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Query: UMLS:C0038454 (stroke)
 147,016 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor (statin)-mediated lowering of serum cholesterol has been associated with a significant reduction in cardiovascular morbidity and mortality. Recent studies suggest that additional non-lipid lowering effects (eg, endothelial stabilization, anti-inflammatory, antithrombogenic) may be important in modulating their effectiveness. Dyslipidemia is common in end-stage renal disease (ESRD), and hemodialysis patients have increased cardiovascular morbidity and mortality. Cerivastatin, a new statin with powerful low-density lipoprotein-cholesterol (LDL-C) lowering capabilities, possesses some unique non-LDL-C-mediated properties that may contribute to a reduction of coronary events in the patient with ESRD. The primary objective of this multicenter multinational study of 1,054 hemodialysis patients is to compare 2 years of treatment with cerivastatin (0.4 mg/d) versus placebo on the composite clinical event rate of myocardial infarction, sudden cardiac death, ischemic stroke, and the need for coronary arterial bypass graft (CABG) or percutaneous transluminal coronary angioplasty (PTCA) procedures in these patients. Changes in lipids, inflammatory proteins including heat stable C-reactive protein (hsCRP), interleukin-6 (IL-6), oncostatin-M, intracellular adhesion molecule-1 (ICAM-1) and monocyte-chemoattractant protein-1 (MCP-1), as well as markers of cardiac muscle pathology, such as troponin I and troponin T, will be assessed in a subset of patients. This study is the first of its kind to assess the effect of a statin on the reduction of cardiovascular morbidity and mortality in an incident hemodialysis population. It will determine whether treatment with cerivastatin can effectively reduce the significant cardiovascular morbidity and mortality.
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PMID:The CHORUS (Cerivastatin in Heart Outcomes in Renal Disease: Understanding Survival) protocol: a double-blind, placebo-controlled trial in patients with esrd. 1115 61

Dyslipemia as a risk factor for ischemic stroke and indications for statins in the prevention of ischemic stroke are revised. The role of cholesterol levels as a risk factor for ischemic stroke is controversial. This could be due to failures in the design of early epidemiological studies. Recent studies, however, do suggest a clearer risk relationship between cholesterol levels and ischemic stroke. Studies conducted on the prevention of ischemic heart disease (IHD) with 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins), using pravastatin and simvastatin, unequivocally show reductions in overall mortality, cardiovascular mortality, acute myocardial infarction and other coronary events. These studies show a reduction in the risk of ischemic stroke, and although relative risk reduction is great, absolute risk reduction is low; the reasons for this are analyzed. Apart from lipid mechanisms, statins act on the atheroma plaque; they have antithrombotic and possibly neuroprotecting properties. Statins reduce the number of strokes due to the decrease of atherothrombotic strokes, cardioembolic strokes secondary to IHD, and lacunar strokes related to atherothrombosis and probably to microatheromas. Although there are currently no specific studies available on the secondary prevention of stroke with statins, which are required to clarify certain points, according to European and American guidelines for prevention, statins would be indicated in the secondary prevention of atherothrombotic stroke, and in cardioembolic and lacunar stroke associated with clinical or silent atherosclerosis (IHD, peripheral artery disease). Patients with ischemic stroke of other etiologies, except for stroke in the young or other unusual causes, are patients with a high vascular risk (cardiac and cerebral) owing to the stroke itself, age and other vascular risk factors, and they should also be treated with statins, at least from the point of view of primary prevention of IHD. Natural statins (pravastatin and simvastatin) play an essential part in secondary prevention of ischemic stroke, together with antiaggregants, anticoagulants, angiotensin-converting enzyme inhibitors and the treatment of other vascular risk factors.
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PMID:Advantages of lipid-lowering therapy in cerebral ischemia: role of HMG-CoA reductase inhibitors. 1124 5

Coronary heart disease is an affliction of the elderly: 84% of those who die from the disease are over 65 years of age. In patients over 55 years, the incidence of stroke more than doubles with each decade of life. The 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, or statins, have been shown to lower cholesterol and lipids in both middle-aged and elderly patients in large clinical trials. Some statins have been shown to improve endothelial function and vasodilation and to normalize thrombin formation, which may be among the mechanisms involved in both coronary event and stroke prevention.
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PMID:Elderly patients at risk for coronary heart disease or stroke: selecting an ideal product for lipid lowering. 1125 64

Stroke is a major cause of mortality and morbidity. The epidemiologic association between elevated serum cholesterol and stroke risk is controversial. However, recent secondary prevention studies with 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) have demonstrated a significant reduction in ischemic stroke without an increase in hemorrhagic stroke. Statins probably reduce stroke by a variety of mechanisms, including modulation of precerebral atherothrombosis in the aorta and the carotid artery, thus preventing plaque disruption and artery-to-artery thromboembolism. Statins also improve endothelial homeostasis by increasing the bioavailability of nitric oxide, which orchestrates the paracrine antiatherosclerotic functions of the endothelium. Studies in experimental models of ischemic stroke show that statin therapy reduces brain infarct size and improves neurologic outcome by directly upregulating brain endothelial nitric oxide synthase. Putative anti-inflammatory actions of statins may also contribute to neuroprotection and stroke prevention. Although the clinical benefit of statins largely depends on lowering low-density lipoprotein cholesterol, accumulating data indicate that many of the pleiotropic effects of statins are attributable to the cellular consequences of depletion of intermediates in the cholesterol biosynthetic pathway (isoprenoids). These molecules play fundamental roles in cell growth, signal transduction, and mitogenesis. In addition to reducing stroke risk, emerging data suggest that statins may reduce dementia. Further studies are needed to fully address the role of statins in the prevention of stroke in patients without established vascular disease and the role of cholesterol modulation in the treatment of dementia.
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PMID:Prevention of stroke and dementia with statins: Effects beyond lipid lowering. 1261 95

Abstract Antithrombotic treatment has now been joined by other evidence-based drug interventions for prevention of stroke, including angiotensin-converting enzyme inhibitors and hydroxymethylglutaryl-CoA reductase inhibitors. The efficacy of oral anticoagulation in atrial fibrillation has not been seen in other stroke-prone groups, although trials are continuing. Diffusion-weighted magnetic resonance imaging improves diagnostic accuracy in acute stroke, which is important in arriving at the right secondary prevention strategy. Carotid endarterectomy has been shown to be beneficial for 50-69% symptomatic -stenosis but with a much narrower therapeutic index than for 70-99% stenosis. A comparison of endarterectomy with angioplasty and/or stent placement has been the subject of one small trial suggesting similar procedural stroke and mortality risks. Device closure of cardiac abnormalities increases in the absence of any trial data, and in spite of a low subsequent stroke risk for young patients with isolated patent foramen ovale treated with aspirin.
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PMID:Stroke prevention: what's new? 1268 Sep 84

Stroke is a leading cause of morbidity and mortality in North America. Primary prevention of stroke includes lifestyle modifications and measures to control blood pressure, cholesterol levels, diabetes mellitus, and atrial fibrillation. Lowering blood pressure in patients with hypertension prevents both hemorrhagic and ischemic stroke (relative risk reduction, 35 to 45 percent). Observational studies suggest that higher cholesterol levels are associated with an increased risk of ischemic stroke, and treatment with statins (3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors) may reduce the risk of fatal and nonfatal stroke by 25 percent. Although high-quality evidence linking tighter glucose control with stroke reduction is lacking, good glucose control and aggressive treatment of hypertension and hyperlipidemia in patients with diabetes mellitus are recommended. The risk of stroke in patients with atrial fibrillation and the role of anticoagulation depend on factors such as age and the presence of comorbid conditions. Controversy exists about the roles of angiotensin-converting enzyme inhibitors and aspirin in the primary prevention of stroke.
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PMID:Stroke: strategies for primary prevention. 1470 57

Patients with type 2 diabetes on dialysis are at a substantially increased risk of cardiovascular and cerebrovascular diseases. Dyslipidemia characterized by moderately elevated low-density lipoprotein cholesterol and high triglycerides and low high-density lipoprotein cholesterol levels is common in this population. We hypothesized that 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors would reduce vascular morbidity and mortality in this patient group. The 'Deutsche Diabetes Dialyse Studie' (4D study) is a prospective, randomized, double-blind study involving 178 dialysis centers throughout Germany. Between March 1998 and October 2002, 1,255 patients were randomized to either atorvastatin 20 mg or placebo; 677 men and 578 women, aged 30-83 years, have been enrolled. The study will be terminated as soon as the predefined number of 424 patients with primary combined end points (i.e., cardiovascular death, nonfatal myocardial infarction, or fatal/nonfatal stroke) will have occurred. The total cohort had the following characteristics at baseline: the mean age was 65.7 years, 54% were men, 89% had a history of hypertension, 21% had coronary artery disease, 17.8% had a history of stroke or a transient ischemic attack, and 45% suffered from peripheral arterial disease. The mean time interval between the diagnosis of diabetes and the onset of dialysis was 17.4 years. On average, the patients were on hemodialysis for 8.3 months. Mean lipid and lipoprotein levels were: total cholesterol 219 +/- 43 mg/dl, low-density lipoprotein cholesterol 126 +/- 30 mg/dl, high-density lipoprotein cholesterol 36 +/- 13 mg/dl, and triglycerides 264 +/- 167 mg/dl. The results of the study will provide important information on the efficacy and safety of atorvastatin to support its use in patients with an impaired renal function who are at a high risk of vascular morbidity and mortality.
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PMID:Randomized controlled trial on the efficacy and safety of atorvastatin in patients with type 2 diabetes on hemodialysis (4D study): demographic and baseline characteristics. 1531 28

'Statins' are 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors - oral cholesterol-lowering drugs that are used to treat hypercholesterolaemia. It is widely accepted that statins have anti-inflammatory effects that are independent of their ability to lower cholesterol. Animal studies and observational clinical studies have indicated that statins might also be effective in treating certain neurological diseases - in particular, multiple sclerosis, Alzheimer's disease and ischaemic stroke. At present, however, results from ongoing prospective, randomized clinical trials are not available.
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PMID:Statins--a cure-all for the brain? 1580 63

The use of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) has been demonstrated to reduce the risk of primary and secondary ischemic stroke in patients with ischemic heart disease (relative risk reduction is 20-30%), confirmed by several prospective randomized placebo-controlled trials. At least one large prospective trial has also shown a similar benefit in patients without underlying ischemic heart disease. This is in contrast to an open-labeled trial conducted in the USA, which failed to demonstrate a significant benefit of statins in reducing stroke risk in hypertensive hyperlipidemic patients. It is less clear if treatment with statins before or after the onset of ischemic stroke also reduces its severity (improves outcome). Experimental animal studies where mice were pretreated with statins, demonstrated a reduced infarct size compared with untreated animals. Treatment with statins after stroke onset has also been demonstrated to enhance recovery without influencing infarct size (by increased angiogenesis, synaptogenesis and blood flow). A few clinical retrospective studies have demonstrated similar results. Prospective blinded placebo-controlled trials to test these findings are still lacking. This review discusses the various prospective trials in stroke prevention and available data on the effects of statins in improving outcome of established ischemic stroke. Alternate mechanisms of statins besides their lipid-lowering effect and relevance in reducing stroke risk and improving outcome are discussed. Finally, based on the present information, an evidence-based perspective about current and future use of statins in the short- and long-term management of ischemic stroke is presented.
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PMID:HMG CoA reductase inhibitors (statins): use in stroke prevention and outcome after stroke. 1585 65

The endothelium integrates and modulates critical functions of the arterial wall. As well as regulating vasomotion, it controls inflammation, coagulation, and thrombosis. Many of these actions are mediated through the release of nitric oxide. Endothelial dysfunction is associated with atherosclerosis and its risk factors. It is independently correlated to adverse cardiovascular events, including myocardial infarction, coronary death, and the need for revascularization. 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) protect against cardiovascular death, myocardial ischemia, myocardial infarction, and stroke. Although cholesterol reduction accounts for some of these benefits, others appear to be independent of cholesterol lowering. The endothelium mediates many of these "lipid-dependent" and "lipid-independent" actions of statins. This chapter reviews the effects of statins on endothelial dysfunction. To do so, a brief outline of the biology of the endothelium is a prerequisite. This will be followed by a summary of the advances in vascular research on cholesterol-dependent and cholesterol-independent effects of statins, with a focus on the endothelium. Ultimately, clinical relevance of observations derived from basic biology will be discussed.
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PMID:Statins and endothelial dysfunction. 1586 15


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