool size was reduced after statin treatment. Hepatic microsomal free cholesterol was lower in the atorvastatin and simvastatin groups. However, only atorvastatin treatment resulted in an 80% decrease of acyl-CoA:cholesterol acyltransferase activity (P < 0.001). In summary, atorvastatin and simvastatin had similar LDL cholesterol lowering properties, but these drugs modified LDL transport and hepatic cholesterol metabolism differently.
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PMID:Hypocholesterolemic effects of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors in the guinea pig: atorvastatin versus simvastatin. 1048 79

The effects of atorvastatin (Lipitor) were evaluated in 40 patients with familial hypercholesterolemia (FH). Following a 6 week drug-free baseline period 20 male and 20 female patients were treated with atorvastatin 40 mg once daily (QD) for the initial 6 weeks increasing to 80 mg QD during the following 6 weeks. Atorvastatin 40 and 80 mg resulted in a dose related reduction in LDL cholesterol of 44 and 50% (P<0.001), respectively. The reduction of triglycerides (TG) was 35% (P<0.001) with 40 and 80 mg atorvastatin. The lipoprotein lipase and the hepatic lipase activity decreased dose independently by 13% (P<0.05) and 18% (P<0.01), respectively. In males, a dose independent increase in high-density lipoprotein (HDL) cholesterol concentration was observed of 8%, (P<0.05). In females, the HDL cholesterol concentration did not change. Baseline LDL size in the females was significantly larger than in the males, being 268+/-6 A and 264+/-8 A (P<0.05), respectively. In males LDL size increased significantly from 264+/-8 A at baseline to269+/-6 A at 40 mg (P<0.05) and to 270+/-5 A (P<0.05) at 80 mg atorvastatin. In females LDL size did not change upon treatment with atorvastatin 40 and 80 mg QD. In conclusion, atorvastatin has the ability to decrease cholesterol and triglyceride concentrations as well as the activity of both lipoprotein and hepatic lipase activity. Additionally it has a favorable effect on LDL size and HDL cholesterol concentration in male, but not in female FH patients.
Atherosclerosis 1999 Sep
PMID:Atorvastatin increases low-density lipoprotein size and enhances high-density lipoprotein cholesterol concentration in male, but not in female patients with familial hypercholesterolemia. 1048

Cardiovascular mortality, mainly due to the rupture of unstable atherosclerotic plaques, is reduced by 3-hydroxy-methyl-glutaryl-coenzyme A (HMG-CoA) reductase inhibitors. Inflammatory cells, attracted to the vascular lesion by chemokines, have been implicated in the process of the plaque rupture. In cultured vascular smooth muscle cells (VSMC) and U937 mononuclear cells we have studied the effect of Atorvastatin (Atv) on nuclear factor kappaB (NF-kappaB) activity, an inducer of the mRNA expression of chemokines such as interferon-inducible protein 10 (IP-10) and monocyte chemoattractant protein 1 (MCP-1). Angiotensin II (Ang II) and tumor necrosis factor alpha (TNF-alpha) increased NF-kappaB activity in VSMC (2 and 5-fold, respectively). Preincubation of cells with 10(-7) mol/l Atv diminished this activation (44 and 53%). The inhibition was reversed by mevalonate, farnesylpyrophosphate (FPP) and geranylgeranylpyrophosphate (GGPP), but not by other isoprenoids. Coinciding with the NF-kappaB activation in VSMC, there was a diminution of cytoplasmic IkappaB levels that was recovered by pretreatment with Atv. Ang II and TNF-alpha induced the expression of IP-10 (1.5 and 3.4-fold) and MCP-1 (2.4 and 4-fold) in VSMC. Atv reduced this overexpression around 38 and 35% (IP-10), and 54 and 39% (MCP-1), respectively. Our results strongly suggest that Atv, through the inhibition of NF-kappaB activity and chemokine gene expression, could reduce the inflammation within the atherosclerotic lesion and play a role in the stabilization of the lesion.
Atherosclerosis 1999 Dec
PMID:Atorvastatin reduces NF-kappaB activation and chemokine expression in vascular smooth muscle cells and mononuclear cells. 1055 11

A total of 531 patients from 57 hospital centres across the UK, who had previously been treated with lipid-lowering agents in combination or alone, in whom the degree of cholesterol reduction was insufficient to achieve European Atherosclerosis Society target levels, were treated with atorvastatin over a 12-week period. The dose of atorvastatin (10, 20 or 80 mg/day) was determined by assignment of risk based on entry level cholesterol levels and the presence of other established CHD risk factors. Atorvastatin was successful in achieving target LDL-cholesterol levels in 86% of mild risk patients, 88% of moderate risk patients and 52% of high risk patients. Compliance with atorvastatin was 96% and treatment was well tolerated. This study demonstrates that atorvastatin is effective in achieving target lipid levels in a large proportion of patients and that the dose required can be predicted by an assessment of the patient's risk profile.
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PMID:An assessment of the efficacy of atorvastatin in treating patients with dyslipidaemia to target LDL-cholesterol goals: the atorvastatin matrix study. 1069 35

HMG-CoA reductase inhibitor drugs or 'statins' have been shown to effectively reduce plasma total cholesterol (CHOL), CHOL associated with low-density-lipoprotein (LDL), and triglycerides (TG). In addition, slight elevations in HDL-CHOL are also typically observed. Poloxamer 407 (P-407), a nonionic surfactant, effectively elevates both plasma CHOL and especially TG in a dose-controlled fashion and results in formation of atherosclerotic lesions in the aortas of C57BL/6 mice without the requirement of dietary cholic acid [1,2]. The purpose of the present study was to assess whether a typical statin, namely atorvastatin (Lipitor(R)) would significantly reduce P-407-induced hypercholesterolemia and hypertriglyceridemia as well as cause regression of atherosclerotic lesions resulting from administration of P-407 to C57BL/6 mice. C57BL/6 mice in the present study were treated with either normal saline (C, controls), 0.5 g/kg of P-407 (P), or a high-fat, high-cholesterol, cholate-containing diet (HF) for 120 days. Mice in all groups were then equally and randomly divided and treated with either atorvastatin or saline for an additional 120 days. Beginning at Day 121 and using mice in groups P and HF as an example, one-fourth of the mice in each group received 20 mg/kg per day of atorvastatin with either concomitant HF feeding or P-407 administration ('progression' treatment groups), one-fourth received 20 mg/kg per day of atorvastatin following cessation of HF feeding or P-407 administration, one-fourth received saline (placebo) with either simultaneous HF feeding or P-407 administration ('progression' placebo groups), and one-fourth received saline (placebo) following cessation of HF feeding or P-407 administration. Total plasma CHOL was significantly (P<0.01) lower for mice in groups P and HF when administered atorvastatin relative to saline, but remained significantly (P<0.05) elevated compared to total plasma CHOL of C mice. With discontinuation of either P-407 administration or HF feeding, total plasma CHOL declined rapidly in both P and HF mice with atorvastatin-treated mice generally demonstrating lower plasma CHOL concentrations relative to saline-treated mice. Total plasma TG was significantly (P<0.01) lower for mice in group P administered atorvastatin relative to saline, but remained significantly (P<0.05) elevated compared to plasma TG of C mice. With discontinuation of P-407 administration, total plasma TG declined rapidly in P mice with atorvastatin-treated mice typically demonstrating lower plasma TG concentrations relative to saline-treated P mice. Aortas of mice treated with 20 mg/kg per day of atorvastatin in both groups P and HF, whether maintained on the HF-diet or treated with P-407 from Day 120 to 240 or whether each treatment was terminated at Day 120, revealed no presence of atherosclerotic lesions relative to saline-treated mice and were indistinguishable from aortas retrieved from C mice. Atorvastatin at a dose of 20 mg/kg per day not only significantly reduced the plasma CHOL and TG concentrations, but also resulted in regression of atherosclerotic lesions induced in C57BL/6 mice by administration of P-407 or ingestion of a HF-diet containing cholic acid.
Atherosclerosis 2000 Apr
PMID:Regression of poloxamer 407-induced atherosclerotic lesions in C57BL/6 mice using atorvastatin. 1072 80

One hundred and ninety-five aged (mean age: 67+/-4.8 years), non-insulin dependent diabetic patients underwent a randomised single-blind study for investigating the effect of statin administration on insulin resistance and respiratory quotient. After 4 weeks run-in period, all patients were randomised in three groups: placebo (n=67), simvastatin (10 mg/day) (n=61) and atorvastatin (5 mg/day) (n=67). Each treatment period lasted 8 weeks. At the beginning, after the run-in and at the end of the study, insulin resistance was assessed by homeostasis model assessment (HOMA) index, while respiratory quotient (Rq) was evaluated by indirect calorimetry. Statins versus placebo significantly lowered plasma total, LDL-, HDL-cholesterol and triglyceride concentrations and improved insulin resistance and Rq and metabolic control. Atorvastatin had a greater effect than simvastatin on plasma triglyceride concentration (-26.3+/-3.1 vs. -19.7+/-2.8%, P<0.03), HOMA index (-13.1+/-0.6 vs. -9.1+/-0.9%, P<0.05), Rq (5.9+/-0.4 vs. 3.1+/-0.5%, P<0.05) and glycosylated haemoglobin (-11.2+/-0.3 vs. -7. 1+/-0.4%, P<0.05). In the whole group of subjects (n=195) and at the end of the study, changes in plasma triglyceride concentrations were significantly correlated with the change in the HOMA index (r=0.44, P<0.001) and age and BMI adjusted-Rq (r=-0.32, P<0.005). Multivariate analyses demonstrated that decline in plasma triglyceride concentration was a significant determinant for explaining the effect of statin on insulin resistance and Rq. In conclusion our study demonstrates that statin administration is useful for controlling dyslipidemia in NIDDM patients and for improving the metabolic control. With regard to this latter aim, atorvastatin seems to be more powerful than simvastatin.
Atherosclerosis 2000 May
PMID:Effects of simvastatin and atorvastatin administration on insulin resistance and respiratory quotient in aged dyslipidemic non-insulin dependent diabetic patients. 1078 42

Most clinical trials of lipid intervention and coronary artery disease prevention have been conducted in study populations that exclude diabetic individuals. Three trials have conducted post hoc analyses of their diabetic subgroups. One of these was a primary intervention trial with gemfibrozil (Helsinki Heart Study). Although this trial found a reduction in coronary events, the numbers were too small to reach significance. The two other trials (the Scandinavian Simvastatin Survival Study [4S] and Cholesterol and Recurrent Events Trial [CARE]) were secondary intervention trials conducted with hydroxymethylglutaryl-CoA reductase inhibitors, simvastatin, and pravastatin. Both of these trials found a reduction in coronary events. Although these two trials present the strongest evidence in support of the clinical benefits of lipid reduction in diabetes, they must be interpreted with caution. They are post hoc subgroup analyses, they looked at mainly hypercholesterolemic populations, and they are secondary intervention studies. Four studies aimed at testing the "lipid hypothesis" specifically in diabetes are currently under way. Three of these studies (Fenofibrate Intervention and Event Lowering in Diabetes [FIELD], Collaborative Atorvastatin Diabetes Study [CARDS], and Lipids in Diabetes Study [LDS]) are primary prevention trials, with clinical events as the primary end point. FIELD uses micronized fenofibrate, CARDS uses atorvastatin, and LDS uses both micronized fenofibrate and cerivastatin alone or in combination. These trials are in the early stages of starting or recruiting. One study (Diabetes Atherosclerosis Intervention Study [DAIS]) using micronized fenofibrate is nearing completion. It is an angiographic study that combines those with and without preexisting clinical coronary disease.
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PMID:Lipid intervention trials in diabetes. 1086 Jan 91

Elevated levels of serum lipids and lipoproteins are known to play a major role in the development of atherosclerosis and subsequent coronary heart disease (CHD). In controlled clinical studies, atorvastatin (Sortis), a new 3-hydroxy-3-methyl-glutaryl-coenzyme-A (HMG-CoA)-reductase inhibitor, proved to be a very effective and safe lipid-lowering agent. The aim of this open-label, multicentre study (without a control group) was to confirm the efficacy and safety of atorvastatin in a private practice group, including 181 Swiss cardiologists, internists, and general practitioners. A total of 877 hyperlipidaemic patients requiring treatment participated in this study. To evaluate the effectiveness of the treatment with atorvastatin over a period of 12 weeks, total plasma cholesterol (TC), HDL cholesterol, LDL cholesterol and triglycerides (TG) were determined every 4 weeks. The initial atorvastatin dose was 10 mg in 78% of patients and 20 mg in 22%. The dose was doubled every 4 weeks until the target values of TC < or = 5.2 mmol/l and TC/HDL < or = 5 were reached. After 12 weeks of treatment with atorvastatin the mean reduction in TC, TC/HDL, LDL and TG compared to baseline levels was 33, 37, 42, and 25% respectively. At the same time the HDL concentration was increased by 9%. These results were evidenced in patients with existing coronary heart disease, in high risk patients without manifest coronary heart disease and in patients with significantly elevated lipid levels (TC > 7.8 mmol/l, TC/HDL > 6.5). After treatment with atorvastatin for 12 weeks, 59% of patients had reached the therapeutic target of TC < or = 5.2 mmol/l. The target of TC/HDL < or = 5 was reached by 79%. Atorvastatin was almost without exception well tolerated, the most frequently reported side effects being nausea, myalgia, and headache. In this open-label multicentre study atorvastatin was found to be effective and well tolerated. The observed reduction in the lipid and lipoprotein concentration is in accordance with the results of published controlled studies. The lipid and lipoprotein concentrations were decreased significantly in patients with slight to moderate elevation of lipid levels as well as in those with significantly raised values.
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PMID:[Evaluating the efficacy and tolerance of atorvastatin in hyperlipidemia in general practice (SWITCH Study)]. 1089 90

The hypertriglyceridemia attends the physiopathology of the atherosclerosis by various mechanisms: association of low levels of high density lipoprotein-cholesterol (HDL-c), modification of quality of low density lipoprotein-cholesterol (LDL-c), influence on hemostatic processes, association with other hazard's factors (obesity, hypertension, etc.). The hypertriglyceridemia distinguishes in primary and secondary. In primary forms the origin is essentially genetic, while the secondary ones are metabolic consequence of various pathologies (renal, thyroid, diabetes mellitus etc.). The hypertriglyceridemia's treatment is founded on a correct feeding and/or on eventual use of drugs. Apart from the secondary forms, in which is obligatory to treat at first the basal disease, the pharmacological therapy of the hypertriglyceridemia is suggested only in resistant cases to alone dietetic therapy and overall in presence of other factors of atherothrombotic hazard. The most utilized drugs are: omega-3 fatty acids, the nicotinic acid and its derivatives, the fibrates and the statins. The stronghold of alpha-glucosidases inhibitors is the acarbose. It reduces the biosynthesis of very low density lipoproteins (VLDL) by the reduction of substrata with an improvement of glucidic metabolism. Atorvastatin and cerivastatin develop a greater action to reduce serum levels of triglycerides as to the foregoing ones because of the better selectivity of receptor binding, the greater halflife and inhibition of the apolipoprotein's B100 synthesis.
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PMID:[Treatment of hypertriglyceridemia. Current aspects]. 1093 25


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