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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.

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: 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.

Background and Purpose: Little is known about informed consent for tissue plasminogen activator (tPA). Our objectives were to determine how frequently informed consent is obtained when tPA is given to stroke patients in clinical practice and whether the person providing consent (patient or surrogate) was the appropriate decision-maker., Methods: This retrospective cohort included acute stroke patients given tPA in 10 Connecticut hospitals (1996-1998). Consent was defined as any documentation of discussion about risks and benefits of tPA. Patients had adequate decision-making capacity if they were alert, oriented, and without aphasia or neglect (patient was appropriate decision-maker). Patients with any of these deficits were considered to have diminished capacity (surrogate was appropriate decision-maker)., Results: Among 63 patients who received tPA, 53 (84%) had informed consent documented; 16/53 (30%) gave their own consent. Among patients with adequate decision-making capacity, 5/8 (63%) had consent by surrogate. Among patients with diminished capacity, 7/38 (18%) provided their own consent., Conclusions: A substantial percentage of patients who received tPA for stroke had no consent documented. Surrogates often provided consent when the patients had capacity; conversely, patients with diminished capacity sometimes provided their own consent. Given the urgency and weight of the decision regarding tPA, more explicit informed consent and capacity assessment should be considered for treatment protocols.

Background: Hyperglycaemia is common among patients with acute ischaemic stroke, and may be due to the physiological stress of the acute stroke event or reflect underlying diabetes mellitus. The under-diagnosis of diabetes in the general population, combined with the association of diabetes and stroke, suggests a rationale for screening for diabetes among hyperglycaemic stroke patients., Aim: To determine how often clinicians screen for diabetes among hyperglycaemic stroke patients without a prior diagnosis of diabetes., Design: Retrospective medical record review., Methods: We reviewed the records of acute ischaemic stroke patients admitted at any of ten Connecticut hospitals from May 1996 through December 1998., Results: We identified 90 acute stroke patients with no prior history of diabetes. The prevalence of hyperglycaemia varied from 31% down to 6%, depending on the maximum glucose cut-off used to define hyperglycaemia: from > or = 140 mg/dl (7.8 mmol/l) to > or = 200 mg/dl (11.1 mmol/l). Only one of the hyperglycaemic patients (1/90, 1%) had any evidence that a clinician screened or planned to screen for undiagnosed diabetes: one patient had a haemoglobin A1c measured during the hospitalization, none received oral glucose tolerance testing while hospitalized, and no discharge summary included a plan to screen for diabetes as an out-patient., Discussion: Hyperglycaemic stroke patients without a previous diagnosis of diabetes are not routinely screened for diabetes. This situation represents an opportunity, currently unused, to identify an important and modifiable condition.

Background: Stroke is an important outcome after acute myocardial infarction. Studies that have examined this relationship have largely excluded older patients, even though half of stroke admissions occur among patients 75 years of age and older., Methods and Results: Among 111 023 medicare patients discharged with a principal diagnosis of acute myocardial infarction during an 8-month period in 1994 to 1995, we identified hospital admissions for ischemic stroke within 6 months of discharge. The rate of admission was 2.5% within 6 months. Independent predictors of ischemic stroke were age greater-than-or-equal 75 years, black race, no aspirin at discharge, frailty, prior stroke, atrial fibrillation, diabetes, hypertension, and history of peripheral vascular disease. To identify individuals at increased risk for stroke, a risk stratification score was constructed from identified factors. The 6-month stroke admission rate for patients with a score of 4 or higher (approximately 20% of the total sample) was approximately 4%., Conclusions: The risk of stroke after myocardial infarction is substantial, with about 1 in 40 patients suffering an ischemic stroke within 6 months of discharge. Simple clinical factors can predict the risk of stroke and, based on these factors, we identified 20% of older patients who have a 1 in 25 chance of being hospitalized for a stroke within 6 months of discharge.

Background: A low level of HDL cholesterol has been identified as a risk factor for stroke in observational studies., Methods and Results: Our objective was to determine whether treatment aimed at raising HDL cholesterol and lowering triglycerides reduces stroke in men with coronary heart disease and low levels of both HDL and LDL cholesterol. The study was a placebo-controlled, randomized trial conducted in 20 Veterans Affairs medical centers. A total of 2531 men with coronary heart disease, with mean HDL cholesterol 0.82 mmol/L (31.5 mg/dL) and mean LDL cholesterol 2.9 mmol/L (111 mg/dL), were randomized to gemfibrozil 1200 mg/d or placebo and were followed up for 5 years. Strokes were confirmed by a blinded adjudication committee. Relative risks were derived from Cox proportional hazards models. There were 134 confirmed strokes, 90% of which were ischemic. Seventy-six occurred in the placebo group (9 fatal) and 58 in the gemfibrozil group (3 fatal), for a relative risk reduction, adjusted for baseline variables, of 31% (95% CI, 2% to 52%, P=0.036). The reduction in risk was evident after 6 to 12 months. Patients with baseline HDL cholesterol below the median may have been more likely to benefit from treatment than those with higher HDL cholesterol., Conclusions: In men with coronary heart disease, low HDL cholesterol, and low LDL cholesterol, gemfibrozil reduces stroke incidence.

Background and Purpose: We sought to measure the overall rate of usage of tissue-type plasminogen activator (tPA) for ischemic stroke at academic medical centers, and to determine whether ethnicity was associated with usage., Methods: Between June and December 1999, 42 academic medical centers in the United States each identified 30 consecutive ischemic stroke cases. Medical records were reviewed and information on demographics, medical history, and treatment were abstracted. Rates of tPA use were compared for African Americans and whites in univariate analysis and after adjustment for age, gender, stroke severity, and type of medical insurance with multivariable logistic regression., Results: Complete information was available for 1195 ischemic stroke patients; 788 were whites and 285 were African Americans: Overall, 49 patients (4.1%) received tPA. In the subgroup of 189 patients without a documented contraindication to therapy, 39 (20.6%) received tPA. Ten (20%) of those receiving tPA had documented contraindication. African Americans were one fifth as likely to receive tPA as whites (1.1% African Americans versus 5.3%; P=0.001), and the difference persisted after adjustment (OR 0.21, 95% CI 0.06 to 0.68; P=0.01). When comparison was restricted to those without a documented contraindication to tPA, the difference remained significant (OR 0.24, 95% CI 0.06 to 0.93; P=0.04). Medical insurance type was independently associated with tPA treatment. After adjustment for ethnicity and other demographic characteristics, those with Medicaid or no insurance were one ninth as likely to receive tPA as those with private medical insurance (OR 0.11, 95% CI 0.02 to 0.17; P=0.003)., Conclusions: tPA is used infrequently for ischemic stroke at US academic medical centers, even among qualifying candidates. African Americans are significantly less likely to receive tPA for ischemic stroke. Contraindications to treatment do not appear to account for the difference.

Background and Purpose: Intracranial hemorrhage is a serious complication of thrombolytic therapy for acute myocardial infarction, especially among the elderly, but little information exists on estimating risk. Better estimation of risk in individual patients may allow for withholding or using alternate therapies among those at highest risk., Methods: To quantify the risk and identify predictors of intracranial hemorrhage associated with thrombolytic therapy, we performed a retrospective cohort study using data from medical charts. The study involved nearly all acute-care hospitals in the United States. All Medicare patients discharged with a principal diagnosis of acute myocardial infarction during a 9-month period in 1994 to 1995 were included. The main outcome measure was intracranial hemorrhage among those treated with thrombolytic therapy., Results: The rate of intracranial hemorrhage was 1.43% (455 of 31 732). In a logistic model, age > or =75 years, female, black race, prior stroke, blood pressure > or =160 mm Hg, tissue plasminogen activator (versus other thrombolytic agent), excessive anticoagulation (international normalized ratio > or =4 or prothrombin time > or =24), and below median weight (< or =65 kg for women; < or =80 kg for men) were independent predictors. A risk stratification scale was developed on the basis of these factors: with none or 1 of the factors (n=6651), the rate of intracranial hemorrhage was 0.69%; with 2 factors (n=10 509), 1.02%; with 3 factors (n=9074), 1.63%; with 4 factors (n=4298), 2.49%; and with > or =5 factors (n=1071), 4. 11% (Mantel-Haenszel; P<0.001)., Conclusions: The rate of intracranial hemorrhage in older patients after treatment with thrombolytic therapy exceeds 1%. Readily available factors can identify elderly patients with acute myocardial infarction at high and low risk for intracranial hemorrhage associated with thrombolytic therapy.

Stroke is the third leading cause of death and a leading cause of adult disability in the United States. Both within and outside of the Veterans Health Administration (VHA), the lack of a systematic approach to stroke prevention and treatment may have contributed to reduced rates of compliance with recommended practices and increased rates of stroke. Gaps in the knowledge base inhibit a systematic approach to high-quality care within the veteran population. Initial recommendations for closing those gaps are proposed. In some cases (eg, systematic anticoagulation management), the VHA is perceived as a leader in applied research; therefore, a systematic national policy for implementing these clinics may significantly reduce stroke rates. In other areas (eg, carotid endarterectomy), databases exist that would help advance quality and outcomes, but short-term studies are necessary to establish their utility. To promote strategic improvement in prevention, treatment, and rehabilitation for veterans who may be at risk or have had a stroke, specific objectives are proposed to (1) identify best practices for the effective delivery of long-term anticoagulation and enhance veterans' access to these services, (2) develop risk-adjusted models for the surgical preventive procedure carotid endarterectomy to understand facility variation in outcomes so practices can be improved, (3) define a systematic acute stroke management system so that high-quality stroke-related care can be generalizable to a variety of VHA settings, and (4) assess the impact of poststroke rehabilitation on risk adjustment and the location of outcomes so as to facilitate the implementation of best rehabilitation practices.

Background and Purpose: After a transient ischemic attack or stroke, the risk for recurrence may be reduced by treatment of hypertension. The purpose of this study was to determine how commonly blood pressure exceeds national guidelines among patients who have had one of these events., Methods: Subjects were 644 women participating in a randomized trial of estrogen for secondary stroke prevention. We measured blood pressure 1 month after the stroke or TIA while patients were under the care of their personal physicians. Among 536 patients, a second measure was made at an average of 2.9 years after the first., Results: The mean age of participants was 71 years, and 73% reported a history of hypertension. At baseline, only 44% (280/644) of the women had blood pressure values within national guidelines (<140/90 mm Hg). With separate guidelines used for diabetics (<130/85 mm Hg) and nondiabetics (<140/90 mm Hg), the proportions of women within the guidelines were 27% and 44%, respectively. Overall, 39% of patients were within the diabetes-adjusted guidelines. Among patients whose blood pressure exceeded 140/90 mm Hg at first examination, 55% were still in excess at follow-up. Features associated with severe hypertension at first examination (>160/100 mm Hg) were history of hypertension, education less than college, and higher cognitive functioning., Conclusions: Blood pressure values in excess of national guidelines are common after stroke and TIA, especially among diabetic patients. Efforts to lower blood pressure control may enhance secondary prevention.

Background and Purpose: Warfarin reduces the rate of stroke among patients with atrial fibrillation. We sought to determine warfarin use within a population sample of elderly patients with atrial fibrillation., Methods: The Connecticut Peer Review Organization conducted a chart review of Medicare patients aged > or = 65 years with a history of atrial fibrillation before a hospitalization during the first 6 months of 1994., Results: Among 488 patients (308 women; 457 white; 173 aged > or = 85 years), 38% (184/488) had a relative contraindication to anticoagulation (history of bleeding, dementia, alcohol use, falls, cancer, or the need for nonsteroidal anti-inflammatory drugs). Among the remaining patients (with known atrial fibrillation, but without a contraindication), only 38% (117/304) had been prescribed warfarin. Of those not prescribed warfarin, 63% (117/187) were also not taking aspirin. There were 272 patients with at least one additional vascular risk factor and no contraindication to anticoagulation. Among these patients at moderate to high risk for stroke, anticoagulation had been prescribed in 40% (109/272). Overal, among those not prescribed warfarin, 58% (95/163) were not taking aspirin. Patients admitted with a stroke were more likely to be significantly underanticoagulated (with international normalized ratio < 1.5) (43.5% versus 20.9% for those without stroke; P < .005). Anticoagulation was most effective for those with an international normalized ratio > or = 2.0., Conclusions: Warfarin anticoagulation with atrial fibrillation, even among "ideal" candidates, appears dramatically underutilized. In addition, among those prescribed warfarin, patients are often undertreated. Increased warfarin use among patients with atrial fibrillation represents an excellent opportunity for stroke prevention in the elderly.

Background and Purpose: We sought to determine whether lactate and N-acetyl signals measured by proton magnetic resonance spectroscopy (MRS) in the first days after stroke correlate with clinical measures of disability and functional outcome., Methods: One-dimensional spectroscopic imaging was performed after stroke on 32 patients using a 2.1-T magnet. The Toronto Stroke Scale score at the time of the MRS study and the Barthel Index score at hospital discharge were determined from patient records. Lesion volume was estimated by a tracing algorithm from the scout magnetic resonance image obtained as part of the MRS study. The scaled lactate and N-acetyl signals from the voxel having the highest measured lactate were used to predict the clinical variables and lesion volume, as well as relative perfusion within the lesion, in those patients who underwent single-photon emission computed tomography (SPECT) blood flow imaging, using a multiple regression analysis. The correlation of lesion volume with the clinical variables was also evaluated., Results: Lesion lactate signal was correlated with the Toronto Stroke Scale score, Barthel Index score, lesion volume, and SPECT score, all at P < .01. The N-acetyl level correlated with the Barthel Index score and lesion volume at P < .05. Lesion volume was also strongly correlated with the clinical variables (P < .0001)., Conclusions: This is the first study to document the clinical predictive value of proton MRS measurements in patients after stroke. The association with functional outcome is stronger for lactate than for N-acetyl. Spectroscopic assessment of the metabolic status of cerebral tissues shortly after infarction may have significant clinical utility.

Background and Purpose: Proton magnetic resonance spectroscopy has documented declines in normal metabolites and long-term elevation of lactate signal after stroke in humans. Within days of stroke, leukocytes infiltrating the infarct zone may produce much of the lactate seen in the subacute and chronic periods., Methods: We examined 10 patients by localized proton magnetic resonance spectroscopy with one-dimensional spectroscopic imaging within the first 60 hours after acute nonhemorrhagic cerebral infarction, a period before abundant leukocyte infiltration. Follow-up studies on day 8 to 17 after stroke were performed on 7 of these patients., Results: Initially, the lactate magnetic resonance signal was elevated in all patients. The N-acetyl-aspartate peak within the lesion was reduced below contralateral normal brain in all but two. At subsequent examination, significant declines had occurred in lesion maximum lactate and N-acetyl-aspartate signals, with average changes of -36 +/- 11% per week and -29 +/- 9% per week, respectively. Declines in lesion creatine/phosphocreatine and in choline-containing compound peaks occurred in some patients but did not attain statistical significance for the group as a whole. Estimated lesion volume correlated positively with both total (r = .75, P = .012) and lesion maximum (r = .74, P = .015) lactate signal., Conclusions: Elevated lactate signal is reliably detectable by magnetic resonance spectroscopy after acute cerebral infarction in humans. Clearance of lactate occurs despite the potential contribution of lactate-producing leukocytes in the subacute stage. Delayed loss of N-acetyl-aspartate signal in second examinations suggests that late death of viable cells may occur within the first 2 weeks after cerebral infarction.

Background and Purpose: Patients with stroke symptoms commonly delay many hours before seeking medical attention. We sought to explore the factors associated with early presentation of stroke patients to physicians., Methods: We prospectively studied 100 consecutive acute stroke patients presenting to three large, urban medical centers. Using a standardized, structured interview and chart review, we assessed patient education about stroke, risk factors, clinical features of the stroke, source of stroke recognition, and timing of presentation. We did not study the distance from the site of stroke onset to the site of physician contact., Results: Stroke onset time was known in 96 of the patients. Mean patient age was 71.3 years, 79% had at least one stroke risk factor, 26% had prior transient ischemic attack, 19% had prior stroke, 74% had some high school education, and 86% had regular physicians. Only 8% had been previously educated about stroke symptoms. Eighty one percent of strokes were ischemic. The mean time to physician contact was 13.4 +/- 2.3 hours (median, 4.0 hours) and to neurologist contact was 21.2 +/- 2.9 hours. A skewed distribution of presentation times accounts for the mean-median differences. A small number of patients presenting very late could have an effect on the correlations between presentation time and the variables studied. Early presentation time was associated with increased age, the sudden onset of a stable deficit, and recognition that the symptoms signified stroke. Only the sudden onset of a stable deficit correlated independently with early presentation time (P = .0048). There was no correlation between presentation time and prior transient ischemic attack or stroke, headache, vomiting, loss of consciousness or seizures at onset, or stroke subtype, but a type II error could not be excluded., Conclusions: Despite their education level, regular health care, and risk factors, especially prior stroke and transient ischemic attack, these patients were not knowledgeable about stroke and delayed many hours before contacting physicians. The course of symptoms and recognition that they signified stroke were associated with earlier presentation. Patient education focused on groups at risk may hasten the presentation and treatment of acute stroke.

Background: Each year at least 35,000 people suffer a stroke while hospitalized, but little is known about the clinical characteristics of such patients or how rapidly they are identified and evaluated. With a recent emphasis on the very early treatment of stroke, in-hospital stroke patients may be candidates for some early interventions., Methods: This was a retrospective study using the stroke registries at two academic medical centers. Data were collected about the clinical characteristics of patients with an in-hospital stroke and who recognized the stroke. Detailed time data were analyzed to determine the time of stroke recognition, medical evaluation, and neurological evaluation. These specific time epochs were analyzed to determine which were responsible for any delays in stroke identification and assessment. Data were analyzed using nonparametric methods, including the Wilcoxon rank sum and Kruskal-Wallis procedure., Results: Sixty-three patients were identified with in-hospital strokes and adequate time data. In-hospital stroke patients were recognized most frequently by nurses (63%) and by the patient (16%). Patients on a cardiology service and general surgery service accounted for 48% of all in-hospital strokes. The mean and median times from stroke recognition to a neurology evaluation were 14.5 and 2.5 hours, respectively. Total delays differed significantly with service and locale (P = .004). Patients on the Duke neurology service were evaluated significantly sooner (median delay, 0.5 hour) than patients on the Duke medical (median delay, 5.8 hours) or Duke surgical (median delay, 20.5 hours; P < .01 by Wilcoxon rank sum) services. Patients on the Yale surgical service were evaluated significantly sooner than patients on the Duke medical (P = .0006) or surgical (P = .0001) services. The time between physician notification and calling for a neurology evaluation accounted for > 60% of the total time delay for patients not on a neurology service., Conclusions: A substantial number of in-hospital stroke patients experience a long delay between symptom recognition and a neurological evaluation. While medical personnel are usually notified very soon after an in-hospital stroke is recognized, such patients often do not receive a rapid neurological evaluation. Additional education of hospital staff may reduce these time delays.

Background and Purpose: Proton magnetic resonance spectroscopy can measure in vivo brain lactate and other metabolites noninvasively. We measured the biochemical changes accompanying stroke in 16 human subjects with cortical or deep cerebral infarcts within the first 3 weeks after symptom onset, and performed follow-up studies on six., Methods: One-dimensional proton spectroscopic imaging encompassing the infarct region was performed with a 2.1-T whole-body magnet using the stimulated echo pulse sequence and an echo time of 270 msec., Results: All but one of the cortical stroke patients had increased lactate within or near the infarct. Persistently elevated cerebral lactate was documented in five of six cases studied serially as long as 251 days after infarction. N-acetylaspartate levels were decreased in most cortical strokes. Elevated lactate, accompanied by minimal reduction in N-acetylaspartate, was recorded in two of four patients in the first week following a small subcortical infarct., Conclusions: Long-term elevation of lactate commonly occurs after stroke. This lactate may arise from ongoing ischemia or infiltrating leukocytes, or it may be a residual of the lactate formed during the initial insult. The ability to observe stroke-elevated lactate pools at any time after lesion onset provides an approach to distinguishing among these possibilities in the future.

Background and Purpose: Although there are strong genetic contributions to coronary artery disease, only a few studies have considered heritable influences on stroke., Methods: We investigated the role of genetic factors in stroke using the Twin Registry maintained by the National Academy of Sciences-National Research Council. The registry includes 15,948 male twin pairs born between 1917 and 1927. In 1985, 9,475 twins responded to a mailed questionnaire, which covered vascular risk factors, cardiac events, and stroke., Results: Analysis of twin pairs in which both responded to the questionnaire, and a question on stroke, indicated proband concordance rates of 17.7% for monozygotic pairs and 3.6% for dizygotic pairs (relative risk = 4.3; chi 2 = 4.94, df = 1; p less than 0.05)., Conclusions: This nearly fivefold increase in the prevalence of stroke among the monozygotic compared with the dizygotic twin pairs suggests that genetic factors are involved in the etiology of stroke. The twin study paradigm holds considerable promise for identifying both genetic and environmental influences on stroke.

We analyzed existing research on the prognosis of patients who have had a transient ischemic attack to identify studies that adhere to basic methodological principles and to identify underinvestigated questions. Studies were eligible for analysis if they were published in peer-reviewed journals after 1950, written in English, and included at least 50 patients with transient ischemia. Studies that included patients with stroke were included only if they reported outcome rates separately for the subgroup of patients with transient ischemia. All eligible studies were extracted by one investigator who recorded adherence to six key methodological principles. Among 60 eligible studies, 54 were observational cohort studies and six were randomized trials. Adherence to the six methodological principles was as follows: eight studies included an adequate description of diagnostic criteria and of procedures used to assure adherence to the criteria, 54 used appropriate end points, two assembled inception cohorts, 10 included an adequate description of end point surveillance, 22 adequately reported and analyzed censored patients, and 10 included a multivariate analysis for predictive variables. No study adhered to all six principles, but two adhered to the three most important ones (appropriate end points, inception cohort, and adequate reporting and analysis of censored patients). Aspects of prognosis after transient ischemia that have not been completely investigated include the severity of subsequent strokes and methods for estimating the outcome risk for individual patients. We conclude that only a few published investigations on prognosis after transient ischemia are methodologically complete. This finding helps explain why it is difficult to interpret many studies. Further research is needed and should target underinvestigated topics.

To determine the influence of family history on vascular disease, we surveyed hospital patients discharged with a diagnosis of transient ischemic attack. Of 117 respondents, 81 knew their family history for myocardial infarction and 81 knew their family history for stroke. Of 83 responding 43 reported a personal history of myocardial infarction, and of 85 responding 66 reported a personal history of stroke. As expected, there was an association between positive family and personal histories of myocardial infarction in younger (aged less than 70 years) patients (Fisher's two-tailed exact test, p = 0.014). This association was reversed for stroke (Fisher's two-tailed exact test, p = 0.017). Older (aged greater than or equal to 70 years) patients had a stronger association between positive family and personal histories of stroke; 14 (74%) of 19 older patients with a positive personal history of stroke had a positive family history of stroke. The reason for this reversal in the relation between family and personal histories of stroke compared with myocardial infarction may relate to the older age at onset of most strokes, differing stroke subtypes in older age groups, or lower rates of fatal myocardial infarction. This study suggests that familial factors may be important in some subtypes of cerebrovascular disease. Familial effects may be different in vascular diseases of the heart and brain.