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

Despite a decade of successful clinical trials for stroke prevention, substantial gaps exist in the application and implementation of this information in community practice. The frequency of guideline use is low, and there remains controversy regarding the standard of practice. Patients with stroke may have multiple risk factors and concomitant stroke mechanisms, factors that are not addressed in stroke clinical trials and guideline statements. New guidelines are needed to account for these complexities and to provide primary care physicians a practical means to achieve stroke prevention. We sought to develop guidelines that can be implemented by primary care physicians to enhance the use of medical and surgical measures for recurrent stroke prevention. We sought to test the applicability of current evidence-based guidelines to daily practice with routine and complex patient case scenarios to determine whether these could be simplified into a more easily applied form for primary care physicians. We used RAND/UCLA Appropriateness Methodology to develop guidelines for the use of interventions supported by randomized controlled trials including carotid revascularization, anticoagulant therapy, antiplatelet therapy, and blood pressure management for the prevention of recurrent stroke. After a systematic literature review of randomized clinical trials we developed a comprehensive list of indications or clinical scenarios to capture decision making. A diverse multidisciplinary panel reviewed and rated each indication according to the RAND Appropriateness Method. First, panelists rated each scenario (1-3 for inappropriate, 4-6 for uncertain, and 7-9 for appropriate) without interaction with other panelists. "Appropriate" was defined as the expected health benefit exceeding its expected negative consequences by a sufficient margin. At a formal interactive session, panelists re-rated all indications. Overall carotid endarterectomy was rated as appropriate when there was 50% to 99% ipsilateral symptomatic carotid artery stenosis, inappropriate with <50% or 100% stenosis (total occlusion), and uncertain when the surgical risk was high. Carotid angioplasty was generally rated as of uncertain value. When there was atrial fibrillation, anticoagulation with warfarin was rated as appropriate when there was a low bleeding risk but of uncertain value when the bleeding risk was high. For patients who were not candidates for warfarin therapy, aspirin, aspirin plus extended-release dipyridamole, or clopidogrel were all rated as appropriate initial therapies. Ticlopidine was considered inappropriate and aspirin plus clopidogrel of uncertain value. With the exception of ticlopidine and aspirin, persons with a prior cerebral ischemic event while on aspirin could receive any of the aforementioned antiplatelet agents or combinations and be considered appropriately treated. The panelists rated a blood pressure of <130/80 mm Hg at 1 year after ischemic stroke as the target level and rated any of the following agents as appropriate initial therapies if there was no diabetes mellitus or proteinuria: diuretics, beta-blockers, angiotensin-converting enzyme inhibitors, angiotensin-converting enzyme receptor blockers, or combinations of a diuretic and an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker. Patient risk played a significant role in deterring the panel from recommending certain therapies; however, the presence of atrial fibrillation or large or small cerebral vessel syndromes rarely had significant influence on treatment decisions. Appropriateness was less where bleeding or surgical risk was excessive. Using consensus evidence from clinical trials, we have developed recurrent stroke prevention guidelines for routine and more complex patient scenarios according to appropriateness methodology. Broad application of these guidelines in primary practice promises to reduce the burden of recurrent stroke.
J Stroke Cerebrovasc Dis
PMID:Determining the appropriateness of selected surgical and medical management options in recurrent stroke prevention: a guideline for primary care physicians from the National Stroke Association work group on recurrent stroke prevention. 1790 76

A common cause of death in end-stage renal disease (ESRD) patients on dialysis is sudden cardiac death (SCD). Compared to the general population, the percentage of cardiovascular deaths that are attributed to SCD is higher in patients treated by dialysis. While coronary artery disease (CAD) is the predominant cause of SCD in dialysis patients, reduced heart rate variability (HRV) may play a role in the higher risk of SCD among other risk factors. HRV refers to beat-to-beat alterations in heart rate as measured by periodic variation in the R-R interval. HRV provides a non-invasive method for investigating autonomic input into the heart. It quantifies the amount by which the R-R interval or heart rate changes from one cardiac cycle to the next. The autonomic nervous system transmits impulses from the central nervous system to peripheral organs and is responsible for controlling the heart rate, blood pressure and respiratory activity. In normal individuals, without cardiac disease, the heart rate has a high degree of beat-to-beat variability. HRV fluctuates with respiration: it increases with inspiration and decreases with expiration and is primarily mediated by parasympathetic activity. HRV has been used to evaluate and quantify the cardiac risk associated with a variety of conditions including cardiac disorders, stroke, multiple sclerosis and diabetes. In this narrative review, we will examine the association between HRV and SCD. This report explains the measurement of HRV and the consequences of reduced HRV in the general population and dialysis patients. Lastly, this review will outline the possible use of HRV as a clinical predictor for SCD in the dialysis population. The current understanding of SCD based on HRV findings among the ESRD population support the use of more aggressive treatment of CAD; greater use of angiotensin converting enzyme inhibitor (ACE-i)/angiotensin receptor blockers (ARBs) and beta-blockers and more frequent and/or nocturnal haemodialysis to improve the survival of a patient with kidney failure.
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PMID:Heart rate variability (HRV) in kidney failure: measurement and consequences of reduced HRV. 1872 54

The metabolic syndrome is closely related to dietary habits and seems to be associated with impairment of cognitive function in humans. Angiotensin receptor blockers are widely used with the expectation of preventing cardiovascular events and stroke and potential amelioration of the metabolic syndrome. We examined the diet-induced changes of cognitive function in mice treated with a high-salt and high-cholesterol diet. C57BL/6J mice were fed a high-salt (2% NaCl in drinking water) and high-cholesterol (1.25% cholesterol, 10% coconut oil) diet (HSCD) or a normal diet (ND), and subjected to 20 trials of a passive avoidance task every week from 8weeks of age. An age-dependent decline of the avoidance rate starting from 10weeks of age was observed in HSCD mice, whereas the avoidance rate gradually increased in the ND group. Oral administration of an angiotensin receptor blocker, olmesartan, at a dose of 3mg/kg per day in drinking water from 8weeks of age prevents this decline of avoidance rate in HSCD mice (49% vs. 82% at 12weeks of age). Treatment with olmesartan significantly decreased serum glucose and cholesterol levels in HSCD mice, with a slight decrease in blood pressure. Administration of olmesartan in HSCD-fed mice showed a 1.6-fold increase in mRNA expression of a neuroprotective factor, MMS2, compared to HSCD-fed mice without olmesartan. Olmesartan attenuated the increase in superoxide anion production detected by dihydroethidium staining in the brain of HSCD mice. Our results suggest that olmesartan could be therapeutically effective in preventing the impairment of quality of life in persons on a high-fat and high-salt diet.
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PMID:Inhibition of cognitive decline in mice fed a high-salt and cholesterol diet by the angiotensin receptor blocker, olmesartan. 1802 65

The renin angiotensin system (RAAS) plays an important role in the pathophysiology of cardiovascular (CV) disease. Modulation of RAAS with angiotensin-converting enzyme inhibitors (ACEi), angiotensin receptor blockers (ARB), and aldosterone inhibitors reduces a range of adverse CV outcomes in patients with or at risk of CV disease. Currently, there is incomplete evidence to show all RAAS modulators provide vascular protection by reducing the incidence of myocardial infarction (MI), stroke and CV death. In patients at high risk for CV events, studies with ACEi designed to test for long-term vascular protection, showed benefit. In contrast, studies of ARBs in patients with hypertension, heart failure, and renal disease have not consistently shown a reduction of CV outcomes. However, none of these studies was specifically designed to examine the impact of ARBs on the vascular protective outcomes of CV death, non-fatal MI, and stroke. The ONTARGET and TRANSCEND studies are designed to determine whether the ARB telmisartan is similar (or non-inferior) or superior to the ACEi ramipril in the reduction of CV events in patients with established CV disease or diabetes with target organ damage. The ONTARGET study has enrolled 25,620, and TRANSCEND 5,776 subjects. The subjects in both trials are similar to those studied in the HOPE study, yet there is greater ethnic diversity, a higher proportion of patients with cerebro-vascular disease, and a greater use of beta blockers and lipid-lowering treatment. The studies completed recruitment in 2004, and are due to complete follow-up and report the results in 2008. The ONTARGET and TRANSCEND studies will provide valuable comparative data on the efficacy of telmisartan and ramipril and their combination in patients at high risk for CV events. Although it is possible that enhanced benefits will be observed with dual therapy, the outcomes with ARB monotherapy remain uncertain.
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PMID:Clinical trial update: focus on the ONTARGET study. 1820 Aug 9

The angiotensin receptor blocker (ARB) telmisartan is a partial agonist of peroxisome proliferator-activated receptor gamma (PPARgamma). Typical PPARgamma agonists suppress the gene expression of angiotensin-converting enzyme (ACE) in vascular tissues. However, it remains unclear whether or not PPARgamma activation by telmisartan can inhibit vascular ACE activity. We compared the effects of PPARgamma agonistic telmisartan and non-agonistic valsartan on ACE, vascular function and oxidative stress in stroke-prone spontaneously hypertensive rats (SHR-SP) and in sodium (1% NaCl)-loaded SHR-SP. SHR-SP and sodium-loaded SHR-SP received placebo, 1 mg/kg telmisartan, or 10 mg/kg valsartan for 2 weeks. Systolic blood pressure (SBP) was equally reduced in SHR-SP given either telmisartan or valsartan compared with SHR-SP given placebo. However, neither telmisartan nor valsartan suppressed SBP in sodium-loaded SHR-SP. Acetylcholine induced significantly less vasorelaxation in SHR-SP than in Wistar-Kyoto rats, but telmisartan and valsartan each significantly prevented such vasorelaxation. However, telmisartan significantly attenuated acetylcholine-induced vasorelaxation in sodium-loaded SHR-SP, whereas valsartan did not. Telmisartan significantly attenuated NADPH oxidase subunit p22(phox) gene expression in both SHR-SP and sodium-loaded SHR-SP, whereas valsartan did not. Likewise, telmisartan also significantly attenuated the significantly increased vascular ACE activity in sodium-loaded SHR-SP, whereas valsartan did not. In conclusion, the partial PPARgamma agonist telmisartan might inhibit vascular ACE activity, and result in the prevention of oxidative stress and endothelial dysfunction more effectively than non-agonistic valsartan.
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PMID:Inhibition of vascular angiotensin-converting enzyme by telmisartan via the peroxisome proliferator-activated receptor gamma agonistic property in rats. 1834 29

This study investigates whether the interaction between angiotensin-converting enzyme (ACE) inhibitors or beta-blockers and the ACE insertion/deletion (I/D) polymorphism or angiotensin receptor II type 1 (AGTR1) 573C/T polymorphism modifies the risk of myocardial infarction (MI) or stroke. In total, 4097 subjects with hypertension were included in this study. The drug-gene interaction on the risk of MI or stroke was determined with a Cox proportional hazard model. The risk of MI was reduced in current users of ACE inhibitors with the AGTR1 573CT or CC genotype compared to ACE inhibitors with the AGTR1 573TT genotype (synergy index (SI):0.32; 95% confidence interval (CI): 0.14-0.70). No significant drug-gene interaction was found on the risk of stroke (SI:0.82; 95% CI: 0.44-1.52) or in beta-blocker users. Also, no significant drug-gene interaction was found with the ACE I/D polymorphism. In conclusion, subjects with at least one copy of the AGTR1 573C allele might have more benefit from ACE inhibitor therapy.
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PMID:Interaction between polymorphisms in the renin-angiotensin-system and angiotensin-converting enzyme inhibitor or beta-blocker use and the risk of myocardial infarction and stroke. 1834 11

Cardiovascular risk is determined by multiple risk factors. Blockade of the renin-angiotensin system is an important approach to the prevention of cardiovascular events. In the largest angiotensin receptor blocker cardiovascular outcome study to date, the ONgoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial (ONTARGET) program will compare the efficacy of therapy with telmisartan and ramipril, in reducing cardiovascular events in patients at high risk (history of coronary artery disease, stroke or transient ischemic attack, peripheral artery disease, or diabetes with evidence of end-organ damage). Recruited patients (n = 31,546) will be followed up for a period of 6 years, and more than 150,000 patient-years of data will be recorded. The primary endpoint is a composite of cardiovascular death, stroke, acute myocardial infarction, and hospitalization for congestive heart failure; secondary endpoints focus on reductions in newly diagnosed heart failure, new-onset type 2 diabetes, cognitive decline, atrial fibrillation, and nephropathy. In addition, an ambulatory blood pressure monitoring substudy will be conducted to assess the effect of treatment on endpoints after adjustment for 24-hour blood pressure values. Other substudies of the treatment effects on erectile dysfunction, blood markers, arterial stiffness, oral glucose tolerance, and the progression of target organ damage are also planned. The results of the ONTARGET program are due in 2008, and the findings are expected to have important clinical implications for the management of patients at high cardiovascular risk.
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PMID:Cardiac and vascular protection: the potential of ONTARGET. 1844 80

Hypertension is one of the major risk factors for cardiovascular morbidity and mortality. Lowering blood pressure (BP) may reduce the risk of stroke by 40% and the risk of ischemic heart disease by 20%. Despite the varied drugs available to lower BP, more than 50% of the hypertensive patients are not well-controlled. The major reason for the failure to control BP is noncompliance which is related to the side effects and inconvenience of drug administration. Aliskiren, a new oral direct renin inhibitor is very effective in BP reduction. It is given once daily and has very few side effects, almost like a placebo. It is well combined with diuretics, angiotensin converting enzyme (ACE) inhibitors and calcium channel blockers. Unlike ACE inhibitors and angiotensin receptor blockers that block the renin angiotensin axis in its last part and thereby raise the rein-levels, the direct renin inhibitor block the renin-angiotensin axis in its beginning and keep the renin levels suppressed. Aliskiren is a promising agent but further prospective studies with morbidity and mortality data as endpoints are required, before the drug can be recommended as a first choice agent.
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PMID:[Is there a need for direct renin inhibitors?]. 1848 62

Combination therapy of hypertension with separate agents or a fixed-dose combination pill offers the potential to lower blood pressure more quickly, obtain target blood pressure, and decrease adverse effects. Antihypertensive agents from different classes may offset adverse reactions from each other, such as a diuretic decreasing edema occurring secondary to treatment with a calcium channel blocker. Most patients with hypertension require more than a single antihypertensive agent, particularly if they have comorbid conditions. Although the Joint National Committee guidelines recommend diuretic therapy as the initial pharmacologic agent for most patients with hypertension, the presence of "compelling indications" may prompt treatment with antihypertensive agents that demonstrate a particular benefit in primary or secondary prevention. Specific recommendations include treatment with angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, diuretics, beta blockers, or aldosterone antagonists for hypertensive patients with heart failure. For hypertensive patients with diabetes, recommended treatment includes diuretics, beta blockers, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and/or calcium channel blockers. Recommended treatment for hypertensive patients with increased risk of coronary disease includes a diuretic, beta blockers, angiotensin-converting enzyme inhibitors, and/or calcium channel blocker. The Joint National Committee guidelines recommend beta blockers, angiotensin-converting enzyme inhibitors, and aldosterone antagonists for hypertensive patients who are postmyocardial infarction; angiotensin-converting enzyme inhibitors and angiotensin receptor blockers for hypertensive patients with chronic kidney disease; and diuretic and angiotensin-converting enzyme inhibitors for recurrent stroke prevention in patients with hypertension.
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PMID:Managing hypertension using combination therapy. 1854 Apr 93

Cardiovascular disease and stroke disproportionately affect the elderly. The risk for stroke and transient ischemic attack increases exponentially with age. Blood pressure is a potent modifiable target for reducing the risk for stroke in the elderly. In elderly patients with isolated systolic hypertension and those with intracranial atherosclerotic disease, blood pressure lowering has consistently been shown to be well tolerated and effective in reducing the risk for stroke and its complications. Evidence suggests that ambulatory blood pressure monitoring may provide a more sensitive means of detecting patients at risk and monitoring therapeutic effect. Agents that modify the renin-angiotensin system, particularly angiotensin receptor blockers, may confer additional benefit in stroke protection beyond blood pressure lowering. Several clinical trials currently in progress promise to provide guidance regarding the optimal choice of agent and degree of blood pressure lowering for prevention of stroke and cognitive decline in elderly patients.
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PMID:Management of hypertension and cerebrovascular disease in the elderly. 1863 16


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