Gene/Protein Disease Symptom Drug Enzyme Compound
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 147,016 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) are the most commonly prescribed agents for hypercholesterolemia and have revolutionized the management of hyperlipidemia and the area of cardiovascular risk reduction. However, recent data suggest that their effects go well beyond the lipid lowering seen with long-term use and may include acute antiinflammatory activity, anticoagulation, immunomodulation, as well as promotion of changes in smooth-muscle tone. Because of these data, promising research has begun into the use of these agents in various critical care areas such as the early phases of sepsis, bacteremia, and ischemic stroke. Recent data also show a decrease in cerebral vasospasm after subarachnoid hemorrhage, an area deficient in therapeutic options. More research is necessary to ascertain the true role of statins in the treatment of these various disorders. Nevertheless, the concept of a statin's role as being only a routine preventive therapy with benefits limited to patients undergoing extended treatment is rapidly becoming inaccurate.
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PMID:Potential roles for statins in critically ill patients. 1772 82

Individuals with diabetes mellitus are at considerably higher risk for coronary artery disease compared with individuals without diabetes. In the United States, diabetes is the most prevalent factor putting patients at risk for coronary events. Intensive control of blood glucose has been demonstrated to reduce the risk for cardiovascular disease in patients with type 1 diabetes, but this has yet to be proved in patients with type 2 diabetes. Aggressive management of established cardiovascular risk factors using blood pressure-lowering and lipid-lowering therapies (particularly the 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, or statins) has been conclusively shown to reduce cardiovascular risk in patients with type 2 diabetes. Patients with type 2 diabetes remain at residual excess risk compared with individuals without diabetes, such that there is still a need for novel therapeutic approaches. Thiazolidinediones (TZDs) may have beneficial effects on cardiovascular disease in diabetes beyond improving blood glucose control. Although the evidence regarding rosiglitazone is yet to mature, completed and ongoing clinical trials with pioglitazone suggest that this TZD may be a novel treatment for managing cardiovascular risk in patients with diabetes. Addition of pioglitazone to existing therapy in high-risk patients with diabetes and atherosclerotic disease improves cardiovascular outcomes, and may be particularly beneficial for patients with previous myocardial infarction or stroke.
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PMID:Prevention of macrovascular disease in patients with diabetes mellitus: opportunities for intervention. 1782 43

This article presents a series of take-home statements, compiled by a multidisciplinary steering committee, concerning significant aspects of macrovascular disease in patients with diabetes mellitus, including the extent of risk, pathogenetic mechanisms, and optimal management for risk reduction. The discussion focuses in particular on the impact of diabetes medications beyond blood glucose control. In summary, these statements are as follows: (1) Patients with diabetes have an increased risk for cardiovascular disease that contributes to decreased life expectancy; (2) prognosis after a cardiovascular event is poorer in patients with diabetes; (3) pathogenetic mechanisms include insulin resistance, endothelial dysfunction, dyslipidemia, chronic inflammation, procoagulability, and impaired fibrinolysis; (4) management of established cardiovascular risk factors, for example with 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) and antihypertensive therapy, reduces cardiovascular event rates in diabetes; (5) correction of hyperglycemia can reduce macrovascular event rates, but the coupling to hyperglycemia is less tight for macrovascular events than it is for reduction of microvascular complications; (6) patients with diabetes should be screened for additional cardiovascular risk factors and appropriate interventions should be initiated; (7) results of observational and interventional studies have indicated that some insulin sensitizers appear to reduce the incidence of cardiovascular events and improve survival; (8) thiazolidinediones have beneficial effects on metabolism that may improve cardiovascular risk, and a randomized clinical trial in patients with advanced atherosclerosis indicates that addition of pioglitazone to therapy for hyperglycemia may reduce the incidence of cardiovascular events such as myocardial infarction and stroke.
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PMID:Optimizing cardiovascular outcomes in diabetes mellitus. 1782 44

Evidence of the effectiveness of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) within continuum of atherothrombotic conditions and particularly in the treatment and prevention of coronary heart disease (CHD) is well established. Large-scale, randomized, prospective trials involving patients with CHD have shown that statins reduce the clinical consequences of atherosclerosis, including cardiovascular deaths, nonfatal myocardial infarction and stroke, hospitalization for acute coronary syndrome and heart failure, as well as the need for coronary revascularization. Direct testing of varying degrees of low-density lipoprotein (LDL)- cholesterol lowering has now been carried out in 4 large outcomes trials: PROVE IT-TIMI 22, A to Z, TNT and IDEAL. However, the question whether more aggressive LDL-cholesterol lowering by high-dose statins monotherapy is an appropriate strategy is still open: higher doses of statins are more effective mainly for the prevention of the nonfatal cardiovascular events but such doses are associated with an increase in hepatotoxicity, myopathy and concerns regarding noncardiovascular death. Moreover, despite the increasing use of statins, a significant number of coronary events still occur and many such events take place in patients presenting with type 2 diabetes and metabolic syndrome. More and more attention is now being paid to combined atherogenic dyslipidemia which typically presented in patients with type 2 diabetes and metabolic syndrome. This mixed dyslipidemia (or 'lipid quartet') - hypertriglyceridemia, low high-density lipoprotein (HDL)-cholesterol levels, a preponderance of small, dense LDL particles and an accumulation of cholesterol-rich remnant particles - emerged as the greatest 'competitor' of LDL-cholesterol among lipid risk factors for cardiovascular disease. Most recent extensions of the fibrates trials (BIP, HHS, VAHIT and FIELD) give further support to the hypothesis that patients with insulin-resistant syndromes such as diabetes and/or metabolic syndrome might be the ones to derive the most benefit from therapy with fibrates. However, different fibrates may have a somewhat different spectrum of effects. Other lipid-modifying strategies included using of niacin, ezetimibe, bile acid sequestrants, CETP inhibitors and omega-3 fatty acids. Particularly, ezetimibe/statins combinations provide superior lipid-modifying benefits compared Tenenbaum/Fisman/Motro/Adler 128 with any statins monotherapy in patients with atherogenic dyslipidemia. Atherogenic dyslipidemia is associated with increased levels of chylomicrons and their remnants containing 3 main components: apolipoprotein B-48, triglycerides and cholesterol ester of intestinal origin. Reduction in accessibility for one of them (specifically cholesteryl ester lessening due to ezetimibe administration) could lead to a decrease of the entire production of chylomicrons and result in a decrease of the hepatic body triglycerides pool as confirmed in number of clinical studies. However, the ENHANCE study showed no difference in the progression of carotid atherosclerosis between ezetimibe/simvastatin vs. simvastatin alone over a 2-year period. Conclusions regarding ezetimibe/statins combinations should not be made until the three large clinical outcome trials will be completed within the next 2-3 years. In addition, bezafibrate as a pan-PPAR activator has clearly demonstrated beneficial pleiotropic effects related to glucose metabolism, insulin sensitivity and pancreatic beta cell protection. Because fibrates, niacin, ezetimibe, omega-3 fatty acids and statins each regulate serum lipids by different mechanisms, combination therapy - selected on the basis of their safety and effectiveness, could be more helpful in achieving a comprehensive lipid control as compared with statins monotherapy.
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PMID:Optimal management of combined dyslipidemia: what have we behind statins monotherapy? 1823 Sep 60

Chronic kidney disease (CKD) creates one of the highest-risk atherosclerotic states that can occur in human beings. The use of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) has gained widespread acceptance in the general population for the purposes of lowering low-density lipoprotein cholesterol (LDL-C) and reducing the future risks of myocardial infarction, stroke, and cardiac death. In patients with CKD, these benefits are believed to be enjoyed to the same or greater degrees. Reductions in LDL-C with statins may be associated with a reduced progression of CKD. Importantly, recent studies suggest statins are associated with a reduction in rates of acute renal failure after cardiopulmonary bypass surgery and exposure to iodinated contrast. In patients with end-stage renal disease (ESRD), recent data suggest that the annual rate of coronary artery calcification can be attenuated or reduced with LDL-C reduction. However, two large trials demonstrating LDL-C reduction with statins and with these drugs have failed to demonstrate a reduction in cardiovascular events in ESRD. Thus, the potential benefits of statins and LDL-C reduction in CKD have to be considered in light of evidence suggesting a reduced benefit, if any, in patients with ESRD. In addition, studies suggest that there are higher adverse drug effects with statins in CKD.
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PMID:Statin therapy in renal disease: harmful or protective? 1825 12

Overwhelming evidence now shows that 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (ie, statins) are safe and effective in primary and secondary prevention of cardiovascular disease. Atherosclerosis, the primary cause of heart disease, is directly and independently related to hypercholesterolemia and inflammation, and statins have multiple and independent effects on these conditions. New evidence for the use of statins in neurologic disease is mounting, and the range of therapeutic applications is formidable. Statins are beginning to show benefits in a wide range of neurologic conditions, from common ischemic stroke to rare congenital neurometabolic storage diseases, from acute brain injury to chronic central nervous system inflammation, and from prevention of neurodegenerative disease to acute neuroprotection. A diverse therapeutic spectrum is explained by shared pathogenetic mechanisms of neurologic disease and the manifold pharmacodynamic effects of statins.
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PMID:Statins in the spectrum of neurologic disease. 1836 80

Based on the findings of retrospective studies, there has been growing interest in the potential therapeutic benefits of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor (statin) therapy in patients with heart failure. The first published prospective randomized study of statins in heart failure patients did not demonstrate improved clinical outcomes (death and nonfatal myocardial infarction or stroke) after treatment with 10 mg daily of rosuvastatin when compared with placebo. However, use of rosuvastatin was associated with a reduced risk of hospitalization when compared with placebo and was well tolerated. Until further information becomes available, routine use of statins is not recommended in the heart failure population.
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PMID:Potential role of statins in the treatment of heart failure. 1860 2

The purpose of this study was to investigate the short-term effects of rosuvastatin (RSV), a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, on transient, focal cerebral ischemia in C57BL/6J ob/ob mice with insulin resistance (IR). Male ob/ob, lean, or wild-type (WT) mice were treated with RSV (10 mg/kg per day, i.p.) or vehicle for 3 days. Ischemia was induced by 60 mins of middle cerebral artery occlusion (MCAO) and cortical blood flow (CBF) was monitored by laser-Doppler flowmetry. Infarct volumes were measured 24 h after reperfusion. IR mice exhibited a higher infarct volume compared with Lean or WT mice, and RSV reduced infarct volume only in obese mice (40%+/-3% versus 32%+/-3%, P<0.05). Blood cholesterol and insulin levels were elevated in ob/ob mice but were unaffected by RSV. The CBF reductions during MCAO were similar in all groups and were not affected by RSV. Although RSV did not increase cortical endothelial NO synthase (eNOS) levels in the ob/ob mice, it attenuated the increased cortical expression of intracellular adhesion molecule-1 (ICAM-1) after MCAO from ob/ob mice. Thus, RSV protects against stroke in IR mice by a mechanism independent of effects on the lipid profile, CBF, or eNOS but dependent on suppression of post-MCAO ICAM-1 expression.
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PMID:Acute treatment with rosuvastatin protects insulin resistant (C57BL/6J ob/ob) mice against transient cerebral ischemia. 1866 82

Basic and animal research implicate inflammatory mechanisms in the pathogenesis and progression of atherosclerosis, plaque rupture, thrombosis, and stroke. Inflammatory biomarkers, particularly high-sensitivity C-reactive protein and lipoprotein-associated phospholipase A2, have been identified as potential predictors of stroke risk and prognosis. Infections may also precipitate stroke. Medications, especially hydroxymethylglutaryl coenzyme A reductase inhibitors (statins), reduce inflammatory marker levels independently of lipid effects, and the ability of statins to reduce coronary events and stroke correlates with their effect on inflammatory biomarkers. Vaccination against influenza may also reduce stroke risk. Determining whether reduction of biomarkers reduces risk of recurrent stroke, however, requires further study before inflammatory markers become a routine part of the evaluation of stroke patients.
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PMID:Inflammatory markers and stroke. 1909 Nov 70

The statins are a group of inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A reductase that are used extensively in medical practice because of their ability to reduce cardiovascular mortality and stroke. Although this protective activity was initially ascribed to the inhibition of cholesterol biosynthesis in the liver, clinical trials and basic research studies indicate that, beyond their cholesterol-lowering activity, statins might affect the function of different cell types in extrahepatic tissues. Here we will review the different mechanisms by which the statins exert their immunomodulatory and anti-inflammatory functions. We propose that statin pleiotropism is a key to the explanation of these activities, as it enables statins to act cooperatively in various steps of the inflammatory reaction, including terminal differentiation of immune cells, endothelial cell function, and regulation of the molecules that steer these cells to the sites at which they exert their immunomodulatory activity.
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PMID:Immunomodulatory and anti-inflammatory activities of statins. 1959 18


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