Transient Ischemic Attacks and Risk of Stroke in an Elderly Poor Population

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1 Transient Ischemic Attacks and Risk of Stroke in an Elderly Poor Population BY A. M. OSTFELD, M.D., R. B. SHEKELLE, Ph.D., AND H. L. KLAWANS, M.D. Abstract: Transient Ischemic A t tacks and Risk of Stroke in an Elderly Poor Population The significance for stroke and correlates of transient ischemic attacks (TIA) were studied prospectively in a population of,77 persons aged to 7. The prevalence of TIA at the beginning of the study was 3 per,. TIA prevalence was substantially higher among blacks and women than among whites and men. Only % of those with TIA were free from any other major evidence of cardiovascular disease., black men and black women with TIA had higher observed incidence rates of stroke than those without TIA. were a notable exception to this trend. There was a positive association between frequency of TIA and risk of stroke. Those with TIA and hypertension experienced higher stroke incidence rates than normotensive persons with TIA. Additional Key Words diabetes mellitus life table analysis epidemiology hypertension nonembolic brain infarction cardiovascular disease prospective study Introduction In October,, a cohort study of the epidemiology and natural history of strokes was begun in an elderly poor urban population in Cook County, Illinois. Previous papers based on the study have described the prevalence of several kinds of morbidity in the cohort, ' some of the methods of determining stroke incidence, 3 and risk factors for cerebrovascular attacks. This paper describes the transient ischemic attacks (TIA) in the cohort, their correlation with other cardiovascular disease in the subjects, and their outcome in terms of completed stroke. Methods The participants in the study were selected during and by probability sampling techniques from the population of non-institutionalized black and white men and women who were to 7 years of age and receiving financial assistance through the Department of Public Aid in Cook County, Illinois. They were interviewed in their homes, and subsequently came to a central facility where a medical examination emphasizing the cardiovascular and nervous systems was performed. The population, sampling procedures, defini- From the Department of Epidemiology and Public Health, Yale University School of Medicine, College Street, New Haven, Connecticut, ; the Department of Preventive Medicine and Community Health, Abraham Lincoln School of Medicine, 33 South Wolcott Street, Chicago, Illinois, 3; and the Presbyterian-St. Luke's Hospital, 73 South Congress Parkway, Chicago, Illinois, 3. tions of disease syndromes, and findings at initial examination have been described previously in greater detail. - Signs and symptoms of neurological dysfunction were recorded on standard forms by the examining physician, and these data were later reviewed by the senior neurologist (H.L.K.). Completed stroke was diagnosed if there was a clear history of focal cerebral deficit which occurred suddenly, lasted at least hours, showed some degree of improvement after the time of maximal involvement, and was compatible with occlusive or hemorrhagic involvement of one or more neck or intracranial arteries. The diagnosis was considered "definite" if neurological signs consistent with the history also were observed; otherwise the diagnosis was considered "possible." Transient ischemic attack (TIA) was diagnosed if there was a history of focal neurological dysfunction which met the criteria for completed stroke except that the deficit lasted less than hours and there were no detectable residua. A diagnosis of TIA was considered "probable" if the symptoms involved the long tracts or at least two cranial nerve nuclei; otherwise the diagnosis was considered "possible." Participants who did not have a diagnosis of definite or possible completed stroke at initial examination were visited semi-annually in their homes by field workers who had been trained in systematic interviewing and observational techniques to detect signs and symptoms of stroke. 3 A series of questions was asked at each visit about the occurrence of specific focal neurological deficits, e.g., "Has one whole side of your body, both your arm and your leg on the same side, ever suddenly gone weak or lost its strength?", and a positive reply was followed by probes to obtain Stroke, Vol., November-December

2 TIAs IN THE ELDERLY information about the event. Observations were systematically made for muscular weakness and incoordination, sensory loss or abnormalities, abnormalities of vision, gait and station, and disturbances of speech or language. A neurologist or senior neurology resident reexamined those participants who developed signs and symptoms suggestive of stroke during the follow-up period. Hospital and medical records, death certificates, and coroner's reports also were obtained. follow-up data were reviewed by the senior neurologist, who was responsible for the final diagnosis for purposes of this study. A diagnosis of stroke during the follow-up period was considered "definite" if based upon both a clear history and confirming signs; it was considered "possible" if based upon a clear history only, upon neurological signs best interpreted as residua of stroke in the absence of a clear history, or upon a death certificate statement only. Whenever possible, differentiation was made between hemorrhagic stroke, brain infarction due to embolism, and nonembolic brain infarction (NBI). Data are presented in the present paper on the association between diagnosis of probable TIA at initial examination and subsequent incidence of two endpoints: definite stroke, probably nonembolic brain infarction and all stroke (definite plus possible). These data have been analyzed by categorizing the participants in terms of one or more variables measured at entry, e.g., presence or absence of probable TIA, and comparing the categories with respect to incidence of the two endpoints. s of incidence and their standard errors have been computed by life table procedure for each of the eight sex-specific, race-specific, and age-specific groups (white and black men and women age to and 7 to 7) within a category, and the sex-specific, race-specific, and age-specific rates have been averaged to obtain adjusted rates for combined groups. The statistic used for testing the significance of a difference between two rates has been the ratio of the difference to its standard error. Two-tailed tests have been used with. set as the level of significance. Results Probable transient ischemic attack (TIA) was diagnosed in 7 (3 per,) of,77 black and white men and women age to 7 and free of completed stroke at initial examination. Prevalence rates of probable TIA, shown by sex, race, and age in table, are consistently higher in black persons than in whites. Overall, probable TIA was diagnosed in 77 per 3, of all black persons and in per, of all white persons (P <.). The prevalence rates for TIA are also consistently higher in women than in men, but the difference between white men and women is small. Probable TIA was diagnosed in 7 per, of all women and in per, of all men (P<.). Differences in prevalence of TIA between persons age to and 7 to 7 are small and not statistically significant. The right carotid arterial system was implicated by the clinical evidence in 3 cases of TIA (7%), Stroke, Vol., November-December the left carotid in cases (7%), and the vertebrobasilar system in cases (%). Two or more episodes of TIA were reported by (%) of the 7 cases; persons (%) reported a single episode only. The frequency of episodes was reported to be one or more episodes per month by persons (7%), was reported to be less frequent by persons (%), and was not determined in cases (% ). Persons with a diagnosis of probable TIA at initial examination are compared in table to persons without this diagnosis in terms of mean serum cholesterol, body mass (weight in kilograms divided by height in meters squared), age, systolic blood pressure, and diastolic blood pressure. None of the differences between groups is statistically significant, and no consistent trends in differences are apparent over the four sex-race categories. These groups are also compared in table 3 in terms of the prevalence of other cardiovascular conditions, history of physician-diagnosed diabetes mellitus, and cigarette smoking habits as determined at initial examination. In each sex-race group, prevalence rates for sclerotic peripheral arteries, intermittent claudication, and angina pectoris are higher in persons with TIA than in persons without TIA, and the differences between the mean rates over all four sex-race groups are statistically significant (P<.). Women with TIA have higher prevalence rates for Grade + hypertensive TABLE Prevalence of Probable Transient Ischemic Attack Among Persons Free of Completed Stroke at Initial Examination: Chicago Stroke Study Total Total Total perioni Age to 7 37, Age 7 to 7 3, Age to 7,77 Casei of TIA 7 7 Prevalence rate per, 7 7 3

3 OSTFELD, SHEKELLE, KLAWANS TABLE Mean Serum Cholesterol, Body Mass, Age, and Systolic and Diastolic Blood Pressures by Sex and Race According to Diagnosis of Probable Transient Ischemic Attack at Initial Examination, Persons to 7 and Free of Completed Stroke at Entry-. Chicago Stroke Study Sex-race category 3 Mean SD Mean Serum cholesterol (mg/dl) Body mass (kg/n 3 Age Systolic blood pressure Diastolic blood pressure retinopathy (Keith-Wagener criteria) and for clinical heart disease than women without TIA, but those i ) (mm Hg) (mm Hg) SD Difference In mean t differences are not observed in men. In all sex-race groups except white men, persons with TIA have TABLE 3 Prevalence of Cardiovascular Conditions, Diabetes Mellitus, and Cigarette Smoking by Sex and Race According to Diagnosis of Probable Transient Ischemic Attack at Initial Examination, Persons Age to 7 and Free of Completed Stroke at Entry: Chicago Stroke Study Conditions Hypertension* Grade + hypertensive retinopathy Sclerotic peripheral arteries Peripheral atherosclerosis Angina pectoris Myocardial infarction Any clinical heart disease Atrial fibrillation Major ECG abnormalities Any ECG abnormality Diabetes mellitus by history Cigarette smoking 3f J 3 7 White men TIA+ TIA- 33 Black men TIA + ria- 3 t J 3 3 3J 3 3 TIA + White women 3 J * * f 3 ria TIA + Biock women Hypertension defined as systolic blood pressure > mm Hg, or diastolic blood pressure > mm Hg, or both. fs per. Denominators are shown at the top of each column. tthis symbol identifies pairs of rates that are significantly different (P <., two-tailed). Stroke, Vol.. November-December J 3 3J 3* 33J 7 7J 3J TIA- 3 3 TA+ Mean rates 3 J 7% J t J TIA

4 TIAs IN THE ELDERLY TABLE Three-Year Incidence s for Definite Nonembolic Brain Infarction and for Stroke by Sex and Race According to Diagnosis of Probable Transient Ischemic Attack at Initial Examination, Persons Age to 7 and Free of Completed Stroke at Entry: Chicago Stroke Study person! 7,, * stroke *s per, computed by life table procedure and age-adjusted by five-year intervals. The rates for all participants are means of four sex-race specific rates higher prevalence rates for myocardial infarction and for history of physician-diagnosed diabetes mellitus. The difference between mean rates over all four sex-race groups is statistically significant for diabetes mellitus but not for myocardial infarction. Differences between persons with and without TIA in prevalence rates for hypertension (systolic pressure and/ or diastolic pressure > mm Hg), electrocardiographical abnormalities, and cigarette smoking are small and not statistically significant. Age-adjusted three-year incidence rates for definite stroke, probably nonembolic brain infarction (NBI) and for all stroke are shown in table by sex and race according to diagnosis of probable TIA at initial examination. These data indicate that white men, black men, and black women with TIA have higher observed incidence rates of definite NBI and of all stroke than persons of the same sex and race without TIA. The group of white women is the exception to this trend; only one case of stroke occurred during the follow-up period in the white women who had probable TIA at entry. Averaged over all four sexrace groups, the mean three-year incidence rate for definite NBI in persons with TIA is 7 per, and in persons without TIA is per,; the % confidence interval for this difference in rate is Stroke, Vol., November-December 7 to 7. The mean three-year incidence rates for all stroke in persons with and without probable TIA is per, and per,, respectively, and the % confidence interval for this difference is to. Although the differences in incidence rates of stroke are in the expected direction (higher in those with TIA) the numbers are small and the standard errors large. Data in table indicate that the risk of definite NBI and of all stroke in persons with probable TIA is not related to the arterial system implicated by the clinical evidence. Persons with TIA suggesting a carotid arterial lesion have incidence rates for definite NBI and for all stroke that are similar to the rates observed in persons with TIA suggesting a vertebrobasilar arterial lesion. The frequency of TIA reported at entry, on the other hand, does appear to be related to risk of definite NBI (table ). Persons reporting one or more TIA per month at initial examination have an observed risk of definite NBI that is five times greater than the risk observed in persons reporting less than one episode per month (P<.). The observed risk of all stroke, however, is only. times greater in persons reporting one or more TIA per month as compared to persons reporting less 3

5 OSTFELD, SHEKELLE, KLAWANS TABLE Three-Year Incidence Raies for Definite Nonembolic Brain Infarction and for Stroke According to the Arterial System Implicated by the Transient Ischemic Attack, Black and White Men and Women Age to 7 and Free of Completed Stroke But With Diagnosis of Probable Transient Ischemic Attack at Entry-. Chicago Stroke Study Arterial system Carotid Vertebrobasilar persons 77 7 s per, computed by life table procedure and adjusted for sex, race, and age. * 7 7 stroke frequent episodes, and the difference is not statistically significant. In persons who were hypertensive at initial examination (systolic blood pressure > and/or diastolic pressure > mm Hg), the three-year incidence rates for definite NBI are per, and per, in persons with and without TIA, respectively (table 7). Although the relative risk is greater than two, the difference between rates is not statistically significant. For all stroke, however, the corresponding three-year incidence rates are per, and per,, and the difference between rates is statistically significant (P<.). The mean systolic and diastolic blood pressures at entry of hypertensive persons with and without TIA are quite similar: / and /, respectively. Although nonhypertensive persons with TIA have higher observed incidence rates for definite NBI and for all stroke than nonhypertensive persons without TIA ( and 3 per, for definite NBI and and per, for all stroke, respectively), the difference in rates are smaller than observed in the hypertensive persons and are not statistically significant. Table shows the association between TIA and risk of definite NBI and of all stroke in persons who TABLE Three-Year Incidence s for Definite Nonembolic Brain Infarction and for Stroke According to the Frequency of Transient Ischemic Attack Reported at Initial Examination, Black and White Men and Women Age to 7 and Free of Completed Stroke But With Diagnosis of Probable Transient Ischemic Attack at Entry: Chicago Stroke Study Frequency One or more TIA per month Less than one TIA per month Unknown persons * *s per, computed by life table procedure and adjusted for sex, race, and age. 3 stroke TABLE 7 Three-Year Incidence s for Definite Nonembolic Brain Infarction and for Stroke According to Diagnosis of Probable Transient Ischemic Attack and Level of Blood Pressure at Initial Examination, White and Black Men and Women Age to 7 and Free of Completed Stroke at Entry: Chicago Stroke Study persons Systolic pressure > and/or diastolic pressure 7 *, Systolic pressure <, and diastolic pressure < 3 > mm Hg mm Hg *s per, computed by life table procedure and adjusted for age, sex, and race. stroke 37 3 Sfroke, Vol.. November-December

6 TIAs IN THE ELDERLY TABLE Three-Year Incidence s for Definite Nonembo/ic Brain Infarction and for Stroke According to Diagnosis of Probable Transient Ischemic Attack and Other Cardiovascular Conditions at Initial Examination, White and Black Men and Women Age to 7 and Free of Completed Stroke at Entry: Chicago Stroke Study personl, 3,7 Other cardiovascular conditions present* 7f 7 Other cardiovascular conditions absent stroke *Participants in this category had one or more of the following conditions present at entry: sclerotic peripheral arteries, diabetes mellitus by history, peripheral atherosclerosis, and clinical heart disease. ts per, computed by life table procedure and adjusted for age, sex, and race had one or more other cardiovascular conditions (sclerotic peripheral arteries, intermittent claudication, clinical heart disease, and diabetes mellitus) at initial examination and in persons who had none of these conditions at initial examination. Only (%) of the 7 persons with probable TIA did not have one or more of these other conditions also at initial examination, and this number is too small for obtaining reliable estimates of incidence. In the participants who did have one or more of these conditions present at initial examination, persons with TIA had higher observed incidence rates for definite NBI than persons without TIA ( and per,, respectively) and also higher incidence rates for all stroke ( and 7 per,, respectively). The difference between rates for definite NBI is not statistically significant (the % confidence interval for the difference is - to 3), but the difference between rates for all stroke is significant P <. (the % confidence interval is to ). Discussion The prevalence of TIA in this elderly population is relatively high, about in. The true rate is probably somewhat higher than that because our criteria for TIA were stringent and the initial histories, not taken by neurologists, may have missed some cases. Previous studies of TIA have been largely limited to whites and virtually no data are available now on black-white differences. The higher prevalence of TIA among blacks in this cohort is compatible with the higher prevalence among blacks of completed stroke at the initial examination and may reflect the well-known higher blood pressures and stroke incidence among blacks in other studies. " The cross-sectional data indicate that TIA is rarely the sole indication of cardiovascular disease Stroke, Vol., November-December for these elderly persons. Instead, the observations indicate that persons with TIA also tend to have coronary and peripheral vascular disease as well. Only % of persons with probable TIA did not have observable sclerotic peripheral arteries, evidence of peripheral vascular disease, clinically evident heart disease or diabetes mellitus. It is likely that treatment of neck vessel diseases in these elderly persons would not affect the overall outlook for their atherosclerotic disease. The incidence data indicate that TIAs are associated with increased risk of stroke particularly if the TIAs occur more often than once a month or are associated with high blood pressure or other cardiovascular disease. This may imply that early treatment of hypertension and other risk factors for atherosclerosis will have a preventive effect. The association between poor health and poverty is so well known as to require little defense here. " Even in the area of stroke, the autopsy studies of Loewenson et al. suggest that, especially among women, the prevalence of cerebral atherosclerosis is higher among the poor. Caldwell et al. found that dropouts from antihypertensive treatment are more likely to be of lower education and income and to be nonwhite. It seems defensible, therefore, to take the position that morbidity and mortality from cerebrovascular disease will be as high or higher in our cohort than in most other U. S. studies. References. Ostfeld AM, Shekeile RB, Tufo HM, et al: Cardiovascular and cerebrovascular disease in an elderly poor urban population. Amer J Public Health : -, 7. Klawans HL, Tufo HM, Ostfeld AM, et al: Neurologic examination in an elderly population. Dis Nerv Syst 3: 7-7, 7

7 OSTFELD, SHEKELLE, KLAWANS 3. Shekelle RB, Klawons HL, Ostfeld AM, et al: A screening procedure for stroke. Amer J Public Health : 77-, 7. Shekelle RB, Ostfeld AM, Klowans HL: Hypertension and risk of stroke in an elderly population. Stroke (Jan-Feb) 7. Cutler SJ, Ederer F: Maximum utilization of the life table method in analyzing survival. J Chron Dis : -7,. Heyman A, Korp HR, et al: Cerebrovascular disease in the bi-racial population of Evans County, Georgia. Stroke : -, 7 7. McDonough JR, et al: Blood pressure and hypertensive disease among Negroes and whites. Ann Int Med: -,. Chapman JM, et al: Epidemiology of vascular lesions affecting the central nervous system: The occurrence of strokes in a sample population under observation for cardiovascular disease. Amer J Public Health : -,. National Center for Health Statistics: Socio-economic characteristics of deceased persons. U. S. -3 deaths. Vital and Health Statistics. PHS Publication, Series,, Washington, D.C., U. S. Government Printing Office (Feb). Kitagawa EM, Hauser PM: Educational differentials in mortality by cause of death. U. S. Demography : -33. Antonovsky A: Social class, life expectancy, and overall mortality. Milbank Mem Fund Quart : -, 7. Loewenson RB, Flora GC, Baker AB: The role of socioeconomic factors in cerebral atherosclerosis. Stroke : 37-33, 7. Caldwell JR, Cobb S, Dowling MD, et al: The dropout problem in antihypertensive treatment. J Chron Dis : 7-, 7 SfroJre, Vol. A. Norember-Decembar

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