Aneurysmal Subarachnoid Hemorrhage in a Mexican Multicenter Registry of Cerebrovascular Disease: The RENAMEVASC Study

L. Ruiz-Sandoval, MD,* Carlos Cantu , MD, PhD, Erwin Chiquete, MD, PhD,* Jose n-Jime nez, MD,x Antonio Arauz, MD, PhD,k Luis M. Carolina Leo Murillo-Bonilla, MD, MSc,{ Jorge Villarreal-Careaga, MD,# a, MD,** and The RENAMEVASC Investigators Fernando Barinagarrementer

Background: Information on risk factors and outcome of persons with aneurysmal

subarachnoid hemorrhage (SAH) in Mexico is unknown. We sought to describe the clinical characteristics, risk factors, and outcome at discharge of Mexican patients with aneurysmal SAH. Methods: A rst-step surveillance system was conducted on consecutive cases conrmed by 4-vessel angiography from November 2002 to October 2004 in 25 tertiary referral centers. Age- and sex-matched control subjects were randomly selected by a 1:1 factor, for multivariate analysis on risk factors. Results: We studied 231 patients (66% women; mean age 52 years, range 16-90 years). In 92%, the aneurysms were in the anterior circulation, and 15% had more than two aneurysms. After multivariate analysis, hypertension (odds ratio 2.46, 95% condence interval 1.59-3.81) and diabetes mellitus (odds ratio 0.34, 95% condence interval 0.17-0.68) were directly and inversely associated with aneurysmal SAH, respectively. Median hospital stay was 23 days (range 2-98 days). Invasive treatment was performed in 159 (69%) patients: aneurysm clipping in 126 (79%), endovascular coiling in 29 (18%), and aneurysm wrapping in 4 (2%). The in-hospital mortality was 20% (mostly due to neurologic causes), and 25% of patients were discharged with a modied Rankin score of 4 or 5. Conclusions: Hypertension is the main risk factor for aneurysmal SAH in hospitalized patients from Mexico. The female:male ratio is 2:1. A relatively low in-hospital mortality and a high frequency of invasive interventions are observed. However, a high proportion of patients are discharged with important neurologic impairment. Key Words: Cerebral aneurysm epidemiologyoutcomerisk factorssubarachnoid hemorrhage. 2009 by National Stroke Association

From the *Department of Neurology and Neurosurgery, Hospital Civil de Guadalajara Fray Antonio Alcalde, Department of Neurosciences, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Department of Neurology, Instituto Nacional de dicas y Nutricio n Salvador Zubira n, Mexico City, Ciencias Me mez Far as, ZapoxDepartment of Neurology, Hospital Regional Go a y Neurocirug a, pan, kStroke Clinic, Instituto Nacional de Neurolog Mexico City, {Department of Neurology, Instituto Panvascular de Occidente, Guadalajara, #Department of Neurology, Hospital General ngeles Quer n; and **Department of Neurology, Hospital A de Culiaca taro, Me xico. e

Received May 22, 2008; revision received September 1, 2008; accepted September 11, 2008. L. Ruiz-Sandoval, MD, Servicio de Address correspondence to Jose a y Neurocirug a, Hospital Civil de Guadalajara Fray AnNeurolog tonio Alcalde, Hospital 278, Guadalajara, Jalisco, Mexico 44280. E-mail: jorulej-1nj@prodigy.net.mx. 1052-3057/$see front matter 2009 by National Stroke Association doi:10.1016/j.jstrokecerebrovasdis.2008.09.019

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Journal of Stroke and Cerebrovascular Diseases, Vol. 18, No. 1 (January-February), 2009: pp 48-55

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49

Depending on the population and study design, it is estimated that subarachnoid hemorrhage (SAH) accounts for less than 10% of the clinical forms of acute cerebrovascular disease.1,2 On the other hand, SAH as a result of rupture of intracranial aneurysms accounts for approximately 3% of all strokes2 and for 85% of all SAH cases.3 Its clinical impact is greater than it appears considering only the frequency of this condition as it affects otherwise healthy young adults. Information regarding frequency, associated risk factors, and outcome of persons with SAH in Mexico is unknown. n Mexicana de EnferTo address this issue, the Asociacio medad Vascular Cerebral created the Registro Nacional Mexicano de Enfermedad Vascular Cerebral (RENAMEVASC),4 which is a nationwide, nongovernmental, nonindustry-sponsored, multicentric register of consecutive patients with acute cerebrovascular disease hospitalized in Mexico. The initial purpose of this national registry was to conduct a rst-step stroke surveillance system, which implies the systematic registering of patients with acute cerebrovascular disease admitted to a hospital or clinic-based facility and following up of the patients until discharge from hospital or death.5 The aim of this RENAMEVASC report on SAH was to describe the clinical and demographic characteristics, risk factors, and outcome at discharge of Mexican patients hospitalized for aneurysmal SAH, with a nationwide representation.

Methods
Patients
This prospective hospital-based multicentric registry was conducted from November 2002 to October 2004 in 25 tertiary referral centers from 14 Mexican states.4 Consecutive patients were registered if a suspected acute ischemic or hemorrhagic stroke was conrmed by head computed tomography scan or magnetic resonance imaging. A standardized, structured questionnaire was used to collect clinical and demographic data from the patient or primary guardian and medical records by the local investigator. Other data registered included in-hospital management and outcome at discharge and at 3 months follow-up. The patients functional status was classied by the modied Rankin scale.4 All data were sent to a reference center in hard version and electronically captured by two investigators, after completion of the registering deadline. For the purpose of this report, patients with SAH due to ruptured intracranial aneurysms conrmed by 4-vessel angiographic techniques were included.6,7 To compare the frequency of putative risk factors between patients with aneurysmal SAH and the general population, 231 ageand sex-matched ambulatory persons without history of SAH were included as control subjects. These people were registered explicitly for the purpose of this study and consisted of persons without any known neurologic disease: (1) relatives of patients who attend to

nonneurologic clinics or services (e.g., internal medicine, gastroenterology, and endocrinology facilities); (2) medical students and their families; and (3) volunteers from outside the hospitals. The internal committee of ethics of every participating center approved the study and the inclusion of control subjects. Informed consent was obtained from the patient, control subject, or the patients legal proxy. Mean arterial pressure (MAP) was calculated from the systolic blood pressure (SBP) and diastolic blood pressure (DBP) measurements at admittance to the emergency department as follows: MAP 5 DBP 1 0.412 (SBP DBP).8,9 This formula corrects for the spurious variation of MAP in hypertensive persons; therefore, it is best suited for cohorts with a high frequency of high blood pressure.8 Hypertension and diabetes mellitus were dened as established by standard guidelines.10,11 For the purpose of the current report, smoking was dened as the consumption (either past or current) of 5 or more cigarettes for at least 2 days per week during 12 months or more, and alcoholism as more than two alcoholic drinks per day (on average). Vasospasm was dened by means of a single angiography of 4 vessels during the diagnostic work-up, at any time of the hospital stay. Parametric continuous variables are expressed as geometric means and SD, or minimum and maximum. Nonparametric continuous variables are expressed as medians. As the median age of the study group was 51 years, we divided the cohort into people aged 49 years or younger and 50 years or older to analyze the association of age with risk factors, clinical characteristics, and outcome. To compare quantitative variables distributed between two groups, Student t test and Mann-Whitney U test were performed in distributions of parametric and nonparametric variables, respectively. Chi-square statistics (i.e., Pearson Chi-square or Fisher exact test, as corresponded) were used to compare nominal variables in bivariate analyses. To nd independent risk factors for aneurysmal SAH (as compared with control subjects) a multivariate analysis was constructed by a binary logistic regression model. Independent variables were chosen if P was less than .1 in bivariate analyses, but relevant nonsignicant variables remained in the model for adjustment. Subsequently a forward-stepwise method was performed. Adjusted odds ratios with 95% condence intervals that resulted in nal step of the model are provided. The tness of the model was evaluated by using the Hosmer-Lemeshow goodness-of-t test, which was considered as reliable if P was greater than .20. All P values reported are 2-sided and regarded as signicant when P was less than .05. Software (SPSS v 13.0) was used for all calculations.

Results
A total of 2000 patients with acute cerebrovascular disease were included in the registry: 1092 ischemic stroke

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J.L. RUIZ-SANDOV AL ET AL.

(either infarct or transient ischemic attack), 580 intracerebral hemorrhage, 59 cerebral venous thrombosis, and 269 nontraumatic SAH. All patients included pertained to the Latin American bioethnic group. In all, 38 patients were excluded because they had a cause of SAH other than ruptured aneurysms, or because they lacked angiography. Therefore, after applying selection criteria, 231 patients were analyzed. There were 153 (66%) women and 78 (34%) men, with a mean age of 51.8 years (median 51 years, range 16-90). In all, 55 (24%) patients were younger than 40 years and 49 (21%) were 65 years or older. Hypertension was more frequent among patients than control subjects, whereas few cases of diabetes mellitus were observed in the SAH group (Table 1). After multivariate analysis controlled for potential confounders, hypertension remained a signicant risk and diabetes an inversely associated factor for aneurysmal SAH. Table 2 shows the distribution of risk factors among patients, stratied by sex and age. Alcohol consumption and smoking were more common in men than in women. Hypertension and diabetes mellitus were more frequent in patients 50 years or older than in younger persons. The onset of the clinical manifestations was registered in 184 cases; of these, 69 (37.5%) occurred during the rst 12 hours of the day (at awakening in 8%, n 5 19) and in 115 (62.5%) during the afternoon or night. No monthly or seasonal patterns in hospitalization for aneurysmal SAH were identied. The hemorrhage was preceded by a physical effort in 29 (12%) cases and by emotional stress in 11 (5%) (without differences according to age or sex). Table 3 shows the clinical manifestations and laboratory work-up at hospital arrival. The main features were headache, vomiting, and impaired consciousness. More men than women presented to hospital with a Glasgow Coma Scale score greater than 13 (80% v 59%, respectively; P 5 .002). Impaired consciousness at event onset and higher blood pressure measures were more frequent

in patients 50 years or older than in younger persons; nonetheless, more seizures were reported in the latter group. Single aneurysms occurred in 85% cases (Table 4). In 92% patients the lesions were located at the anterior circulation. There were no differences in vascular topography according to age or sex (Table 4). Other anatomic characteristics of the aneurysms, such as size, neck, and dome, were not registered. Duration of the hospital stay had a median of 23 days (range 2-98 days) (Table 5). In all, 157 (68%) patients required entering the intensive care department at any time of their hospitalization, whereas 74 (32%) patients were treated completely in general wards. The need for mechanical ventilation occurred in 91 (39%) cases. We lacked information regarding the time to angiography or time to surgery or endovascular intervention after hospital arrival. Invasive treatment of the aneurysms was performed in 159 (69%) patients by using the following techniques: clipping of ruptured aneurysm in 126 (79% of those surgically treated), endovascular coiling in 29 (18%, all of them performed in a single center), and aneurysm wrapping in 4 (2%) patients. The type of management (any invasive intervention v only medical treatment) did not differ with age (P 5 .31, for persons aged $ 50 v younger individuals), sex (P 5 .45, for men v women), or aneurysm topography (P 5 .20, for anterior v posterior circulation); however, aneurysm wrapping was performed only for aneurysms of the anterior circulation (P , .001). Hydrocephalus was observed in 22% cases; of them, 72% received a shunting procedure. Pneumonia was the most frequent systemic complication (87/ 231, 38%), followed by urinary tract infections (47/231, 20%), cardiac arrhythmia (17/231, 7%), and lower-limb deep-vein thrombosis (4/231, 2%). In all, 46 (20%) patients died in the hospital; 25 (54%) with a neurologic cause, 13 (28%) with a systemic nonneurologic complication, and 8 (17%) with both groups of causes. At

Table 1. Case-control analysis on risk factors for aneurysmal subarachnoid hemorrhage: Bivariate analysis and a multivariate logistic regression model Group Variable Age, y, mean (range) Female, n (%) Hypertension, n (%) Diabetes mellitus, n (%) Alcoholism, n (%) Current smoker, n (%) Former smoker, n (%) Patients (n 5 231) 51.6 (16-90) 156 (66) 96 (42) 16 (7) 30 (13) 68 (29) 15 (6) Control subjects (n 5 231) 51.6 (16-90) 156 (66) 67 (29) 35 (15) 35 (15) 61 (26) 12 (5) P value* .99 .99 .005 .005 .50 .47 .55 Multivariate OR (95% CI)y NS NS 2.46 (1.59-3.81) 0.34 (0.17-0.68) NS NS NS

Abbreviations: CI, condence interval; NS, not signicant; OR, odds ratio. *P value for differences between patient and control groups; Student t test or Fisher exact test, as appropriate. yHosmer-Lemeshow goodness-of-t test: Chi-square 5 0.48, 2 df, P 5 .98. The rest of the variables that resulted with P $ .1 in bivariate analysis remained in the multivariate model for adjustment; however, their multivariate ORs are not shown to avoid confusion.

ANEURYSMAL SUBARACHNOID HEMORRHAGE IN MEXICAN HOSPITALS

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Table 2. Risk factors for aneurysmal subarachnoid hemorrhage stratied by sex and age Sex Variable Age, y, mean (range) Hypertension, n (%) Diabetes mellitus, n (%) Alcoholism, n (%) Current smoker, n (%) Former smoker, n (%) Total 51.6 (16-90) 96 (42) 16 (7) 30 (13) 68 (29) 43 (19) Male 49.1 (16-90) 29 (37) 6 (8) 21 (27) 30 (38) 19 (24) Female 52.8 (17-90) 67 (44) 10 (6) 9 (6) 38 (25) 24 (16) P value* .89 .33 .74 ,.001 .03 .11 #49 38.1 (16-49) 26 (24) 2 (2) 13 (12) 35 (33) 18 (17) Age, y $50 63.0 (50-90) 70 (56) 14 (11) 17 (14) 33 (26) 25 (20) P valuey ,.001 ,.001 .005 .76 .27 .56

*P value for differences between men and women; Student t test or Fisher exact test, as appropriate. yP value for differences between persons 49 years old or younger and 50 years of age or older; Student t test or Fisher exact test, as appropriate.

discharge, 25 (11%) had severe disabilities with dependence on others for activities of daily living, 33 (14%) with partial dependence and walking impairment, 43 (19%) with disabilities but able to walk without assistance, 30 (13%) with mild disabilities, 30 (13%) with minimal impairment, and 23 (10%) completely asymptomatic (Table 5). Table 6 shows the analyses on in-hospital mortality according to different clinical scales. Of note, the presence of radiographic ndings typical of cerebral vasospasm was not associated with in-hospital mortality.

Discussion
Cerebrovascular disease is the fourth cause of death in the general population of Mexico, accounting for more than 27,000 (5.5% of total) deaths by 2006.12 In previous hospital series from Mexico, the proportion of cases of

SAH among forms of stroke has been reported to be around 15%.13-15 We found that the main risk factor for aneurysmal SAH was hypertension, whereas diabetes mellitus was inversely related with this condition; which is consistent with previous studies.16 According to other reports,17-20 we found that the female:male ratio is 2:1. A high number of persons younger than 40 years was observed, contrasting with the respective frequency reported for other countries, including those with a very high incidence of SAH.17,21 This phenomenon could be due at least in part to the high proportion of young Mexican inhabitants. Other possible explanations could be that congenital vascular abnormalities and other conditions associated with the aneurysm formation or rupture has a high representation in our young population, or that the young have

Table 3. Clinical manifestations and laboratory analysis at hospital arrival, stratied by sex and age Sex Variable Headache, n (%) Vomiting, n (%) Probable seizures, n (%) Impaired consciousness at event onset, n (%) Systolic blood pressure, mm Hg, mean (SD)z Mean arterial pressure, mm Hg, mean (SD)z Pulse pressure, mm Hg, mean (SD)z Glucose, mg/dL, mean (SD) International normalized ratio, mean (SD) Hematocrit, %, mean (SD) Platelets, 310-4, mean (SD) Total 209 (90) 152 (66) 49 (21) 130 (56) 142 (28) 110 (18) 55 (21) 136 (63) 1.11 (0.17) 40 (6) 24.6 (8.4) Male 67 (89) 48 (61) 17 (22) 32 (41) 137 (21) 107 (15) 51 (16) 136 (68) 1.10 (0.15) 43 (7) 22.3 (7.6) Female 142 (94) 104 (68) 32 (21) 98 (64) 145 (30) 111 (20) 57 (22) 136 (60) 1.13 (0.18) 39 (5) 25.8 (8.6) P value* .21 .33 .87 .001 .09 .10 .07 .98 .54 ,.001 .003 #49 99 (94) 72 (68) 31 (29) 50 (47) 134 (24) 105 (17) 50 (16) 130 (58) 1.13 (0.17) 40 (7) 25.0 (9.4) Age, y $50 110 (91) 80 (64) 18 (14) 80 (64) 149 (29) 113 (19) 60 (23) 142 (67) 1.09 (0.17) 41 (6) 24.2 (7.4) P valuey .34 .53 .006 .01 .01 .004 .002 .17 .40 .28 .45

*P value for differences between men and women; Fisher exact test or Student t test, as appropriate. yP value for differences between persons 49 years old or younger and 50 years of age or older; Fisher exact test or Student t test, as appropriate. zData available on 224 persons.

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Table 4. Number and vascular topography of the intracranial aneurysms as assessed by angiographic studies Sex Variable No. of aneurysms* 1, n (%) .1, n (%) Anterior circulation (n 5 213, 92%)y Posterior communicating artery, n (%) Anterior communicating artery, n (%) Middle cerebral artery, n (%) Internal carotid artery (supraclinoid), n (%) Internal carotid artery (opthalmic), n (%) Posterior circulation (n 5 18, 8%)z Posterior cerebral artery, n (%) Basilar artery, n (%) Vertebral artery, n (%) Total Male Female #49 Age, y $50

197 (85) 34 (15) 64 (28) 61 (26) 46 (20) 27 (12) 15 (6)

67 (86) 11 (14) 20 (26) 22 (28) 16 (21) 8 (10) 4 (5)

130 (85) 23 (15) 44 (29) 39 (26) 30 (20) 19 (12) 11 (7)

91 (86) 15 (14) 28 (26) 25 (24) 23 (22) 16 (15) 7 (6)

106 (85) 19 (15) 36 (29) 36 (29) 23 (18) 11 (9) 8 (6)

5 (2) 7 (3) 6 (3)

0 (0) 4 (5) 4 (5)

5 (3) 3 (2) 2 (1)

2 (2) 1 (1) 4 (4)

3 (2) 6 (5) 2 (2)

*P 5 .99, for comparison in frequency of number of aneurysms between men and women; and P 5 .85, for comparison between persons 49 years old or younger and 50 years of age or older; Fisher exact test. yP 5 .93, for comparison in homogeneity of aneurysmal localization of the anterior circulation between men and women; and P 5 .57, for comparison between persons 49 years old or younger and 50 years of age or older; Pearson Chi square. zP 5 .06, for comparison in homogeneity of aneurysmal localization of the posterior circulation between men and women; and P 5 .15, for comparison between persons 49 years old or younger and 50 years of age or older; Pearson Chi square.

a low prehospital mortality and reach the hospital more frequently than do older persons. The rate of microsurgical intervention or endovascular therapy was higher in our study, as compared with other reports.19,22,23 Indeed, this is possibly due to the fact that our cohort corresponds to patients hospitalized in urban teaching hospitals, where the patients are treated almost entirely with microsurgical clipping.24 In the United States, higher rates of any invasive procedure in the urban setting were observed, when compared with rural facilities.23 In Mexico most of the invasive procedures are performed in governmental teaching hospitals or in public-insurance settings, which implies a minimal cost

to the patient and possibly a high chance of being surgically treated.24 We observed a lower mortality than that previously reported.19,23-27 Our explanation to this nding is that RENAMEVASC is a hospital-based study on persons who reached medical assistance in urban teaching hospitals, and who had a diagnosis based on 4-vessel angiography. Many patients with the extreme medical conditions after SAH could be lost in the prehospital part of their disease evolution, due to a wrong diagnosis or death. Also, some patients who arrived at our centers may not have been correctly diagnosed as having SAH, or may not have been documented by angiography and thus, were not

Table 5. Events during hospitalization and clinical outcome at discharge stratied by sex and age Sex Variable Days of hospitalization, median (minimum and maximum) In-hospital systemic complications, n (%) Modied Rankin score at discharge 0-2, n (%) 3-6, n (%) Total 23 (2-98) 107 (46) Male 24 (3-92) 34 (44) Female 23 (2-98) 73 (48) P value* .81 .55 .77 83 (36) 148 (64) 29 (37) 49 (63) 54 (35) 99 (65) 46 (43) 60 (57) 37 (30) 88 (70) #49 19 (2-98) 43 (41) Age, y $50 28 (2-82) 64 (51) P valuey .24 .11 .03

*P value for differences between men and women; Mann-Whitney U test or Fisher exact test as appropriate. yP value for differences between persons 49 years old or younger and 50 years of age or older; Mann-Whitney U test or Fisher exact test, as appropriate.

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53

Table 6. In-hospital mortality according to clinical and brain imaging characteristics at hospital arrival Sex Variable Hunt-Hess scalex Grade I-II, n (%) Grade III-V, n (%) Fisher scale// Grade I-II, n (%) Grade III-IV, n (%) Glasgow Coma Scale{ Points 13-15, n (%) Points 9-12, n (%) Points 3-8, n (%) Cerebral vasospasm# Present, n (%) Absent, n (%) Total Male Female P value* .09 133 (66) 51 (74) 82 (62) 69 (34) 51 (38) 18 (26) .86 52 (26) 17 (25) 35 (26) 149 (74) 52 (75) 97 (74) .007 149 (67) 61 (80) 88 (59) 43 (19) 9 (12) 34 (23) 32 (14) 6 (8) 26 (18) .36 88 (44) 26 (39) 62 (47) 110 (56) 40 (61) 70 (53) 41 (43) 47 (46) 55 (57) 55 (54) 78 (76) 71 (59) 12 (11) 31 (25) 13 (13) 19 (16) .67 15 (44) 19 (56) 73 (45) 91 (55) 28 (29) 24 (23) 68 (71) 81 (77) .01 17 (39) 14 (33) 12 (28) 132 (73) 29 (16) 20 (11) .99 72 (73) 61 (59) 26 (27) 43 (41) .34 0 (0) 52 (31) 34 (100) 115 (69) ,.001 Age, y #49 $50 P valuey .04 14 (40) 21 (60) 119 (71) 48 (29) ,.001 In-hospital death Present Absent P valuez .001

*P value for differences between men and women; Pearson Chi square or Fisher exact test, as appropriate. yP value for differences between persons 49 years old or younger and 50 years of age or older; Pearson Chi square or Fisher exact test, as appropriate. zP value for differences between fatal and nonfatal cases; Pearson Chi square or Fisher exact test, as appropriate. x Data available on 202 persons. // Data available on 201 persons. { Data available on 224 persons. # Data available on 198 persons.

registered. It is well known that many patients die before they reach medical attention or diagnosis, and a considerable proportion of patients are missed during an emergency department visit, mainly due to a wrong diagnostic impression.28 As expected,7 the global neurologic impairment and SAH grade at hospital arrival were associated with inhospital mortality, and notably, the vasospasm did not explain any effect on short-term outcome. However, our denition of vasospasm was limited, based on a single angiography performed at any time during hospitalization, which is not a standard procedure to dene this very dynamic phenomenon. Therefore, the consequences and magnitude of clinically signicant vasospasm could not be described with precision. This problem represents a limitation of our study. Nevertheless, vasospasm is not the only factor associated with neurologic worsening after SAH and its contribution on outcome may be small, as could be inferred from clinical trials aimed to prevent or reverse vasospasm to change the fate of SAH.29 Indeed, our study has other limitations. This is a hospital-based registry with a rather small sample size on patients admitted to referral centers with neurosurgical departments, which may favor hospitalization of patients suitable for a surgical intervention, with the corresponding high recording of the hemorrhagic forms of cerebrovascular disease (i.e., intracerebral hemorrhage and SAH).13-15 Although it has been recognized that hemorrhagic stroke is more frequent among Hispanics, when

compared with non-Hispanic whites,1,30,31 populationbased studies on stroke incidence have shown that the proportion of aneurysmal SAH among subtypes of cerebrovascular disease is less than 10%, which includes populations with Mexican ancestry.30,31 A long-term follow-up was not possible for all patients of our registry, and only 35% persons of our sample were followed up for 3 months or more (data not shown). A population-based study on incidence, conditioning factors, and long-term outcome of persons with aneurysmal SAH in Mexico is urgently needed. This issue will be certainly solved by the US National Institutes of Healthsponsored Brain Attack Surveillance in Durango City (BASID) Study. The RENAMEVASC prospective study is the rst attempt in describing the general characteristics of aneurysmal SAH in Mexico with a nonsponsored and completely voluntary multicentric organization. Person-oriented data were registered with clinical and radiologic information on aneurysmal topography and short-term outcome, information that could be hardly provided in prospective nonsponsored studies. In conclusion, hypertension is the main risk factor for aneurysmal SAH in Mexico; however, other contributing risk factors could not be completely excluded with the methodology of this study.6,15 The female:male ratio of hospitalized patients with aneurysmal SAH is 2:1, and a considerably high proportion of patients are young. Most aneurysms are solitary and located at the anterior circulation. We observed a high rate of invasive therapy,

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J.L. RUIZ-SANDOV AL ET AL. 3. van Gijn J, Kerr RS, Rinkel GJE. Subarachnoid hemorrhage. Lancet 2007;369:306-318. C, Ruiz-Sandoval JL, et al. Short-term 4. Arauz A, Cantu prognosis of transient ischemic attacks: Mexican multicenter stroke registry [in Spanish]. Rev Invest Clin 2006; 58:530-539. 5. Bonita R, Mendis S, Truelsen T, et al. The global stroke initiative. Lancet Neurol 2004;3:391-393. 6. Matsuda M, Watanabe K, Saito A, et al. Circumstances, activities, and events precipitating aneurysmal subarachnoid hemorrhage. J Stroke Cerebrovasc Dis 2007;16:25-29. 7. Kazumata K, Kamiyama H, Ishikawa T. Reference table predicting the outcome of subarachnoid hemorrhage in the elderly, stratied by age. J Stroke Cerebrovasc Dis 2006;15:14-17. 8. Meaney E, Alva F, Moguel R, et al. Formula and nomogram for the sphygmomanometric calculation of the mean arterial pressure. Heart 2000;84:64. 9. Chiquete E, Ruiz-Sandoval MC, Alvarez-Palazuelos LE, et al. Hypertensive intracerebral hemorrhage in the very elderly. Cerebrovasc Dis 2007;24:196-201. 10. Chobanian AV, Bakris GL, Black HR, et al. The seventh report of the joint national committee on prevention, detection, evaluation, and treatment of high blood pressure: The JNC 7 report. JAMA 2003;289:2560-2572. 11. American Diabetes Association. Diagnosis and classication of diabetes mellitus. Diabetes Care 2006;28:S37-S42. a de Salud, 12. Statistics on general mortality. Secretar xico, 2006. Available from: URL:http://www.salud. Me gob.mx/. Accessed April 2, 2008. 13. Chiquete E, Ruiz-Sandoval JL. Prehospital events and inhospital mortality after acute stroke in a Mexican cohort [in Spanish]. Rev Mex Neuroci 2007;8:41-48. 14. Gardeal G, Segura MA, Ramos F, et al. Intracranial aneurysms: Review of 100 cases in a period of 12 years at the General Hospital of Mexico [in Spanish]. Arch Neurocien (Mex) 1996;1:288-291. 15. Connolly ES Jr, Poisik A, Winfree CJ, et al. Cigarette smoking and the development and rupture of cerebral aneurysms in a mixed race population: Implications for population screening and smoking cessation. J Stroke Cerebrovasc Dis 1999;8:248-253. 16. Feigin VL, Rinkel GJ, Lawes CM, et al. Risk factors for subarachnoid hemorrhage: An updated systematic review of epidemiological studies. Stroke 2005; 36:2773-2780. 17. Rooij NK, Linn FH, van der Plas JA, et al. Incidence of subarachnoid hemorrhage: A systematic review with emphasis on region, age, gender and time trends. J Neurol Neurosurg Psychiatry 2007;78:1365-1372. 18. Wermer MJH, van der Schaaf IC, Algra A, et al. Risk of rupture of unruptured intracranial aneurysms in relation to patient and aneurysm characteristics: An updated meta-analysis. Stroke 2007;38:1404-1410. 19. Qureshi AI, Suri MF, Nasar A, et al. Trends in hospitalization and mortality for subarachnoid hemorrhage and unruptured aneurysms in the United States. Neurosurgery 2005;57:1-8. 20. Nagura J, Suzuki K, Hayashi M, et al. Stroke subtypes and lesion sites in Akita. Japan. J Stroke Cerebrovasc Dis 2005;14:1-7. ho nen M, et al. A multinational 21. Ingall T, Asplund K, Ma comparison of subarachnoid hemorrhage epidemiology in the WHO MONICA stroke study. Stroke 2000; 31:1054-1061.

owing to the characteristics of our study design and the Mexican health care system. A low in-hospital mortality was observed, possibly due to a low registering of fatal cases that occurred before aneurysm documentation. However, a high proportion of patients are discharged with important neurologic impairment.
The RENAMEVASC Investigators: Steering Committee -Brito, A. Arauz-Go ngora, J. L. Ruiz-Sandoval, J. C. Cantu Villarreal-Careaga, L. Murillo-Bonilla, R. Rangel-Guerra, F. Barinagarrementeria Coordinating Ofce -Brito, L. Murillo-Bonilla C. Cantu Participants The following centers and investigators participated in the -Brito (Instituto Nacional de RENAMEVASC study: C. Cantu n, Ciudad de Ciencias Medicas y Nutricion Salvador Zubira Mexico); A. Arauz-Gongora, L. Murillo-Bonilla, and L. a y Neurocirug a, Hoyos (Instituto Nacional de Neurolog Ciudad de Mexico); J. L. Ruiz-Sandoval and E. Chiquete (Hospital Civil de Guadalajara, Jalisco); J. Villarreal-Careaga n-Reyes (Hospital General de Culiaca n, and F. Guzma Sinaloa); F. Barinagarrementeria (Hospital Angeles de Quer taro, Quere taro); J. A. Ferna ndez (Hospital Jua rez, Ciudad e xico); B. Torres (Hospital General de Leo n, Guanade Me n-Jime nez (Hospital Regional ISSSTE, Zapopan, juato); C. Leo guez-Leyva (Hospital General de San Luis Jalisco); I. Rodr , San Luis Potosi); R. Rangel-Guerra (Hospital UniverPotos n, Monterrey, Nuevo Leo n); M. Ban os sitario de Nuevo Leo xico); L. (Hospital General de Balbuena, Ciudad de Me de Monterrey, Espinosa and M. de la Maza (Hospital San Jose n); H. Colorado (Hospital General ISSSTE, VeraNuevo Leo cruz, Veracruz); M. C. Loy-Gerala (Hospital General de Puebla, Puebla); J. Huebe-Rafool (Hospital General de Pachuca, Hidalgo); G. Aguayo Leytte (Hospital General de Aguascalientes, Aguascalientes); G. Tavera-Guittings (Hospital General ISSSTE, Campeche, Campeche); V. Garcia-Talavera xico); O. Ibarra y (Hospital IMSS La Raza, Ciudad de Me M. Segura (Hospital General de Morelia, Morelia); J. L. Sosa (Hospital General de Villahermosa, Tabasco); O. Tala s-Murra (Hospital General ISSSTE, Torreo n, Coahuila); ma ga (Hospital Universitario de Torreo n, M. Alanis-Quiro Coahuila); J. M. Escamilla (Hospital de la Marina Nacional, xico); M. A. Alegr a (Hospital Central Militar, Ciudad de Me xico); and J. C. Angulo (Hospital General, Ciudad de Me Veracruz, Veracruz).

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