UMLS:C0038454 - FACTA Search

Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Target Concepts:

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

The pathogenesis of arteriosclerosis is not yet fully understood. The growing body of scientific information strongly indicates that the plasma lipoproteins are playing a crucial role in the development of this disease. We now have conclusive information that dietary cholesterol can produce arteriosclerosis in animals and its removal from the diet can result in regression of these lesions. Most importantly, we know that reducing plasma cholesterol in humans will prevent mortality and morbidity related to the clinical sequelae of arteriosclerosis. A diet can be prescribed that can produce profound reductions in lipoprotein levels in many individuals. The rate of success in achieving modifications that reduce plasma cholesterol is very high. Most patients over time find a diet with reduced cholesterol and saturated fat to be quite palatable. As food suppliers become more active in emphasizing low fat, low cholesterol products, and as restaurants see a demand for healthier entrees, the task for the physician and nutritionist will become much easier. Achieving sustained weight reduction is a much more difficult problem, but this too can be accomplished in many patients if the health professionals maintain a hopeful supportive approach. Ultimately, it is the patient's responsibility to bring about these lifestyle changes. It is the physician's and nutritionist's job to monitor the process and provide sound information and encouragement. For individuals with severe lipoprotein disorders such as familial hypercholesterolemia where diet therapy is helpful but not adequate, the use of medications is now indicated (bile acid binding resins and nicotinic acid). Other medications that promise additional effectiveness and safety are under development (Compactin, Mevinolin). It is our belief that control of coronary heart disease and stroke requires appropriate treatment of lipoprotein disorders and the methods for a strong beginning in this endeavor are at hand.
...
PMID:Treatment of common lipoprotein disorders. 633 Jul 92

Monumental advances in the field of lipid metabolism and its relationship to atherosclerotic cardiovascular disease have been achieved during the last half century. Epidemiologic studies have defined lipid disorders as highly significant independent risk factors for coronary heart disease, along with diabetes mellitus, hypertension and smoking. Primary and secondary prevention studies including the Coronary Primary Prevention Trial, Helsinki Heart Study, and the Coronary Drug Project have shown that lowering the atherogenic low density lipoproteins (LDL) and very low density lipoproteins (VLDL) whilst raising the high density lipoproteins (HDL) significantly decreases the risk for coronary disease. Striking evidence that aggressive therapy (to sharply lower LDL and raise HDL with newer drugs) prevents progression and induces regression of coronary narrowing has been obtained in numerous recent studies using quantitative coronary arteriography. An interesting and unexpected lesson learned from these arteriographic studies was that a highly significant reduction within months in several studies in coronary events was out of proportion to improvements in luminal narrowing. Recently, three major clinical trials to assess the effects of cholesterol reduction by the newly discovered HMG CoA reductase inhibitors (statins) have been published. Pravastatin significantly reduced coronary events in hypercholesterolemic patients [mean LDL-Chol. = 5.0 mM/L (192 mg/dl)] without a history of myocardial infarction. In a secondary prevention study, simvastatin also reduced coronary complications in hypercholesterolemic patients [mean LDL-Chol. = 4.9 mM/L (190 mg/dl)] with pre-existing coronary disease. Very recently, pravastatin treatment significantly reduced coronary events and stroke in patients with a history of myocardial infarction and average cholesterol levels [mean LDL-Chol. = 3.6 mM/L (139 mg/dl)], representing the majority of patients with coronary disease. In all these studies, reduction in cardiovascular events was approximately one-third. In subgroup analyses, men, women, elderly, smokers and hypertensives benefited from cholesterol lowering. There was no significant increase in non-cardiovascular causes of death. In the United States of America, the National Cholesterol Education Program (NCEP) Adult Treatment Panel, representing major health organizations, developed national guidelines on the detection, evaluation and treatment of high blood cholesterol in adults. In a given patient, the Panel recognizes the importance of weighing all cardiovascular disease risk factors including age (men > 45 years, postmenopausal women), family history of premature coronary disease, smoking, hypertension, diabetes and HDL-Cholesterol (< 35 mg/dl) in determining how aggressive therapy should be. The patient with manifest coronary heart disease (CHD) is given a special position as such patients are at highest risk for recurrent events. Major goals of therapy are to lower the LDL-Cholesterol to 2.6 mM/L (< 100 mg/dl) in the CHD patient. In non-CHD patients with two or more risk factors, the LDL-Cholesterol goal is 3.4 mM/L (130 mg/dl). In those with fewer risk factors, the goal is 4.2 mM/L (160 mg/dl). These guidelines should be modified as appropriate for Singapore. Patients with elevated triglycerides usually have low HDL-Cholesterol levels and often represent a heterogeneous group who may have other concurrent abnormalities including the presence of small dense LDL, insulin resistance, hypertension, obesity, overt diabetes and combined hyperlipidemia. Such patients merit individualized treatment. The prevalence of this syndrome may be more common in Singapore and requires further investigation. Current therapeutic guidelines emphasize the need for weight loss and dietary restriction of total and especially saturated fat (< 7% to 10% total calories), cholesterol (< 200 to 300 mg/day), and exercise. (ABSTRACT TRUNCATED)
...
PMID:Cholesterol and atherosclerosis: a contemporary perspective. 939 24

The PROspective Study of Pravastatin in the Elderly at Risk (PROSPER) is a randomized, double-blind, placebo-controlled trial designed to test the hypothesis that treatment with pravastatin will diminish risk of subsequent major vascular events in a cohort of men and women (70 to 82 years old) with preexisting vascular disease or significant risk of developing this condition. Five thousand eight hundred four men and women in addition to receiving advice on diet and smoking, have been randomized equally to treatment with 40 mg pravastatin/day or matching placebo in 3 centers (Cork, Ireland, Glasgow, Scotland, and Leiden, The Netherlands). Following an average 3.5-year intervention period, a primary assessment will be made of the influence of this therapy on major vascular events (a combination of coronary heart disease, death, nonfatal myocardial infarction, and fatal and nonfatal stroke). A number of additional analyses will also be conducted on the individual components of the primary end point, on men, on women, and on subjects with and without previous evidence of vascular disease. Finally, an assessment will be made of the effects of treatment on cognitive function, disability, hospitalization or institutionalization, vascular mortality, and all-cause mortality.
...
PMID:The design of a prospective study of Pravastatin in the Elderly at Risk (PROSPER). PROSPER Study Group. PROspective Study of Pravastatin in the Elderly at Risk. 1056 29

Statins represent a promising class of agents to prevent stroke. In randomized trials of middle-aged patients with coronary artery disease, statins reduce the incidence of stroke. The reduction in stroke may not be solely related to cholesterol or low-density lipoprotein reduction but may involve nonsterol mechanisms effects on endothelial cells, macrophages, platelets, and smooth muscle cells. Statins also reduce the size of cerebral infarction in a murine stroke model, suggesting a neuroprotective effect. The best current evidence for stroke prevention is with pravastatin and simvastatin. Pravastatin reduces the risk of stroke in patients with coronary artery disease and average cholesterol levels; simvastatin reduces the risk of the combined endpoint of stroke and transient ischemic attack in hypercholesterolemic patients with coronary artery disease. Future studies of statins are needed in stroke populations, particularly the elderly.
...
PMID:HMG-CoA reductase inhibitors (statins): a promising approach to stroke prevention. 1106 Dec 79

Five large randomized clinical trials show the benefits of lipid lowering with statins on cardiac morbidity and mortality. Three of these were secondary-prevention trials--the Long-term Intervention with Pravastatin in Ischemic Disease (LIPID) study, Cholesterol and Recurrent Events (CARE), and Scandinavian Simvastatin Survival Study (4S). The CARE and LIPID studies, performed with pravastatin, comprise populations that are representative of the majority of patients with coronary disease in that they included subjects with 'average' cholesterol levels. The 4S study, using simvastatin, comprised a patient population with elevated lipid levels. Pooled data from three trials, CARE, LIPID, and the West of Scotland Coronary Prevention Study (WOSCOPS), were examined in the Pravastatin Pooling Project (PPP). Individual patient data from these three event trials were pooled into a single database, permitting subgroup analyses and providing increased power. In the PPP, pravastatin-treated patients had significantly lower all-cause mortality (7.9, vs. 9.8% in those receiving placebo, a relative risk reduction of 20%). Pravastatin treatment was associated with a significant 24% reduction in CHD mortality and a nonsignificant difference in other vascular deaths (17%) and noncardiovascular deaths (12%). However, the reductions in absolute risk were much larger in those with a history of coronary heart disease than in those without. In the combined analysis of CARE and LIPID, there was also a uniform relative risk reduction in both men and women. In high-risk groups such as diabetics, smokers, hypertensives, and the elderly, there were also significant risk reductions in clinical end points. Finally, in the 598 participants, who had a stroke (90% of which were non-fatal), CARE and LIPID individually demonstrated reductions in non-fatal and total stroke. These data confirm that benefits of treatment in secondary prevention of coronary heart disease encompasses prevention of stroke as well as coronary heart disease events. The benefits are found in those who have had unstable angina as well as myocardial infarction. These findings strengthen even further the case for much more widespread use of statins in secondary prevention.
...
PMID:Clinical relevance of statins: their role in secondary prevention. 1128 52

The development of the HMG-CoA reductase inhibitors (the statins) has lead to important advances in the management of cardiovascular disease. There have several landmark mortality and morbidity clinical trials with the statins. The 4S (Scandinavian Simvastatin Survival Study) was the first large-scale randomised cholesterol-lowering trial to show a decrease in mortality. In patients with coronary heart disease and relatively high cholesterol, simvastatin decreased mortality, hospital stays, the risk of undergoing myocardial re-vascularisation, stroke and transient ischaemic attack. The CARE (Cholesterol and Recurrent Events) trial showed that lowering average cholesterol levels after myocardial infarction with pravastatin reduced a composite primary end point of coronary mortality and myocardial infarction, coronary bypass surgery, angioplasty and strokes. The LIPID (Long-term Intervention with Pravastatin in Ischaaemic Disease) study showed that lowering average cholesterol levels after previous myocardial infarction or unstable angina reduced mortality. WOSCOPS (The West of Scotland Coronary Prevention Study) was the first trial to demonstrate the benefit of pravastatin, as primary prevention for cardiovascular disease, in men with high cholesterol levels. AFCAPS/Tex CAPS (The Air Force/Texas Coronary Atherosclerosis Prevention Study) showed that the benefits of lowering cholesterol levels were also evident in healthy men and women who initially had average cholesterol levels. Rather surprisingly the reductions in mortality and morbidity with statins are only associated with small improvements in coronary angiographic findings. A preliminary study indicated than lovastatin prevented restenosis, but larger and better-controlled studies indicate that the statins do not have beneficial effects in restenosis. Effects other than lipid-lowering or as a consequence of their lipid-lowering may contribute to the beneficial effects of statins. These effects include improvement in vascular endothelial function, cardiac remodelling, changes in blood rheology, anti-oxidant, anti-inflammatory and anti-hypertensive actions.
...
PMID:Statins in the 21st century: end of the simple story? 1177 84

Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardio (GISSI)-Prevenzione was conceived as a population, pragmatic trial on patients with recent myocardial infarctions conducted in the framework of the Italian public health system. In GISSI-Prevenzione, patients were invited to follow Mediterranean dietary habits, and were treated with up-to-date preventive pharmacological interventions. Long-term n-3 PUFA (1 g daily) but not vitamin E (300 mg daily) was beneficial for death and for combined death, nonfatal myocardial infarction, and stroke. All the benefit, however, was attributable to the decrease in risk for overall, cardiovascular, cardiac, coronary, and sudden death. At variance with the orientation of a scientific scenario largely dominated by the "cholesterol-heart hypothesis," GISSI-Prevenzione results indicate n-3 PUFA (virtually devoid of any cholesterol-lowering effect) as a relevant pharmacological treatment for secondary prevention after myocardial infarction. As to the relevance and comparability of GISSI-Prevenzione results, up to 5.7 lives could be saved every 1000 patients with previous myocardial infarction treated with n-3 PUFA (1 g daily) per year. Such a result is comparable to that observed in the Long-Term Intervention with Pravastatin in Ischaemic Disease (LIPID) trial, where 5.2 lives could be saved per 1000 hypercholesterolemic, coronary heart disease patients treated with pravastatin for 1 yr. The choice of a relatively low-dose regimen (1-g capsule daily) more acceptable for long-term treatment in a population of patients following Mediterranean dietary habits, and the pattern of effects seen in GISSI-Prevenzione (namely, reduction of overall mortality with no decrease in the rate of nonfatal myocardial infarction) all strongly suggest that n-3 PUFA treatment should be considered a recommended new component of secondary prevention. The importance of this combined/additive effect is further suggested by the analyses of the interplay between diet and n-3 PUFA: There is an interesting direct correlation between size of the effect and "correctness" of background diets. It can be anticipated that a conceptual barrier must be overcome: A "dietary drug" should be added to "dietary advice," which remains fundamental to allow this statement to become true in clinical practice.
...
PMID:Efficacy of n-3 polyunsaturated fatty acids after myocardial infarction: results of GISSI-Prevenzione trial. Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardico. 1183 85

The drugs in the group of the "statins" lower blood lipids, especially cholesterol, thereby reducing a risk factor for, and diminishing the incidence of, clinically important cerebrocardiovascular events. Cardiovascular events and stroke are significant causes of morbidity and mortality in China and the United States. Statins reduce platelet-mediated thrombus formation and atherosclerotic progression through mechanisms not completely elucidated. While important, the lipid-lowering action of statins does not completely explain their multifaceted benefits. Nonlipid related mechanisms are essential to such effects. The authors explore these nonlipid related mechanisms of action of pravastatin that may translate into clinically relevant benefits. This study was conducted in Guangzhou, China. Twenty-one hypercholesterolemic patients were treated with pravastatin--10-20 mg/day for 12 weeks. Blood for tests was obtained at baseline and after 8 and 12 weeks of pravastatin therapy. After 8- and 12-weeks of therapy, significant decreases were observed in the following: (1) total blood cholesterol and low density lipoprotein-C (P < 0.01), (2) ADP-induced maximum platelet aggregation (P < 0.01), (3) TXB2 or thromboxane B2 in platelets (P < 0.01), and (4) expression of GMP-140 or granule membrane protein-140 (P < 0.01). The therapeutic effects of the drug did not vary significantly with length of therapy. Pravastatin induces inhibition of platelet aggregation and expression of TXB2 and GMP-140, the likely causes of thrombus formation, atherosclerotic progression, and subsequently cardiovascular events. These potential beneficial events occur within 8 weeks of pravastatin therapy.
...
PMID:Inhibition of platelet aggregation and expression of alpha granule membrane protein 140 and thromboxane B2 with pravastatin therapy for hypercholesterolemia. 1185 67

BACKGROUND: PROSPER was designed to investigate the benefits of treatment with pravastatin in elderly patients for whom a typical doctor might consider the prescription of statin therapy to be a realistic option. METHODS: The PROspective Study of Pravastatin in the Elderly at Risk (PROSPER) is a randomised, double blind, placebo-controlled trial to test the hypothesis that treatment with pravastatin (40 mg/day) will reduce the risk of coronary heart disease death, non-fatal myocardial infarction, and fatal or non-fatal stroke in elderly men and women with pre-existing vascular disease or with significant risk of developing this condition. RESULTS: In Scotland, Ireland, and the Netherlands, 23,770 individuals were screened, and 5,804 subjects (2,804 men and 3,000 women), aged 70 to 82 years (average 75 years) and with baseline cholesterol 4.0-9.0 mmol/l, were randomised. Randomised subjects had similar distributions with respect to age, blood pressure, and body mass index when compared to the entire group of screenees, but had a higher prevalence of smoking, diabetes, hypertension, and a history of vascular disease. The average total cholesterol level at baseline was 5.4 mmol/l (men) and 6.0 mmol/l (women). CONCLUSIONS: Compared with previous prevention trials of cholesterol-lowering drugs, the PROSPER cohort is significantly older and for the first time includes a majority of women. The study, having achieved its initial goal of recruiting more than 5,500 elderly high-risk men and women, aims to complete all final subject follow-up visits in the first half of 2002 with the main results being available in the fourth quarter of 2002.
...
PMID:A Prospective Study of Pravastatin in the Elderly at Risk (PROSPER): Screening Experience and Baseline Characteristics. 1209 48

Little information exists to quantify the functional status and economic consequences of lipid-lowering therapy in elderly patients. We describe the design of the cost-effectiveness component of the first large, randomized, placebo-controlled trial of lipid-lowering therapy in subjects aged 70 years or older. The PROspective Study of Pravastatin in the Elderly at Risk has randomized 5804 men and women 70-82 years old, with existing vascular disease or related risk factors, to receive 40 mg/d of pravastatin or placebo. The cost-effectiveness study will be based on within-trial observations of differences between the two study arms in rates of myocardial infarction, stroke and related vascular disease outcomes (including vascular dementia). In addition to comparing within-trial clinical outcomes, we will model the projected changes in life expectancy and cardiovascular outcome rates that would be seen with lifelong use of the drug, based on the risk reduction rates seen in the trial as well as baseline observational data from the three countries where the trial is being conducted (Scotland, Ireland and the Netherlands). A state transition (Markov) model will be constructed to estimate the likely states of health, functional status and health care resource utilization (including lipid-lowering drug costs) in a cohort of elderly patients with versus without pravastatin therapy over a series of 1-year cycles until death. In addition, a standard measure of utility (the Health Utilities Index) will be administered to all study subjects to permit calculation of quality-adjusted life-years gained with this regimen. This approach will make it possible to go beyond the calculation of a single endpoint for each subject, and to translate the trial findings into definitions of effectiveness and outcomes that will be relevant to the ongoing debate concerning how best to relate the benefits of such medications to their costs.
...
PMID:Measuring the cost-effectiveness of lipid-lowering drugs in the elderly: the outcomes research and economic analysis components of the PROSPER trial. 1250 50

1 2 3 4 Next >>