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OBJECTIVE: This study was undertaken to assess whether estrogen therapy (ET) reduces the risk of cognitive decline in women with cerebrovascular disease. STUDY DESIGN: We conducted a randomized, double-blind trial of estradiol 17beta versus placebo for secondary stroke prevention in 664 postmenopausal women with a recent stroke or transient ischemic attack. The Mini-Mental State Examination (MMSE) and 5 domain measures were obtained at baseline and exit. RESULTS: Among 461 women withdrawn alive without stroke, ET did not have a significant effect on cognitive measures after an average of 3 years (relative risk of MMSE decline: 0.74, 95% CI, 0.49-1.13). In women with normal MMSE at entry, estrogen was associated with less decline (relative risk, 0.46, 95% CI, 0.24-0.87). CONCLUSION: In this study, estradiol did not have significant effects on cognitive measures. However, in women with normal function at baseline, there may be a benefit for ET in reducing the risk for cognitive decline. [ABSTRACT FROM AUTHOR]

Objective: To establish, in a single resource, up-to-date recommendations for primary care physicians regarding prevention strategies for a first stroke.Participants: Members of the National Stroke Association's (NSA's) Stroke Prevention Advisory Board and Cedars-Sinai Health System Department of Health Services Research convened on April 9, 1998, in an open meeting. The conference attendees, selected to participate by the NSA, were recognized experts in neurology (9), cardiology (2), family practice (1), nursing (1), physician assistant practices (1), and health services research (2).Evidence: A literature review was carried out by the Department of Health Services Research, Cedars-Sinai Health System, Los Angeles, Calif, using the MEDLINE database search for 1990 through April 1998 and updated in November 1998. English-language guidelines, statements, meta-analyses, and overviews on prevention of a first stroke were reviewed.Consensus Process: At the meeting, members of the advisory board identified 6 important stroke risk factors (hypertension, myocardial infarction [MI], atrial fibrillation, diabetes mellitus, blood lipids, asymptomatic carotid artery stenosis), and 4 lifestyle factors (cigarette smoking, alcohol use, physical activity, diet).Conclusions: Several interventions that modify well-documented and treatable cardiovascular and cerebrovascular risk factors can reduce the risk of a first stroke. Good evidence for direct stroke reduction exists for hypertension treatment; using warfarin for patients after MI who have atrial fibrillation, decreased left ventricular ejection fraction, or left ventricular thrombus; using 3-hydroxy-3 methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors for patients after MI; using warfarin for patients with atrial fibrillation and specific risk factors; and performing carotid endarterectomy for patients with stenosis of at least 60%. Observational studies support the role of modifying lifestyle-related risk factors (eg, smoking, alcohol use, physical activity, diet) in stroke prevention. Measures to help patients improve adherence are an important component of a stroke prevention plan. [ABSTRACT FROM AUTHOR]

In this Decade of the Brain, research is changing the approach to stroke: No longer something to wait out, it's becoming amenable to intervention. This puts a premium on asking the right questions early. [ABSTRACT FROM AUTHOR]

Background: Patients with ischemic stroke or transient ischemic attack (TIA) are at increased risk for future cardiovascular events despite current preventive therapies. The identification of insulin resistance as a risk factor for stroke and myocardial infarction raised the possibility that pioglitazone, which improves insulin sensitivity, might benefit patients with cerebrovascular disease., Methods: In this multicenter, double-blind trial, we randomly assigned 3876 patients who had had a recent ischemic stroke or TIA to receive either pioglitazone (target dose, 45 mg daily) or placebo. Eligible patients did not have diabetes but were found to have insulin resistance on the basis of a score of more than 3.0 on the homeostasis model assessment of insulin resistance (HOMA-IR) index. The primary outcome was fatal or nonfatal stroke or myocardial infarction., Results: By 4.8 years, a primary outcome had occurred in 175 of 1939 patients (9.0%) in the pioglitazone group and in 228 of 1937 (11.8%) in the placebo group (hazard ratio in the pioglitazone group, 0.76; 95% confidence interval [CI], 0.62 to 0.93; P=0.007). Diabetes developed in 73 patients (3.8%) and 149 patients (7.7%), respectively (hazard ratio, 0.48; 95% CI, 0.33 to 0.69; P<0.001). There was no significant between-group difference in all-cause mortality (hazard ratio, 0.93; 95% CI, 0.73 to 1.17; P=0.52). Pioglitazone was associated with a greater frequency of weight gain exceeding 4.5 kg than was placebo (52.2% vs. 33.7%, P<0.001), edema (35.6% vs. 24.9%, P<0.001), and bone fracture requiring surgery or hospitalization (5.1% vs. 3.2%, P=0.003)., Conclusions: In this trial involving patients without diabetes who had insulin resistance along with a recent history of ischemic stroke or TIA, the risk of stroke or myocardial infarction was lower among patients who received pioglitazone than among those who received placebo. Pioglitazone was also associated with a lower risk of diabetes but with higher risks of weight gain, edema, and fracture. (Funded by the National Institute of Neurological Disorders and Stroke; ClinicalTrials.gov number, NCT00091949.).

Background: Recurrent vascular events remain a major source of morbidity and mortality after stroke or transient ischemic attack (TIA). The IRIS Trial is evaluating an approach to secondary prevention based on the established association between insulin resistance and increased risk for ischemic vascular events. Specifically, IRIS will test the effectiveness of pioglitazone, an insulin-sensitizing drug of the thiazolidinedione class, for reducing the risk for stroke and myocardial infarction (MI) among insulin resistant, nondiabetic patients with a recent ischemic stroke or TIA., Design: Eligible patients for IRIS must have had insulin resistance defined by a Homeostasis Model Assessment-Insulin Resistance > 3.0 without meeting criteria for diabetes. Within 6 months of the index stroke or TIA, patients were randomly assigned to pioglitazone (titrated from 15 to 45 mg/d) or matching placebo and followed for up to 5 years. The primary outcome is time to stroke or MI. Secondary outcomes include time to stroke alone, acute coronary syndrome, diabetes, cognitive decline, and all-cause mortality. Enrollment of 3,876 participants from 179 sites in 7 countries was completed in January 2013. Participant follow-up will continue until July 2015., Summary: The IRIS Trial will determine whether treatment with pioglitazone improves cardiovascular outcomes of nondiabetic, insulin-resistant patients with stroke or TIA. Results are expected in early 2016., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Background: New approaches are needed to treat patients with stroke. Among acute ischemic stroke patients, our primary objectives were to describe the prevalence of sleep apnea and demonstrate the feasibility of providing auto-titrating continuous positive airway pressure (auto-CPAP). A secondary objective was to examine the effect of auto-CPAP on stroke severity., Methods: Stroke patients randomized to the intervention group received 2 nights of auto-CPAP, but only those with evidence of sleep apnea received auto-CPAP for the remainder of the 30-day period. Intervention patients received polysomnography 30 days post-stroke. Control patients received polysomnography at baseline and after 30 days. Acceptable auto-CPAP adherence was defined as ≥ 4 h/night for ≥ 75% nights. Change in stroke severity was assessed comparing the NIH Stroke Scale (NIHSS) at baseline versus at 30 days., Results: The 2 groups (intervention N = 31, control N = 24) had similar baseline stroke severity (both median NIHSS, 3.0). Among patients with complete polysomnography data, the majority had sleep apnea: baseline, 13/15 (86.7%) control patients; 30 days, 24/35 (68.6%) control and intervention patients. Intervention patients had greater improvements in NIHSS (-3.0) than control patients (-1.0); P = 0.03. Among patients with sleep apnea, greater improvement was observed with increasing auto-CPAP use: -1.0 for control patients not using auto-CPAP; -2.5 for intervention patients with some auto-CPAP use; and -3.0 for intervention patients with acceptable auto-CPAP adherence., Conclusions: The majority of acute stroke patients had sleep apnea. Auto-CPAP was well tolerated, appears to improve neurological recovery from stroke, and may represent a new therapeutic approach for selected patients with acute cerebral infarction.

Background: We examined the prevalence of cardiac and cerebrovascular disease among hospitalized patients with and without multiple sclerosis (MS)., Methods: This study used the Statewide Planning and Research Cooperate System data set of over 15 million hospitalizations in New York City from 1988 through 2002. We identified MS patients 40-84 years of age who were hospitalized for reasons other than MS or related complications. MS patients were matched 1:2 on age, gender, race/ethnicity, and insurance. Outcomes included a principal discharge diagnosis of ischemic heart disease [International Classification of Diseases, Ninth Revision (ICD-9) 410-414], myocardial infarction (ICD-9 410), and ischemic stroke (ICD-9 434, 436). Multivariate logistic regression was used to compare vascular disease outcomes in MS and non-MS patients controlling for demographic and clinical factors., Results: Our study included 9,949 hospitalizations among MS patients and 19,898 hospitalizations for matched non-MS controls. MS patients were less likely to be hospitalized for ischemic heart disease (OR = 0.58, 95% CI = 0.51-0.66) or myocardial infarction (OR = 0.78, 95% CI = 0.64-0.96), but more likely to be hospitalized for ischemic stroke (OR = 1.66, 95% CI = 1.33-2.09) than matched non-MS controls., Conclusion: MS patients have decreased rates of hospital admission for ischemic heart disease and myocardial infarction, but increased rates of hospitalization for ischemic stroke as compared to the general non-MS population., (Copyright 2008 S. Karger AG, Basel.)

Background: We sought to describe the proportion of acute ischemic stroke admissions for very old patients (> or =85 years), compare the characteristics of very old versus younger patients and identify factors among very old patients associated with adverse outcomes., Methods: The 2000 Healthcare Cost and Utilization Project data included acute ischemic stroke hospitalizations for patients > or =45 years. The combined outcome was in-hospital mortality or discharge to a long-term care facility., Results: Among 15,020 stroke hospitalizations, 20.4% were for very old patients. The outcome rate was higher in hospitalizations for very old patients (2,176/3,058, 71.2%; versus 5,748/11,962, 48%; p < 0.0001). More hospitalizations for very old patients were for women (73.5 versus 55.1%; p < 0.0001), fewer for Blacks (6.1 versus 12.3%; p < 0.0001) and fewer at teaching hospitals (30.4 versus 36.2%; p < 0.0001). Among very old patients, factors that were independently associated with the outcome included: age [years; adjusted OR = 1.02 (95% CI = 1.000-1.05)], female gender [1.4 (1.18-1.68)], atrial fibrillation [1.37 (1.15-1.63)], acute myocardial infarction [1.68 (1.20-2.35)], respiratory failure [3.59 (1.60-8.05)] and teaching hospital admission [0.82 (0.69-0.98)]. Similar results were observed in the hospitalizations for younger patients. The adjusted OR for the outcome displayed geographic disparities in both age groups, but the pattern of the geographic variation was not similar between the two age groups., Conclusions: The very old constitute a substantial proportion of stroke hospitalizations. Hospitalizations for very old patients are more likely to end in death or discharge to a long-term care facility than hospitalizations for younger patients. The pattern of geographic disparity in poststroke adverse outcomes differs between younger and very old patients., (Copyright 2008 S. Karger AG, Basel.)

Background/aims: The results of studies about dietary fish consumption and stroke risk have been conflicting. We sought to examine the relationship between dietary fish and seafood consumption and the risk of stroke or transient ischemic attack (TIA)., Methods: We used data from the National Academy of Sciences-National Research Council Twin Registry, a prospective cohort of white male twins born in the US (1917-1927). Participants were asked about fish and seafood consumption in 1972 and 1985. Self-report or death-certificate report of stroke or TIA was obtained in 1996-1998., Results: Among 5,355 participants, 579 (10.8%) had a stroke or TIA. In unmatched analyses, dietary fish and seafood consumption was not associated with stroke or TIA: 10.4% (91/872) of frequent fish or seafood consumers had a stroke or TIA versus 10.9% (488/4,483) of infrequent consumers, p = 0.70. In an analysis of matched twin pairs, frequent fish or seafood consumption was also not associated with stroke or TIA: hazard ratio 0.89, 95% CI 0.59-1.36., Conclusions: These data, from a prospective cohort of white male twins, do not support an association between dietary fish and seafood consumption and stroke or TIA., (Copyright (c) 2007 S. Karger AG, Basel.)

Of the 55 million deaths that occur annually, 1 in 10 is attributable to stroke. As a consequence, cerebrovascular disease is the second leading cause of death worldwide, and stroke is among the most devastating consequences of vascular disease, causing long-term disability and incurring high personal, societal, and financial costs. However, stroke is a highly preventable disease in the majority of patients. The goal of stroke prevention strategies is to identify high-risk patients through the presence of modifiable and nonmodifiable risk factors and to target these modifiable risk factors through the use of appropriate pharmacologic and nonpharmacologic interventions. Clinical and epidemiologic studies point toward three major risk-reducing pharmacologic therapies that together may dramatically reduce stroke risk. First, landmark clinical trials have demonstrated that the reduction of blood pressure in persons at risk for cerebrovascular disease significantly reduces stroke risk. Second, ample evidence supports the use of antiplatelet therapy, such as aspirin, in patients at high risk for a cerebrovascular event. Third, an abundance of data suggests that lipid-lowering therapy with a statin reduces stroke risk in most moderate- to high-risk patients regardless of baseline cholesterol levels. Together, these data suggest that intensive therapy with agents from multiple drug classes that target two or more risk factors for cerebrovascular disease may provide additive-or even synergistic-reductions in stroke risk.

Purpose: Despite dramatic changes in heart failure management during the 1990s, little is known about the national heart failure mortality trends during this time period, particularly among the elderly. The purpose of this study was to determine temporal trends in outcomes of elderly patients with heart failure between 1992 and 1999., Subjects and Methods: We analyzed a national sample of 3,957,520 Medicare beneficiaries aged 65 years or more who were hospitalized with heart failure between 1992 and 1999, assessing temporal trends in 30-day and 1-year all-cause mortality and 30-day and 6-month all-cause hospital readmission. In risk-adjusted analyses, mortality and readmission for each year between 1994 and 1999 were compared with the referent year of 1993., Results: Crude 30-day and 1-year mortality decreased slightly (range for 1992-1999: 11.0%-10.3% and 32.5%-31.7%, respectively), whereas 30-day and 6-month readmission increased (10.2%-13.8% and 35.4%-40.3%, respectively). After risk adjustment, there was no change in 30-day mortality between 1993 and 1999 (eg, for 1999 vs 1993, odds ratio [OR] 1.01, 95% confidence interval [CI], 1.00-1.02). One-year mortality was lower in 1994 compared with 1993 (OR 0.91, 95% CI, 0.90-0.92), but data from subsequent years suggested no continuous improvement after 1994 (1999 vs 1993: OR 0.93, 95% CI, 0.92-0.94). Thirty-day readmission increased (1999 vs 1993: OR 1.09, 95% CI, 1.07-1.10), but there was no change in 6-month readmission (1999 vs 1993: OR 1.00, 95% CI, 0.99-1.01)., Conclusion: We found no substantial improvement in mortality and hospital readmission during the 1990s among elderly patients hospitalized with heart failure. These findings suggest that recent innovations in heart failure management have not yet translated into better outcomes in this population.

Background and Purpose: This guideline provides an overview of the evidence on various established and potential stroke risk factors and provides recommendations for the reduction of stroke risk., Methods: Writing group members were nominated by the committee chair on the basis of each writer's previous work in relevant topic areas and were approved by the American Heart Association Stroke Council's Scientific Statement Oversight Committee. The writers used systematic literature reviews (covering the time period since the last review published in 2001 up to January 2005), reference to previously published guidelines, personal files, and expert opinion to summarize existing evidence, indicate gaps in current knowledge, and when appropriate, formulate recommendations based on standard American Heart Association criteria. All members of the writing group had numerous opportunities to comment in writing on the recommendations and approved the final version of this document. The guideline underwent extensive peer review before consideration and approval by the AHA Science Advisory and Coordinating Committee., Results: Schemes for assessing a person's risk of a first stroke were evaluated. Risk factors or risk markers for a first stroke were classified according to their potential for modification (nonmodifiable, modifiable, or potentially modifiable) and strength of evidence (well documented or less well documented). Nonmodifiable risk factors include age, sex, low birth weight, race/ethnicity, and genetic factors. Well-documented and modifiable risk factors include hypertension, exposure to cigarette smoke, diabetes, atrial fibrillation and certain other cardiac conditions, dyslipidemia, carotid artery stenosis, sickle cell disease, postmenopausal hormone therapy, poor diet, physical inactivity, and obesity and body fat distribution. Less well-documented or potentially modifiable risk factors include the metabolic syndrome, alcohol abuse, drug abuse, oral contraceptive use, sleep-disordered breathing, migraine headache, hyperhomocysteinemia, elevated lipoprotein(a), elevated lipoprotein-associated phospholipase, hypercoagulability, inflammation, and infection. Data on the use of aspirin for primary stroke prevention are reviewed., Conclusions: Extensive evidence is available identifying a variety of specific factors that increase the risk of a first stroke and providing strategies for reducing that risk.

Background: To determine whether altruism as reason for participation in research is independently associated with adherence to a medical regimen in a clinical trial., Methods: Participants were 475 participants in the Women's Estrogen for Stroke Trial. Before randomization to estrogen or placebo, all women were questioned about reason for participation and baseline features that may contribute to adherence. Adherence was defined as completion of at least 80% of expected pill intake during the trial., Results: Women who reported at least one altruistic reason for participation were more likely to be college educated, have a higher level of social support, and a better functional status. They were also more likely to be adherent to their study medication {155 of 212 (73%) vs. 158 of 253 (62.5%), P < .01}. On stratified analysis and multivariable regression, the relationship between altruism as reason for participation and adherence was independent of other sociodemographic, psychosocial, and clinical features (relative risk 1.17, Confidence interval 1.03-1.32)., Conclusion: Altruism may explain a small portion of the variation in adherence among research participants. This relationship may have implications for recruitment of participants in clinical research. The possible contribution of altruism to the relationship between adherence and outcomes in clinical trials is worthy of further investigation.

Background: Despite current preventive therapies, patients with transient ischemic attack (TIA) and ischemic stroke remain at high risk for recurrent brain disease and cardiovascular events. In an effort to develop new therapies, abnormal glucose tolerance has recently been proposed as an interventional target. Among persons not otherwise known to be diabetic, impaired glucose tolerance (IGT) and diabetic glucose tolerance (DGT) are each associated with an increased risk for incident vascular disease, vascular disease mortality, and all-cause mortality. We conducted this study to determine if IGT and DGT are sufficiently common among patients with TIA and ischemic stroke to warrant therapeutic trials of antihyperglycemic agents., Methods: Men and women older than 45 years were recruited from 3 hospitals in south central Connecticut. Eligibility criteria included a recent TIA or nondisabling ischemic stroke, no history of physician-diagnosed diabetes mellitus, and a fasting plasma glucose level less than 126 mg/dL (<7.0 mmol / L). After an overnight fast, subjects were admitted to a clinical research center for a standard 75-g oral glucose tolerance test. Impaired glucose tolerance was defined by a 2-hour plasma glucose value of 140 to 199 mg/dL (7.8-11.0 mmol / L) and DGT by a value of 200 mg/dL or greater (> or =11.1 mmol/L)., Results: Between June 2000 and August 2003, we enrolled 98 eligible patients. The average time from TIA or stroke to measurement of glucose tolerance was 105 days (range, 24-180 days) and the median age was 71 years. Twenty-seven subjects (28%) had IGT and 24 (24%) had diabetes. In a forward stepwise logistic regression model, only a fasting plasma glucose level of 110 mg/dL or greater (> or =6.1 mmol / L) and lower waist circumference were associated with an increased risk for IGT or DGT., Conclusions: Impaired glucose tolerance and DGT are present in most persons with a recent TIA or ischemic stroke who have no history of diabetes and a fasting plasma glucose level less than 126 mg/dL (<7.0 mmol / L). Our findings bring new urgency to the initiation of research to examine the effectiveness of antihyperglycemic therapies among patients with cerebrovascular disease and abnormal glucose tolerance.

Background: Prior research has indicated an association between insulin resistance and stroke; we sought to determine if this association persists after adjusting for stroke risk factors, including glycemic control., Methods: We used data from the Third National Health and Nutrition Survey (1988-1994), including participants aged > or =40 years. We assessed insulin sensitivity using the homeostasis model assessment (HOMA): HOMA = (FPGSI x FPI)/22.5, where FPGSI refers to fasting plasma glucose (mmol/l) and FPI refers to fasting plasma insulin (microU/l). Increasing HOMA indicates decreasing insulin sensitivity. We used glycosylated hemoglobin (HbA1c) to measure glycemic control. Multivariable logistic regression analysis was used to identify factors that were independently associated with stroke., Results: Among 3,844 participants, 168 (4%) reported a stroke history. Participants with stroke had lower insulin sensitivity than participants without stroke: HOMA mean +/- standard deviation, 4.0 +/- 4.0 vs. 3.3 +/- 3.0; p = 0.022. HOMA was independently associated with stroke (odds ratio 1.06, 95% CI: 1.01-1.12; adjusted for age, hypertension, myocardial infarction, claudication, activity, and HbA1c). The strength of the association between HOMA and stroke was similar to the association between claudication and stroke (index R(2): 0.0032 vs. 0.0036)., Conclusions: Impaired insulin sensitivity is independently associated with stroke, even after adjustment for glycemic control., (Copyright (c) 2005 S. Karger AG, Basel.)