- Email: [email protected]
ethnic disparities in stroke
Seminars in Cerebrovascular Diseases and Stroke Vol. 3 No. 2 2003
The Epidemiology of Stroke Outcomes Research: Illustration of an Approach to Outcomes Methodology Using Racial/Ethnic Disparities in Stroke R O N N I E D. H O R N E R Bethesda, Maryland
ABSTRACT Stroke is associated with numerous health outcomes, the study of which is important for identifying best practices. However, it is equally important to understand the process to generating that knowledge. The methodological approach to stroke outcomes research is founded on first principles of epidemiological inquiry. These principles include defining the inquiry through a conceptual model; identifying and prioritizing the fundamental research questions; systematically addressing the research questions in order of importance; and exploring possible nuances to identified associations. To illustrate these principles in practice, the line of investigation into the reasons for racial/ethnic disparities in stroke mortality is used as a case study. Key words: cerebrovascular accident, epidemiological methods, ethnic groups, outcomes assessment (health care), racial stocks.
Stroke is associated with a broad array of health-related effects: physical, psychological, social, financial, and symptomatic, which often become permanent deficits. 1 A systematic study of these associated effects has numerous uses. Of the most obvious use, this type of study may yield clues to "best practices" (ie, clinical treatment practices that are associated with improved outcomes). Conversely, it may identify practices to be avoided or "worst practices." Another important product of the study of health outcomes, when conducted in a natural history context, is a baseline level by which to compare new therapies or practices. Epidemiology, as the study of the occurrence of illness, provides one approach to the systematic study of the health outcomes associated with stroke as well as those associated with other health conditions. Through first principles of ep!demiologic inquiry, we may come to
appreciate not only the consequences of a disease, such as stroke, but also may identify points of intervention and the array of possible interventions for those points. It is this latter product (ie, the generation of new knowledge for the purpose of intervention) that is the relatively more important objective of epidemiologic research because, as the scientific arm of public health, the goal of epidemiologic research is to promote health, prevent disease, and reduce or eliminate the negative sequelae of disease. Although knowledge of stroke-related outcomes, per se, is important, it is equally important to understand the process to generating that knowledge. Thus, although there is an epidemiology of stroke outcomes, we also have an epidemiology of stroke outcomes research in which the focus is on the approach by which to generate the knowledge regarding those outcomes. It is this latter epidemiology that is of interest here. We will examine the fundamental principles of stroke outcomes research. This examination is illustrative in nature (ie, these fundamental principles are illustrated by examples from the relevant literature on stroke and, specifically, from the line of research that seeks to explain racial and/or ethnic-related disparities in stroke occurrence and strokerelated health outcomes). Disparities in stroke represent an
/
From the NINDS~IH, Neuroscience Center, Bethesda, MD.
Address reprint requests to Ronnie D. Homer, PhD, NINDS/NIH, Neuroscience Center, Room 2149, 6001 Executive Blvd, Bethesda, MD 20892-9535 (For express mail, use Rockville, MD 20852). E-mail: [email protected] 9 2003 Elsevier Inc. All rights" reserved.
1528-9931/03/0302-0002530.00/0 doi: 10.1053/scds.2003.0015
67
68
Seminars in Cerebrovascular Diseases and Stroke Vol. 3 No. 2 June 2003 I
l
C,n,o,
I
Disease
II
~ ,~
I
Clinical Ha r izon
~
,., I
7
__J --
I9 Chronicity
--
/
'/.
~ / / 7 7 / . ~ / / / / / /I /\ J
InaPoPraren Subclinical~
k I
/ ''/B
'
inapparent 1~ ' ' ~ . condition
/^ I / ~ - , ~ , ab.br.tive.'~ !/ ",,-condition ~'
f
I
',
PRE
i
\
I
I
Residual Disability
"~"-
\
I I I i
Outcome; Death
\ \~C ~. ,
,
>.
I DISABILITY
STAGE OF.DISEASE SUSCEPTIBILITY I. -I CLINICAL DISEASE J I -. I TISSUE Ii Pre I I CHANGES I Pothogenesis ~ PothogenesiS I .I I LEVEL OF I i i I Primary I Secondary I Tertiary PREVENTION t tI . . . . I ~l''" Treatment and MODES OF IHealth Promotion Detection I ,(1-- Rehabilitation INTERVENTION I Specific I Early I I Protection I Diagnosis I Limitation I I Prompt I of Disability I i I I ~ Treatment I
I RECOVERY. ........... ~11 Resolution or I Sequeloe I , I , ,.. I, , II ,= t " i I I I
I II i I
Fig. 1. Schematic of the natural history of disease. Reprinted from Epidemiology: An Introductory Text, 2nd Edition by Mausner and Kramer with permission from WB Saunders, Inc.
intriguing and important social and scientific issue, not only because of the magnitude of observed disparities (eg, an almost 2-fold higher stroke mortality in African Americans vis-h-vis white Americans) but also because of the persistence of those disparities for decades, despite a general decline in stroke mortality.2 Moreover, from an epidemiclogic perspective, those groups having the disparities may be regarded as high-risk groups and, hence, investigation into the reasons for the increased burden of disease may yield information that can be used to reduce stroke incidence or mortality in the larger, national population, as well as among those within the high-risk group. ,
A First Principle: Define the Inquiry through Conceptual Models Racial/ethnic disparities in stroke outcomes exist broadly, ranging from the occurrence of stroke, the most fundamental of outcomes, to burden of disease, as reflected by mortality and, among survivors, residual stroke-related deficits and recurrent stroke. In this arena, the research focus is on the explanation of the observed difference~ so that effective interventions might be identified to reduce or eliminate the disparities in outcomes. If the inquiry is to be systematic and, hence, thorough, a
conceptual model is essential because it ensures that all key research questions are identified, the (anticipated) explanatory factors and the (anticipated) linkage of those factors are delineated, and that a foundation exists on which to interpret the findings. Natural History for Epidemiologic
of Disease: Studies
A Model
On a number of counts, the natural history of disease is a preferred conceptual framework for organizing the investigation of disparities in stroke outcomes (Fig 1). For one, the research issues can only be answered through observational studies, which is epidemiology. For another, and of particular note, are the 3 phases of the framework: the predisease or presymptomatic phase, the clinical phase, and the sequelae phase that are tied explicitly to levels of intervention. It is intervention to reduce or eliminate the disparities that is the ultimate goal of this line of inquiry) Thus, the first phase is the arena of primary intervention, most often referred to as prevention, in which the focus is on the promotion of health and prevention or delay of disease onset. Stroke incidence is our concern here. Etiologic studies and studies of risk factors and their modification are types of scientific research
The Epidemiologyof StrokeOutcomes Research 9 Horner 69
HealthCareReceivedII i
&
PatientFactorsper HealthDecisionModel l
PatientSociodemographics~
.?
-I C Recommenda. Uon(s) Regarding HealthCare ~
HealthCareProvider's Attitudes,Beliefs,and OtherFactors(Financial, Organizational)
Patient'sClinical I Presentation~A I HealthCareProvider's Knowledge,Experiences, andPreferences RegardingHealthCare
Fig, 2. Conceptual model of the interaction between the patient and provider within the health care system: key components and points of intervention (A, B, C).
activities that target this phase. These studies of risk factors may include basic neuroscience studies, such as studies that explore the genetic contribution to disease occurrence and gene-environment interactions. Case fatality and residual deficits and, hence, practice patterns, are concerns of the last 2 phases. The clinical phase is that of early detection (ie, screening) and early intervention to minimize sequelae. This is the phase of secondary prevention. The third phase, disease sequelae, is the tertiary intervention phase. The objective of this latter phase is to minimize problematic outcomes of disease, which range from disability to death, and to maximize positive outcomes (eg, recovery of function). The outcomes associated with this phase are the outcomes that typically come to mind when outcomes research is mentioned (eg, death, physical and psychological disability).
Enhancement of the Natural History of Disease Model for Investigation of Practice Patterns For studies of practice patterns, whether or not related to race/ethnicity, the natural history model needs to be augmented with a more detailed model of the patientprovider-health system interaction that "drives" the use of health care practices. One model for guiding the investigation of outcomes associated with various practices is that shown in Figure 2. It relies heavily on the health decision-model and provides the more precise view of the patient-provider interaction. 4,5 An earlier version of this model was used to organize the an'ay of considerations for understanding racial/ethnic differences in the use of carotid endarterectomy. 6 Carotid endarterectomy, and other procedures to diagnose and
treat stroke and other cerebrovascular diseases are well documented to show racial variation in use with higher use in white patients, despite the apparent higher need in blacks because of the burden of stroke. 7 Under the proposed model, key components to consider for explaining the lower usage in African Americans include the patient's ability to access health care, presenting signs and symptoms, the provider's gathering, evaluation and filtration of the evidence and assortment of options, and the negotiation between patient and provider for the care to be received. The structured line of inquiry is designed to examine systematically the potential explanations proposed for the observed disparity in health care use, beginning with the most plausible or, perhaps, the least disconcerting explanation. Thus, the initial point of departure is to determine if there are racial differences in clinical indications for the procedure. The question is, do blacks receive carotid endarterectomy less often because the prevalence of indications is lower (ie, insignificant carotid stenosis), or the risks of the procedure outweigh the benefits? As each proposed explanation is refuted, the next one is examined. Of course, it must be recognized that if one explanation fails to be rejected, this does not necessarily exclude "higher order" explanations. More than one explanatory factor may be operating and, more subtly, a given causative factor may be obscured by another factor, only to emerge after that factor is rectified.
Another First Principle: Fundamental Research Questions Are a Priority Although this principle may seem obvious, it is amazing how often some fundamental research questions are
70
Seminarsin Cerebrovascular Diseases and Stroke Vol. 3 No. 2 June 2003 IIIAfr. Am.
E]White
_
IIIMr. Am.
E]White
2O
10 5 0
1980
1999
Stroke Hospitalizations (per 1,000 population)
1980
1999
In-hospital Mortality (per 100 Stroke Discharges)
Source: Adapted from [9]
Fig. 3. Racial differences in stroke: incidence and case fatality rates by patient face/ethnicity.
either neglected or assumed answered. In the inquiry into racial/ethnic disparities in stroke, one dominating issue concerns the role of stroke occurrence as an explanation of the 2-fold higher mortality from stroke overall and within stroke types in African Americans. s The disparity in stroke mortality may be a function of disparities in the incidence rate (ie, occurrence) or the case fatality rate (ie, survival), or both. This result is an important, fundamental issue because the source of the higher mortality suggests the most useful intervention point(s) and the associated interventions. If the disparity in mortality derives from a difference in incidence, this argues for stroke prevention programs. If case fatality is the more important source of the mortality difference, this suggests programs focused on improving patterns of care. Because of the relationship among incidence, survival, and mortality, if either incidence or case fatality can be excluded, then the other must be responsible. On the other hand, if one is included, the other will have to be examined because it also may be contributing to mortality. The evidence as it is currently emerging suggests that disparity in stroke incidence, more than in case fatality, is responsible for the higher stroke mortality observed in African Americans. National data using hospitalizations as a measure of incidence and in-hospital mortality (ie, case fatality), indicate the rate of hospitalization for stroke has been persistently higher for African Americans than white Americans and, disturbingly, may have increased between 1980 and 1999 in African Americans, while decreasing for white Americans (Fig 3). 9 In-hospital mortality,, by comparison, was lower for African Americans a~d remained lower over the 20-year period. The Northern Manhattan and Cincinnati cohort studies support these findings and conclusion and, because of their more rigorous study designs, may be considered to provide more convincing evidence. 1~ Investigations of
incidence versus case fatality require a study design that can generate rates and, therefore, that involves a defined at-risk population (ie, denominator) and complete (or nearly complete) ascertainment of events, whether stroke, per se, or death in the patients who had a stroke (ie, numerator). The cohort study is an ideal design for these investigations in which the cohort is comprised of all patients who had a stroke within a defined population. Typically, the cohort of patients who had a stroke is comprised of those presenting at the hospital(s) serving a given population. This result is justified by the assumption that virtually all patients who had a stroke, including those who die of their stroke outside the hospital, will present at one of the hospitals. The assumption is a reasonably valid one, at least in the United States. 12 This type of design is elegant in its simplicity, allowing the investigator to address both the issue of incidence rates and case fatality rates. For the evaluation of incidence rates, the denominator is the population within the hospital(s) service area, with the hospitalized patients who had a stroke becoming the denominator for the study of stroke survival. Review of the medical or hospital records may be used if there is a need to distinguish between first and recurrent stroke.
E x p l o r e N u a n c e s of a n A s s o c i a t i o n : A n o t h e r First Principle These findings of similar stroke case fatality rates among racial/ethnic groups may not be as clean-cut as one might hope. Although the overall rates appear similar, further inquiry reveals that age is an important modifier (Fig 4). 9,13 Although stroke fatality rates were similar among African Americans, Hispanics, and white Americans 65 years or older, African Americans and Hispanics younger than 65 years had substantially higher early poststroke mortality rates, compared with younger white Americans. However, the higher mortality did not persist at 1-year poststroke, suggesting that the source may be with acute care rather than care in the postdischarge setting. L3 This finding of age as a modifier of the association between race/ethnicity and the stroke case fatality rate presents yet another line of inquiry, and illustrates that, while exploring racial variations and other risk relationships in disease, the investigator should examine associations closely to be certain that subtleties of the relationship axe not missed. To understand differences better in stroke case fatality rates, or the lack thereof, factors in addition to age, specifically stroke characteristics such as stroke type, severity, and whether it is a first event, are potential modifiers or confounders of observed outcomes. This observation leads to many important questions. For example, small-vessel strokes that tend to have a better prognosis are more common in African Ameri-
The Epidemiologyof Stroke Outcomes Research 9 Horner 71 cans. However, hemorrhagic strokes that have a worse prognosis are also more prevalent in African Americans. 14 Is the distribution in stroke types confbunding the case fatality rate in older patients who had a stroke? Is the case fatality rate for specific types of stroke (eg, lacunar strokes) similar among the various racial/ethnic groups? Answers to these types of questions will indicate whether there is confounding or modification of the association between race and the case fatality rate for stroke with or without adjustment for age. Efforts to determine whether stroke severity might explain racial differences in stroke outcomes have been few in number. Early studies that used proxy measures of severity (ie, case fatality rate and residual disability) established the possibility of racial/ethnic differences in stroke severity. 15,16The latter study was a secondary data analysis of a prospective cohort study design that showed that African Americans had a clinically significant 9.5% lower Fugl-Meyer score, a measure of physical impairment, than white Americans at 180 days poststroke. 16 Secondary analysis can be an efficient strategy for generating an assessment of a hypothesized association, if only an initial one. It is typically only an initial assessment because the database has one or more design features that, for the proposed research question, represent methodological shortcomings. This situation is to be anticipated, a consequence of the original study not being designed to answer the proposed research question. Of the potential limitations, the preferred measure of the outcome may not be present, or the measure of the key explanatory variable may be absent. Thus, the investigator has to be creative by using proxy variables. Another common methodological limitation is insufficient sample size, especially when the original study was not explicitly interested in the now desired subgrouping. In the study cited, as noted, there were measures of physical and functional impairment: the FuglMeyer and Barthel Index, respectively. However, the sample size for African Americans may not have been optimal (n = 41) and data on stroke subtypes were not available. Although racial differences were found for physical impairment, no statistically significant differences were found for functional impairment, although ability to perform activities of daily living was lower, on average, among the African American stroke survivors. Why physical impairment did not translate into obvious functional impairment could be a consequence of shortcomings within the measure used (ie, ability of the measure to reflect clinically important impairment) or confounding due to failure to adjust for important differences in the stroke or other reasons. Clearly, further inquiry is necessary to understand fully whether differences in stroke characteristics explain the observed racial differences in case fatality rates for stroke.
Of other methodological improvements, future studies will need to examine more precisely the issue of race and stroke severity through direct measures of severity. For the reasons indicated previously, stroke subtype is an especially important characteristic to include in these studies because the risk of death varies with the type of stroke. This type of a more precise study was conducted as a secondary analysis of a cohort composed of veterans with stroke, in whom stroke severity was measured by a retrospective chart-based measure: the modified Canadian Neurological Scale. 17 (A prospective severity scale may be preferable generally but obviously was not feasible for this secondary analysis.) Stroke type (ie, ischemic versus hemorrhagic) was also included in the model, but inclusion of subtypes of ischemic strokes would have been an even better modeling strategy. A modest but statistically significant difference in stroke severity was found. The average (ie, unadjusted) stroke severity score was 7.96 for African Americans and 8.32 for white Americans (P = 0.035). However, Afiican Americans did not have a significantly worse in-hospital mortality rate (12.7% versus 9.5%, respectively; P = 0.12) nor were they significantly more likely to be admitted to intensive care (23.6% versus 18.7%, respectively; P = 0.08). The lack of statistical significance on these latter outcomes detracts from the ability to conclude convincingly that severity has a role explaining racial differences in case fatality rates. Moreover, although age and stroke type were associated with severity, the model did not include interaction terms, especially the race-age interaction with the case fatality rate that was shown previously. A logical follow-up to the findings is age or stroke subtype-specific analyses. Of particular importance, there should be studies of racial/ ethnic differences in severity among younger patients who had a stroke. Although modest, the difference in severity may also be associated with a difference in residual physical or, perhaps, psychological deficits. These questions also remain to be explored fully. The use of extant databases is an established research practice to gain preliminary insights but is often hampered by the absence of specific key variables in the data set. Thus, large hospital or other administrative health care databases (eg, Medicare, Medicaid data) may lack details on stroke characteristics (eg, stroke severity, subtype). This is a situation in which a proven proxy variable could enhance any analyses involving those databases. In this regard; a reasonable case has been made for the use of mechanical ventilation as a proxy for coma (ie, severe stroke), with due consideration to the caveats in interpretation. ~8,~9 Perhaps the more important contribution of this research was to show a methodological approach to conducting proxy-identification studies. The search for the proxy variable should be predicated on a conceptual framework so that there is a theoretical (with
72
Seminarsin Cerebrovascular Diseasesand Stroke Vol. 3 No. 2 June 2003
empirical support) basis for targeting one or more proxy variables for evaluation.
Phase 2: Following Up on the Logical Next Questions The role of practice patterns (ie, variation in acute and postacute care, including the use of rehabilitation) remains a promising area of inquiry for understanding the complicated association between race and case fatality rates for stroke. In this area of inquiry, the research questions deal with the entire spectrum of care, beginning with time from stroke onset to presentation, through rehabilitation and into care received in the postdischarge environment. Extant databases may be useful for providing preliminary data on best practices, especially when important clinical data (ie, characteristics that would be considered by the attending physician for determining care) are included directly or as proxy variables. However, as is all too apparent, highly detailed clinical data are not often present, especially in the large national surveys or medical administrative databases and, hence, observed associations may not hold when a more precise assessment is made. Again, cohort studies tend to be a preferred study design, but care must be taken to ensure that the cohort represents the population at risk. Thus, for example, studies of time to hospital care could provide a biased estimate if based on patients who had a stroke and were admitted to the hospital (ie, stroke survivors).
Beginning at the Beginning: Time to Presentation Time to presentation may be an important determinant of the array of therapies available to the provider to treat effectively the patient who had a stroke. A delay in the patient with an acute stroke presenting at the hospital is one aspect of the broader issue of delay in receipt of appropriate care. Delay in the receipt of care, even postacute care, may be a strong modifier of health outcomes. For example, the timely use of stroke rehabilitation units is associated with improved survival in the immediate discharge period, and this survival advantage is retained for years. 2~ Studies of time tO presentation are important in that tPA, a proven effective acute therapy, requires that the patient present promptly after stroke onset (ie, within 3 hours). There is recent evidence of a racial disparity in the use of tPA, 21 and delayed presentation has been offered as one' of several alternatives to racism as explanations for,.this disparity.22 However, several studies have yielded conflicting results in this area. Some recent studies have found that African Americans and white Americans arrive within approximately the same time,
on average. 23,24 One study found that African Americans presented slightly earlier, on average, but waited slightly longer for initial care within the emergency department (Fig 5). 23 Another of these studies discovered that African Americans presented significantly later than white Americans, 24 but this initial race effect disappeared with adjustment for other factors, including younger age, less severe stroke, no history of stoke, and failure to use the emergency medical system. Perhaps this literature is relevant to understanding the racial differences in case fatality rates when stratified by patient's age. Piecing together these reports with evidence on the effectiveness of community-based stroke awareness campaigns, some investigators have concluded that younger individuals and those with "milder" symptoms may not fully appreciate the presenting symptoms and signs of stroke, and, so, may delay seeking care. 25 These findings may be used to identify points of intervention that may yield reductions in stroke mortality in younger African Americans.
Race, Provider, and Acute Stroke Practices Beyond time to presentation, differences in acute and postacute care practices within the hospital may also explain any racial disparities in outcomes. The author saw that at least one report indicates that use of tPA differs by the patient's race, although it may be a function of time to presentation. 21,22 However, it is also becoming clear, for example, that patients who had a stroke who are under the care of neurologists have improved outcomes, although there is only a partial understanding of the reasons for this phenomenon. 26,27 For the topic at hand, the question is: Are African Americans systematically less likely to be under the care of neurologists? The answer to this research question remains to be determined, although a study of racial differences in stroke care within Department of Veterans Affairs (VA) hospitals indicated a similar proportion of African American and white patients who had a stroke, were under the care of a neurologist. 28 However, because the VA health care system is an equal-access system for those patients who qualify, this finding may not hold within the private health care sector. It should be noted that, when multiple hospitals are involved, differences in the racial composition of the hospital catchment area populations could confound an association. Studies that focus on specific practices during the hospital stay are a logical follow-up to the intriguing finding that improved outcomes are associated with neurologic care. These studies could use similar methodology, as used in the studies of neurologists versus other providers in stroke outcomes (ie, any use of a particular diagnostic or therapeutic procedure). In a very recent report, no racial differences were found in the use of
The Epidemiology of Stroke Outcomes Research 9
specific key acute stroke practices? a However, again, because the cohort was composed of veterans who were hospitalized within VA hospitals, the patterns may not hold within the private health care sector. If acute care practices do not differ by the patient's race, postacute care practices may. Studies of racial differences in the use of rehabilitation have ranged from those using the large, detail-poor databases, like the Medicare data, 29 to studies of cohorts that are well characterized clinically but may have less detailed data on specific practices) ~ In general, these studies indicated that African Americans may be slightly m o r e likely to gain access to rehabilitation. The adjusted relative likelihood of receiving inpatient rehabilitation for African American as compared with white Medicare patients who had a stroke was 1.06 (95% CI = 0.93, 1.33; P = 0.22), a finding similar to that in African American and white patients who had a stroke and were seen at V A hospitals, in which the adjusted relative odds were 1.28 (P : 0.13). 29,3o However, time to initiation of the rehabilitation was relatively longer for black patients than white patients (4.4 versus 3.8 days, respectively; P < 0.05), and those who had a delay had relatively worse functional recovery, as measured by the ability to perform activities of daily living. 3~ However, closer inspection of the associations indicated that it was in socioeconomically poorer African Americans that the delay occurred, and it was in this group that recovery in physical function was slower and to a lower level. Data on specific rehabilitation practices were not available in the dataset, so racial differences in the quality of rehabilitative care could not be assessed. Curiously, functional level at discharge was similar in all groups: higher and lower socioeconomic status white and African American patients. Other studies also show similar levels in functioning at initiation and discharge from rehabilitation among whites and African Americans. 31,32 This result would seem to suggest that race and socioeconomic status are interacting in the postdischarge sit-
Horner
73
5 4
o 3~ "6
3
6 ~'
2
C
IIAfr. Am, DWhite
o
i
Pre-Hosp.
i
Within ED
Total
Source: Adapted from [24]
Fig. 5. Racial differences in time to presentation at the hospital and wait time within the emergency department.
uation to modify the benefits of rehabilitation. Again, this is another line of inquiry reaffirming that race-based nuances in the patterns and outcomes of stroke rehabilitation exist that might not be apparent without more detailed study. A similar story is found for practices targeted at the prevention of future stroke, whether first or subsequent strokes. A series of investigations into racial/ethnic differences in the use of carotid endarterectomy is representative of the systematic exploration of an issue that is necessary to understand fully racial/ethnic disparities in practice patterns. Based on hospital discharge data from the VA health care system, disparities were found in use of the procedure that were similar to those occurring in the private sector (Fig 6). 33 This is an important finding, because the VA system, beyond being an equal access system for those who are eligible, has minimal financial incentives for providers to perform procedures because the providers are salaried. Thus, many financial consid-
I
Non-VA
Carotid A n g i o g r a p h y
50
I
VA
40
9
Am.
[]Hispanics
[]Whites I Non-VA
30
I-TWhites [] Hispanics IIAfr. Am. Carotid Endarterectomy
~= 20
VA
~10
0
r
0 40-69 yrs.
70+ yrs
Source: Adapt:ed from [13]
Fig. 4. Patient race/ethnicity and stroke case fatality rate: modifying effect of age.
20 40 60 Rate per 100 patients
80
Sources: Adapted from [33] ands unpublished data from Academic Medical Center Consortium
Fig. 6. Racial/ethnic differences in the use of carotid angiography and carotid endarterectomy: Department of Veteran Affairs (VA) versus academic medical center (non-VA) hospitals.
74
N,sh,te
Seminarsin Cerebrovascular Diseasesand Stroke Vol. 3 No. 2 June 2003
erations that may affect patterns o f care in the private health care sector are believed to be minimal within the VA health care system. Subsequent cohort studies were performed to "ferretout" the reasons for the 2 to 3-fold higher use in white than in black patients. In conformity with the conceptnal model, 6 these studies begin, logically, with the most obvious factor (ie, clinical indications), and find that clinical factors cannot fully explain the differences observed. 34 Inquiries of patient and provider perceptions of carotid endarterectomy reveal that patient concerns about invasive therapies is an additional factor to clinical indication. 35,36 Although it is tempting to quit at this point, there is a next step and that is to determine why the patient concerns exist. The model of patient-provider interaction (Fig 2) suggests ways the next generation of studies might unfold to identify points of intervention to ensure that patients who would benefit from a particular procedure (eg, carotid endarterectomy) will not have barriers to receiving it. It may be worth noting that among patients of the VA health care system who receive carotid endarterectomy, similar outcomes are experienced, suggesting a similar quality of c a r e s
Stroke Incidence and Racial Disparities: Risk Factors as Guides to Prevention Previously, it was argued that the substantial racial/ ethnic difference in stroke mortality was more a consequence of stroke incidence than case fatality9 When the issue is incidence, as previously noted, the objective is prevention9 As shown in the natural history of disease model, prevention is keyed to the presymptomatic phase of disease and, hence, to modification of the risk factor profile because disease is not a random occurrence but a function of person, agent, time, and space. 3~ Thus, the focus of this line of inquiry is to determine if the racial/ ethnic disparities in stroke incidence are attributable to 9 i, disparities in the prevalence of estabhshed risk factors, a differential effect of these risk factors, or unique risk factors9 For example, theoretically, it is postulated that hypertension and ather0sclerosis may operate differently in African Americans than white Americans and, may in part, explain the observed differences in stroke subtypes. 39,4~ Support/for this hypothesis is found in the large database studies from which there is indication that known risk factors, particularly hypertension and diabetes mellitus, may be more important in disease etiology in African Americans than white Americans. 4~ There is further evidence from established stroke cohorts that the well-known stroke risk factors might have differential importance among racial/ethnic groups9 Hypertension and diabetes mellitus appear to be more im-
4O ~10re2030~ zzAfr.~A~ []H 0
~
HTN
DM
CAD
Inactive
Source: Adal:Cedfrom [42]
Fig. 7. Racial/ethnic differences in the impact of reducing selected stroke risk factors.
portant stroke risk factors for African Americans and Hispanics, while coronary artery disease and atrial fibrillation are more important ones for white Americans, and physical inactive is similar in prevalence among racial/ ethnic groups. 4a Moreover, there is a race/ethnicity-specific hierarchy to the etiologic importance of the risk factors that may not be fully correlated with their prevalence (Fig 7). Furthermore, differences in stroke risk profiles appear to exist between men and women within racial/ethnic groups. 43 Thus, although hypertension, diabetes mellitus, and physical inactivity are potent risk factors for stroke in African American men and women, these factors were relatively more important for African American women. Smoking cigarettes, on the other hand, appears to be a substantially more potent risk factor for African American men than women. This knowledge argues for the tailoring of intervention programs, not only on race/ethnicity, but sex and probably age, as well. In addition to these well-established risk factors for stroke, unique factors may also be involved, at least among some racial/ethnic groups9 For example, there is emerging evidence that societal racism may contribute indirectly to the high stroke rates in African Americans through effects on blood pressure. 44 Although identification of the unique factors is intellectually challenging, the pragmatism of this effort remains to be determined9 Is it possible to eliminate discrimination in a society? The answer is probably not in the short term. Therefore, the most pragmatic approach to reducing stroke incidence in African Americans may be to target those factors in which there are proven interventions and to seek ways to implement more effectively those interventions in culturally diverse populations. At this point, we move back to the realm of stroke prevention practices and ways that interventions proven to be effective (eg, blood pressure control) might be more effectively implemented in African American and Hispanic populations9 Those patients at highest risk for
The Epidemiology of Stroke Outcomes Research 9 Horner 75 stroke may be least aware of the risk factors for stroke and the need to control those factors. 45,46 W e have already examined the approach to a similar line o f research in our discussion of acute stroke practice patterns. This type o f approach could also be used here to determine how best to proceed with prevention efforts.
7.
8.
Roadmap for Future Stroke Outcomes Studies W e have seen that as there is an epidemioiogy o f stroke outcomes, so there is an epidemiology of stroke outcomes research. As illustrated in this review of the study of racial disparities in the occurrence of stroke and stroke outcomes, there are a number of fundamental methodological principles to guide stroke outcomes research. Foremost, there is a need for a conceptual model that is appropriate to the research objective. F r o m first principles of epidemiological science, illness (or disease or a health condition) is viewed not as a random occurrence but as a function of person, disease agent, place, and time. This principle can be extended to the examination of other health outcomes in patients with a given disease. Thus, by investigating variations in occurrence, we m a y identify effective interventions to prevent stroke or reduce its sequelae. The underlying theoretical model also suggests the array of factors that may influence the outcome of interest and, hence, factors that must be considered in inTestigating an outcome. Finally, the model indicates the nature of the associations between those factors and health outcomes. The ultimate goal to this systematic generation and application of k n o w l e d g e is improvement in health for all individuals.
9.
10.
11.
12.
13.
14.
15. 16.
17. 18.
References 19. 1. Meenan RF, Felson DT: Clinical epidemiology, overview, in Gail MH, Benichou J (eds): Encyclopedia of Epidemiologic Methods. New York, NY, Wiley & Sons, 2000, pp 188-192 2. Keppel KG, Pearcy JN, Wagener DK: Trends in racial and ethnic-specific rates for the health status indicators: United States, 1990-98. Health People 2000 Stat Notes 23:1-16, 2002 3. Mausner J, Kramer S: Epidemiology: An Introductory Text (ed 2). Philadelphia, PA, WB Saunders, 1985 4. Eaker SA, Kirscht JP, Becker MH: Understanding and improving patient compliance. Ann Intern Med 100:25868, 1984 5. Stewart AL, Napoles-Springer A, Perez-Stable EJ, et ah Interpersonal processes of care in diverse populations. Milbank Q 77:305-39, 1999 6. Homer RD, Oddone EZ, Matchar DB: Theories explaining racial variation in the utilization of diagnostic and thera-
20. 21.
22. 23.
24.
peutic procedures for cerebrovascular disease. Milbank Q 73:443 462, 1995 Elixhauser A, Harris DR, Coffy RM: Trends in Hospital Procedures Performed on Black Patients and White Patients: 1980-87. Provider Studies Research Note 20. Rockville, MD, Agency for Health Care Policy and Research, Public Health Service, 1994. AHCPR publication 94-0003 Ayala C, Greenlund KJ, Croft JB, et al: Racial/ethnic disparities in mortality by stroke subtype in the United States, 1995-1998. Am J Epidemiol 154:1057-1063, 2001 Kennedy BS, Kasl SV, Brass LM, et al: Trends in hospitalized stroke for blacks and whites in the United States, 1980-1999. Neuroepidemiology 21:131-141, 2002 Sacco RL, Hauser WA, Mohr JP: Hospitalized stroke in blacks and Hispanics in North Manhattan. Stroke 22:14911946, 1991 Broderick J, Brott T, Kothari R, et al: The Greater Cincinnati/Northern Kentucky Stroke Study: Preliminary firstever and total incidence rates of stroke among blacks. Stroke 29:415-21, 1998 Sacco RL, Boden-Albala B, Gan R, et al: Stroke incidence among white, black and Hispanic residents of an urban community. The Northern Manhattan Stroke Study. Am J Epidemiol 147:259-268, 1998 Sacco RL, Hauser WA, Mohr JP, et al: One-year outcome after cerebral infarction in whites, blacks and Hispanics. Stroke 22:305-311, 1991 Friday G, Lai SM, Alter M, et al: Stroke in the Lehigh Valley: Racial/ethnic differences. Neurology 39:11651168, 1989 Kuhlemeier KV, Steins SA: Racial disparities in severity of cerebrovascular events. Stroke 25:2126-2131, 1994 Homer RD, Matchar DB, Divine GB, et al: Racial disparities in iscbemic stroke-related physical and functional impairments. Stroke 22:1497-1501, 1991 Jones MR, Homer RD, Edwards LJ, et al: Racial variation in initial stroke severity. Stroke 31:563-567, 2000 Homer RD, Sloane R, Kahn KL: Is 'use of mechanical ventilation' a reasonable proxy indicator of coma among Medicare patients hospitalized for acute stroke? Health Serv Res 32:841-859, 1998 Retchin SM, Ballard DJ: Establishing standards for the utility of administrative claims data. Health Serv Res 32: 861-686, 1998 (commentary) Indredavik B, Bakke F, Slordahl SA, et al: Stroke unit treatment: 10-year follow-up. Stroke 30:1524-1527, 1999 Johnston SC, Fung LH, Gillum LA, et al: Utilization of intravenous tissue-type plasminogen activator for ischemic stroke at academic medical centers: the influence of ethnicity. Stroke 32:1061-1068, 2001 Evans A, Duckworth S, Kalra L: Racism and tPA use in African Americans. Stroke 32:2439, 2001 (letter) Morris DL, Rosamond W, Madden K, et al: Prehospital and emergency department delays after acute stroke: The Genentech Stroke Presentation Survey. Stroke 31:25852590, 2000 Lacy CR, Suh DC, Bueno M, et al: Delay in presentation and evaluation for acute stroke: Stroke Time Registry for Outcomes, Knowledge and Epidemiology. Stroke 32:6369, 2001
76
Seminarsin Cerebrovascular Diseasesand Stroke Vol. 3 No. 2 June 2003
25. Goldstein LB, Edwards MG, Wood DP: Delay between stroke onset and emergency department evaluation. Neuroepidemiology 20:196-200, 2001 26. Homer RD, Matchar DB, Divine G, et al: Relationship between physician specialty and the selection and outcome of ischemic stroke patients. Health Serv Res 30:275-287, 1995 27. Mitchell JB, Ballard DJ, Whisnant JP, et al: What role do neurologists play in determining the costs and outcomes of stroke patients? Stroke 27:1937-1943, 1996 28. Goldstein LB, Matchar DB, Hoff J, et al: VA Stroke (VASt) Study: Lack of race/ethnic-based differences in utilization of stroke-related procedures or services. Ann Neurol 52:S13, 2002 (suppl 1) 29. Homer RD, Hoenig H, Sloane R, et al; Racial differences in utilization of inpatient rehabilitation services among elderly stroke patients. Stroke 28:19-25, 1997 30. Homer RD, 'Swanson JW, Bosworth HB, et al: Effects of race and poverty on the process and outcome of inpatient rehabilitation services among stroke patients. Stroke 34: 1027-1031, 2003 31. McElligott JM, Dolezal J, Hamilton J: Strokes racial variations, and effective inpatient rehabilitation in a rural setting. Arch Phys Med Rehabil 74:1278, 1993 (abstr) 32. Kuhlemeier KV, Steins SA: Rehabilitation after stroke: Gender and racial disparities. Arch Phys Med Rehabil 72:840-841, 1991 (abstr 105) 33. Oddone EZ, Homer RD, Monger ME, et al: Racial variation in the rates of carotid angiography and endarterectomy in patients with stroke and transient ischemic attack. Arch Intern Med 153:2781-2786, 1993 34. Oddone EZ, Homer RD, Sloane R, et al: Race, presenting signs and symptoms, use of carotid artery imaging and appropriateness of carotid endarterectomy. Stroke 30: 1350-1356, 1999 35. Oddone EZ, Homer RD, Diers T, et al: Understanding racial variation in the utilization of carotid endarterectomy: Role of patient preferences. J Natl Med Assoc 90:25-33, 1998
36. Oddone EZ, Homer RD, Johnston DCC, et al: Carotid endarterectomy and race: Do clinical indications and patient preferences account for differences? Stroke 33:29362943, 2002 37. Homer RD, Oddone EZ, Stechuchak K, et ah Racial variations in postoperative outcomes of carotid endarterectomy: Evidence from the Veterans Affairs National Surgical Quality Improvement Program. Med Care 40:I35-I43, 2002 (suppl 1) 38. Stallones RA: To advance epidemiology. Annu Rev Public Health 1:69-82, 1980 39. Kuller L, Reisler DM: An explanation for variations in distribution of stroke and arteriosclerotic heart disease among populations and racial groups. Am J EpidemioI 93:1-9, 1971 40. Reed DW: The paradox of high risk of stroke in populations with low risk of coronary heart disease. Am J Epidemiol 131:579-588, 1990 41. Sacco RL, Kargman DE, Gu Q, et al: Race-etbnicity and determinants of intracranial atherosclerotic cerebral infarction. The Northern Manhattan Stroke Study. Stroke 26:1420, 1995 42. Sacco RL, Boden-Albala B, Abel G, et al: Race-ethnic disparities in the impact of stroke risk factors: the northern Manhattan stroke study. Stroke 32:1725-1731, 2001 43. Worrall BB, Johnston KC, Kongable G, et al: Stroke risk factor profiles in African American women: An interim report from the African-American Antiplatelet Stroke Prevention Study. Stroke 33:913-919, 2002 44. Clark VR: The perilous effect of racism on blacks. Ethn Dis 11:769-772, 2001 45. Schneider AT, Pancioli AM, Khoury JC, et al: Trends in community knowledge of the warning signs and risk factors for stroke. JAMA 289:343-346, 2003 46. Ruland S, Raman R, Chaturvedi S, et al: Awareness, treatment, and control of vascular risk factors in African Americans with stroke. Neurology 60:64-68, 2003.
The Epidemiology of Stroke Outcomes Research: Illustration of an Approach to Outcomes Methodology Using Racial/Ethnic Disparities in Stroke R O N N I E D. H O R N E R Bethesda, Maryland
ABSTRACT Stroke is associated with numerous health outcomes, the study of which is important for identifying best practices. However, it is equally important to understand the process to generating that knowledge. The methodological approach to stroke outcomes research is founded on first principles of epidemiological inquiry. These principles include defining the inquiry through a conceptual model; identifying and prioritizing the fundamental research questions; systematically addressing the research questions in order of importance; and exploring possible nuances to identified associations. To illustrate these principles in practice, the line of investigation into the reasons for racial/ethnic disparities in stroke mortality is used as a case study. Key words: cerebrovascular accident, epidemiological methods, ethnic groups, outcomes assessment (health care), racial stocks.
Stroke is associated with a broad array of health-related effects: physical, psychological, social, financial, and symptomatic, which often become permanent deficits. 1 A systematic study of these associated effects has numerous uses. Of the most obvious use, this type of study may yield clues to "best practices" (ie, clinical treatment practices that are associated with improved outcomes). Conversely, it may identify practices to be avoided or "worst practices." Another important product of the study of health outcomes, when conducted in a natural history context, is a baseline level by which to compare new therapies or practices. Epidemiology, as the study of the occurrence of illness, provides one approach to the systematic study of the health outcomes associated with stroke as well as those associated with other health conditions. Through first principles of ep!demiologic inquiry, we may come to
appreciate not only the consequences of a disease, such as stroke, but also may identify points of intervention and the array of possible interventions for those points. It is this latter product (ie, the generation of new knowledge for the purpose of intervention) that is the relatively more important objective of epidemiologic research because, as the scientific arm of public health, the goal of epidemiologic research is to promote health, prevent disease, and reduce or eliminate the negative sequelae of disease. Although knowledge of stroke-related outcomes, per se, is important, it is equally important to understand the process to generating that knowledge. Thus, although there is an epidemiology of stroke outcomes, we also have an epidemiology of stroke outcomes research in which the focus is on the approach by which to generate the knowledge regarding those outcomes. It is this latter epidemiology that is of interest here. We will examine the fundamental principles of stroke outcomes research. This examination is illustrative in nature (ie, these fundamental principles are illustrated by examples from the relevant literature on stroke and, specifically, from the line of research that seeks to explain racial and/or ethnic-related disparities in stroke occurrence and strokerelated health outcomes). Disparities in stroke represent an
/
From the NINDS~IH, Neuroscience Center, Bethesda, MD.
Address reprint requests to Ronnie D. Homer, PhD, NINDS/NIH, Neuroscience Center, Room 2149, 6001 Executive Blvd, Bethesda, MD 20892-9535 (For express mail, use Rockville, MD 20852). E-mail: [email protected] 9 2003 Elsevier Inc. All rights" reserved.
1528-9931/03/0302-0002530.00/0 doi: 10.1053/scds.2003.0015
67
68
Seminars in Cerebrovascular Diseases and Stroke Vol. 3 No. 2 June 2003 I
l
C,n,o,
I
Disease
II
~ ,~
I
Clinical Ha r izon
~
,., I
7
__J --
I9 Chronicity
--
/
'/.
~ / / 7 7 / . ~ / / / / / /I /\ J
InaPoPraren Subclinical~
k I
/ ''/B
'
inapparent 1~ ' ' ~ . condition
/^ I / ~ - , ~ , ab.br.tive.'~ !/ ",,-condition ~'
f
I
',
PRE
i
\
I
I
Residual Disability
"~"-
\
I I I i
Outcome; Death
\ \~C ~. ,
,
>.
I DISABILITY
STAGE OF.DISEASE SUSCEPTIBILITY I. -I CLINICAL DISEASE J I -. I TISSUE Ii Pre I I CHANGES I Pothogenesis ~ PothogenesiS I .I I LEVEL OF I i i I Primary I Secondary I Tertiary PREVENTION t tI . . . . I ~l''" Treatment and MODES OF IHealth Promotion Detection I ,(1-- Rehabilitation INTERVENTION I Specific I Early I I Protection I Diagnosis I Limitation I I Prompt I of Disability I i I I ~ Treatment I
I RECOVERY. ........... ~11 Resolution or I Sequeloe I , I , ,.. I, , II ,= t " i I I I
I II i I
Fig. 1. Schematic of the natural history of disease. Reprinted from Epidemiology: An Introductory Text, 2nd Edition by Mausner and Kramer with permission from WB Saunders, Inc.
intriguing and important social and scientific issue, not only because of the magnitude of observed disparities (eg, an almost 2-fold higher stroke mortality in African Americans vis-h-vis white Americans) but also because of the persistence of those disparities for decades, despite a general decline in stroke mortality.2 Moreover, from an epidemiclogic perspective, those groups having the disparities may be regarded as high-risk groups and, hence, investigation into the reasons for the increased burden of disease may yield information that can be used to reduce stroke incidence or mortality in the larger, national population, as well as among those within the high-risk group. ,
A First Principle: Define the Inquiry through Conceptual Models Racial/ethnic disparities in stroke outcomes exist broadly, ranging from the occurrence of stroke, the most fundamental of outcomes, to burden of disease, as reflected by mortality and, among survivors, residual stroke-related deficits and recurrent stroke. In this arena, the research focus is on the explanation of the observed difference~ so that effective interventions might be identified to reduce or eliminate the disparities in outcomes. If the inquiry is to be systematic and, hence, thorough, a
conceptual model is essential because it ensures that all key research questions are identified, the (anticipated) explanatory factors and the (anticipated) linkage of those factors are delineated, and that a foundation exists on which to interpret the findings. Natural History for Epidemiologic
of Disease: Studies
A Model
On a number of counts, the natural history of disease is a preferred conceptual framework for organizing the investigation of disparities in stroke outcomes (Fig 1). For one, the research issues can only be answered through observational studies, which is epidemiology. For another, and of particular note, are the 3 phases of the framework: the predisease or presymptomatic phase, the clinical phase, and the sequelae phase that are tied explicitly to levels of intervention. It is intervention to reduce or eliminate the disparities that is the ultimate goal of this line of inquiry) Thus, the first phase is the arena of primary intervention, most often referred to as prevention, in which the focus is on the promotion of health and prevention or delay of disease onset. Stroke incidence is our concern here. Etiologic studies and studies of risk factors and their modification are types of scientific research
The Epidemiologyof StrokeOutcomes Research 9 Horner 69
HealthCareReceivedII i
&
PatientFactorsper HealthDecisionModel l
PatientSociodemographics~
.?
-I C Recommenda. Uon(s) Regarding HealthCare ~
HealthCareProvider's Attitudes,Beliefs,and OtherFactors(Financial, Organizational)
Patient'sClinical I Presentation~A I HealthCareProvider's Knowledge,Experiences, andPreferences RegardingHealthCare
Fig, 2. Conceptual model of the interaction between the patient and provider within the health care system: key components and points of intervention (A, B, C).
activities that target this phase. These studies of risk factors may include basic neuroscience studies, such as studies that explore the genetic contribution to disease occurrence and gene-environment interactions. Case fatality and residual deficits and, hence, practice patterns, are concerns of the last 2 phases. The clinical phase is that of early detection (ie, screening) and early intervention to minimize sequelae. This is the phase of secondary prevention. The third phase, disease sequelae, is the tertiary intervention phase. The objective of this latter phase is to minimize problematic outcomes of disease, which range from disability to death, and to maximize positive outcomes (eg, recovery of function). The outcomes associated with this phase are the outcomes that typically come to mind when outcomes research is mentioned (eg, death, physical and psychological disability).
Enhancement of the Natural History of Disease Model for Investigation of Practice Patterns For studies of practice patterns, whether or not related to race/ethnicity, the natural history model needs to be augmented with a more detailed model of the patientprovider-health system interaction that "drives" the use of health care practices. One model for guiding the investigation of outcomes associated with various practices is that shown in Figure 2. It relies heavily on the health decision-model and provides the more precise view of the patient-provider interaction. 4,5 An earlier version of this model was used to organize the an'ay of considerations for understanding racial/ethnic differences in the use of carotid endarterectomy. 6 Carotid endarterectomy, and other procedures to diagnose and
treat stroke and other cerebrovascular diseases are well documented to show racial variation in use with higher use in white patients, despite the apparent higher need in blacks because of the burden of stroke. 7 Under the proposed model, key components to consider for explaining the lower usage in African Americans include the patient's ability to access health care, presenting signs and symptoms, the provider's gathering, evaluation and filtration of the evidence and assortment of options, and the negotiation between patient and provider for the care to be received. The structured line of inquiry is designed to examine systematically the potential explanations proposed for the observed disparity in health care use, beginning with the most plausible or, perhaps, the least disconcerting explanation. Thus, the initial point of departure is to determine if there are racial differences in clinical indications for the procedure. The question is, do blacks receive carotid endarterectomy less often because the prevalence of indications is lower (ie, insignificant carotid stenosis), or the risks of the procedure outweigh the benefits? As each proposed explanation is refuted, the next one is examined. Of course, it must be recognized that if one explanation fails to be rejected, this does not necessarily exclude "higher order" explanations. More than one explanatory factor may be operating and, more subtly, a given causative factor may be obscured by another factor, only to emerge after that factor is rectified.
Another First Principle: Fundamental Research Questions Are a Priority Although this principle may seem obvious, it is amazing how often some fundamental research questions are
70
Seminarsin Cerebrovascular Diseases and Stroke Vol. 3 No. 2 June 2003 IIIAfr. Am.
E]White
_
IIIMr. Am.
E]White
2O
10 5 0
1980
1999
Stroke Hospitalizations (per 1,000 population)
1980
1999
In-hospital Mortality (per 100 Stroke Discharges)
Source: Adapted from [9]
Fig. 3. Racial differences in stroke: incidence and case fatality rates by patient face/ethnicity.
either neglected or assumed answered. In the inquiry into racial/ethnic disparities in stroke, one dominating issue concerns the role of stroke occurrence as an explanation of the 2-fold higher mortality from stroke overall and within stroke types in African Americans. s The disparity in stroke mortality may be a function of disparities in the incidence rate (ie, occurrence) or the case fatality rate (ie, survival), or both. This result is an important, fundamental issue because the source of the higher mortality suggests the most useful intervention point(s) and the associated interventions. If the disparity in mortality derives from a difference in incidence, this argues for stroke prevention programs. If case fatality is the more important source of the mortality difference, this suggests programs focused on improving patterns of care. Because of the relationship among incidence, survival, and mortality, if either incidence or case fatality can be excluded, then the other must be responsible. On the other hand, if one is included, the other will have to be examined because it also may be contributing to mortality. The evidence as it is currently emerging suggests that disparity in stroke incidence, more than in case fatality, is responsible for the higher stroke mortality observed in African Americans. National data using hospitalizations as a measure of incidence and in-hospital mortality (ie, case fatality), indicate the rate of hospitalization for stroke has been persistently higher for African Americans than white Americans and, disturbingly, may have increased between 1980 and 1999 in African Americans, while decreasing for white Americans (Fig 3). 9 In-hospital mortality,, by comparison, was lower for African Americans a~d remained lower over the 20-year period. The Northern Manhattan and Cincinnati cohort studies support these findings and conclusion and, because of their more rigorous study designs, may be considered to provide more convincing evidence. 1~ Investigations of
incidence versus case fatality require a study design that can generate rates and, therefore, that involves a defined at-risk population (ie, denominator) and complete (or nearly complete) ascertainment of events, whether stroke, per se, or death in the patients who had a stroke (ie, numerator). The cohort study is an ideal design for these investigations in which the cohort is comprised of all patients who had a stroke within a defined population. Typically, the cohort of patients who had a stroke is comprised of those presenting at the hospital(s) serving a given population. This result is justified by the assumption that virtually all patients who had a stroke, including those who die of their stroke outside the hospital, will present at one of the hospitals. The assumption is a reasonably valid one, at least in the United States. 12 This type of design is elegant in its simplicity, allowing the investigator to address both the issue of incidence rates and case fatality rates. For the evaluation of incidence rates, the denominator is the population within the hospital(s) service area, with the hospitalized patients who had a stroke becoming the denominator for the study of stroke survival. Review of the medical or hospital records may be used if there is a need to distinguish between first and recurrent stroke.
E x p l o r e N u a n c e s of a n A s s o c i a t i o n : A n o t h e r First Principle These findings of similar stroke case fatality rates among racial/ethnic groups may not be as clean-cut as one might hope. Although the overall rates appear similar, further inquiry reveals that age is an important modifier (Fig 4). 9,13 Although stroke fatality rates were similar among African Americans, Hispanics, and white Americans 65 years or older, African Americans and Hispanics younger than 65 years had substantially higher early poststroke mortality rates, compared with younger white Americans. However, the higher mortality did not persist at 1-year poststroke, suggesting that the source may be with acute care rather than care in the postdischarge setting. L3 This finding of age as a modifier of the association between race/ethnicity and the stroke case fatality rate presents yet another line of inquiry, and illustrates that, while exploring racial variations and other risk relationships in disease, the investigator should examine associations closely to be certain that subtleties of the relationship axe not missed. To understand differences better in stroke case fatality rates, or the lack thereof, factors in addition to age, specifically stroke characteristics such as stroke type, severity, and whether it is a first event, are potential modifiers or confounders of observed outcomes. This observation leads to many important questions. For example, small-vessel strokes that tend to have a better prognosis are more common in African Ameri-
The Epidemiologyof Stroke Outcomes Research 9 Horner 71 cans. However, hemorrhagic strokes that have a worse prognosis are also more prevalent in African Americans. 14 Is the distribution in stroke types confbunding the case fatality rate in older patients who had a stroke? Is the case fatality rate for specific types of stroke (eg, lacunar strokes) similar among the various racial/ethnic groups? Answers to these types of questions will indicate whether there is confounding or modification of the association between race and the case fatality rate for stroke with or without adjustment for age. Efforts to determine whether stroke severity might explain racial differences in stroke outcomes have been few in number. Early studies that used proxy measures of severity (ie, case fatality rate and residual disability) established the possibility of racial/ethnic differences in stroke severity. 15,16The latter study was a secondary data analysis of a prospective cohort study design that showed that African Americans had a clinically significant 9.5% lower Fugl-Meyer score, a measure of physical impairment, than white Americans at 180 days poststroke. 16 Secondary analysis can be an efficient strategy for generating an assessment of a hypothesized association, if only an initial one. It is typically only an initial assessment because the database has one or more design features that, for the proposed research question, represent methodological shortcomings. This situation is to be anticipated, a consequence of the original study not being designed to answer the proposed research question. Of the potential limitations, the preferred measure of the outcome may not be present, or the measure of the key explanatory variable may be absent. Thus, the investigator has to be creative by using proxy variables. Another common methodological limitation is insufficient sample size, especially when the original study was not explicitly interested in the now desired subgrouping. In the study cited, as noted, there were measures of physical and functional impairment: the FuglMeyer and Barthel Index, respectively. However, the sample size for African Americans may not have been optimal (n = 41) and data on stroke subtypes were not available. Although racial differences were found for physical impairment, no statistically significant differences were found for functional impairment, although ability to perform activities of daily living was lower, on average, among the African American stroke survivors. Why physical impairment did not translate into obvious functional impairment could be a consequence of shortcomings within the measure used (ie, ability of the measure to reflect clinically important impairment) or confounding due to failure to adjust for important differences in the stroke or other reasons. Clearly, further inquiry is necessary to understand fully whether differences in stroke characteristics explain the observed racial differences in case fatality rates for stroke.
Of other methodological improvements, future studies will need to examine more precisely the issue of race and stroke severity through direct measures of severity. For the reasons indicated previously, stroke subtype is an especially important characteristic to include in these studies because the risk of death varies with the type of stroke. This type of a more precise study was conducted as a secondary analysis of a cohort composed of veterans with stroke, in whom stroke severity was measured by a retrospective chart-based measure: the modified Canadian Neurological Scale. 17 (A prospective severity scale may be preferable generally but obviously was not feasible for this secondary analysis.) Stroke type (ie, ischemic versus hemorrhagic) was also included in the model, but inclusion of subtypes of ischemic strokes would have been an even better modeling strategy. A modest but statistically significant difference in stroke severity was found. The average (ie, unadjusted) stroke severity score was 7.96 for African Americans and 8.32 for white Americans (P = 0.035). However, Afiican Americans did not have a significantly worse in-hospital mortality rate (12.7% versus 9.5%, respectively; P = 0.12) nor were they significantly more likely to be admitted to intensive care (23.6% versus 18.7%, respectively; P = 0.08). The lack of statistical significance on these latter outcomes detracts from the ability to conclude convincingly that severity has a role explaining racial differences in case fatality rates. Moreover, although age and stroke type were associated with severity, the model did not include interaction terms, especially the race-age interaction with the case fatality rate that was shown previously. A logical follow-up to the findings is age or stroke subtype-specific analyses. Of particular importance, there should be studies of racial/ ethnic differences in severity among younger patients who had a stroke. Although modest, the difference in severity may also be associated with a difference in residual physical or, perhaps, psychological deficits. These questions also remain to be explored fully. The use of extant databases is an established research practice to gain preliminary insights but is often hampered by the absence of specific key variables in the data set. Thus, large hospital or other administrative health care databases (eg, Medicare, Medicaid data) may lack details on stroke characteristics (eg, stroke severity, subtype). This is a situation in which a proven proxy variable could enhance any analyses involving those databases. In this regard; a reasonable case has been made for the use of mechanical ventilation as a proxy for coma (ie, severe stroke), with due consideration to the caveats in interpretation. ~8,~9 Perhaps the more important contribution of this research was to show a methodological approach to conducting proxy-identification studies. The search for the proxy variable should be predicated on a conceptual framework so that there is a theoretical (with
72
Seminarsin Cerebrovascular Diseasesand Stroke Vol. 3 No. 2 June 2003
empirical support) basis for targeting one or more proxy variables for evaluation.
Phase 2: Following Up on the Logical Next Questions The role of practice patterns (ie, variation in acute and postacute care, including the use of rehabilitation) remains a promising area of inquiry for understanding the complicated association between race and case fatality rates for stroke. In this area of inquiry, the research questions deal with the entire spectrum of care, beginning with time from stroke onset to presentation, through rehabilitation and into care received in the postdischarge environment. Extant databases may be useful for providing preliminary data on best practices, especially when important clinical data (ie, characteristics that would be considered by the attending physician for determining care) are included directly or as proxy variables. However, as is all too apparent, highly detailed clinical data are not often present, especially in the large national surveys or medical administrative databases and, hence, observed associations may not hold when a more precise assessment is made. Again, cohort studies tend to be a preferred study design, but care must be taken to ensure that the cohort represents the population at risk. Thus, for example, studies of time to hospital care could provide a biased estimate if based on patients who had a stroke and were admitted to the hospital (ie, stroke survivors).
Beginning at the Beginning: Time to Presentation Time to presentation may be an important determinant of the array of therapies available to the provider to treat effectively the patient who had a stroke. A delay in the patient with an acute stroke presenting at the hospital is one aspect of the broader issue of delay in receipt of appropriate care. Delay in the receipt of care, even postacute care, may be a strong modifier of health outcomes. For example, the timely use of stroke rehabilitation units is associated with improved survival in the immediate discharge period, and this survival advantage is retained for years. 2~ Studies of time tO presentation are important in that tPA, a proven effective acute therapy, requires that the patient present promptly after stroke onset (ie, within 3 hours). There is recent evidence of a racial disparity in the use of tPA, 21 and delayed presentation has been offered as one' of several alternatives to racism as explanations for,.this disparity.22 However, several studies have yielded conflicting results in this area. Some recent studies have found that African Americans and white Americans arrive within approximately the same time,
on average. 23,24 One study found that African Americans presented slightly earlier, on average, but waited slightly longer for initial care within the emergency department (Fig 5). 23 Another of these studies discovered that African Americans presented significantly later than white Americans, 24 but this initial race effect disappeared with adjustment for other factors, including younger age, less severe stroke, no history of stoke, and failure to use the emergency medical system. Perhaps this literature is relevant to understanding the racial differences in case fatality rates when stratified by patient's age. Piecing together these reports with evidence on the effectiveness of community-based stroke awareness campaigns, some investigators have concluded that younger individuals and those with "milder" symptoms may not fully appreciate the presenting symptoms and signs of stroke, and, so, may delay seeking care. 25 These findings may be used to identify points of intervention that may yield reductions in stroke mortality in younger African Americans.
Race, Provider, and Acute Stroke Practices Beyond time to presentation, differences in acute and postacute care practices within the hospital may also explain any racial disparities in outcomes. The author saw that at least one report indicates that use of tPA differs by the patient's race, although it may be a function of time to presentation. 21,22 However, it is also becoming clear, for example, that patients who had a stroke who are under the care of neurologists have improved outcomes, although there is only a partial understanding of the reasons for this phenomenon. 26,27 For the topic at hand, the question is: Are African Americans systematically less likely to be under the care of neurologists? The answer to this research question remains to be determined, although a study of racial differences in stroke care within Department of Veterans Affairs (VA) hospitals indicated a similar proportion of African American and white patients who had a stroke, were under the care of a neurologist. 28 However, because the VA health care system is an equal-access system for those patients who qualify, this finding may not hold within the private health care sector. It should be noted that, when multiple hospitals are involved, differences in the racial composition of the hospital catchment area populations could confound an association. Studies that focus on specific practices during the hospital stay are a logical follow-up to the intriguing finding that improved outcomes are associated with neurologic care. These studies could use similar methodology, as used in the studies of neurologists versus other providers in stroke outcomes (ie, any use of a particular diagnostic or therapeutic procedure). In a very recent report, no racial differences were found in the use of
The Epidemiology of Stroke Outcomes Research 9
specific key acute stroke practices? a However, again, because the cohort was composed of veterans who were hospitalized within VA hospitals, the patterns may not hold within the private health care sector. If acute care practices do not differ by the patient's race, postacute care practices may. Studies of racial differences in the use of rehabilitation have ranged from those using the large, detail-poor databases, like the Medicare data, 29 to studies of cohorts that are well characterized clinically but may have less detailed data on specific practices) ~ In general, these studies indicated that African Americans may be slightly m o r e likely to gain access to rehabilitation. The adjusted relative likelihood of receiving inpatient rehabilitation for African American as compared with white Medicare patients who had a stroke was 1.06 (95% CI = 0.93, 1.33; P = 0.22), a finding similar to that in African American and white patients who had a stroke and were seen at V A hospitals, in which the adjusted relative odds were 1.28 (P : 0.13). 29,3o However, time to initiation of the rehabilitation was relatively longer for black patients than white patients (4.4 versus 3.8 days, respectively; P < 0.05), and those who had a delay had relatively worse functional recovery, as measured by the ability to perform activities of daily living. 3~ However, closer inspection of the associations indicated that it was in socioeconomically poorer African Americans that the delay occurred, and it was in this group that recovery in physical function was slower and to a lower level. Data on specific rehabilitation practices were not available in the dataset, so racial differences in the quality of rehabilitative care could not be assessed. Curiously, functional level at discharge was similar in all groups: higher and lower socioeconomic status white and African American patients. Other studies also show similar levels in functioning at initiation and discharge from rehabilitation among whites and African Americans. 31,32 This result would seem to suggest that race and socioeconomic status are interacting in the postdischarge sit-
Horner
73
5 4
o 3~ "6
3
6 ~'
2
C
IIAfr. Am, DWhite
o
i
Pre-Hosp.
i
Within ED
Total
Source: Adapted from [24]
Fig. 5. Racial differences in time to presentation at the hospital and wait time within the emergency department.
uation to modify the benefits of rehabilitation. Again, this is another line of inquiry reaffirming that race-based nuances in the patterns and outcomes of stroke rehabilitation exist that might not be apparent without more detailed study. A similar story is found for practices targeted at the prevention of future stroke, whether first or subsequent strokes. A series of investigations into racial/ethnic differences in the use of carotid endarterectomy is representative of the systematic exploration of an issue that is necessary to understand fully racial/ethnic disparities in practice patterns. Based on hospital discharge data from the VA health care system, disparities were found in use of the procedure that were similar to those occurring in the private sector (Fig 6). 33 This is an important finding, because the VA system, beyond being an equal access system for those who are eligible, has minimal financial incentives for providers to perform procedures because the providers are salaried. Thus, many financial consid-
I
Non-VA
Carotid A n g i o g r a p h y
50
I
VA
40
9
Am.
[]Hispanics
[]Whites I Non-VA
30
I-TWhites [] Hispanics IIAfr. Am. Carotid Endarterectomy
~= 20
VA
~10
0
r
0 40-69 yrs.
70+ yrs
Source: Adapt:ed from [13]
Fig. 4. Patient race/ethnicity and stroke case fatality rate: modifying effect of age.
20 40 60 Rate per 100 patients
80
Sources: Adapted from [33] ands unpublished data from Academic Medical Center Consortium
Fig. 6. Racial/ethnic differences in the use of carotid angiography and carotid endarterectomy: Department of Veteran Affairs (VA) versus academic medical center (non-VA) hospitals.
74
N,sh,te
Seminarsin Cerebrovascular Diseasesand Stroke Vol. 3 No. 2 June 2003
erations that may affect patterns o f care in the private health care sector are believed to be minimal within the VA health care system. Subsequent cohort studies were performed to "ferretout" the reasons for the 2 to 3-fold higher use in white than in black patients. In conformity with the conceptnal model, 6 these studies begin, logically, with the most obvious factor (ie, clinical indications), and find that clinical factors cannot fully explain the differences observed. 34 Inquiries of patient and provider perceptions of carotid endarterectomy reveal that patient concerns about invasive therapies is an additional factor to clinical indication. 35,36 Although it is tempting to quit at this point, there is a next step and that is to determine why the patient concerns exist. The model of patient-provider interaction (Fig 2) suggests ways the next generation of studies might unfold to identify points of intervention to ensure that patients who would benefit from a particular procedure (eg, carotid endarterectomy) will not have barriers to receiving it. It may be worth noting that among patients of the VA health care system who receive carotid endarterectomy, similar outcomes are experienced, suggesting a similar quality of c a r e s
Stroke Incidence and Racial Disparities: Risk Factors as Guides to Prevention Previously, it was argued that the substantial racial/ ethnic difference in stroke mortality was more a consequence of stroke incidence than case fatality9 When the issue is incidence, as previously noted, the objective is prevention9 As shown in the natural history of disease model, prevention is keyed to the presymptomatic phase of disease and, hence, to modification of the risk factor profile because disease is not a random occurrence but a function of person, agent, time, and space. 3~ Thus, the focus of this line of inquiry is to determine if the racial/ ethnic disparities in stroke incidence are attributable to 9 i, disparities in the prevalence of estabhshed risk factors, a differential effect of these risk factors, or unique risk factors9 For example, theoretically, it is postulated that hypertension and ather0sclerosis may operate differently in African Americans than white Americans and, may in part, explain the observed differences in stroke subtypes. 39,4~ Support/for this hypothesis is found in the large database studies from which there is indication that known risk factors, particularly hypertension and diabetes mellitus, may be more important in disease etiology in African Americans than white Americans. 4~ There is further evidence from established stroke cohorts that the well-known stroke risk factors might have differential importance among racial/ethnic groups9 Hypertension and diabetes mellitus appear to be more im-
4O ~10re2030~ zzAfr.~A~ []H 0
~
HTN
DM
CAD
Inactive
Source: Adal:Cedfrom [42]
Fig. 7. Racial/ethnic differences in the impact of reducing selected stroke risk factors.
portant stroke risk factors for African Americans and Hispanics, while coronary artery disease and atrial fibrillation are more important ones for white Americans, and physical inactive is similar in prevalence among racial/ ethnic groups. 4a Moreover, there is a race/ethnicity-specific hierarchy to the etiologic importance of the risk factors that may not be fully correlated with their prevalence (Fig 7). Furthermore, differences in stroke risk profiles appear to exist between men and women within racial/ethnic groups. 43 Thus, although hypertension, diabetes mellitus, and physical inactivity are potent risk factors for stroke in African American men and women, these factors were relatively more important for African American women. Smoking cigarettes, on the other hand, appears to be a substantially more potent risk factor for African American men than women. This knowledge argues for the tailoring of intervention programs, not only on race/ethnicity, but sex and probably age, as well. In addition to these well-established risk factors for stroke, unique factors may also be involved, at least among some racial/ethnic groups9 For example, there is emerging evidence that societal racism may contribute indirectly to the high stroke rates in African Americans through effects on blood pressure. 44 Although identification of the unique factors is intellectually challenging, the pragmatism of this effort remains to be determined9 Is it possible to eliminate discrimination in a society? The answer is probably not in the short term. Therefore, the most pragmatic approach to reducing stroke incidence in African Americans may be to target those factors in which there are proven interventions and to seek ways to implement more effectively those interventions in culturally diverse populations. At this point, we move back to the realm of stroke prevention practices and ways that interventions proven to be effective (eg, blood pressure control) might be more effectively implemented in African American and Hispanic populations9 Those patients at highest risk for
The Epidemiology of Stroke Outcomes Research 9 Horner 75 stroke may be least aware of the risk factors for stroke and the need to control those factors. 45,46 W e have already examined the approach to a similar line o f research in our discussion of acute stroke practice patterns. This type o f approach could also be used here to determine how best to proceed with prevention efforts.
7.
8.
Roadmap for Future Stroke Outcomes Studies W e have seen that as there is an epidemioiogy o f stroke outcomes, so there is an epidemiology of stroke outcomes research. As illustrated in this review of the study of racial disparities in the occurrence of stroke and stroke outcomes, there are a number of fundamental methodological principles to guide stroke outcomes research. Foremost, there is a need for a conceptual model that is appropriate to the research objective. F r o m first principles of epidemiological science, illness (or disease or a health condition) is viewed not as a random occurrence but as a function of person, disease agent, place, and time. This principle can be extended to the examination of other health outcomes in patients with a given disease. Thus, by investigating variations in occurrence, we m a y identify effective interventions to prevent stroke or reduce its sequelae. The underlying theoretical model also suggests the array of factors that may influence the outcome of interest and, hence, factors that must be considered in inTestigating an outcome. Finally, the model indicates the nature of the associations between those factors and health outcomes. The ultimate goal to this systematic generation and application of k n o w l e d g e is improvement in health for all individuals.
9.
10.
11.
12.
13.
14.
15. 16.
17. 18.
References 19. 1. Meenan RF, Felson DT: Clinical epidemiology, overview, in Gail MH, Benichou J (eds): Encyclopedia of Epidemiologic Methods. New York, NY, Wiley & Sons, 2000, pp 188-192 2. Keppel KG, Pearcy JN, Wagener DK: Trends in racial and ethnic-specific rates for the health status indicators: United States, 1990-98. Health People 2000 Stat Notes 23:1-16, 2002 3. Mausner J, Kramer S: Epidemiology: An Introductory Text (ed 2). Philadelphia, PA, WB Saunders, 1985 4. Eaker SA, Kirscht JP, Becker MH: Understanding and improving patient compliance. Ann Intern Med 100:25868, 1984 5. Stewart AL, Napoles-Springer A, Perez-Stable EJ, et ah Interpersonal processes of care in diverse populations. Milbank Q 77:305-39, 1999 6. Homer RD, Oddone EZ, Matchar DB: Theories explaining racial variation in the utilization of diagnostic and thera-
20. 21.
22. 23.
24.
peutic procedures for cerebrovascular disease. Milbank Q 73:443 462, 1995 Elixhauser A, Harris DR, Coffy RM: Trends in Hospital Procedures Performed on Black Patients and White Patients: 1980-87. Provider Studies Research Note 20. Rockville, MD, Agency for Health Care Policy and Research, Public Health Service, 1994. AHCPR publication 94-0003 Ayala C, Greenlund KJ, Croft JB, et al: Racial/ethnic disparities in mortality by stroke subtype in the United States, 1995-1998. Am J Epidemiol 154:1057-1063, 2001 Kennedy BS, Kasl SV, Brass LM, et al: Trends in hospitalized stroke for blacks and whites in the United States, 1980-1999. Neuroepidemiology 21:131-141, 2002 Sacco RL, Hauser WA, Mohr JP: Hospitalized stroke in blacks and Hispanics in North Manhattan. Stroke 22:14911946, 1991 Broderick J, Brott T, Kothari R, et al: The Greater Cincinnati/Northern Kentucky Stroke Study: Preliminary firstever and total incidence rates of stroke among blacks. Stroke 29:415-21, 1998 Sacco RL, Boden-Albala B, Gan R, et al: Stroke incidence among white, black and Hispanic residents of an urban community. The Northern Manhattan Stroke Study. Am J Epidemiol 147:259-268, 1998 Sacco RL, Hauser WA, Mohr JP, et al: One-year outcome after cerebral infarction in whites, blacks and Hispanics. Stroke 22:305-311, 1991 Friday G, Lai SM, Alter M, et al: Stroke in the Lehigh Valley: Racial/ethnic differences. Neurology 39:11651168, 1989 Kuhlemeier KV, Steins SA: Racial disparities in severity of cerebrovascular events. Stroke 25:2126-2131, 1994 Homer RD, Matchar DB, Divine GB, et al: Racial disparities in iscbemic stroke-related physical and functional impairments. Stroke 22:1497-1501, 1991 Jones MR, Homer RD, Edwards LJ, et al: Racial variation in initial stroke severity. Stroke 31:563-567, 2000 Homer RD, Sloane R, Kahn KL: Is 'use of mechanical ventilation' a reasonable proxy indicator of coma among Medicare patients hospitalized for acute stroke? Health Serv Res 32:841-859, 1998 Retchin SM, Ballard DJ: Establishing standards for the utility of administrative claims data. Health Serv Res 32: 861-686, 1998 (commentary) Indredavik B, Bakke F, Slordahl SA, et al: Stroke unit treatment: 10-year follow-up. Stroke 30:1524-1527, 1999 Johnston SC, Fung LH, Gillum LA, et al: Utilization of intravenous tissue-type plasminogen activator for ischemic stroke at academic medical centers: the influence of ethnicity. Stroke 32:1061-1068, 2001 Evans A, Duckworth S, Kalra L: Racism and tPA use in African Americans. Stroke 32:2439, 2001 (letter) Morris DL, Rosamond W, Madden K, et al: Prehospital and emergency department delays after acute stroke: The Genentech Stroke Presentation Survey. Stroke 31:25852590, 2000 Lacy CR, Suh DC, Bueno M, et al: Delay in presentation and evaluation for acute stroke: Stroke Time Registry for Outcomes, Knowledge and Epidemiology. Stroke 32:6369, 2001
76
Seminarsin Cerebrovascular Diseasesand Stroke Vol. 3 No. 2 June 2003
25. Goldstein LB, Edwards MG, Wood DP: Delay between stroke onset and emergency department evaluation. Neuroepidemiology 20:196-200, 2001 26. Homer RD, Matchar DB, Divine G, et al: Relationship between physician specialty and the selection and outcome of ischemic stroke patients. Health Serv Res 30:275-287, 1995 27. Mitchell JB, Ballard DJ, Whisnant JP, et al: What role do neurologists play in determining the costs and outcomes of stroke patients? Stroke 27:1937-1943, 1996 28. Goldstein LB, Matchar DB, Hoff J, et al: VA Stroke (VASt) Study: Lack of race/ethnic-based differences in utilization of stroke-related procedures or services. Ann Neurol 52:S13, 2002 (suppl 1) 29. Homer RD, Hoenig H, Sloane R, et al; Racial differences in utilization of inpatient rehabilitation services among elderly stroke patients. Stroke 28:19-25, 1997 30. Homer RD, 'Swanson JW, Bosworth HB, et al: Effects of race and poverty on the process and outcome of inpatient rehabilitation services among stroke patients. Stroke 34: 1027-1031, 2003 31. McElligott JM, Dolezal J, Hamilton J: Strokes racial variations, and effective inpatient rehabilitation in a rural setting. Arch Phys Med Rehabil 74:1278, 1993 (abstr) 32. Kuhlemeier KV, Steins SA: Rehabilitation after stroke: Gender and racial disparities. Arch Phys Med Rehabil 72:840-841, 1991 (abstr 105) 33. Oddone EZ, Homer RD, Monger ME, et al: Racial variation in the rates of carotid angiography and endarterectomy in patients with stroke and transient ischemic attack. Arch Intern Med 153:2781-2786, 1993 34. Oddone EZ, Homer RD, Sloane R, et al: Race, presenting signs and symptoms, use of carotid artery imaging and appropriateness of carotid endarterectomy. Stroke 30: 1350-1356, 1999 35. Oddone EZ, Homer RD, Diers T, et al: Understanding racial variation in the utilization of carotid endarterectomy: Role of patient preferences. J Natl Med Assoc 90:25-33, 1998
36. Oddone EZ, Homer RD, Johnston DCC, et al: Carotid endarterectomy and race: Do clinical indications and patient preferences account for differences? Stroke 33:29362943, 2002 37. Homer RD, Oddone EZ, Stechuchak K, et ah Racial variations in postoperative outcomes of carotid endarterectomy: Evidence from the Veterans Affairs National Surgical Quality Improvement Program. Med Care 40:I35-I43, 2002 (suppl 1) 38. Stallones RA: To advance epidemiology. Annu Rev Public Health 1:69-82, 1980 39. Kuller L, Reisler DM: An explanation for variations in distribution of stroke and arteriosclerotic heart disease among populations and racial groups. Am J EpidemioI 93:1-9, 1971 40. Reed DW: The paradox of high risk of stroke in populations with low risk of coronary heart disease. Am J Epidemiol 131:579-588, 1990 41. Sacco RL, Kargman DE, Gu Q, et al: Race-etbnicity and determinants of intracranial atherosclerotic cerebral infarction. The Northern Manhattan Stroke Study. Stroke 26:1420, 1995 42. Sacco RL, Boden-Albala B, Abel G, et al: Race-ethnic disparities in the impact of stroke risk factors: the northern Manhattan stroke study. Stroke 32:1725-1731, 2001 43. Worrall BB, Johnston KC, Kongable G, et al: Stroke risk factor profiles in African American women: An interim report from the African-American Antiplatelet Stroke Prevention Study. Stroke 33:913-919, 2002 44. Clark VR: The perilous effect of racism on blacks. Ethn Dis 11:769-772, 2001 45. Schneider AT, Pancioli AM, Khoury JC, et al: Trends in community knowledge of the warning signs and risk factors for stroke. JAMA 289:343-346, 2003 46. Ruland S, Raman R, Chaturvedi S, et al: Awareness, treatment, and control of vascular risk factors in African Americans with stroke. Neurology 60:64-68, 2003.