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Query: UMLS:C0038454 (stroke)
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The cross-sectional study entitled Health Profile of Skaraborg County, 1977 (HPS 77), forms part of an evaluation of a care programme for persons suffering from high blood pressure. Concurrently with the implementation of the study, epidemiological data were collected concerning the health profile of an entire county, with the aim of facilitating comparisons between the municipalities in the county. This paper describes how the study was implemented and gives an analysis of non-participation and validity. A comparison is made between participants and non-participants with regard to record data obtained from the National Health Insurance Fund, hospital records and the register of the Temperance Board. The non-participants differ in most respects from the participants, who have a more marked pattern of disorders in their case histories. In a longitudinal non-participants analysis, participants are compared with non-participants with respect to mortality during the following four-year period. In this study the non-participants differed, in having a higher mortality rate. The validity of the questionnaire is discussed on the basis of three different analyses. The validity varied considerably, depending on the questions studied. For example, 53% of those with myocardial infarction in the questionnaire were confirmed in hospital records. This was also true for 62% of those with stroke and 49% of those with angina pectoris in a follow-up interview. Medication for hypertension was confirmed in 94%. Ten of twelve participants who reported three or more symptoms of mental disorders were confirmed at interview with a physician. Studies like HPS 77 could be useful when planning preventive as well as curative measures. Thus it is important to describe not only the implementation of the study, but also its validity and the importance of non-participation for the results presented.
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PMID:Health profile of Skaraborg County 1977. A Swedish rural cross-sectional study. 633 23

The results of several large therapeutic cardiovascular trials were reported in 2002. The LIFE study concluded that losartan is superior compared to atenolol in terms of prevention of cardiovascular morbidity and mortality, the benefit being for CVA without changing the incidence of myocardial infarction. The OPTIMAAL study stated the disappointing results of post-infarct losartan. The IONA study represents a first demonstration with nicorandil of benefit not only in angina crises but equally on cardiac morbidity and mortality. The HPS study confirms the benefit of a statin in secondary prevention but for the first time, no matter what the initial level of LDL-cholesterol. Finally in the LIPS study, it is reported that statins reduce major cardiovascular events after coronary angioplasty. The year 2002 was marked elsewhere by imagination after the publication of the RAVEL study on coated stents delivering anti-proliferative drugs in order to avoid coronary restenosis. Three drugs were the subject of work confirming their potential significance in cardiovascular pathology: a) ezetimibe, representing a new class of cholesterol lowering drugs with which the association with statins seems especially synergic, b) nesiritide recombinant type B natriuretic peptide, whose significance was confirmed in acute cardiac insufficiency. c) levosimendan (calcium sensitisor) which moreover can be a significant treatment in cardiac decompensation as suggested by the LIDO study with a follow up of 180 days. By contrast, omapatrilate did not confirm its potential superiority over ACE inhibitors in the treatment of cardiac insufficiency. Some encouraging data were reported in 2002 in the field of therapeutic angiogenesis as much at the myocardial level as in lower limb arteritis. Finally, 2002 was marked by the publication of the WHI study which intensified suspicions regarding hormonal substitution treatment, confirming the advantage of not only secondary but perhaps primary cardiovascular prevention.
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PMID:[The best of clinical pharmacology in 2002]. 1261 62

The efficacy of pravastatin and simvastatin was first shown several years ago in patients with coronary heart disease. Other trials have since been published. In the HPS trial, which studied patients with coronary heart disease, other cardiovascular conditions, or diabetes, simvastatin significantly reduced the risk of death, coronary events and stroke when compared with placebo. In the ALLHAT-LLT trial, in patients with treated hypertension, pravastatin did not reduce overall mortality. In the PROSPER trial, in patients aged over 70 with cardiovascular disease or cardiovascular risk factors, pravastatin reduced the incidence of coronary events relative to placebo, but did not reduce overall mortality. Pharmacovigilance studies suggest there is no difference between these four statins in terms of their potential to cause rhabdomyolysis. Taken together, these trials show that statin use can be extended to patients with levels of LDL-cholesterol over 2.4 mmol/l (0.9 g/l) if they have coronary heart disease (and no hypercholesterolaemia), a history of ischaemic stroke, or lower-limb arterial disease. Statins can also be prescribed for diabetic patients with no signs of cardiovascular disease but whose LDL-cholesterol exceeds 3.4 mmol/l (1.3 g/l). Clinical trial data support the use of pravastatin or simvastatin in these situations, at a dose of 20 or 40 mg daily. Plasma creatine phosphokinase assay should be done if muscle symptoms occur or if the patient has a particular risk of rhabdomyolysis.
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PMID:Statins: new data in secondary prevention and diabetes. Pravastatin and simvastatin are the best-assessed statins. 1290 97

Dyslipidaemia is common in patients with Type 2 diabetes and is held to be responsible for considerable CVD-related morbidity and mortality. Patients with Type 2 diabetes are at high risk from complications associated with atherosclerosis and should therefore receive preventive interventions. At the level of the adipocyte, impaired insulin action leads to increased rates of intracellular hydrolysis of triglycerides with the release of NEFA. The rise in NEFA provides substrate for the liver that, in the presence of impaired insulin action and relative insulin deficiency, is associated with complex alterations in plasma lipids: * Plasma VLDL levels are raised. (i). Increased VLDL levels are associated with post-prandial hyperlipidaemia that is compounded by impaired LPL activity. The latter may be independently associated with CAD. (ii). Remnant particles can deliver more cholesterol to macrophages than LDL-C particles. Thrombogenic alterations in the coagulation system also ensue from hypertriglyceridaemia. * Plasma HDL-C levels are reduced. (i). The reduction in cardioprotective HDL-C means a reduction of cholesterol efflux from the tissues--the first step in reverse cholesterol transport to the liver from peripheral tissues. (ii). The antioxidant and antiatherogenic activities of HDL-C are reduced when circulating levels are low. * LDL-C particles become small and dense. Small, dense LDL-C particles are held to be more atherogenic than their larger, buoyant counterparts because they (a) are more liable to oxidation and (b) may more readily adhere to and subsequently invade the arterial wall. The atherogenicity of LDL-C may also be enhanced by nonenzymatic glycation. Metabolic and lipid abnormalities can often be improved with lifestyle changes, including dietary modification, weight loss, smoking cessation and increased exercise. Although attainment of better glycaemic control may improve diabetic dyslipidaemia, pharmacological intervention is usually required. Several large-scale clinical trials, including 4S and more recently HPS, have clearly demonstrated the benefits of statins in reducing cardiovascular events. By virtue of their high absolute risk of CVD, many patients with Type 2 diabetes may achieve a greater risk reduction than their non-diabetic counterparts. For example, in 4S there was a 43% reduction in total mortality risk among patients with diabetes compared with 29% for non-diabetics and a reduced risk of MI by 55% vs. 32% for diabetic and non-diabetics, respectively. In the diabetic subgroup in HPS, there were reductions of approximately 25-30% in the risk of first major vascular events. More recently, the lipid-lowering arm of the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT) was halted early because of a significant reduction in cardiovascular events compared with placebo. Surprisingly an analysis of subgroups failed to show significance among the diabetic population, although the sample size, shortened follow-up period and higher drop-in statin use among diabetics on placebo may have affected results. The Collaborative Atorvastatin Diabetes Study (CARDS), involving 2800 patients with Type 2 diabetes, was halted 2 years early in June 2003 because patients allocated atorvastatin had significant reductions in MI, stroke and surgical procedures compared with those receiving placebo. The UKPDS demonstrated that the appearance and progression of certain microvascular complications of Type 2 diabetes could be reduced by treatment directed at hyperglycaemia and hypertension. In addition, correction of dyslipidaemia in patients with diabetes is important in reducing the high toll from macrovascular disease. The subjects in the HPS had similar lipid profiles to the participants in UKPDS, suggesting that additional benefit would accrue from a therapeutic assault on the main cardiovascular risk factors simultaneously. We now have firm evidence that appropriate use of statins in patients with Type 2 diabetes can significantly reduce cardiovascular morbidity and mortality.
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PMID:Lipoprotein abnormalities and their consequences for patients with type 2 diabetes. 1498 18

Cerebrovascular risk represents a progressive and evolving concept owing to the particular distribution of risk factors in patients with ischemic stroke and in light of the newest stroke subtype classifications that account for pathophysiological, instrumental, and clinical criteria. Age represents the strongest nonmodifiable risk factor associated with ischemic stroke, while hypertension constitutes the most important modifiable cerebrovascular risk factor, confirmed by a host of epidemiological data and by more recent intervention trials of primary (HOT, Syst-Eur, LIFE) and secondary (PROGRESS) prevention of stroke in hypertensive patients. To be sure, a curious relationship exists between stroke and diabetes. Although the Framingham Study, The Honolulu Heart Program, and a series of Finnish studies reported a linear relationship between improved glucose metabolism and cerebral ischemia, the clinical and prognostic profile of diabetic patients with ischemic stroke remains to be fully understood. Our group, on the basis of TOAST classification--a diagnostic classification of ischemic stroke developed in 1993 that distinguishes five different clinical subtypes of ischemic stroke: large-artery atherosclerosis (LAAS), cardioembolic infarct (CEI), lacunar infarct (LAC), stroke of other determined origin (ODE), and stroke of undetermined origin (UDE), and now extensively used in clinical and scientific context--analysed the prevalence of cerebrovascular risk factors and the distribution of TOAST subtypes in more 300 patients with acute ischemic stroke in two consecutives studies that reported the significant association between diabetes and the lacunar subtype and a better clinical outcome for diabetic patients, most likely related to the higher prevalence of the lacunar subtype. Well-confirmed are the roles of cigarette smoking, atrial fibrillation, and asymptomatic carotid stenosis as cerebrovascular risk factors. Particularly interesting seems to be the function of inflammation markers (CRP, TNF-alpha, IL-1 beta, ISPs) as potential risk factors. Still elusive remains the association between cholesterol serum levels and stroke, on the basis of the epidemiological data regarding this causative relationship, confirmed only by the results of intervention trials (4S, LIPID, CARE, HPS, ASCOT). Ultimately, cerebrovascular risk appears peculiar owing to the unique relationship between some modifiable risk factors (mainly diabetes and cholesterol) and the possible preferential association with stroke subtypes and specific cerebrovascular risks.
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PMID:Cerebrovascular risk factors and clinical classification of strokes. 1563 Jun 37

Statins have become a leading prescription drug in France. Indications have been greatly extended over the last five years subsequent to publication of many multicentric prospective trials. Besides their preventive properties for coronary artery disease, their efficacy for the prevention of stroke also appears to be demonstrated in coronary patients (CARE and LIPID studies) and in subjects at risk (HPS and ASCOT-LLA studies) irrespective of the serum cholesterol level, the relative risk of stroke being decreased by 30 percent compared with placebo. This preventive capacity would involve pathways other than cholesterol and/or LDL-cholesterol lowering mechanisms, and would probably involve a direct effect on inflammation, coagulation, modulation of certain atherogenic processes, and endothelial function. There remains however certain questions concerning the exact role of statins on secondary prevention of stroke (SPARCL study), their real usefulness in the elderly subject (PROSPER study), and the relative superiority of individual statins.
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PMID:[Statins and prevention of strokes]. 1579 27

Statins have a good overall safety profile to date, with no increase in haemorrhagic stroke or cancer. They have favourable effects in the primary prevention of cardiovascular disease in high-risk young as well as elderly populations. Statins reduce the incidence of stroke in high-risk populations (mainly CHD patients, diabetics and hypertensives) even with a normal baseline blood cholesterol level, which argues for a global cardiovascular risk-based treatment strategy. As for CHD, stroke reduction was mainly observed in studies with large between-group LDL cholesterol difference. In patients with prior strokes, statins reduce the incidence of coronary events, but it is not yet proven that they actually reduce the incidence of recurrent strokes in secondary prevention. From a practical point of view, since there was a favourable treatment effect overall in stroke and TIA patients in HPS, it seems reasonable to treat stroke patients with a statin and total cholesterol >135 mg/dL (3.5 mmol/dL). On-going research is aiming to refine patient selection. As anticipated by current US recommendations, patients who are likely to benefit most are those with carotid atherosclerosis, diabetes mellitus, previous coronary heart disease, hypertension, hypercholesterolaemia, or cigarette smoking and LDL cholesterol > 100 mg/dL.
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PMID:Stroke prevention, blood cholesterol and statins. 1625 11

Several large-scale clinical trials have assessed the efficacy of atorvastatin in the primary and secondary prevention of cardiovascular events in patients with diabetes mellitus and/or metabolic syndrome. In primary prevention, CARDS (Collaborative Atorvastatin Diabetes Study) showed that atorvastatin 10 mg/day (vs placebo) reduced relative risk of the composite primary endpoint (acute coronary heart disease [CHD] events, coronary revascularisation, or stroke) by 37% (p = 0.001). This decrease was similar to decreases in major cardiovascular events in the ASCOT-LLA (Anglo-Scandinavian Cardiac Outcomes Trial-Lipid Lowering Arm) trial and HPS (Heart Protection Study). However, in CARDS, atorvastatin efficacy was evident as early as 6 months after starting treatment, whereas in HPS, simvastatin efficacy was noticeable only from about 15-18 months after starting treatment. In the ASCOT-LLA trial, in 2226 hypertensive diabetic patients without previous cardiovascular disease, atorvastatin (vs placebo) reduced the relative risk of all cardiovascular events and procedures by 25% (p = 0.038). In secondary prevention, substudies of the GREACE (GREek Atorvastatin and Coronary-heart-disease Evaluation), TNT (Treating to New Targets) and PROVE-IT (PRavastatin Or atorVastatin Evaluation and Infection Therapy) trials reported results for the approximately 15-25% of study participants who had diabetes. In the GREACE substudy, atorvastatin (vs physicians' standard care) significantly reduced the relative risk of total mortality by 52% (p = 0.049), coronary mortality by 62% (p = 0.042), coronary morbidity by 59% (p < 0.002) and stroke by 68% (p = 0.046). In the TNT substudy, incidence of the primary endpoint was significantly lower in diabetic patients treated with atorvastatin 80 mg/day rather than 10 mg/day (13.8% vs 17.9%; relative risk 0.75; p = 0.026). In the PROVE-IT substudy, a significantly lower incidence of acute cardiac events was reported for atorvastatin versus pravastatin recipients (21.1% vs 26.6%; p = 0.03) and, therefore, an absolute risk reduction of 5.5% was associated with atorvastatin therapy. ASPEN (Atorvastatin Study for Prevention of coronary heart disease Endpoints in Non-insulin-dependent diabetes mellitus) - a mixed primary and secondary prevention trial in diabetic patients - found that a 29% lower low-density lipoprotein-cholesterol level was seen with atorvastatin than placebo at endpoint (p < 0.0001); however, the reduction in composite primary endpoint of major cardiovascular events (cardiovascular mortality, nonfatal major cardiovascular event or stroke, and unstable angina requiring hospitalisation) with atorvastatin (13.7% vs 15.0% with placebo), and reduction in acute myocardial infarction relative risk of 27% with atorvastatin were not statistically significant. In CHD patients with metabolic syndrome (n = 5584) in a sub-analysis of the TNT trial, intensive versus lower-dosage atorvastatin therapy reduced the relative risk of major cardiovascular and cerebrovascular events by 29% (p < 0.0001). The analysis also revealed that CHD patients with, rather than those without, metabolic syndrome had a 44% greater level of absolute cardiovascular risk, thus clearly underscoring the clinical feasibility of administering intensive lipid-lowering therapy to CHD patients with metabolic syndrome. In summary, several patient populations, from definitive, large-scale studies, are now available to corroborate the integral place of atorvastatin--in line with various regional and internationally accepted disease management guidelines--in the primary and secondary prevention of cardiovascular events in patients with diabetes and/or metabolic syndrome.
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PMID:Atorvastatin efficacy in the prevention of cardiovascular events in patients with diabetes mellitus and/or metabolic syndrome. 1791 May 20

An association between hypercholesterolaemia and ischaemic stroke has not yet been clearly defined by observational studies. In clinical trials, however, cholesterol-lowering treatments appear to consistently reduce stroke risk. Data are now available from various primary prevention studies - ALLHAT-LLT (Antihypertensive and Lipid-Lowering treatment to prevent Heart Attack, Lipid-Lowering Therapy), ASCOT-LLA (Anglo-Scandinavian Cardiac Outcomes Trial, Lipid-Lowering Arm), CARDS (Collaborative Atorvastatin Diabetes Study, WOSCOPS (West of Scotland COronary Prevention Study) - and secondary prevention studies - 4S (Scandinavian Simvastatin Survival Study), CARE (Cholesterol and Recurrent Events), GREACE (GREek Atorvastatin and Coronary-heart-disease Evaluation), HPS (Heart Protection Study), LIPID (Long-term Intervention with Pravastatin in Ischaemic Disease), MIRACL (Myocardial Ischemia Reduction with Aggressive Cholesterol Lowering), SPARCL (Stroke Prevention by Aggressive Reduction in Cholesterol Levels), TNT (Treating to New Targets) - confirming the ability of statins to reduce stroke risk. Regarding primary prevention, post hoc analyses showed pravastatin reduced the relative risk of stroke by 9-11% (not statistically significant) in the ALLHAT-LLT and WOSCOPS trials, whereas atorvastatin reduced this risk by 27-48% in the ASCOT-LLA (p = 0.024) and CARDS trials. It remains to be established in prospective studies whether cholesterol-lowering is effective in the primary prevention of stroke. Regarding secondary prevention, in five placebo-controlled studies (4S, CARE, HPS, LIPID, MIRACL) involving a total of >40 000 patients with coronary heart disease (CHD), statin therapy reduced the relative risk of fatal or nonfatal stroke by 19-50% (p < or = 0.048); the largest decrease was produced by atorvastatin in the MIRACL study (-50%, p = 0.045). In addition, high-dosage atorvastatin reduced stroke risk by 25% (p = 0.02) relative to lower-dosage therapy in the TNT trial, and by 47% (p = 0.034) relative to 'usual' care in the GREACE study. A post hoc analysis of data for 3280 HPS study participants who had had a previous stroke revealed that simvastatin reduced major vascular events by 20% (p = 0.001).The SPARCL study assessed the secondary preventive efficacy of atorvastatin versus placebo in 4731 patients with a history of stroke or transient ischaemic attack (TIA), but without CHD. Atorvastatin reduced the adjusted relative risk of fatal or nonfatal stroke by 16% (p = 0.03), and that of fatal stroke alone by 43% (p = 0.03). Among secondary study endpoints, atorvastatin reduced the relative risks of stroke and TIA (-23%; p < 0.001), TIA alone (-26%; p = 0.004), and ischaemic stroke (-22%; p = 0.01). Overall, SPARCL study findings suggest that intensive atorvastatin therapy should be started immediately after a stroke or TIA. In summary, atorvastatin has developed a well defined role in the primary and secondary prevention of cerebrovascular disease, and appears to have a particularly prominent place in preventing such disease in CHD patients, and in the post-stroke and post-TIA setting in patients without CHD.
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PMID:Atorvastatin: its clinical role in cerebrovascular prevention. 1791 May 21

This review considers the evidence showing that statins can prevent first or recurrent stroke or improve its outcome in subjects at moderate or high risk for cardiovascular disease (CVD). Data are reviewed according to trial design (observational or prospective) and baseline CVD risk. Two (ASCOT, CARDS) out of five primary CVD prevention statin trials showed a considerable reduction in stroke rates. In two (MIRACL and PROVE IT) out of five acute coronary syndrome trials, the prevention of first stroke was significant. Most secondary prevention trials (4S, CARE, LIPID, HPS, GREACE and TNT) showed a beneficial effect of statins in stroke prevention. Finally, SPARCL, the only secondary stroke prevention trial in subjects without overt coronary heart disease (CHD), showed a significant reduction in total and ischaemic (fatal and nonfatal) stroke rate, although a small but significant increase in nonfatal haemorrhagic stroke was noted. There was also a significant reduction in CHD-related events. The possible mechanisms responsible for statin-associated stroke prevention are discussed. The evidence suggests the need to consider early and long-term statin treatment (with substantial low-density lipoprotein cholesterol reduction) in all patients at high risk of any type of major vascular event, without discriminating CHD from stroke. Thus, statins may be beneficial to both the heart and the brain.
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PMID:Statins for the prevention of first or recurrent stroke. 1839 14


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