Survey of Stroke Epidemiology Studies

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1 Survey of Stroke Epidemiology Studies COMMITTEE ON CRITERIA AND METHODS, COUNCIL OF EPIDEMIOLOGY, AMERICAN HEART ASSOCIATION REPORT PREPARED BY: LEWIS H. KULLER, M.D., LEONARD P. COOK, AND GARY D. FRIEDMAN, M.D.* Abstract: Survey of Stroke Epidemiology Studies The Committee on Criteria and Methods of the Epidemiological Council of the American Heart Association conducted a survey of epidemiological studies of stroke. A questionnaire was sent to investigators who were involved in stroke epidemiological research. Forty studies have been reviewed. Stroke epidemiological studies include a wide range of populations and geographic areas of the United States. Of the prospective studies only five were primarily stroke-oriented, while the remaining initially involved the study of coronary artery disease. Relatively few stroke studies identify cases by clinical examination at the time of the stroke; most depend on examination sometime after the stroke, review of hospital records, physician's reports and patient interviews. In relatively few of the studies are the cases being examined by a neurologist. There is a need for better methods of stroke-case ascertainment, for standardized diagnostic techniques that can be used in field studies, and for the evaluation of specific disabilities following a stroke. Additional Key Words transient ischemic attacks diagnostic procedures duration of stroke neurological examination Downloaded from by on November, 0 The Committee on Criteria and Methods of the Council on Epidemiology, American Heart Association, has been concerned with the criteria and methods for the diagnosis and classification of strokes in epidemiological studies. A logical first step in arriving at appropriate recommendations was to survey the investigators active in the field to determine what was actually being done. Methods Investigators believed to be working in the field of stroke were identified from a list of grantees of the National Institute of Neurological Diseases and Stroke, the National Heart and Lung Institute, and members and fellows of The Council on Cerebrovascular Disease and the Council on Epidemiology of the American Heart Association. A questionnaire was mailed to 09 investigators. From the Johns Hopkins University, School of Hygiene and Public Health, North Wolfe Street, Baltimore, Maryland, 0. Stroka, Vol., Sopfember-Ocfober 9 About half () of the 09 questionnaires were returned and from these, 0 separate studies related to stroke epidemiology were identified. A careful comparison of the names of nonrespondents with those of known investigators and authors in the field of stroke epidemiology convinced us that at most two or three study groups did not return their questionnaires. Replies were also received from six hospital-based studies which dealt with the follow-up of selected patients in order to evaluate the natural history following a stroke. These studies will not be considered further in this report. Results TYPES OF STUDIES As shown in table, prospective studies of stroke have been reported. Five of the deal primarily with stroke, while the remaining were originally designed to investigate arteriosclerotic heart disease. Six of the prospective studies are community based, five are being conducted in specific occupational groups, and the remaining six are 9

2 KULLER, COOK, FRIEDMAN TABLE Distribution of Stroke Epidemiology Studies According to Study Design, Type of Population and Degree of Emphasis on Stroke Study population Community Hospital/clinic Occupational Autopsy/death certificate Racial/ethnic Elderly Other Primarily stroke Not primarily stroke Prospective R sfrosp ch v - proipecttv* Study Crousoctlonal design Retrospective xporlmentol Toted Downloaded from by on November, 0 equally divided among hospital/clinic populations, racial/ethnic groups and elderly populations. Both sexes, most age and racial groups, and various geographic areas of the United States are represented in the prospective studies. Two of the studies are concerned primarily with transient ischemic attacks, while the other are concerned with risk factors related to both stroke and coronary heart disease. About 9,000 people are under surveillance by all of the prospective studies combined. Four of the investigations were described as retrospective-prospective or historical prospective studies. The populations being studied include an occupational group, a group of former college students, and two community population samples. One of the four studies includes transient cerebral ischemia as a risk factor. TABLE Two of three cross-sectional studies are hospital-based stroke registries and the third is a study of risk factors in Japanese-Americans. The eight retrospective studies include three postmortem investigations (an evaluation of geographic differences in stroke mortality in the United States), two studies dealing with hospital populations including a study of the relationship of oral contraceptives to stroke, and two community studies. Of the eight experimental or therapeutic trials reported, four were primarily oriented to stroke and the other four to the treatment of hypertension or coronary risk factors. METHODS OF CASE ASCERTAINMENT Investigators in of the 0 studies ascertained at least some of the cases themselves. In the remaining, case ascertainment depended on hospital records, reports of attending physician or patient, and other records (table Method* of Cose Ascertainment Used in Each of the Various Types of Stroke Epidemiology Studies Method of case ascertainment Hospital records Study physician examination Death certificate Attending physician reports Autopsy protocols Reports by patients or subjects Other Only one method used Multiple methods used Prospective 9 0 R *troftp Act! v - protpattlvo Study design Crosssectional Retrospective Experimented Toted 9 0 Stroke, Vol., Ssptember-Odober J9

3 STROKE EPIDEMIOLOGY STUDIES Downloaded from by on November, 0 TABLE Usual Intervention Between Stroke Onset and Patient Examination by Study Physician Prospective and All Studies Combined Intoned < day - days wk-< mo mo-< mo > mos Unknown Not applicable Not stated Profptctiv* 0 0 ). Most of the studies ascertained cases from more than one source. Practically all of the prospective studies included at least some examination by a study physician, as did the experimental studies. It should be noted, however, that in most cases the examination by the study physician usually took place some time after the stroke (table ). In only two of the prospective studies did the study physician's clinical examination usually occur within a week after the stroke. Thus, most of the stroke studies depend on a history of stroke obtained either from clinical records or from the patient, later validated by a clinical examination and evaluation by a study physician. In only studies (including seven prospective, two retrospective, and three experimental) were at least some of the examinations completed by a neurologist (table ). Seventeen of the studies included a standardized neurological examination by either a neurologist or a staff physician. TABLE Percentage of Patients Examined by a Neurologist, According to Study Design Study dmlgn Examination by neurologist Proipoctivo RstroipocthroproipMttvo Cros»->««tlonat RatrospoctW* None %-9% 0%-00% Unknown Not applicable Not stated DIAGNOSTIC PROCEDURES Diagnostic procedures such as spinal puncture, EEG and angiography were performed by the study physician in only nine of the 0 studies (table ). They were done most often in the experimental trials (four out of eight). The other five studies that reported these procedures include two prospective, two retrospective and one retrospective-prospective study. The other studies depended on diagnostic procedures that were part of the routine workup of patients in the hospital. Hospital records of stroke patients were reviewed by the study physicians in 9 of the studies using hospital records (table ). In only four of the studies was a special form included in the hospital chart to be completed by a physician during the initial examination of the stroke patient. In many of the other studies ( of 0) a special form was used to abstract the clinical information included in the hospital record. In most of the studies ( of 0) a history of stroke symptoms was obtained from the patient. In 0 of the some type of standardized questionnaire was used to obtain the history. In this survey, no attempt was made to determine the validity of these questionnaires or whether any of them were used in more than one study. Except for three retrospective studies, few other investigations used autopsies as a principal source of stroke data. In only eight studies were at least some of the autopsies performed by a pathologist who was a member IxporimantoJ Stroke, Vol., September-October 9

4 KULLER, COOK, FRIEDMAN Downloaded from by on November, 0 TABLE Number of Sfvdies in Which Diagnosfic Procedures are Preferred by Study or Of/ier Physicians MognoiHc pro<* ur* Spinal puncture Angiography EEG Skull x-ray Radioisotope Thermography Study physidulf Othsr phyiidans 0 9 of the research group. In several studies some of the brain examinations were done by a neuropathologist. Thus, at present, epidemiological studies that emphasize the pathology of cerebrovascular disease consist primarily of retrospective analyses of the correlation of cerebral pathology and antemortem hospital records. DEFINITION AND CLASSIFICATION OF STROKE AND TIA Generally the definition of stroke was based on a history of an acute onset of neurological deficit such as aphasia, hemiplegia, hemianesthesia and sometimes loss of consciousness. Several of the studies also included the length of disability as a parameter in the definition of stroke. However, there was no consistent minimal time limit of disability used in the different studies. Many of the studies also identified patients with transient ischemic attacks. The most frequent definition of a transient ischemic attack was a focal neurological deficit of less than hours' duration (0 studies). These TABLE Person Abstracting Hospital Records According to Whether Special Form or No Special Form Used: Studies Using Hospital Records Panon afcttroctlng hoipitoi rmord (pedal form Study physician Attending physician Nurse Other medical person Nonmedical person Number of trudl** No spatial form ten studies include one that set six hours as the maximum TIA duration. One other study used hours as the maximum. Only studies could provide a breakdown of the types of stroke. Cerebral infarction accounted for over 0% of the cases in the majority of these studies. Other types of stroke accounted for less than one-quarter of all patients in all but one study. In this study the investigator stated that all the cerebrovascular events were due to cerebral emboli. Discussion A survey of epidemiological studies of cerebrovascular disease within the United States has been completed. Forty studies with at least some epidemiological aspects have been reported. In general, the studies include all age groups and most racial groups within the United States. Many of the studies are "spinoffs" of epidemiological studies of arteriosclerotic heart disease. At least four of the studies are primarily concerned with transient ischemic attack and three with the pathology of cerebrovascular disease. The study designs include prospective, retrospective, retrospectiveprospective, cross-sectional, and experimental types. Although the methods of data collection vary, study cases are usually ascertained initially from regular medical sources such as hospitals, physicians, or by interviewing the study subjects. The respondents are often interviewed and examined by a member of the study staff in order to verify the stroke diagnosis and determine residual disability. It would appear that the accuracy of the diagnosis of the specific type of stroke is often dependent on the quality of the initial work-up of the patient in the community. Very few of the study groups use specific diagnostic tests to determine the type of stroke. Similarly, those groups that perform their own diagnostic procedures usually do so quite some time after the stroke rather than immediately after. The definition of stroke is usually based either on a history of neurological deficit of relatively sudden onset or on specific abnormalities found on physical examination. Some of the studies also require that the disability be present for a certain duration (usually at least hours) in order to separate completed stroke from transient ischemic attack. The definitions of transient ischemic attack also Sfrok; Vol., September-October 9

5 STROKE EPIDEMIOLOGY STUDIES Downloaded from by on November, 0 varied from study to study; a history of a neurological deficit which clears in a defined period of time was the usual definition. Most of the studies depend on a history of such symptoms as reported by the patient directly or abstracted from medical records. In epidemiological studies of coronary heart disease, the electrocardiogram can be used as a reasonably adequate measure of the presence or absence of a myocardial infarction. Unfortunately, there now exists no analogous simple objective measure to confirm the diagnosis of a stroke. The axis of objectivity of the stroke diagnosis can vary from the pathological diagnosis of a cerebral lesion, i.e., infarction or hemorrhage, to a history of a "stroke" or "stroke symptom" reported by a respondent on a questionnaire. The various types of clinical neurological examinations would lie somewhere along this axis. The more refined methods of diagnosis involve some reduction in the scope of case ascertainment. Thus, studies limited to detailed neuropathology can include only those subjects who have died and then been subjected to a postmortem neuropathological examination. Because of the relatively low prevalence of stroke in all but the oldest age groups and because of prevailing low autopsy percentages, studies utilizing neuropathology are limited to case-control studies in which no antemortem data have usually been collected in a systematic way. It is doubtful whether prospective studies utilizing only the neuropathological diagnosis of stroke are feasible in the United States at present. Similarly, the utilization of detailed clinical neurological examination as a primary source of case-finding presents some interesting problems. The prompt ascertainment of new stroke patients is difficult in most communities because of the multitude of facilities that stroke patients may utilize. Furthermore, a substantial percentage of patients may die before they are seen by a neurologist. In selected communities and situations where it may be possible to have a careful systematic evaluation of most acute stroke patients (i.e., a small community with a single hospital), the problems of small sample size and/or patient selection due to referrals to a teaching or other specialized hospital are matters of concern. Except in these situations, Sirokt, Vol., Sepfember-Ocfober 9 the expense, in both time and money, of a detailed neurological examination for research purposes may preclude its use. The neurological examination may be delayed beyond the acute phase as has been reported in most of the studies surveyed. Three different approaches have been noted: () The stroke patient is initially identified during the acute phase. The neurological examination by the study physician is done later. () A history of previous stroke or stroke symptoms is obtained from the patient and the diagnosis is then confirmed by a neurological examination. () A neurological screening examination is done on all participants in a study regardless of their history of stroke. Unfortunately, the objective evidence of a stroke may have disappeared or become relatively nonspecific by the time of the latter neurological examination. Furthermore, the rate of resolution of specific disability after a stroke may be related to other variables of interest to the investigator resulting in possible spurious associations. The detailed neurological examination of all study subjects irrespective of a history of stroke is expensive, time-consuming and probably of low yield because of the low incidence and prevalence of stroke. The percentage of stroke patients who can be identified only with this neurological examination, i.e., without a history, may be small. A history of stroke or stroke symptoms is the crudest method of defining stroke. It is also the simplest and most economical in large-scale studies. The validity of this approach may be suspect both because of failure to report actual strokes that have occurred (lack of sensitivity) and because of false labeling as stroke of other clinical syndromes (lack of specificity). However, to our knowledge the validity of this method has not been tested. Stroke may be classified on the basis of pathology, i.e., cerebral hemorrhage, infarction, etc.; on the basis of duration from transient ischemia (clinical stage) to a completed stroke with permanent residua; or in relation to the location of the specific vascular lesion, intracranial, extracranial, etc. The importance of these classifications in relation to the variables being studied has not been adequately demonstrated. At least one major risk factor, hypertension, appears to be related to most types of stroke. On the other hand,

6 KULLER, COOK, FRIEDMAN Downloaded from by on November, 0 other risk factors may be related to one or more specific types of stroke or to location of the underlying disease. Experiences with other diseases indicates that it is useful to classify larger disease groups into subgroups. For example, in coronary disease, angina pectoris has different risk factors than myocardial infarction. It is readily apparent that few epidemiological studies of stroke have utilized diagnostic techniques adequate to classify stroke cases on the basis of pathogenesis, temporal distribution and specific localization of arterial lesions. Determining the duration of disability used to differentiate a cerebral infarction from a transient ischemic attack presents methodological problems. Since complete functional recovery apparently can occur with pathological evidence of definite brain damage, complete clinical recovery cannot be used as the criterion for diagnosing a transient ischemic attack. Most authorities use duration to complete recovery as the criterion. Pathology seems to be only of partial help in differentiating stroke types. For example, regarding the question of thrombosis versus embolus, the obstructing clot may have become so changed and organized by the time of autopsy that it is no longer possible to tell whether it developed in situ or was carried from a distance. In some instances the diagnosis of cerebral emboli may depend heavily upon other observations such as a history of atrial fibrillation or the presence of cardiac mural thrombi as potential sources of emboli, or upon evidence, both clinical and pathological, of embolization to other organs. This can hardly be considered a foolproof or completely independent means of differentiating thrombi from emboli. Recommendations. The various components of clinical, laboratory and pathological criteria of stroke need to be formally evaluated. In particular, their sensitivity (proportion of true strokes which are detected) and specificity (proportion of non-strokes which are correctly labeled as such) and reproducibility need to be determined. The contribution that the more difficult and expensive procedures make to case detection, over and above that made by simpler techniques, needs to be measured. Examples of recommended evaluations would be: a. A determination of the proportion of patients who are known to have had a stroke, who will later answer "yes" to the question, "Have you ever had a stroke?" This would determine the sensitivity of this question. b. Regarding individuals with a neurological deficit such as hemiparesis or aphasia, the proportion whose disability is due to a stroke rather than to other diseases such as neoplasms, metabolic disease or trauma should be determined. This would lead to a measure of the specificity of these examination findings with regard to the diagnosis of prior stroke. Of course, age would have to be taken into account. c. A measure is needed of the percentage of strokes that would be missed by a general physician performing a standard brief, specially designed history and physical examination as compared to a detailed examination by a neurologist. The additional yield of cases by the neurologist may not be sufficient to justify the extra effort and expense involved for largescale epidemiological studies. Furthermore, it will be important to determine whether the "missed cases" differ from those identified previously. d. It is rarely possible to obtain lumbar puncture (LP) data on 00% of stroke patients in a study. If the clinical picture provides reasonably accurate means of distinguishing cerebral hemorrhage from cerebral thrombosis, reliance on the cerebrospinal fluid examination may not be necessary for epidemiological studies. A simple evaluation of the ability of clinical criteria to distinguish hemorrhage from thrombosis should be performed for stroke cases on which LPs were done. For each case a decision could be made using clinical criteria alone, with the LP findings concealed. The results could be compared with the spinal puncture findings.. The rate of disappearance of disability in stroke patients needs further study. At each succeeding time interval from the initial stroke event (e.g., one week, one month, six months, one year, five years), what proportion of stroke patients no longer show any obvious disability or physical examination findings? The relationship, if any, of this rate of disappearance to Stroke, Vol., Soptemb*r-October 9

7 STROKE EPIDEMIOLOGY STUDIES Downloaded from by on November, 0 possible stroke risk factors should be determined. If a risk factor is associated with more rapid disappearance of findings, its relationship to stroke may be obscured if strokes are not ascertained promptly.. The role of special diagnostic procedures in epidemiological studies of stroke needs to be clarified. For example, in patients with completed strokes, do the research benefits of cerebral angiography justify the small but not negligible risks to the patient? On the other hand, without angiography how can other tests such as thermography, pulse wave propagation, or retinal pulses be evaluated?. The need for simple objective indicators of stroke (analogous to the electrocardiogram for myocardial infarction) is apparent. These indicators need not be restricted to the assessment of anatomical brain damage per se. Objective tests of various forms of disability such as muscular weakness or aphasia may deserve more use in screening for stroke.. Clear-cut objective measurements are probably most needed in the evaluation of the natural history of stroke and in experimental or therapeutic trials of acute care and rehabilitation. Accurate replicable techniques that could be applied to relatively large numbers of patients are badly needed.. Because of the low incidence of stroke in the younger age groups, retrospective or cross-sectional studies should be encouraged as the most practical approach to the study of stroke in this portion of the population.. The duration of symptoms used to define transient ischemic attacks and strokes or to distinguish between the two are not standardized. It is probably premature to suggest that specific durations (e.g., upper limit for TIA of hours) be universally adopted. It is recommended that the actual or approximate duration of disability be recorded, when known, to aid in comparability among studies. Then, all cases with disability of any given duration category could be identified in each study and their characteristics assessed. Furthermore, contrasts could then be made between subgroups such as persons with TIAs lasting less than one hour versus those with TIAs lasting from one to hours. Acknowledgments We would like to thank all the investigators who responded to the survey for their assistance in providing information about their studies. Copies of the questionnaires and a list of the studies may be obtained from the American Heart Association, East rd Street, New York, New York, 000 (Mr. Cook). Stroke, Vol., September-October 9