Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0242339 (dyslipidemia)
 13,927 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The metabolic syndrome (MS) is a constellation of coronary risk factors. Atherogenic dyslipidemia is an important factor in cardiovascular risk in these patients, and treatment of atherogenic dyslipidemia has been identified as an important goal of therapy in patients with MS. This post hoc analysis of data from a 6-week, randomized, open-label, parallel-group, comparative trial (Statin Therapies for Elevated Lipid Levels compared Across doses to Rosuvastatin [STELLAR]) assessed the effects of rosuvastatin 10, 20, and 40 mg, atorvastatin 10, 20, 40, and 80 mg, simvastatin 10, 20, 40, and 80 mg, and pravastatin 10, 20, and 40 mg on plasma lipids in hypercholesterolemic patients (low-density lipoprotein cholesterol >/=160 and <250 mg/dl; triglycerides <400 mg/dl) who had >/=3 of the 5 National Cholesterol Education Program Adult Treatment Panel III criteria for MS (body mass index >30 kg/m(2) substituted for waist circumference). Of 2,268 patients, 811 met criteria for MS. Percent reductions in low-density lipoprotein cholesterol ranged from 20% in the pravastatin 10-mg group to 55% in the rosuvastatin 40-mg group. In patients with MS, triglyceride reductions were 22% to 34% with rosuvastatin, 23% to 33% with atorvastatin, 15% to 23% with simvastatin, and 12% to 15% with pravastatin. High-density lipoprotein cholesterol increased by 8% to 11% with rosuvastatin, 5% to 9% with atorvastatin, 8% to 10% with simvastatin, and 3% to 7% with pravastatin. Rosuvastatin, atorvastatin, simvastatin, and pravastatin treatment had favorable effects in hypercholesterolemic patients on the atherogenic dyslipidemia associated with MS. Rosuvastatin had the most favorable effect on the atherogenic lipid profile of MS overall.
 ...
PMID:Effects of rosuvastatin, atorvastatin, simvastatin, and pravastatin on atherogenic dyslipidemia in patients with characteristics of the metabolic syndrome. 1567 May 45

Identification and management of dyslipidemia is an important element in the multi-factorial approach to prevent coronary heart disease. Diabetic dyslipidemia typically consists of elevated triglyceride, low high-density lipoprotein cholesterol, predominance of small, dense low-density lipoprotein (LDL) particles, and average LDL cholesterol (LDL-C). Lipid-lowering therapy has a beneficial effect on cardiovascular outcomes. Statin treatment is beneficial in patients who are older than 40 years of age, irrespective of the LDL-C value. To achieve lipid targets, attention should be directed first toward nonpharmacologic therapeutic interventions, such as diet, exercise, smoking cessation, weight loss, and improving glycemic control. Although statin therapy is recommended for most subjects, judicious use of combination therapy should be considered in the highest risk subjects.
 ...
PMID:Management of diabetic dyslipidemia. 1575 19

Calcineurin inhibitors potentially contribute to risk of cardiovascular events through the development of new-onset diabetes mellitus, hypertension and hyperlipidemia. The exact extent to which calcineurin inhibitors affect these risk factors is difficult to establish since pre-existing renal disease and concomitant immunosuppressive agents (such as steroids or TOR inhibitors) also exert an effect. Clinical trials have consistently shown a higher incidence of new-onset diabetes mellitus with tacrolimus, which has been borne out in large-scale registry analyses. However, the risk of hypertension is approximately 5% higher with cyclosporine than tacrolimus, as is the risk of hyperlipidemia. Statin therapy is effective in treating dyslipidemia and has significant benefits in renal transplant patients. An individualized approach to choice of calcineurin inhibitor, by which cyclosporine or tacrolimus are selected based on the patient's particular risk profile, may thus help to reduce the toll of cardiovascular mortality among renal transplant recipients in the future.
 ...
PMID:Assessing the relative risk of cardiovascular disease among renal transplant patients receiving tacrolimus or cyclosporine. 1577 54

HMG-CoA reductase inhibitors (statins) are effective lipid-altering drugs for the treatment of dyslipidemia in patients with type 2 diabetes mellitus. We conducted a randomized, double-blind, placebo-controlled, crossover design trial to determine the effects of simvastatin, 80 mg/day, on plasma lipid and lipoprotein levels and on the metabolism of apolipoprotein B (apoB) in VLDL, intermediate density lipoprotein (IDL), and LDL and of triglycerides (TGs) in VLDL. Simvastatin therapy decreased TG, cholesterol, and apoB significantly in VLDL, IDL, and LDL. These effects were associated with reduced production of LDL-apoB, mainly as a result of reduced secretion of apoB-lipoproteins directly into the LDL density range. Statin therapy also reduced hepatic production of VLDL-TG. There were no effects of simvastatin on the fractional catabolic rates of VLDL-apoB or -TG or LDL-apoB. The basis for decreased VLDL-TG secretion during simvastatin treatment is not clear, but recent studies suggest that statins may activate peroxisomal proliferator-activated receptor alpha (PPARalpha). Activation of PPARalpha could lead to increased hepatic oxidation of fatty acids and less synthesis of TG for VLDL assembly.
 ...
PMID:Treatment with high-dose simvastatin reduces secretion of apolipoprotein B-lipoproteins in patients with diabetic dyslipidemia. 1616 40

Safety has become a central issue in the management of dyslipidemia with statins. A review of New Drug Applications (NDAs) and the US Food and Drug Administration (FDA) Web site was conducted for all 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, or statins, with a major focus on cerivastatin and rosuvastatin. The findings provide insight into the incidence of adverse events for this class of drugs and support the significant benefits of statins relative to associated risks. These data delineate the nature of statin associated liver, muscle, and renal adverse events. Although transaminase levels increase in a dose-related fashion with statins, a definitive correlation between statin therapy and hepatotoxicity is not supported by statin NDA data. Statin-induced myopathy is a relatively rare event (1 in 1,000) and rhabdomyolysis is even rarer (1 in 10,000). The cerivastatin NDA, along with its supplementary NDA, was the first to demonstrate a clear statin dose-response relation with myopathy and a threshold effect above which myotoxicity increases significantly. Proteinuria was identified as a consequence of statin therapy with data from the rosuvastatin NDA, and subsequent analysis suggests a class effect that is dose related but transient. Studies in cell culture suggest the mechanism is a pharmacologic effect on the proximal renal tubule. The available evidence suggests no clear renal toxicity with currently approved statins, because no declines in renal function or glomerular filtration rate have been documented over time. Overall, currently marketed statins have a very favorable benefit-to-risk relation with respect to liver, muscle, and renal issues.
 ...
PMID:Statin safety: lessons from new drug applications for marketed statins. 1658 28

The large administrative databases of health plans contain information on drug-related medical adverse events (AE) and constitute an increasingly powerful tool for the assessment of drug safety. We conducted a retrospective observational study using an administrative managed care claims database covering 9 million members from diverse regions of the United States. Patients aged >or=18 years who received >or=2 prescriptions for lipid-lowering drugs between July 1, 2000 and December 1, 2004 were included in the study. Hospitalizations with diagnosis codes (International Classification of Diseases, 9th Revision, Clinical Modification [ICD-9]) related to muscle, kidney, and liver were determined for patients exposed to 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins), fibrates, extended-release niacin, cholesterol absorption inhibitors, or statin combination therapy. A total of 473,343 patients contributed 490,988 person-years of monotherapy and 11,624 person-years of combination dyslipidemia therapy. Rates of hospitalization due to AEs in patients on monotherapy with currently available statins were similar, whereas the incidence of hospitalization for muscle disorders increased 6.7-fold with cerivastatin therapy. Patients who received a lipid-lowering medication with a concomitant cytochrome P450 3A4 (CYP3A4) inhibitor had a 6-fold increased rate of muscle disorders, including rhabdomyolysis. Hypertension was associated with a 5-fold increase in both muscle and renal events, whereas patients with diabetes mellitus had a 2.5-fold increased risk of renal events. No hospitalized cases of the index AEs were observed in study subjects during the 6-month period before initiation of the lipid-lowering drug. Statin monotherapy as currently prescribed is generally well tolerated and safe.
 ...
PMID:Statin safety: an assessment using an administrative claims database. 1658 31

The metabolic syndrome appears to affect a significant proportion of the population and is associated with increased risk for development of cardiovascular disease as well as of type-2 diabetes. No single treatment for the metabolic syndrome as a whole yet exists. While the primary management of patients with the metabolic syndrome involves healthy lifestyle promotion, the atherogenic dyslipidemia is a primary target for cardiovascular disease risk reduction in these patients. Statin therapy provides effective reduction of LDL-cholesterol, which represents the primary therapeutic goal of lipid-lowering therapy in patients at risk for cardiovascular disease. Fibrates in turn are effective in normalizing lipid levels (mainly triglycerides and HDL-cholesterol) in patients with the metabolic syndrome and may improve insulin resistance. Whereas statins remain the drug of choice for patients who need to achieve the LDL-cholesterol goal, fibrate therapy may represent an alternative for those with low HDL-cholesterol and high triglyceride levels. The simultaneous use of fibrates could be indicated in patients whose LDL-cholesterol is controlled by statin therapy but whose HDL-cholesterol and/or triglycerides are still inappropriate. Such a combination, however, needs careful monitoring due to the potential hazard of adverse drug interactions. Nicotinic acid and ezetimibe may be useful agents for therapy, particularly when combined with statins. A number of emerging therapies offer potential as future options for the pharmacological treatment of metabolic syndrome.
 ...
PMID:Hypolipidemic therapy for the metabolic syndrome. 1662 89

Diabetes is associated with a high risk of cardiovascular disease. The management of dyslipidemia, a well-recognized and modifiable risk factor among patients with type 2 diabetes, is an important element in the multifactorial approach to prevent coronary heart disease. Diabetic dyslipidemia typically consists of elevated triglyceride, low high-density lipoprotein cholesterol (HDL-C), and the predominance of small dense low-density lipoprotein (LDL) particles. LDL cholesterol (LDL-C) levels in patients with diabetes are similar to those found in the rest of the population. During the past few years, clinical trials have provided evidence that lipid-lowering therapy has a similar beneficial effect on cardiovascular outcomes in diabetic and nondiabetic individuals. According to current guidelines, the primary lipid target is an LDL-C <100 mg/dL (<70 mg/dL in very high-risk patients) and, to this end, statins are the agents of choice. The appropriate management of dyslipidemia in patients with diabetes, particularly in individuals with low LDL-C, remains controversial. To achieve lipid targets, attention should be directed first toward nonpharmacologic therapeutic interventions to control dyslipidemia, such as diet, exercise, smoking cessation, weight loss, and glycemic control. Statin therapy is recommended for most subjects but, frequently, a combination of lipid-lowering agents is required. A number of combinations are possible, and several factors should be considered to improve the safety of this strategy.
 ...
PMID:Management of dyslipidemia in diabetes. 1662 21

The renoprotective effect of statins has been recently disputed because of observations of proteinuria associated with rosuvastatin treatment, the newest drug of the class. Statin-induced proteinuria findings were mainly based on crudely quantitative dipstick assays. The authors quantitatively evaluated the effect of rosuvastatin at the recommended starting dose of 10 mg/d, on urine protein excretion in patients with primary dyslipidemia. Serum lipid and nonlipid parameters as well as urinary electrolyte, creatinine, and protein (total, albumin, immunoglobulin G, and alpha-1 microglobulin) levels were measured in 40 patients treated with rosuvastatin and 30 controls at baseline and after 12 weeks. The protein-to-creatinine ratios were used to assess urinary protein excretion. Rosuvastatin improved the lipid profile, produced no deterioration of kidney function, but induced a small but significant increase in the excretion of alpha-1 microglobulin (by 16%, P < .05) indicating that statin-related proteinuria involves low-molecular-weight proteins and is of proximal tubular origin.
 ...
PMID:Rosuvastatin increases alpha-1 microglobulin urinary excretion in patients with primary dyslipidemia. 1705 Jul 99

Atherothrombosis results from direct interaction between the atherosclerotic plaque and arterial thrombosis, and underlies most forms of cardiovascular disease (CVD). The pathophysiology of atherosclerosis is now recognised to involve endothelial dysfunction and dyslipidemia with cholesterol accumulation, as well as critical immuno-inflammatory and apoptotic dimensions. Erosion or rupture of a vulnerable, lipid-rich, inflammatory atherosclerotic plaque triggers the formation of a platelet-rich thrombus that may partially or completely occlude the artery, with resultant clinical scenarios including stable and unstable angina, acute myocardial infarction (MI) and ischaemic stroke. Insight into the pathophysiology of atherothrombosis indicates that an integrated risk factor approach, focusing particularly on management of dyslipidaemia (with a statin) and thrombosis (with aspirin), may constitute an optimal therapeutic approach. Both agents have established roles in secondary prevention. Statin action on atherogenic lipoproteins mediates plaque stabilisation, modification of plaque morphology and attenuation of inflammation, and may lead to plaque regression, while aspirin reduces platelet activation and aggregation, decreases release of inflammatory cytokines at sites of vascular injury and attenuates vasoconstriction. Given these complementary modes of action, this combination would be a logical choice for reducing atherothrombotic risk in patients with CVD. Meta-analysis of 5 major clinical studies has demonstrated that the combination of pravastatin plus aspirin was significantly more effective than either agent alone in reducing the relative risk of key cardiovascular endpoints including MI and ischaemic stroke. This combination may therefore represent an important, cost-efficient therapeutic approach to reduction of cardiovascular risk and prevention of recurrent events in stable CVD.
 ...
PMID:From pathophysiology to targeted therapy for atherothrombosis: a role for the combination of statin and aspirin in secondary prevention. 1707 Sep 23


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>