Race-Ethnicity and Determinants of Intracranial Atherosclerotic Cerebral Infarction
The Northern Manhattan Stroke Study
Background and Purpose The aim of this investigation was to determine the importance of race as a determinant of intracranial atherosclerotic stroke in a community-based stroke sample.
Methods Residents from northern Manhattan over age 39 years hospitalized for acute ischemic stroke (n=438, black 35%, Hispanic 46%, white 19%) were prospectively evaluated. Index ischemic strokes were classified as atherosclerotic (17%), lacunar (30%), cardioembolic (21%), cryptogenic (31%), and other (1%). Atherosclerotic infarcts were subdivided into extracranial (9%) and intracranial (8%) atherosclerosis.
Results The proportion of extracranial atherosclerotic stroke was similar among the three race-ethnic groups, while intracranial atherosclerosis was more frequent in blacks and Hispanics. The unadjusted odds ratio for nonwhites (blacks and Hispanics combined) was 0.8 (confidence interval [CI], 0.4 to 1.8) for extracranial and 7.8 (CI, 1.04 to 57.7) for intracranial atherosclerosis. Patients with intracranial disease were significantly younger and had an increased frequency of hypercholesterolemia and insulin-dependent diabetes compared with those with nonatherosclerotic disease. The odds ratio for the association of nonwhite race-ethnicity and intracranial atherosclerosis was reduced to 5.2 (CI, 0.7 to 40) after controlling for age and to 4.4 (CI, 0.6 to 35) after controlling for age, education, insulin-dependent diabetes, and hypercholesterolemia.
Conclusions The greater prevalence of diabetes and hypercholesterolemia among blacks and Hispanics from northern Manhattan accounted for much of the increased frequency of intracranial atherosclerotic stroke. Further control of these risk factors could reduce the frequency of this stroke subtype and minimize the disparities among different race-ethnic groups.
Atherosclerotic infarction accounts for a sizable proportion of cerebral infarcts. Infarction occurs from extracranial or intracranial atherosclerotic disease due to flow failure or artery-to-artery embolism. African Americans and Asians have been found to have more intracranial atherosclerosis than whites, while Hispanics have not been separately studied.1 2 3 4 5 6 7 8 9 10 11 12 Whether race is an independent predictor of intracranial atherosclerotic stroke or is confounded by differences in the prevalence of stroke risk factors has not been clearly determined. Former studies have not been community based and have depended on cerebral angiography or autopsy to confirm the diagnosis of large-vessel intracranial atherosclerosis. More recently, duplex Doppler sonography has advanced the diagnosis of extracranial atherosclerosis, and transcranial Doppler (TCD) has made the diagnosis of intracranial atherosclerotic stroke more attainable. The aim of our investigation was to determine whether race-ethnicity was an independent determinant of intracranial atherosclerotic stroke in an urban, ethnically diverse community.
Subjects and Methods
The Northern Manhattan Stroke Study (NOMASS) is an ongoing, prospective registry of stroke patients who reside in the region. Northern Manhattan consists of the area north of 145th Street and south of 218th Street and is bounded on the west by the Hudson River and separated from the Bronx on the east by the Harlem River. In 1990, nearly 260 000 people lived in the region, with 40% over the age of 39 years. There is a rich ethnic distribution in this community, with 15% white, 20% black, and 63% Hispanic residents. There is only one hospital in the area, the Presbyterian Hospital of the City of New York, and statewide planning data have indicated that approximately 80% of all patients with cerebral infarction are hospitalized at Presbyterian Hospital.
Patients eligible for this cohort study were uniformly and prospectively enrolled if they met the following criteria: (1) diagnosis of acute cerebral infarction, (2) over age 39 years at stroke, (3) resident of the northern Manhattan community, and (4) hospitalization at the Milstein Building of Columbia–Presbyterian Medical Center from 1990 to 1993. Patients with transient ischemic attack (ie, neurological deficits lasting less than 24 hours and no ischemic infarct found on brain imaging) were excluded. Over a 3.5-year period, 2091 patients were screened, and 500 were found to be eligible. Ineligible patients included 833 living outside of northern Manhattan, 218 with transient ischemic attack, 165 with intracerebral hemorrhage, 146 with subarachnoid hemorrhage, 146 with other neurological diagnoses, 32 under age 40 years, 6 for unknown reasons, and 45 who were previously enrolled in the cohort. Of the 500 eligible subjects, 447 were enrolled in the study. Only 53 eligible subjects were not enrolled: 19 were discharged before they could be enrolled, 12 were too ill to sign consent, 11 died before enrollment, 7 were not enrolled for other reasons, 2 refused to participate, 1 was previously enrolled, and 1 was not enrolled for unknown reasons.
As in the United States census, race-ethnic group was defined by self-identification. White and black (not Hispanic) were defined by skin color. Hispanics were defined as persons of Hispanic-Spanish origin or descent with light or dark skin. Individuals with mixed race-ethnicity were defined by the patient’s choice of a single ethnic group or the maternal ethnic group. Race-ethnic group was categorized into four groups: Hispanic, black non-Hispanic, white non-Hispanic, and other non-Hispanic.
A daily admission report was generated by the Clinical Information System Department (Presbyterian Hospital) and reviewed by the research team to identify eligible patients. Admission diagnoses with stroke, as well as a variety of other neurological syndromes (eg, transient ischemic attack, intracerebral hemorrhage, aphasia, hemiparesis, weakness, coma), were screened. A research assistant and a study neurologist screened the medical record to determine eligibility. After receiving permission from the attending physician, a member of the research team explained the study and obtained written consent from the patient and often the family. The protocol was approved by the Columbia University Institutional Review Board.
Index Ischemic Stroke Evaluation
Each patient was personally examined within 1 week of ischemic stroke onset by one of the study neurologists. Data were collected through in-person interview of the patient and family and by review of hospital records. Details of medical, neurological, and social history, stroke risk factors, general and neurological examinations, and laboratory studies were ascertained.
Pertinent historical variables identified on admission were hypertension, diabetes, hypercholesterolemia, prior stroke or transient ischemic attack, myocardial infarction, coronary artery disease, angina, congestive heart failure, atrial fibrillation, other arrhythmias, and valvular heart disease. Any cardiac disease was defined by a history of at least one of the above cardiac conditions. Hypertension was defined on admission when a patient or family stated that they been told of the diagnosis and was categorized as treated or untreated. Systolic and diastolic blood pressures were recorded after admission to the hospital rather than using the emergency department measurements, which are characteristically elevated above baseline levels. Cigarette smoking and ethanol use were recorded and characterized as current or not, and the amounts were recorded as packs per day and the usual number of drinks per day, week, or month, respectively. The initial cholesterol, hematocrit, and blood glucose levels available after ischemic stroke were recorded as continuous measurements.
Infarct Subtype Classification
Neurovascular evaluation on admission included computed tomographic (CT) scan of the head, electrocardiogram, extracranial duplex Doppler ultrasonogram, TCD scan, two-dimensional echocardiogram, Holter monitor results, and when available, findings from magnetic resonance imaging, conventional cerebral angiogram, and magnetic resonance angiogram. At the time of hospital discharge, a diagnosis was determined, taking into account all the available data to characterize each ischemic stroke by causal mechanism on the basis of a modified Stroke Data Bank scheme.13 Ischemic strokes were classified in the following categories: infarction due to atherosclerosis, embolism from a commonly accepted cardiac source, lacune, cryptogenic infarction, and stroke from other unusual causes.
Atherosclerotic stroke was attributed to perfusion failure distal to the site of severe stenosis or occlusion, or it represented cases where the stenosis was insufficient in itself to account for stroke on hemodynamic grounds but possibly served as an embolic source. This subtype characterized patients who usually presented with focal neurological symptoms and signs, brain imaging evidence of a superficial or large, deep infarction, and evidence of stenosis or occlusion detected by Doppler sonography or angiography. Atherosclerotic stroke was subdivided into extracranial or intracranial categories depending on the location of the stenosis or occlusion. Extracranial sites included the common and internal carotid arteries at the bifurcation and the extradural portions of the vertebral arteries. Intracranial sites included the internal carotid siphon, middle cerebral artery stem or branches, anterior cerebral artery, intradural vertebral artery, basilar artery, and posterior cerebral artery stem.
Classification as extracranial atherosclerotic disease required more than 60% stenosis in the symptomatic carotid artery or occlusion or high-resistance flow in the vertebral artery. Doppler criteria (Diasonics Inc) for stenosis or occlusion were 60% to 80% stenosis when the ratio of internal to common carotid artery velocity was >3.0 with no or minimal aliasing; 80% to 99% stenosis when the internal carotid artery peak velocity was >190 cm/s, turbulence was present, and aliasing was detected; occlusion when no flow was detected in a well-imaged artery lumen; and high-resistance flow when there was no detectable anterograde flow in diastole. TCD measurements were made of the middle, anterior, posterior cerebral, and basilar arteries using EME Carolina equipment with a 2-MHz probe. Segmental arterial velocities were recorded and compared on either side, with evidence of intracranial stenosis based on the finding of a significant asymmetry (ratio >2.0) between the peak velocities of the ipsilateral to contralateral arteries or a peak velocity >120 cm/s in the symptomatic artery. If conventional cerebral angiography or magnetic resonance angiography was performed, an occlusion or >60% stenosis of the symptomatic internal carotid origin or vertebral artery was required for the diagnosis of extracranial atherosclerosis; evidence of focal narrowing or occlusion of the symptomatic intracranial artery was required for intracranial atherosclerosis.
Patients with inadequate evaluations, conflicting data, or adequate evaluations that failed to confirm the initial impression of the stroke subtype were diagnosed as cryptogenic infarction. This ensured a more specific classification of the atherosclerotic diagnostic categories. For this analysis, patients were subdivided into three groups: infarction due to extracranial atherosclerosis, infarction due to intracranial atherosclerosis, and nonatherosclerotic infarction. The latter category consisted of the combination of cardioembolism, lacune, and cryptogenic infarction.
The distributions of certain variables identified on admission for index ischemic infarction were compared among the three diagnostic categories. Extracranial and intracranial atherosclerosis were compared separately from nonatherosclerotic infarction. Univariate analyses were performed, and significance was judged based on the χ2 test for categorical variables, Fisher’s exact test for instances in which the individual cells of a 2×2 table had counts less than 5, or the t test for continuous variables. Multivariate analyses were performed using a logistic regression model to identify factors simultaneously predictive of the diagnostic category. Variables were selected for entry if probability value was less than .10 after univariate testing or a priori. Modeling was done using the selected factors as independent variables and extracranial or intracranial atherosclerosis as the dependent variables. There was no assumption of multivariate normality for these covariates. The full set of potential factors was considered by stepwise elimination of those with probability values greater than .05. Odds ratios were calculated from the β coefficients and their standard errors.
Description of the Cohort
The cohort for this analysis consisted of 438 northern Manhattan residents over age 39 years hospitalized at Presbyterian Hospital for acute cerebral infarction and enrolled in the Northern Manhattan Stroke Study. The mean age at ischemic stroke was 70 years (range, 40 to 97 years; 71% aged 65 years or older), and 54% were women. Within the ethnically mixed cohort there were 197 Hispanics, 155 black non-Hispanics, 82 white non-Hispanics, and 4 classified as other non-Hispanic. Atherosclerotic stroke accounted for 17% of the index ischemic strokes, lacunar infarction 30%, cardiac embolism 21%, cryptogenic infarcts 31%, and other causes for 1%. Extracranial atherosclerotic stroke was diagnosed in 40 patients (9%) and intracranial atherosclerotic stroke in 33 (8%). The stroke diagnostic evaluations were extensive: 73% had more than one head CT scan, 92% had extracranial duplex Doppler, 75% had TCD, and 88% had echocardiography. Because the diagnosis of intracranial atherosclerotic stroke could be made on the basis of TCD findings, a greater proportion of patients with intracranial atherosclerotic stroke had TCD (91%) compared with those with extracranial (78%) and nonatherosclerotic stroke (74%). TCD was performed successfully in slightly more Hispanics (83%) than blacks (69%) and whites (68%). Cerebral angiography was performed in 48% of those diagnosed with extracranial atherosclerotic stroke, 45% of those with intracranial atherosclerotic stroke, and only 5% of those with nonatherosclerotic stroke.
Cerebral Infarct Subtypes and Race-Ethnicity
There were no differences in cerebral infarct subtypes by sex; however, infarct subtypes differed among the three race-ethnic groups (Figure⇓). Cardioembolism was more frequent in whites, and lacunes were more frequent in blacks and Hispanics. The proportion of extracranial atherosclerotic stroke was similar among the three race-ethnic groups: 11% of whites, 8% of blacks, and 9% of Hispanics. Intracranial atherosclerotic stroke was significantly more frequent in blacks and Hispanics than whites: 1% of whites, 6% of blacks, and 11% of Hispanics (P=.014). The ratio of extracranial to intracranial disease was 1.2 in blacks, 0.9 in Hispanics, and 9.0 in whites. Only 1 white patient had an intracranial atherosclerotic stroke. The unadjusted odds ratio for nonwhites (blacks and Hispanics combined) was 0.8 (confidence interval [CI], 0.4 to 1.8) for extracranial and 7.8 (CI, 1.04 to 57.7) for intracranial atherosclerotic stroke.
Among those with extracranial atherosclerotic disease, the internal carotid artery was more frequently affected than the vertebral artery in all three race-ethnic groups (Table 1⇓). There was an increasing proportion of vertebral artery stenosis or occlusion in Hispanics and blacks compared with whites. The one white patient with intracranial atherosclerotic stroke had basilar stenosis. Nearly half of the blacks with intracranial atherosclerotic disease had basilar stenosis, whereas the middle cerebral artery stem was the most frequent site for Hispanics.
Cerebral Infarct Subtypes and Vascular Risk Factors
Patients with intracranial atherosclerotic stroke were significantly younger than those with extracranial and nonatherosclerotic stroke (Table 2⇓). Patients with extracranial atherosclerotic stroke were slightly better educated than the other two groups. Untreated hypertension was slightly more prevalent in the atherosclerotic groups (Table 3⇓). Cardiac disease was slightly less frequent among those with intracranial disease compared with nonatherosclerotic stroke, but this was unadjusted for age.
A history of hypercholesterolemia was significantly more frequent among those with extracranial and intracranial atherosclerotic disease, and mean serum cholesterol level was significantly elevated among those with extracranial disease (Table 4⇓). The unadjusted odds ratio for hypercholesterolemia was 3.4 (CI, 1.7 to 6.5) for extracranial and 2.9 (CI, 1.4 to 6.0) for intracranial atherosclerotic stroke. Diabetes was most frequent among those with intracranial atherosclerotic stroke, intermediate with extracranial disease, and least among those with nonatherosclerotic stroke. Insulin-dependent diabetes was more prevalent in both extracranial and intracranial atherosclerotic stroke compared with nonatherosclerotic stroke, with unadjusted odds ratios of 3.1 (CI, 1.4 to 6.8) and 3.4 (CI, 1.5 to 8.0), respectively.
History of cigarette smoking and alcohol use was not significantly different among the three diagnostic groups; however, the mean number of drinks per week was significantly less in the extracranial atherosclerotic group. Claudication and transient ischemic attacks were more prevalent among those with extracranial compared with intracranial disease.
Independent Discriminators of Infarct Subtype
Prior analyses of this northern Manhattan cohort have demonstrated that the prevalence of risk factors differs among the race-ethnic groups. In particular, Hispanics had more diabetes, and blacks had a slightly higher mean cholesterol level (Table 5⇓). Logistic regression confirmed that younger age, history of hypercholesterolemia, and insulin-dependent diabetes were predictors of intracranial atherosclerosis. The odds ratio for the association of nonwhite (black or Hispanic) race-ethnicity and intracranial atherosclerosis was reduced from 7.9 to 5.2 (CI, 0.7 to 40) after controlling for age and to 4.4 (CI, 0.6 to 35) after controlling for age, education, insulin-dependent diabetes, and hypercholesterolemia (Table 6⇓).
Despite a decline in stroke mortality in all race-gender groups, the relative difference between races in stroke mortality has remained fairly uniform at nearly a twofold increase in stroke mortality in blacks compared with whites.14 Moreover, stroke is still among the major causes of the excess mortality among African Americans compared with mortality in whites.15 Differences in stroke subtype distributions by race-ethnicity may help account for some of the differences in overall mortality. Some have observed that the death rate from cerebral hemorrhage in blacks is about twice that of whites and that subarachnoid hemorrhage is at least twice as frequent in blacks.16 17 Because hemorrhagic stroke subtypes have greater case-fatality rates, any increase in the proportion of these stroke subtypes in a specific race-ethnic group would result in a greater overall mortality from stroke. The same would be true if certain cerebral infarction subtypes, associated with a worse prognosis, were more frequent in specific race-ethnic groups. However, few studies have had enough of a race-ethnic mixture to compare stroke subtypes in multiethnic groups in the same region.
The first observation regarding stroke subtype distribution in our cohort was that atherosclerotic infarction, whether extracranial or intracranial, accounted for only 17% of the cerebral infarcts. Extracranial atherosclerotic stroke was diagnosed in 9% and intracranial in 8%. This is less than the proportions reported in older studies, in which atherosclerotic infarction diagnoses were sometimes based on presumed mechanism without confirmatory laboratory data, and there was not a category of cryptogenic infarction. In the Northern Manhattan Stroke Study, if there were insufficient data to reliably categorize patients as atherosclerotic, patients were classified as having cryptogenic infarction. The frequency of cryptogenic infarction did not differ by race-ethnicity; however, lacunes were more frequent among blacks and Hispanics, and cardioembolism was more frequent among whites. These differences are a reflection of the increased frequency of hypertension and diabetes in blacks and Hispanics and of the increased frequency of ischemic cardiac disease among whites.
In our cohort, the proportion of extracranial atherosclerotic stroke was similar among the three race-ethnic groups, while intracranial atherosclerotic stroke was more prevalent in blacks and Hispanics compared with whites. Patients with intracranial atherosclerotic stroke were younger and had an increased frequency of hypercholesterolemia and insulin-dependent diabetes. The odds ratio for the association of nonwhite (black or Hispanic) race-ethnicity and intracranial atherosclerotic stroke was reduced from 7.8 to 5.2 after controlling for age and to 4.4 after controlling for age, education, insulin-dependent diabetes, and hypercholesterolemia. This implies that race-ethnicity is a determinant of intracranial atherosclerotic stroke, but that differences in stroke risk factors (particularly insulin-dependent diabetes and hypercholesterolemia) account for some of the effect.
Hispanics can now be added to the list of ethnic groups with an increased risk of intracranial atherosclerotic stroke. In northern Manhattan, the Hispanic cohort was similar to blacks with regard to stroke subtype distribution. In other studies, blacks have been found to be underrepresented among patients with carotid endarterectomies18 and have an increased frequency of intracranial occlusive disease.1 2 3 4 5 6 7 8 9 Japanese and Chinese patients also have been found to have an increased frequency of intracranial atherosclerotic disease.9 10 11 12 Autopsy studies of the circle of Willis have demonstrated that US blacks had significantly greater atherosclerotic disease of the intracranial vessels than US whites, while African blacks had the least amount of atherosclerosis.19 Other autopsy studies have confirmed these observations in blacks, as well as reported less atherosclerotic disease of the aorta and coronary arteries compared with whites.20 21 Angiographic studies have reported more atherosclerotic lesions of the supraclinoid carotid, middle, and anterior cerebral artery stems and basilar artery in blacks, while whites had greater atherosclerotic involvement of the internal carotid artery at the bifurcation, the origin of the vertebral artery, or the extracranial vertebral artery.1 2 3 4 5 6 7 The authors often acknowledge the problem of selection bias, which could influence the findings in any hospital-based study or clinical trial that requires an invasive procedure to arrive at the diagnosis. More recently, studies have used noninvasive techniques; one study has found race to be a significant independent risk factor for predicting carotid stenosis,8 whereas two studies have not found race-ethnic differences.22 23 Cross-sectional studies still have the problem of selection bias, since none have been community based and socioeconomic differences may confound the results. Even with noninvasive tests there can be some detection bias if the likelihood of undergoing a successful test such as TCD sonography differs by race-ethnic group. This could lead to differential bias in the diagnosis of intracranial atherosclerotic stroke. In our cohort, Hispanics were more likely to have successful TCD than blacks and whites, perhaps because of their younger age, which improved the ability to obtain a temporal window of insonation. This degree of diagnostic bias, however, would not account for the black-white difference in stroke subtype and is too small to account for the Hispanic-white difference.
Our cohort offers several advantages for the study of stroke subtypes. It is both hospital and community based, since all of our cases were from the immediate region surrounding the only hospital in the area. Our estimates indicate that 80% of all patients with ischemic strokes that occur in northern Manhattan were hospitalized at Presbyterian Hospital and that the proportion of nonhospitalized stroke is less than 10%. This helps to minimize selection and referral biases and maximize accuracy of stroke diagnoses and uniformity of acute-stage evaluations by race-ethnic group. In other ongoing studies, we are gathering information regarding patients with stroke who are not hospitalized at Presbyterian Hospital to evaluate stroke subtypes and ensure that our stroke sample is representative of the underlying population. The urban region also allows for the evaluation of black and Hispanic patients, often underrepresented in stroke studies.
Part of the difficulty in classification of ischemic stroke stems from the inability to discriminate between infarct subtypes on clinical grounds alone. In the Stroke Data Bank, some clinical characteristics were helpful in distinguishing infarct subtypes; however, clinical features that were observed at stroke onset were not reliable enough to lead to a definite determination of infarct subtype without confirmatory laboratory data.24 25 The choice of diagnostic laboratory tests may be influenced by physician bias, safety considerations, availability of certain technologies, and socioeconomic considerations. Studies that rely on cerebral angiography to diagnose cerebral atherosclerosis could be more susceptible to such selection biases, particularly if the decision to pursue an angiogram in a patient with cerebral infarction was differential across race-ethnic groups. The use of noninvasive tests for the determination of cerebral infarction subtypes has helped minimize concerns about patient safety and eliminate race-ethnic selection biases. Moreover, TCD and magnetic resonance angiography have made the diagnosis of intracranial atherosclerotic infarction possible without the use of conventional cerebral angiography. In the Northern Manhattan Stroke Study, atherosclerotic stroke subtypes were diagnosed based on the frequent use of such noninvasive tests.
The explanation for the increased frequency of intracranial atherosclerotic stroke in black, Chinese, Japanese, and Hispanic individuals is not known. Genetic differences may play some role, but given the diversity of these population groups it seems unlikely that they would share a common genetic explanation that could promote intracranial atherosclerosis. In northern Manhattan, blacks and Hispanics were younger, had a greater frequency of hypertension and diabetes, were more obese, and had a decreased prevalence of cardiac disease compared with whites. Because some of these factors are clearly independent predictors of intracranial atherosclerotic stroke, they account for part of the increased risk of this stroke subtype in certain populations who have a greater prevalence of these conditions. Interactions among these risk factors could be particularly important but are difficult to detect without larger sample sizes. Alternatively, the absence of a particular set of risk factors or the protective effect of some factor, as yet undetermined, may account for the lack of intracranial atherosclerotic disease among whites.
Prior cross-sectional studies that have reported on racial differences in intracranial atherosclerotic stroke have also documented an increased prevalence of certain stroke risk factors in these race-ethnic groups. Some of the angiographic studies have found that hypercholesterolemia and ischemic heart disease were more frequent in whites, while hypertension and diabetes were more frequent in blacks.3 9 However, race-ethnicity still had retained an effect even after these conditions were controlled for in the analyses. Other potential stroke risk factors that have not been investigated but could also help account for race-ethnic stroke subtype differences include diet, lipoprotein(a) levels, cholesterol fractions, coagulation factors, homocysteine, and level of stress. Further study in population-based cohorts should help provide other answers to these race-ethnic disparities in stroke subtype.
This work was supported by grants from the National Institute of Neurological Disorders and Stroke (R01-NS-27517, R01-NS-29993, and T32-NS-07153).
Presented in part in abstract form at the 19th Joint Conference on Stroke and Cerebrovascular Disease, San Diego, Calif, February 17-19, 1994.
- Received August 19, 1994.
- Revision received October 17, 1994.
- Accepted October 17, 1994.
- Copyright © 1995 by American Heart Association
Heyden S, Heyman A, Goree JA. Non-embolic occlusion of the middle cerebral and carotid arteries: a comparison of predisposing factors. Stroke. 1970;1:363-369.
Gorelick PB, Caplan LR, Hier DB, Parker SL, Patel D. Racial differences in the distribution of anterior circulation occlusive disease. Neurology. 1984;34:54-57.
Gorelick PB, Caplan LR, Hier DB, Patel D, Langenberg P, Pessin MS, Biller J, Kornack D. Racial differences in the distribution of posterior circulation occlusive disease. Stroke. 1985;16:785-790.
Gorelick PB, Caplan LR, Langenberg P, Hier DB, Pessin M, Patel D, Taber J. Clinical and angiographic comparison of asymptomatic occlusive cerebrovascular disease. Neurology. 1988;38:852-858.
Caplan LR, Gorelick PB, Hier DB. Race, sex and occlusive cerebrovascular disease: a review. Stroke. 1986;17:648-655.
Caplan L, Babikian V, Helgason C, Hier DB, DeWitt D, Patel D, Stein R. Occlusive disease of the middle cerebral artery. Neurology. 1985;35:975-982.
Gil-Peralta A. Alter M, Lai SM, Friday G, Otero A, Katz M, Comerota AJ. Duplex Doppler and spectral flow analysis of racial differences in cerebrovascular atherosclerosis. Stroke. 1990;21:740-744.
Brust RW. Patterns of cerebrovascular disease in Japanese and other population groups in Hawaii: an angiographical study. Stroke. 1975;6:539-542.
Nishimaru K, McHenry LC, Toole JF. Cerebral angiographic and clinical differences in carotid system transient ischemic attacks between American, Caucasian, and Japanese patients. Stroke. 1984;15:56-59.
Foulkes MA, Wolf PA, Price TR, Mohr JP, Hier DB. The Stroke Data Bank: design, methods, and baseline characteristics. Stroke. 1988;19:547-554.
Cooper R, Sempos C, Hsieh SC, Kovar MG. Slowdown in the decline of stroke mortality in the United States, 1978-1986. Stroke. 1990;21:1274-1279.
Cooper ES. Clinical cerebrovascular disease in hypertensive blacks. J Clin Hypertens. 1987;3(suppl):79S-84S.
Maxwell JG, Rutherford EJ, Covington D, Clancy TV, Tackett AD, Robinson N, Johnson G. Infrequency of blacks among patients having carotid endarterectomy. Stroke. 1989;20:22-26.
Ryu JE, Murros K, Espeland MA, Rubens J, McKinney WM, Toole JF, Crouse JR. Extracranial carotid atherosclerosis in black and white patients with transient ischemic attacks. Stroke. 1989;20:1133-1137.
Cohen SN, Goldman C. Comparison by duplex scan of racial differences in stroke risk factors. Ann Neurol. 1991;30:280-281.
Timsit SG, Sacco RL, Mohr JP, Foulkes MA, Tatemichi TK, Wolf PA, Price TR, Hier DB. Early clinical differentiation of cerebral infarction from severe atherosclerotic stenosis and cardioembolism. Stroke. 1992;23:486-491.
Kittner SJ, Shakness CM, Price TR, Plotnick GD, Dambrosia JM, Wolf PA, Mohr JP, Hier DB, Kase CS, Tuhrim S. Infarcts with a cardiac source of embolism in the NINCDS Stroke Data Bank: historical features. Neurology. 1990;40:281-284.