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Biomedical subjects

Robert G Hart

Publications and source records attributed to Robert G Hart.

At least 19 recordsLinked to original sources

Additive role of plasma von Willebrand factor levels to clinical factors for risk stratification of patients with atrial fibrillation.

BACKGROUND AND PURPOSE: To aid decisions for thromboprophylaxis in atrial fibrillation (AF), several risk stratification schemes that predict stroke risk according to clinical and echocardiographic features have been published. von Willebrand factor (vWf) is a plasma markers of endothelial damage/dysfunction and is associated with the risk of stroke and vascular events in AF patients. This study determined the additive role of plasma vWf levels to clinical factors for risk stratification in patients with AF. METHODS: We classified 994 AF patients who were enrolled in the SPAF III trial as being at low, moderate, or high risk of stroke and thromboembolism according to the Birmingham and CHADS(2) risk stratification schemes. vWf levels were classified as elevated when >or=158 IU /dL. Rates of ischemic stroke and vascular events within each clinical risk stratum with and without plasma vWf levels were compared. RESULTS: The accuracy of both clinical risk stratification schemes was similar for predicting event rates (Birmingham: ischemic strokes, 0.642; vascular events, 0.670; CHADS(2): ischemic strokes, 0.672; vascular events, 0.672). Subsequent addition of categorized vWf levels to both clinical risk stratification schemes further refined risk stratification for stroke and vascular events. When added to the Birmingham and CHADS(2) clinical risk stratification, high vWf levels were independently associated with a risk of vascular events (hazard ratio, 2.05; 95% confidence interval, 1.30 to 3.22 and 2.01, 1.27 to 3.18 with Birmingham and CHADS(2), respectively) but not ischemic stroke. CONCLUSIONS: When added to clinical risk stratification schemes (Birmingham; CHADS(2)), plasma vWf levels refined clinical risk stratification for stroke and vascular events among AF patients. vWf levels may aid decisions about thromboprophylaxis, particularly among AF patients at moderate risk.

Aged↗

Primary prevention of ischemic stroke: a guideline from the American Heart Association/American Stroke Association Stroke Council: cosponsored by the Atherosclerotic Peripheral Vascular Disease Interdisciplinary Working Group; Cardiovascular Nursing Council; Clinical Cardiology Council; Nutrition, Physical Activity, and Metabolism Council; and the Quality of Care and Outcomes Research Interdisciplinary Working Group: the American Academy of Neurology affirms the value of this guideline.

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.

Brain Ischemia↗

National Stroke Association guidelines for the management of transient ischemic attacks.

OBJECTIVE: Transient ischemic attacks are common and important harbingers of subsequent stroke. Management varies widely, and most published guidelines have not been updated in several years. We sought to create comprehensive, unbiased, evidence-based guidelines for the management of patients with transient ischemic attacks. METHODS: Fifteen expert panelists were selected based on objective criteria, using publication metrics that predicted nomination by practitioners in the field. Prior published guidelines were identified through systematic review, and recommendations derived from them were rated independently for quality by the experts. Highest quality recommendations were selected and subsequently edited by the panelists using a modified Delphi approach with multiple iterations of questionnaires to reach consensus on new changes. Experts were provided systematic reviews of recent clinical studies and were asked to justify wording changes based on new evidence and to rate the final recommendations based on level of evidence and quality. No expert was allowed to contribute to recommendations on a topic for which there could be any perception of a conflict of interest. RESULTS: Of 257 guidelines documents identified by systematic review, 13 documents containing 137 recommendations met all entry criteria. Six iterations of questionnaires were required to reach consensus on wording of 53 final recommendations. Final recommendations covered initial management, evaluation, medical treatment, surgical treatment, and risk factor management. INTERPRETATION: The final recommendations on the care of patients with transient ischemic attacks emphasize the importance of urgent evaluation and treatment. The novel approach used to develop these guidelines is feasible, allows for rapid updating, and may reduce bias.

Health Planning Guidelines↗

What's new in stroke? The top 10 for 2004/05.

During the past decade, stroke has emerged from the dark ages of therapeutic nihilism to the current dawn of treatment activism, fueled by an unprecedented amount of high-quality clinical research. Here, the choices for the "Top 10" studies of 2004/05 influencing the management of patients with stroke and threatened stroke are reviewed. Nine are randomized, clinical trials involving a total of 61,810 participants. Three studies involved intracerebral hemorrhage, an important stroke subtype in which few trials have previously been carried out. Three studies involved acute treatment of stroke, and their results emphasize that "time is brain," and minutes count, in management of acute ischemic and hemorrhagic stroke. The 10th study was a longitudinal cohort analysis of participants with atrial fibrillation pooled from six clinical trials that validated predictive schemes to identify those who benefit most from anticoagulation. The practical management implications of these studies refine and improve care of geriatric patients with cerebrovascular disease.

Anticoagulants↗

Headache improvement through TMD stabilization appliance and self-management therapies.

The purpose of this study was to assess headache response of unselected neurology clinic chronic headache patients to TMD stabilization appliance and self-management therapies, and to identify features of patients whose headaches are more likely to improve from these therapies. Twenty chronic headache patients in a nontreatment control period were provided appliance and self-management therapies, evaluated five weeks after therapy, and those who chose to continue using their appliances were evaluated three months later. The mean pretreatment Headache Disability Inventory (HDI) score of 64.5 suggested the headaches were severe. After five weeks, the mean HDI score decreased by 17 percent (p<0.003), headache medication consumption dropped by 18 percent (p<0.0001), and headache symptoms decreased by 19 percent (p<0.002). Comparing the three months with pretreatment follow-up, the fourteen participants who chose to continue using their appliances had a mean HDI score decrease of 23 percent (p<0.003), headache medication consumption drop of 46 percent (p<0.001), and headache symptom decrease of 39 percent (p<0.001). There was no correlation between response and headache type (p=0.722). These results suggest appliance and self-management therapies can be beneficial for many severe headache patients, irrespective of the headache type (tension-type, migraine without aura, and migraine with aura).

Adult↗

Perindopril-based blood pressure-lowering reduces major vascular events in patients with atrial fibrillation and prior stroke or transient ischemic attack.

BACKGROUND AND PURPOSE: Patients with atrial fibrillation have a high risk of stroke and other vascular events even if anticoagulated. The primary objective here is to determine whether routine blood pressure-lowering provides additional protection for this high-risk patient group. METHODS: This study was a subsidiary analysis of the Perindopril Protection Against Recurrent Stroke Study (PROGRESS)--a randomized, placebo-controlled trial that established the beneficial effects of blood pressure--lowering in a heterogeneous group of patients with cerebrovascular disease. A total of 6105 patients were randomly assigned to either active treatment (2 to 4 mg perindopril for all participants plus 2.0 to 2.5 mg indapamide for those without an indication for or a contraindication to a diuretic) or matching placebo(s). Outcomes are total major vascular events, cause-specific vascular outcomes, and death from any cause. RESULTS: There were 476 patients with atrial fibrillation at baseline, of whom 51% were taking anticoagulants. In these patients, active treatment lowered mean blood pressure by 7.3/3.4 mm Hg and was associated with a 38% (95% confidence interval [CI], 6 to 59) reduction in major vascular events and 34% (95% CI, -13 to 61) reduction in stroke. The benefits of blood pressure-lowering in patients with atrial fibrillation were achieved irrespective of the use of anticoagulant therapy (P homogeneity=0.8) or the presence of hypertension (P homogeneity=0.4). CONCLUSIONS: For most patients with atrial fibrillation, routine blood pressure-lowering is likely to provide protection against major vascular events additional to that conferred by anticoagulation.

Aged↗

Clinical research in primary stroke prevention: needs, opportunities, and challenges.

Most ( approximately 70%) of strokes are first-ever strokes, and hence to substantially reduce the neurological burden, primary prevention is crucial. Here, highlights of the National Institute of Neurological Disorders and Stroke workshop "Stroke Risk Assessment and Future Stroke Primary Prevention Trials" held January 12-13, 2004 are summarized. The Workshop discussions focused on stroke risk assessment; the high-risk vs. population-based approaches to primary prevention; desirable characteristics of candidate treatments and potential novel treatments, such as the 'polypill'; subclinical disease as risk assessment tool and as surrogate outcome, and methodological issues in stroke primary prevention trials. The importance of assessing cognitive decline as an important consequence of covert and overt vascular injury of the brain was emphasized. The scientific or logistic barriers to stroke primary prevention trials are challenging, but are not insurmountable.

Cardiovascular Diseases↗

Avoiding central nervous system bleeding during antithrombotic therapy: recent data and ideas.

BACKGROUND: Approximately 7000 intracerebral hemorrhages (ICHs) annually in the US are caused by use of antithrombotic therapies. We review the incidence, risk factors, and predictors of ICH in patients receiving long-term anticoagulation or antiplatelet therapy. SUMMARY OF REVIEW: ICH rates range from 0.3% to 0.6% per year during oral anticoagulation in recent reports. Major risk factors are advanced patient age, elevated blood pressure, intensity of anticoagulation, and previous cerebral ischemia. Combining antiplatelet agents with anticoagulation and the combined use of aspirin plus clopidogrel appear to increase ICH risk. Modest blood pressure-lowering halves the frequency of ICH during antiplatelet therapy. CONCLUSIONS: ICH is an uncommon, but often fatal, complication of antithrombotic therapy that particularly afflicts patients with previous stroke. Recent data support that keeping international normalized ratio < or =3.0, control of hypertension, and avoiding the combination of aspirin with warfarin reduce its frequency.

Administration, Oral↗

Occurrence and characteristics of stroke events in the Atrial Fibrillation Follow-up Investigation of Sinus Rhythm Management (AFFIRM) study.

BACKGROUND: Atrial fibrillation (AF) is a risk factor for stroke, especially when accompanied by other high-risk cardiovascular predictors. The Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) Study was a multicenter comparison of high-risk patients with AF who were randomized to either a sinus rhythm control or a rate control strategy. METHODS: Physicians were encouraged to continue anticoagulation therapy for their patients. Patients in the sinus rhythm control group could stop warfarin sodium therapy after 4 (preferably a minimum of 12) weeks if they maintained sinus rhythm while receiving an antiarrhythmic drug. RESULTS: The AFFIRM Study enrolled 4060 patients. Mortality was the same in both groups. Two hundred eleven patients (8.2%) had a stroke event. Ischemic stroke occurred in 157 patients (6.3%), primary intraparenchymal hemorrhage in 34 (1.2%), and subdural or subarachnoid hemorrhage in 24 (0.8%). The most frequently determined ischemic stroke mechanism was cardioembolic (35/71 [49%]). Treatment assignment had no significant effect on the occurrence of ischemic stroke. Patients in AF at the time of the stroke event had a 60% greater chance of having an ischemic stroke, and those taking warfarin at the time of follow-up had a 69% decrease in the risk of having an ischemic stroke. CONCLUSIONS: In the AFFIRM Study, stroke rates were not significantly different in the rate control and sinus rhythm control arms. However, several clinical and therapeutic variables were associated with stroke risk. In patients with a history of AF at high risk for stroke or death, the presence of AF increases the risk of having a stroke, and warfarin therapy reduces the risk of having a stroke. The beneficial effect of warfarin therapy is seen not only in patients in AF but also in patients with a history of AF but who presumably remain in sinus rhythm.

Aged↗

Atrial fibrillation and stroke: four treatment controversies.

Atrial fibrillation is an important cause of disabling ischemic stroke, and adjusted-dose warfarin is highly effective for prevention and remains the therapy of choice for high-risk patients. Ximelagatran, a novel oral anticoagulant, is clinically equivalent to warfarin for preventing stroke in patients with atrial fibrillation, but concerns about potential hepatic toxicity have precluded US Food and Drug Administration approval. Many patients with low-risk atrial fibrillation do not benefit substantially from anticoagulation, and these patients can be reliably identified using the CHADS2 stroke risk stratification scheme. A target International Normalized Ratio (INR) range of 2 to 3 is usually recommended for anticoagulation of patients with atrial fibrillation, but a lower INR target (2, range 1.6-2.5) may be a reasonable benefit/risk trade-off for primary prevention in those aged older than 75 years. Adding aspirin to adjusted-dose anticoagulation increases bleeding (including central nervous system bleeding), is of uncertain value, and should only be done after careful consideration and with vigorous efforts to control blood pressure.

Journal Article↗

Data and safety monitoring in clinical research: a National Institute of Neurologic Disorders and Stroke perspective.

The National Institute of Neurologic Disorders and Stroke supports a broad spectrum of research in the diagnosis and treatment of neurologic disease. Emergency medicine is increasingly involved in clinical research for patients with neurologic emergencies. Independent data and safety monitoring are critical components of clinical trials to ensure the protection of patients and the scientific integrity of the research. We review National Institute of Neurologic Disorders and Stroke principles of data and safety monitoring and provide examples to illustrate key concepts.

Black or African American↗

Optimal INR for prevention of stroke and death in atrial fibrillation: a critical appraisal.

INTRODUCTION: Patients with nonvalvular atrial fibrillation are at increased risk for systemic embolism, predominantly disabling stroke. To study how stroke and mortality rates vary with different degrees of anticoagulation reflected by the international normalised ratio (INR) we critically assess information from different sources. MATERIALS AND METHODS: 1. Computerized search of the medical literature published between 1980 and July 2004 was performed using MEDLINE applied to various combinations of the search terms of atrial fibrillation, warfarin, anticoagulation, anticoagulation intensity, and INR, not restricted by language. 2. We performed a record linkage analysis with death hazard estimated as a continuous function of INR based on 21,967 patients. Similarly the risk of admission to hospital or death due to diseases of the vessels of the brain was estimated. 3. Re-analysis of data earlier published by Hylek et al. from year 2003. RESULTS AND CONCLUSIONS: 1. One randomised study showed a significantly lower risk of stroke for mean INR 2.4 compared to mean INR 1.3 combined with aspirin. Remaining studies found INRs of 2-2.5 to be as efficacious as higher anticoagulation intensities.2. Mortality as well as risk of admission to hospital or death due to diseases of the vessels of the brain followed U-shaped curves with minimum at INR 2.2 and 2.4, respectively. At high INR the risk increased 2.3 times per 1 unit increase of INR for death and 1.7 times for events in the vessels of the brain.3. The re-analysing of data of Hylek et al. indicated that there might be a substantial increase of the risk of intracranial hemorrhage when INR is increased from 2.5 to 4. We conclude that INRs in the interval 2.0--2.5 give the lowest risk of stroke and death in patients with nonvalvular atrial fibrillation.

Aged↗

Selecting patients with atrial fibrillation for anticoagulation: stroke risk stratification in patients taking aspirin.

BACKGROUND: The rate of stroke in atrial fibrillation (AF) depends on the presence of comorbid conditions and the use of antithrombotic therapy. Although adjusted-dose warfarin is superior to aspirin for reducing stroke in AF, the absolute risk reduction of warfarin depends on the stroke rate with aspirin. This prospective cohort study tested the predictive accuracy of 5 stroke risk stratification schemes. METHODS AND RESULTS: The study pooled individual data from 2580 participants with nonvalvular AF who were prescribed aspirin in a multicenter trial (Atrial Fibrillation, Aspirin, Anticoagulation I study [AFASAK-1], AFASAK-2, European Atrial Fibrillation Trial, Primary Prevention of Arterial Thromboembolism in patients with nonrheumatic Atrial Fibrillation in primary care study, and Stroke Prevention and Atrial Fibrillation [SPAF]-III high risk or SPAF-III low risk). There were 207 ischemic strokes during 4887 patient-years of aspirin therapy. All schemes predicted stroke better than chance, but the number of patients categorized as low and high risk varied substantially. AF patients with prior cerebral ischemia were classified as high risk by all 5 schemes and had 10.8 strokes per 100 patient-years. The CHADS(2) scheme (an acronym for Congestive heart failure, Hypertension, Age >75, Diabetes mellitus, and prior Stroke or transient ischemic attack) successfully identified primary prevention patients who were at high risk of stroke (5.3 strokes per 100 patient-years). In contrast, patients identified as high risk by other schemes had 3.0 to 4.2 strokes per 100 patient-years. Low-risk patients identified by all schemes had 0.5 to 1.4 strokes per 100 patient-years of therapy. CONCLUSIONS: Patients with AF who have high and low rates of stroke when given aspirin can be reliably identified, allowing selection of antithrombotic prophylaxis to be individualized.

Aged↗

Predictors of stroke in patients paced for sick sinus syndrome.

OBJECTIVES: This study was an analysis of factors associated with stroke in a population of patients paced for sinus node dysfunction in a large prospective clinical trial (Mode Selection Trial [MOST]). BACKGROUND: The effects of dual-chamber versus single-chamber ventricular pacing on subsequent stroke in patients with sinus node dysfunction are not known. METHODS: A total of 2,010 patients with sinus node dysfunction were randomized to ventricular or dual-chamber pacing and followed for a median of 33.1 months. RESULTS: The median participant age was 74 years. During 5,664 patient-years of follow-up, 90 strokes (11 hemorrhagic) occurred. By life-table analysis, the rate of stroke was 2.2% (95% confidence interval [CI] 1.6 to 2.9) at one year and 5.8% (95% CI 4.5 to 7.1) at four years. The incidence of stroke was not significantly different in dual-chamber (4%) as compared with ventricular-paced patients (4.9%) (hazard ratio [HR] 0.82, 95% CI 0.54 to 1.25, p = 0.36). Multivariable analysis demonstrated that significant predictors of stroke included prior stroke or transient ischemic attack, Caucasian race, hypertension, prior systemic embolism, and New York Heart Association functional class III or IV (p < 0.05); pacing mode remained non-significant after adjustment for these factors (p = 0.37). Clinically reported atrial fibrillation after implantation was a risk factor for stroke in this cohort after adjustment for other predictors of stroke (p = 0.042, HR 1.68 [95% CI 1.02 to 2.76]). CONCLUSIONS: Clinical characteristics, but not mode of pacing, were associated with subsequent stroke in patients paced for sinus node dysfunction.

Age Factors↗

Transient ischemic attacks in patients with atrial fibrillation: implications for secondary prevention: the European Atrial Fibrillation Trial and Stroke Prevention in Atrial Fibrillation III trial.

BACKGROUND AND PURPOSE: Transient ischemic attacks (TIAs) are infrequent in patients with atrial fibrillation, and little is known about the long-term prognosis and response to antithrombotic therapy. METHODS: This study was a pooled analysis of participants in 2 randomized trials, the European Atrial Fibrillation Trial and the Stroke Prevention in Atrial Fibrillation III Trial, comparing those with prior TIA to those with prior stroke. RESULTS: Among 834 atrial fibrillation patients with prior TIA (n=222), prior ischemic stroke (n=551), or both (n=61), the mean age was 71 years, 64% were men, and 56% had hypertension. The frequency of major vascular risk factors was similar for both types of cerebral ischemia. The annualized rate of ischemic stroke during aspirin therapy was 7% per year (95% confidence interval, 4 to 12) for prior TIA and 11% per year (95% confidence interval, 9 to 15) for prior stroke (P=0.08 for rate difference) and was reduced by 56% (P=0.09) and 63% (P<0.001), respectively, by anticoagulation. CONCLUSIONS: Atrial fibrillation patients with TIA have a lower long-term risk of subsequent stroke than those with prior stroke, but their stroke risk during aspirin therapy is still high. For atrial fibrillation patients with either type of cerebral ischemia, recent or remote, secondary prevention with adjusted-dose warfarin instead of aspirin results in substantial absolute reductions in ischemic stroke.

Aged↗