PubMed Health⌕ Search

Biomedical subjects

Robert S Rosenson

Publications and source records attributed to Robert S Rosenson.

At least 19 recordsLinked to original sources
PubMed2007

Efficacy and safety of rosuvastatin 40 mg versus atorvastatin 80 mg in high-risk patients with hypercholesterolemia: results of the POLARIS study.

POLARIS investigated the efficacy and safety of rosuvastatin 40 mg and atorvastatin 80 mg in high-risk patients with hypercholesterolemia. Patients (n=871) were randomized to rosuvastatin 40 mg/day or atorvastatin 80 mg/day for 26 weeks. The primary endpoint was percentage change in LDL-C levels at 8 weeks. Secondary assessments included safety and tolerability, NCEP ATP III LDL-C goal achievement, change in other lipids and lipoproteins at 8 and 26 weeks, and health economics. Mean LDL-C levels were reduced significantly more with rosuvastatin 40 mg than with atorvastatin 80 mg at 8 weeks (-56% versus -52%, p<0.001). The proportion of patients achieving the NCEP ATP III LDL-C goal at 8 weeks was significantly higher in the rosuvastatin 40 mg group (80% versus 72%, p<0.01). Significant differences in the change from baseline in high-density lipoprotein cholesterol (HDL-C) (+9.6% versus +4.4%) and apolipoprotein (Apo)A-I levels (+4.2 versus -0.5) were observed between rosuvastatin and atorvastatin (all p<0.05). Both treatments were well tolerated. Based on a US analysis, rosuvastatin used fewer resources and delivered greater efficacy. Intensive lipid-lowering therapy with rosuvastatin 40 mg/day provided greater LDL-C-lowering efficacy than atorvastatin 80 mg/day, enabling more patients to achieve LDL-C goals. Rosuvastatin may therefore improve LDL-C goal achievement in high-risk patients with hypercholesterolemia.

Aged↗
PubMed2006

An assessment of statin safety by muscle experts.

The National Lipid Association's (NLA) Muscle Safety Expert Panel was charged with the duty of examining the definitions, causative factors, and management of statin myopathy. The Panel was asked to use its evidence-based findings to form recommendations in response to a series of specific questions posed by the Task Force. The panel was composed of a clinical cardiologist, an exercise physiologist and skeletal muscle expert, and an expert in preventive cardiology who also examined skeletal muscle complications of statin use.

Biopsy↗
PubMed2006

Low high-density lipoprotein cholesterol and cardiovascular disease: risk reduction with statin therapy.

A low level of high-density lipoprotein cholesterol (HDL-C) is a major risk factor for cardiovascular disease; however, patients with low levels of HDL-C without raised low-density lipoprotein cholesterol (LDL-C) levels are not currently eligible for lipid-lowering therapy. Many individuals with low levels of HDL-C have a combination of cardiovascular risk factors that include high LDL particle concentrations. Lowering LDL particle concentration and its surrogate measure, LDL-C, is an important approach to reducing cardiovascular risk. Statins are the most effective agents for lowering levels of LDL and can significantly increase levels of HDL-C. Extending statin therapy to patients with low levels of HDL-C but with LDL-C levels below target may have benefits for cardiovascular disease reduction in these patients.

Atorvastatin↗
PubMed2006

Statins: panacea for sepsis?

Sepsis occurs when the immune system responds to a localised infection at a systemic level, thereby causing tissue damage and organ dysfunction. Statins have proven health benefits in many diseases involving vascular inflammation and injury. Recent animal data suggest that the administration of a statin before a sepsis-inducing insult reduces morbidity and improves survival. The immunomodulatory and anti-inflammatory effects of statins, collectively referred to as pleiotropic effects, lend biological plausibility to such findings. Limited human data hint at reduced mortality rates in bacteraemic patients, and a reduced risk of sepsis in patients with bacterial infections concurrently taking statins. These lines of evidence point to a potential new treatment and prevention modality for sepsis. The stage is set for randomised controlled clinical trials that will determine whether statins represent a safe and beneficial treatment in critically ill, septic patients and whether statins are effective at preventing sepsis in high-risk clinical settings.

Animals↗
PubMed2005

Assessing risk across the spectrum of patients with the metabolic syndrome.

The metabolic syndrome represents a constellation of interrelated risk factors that identify individuals at increased risk for the development of type 2 diabetes mellitus and cardiovascular events. Currently, the major cardiovascular risk factors and validated risk-assessment tools do not adequately account for the increased cardiovascular risk that accompanies the metabolic syndrome. In prospective population studies, cardiovascular risk assessment in individuals with the metabolic syndrome is improved by measures of low-density lipoprotein (LDL) particle number, C-reactive protein, and plasminogen activator inhibitor-1 levels. Although adiponectin and soluble tumor necrosis factor receptor-2 may be more integrally involved in insulin resistance, the studies with these biomarkers are less extensive. Risk assessment models for patients with the metabolic syndrome should consider inclusion of LDL particle number, inflammatory markers, and levels of plasminogen activator inhibitor-1.

Adiponectin↗
PubMed2005

Short-term reduction in bone markers with high-dose simvastatin.

The effect of statins on bone mass and fracture rates is uncertain. Therefore, we investigated whether statin therapy acutely altered bone turnover as measured by changes in bone serum markers (bone-specific alkaline phosphatase, osteocalcin, and type I collagen N-telopeptide cross-links). Fasting blood samples were obtained from 55 (M/F 39/16) healthy nonsmoking adults (mean +/- standard deviation: age, 50.4+/-7.5 years; body mass index, 27.8+/-4.9 kg/m(2)) with low-density lipoprotein cholesterol concentrations between 3.38-4.90 mmol/l. Subjects were randomized to four possible 8-week treatment regimens: placebo (n =14), pravastatin 40 mg/daily (n =12), simvastatin 20 mg/daily (n =14) or simvastatin 80 mg/daily (n =15). High-dose simvastatin (80 mg/daily) produced a significant reduction in bone-specific alkaline phosphatase as compared with other treatment regimens (p =0.009). However, there were no changes in urinary N-telopeptide cross-links, a sensitive marker of bone resorption. Short-term use of high-dose simvastatin lowers the level of the serum bone marker bone-specific alkaline phosphatase, which suggests the possibility of reduced bone turnover.

Adult↗
PubMed2005

Colesevelam HCl reduces LDL particle number and increases LDL size in hypercholesterolemia.

BACKGROUND: Although LDL-cholesterol (LDL-C) remains the target of cholesterol-lowering therapy, high levels of LDL particle numbers better differentiate cardiovascular risk than LDL-C concentrations. Colesevelam HCl, a novel bile acid sequestrant, has also been shown to reduce mean LDL-C by 18% with the maximum dose. The effect of colesevelam HCl on LDL particle number and particle size has not been previously published. LDL particle number and particle size were measured by NMR spectroscopy. METHODS: In this multi-center, double-blind, placebo-controlled study, 149 patients with moderate hypercholesterolemia (LDL-C > 160 mg/dL [4.14 mmol/L]; triglycerides < 300 mg/dL [3.39 mmol/L]) were randomized to colesevelam HCl (1.5-3.75 g/d) or placebo for 6 weeks. RESULTS: Colesevelam HCl reduced LDL particle number by 6.8% at a dosage of 3.0 g/d (P = 0.031), and 13.7% (P = 0.0002) at a dosage of 3.75 g/d. Baseline levels of triglycerides or LDL size did not influence changes in LDL particle number. Further, mean LDL particle size increased with colesevelam HCl 3.75 g/d (1.1% increase versus baseline, P < 0.05). CONCLUSION: For patients with moderate hypercholesterolemia, treatment with colesevelam HCl at the recommended starting dose of 3.75 g/d lowered LDL particle number, and increased mean LDL particle size.

Allylamine↗
PubMed2005

HDL-C and the diabetic patient: target for therapeutic intervention?

A low level of high-density lipoprotein cholesterol (HDL-C) is a key feature of the metabolic syndrome and type 2 diabetes. HDL particles exert an anti-atherogenic effect, and low HDL-C levels are associated with increased cardiovascular disease risk. The profile of lipoprotein sub-classes may also be abnormal in patients with the metabolic syndrome or type 2 diabetes, with an excess of atherogenic small low-density lipoprotein (LDL) particles. Statins are first-line lipid-modifying drugs that, in addition to varying in their effects on LDL-C, differ in their effects on HDL-C. Rosuvastatin has been shown to be at least as effective at increasing HDL-C compared with atorvastatin, pravastatin or simvastatin. Selecting an agent that will increase HDL-C levels, as well as lowering LDL-C levels, may be particularly beneficial in the treatment of patients with the metabolic syndrome and type 2 diabetes.

Arteriosclerosis↗
PubMed2005

Low HDL-C: a secondary target of dyslipidemia therapy.

Current guidelines for the prevention of coronary heart disease (CHD) focus on lowering low-density lipoprotein cholesterol (LDL-C) as the primary target of lipid-modifying therapy. However, there is increasing interest in high-density lipoprotein cholesterol (HDL-C) as a secondary target of therapy. A wealth of epidemiologic data demonstrate that low levels of HDL-C are associated with an increased risk of CHD events, and data from large-scale clinical trials with statins and fibrates indicate that observed clinical benefits are related, at least in part, to improvements in HDL-C levels. Raising HDL-C levels with therapeutic lifestyle changes and pharmacologic intervention might afford opportunities to further reduce the risk of CHD beyond LDL-C lowering. Statins are first-line pharmacotherapy for dyslipidemia and can also improve HDL-C levels, although the extent to which they modify HDL-C varies. Combining a fibrate or niacin with statin therapy raises HDL-C more than a statin alone but might be associated with reduced tolerability and increased adverse reactions. Several new therapeutic approaches to raising HDL-C are in development, including an HDL mimetic and inhibitors of cholesteryl ester transfer protein. Although lowering LDL-C remains the primary target of lipid-modifying therapy, dyslipidemia therapies that are efficacious for both LDL-C reduction and raising HDL-C might offer further improvements in CHD risk reduction.

Arteriosclerosis↗
PubMed2005

New approaches in the intensive management of cardiovascular risk in the metabolic syndrome.

When risk factors such as dyslipidemia and hypertension are inadequately controlled in subjects with the metabolic syndrome by lifestyle interventions, pharmacologic approaches are warranted. Statins are first-line pharmacotherapy for dyslipidemia due to their efficacy for lowering low-density lipoprotein (LDL) cholesterol and may also improve high-density lipoprotein (HDL) cholesterol and triglyceride levels. Fibrates and niacin may be useful in combination with a statin for additionally lowering triglycerides or raising HDL cholesterol. Adequate control of hypertension will usually require two or more drugs; agents that block the renin-angiotensin system are particularly useful in this population, given their demonstrated benefits for reducing the burden of cardiovascular events and end-stage renal disease independent of blood-pressure lowering. A multifaceted approach to risk factor management for the metabolic syndrome will have benefits for prevention of type 2 diabetes and cardiovascular disease.

Antihypertensive Agents↗
PubMed2005

Association between reduced low density lipoprotein oxidation and inhibition of monocyte chemoattractant protein-1 production in statin-treated subjects.

Monocyte chemoattractant protein-1 (MCP-1) is essential in atherogenesis. Oxidized lipids regulate MCP-1 expression and release from mononuclear cells. In this study we investigated (1) whether statin therapy reduces lipopolysaccharide (LPS)-stimulated MCP-1 production in human whole-blood samples and (2) the relationships between in vitro low-density lipoprotein (LDL) oxidation and MCP-1 production. Fasting blood samples were obtained from 55 healthy nonsmoking adults with moderate hypercholesterolemia who were participating in a randomized double-blind 8-week trial comparing the effects of statin therapy with those of placebo on cytokine production. Samples were analyzed for resistance to copper-mediated LDL oxidation (lag time in minutes), as well as MCP-1- and interleukin-8 (IL-8)-stimulated production. Statin therapy reduced MCP-1 production (mean +/- SD) -161 +/- 399 pg/mL/mm 3 white cells) compared with 267 +/- 985 pg/mL/mm 3 in the placebo group, but changes were not different between active and placebo groups ( P = .13). Statin therapy also increased lag times (median [interquartile range]; 20.5 [7.0-51.2] minutes vs -17.0 [-5.3-16.5] minutes; P = .067 for group difference). Inhibition of MCP-1 production correlated with prolongation of lag time ( r = .46, P = .0056) in statin-treated subjects. Statin therapy reduced MCP-1 production in the whole blood of human subjects and these changes were correlated with improvement in LDL oxidative resistance.

Adult↗
PubMed2005

Low high-density lipoprotein cholesterol disorders and cardiovascular risk: contribution of associated low-density lipoprotein subclass abnormalities.

PURPOSE OF REVIEW: Discuss the contribution of low-density lipoprotein subclass abnormalities to cardiovascular risk among individuals with low high-density lipoprotein cholesterol levels. RECENT FINDINGS: Low high-density lipoprotein cholesterol levels are commonly encountered among patients with early onset cardiovascular disease. Most often, a low high-density lipoprotein cholesterol level is not an isolated abnormality, but it is usually associated with a number of other lipoprotein abnormalities. Data from the Framingham Offspring Study demonstrate that among subjects with high-density lipoprotein cholesterol, 1.0 mmol/L (39 mg/dL), low-density lipoprotein particle numbers were considerably higher than indicated by the level of low-density lipoprotein cholesterol because these subjects had excess numbers of small cholesterol-depleted low-density lipoprotein particles. Elevated numbers of low-density lipoprotein particles identify individuals at highest risk for atherosclerotic vascular disease and cardiovascular events. SUMMARY: As high levels of low-density lipoprotein particles are a robust predictor of cardiovascular events, strategies targeted at raising low levels of high-density lipoprotein cholesterol must account for low-density lipoprotein particle interactions.

Atherosclerosis↗
PubMed2005

Cholesterol lowering in diabetes. New evidence supports aggressive LDL-C targets.

Recent guidelines for treating patients with diabetes categorize the disorder as a coronary heart disease (CHD) equivalent and urge aggressive treatment of modifiable risk factors, such as plasma levels of low-density lipoprotein cholesterol (LDL-C). In this article, Dr Rosenson discusses the rationale for cholesterol lowering in patients with diabetes, the lipoprotein abnormalities that accompany insulin resistance, and the prognostic significance of high LDL particle numbers. He also highlights major findings from recent clinical trials to explore statin therapy and other treatment strategies for lowering lipoprotein levels in this patient population.

Cholesterol, LDL↗
PubMed2004

Current overview of statin-induced myopathy.

Statins are an efficacious and well-tolerated class of lipid-altering agents that have been shown to reduce the risk of initial and recurrent cardiovascular events. However, cerivastatin was withdrawn from the world market because of its potential for severe myotoxic effects. Since the benefits of statin treatment outweigh the small risk of adverse events, statins remain the first-line therapy for lipid lowering and preventing atherosclerotic cardiovascular diseases. The risk of myopathy may be minimized with the appropriate choice of agent and by identifying patients at risk of myotoxic effects. Elderly or female patients, or those with concomitant medications or impaired metabolic processes, may be at increased risk and should be monitored closely. The risk of myopathy may also be inferred from the pharmacologic and pharmacokinetic properties of the statin used. Since myotoxic events are more frequent at higher doses, statins that are effective in reducing cholesterol levels and helping patients to reach target levels at start doses may be useful. The lipophilicity of a statin and its potential for drug-drug interactions may also help to determine the likelihood of muscular effects. Drug-drug interactions may be avoided by selecting a statin that does not share the same metabolic pathway.

Anticholesteremic Agents↗