Biomedical subjects
Publications and source records attributed to Lawrence M Brass.
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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.
The National Lipid Association's (NLA) Statin Safety Task Force charged the Neurology Expert Panel with the task of reviewing the scientific evidence related to adverse effects with statins and providing assessments and advice regarding the safety of statins. The evidence included key adverse reaction statin literature identified via a Medline search by the Task Force and Panel members and the commissioned reviews and research presented in this supplement. Panel members were asked to use this evidence to independently form explicit answers to a series of questions posed by the Task Force. Panelists were asked to grade the type of literature and the confidence they had in it in forming their answers using prescribed scales. Panelists were encouraged to seek the highest level of evidence available to answer their questions and to concentrate on literature involving humans. In addition, the Neurology Expert Panel was asked to propose recommendations to regulatory authorities, health professionals, patients, researchers, and the pharmaceutical industry to address statin safety issues.
Payment-for-quality programs are emerging in the wake of rising healthcare costs and a demonstrated need for quality improvement in healthcare delivery in the United States. These programs, also known as "pay-for-performance" or "pay-for-value" programs, attempt to realign financial incentives with the quality of care delivered. The American Heart Association's Reimbursement, Coverage, and Access Policy Development Workgroup provides in this statement a set of principles and recommendations for the development, implementation, and evaluation of these programs. The statement also suggests future areas for research around the realignment of financial incentives to improve both the quality of care delivered and patient outcomes.
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: Previous studies have suggested that the obstructive sleep apnea syndrome may be an important risk factor for stroke. It has not been determined, however, whether the syndrome is independently related to the risk of stroke or death from any cause after adjustment for other risk factors, including hypertension. METHODS: In this observational cohort study, consecutive patients underwent polysomnography, and subsequent events (strokes and deaths) were verified. The diagnosis of the obstructive sleep apnea syndrome was based on an apnea-hypopnea index of 5 or higher (five or more events per hour); patients with an apnea-hypopnea index of less than 5 served as the comparison group. Proportional-hazards analysis was used to determine the independent effect of the obstructive sleep apnea syndrome on the composite outcome of stroke or death from any cause. RESULTS: Among 1022 enrolled patients, 697 (68 percent) had the obstructive sleep apnea syndrome. At baseline, the mean apnea-hypopnea index in the patients with the syndrome was 35, as compared with a mean apnea-hypopnea index of 2 in the comparison group. In an unadjusted analysis, the obstructive sleep apnea syndrome was associated with stroke or death from any cause (hazard ratio, 2.24; 95 percent confidence interval, 1.30 to 3.86; P=0.004). After adjustment for age, sex, race, smoking status, alcohol-consumption status, body-mass index, and the presence or absence of diabetes mellitus, hyperlipidemia, atrial fibrillation, and hypertension, the obstructive sleep apnea syndrome retained a statistically significant association with stroke or death (hazard ratio, 1.97; 95 percent confidence interval, 1.12 to 3.48; P=0.01). In a trend analysis, increased severity of sleep apnea at baseline was associated with an increased risk of the development of the composite end point (P=0.005). CONCLUSIONS: The obstructive sleep apnea syndrome significantly increases the risk of stroke or death from any cause, and the increase is independent of other risk factors, including hypertension.
BACKGROUND AND PURPOSE: To identify risk factors for intracerebral hemorrhage (ICH), we examined data from the Hemorrhagic Stroke Project (HSP), a case-control study of hemorrhagic stroke among men and women aged 18 to 49 years. METHODS: Case subjects for the HSP were recruited from 44 hospitals in the United States. Eligibility criteria included an ICH within 30 days preceding enrollment, no history of stroke or known brain lesion. For this report, we focused on patients with primary ICH, defined as not associated with an aneurysm, arteriovenous malformation or other structural lesion. Two control subjects were sought for each case subject. A multivariate regression analysis was performed to determine risk factors for primary ICH. RESULTS: A total of 1714 patients with hemorrhagic stroke were identified for participation in the HSP. Of these, 217 cases met the criteria for primary ICH. Cases with primary ICH were matched to 419 controls. Independent risk factors for ICH included hypertension (adjusted odds ratio [OR], 5.71; 95% CI, 3.61 to 9.05), diabetes (adjusted OR, 2.40; 95% CI, 1.15 to 5.01), menopause (adjusted OR, 2.50; 95% CI, 1.06 to 5.88), current cigarette smoking (adjusted OR, 1.58; 95% CI, 1.02 to 2.44), alcoholic drinks> or =2/day (adjusted OR, 2.23; 95% CI, 1.16 to 4.32), caffeinated drinks> or =5/day (adjusted OR, 1.73; 95% CI, 1.08 to 2.79), and caffeine in drugs (adjusted OR, 3.55; 95% CI, 1.24 to 10.20). CONCLUSIONS: Among young men and women, the major risk factors for primary ICH can be modified, suggesting that this type of stroke may be preventable. Our findings for caffeine and menopause warrant further study.
BACKGROUND AND PURPOSE: To develop recommendations for the establishment of comprehensive stroke centers capable of delivering the full spectrum of care to seriously ill patients with stroke and cerebrovascular disease. Recommendations were developed by members of the Brain Attack Coalition (BAC), which is a multidisciplinary group of members from major professional organizations involved with the care of patients with stroke and cerebrovascular disease. SUMMARY OF REVIEW: A comprehensive literature search was conducted from 1966 through December 2004 using Medline and Pub Med. Articles with information about clinical trials, meta-analyses, care guidelines, scientific guidelines, and other relevant clinical and research reports were examined and graded using established evidence-based medicine approaches for therapeutic and diagnostic modalities. Evidence was also obtained from a questionnaire survey sent to leaders in cerebrovascular disease. Members of BAC reviewed literature related to their field and graded the scientific evidence on the various diagnostic and treatment modalities for stroke. Input was obtained from the organizations represented by BAC. BAC met on several occasions to review each specific recommendation and reach a consensus about its importance in light of other medical, logistical, and financial factors. CONCLUSIONS: There are a number of key areas supported by evidence-based medicine that are important for a comprehensive stroke center and its ability to deliver the wide variety of specialized care needed by patients with serious cerebrovascular disease. These areas include: (1) health care personnel with specific expertise in a number of disciplines, including neurosurgery and vascular neurology; (2) advanced neuroimaging capabilities such as MRI and various types of cerebral angiography; (3) surgical and endovascular techniques, including clipping and coiling of intracranial aneurysms, carotid endarterectomy, and intra-arterial thrombolytic therapy; and (4) other specific infrastructure and programmatic elements such as an intensive care unit and a stroke registry. Integration of these elements into a coordinated hospital-based program or system is likely to improve outcomes of patients with strokes and complex cerebrovascular disease who require the services of a comprehensive stroke center.
BACKGROUND AND PURPOSE: In the US, blacks have a higher incidence of stroke and more severe strokes than whites. Our objective was to determine if differences in income, education, and insurance, as well as differences in the prevalence of stroke risk factors, accounted for the association between ethnicity and stroke. METHODS: We used data from the Third National Health and Nutrition Survey (NHANES III), a cross-sectional sample of the noninstitutionalized US population (1988-1994), and included blacks and whites aged 40 years or older with a self-reported stroke history. Income was assessed using a ratio of income to US Census Bureau annual poverty threshold. RESULTS: Among 11 163 participants, 2752 (25%) were black and 619 (6%) had a stroke history (blacks: 160/2752 [6%]; whites: 459/8411 [6%]; P=0.48). Blacks had a higher prevalence of 5 risk factors independently associated with stroke: hypertension, treated diabetes, claudication, higher C-reactive protein, and inactivity; whites had a higher prevalence of 3 risk factors: older age, myocardial infarction, and lower high-density lipoprotein cholesterol. Ethnicity was independently associated with stroke after adjusting for the 8 risk factors (adjusted odds ratio, 1.32; 95% CI, 1.04 to 1.67). Ethnicity was not independently associated with stroke after adjustment for income and income was independently associated with stroke (adjusted odds ratios for: ethnicity, 1.15; 95% CI, 0.88 to 1.49; income, 0.89; 95% CI, 0.82 to 0.95). Adjustment for neither education nor insurance altered the ethnicity-stroke association. CONCLUSIONS: In this study of community-dwelling stroke survivors, ethnic differences exist in the prevalence of stroke risk factors and income may explain the association between ethnicity and stroke.
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.
BACKGROUND AND PURPOSE: Physical performance for walking, reaching, turning, and other common tasks is a major determinant of functional independence after stroke. Current strategies to preserve physical performance focus on prevention of recurrent stroke. Loss of physical performance, however, may occur in the absence of recurrence. To examine this possibility, we measured change in physical performance, independent of subsequent stroke, among women with a recent ischemic stroke or transient ischemic attack (TIA). METHODS: Among 664 postmenopausal women who participated in a clinical trial of estrogen therapy after stroke or TIA, we administered the Physical Performance Test (PPT) at baseline (mean 58 days from the cerebrovascular event) and annually. Women who died or had a stroke during follow-up were censored. Decline or improvement in physical performance was defined as a change in the PPT score from baseline of at least 3 points. Sustained decline or improvement was defined as 2 consecutive years during which the score had declined or improved, respectively, relative to the baseline score. RESULTS: With each year of follow-up, a smaller proportion of the cohort demonstrated improvement (16% in year 1, 6% in year 5) and a larger proportion demonstrated decline (15% in year 1, 35% in year 5). In an analysis restricted to 259 women with 3 years of follow-up, 46 (18%) experienced a nonsustained decline in physical performance, and 39 (15%) experienced a sustained decline. CONCLUSIONS: Decline in physical performance is common after an ischemic stroke or TIA even in the absence of a recurrent neurological event. Our findings suggest that specific interventions to maintain and improve physical performance may be important for reducing long-term disability.
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.
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.
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: Warfarin therapy is effective for the prevention of stroke in patients with atrial fibrillation. However, warfarin therapy is underutilized even among ideal anticoagulation candidates. The purpose of this study was to examine the use of warfarin in both inpatients and outpatients with atrial fibrillation within a Veterans Affairs (VA) hospital system. METHODS: This retrospective medical record review included outpatients and inpatients with atrial fibrillation. The outpatient cohort included all patients seen in the outpatient clinics of the VA Connecticut Healthcare System during June 2000 with a diagnosis of atrial fibrillation. The inpatient cohort included all patients discharged from the VA Connecticut Healthcare System West Haven Medical Center with a diagnosis of atrial fibrillation during October 1999 - March 2000. The outcome measure was the rate of warfarin prescription in patients with atrial fibrillation. RESULTS: A total of 538 outpatients had a diagnosis of atrial fibrillation and 73 of these had a documented contraindication to anticoagulation. Among the 465 eligible outpatients, 455 (98%) were prescribed warfarin. For the inpatients, a total of 212 individual patients were discharged with a diagnosis of atrial fibrillation and 97 were not eligible for warfarin therapy. Among the 115 eligible inpatients, 106 (92%) were discharged on warfarin. CONCLUSIONS: Ideal anticoagulation candidates with atrial fibrillation are being prescribed warfarin at very high rates within one VA system, in both the inpatient and outpatient settings; we found warfarin use within our VA was much higher than that observed for Medicare beneficiaries in our state.
Bench research suggests that postmenopausal hormonal therapy is associated with beneficial effects on the brain and vascular system. Observational data suggest that postmenopausal hormone replacement therapy is associated with a 25% to 50% lower rate of cardiovascular disease; however, observational data for hormonal therapy is associated with the potential for significant biases. Clinical trial data are needed. There are 3 major clinical trials that inform us about stroke and postmenopausal hormone replacement therapy. Two trials focused on secondary prevention: the Heart and Estrogen/progesterone Replacement Study (HERS) and the Women's Estrogen for Stroke Trial (WEST). One examined primary prevention: the Women's Health Initiative (WHI). All indicate that postmenopausal hormone therapy is not effective for reducing the risk of a recurrent stroke or death among women with established vascular disease or for prevention of a first stroke. Similar results exist for cardiovascular disease. The results of these trials are now reflected in national guidelines. Hormone therapy should not be initiated to prevent vascular disease among postmenopausal women. As a result of these trials, the portion of postmenopausal women using hormone replacement therapy in the United States has fallen by more than half over the past decade.