A leading hypothesis on the pathophysiology of Alzheimer's disease (AD) is the mis-metabolism of amyloid precursor protein. This mis-metabolism causes the 42-amino acid form of A beta(Abeta42) to form oligomers that in turn start a chain of events leading to the accumulation of amyloid plaques. Vascular factors such as hypertension, ...

Statins are administered daily, but because of their long half-lives, atorvastatin and rosuvastatin can be given every other day (q.o.d.). We examined the effect of q.o.d. statin therapy in 25 patients treated with either atorvastatin (mean dose, 18.8 mg q.o.d.) or rosuvastatin (mean dose, 9.7 mg q.o.d.). Low-density lipoprotein cholesterol ...

BACKGROUND: Blood lipid abnormalities in patients on highly active antiretroviral therapy (HAART) have been associated with exposure to protease inhibitors (PIs), particularly ritonavir. First therapy with a non-nucleoside reverse transcriptase inhibitor (NNRTI) leads to relatively favourable lipid profiles. We report on medium-term lipid profiles (up to 5 years) for antiretroviral-naive ...

Although many risk factors influence atherogenesis, LDL appears to play a primary role in this process. In prospective epidemiology, coronary risk increases as LDL cholesterol increases, throughout the entire range of concentrations encountered in healthy humans. Coronary risk is minimal in individuals and populations whose serum cholesterol remains quite low ...

Retrospective clinical studies indicate that individuals chronically treated with cholesterol synthesis inhibitors, statins, are at lower risk of developing AD (Alzheimer's disease). Moreover, treatment of guinea pigs with high doses of simvastatin or drastic reduction of cholesterol in cultured cells decrease Abeta (beta-amyloid peptide) production. These data sustain the concept ...

Statins have very important influences on adipocyte physiology, particularly via their effects on sterol regulatory element binding proteins (SREBPs), which are extremely important transcription factors for the regulation of adipocyte physiology. SREBP-1c activation in fat cell by the cytosolic cholesterol deprivation through HMG-reductase inhibition is responsible for most of the ...

Osteoporosis remains a significant clinical problem despite the availability of effective therapies. The main therapy still needed is an anabolic agent for the treatment of osteoporosis. This study examined the in vivo effect of the enzyme 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor simvastatin, which controls the first step in the ...

During the last years, several clinical studies have been published trying to elucidate the effect of statin treatment on amyloid precursor protein (APP) processing and metabolism of brain cholesterol in Alzheimer's disease (AD) in humans. We present an open biochemical study where 19 patients with AD have been treated with ...

New approaches to atherosclerosis-related diseases include novel uses of proven treatments and development of innovative agents. Several commonly used cardiovascular drugs such as dihydropyridine calcium antagonists, ACE inhibitors containing the sulphydryl group, or highly lipophilic beta-blockers have some anti-atherosclerotic activities. Moreover, new clinical trials suggesting that additional reduction of low-density ...

A working group from the Adult Treatment Panel III of the national Cholesterol Educational Program issued a revised algorithm for low-density lipoprotein (LDL)-cholesterol lowering in very high-risk cardiovascular disease patients. The rationale of these recommendations was primarily established from pooled analysis of multiple clinical trials of LDL-cholesterol-lowering therapies and limited ...

BACKGROUND: Cholesterol ester storage disease (CESD) is an autosomal recessive illness that results from mutations in the LIPA gene encoding lysosomal acid lipase. CESD patients present in childhood with hepatomegaly and dyslipidemia characterized by elevated total and low-density lipoprotein cholesterol (LDL-C), with elevated triglycerides and depressed high-density lipoprotein cholesterol (HDL-C). ...

Ezetimibe, a cholesterol absorption inhibitor, can be combined with statins to lower LDL-cholesterol. We evaluated additional ezetimibe (10 mg/day) in a placebo-controlled, double blind, randomized cross-over study in 20 patients (age 56+/-9 years, m:f 10:10, BMI 27.5+/-4.0 kg/m(2)) suffering from severe hypercholesterolemia and CHD who were treated by statins and ...

Epidemiologists have found a decreased risk of developing Alzheimer's disease (AD) in people taking statins (cholesterol biosynthesis inhibitors). We have reported previously that, in cell culture, lovastatin decreases the output of beta-amyloid, a peptide that is toxic to neurones, and is reputably the prime cause of neurodegeneration seen in AD. ...

Stavudine (d4T) has been associated with lipoatrophy and hyperlactatemia. In recent studies, d4T has also been related to both hypercholesterolemia and hypertriglyceridemia. Replacing d4T with another nucleoside analogue such as abacavir (ABC) may reduce lactate levels and improve lipoatrophy in the long term. However, the impact of this strategy on ...

PURPOSE: To provide nurse practitioners (NPs) with clinical and practical information about the use of niacin in the treatment of dyslipidemia. DATA SOURCES: Research-based and review articles in the medical literature and National Cholesterol Education Program guidelines. CONCLUSIONS: Niacin provides beneficial effects on all major lipid fractions, particularly high-density lipoprotein ...

Hypolipidemic drugs are potent serum cholesterol lowering agents used for prevention of coronary heart disease. In addition to their cholesterol lowering effect, these drugs exhibit both pleiotropic beneficial and various neurological side effects. Therefore, we analysed effect of the hypolipidemic drugs, fenofibrate and statins, on membrane lipid composition in the ...

The evidence linking cholesterol levels in the blood to vascular risk is now incontrovertible and the introduction of HMG CoA (3-hydroxy-3-methylglutaryl coenzyme A) reductase inhibitor (or statin) therapy into clinical practice has now revolutionized the management of lipid disorders and silenced at a stroke the critics of cholesterol control as ...

OBJECTIVE: Because the lipoprotein effects of statin and fibric acid derivatives therapies differ, we studied the effects of these therapies in patients with hyperlipidemia on lipoproteins, vasomotor function, and plaque stability. METHODS: We administered simvastatin, 20 mg daily, to 27 patients with hypercholesterolemia and coronary artery disease, or fenofibrate, 200 ...

BACKGROUND: Reduction in cardiovascular events with statins has been in part attributed to their anti-inflammatory properties. OBJECTIVE: Evaluate the effects of atorvastatin on levels of inflammatory markers, such as tumor necrosis factor-alpha (TNF), interleukins (IL-1 and IL-6), soluble intercellular adhesion molecule-1 (sICAM-1) and C-reactive protein (CRP) in hypercholesterolemic patients (LDL-cholesterol ...

It has been suggested that a high serum cholesterol level is a risk factor for Alzheimer's disease (AD), that treatment with cholesterol-lowering drugs (statins) reduces the frequency of AD development, and that the polymorpholism of genes encoding proteins regulating cholesterol metabolism is associated with the frequency of AD development. However, ...

Among the pleiotropic effects of statins, their antioxidant action may be involved in their protective effects. Thus, we investigated the antioxidant effect of simvastatin, associated or not with alpha-tocopherol, on levels of electronegative low-density lipoprotein (LDL-), nitrotyrosine, thiols (homocysteine, glutathione, cysteine, methionine), and lipid-soluble antioxidants in blood plasma of hypercholesterolemic ...

Elevated low-density lipoprotein (LDL)-cholesterol is associated with a significantly increased risk of coronary heart disease. Ezetimibe is the first member of a new class of selective cholesterol absorption inhibitors. It impairs the intestinal reabsorption of both dietary and hepatically excreted biliary cholesterol. Ezetimibe is an effective and safe agent for ...

Heterozygous familial hypercholesterolemia (FH) affects one in every 500 persons and is the most common cause of markedly elevated cholesterol levels in children. Other causes of primary hyperlipidemia include familial combined hyperlipidemia, which is also common (approximately 1%) but not usually manifest until after puberty, and very rare genetic disorders ...

BACKGROUND: A low-carbohydrate diet remains controversial, especially in patients with arteriosclerotic heart disease. HYPOTHESIS: This study was undertaken to evaluate the effect of a low-carbohydrate diet on the lipid levels in obese patients with known arteriosclerotic heart disease on chronic statin therapy. METHODS: Thirty-eight overweight patients with angiographically documented arteriosclerotic ...

(1) Simvastatin and pravastatin are the drugs of choice for secondary or primary prevention of cardiovascular events in patients with hypercholesterolaemia. Both these statins have proven clinical efficacy. If statin therapy is inadequate, the dose can be increased or a drug combination can be tried, while keeping a lookout for ...

OBJECTIVE: To conduct a post-hoc assessment of the lipid-modifying effects of adding the cholesterol absorption inhibitor, ezetimibe, to on-going statin therapy in patients with diabetes mellitus (DM) or metabolic syndrome (MetS). RESEARCH DESIGN AND METHODS: This was a post-hoc analysis of data from a randomized, double-blind, placebo-controlled trial designed to ...

Since they share a common mode of action and certain structural features, all statins exhibit the same broad pharmacological effects. Nevertheless, important differences exist between the statins in terms of LDL cholesterol-lowering, endpoint reduction, pleiotropic effects and toxicity. For this reason, it is incorrect to view all statins as being ...

BACKGROUND: Although available guidelines suggest reducing low-density lipoprotein cholesterol (LDL-C) to below 100 mg/dL (2.6 mmol/L), the importance of target-oriented therapy remains controversial. To assess whether achieving guideline-based targets is of benefit, the relationship between clinical outcomes and lipid levels (baseline and on-study) was evaluated in the GREek Atorvastatin and ...

Statins (3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors) are the drug of first choice for lowering low-density lipoprotein cholesterol (LDL-C) levels and reducing risk of coronary heart disease (CHD). Current therapeutic use of statins, however, has resulted in only a small percentage of patients reaching their LDL-C treatment goal. Despite the clinical ...

Although each revision of the US National Cholesterol Education Program guidelines has made increasing provision for the use of global risk assessment in determining need for and intensity of therapy, the guidelines' continued focus on low-density lipoprotein (LDL) cholesterol may result in inadequate or no treatment for individuals at high ...

BACKGROUND: Rosuvastatin is a new statin indicated to reduce elevated levels of total cholesterol, low-density lipoprotein cholesterol (LDL-C), and triglycerides and to increase levels of high-density lipoprotein cholesterol (HDL-C) in patients with primary hypercholesterolemia, mixed dyslipidemia, and homozygous familial hypercholesterolemia. OBJECTIVE: The purpose of this article was to review the ...

Patients with cardiac syndrome X with mild hypercholesterolemia were randomized to placebo (n = 20) or simvastatin 20 mg/day (n = 20). In the simvastatin group, there was a significant (26%; p < 0.0001) decrease in total cholesterol, a 38% (p < 0.0001) decrease in low-density lipoprotein cholesterol levels, and ...

In this prospective study, we found beneficial short-term effects from atorvastatin therapy, including effects on low-density lipoprotein subfractions and remnant-like lipoprotein particle cholesterol, antioxidant effects, and alterations in endothelial function that may be important in early benefit from statin therapy; some effects would support much earlier benefit than previously reported. ...

The risk of coronary heart disease is increased for any given low-density lipoprotein (LDL) cholesterol level in patients with high levels of triglycerides because some triglyceride-rich lipoproteins are atherogenic. This paper reports the results of a pilot clinical trial aimed to evaluate a novel triglyceride-lowering drug in combination with pravastatin ...

OBJECTIVE: High-density lipoprotein (HDL)-associated paraoxonase (PON) activity may play an important role in the inhibition of low-density lipoprotein (LDL) oxidation. Previous studies have demonstrated that serum PON activity is decreased in patients with hyperlipoproteinaemia and coronary heart disease. The study presented here examined the effect of short-term treatment with simvastatin ...

BACKGROUND: Small studies have suggested that lipid-lowering strategies, and particularly statins, could influence blood pressure (BP) control. The aim of the present study was to evaluate the effect of different lipid-lowering strategies on BP control of subjects with hypercholesterolemia who were enrolled in the prospective, population-based, longitudinal Brisighella Heart Study. ...

Individuals expressing the polymorphic CYP3A5 enzyme might show a more than average efficiency in the metabolism of lovastatin, simvastatin and atorvastatin. We studied whether the expression of CYP3A5 is associated with an impaired lipid-lowering response to statins in 69 Caucasian patients. Lovastatin, simvastatin and atorvastatin were significantly less effective in ...

The treatment of dyslipidemia is beyond doubt one of the cornerstones of cardiovascular prevention. If we want to touch and comment on at least the principal news in this broad field, we must simplify and pay attention to only a few selected areas. The focus of this article is on ...

There is currently intense research interest in the properties of HMG-CoA reductase inhibitors (statins) beyond their well-documented lipid-lowering action. Studies have consistently demonstrated that administration of statin therapy decreases levels of the inflammatory marker C-reactive protein (CRP), a marker associated with an increased risk of cardiovascular events. This effect appears ...

OBJECTIVE: To investigate the impact of Vitamin E on lipids and peroxidation during statin treatment. RESEARCH DESIGN AND METHODS: T1DM patients with high cholesterol received Atorvastatin 20mg with either placebo (group AP, n = 11) or d-alpha-tocopherol 750 IU (group AE, n = 11) daily. They were monitored for blood ...

Despite their inherited nature, familial dyslipidemias show large intra- and interfamilial variability in phenotypic expression, clinical presentations, and levels of abnormalities of serum lipid fractions. Once diagnosed, patients shall be considered at high cardiovascular risk and treated as per secondary prevention National Cholesterol Education Program III guidelines. Comorbidity treatments (ie, ...

Reductions in low-density lipoprotein (LDL) cholesterol with statins have been shown to significantly reduce risk of coronary heart disease (CHD) in the primary- and secondary-prevention settings. Benefit has been observed even in high-risk patients whose baseline LDL cholesterol levels were below the drug initiation levels recommended by current treatment guidelines. ...

OBJECTIVE: Anti-atherosclerotic effects of statins might be mediated partly by pleiotropic cholesterol-lowering independent mechanisms. We used nonhuman primates and examined whether treatment with pravastatin or antimonocyte chemoattractant protein-1 (MCP-1) therapy can induce regression and stabilization of established atherosclerotic lesions through cholesterol-lowering independent mechanisms. METHODS AND RESULTS: Advanced atherosclerosis was induced ...

Recent epidemiological studies suggest that inhibitors of 3-hydroxy-3-methyl-glutaryl CoA reductase, so-called statins, are effective in lowering the prevalence of Alzheimer's disease. Whether the effect of statins is due to a local inhibition of cholesterol synthesis in the brain or whether it is mediated by the reduced levels of cholesterol in ...

The efficacy of statins in lowering low-density lipoprotein cholesterol (LDL-C) and reducing coronary heart disease risk is well established; however, recent evidence suggests that more aggressive lipid management, even beyond achievement of currently recommended LDL-C goals, may provide additional clinical benefits. A novel approach to the aggressive lowering of LDL-C ...

The aim of this study was to evaluate the effects of the selective oestrogen receptor modulator, raloxifene, and those of statin, atorvastatin, in reducing the cardiovascular risks associated with the post-menopausal status. A detailed study of serum lipid concentrations was performed in four groups of post-menopausal women receiving either placebo, ...

OBJECTIVE: We investigated whether statin improves nitric oxide (NO) bioactivity and reduces serological markers of oxidant stress and inflammation and whether statin-induced reduction in markers of oxidant stress and inflammation is mediated by improvement in NO bioactivity or lipoprotein changes, compared with American Heart Association Step I Diet (Diet). METHODS: ...

OBJECTIVE: The effects of hormone replacement therapy (HRT) can affect many aspects relevant to cardiovascular disease, including vasomotor function, inflammation, and hemostasis. Recent studies have demonstrated that current doses of HRT exert a mixture of both protective and adverse effects. In the current study, we compared the effects of lower ...

OBJECTIVE: The Third Report of the Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults, Adult Treatment Panel III (ATP III) encouraged reduced low-density lipoprotein (LDL) cholesterol levels for a greater number of patients and reemphasized the benefits of high-density lipoprotein (HDL) cholesterol. The purpose of ...

In familial hypercholesterolemia, a defect in low-density lipoprotein receptors causes lifelong two- to threefold elevations in serum low-density lipoprotein-cholesterol levels. This leads to early atherosclerotic changes in infancy. Lifelong hypolipidemic treatment that can be started at a young age is thus greatly needed. Early diagnosis of familial hypercholesterolemia is important, ...