Differences in Stroke Subtypes Among Natives and Caucasians in Boston and Buenos Aires
Background and Purpose—Several issues regarding ethnic-cultural factors, sex-related variation, and risk factors for stroke have been described in the literature. However, there have been no prospective studies comparing ethnic differences and stroke subtypes between populations from South America and North America. It has been suggested that natives from Buenos Aires, Argentina, may have higher frequency of hemorrhagic strokes and penetrating artery disease than North American subjects. The aim of this study was to validate this hypothesis.
Methods—We studied the database of all consecutive acute stroke patients admitted to the Ramos Mejia Hospital (RMH) in Buenos Aires and to the Beth Israel Deaconess Medical Center (BIMC) in Boston, Massachusetts, from July 1997 to March 1999. Stroke subtypes were classified according to the Trial of Org 10172 in Acute Stroke Treatment (TOAST) criteria. All information on patients (demographic, clinical, and radiographic) was recorded prospective to the assessment of the stroke subtype.
Results—Three hundred sixty-one and 479 stroke patients were included at RMH and BIMC stroke data banks, respectively. Coronary artery disease was significantly more frequent in BIMC (P<0.001), whereas tobacco and alcohol intake were significantly more frequent in RMH (P<0.001). Intracerebral hemorrhage (P<0.001) and penetrating artery disease (P<0.001) were significantly more frequent in the RMH registry, whereas large-artery disease (P<0.02) and cardioembolism (P<0.001) were more common in the BIMC data bank.
Conclusions—Penetrating artery disease and intracerebral hemorrhage were the most frequent stroke subtypes in natives from Buenos Aires. Lacunar strokes and intracerebral hemorrhage were more frequent among Caucasians from Buenos Aires than Caucasians from Boston. Poor risk factor control and dietary habits could explain these differences.
Several factors contribute to stroke incidence. Risk factors vary worldwide, depending on ethnicity and regional differences.1 2 3 Few prospective studies have compared stroke subtypes in natives and Caucasians from different countries.4 5 6 7 8 9 Some of these studies suggest a similar frequency of risk factors but a varying incidence of stroke subtypes. The literature suggests higher frequency of hemorrhagic stroke among Asians,10 11 12 blacks,13 14 and natives from Ecuador.4 In addition, natives from South America may have a higher incidence of penetrating artery disease. However, this hypothesis has not been previously tested.
The purpose of this study was to analyze clinical characteristics and risk factors among natives and Caucasians, comparing 2 specified communities in Boston, Massachusetts, and Buenos Aires, Argentina, to better understand ethnic differences.
Subjects and Methods
We studied the database of all consecutive acute stroke patients admitted to the Ramos Mejia Hospital (RMH) in Buenos Aires and to the Beth Israel Deaconess Medical Center in Boston (BIMC) from July 1997 to March 1999. We considered clinical features, epidemiological characteristics (including ethnicity), neuroradiological findings, and National Institutes of Health Stroke Scale score at admission. We used the same forms to include patients in both stroke data banks. All information on patients (demographic, clinical, and radiographic) was recorded prospective to the assessment of stroke subtype. Patients had the appropriate workup (MRI, MR angiography, Doppler of the neck vessels, hypercoagulable battery, transesophageal echocardiogram, cerebral angiography) to determine the etiology of the stroke according to the Trial of Org 10172 in Acute Stroke Treatment (TOAST) classification.15 Patients were evaluated by at least 2 neurologists. All patients with stroke were admitted to the RMH or BIMC.
Clinical characteristics and other items were recorded on a form especially designed for this study, which included date and hour of admission, symptoms at onset, vascular territory, risk factors, primary diagnosis (TOAST classification), and neurological examination. Also included in the forms were brain templates that were based on the Damasio model16 for lesion localization.
Ethnicity was defined according to the criteria of the 4 past generations. Those patients whose great-grandparents, grandparents, or parents were from Europe were considered Caucasians. Those patients whose parents were not descended from Europeans were considered natives. Those patients whose parents were born in Mexico were considered Hispanics.
Stroke was defined according to the World Health Organization criteria17 : rapidly developed clinical signs of focal disturbance of cerebral function, lasting >24 hours or leading to death, with no other apparent cause than cerebrovascular disease. Hemorrhagic or ischemic strokes were determined by CT scan or MRI.
Ischemic strokes were classified into the following categories: infarction due to extracranial or intracranial atherosclerosis, embolism from a commonly accepted cardiac source, lacunar infarction, undetermined or cryptogenic infarction, and stroke from other unusual causes, as in the TOAST classification.15
Large deep infarcts presenting with lacunar syndrome with neither cardiac source of embolus nor large-artery atherosclerosis were classified as undetermined, in light of recent studies showing that large striatocapsular infarcts were unlikely to be due to small-vessel disease.18 19 20 21 Occasionally, small deep infarcts presenting with lacunar syndrome and a negative evaluation for source of embolus or large-artery disease were classified as cryptogenic if the infarct location or arterial involvement was not typical for lacunes (eg, midbrain, anterior choroidal artery territory), if there was incidental radiological evidence of previous asymptomatic nonlacunar infarct in the same vascular territory as the index lacune, or if a potential source of embolism was suggested although not definite (eg, spontaneous echo contrast, multiple filamentous strands). This category was designed to ensure that the other categories contain a minimum of instances of contentious classification. Infarction of other determined cause includes dissection, fibromuscular dysplasia, vasculitis, sickle cell anemia, stroke in the setting of migraine, mycotic aneurysms, and other diagnosed but rare or unusual forms of stroke (Table 1⇓⇓).
Hemorrhagic stroke was defined as a sudden development of neurological deficit with intracranial hemorrhage (ICH) or subarachnoid hemorrhage (SAH) on cerebral CT or MRI. Those patients with traumatic hemorrhage, hemorrhagic transformation due to cerebral infarction, and hemorrhage secondary to anticoagulant use were excluded. When both an ICH and a SAH were present, the radiologist considered which one was primarily responsible for the bleeding.
All brain images were evaluated by radiologists who were blinded to the clinical findings. Hypertension was defined as on antihypertensive therapy or measurements on 2 examinations of systolic pressure >140 mm Hg or diastolic pressure >90 mm Hg or any combination of them. Moderate alcohol consumption was defined as >50 g/d (equivalent to 500 mL [2 drinks] of wine, 1000 mL of beer, or >5 drinks [units] of spirits). Smoking was defined as >10 cigarettes per day. Other risk factors were defined according to the Framingham Study.22
EPI Info 6.0 and SPSS were used for the data analyses. Student’s t tests were used for comparisons of continuous data, and χ2 analyses and Fisher’s exact tests were used for the categorical data. In Table 1⇑, the “H” analyses studied the association between the 2 hospitals in the overall cohort and each of the individual characteristic variables (eg, age, sex). The “C” analyses studied the relation between the characteristic (demographic and risk factor) variables and stroke subtype. To test whether the relationship between stroke subtype and hospital was modified by demographic characteristics and risk factors, interaction “H× C” analyses were performed when the data were complete.
Three hundred sixty-one and 479 patients were included in the RMH and BIMC stroke data banks, respectively. Mean age was 62 and 69 years, respectively, in each registry (P<0.001). Among stroke patients at RMH, 168 (46%) were Caucasians, 190 (53%) were natives, and 3 (1%) were Asians. In the BIMC, 410 patients (86%) were Caucasians, 49 (10%) were blacks, 15 (3%) were Hispanics (natives from Mexico), and 5 (1%) were Asians. Table 1⇑ shows population characteristics and risk factors according to the stroke subtypes in the RMH and BIMC data banks.
Hypertension was the most frequent risk factor, present in 75% and 65% of the patients in the RMH and BIMC databases, respectively. Forty-seven (13%) and 86 (18%) of the patients had previous stroke in the RMH and BIMC, respectively.
Coronary artery disease was significantly more frequent in BIMC (P<0.001), whereas tobacco use was significantly more frequent in RMH (P<0.001). Moderate to high alcohol intake (>2 drinks daily) also was more frequent in the RMH data bank (P<0.001). There were no other significant differences among risk factors.
Clinical Features and Stroke Subtypes
Hemorrhagic stroke (P<0.001) and penetrating artery disease (P<0.001) were significantly more frequent in the RMH registry, whereas large-artery disease (P<0.001) and cardioembolism (P<0.001) were more common in the BIMC data bank (Table 2⇑). Twenty-seven (24%) and 84 (76%) of the 111 patients in the RMH data bank had SAH and ICH, respectively. Forty percent, 59%, and 1% of the patients were Caucasians, natives, and Asian, respectively. Among 69 patients with hemorrhagic stroke in the BIMC data bank, 5 patients (7%) had SAH and 64 (93%) had ICH (Table 2⇑). Eighty-seven percent of the patients were Caucasians, 7% were blacks, 4% were Hispanics, and 2% were Asians. Forty-five (12%) and 49 patients (10%) were younger than 45 years in the RMH and BIMC registries, respectively.
We also sought to determine differences in the major lacunar syndromes between both registries. We did not find statistically significant differences, except for hemiparesis-ataxia syndrome, which was more common in the BIMC (P<0.01) (Table 3⇑).
When we compared stroke subtypes between Caucasians from RMH and Caucasians from BIMC, we found a statistically significant higher frequency of penetrating artery disease (P<0.01) and hemorrhagic stroke (P<0.01) in the Caucasians in the RMH data bank. When we considered both data banks together, hemorrhagic stroke was statistically significantly higher in non-Caucasians than in Caucasians (P<0.001).
Few studies have compared stroke populations to determine the frequency of stroke subtypes in natives from South America. ICH and penetrating artery disease were the most common stroke subtypes in the RMH data bank, whereas cardioembolic stroke was the most frequent stroke subtype in the BIMC data bank.
When we analyzed ethnic subgroups, Caucasians from RMH (Buenos Aires) had higher frequency of hemorrhagic stroke and penetrating artery disease than Caucasians from BIMC (Boston). When we compared stroke subtypes in the RMH data bank, natives had higher frequency of hemorrhage and penetrating artery disease than Caucasians in the same population.
Finally, when we compared stroke subtypes between non-Caucasians from RMH and BIMC versus Caucasians in both data banks together, non-Caucasians had higher frequency of ICH. However, there were no significant differences in the frequency of ischemic stroke subtypes.
Demographic variables and risk factors are potential confounders of the association between stroke subtype and hospital (C analyses in Table 1⇑), and some significant differences were found between the 2 hospitals. For example, patients in the BIMC registry were older and had a higher frequency of coronary artery disease. Natives from Buenos Aires had a higher frequency of tobacco use and alcohol intake. The results of the H×C analyses across the strata also implied effect modification of this association by age, race, and history of prior stroke. Therefore, while the results were supportive of a significant difference in subtypes between the 2 hospitals, the relationship may, at least in part, be explained by different demographic variables and risk factors. Other regional factors such as genetic predisposition, dietary habits, and weather conditions may contribute to explain these differences.
Stroke information in developing countries is difficult to obtain.1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 This could be the reason for the very few South American stroke registries or hospital-based studies reported in the literature. Stroke mechanisms and subgroups primarily depend on clinical, neuroradiological, cardiovascular, and hematologic evaluations. Data from white/Caucasian populations show that 15% to 20% are hemorrhagic strokes and 80% to 85% are ischemic strokes. However, higher rates of hemorrhagic strokes in Asians, blacks, and Indians from Ecuador have been reported, suggesting ethnic differences in the incidence of intracranial bleeding. Other reports suggest that Hispanics have higher frequency of hemorrhagic stroke than non-Hispanics.6 7 8 In a hospital-based study in Arizona, Frey et al9 analyzed the frequency of risk factors and stroke subtypes among Whites, Hispanics, and Native American patients. Lacunar and hemorrhagic strokes were more common in Native American subjects. Coronary artery disease and smoking were more frequent in whites, whereas heavier alcohol intake was more frequent in Native American subjects. No studies compared natives and Caucasians from South America with a population from North America.
As cited above, major difficulties are encountered in performing prospective studies of ethnic-racial groups. First, we recognized that a hospital-based data bank has disadvantages, such as difficulty in providing information on incidence and recurrence.24 Second, ethnicity selection criteria vary according to the available data, including (1) the information available in the clinical records, (2) self-definition, (3) last name origin, (4) phenotype, and (5) patient family history (third- or fourth-degree relatives). We consider that the last criterion may have the best sensitivity. Third, several names are used to define people in Latin America (eg, Hispanics, natives, mestizos, Latinos, Indians). These populations could be different in terms of risk factors, stroke incidence, mortality rates, and stroke subtypes.7 8 25 26 Stroke risk factors, diet, and environmental conditions among Indians or native people in South American countries may vary from one country to another. In addition, different Indian tribes may differ substantially in their genetic predisposition. However, mestizos from Ecuador and South American Indians from Argentina have similar characteristics on the basis of reported data.
In summary, natives and Caucasians from Buenos Aires may have higher risk for ICH and for penetrating artery disease. Dietary and poor control of risk factors may explain these differences. More data from different countries are needed to resolve this controversy. Community-based studies will help in the determination of the incidence, recurrence, and mortality rates in developing countries.
- Received October 14, 1999.
- Revision received July 19, 2000.
- Accepted July 19, 2000.
- Copyright © 2000 by American Heart Association
Fisher M, Bogousslavsky J. Epidemiology. In: Fisher M, Bogousslavsky J, eds. Current Reviews of Cerebrovascular Disease. 3rd ed. Boston, Mass: Butterworth-Heinemann; 1997:chap 20.
Ginsberg M, Bogousslavsky J. In: Ginsberg MD, Bogousslavsky J, eds. Cerebrovascular Disease: Pathophysiology, Diagnosis, and Management. Vol 2. Malden, Mass: Blackwell Science; 1998:827–920.
Del Brutto OH, Mosquera A, Sanches X, Santos J, Noboa CA. Stroke subtypes among Hispanics living in Guayaquil, Ecuador. Stroke.. 1993;24:1833–1836.
Barinagarrementeria F, Ruiz-Sandoval JL, Arauz A, Amaya L, Cantu C. A hospital stroke registry in Mexico City: analysis of 2045 patients. Neurology. 1999;52(suppl 2):A442. Abstract.
Sacco RL, Hauser WA, Mohr JP, Foulkes MA. One-year outcome after cerebral infarction in whites, blacks, and Hispanics. Stroke.. 1991;22:305–311.
Frey JL, Jahnke HK, Bulfinch EW. Differences in stroke between white, Hispanic and Native American patients: the Barrow Neurological Institute stroke database. Stroke.. 1998;29:29–33.
Yatsu FM. Strokes in Asians and Pacific-Islanders, Hispanics, and Native Americans. Circulation. 1991;83:1471–1472.
Venketasubramanian N, Sadasivan B, Tan A. Stroke patterns in Singapore hospital-based stroke data bank. Cerebrovasc Dis.. 1994;4:250. Abstract.
Kay R, Woo J, Kreel L, Wong HY, Teoh R, Nicholls MG. Stroke subtypes among Chinese living in Hong Kong: the Shatin Stroke Registry. Neurology.. 1992;42:985–987.
Rosman KD. The epidemiology of stroke in an urban black population. Stroke.. 1986;17:667–669.
Gillium RF, Gorelick PB, Cooper ES. Stroke in Blacks. Basel, Switzerland: Karger; 1999:1–233.
Adams HP Jr, Bendixen BH, Kappelle LJ, Biller J, Love BB, Gordon DL, Marsh EE III. Classification of subtype of acute ischemic stroke: definitions for use in a multicenter clinical trial: TOAST: Trial of Org 10172 in Acute Stroke Treatment. Stroke.. 1993;24:35–41.
Bladin PF, Berkovic SF. Striatocapsular infarction: large infarcts in the lenticulostriate arterial territory. Neurology.. 1984;34:1423–1430.
Weiller C, Ringelstein EB, Reiche W, Thron A, Bell U. The large striatocapsular infarct: a clinical and pathophysiological entity. Arch Neurol.. 1990;10:1085–1091.
Kittner SJ, Sharkness CM, Price TR, Plotnick GD, Dambrosia JM, Wolf PA, Mohr JP, Hier DB, Kase CS, Tuhrim S. Infarcts with a cardiac source of embolism in the NINCDS Stroke Data Bank: historical features. Neurology.. 1990;40:281–284.
National Institutes of Health. The Framingham Study: An Epidemiological Investigation of Cardiovascular Disease. Washington, DC: US Dept of Health, Education, and Welfare; 1971. Section 27:1–42.
Jaillard AS, Hommel M, Mazetti P. Prevalence of stroke at high altitude (3380 m) in Cuzco, a town of Peru. Stroke.. 1995;26:562–568.
Giroud M, Gras P, Dumas R. Usefulness of a population-based stroke registry. Cerebrovasc Dis. 1991;1(suppl):45–49.
Gillum RF. Epidemiology of stroke in Hispanic Americans. Stroke.. 1995;26:1707–1712.
Caplan LR, Gorelick PB, Hier DB. Race, sex, and occlusive cerebrovascular disease: a review. Stroke.. 1986;17:648–655.