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

   ´                                      ´
Jose L. Ruiz-Sandoval, MD,*† Carlos Cantu, MD, PhD,‡ Erwin Chiquete, MD, PhD,*†
                    ´      ´
         Carolina Leon-Jimenez, MD,x Antonio Arauz, MD, PhD,k Luis M.
            Murillo-Bonilla, MD, MSc,{ Jorge Villarreal-Careaga, MD,#
                              ´
 Fernando Barinagarrementerıa, MD,** and The RENAMEVASC Investigators



                         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 pa-
                         tients with aneurysmal SAH. Methods: A first-step surveillance system was con-
                         ducted on consecutive cases confirmed 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 fac-
                         tors. 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% confidence interval 1.59-3.81) and diabetes mellitus (odds ratio 0.34, 95% confi-
                         dence 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%), en-
                         dovascular 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 dis-
                         charged with a modified Rankin score of 4 or 5. Conclusions: Hypertension is the
                         main risk factor for aneurysmal SAH in hospitalized patients from Mexico. The fe-
                         male: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 dis-
                         charged with important neurologic impairment. Key Words: Cerebral aneurysm—
                         epidemiology—outcome—risk factors—subarachnoid hemorrhage.
                         Ó 2009 by National Stroke Association




  From the *Department of Neurology and Neurosurgery, Hospital
                                                                          Received May 22, 2008; revision received September 1, 2008;
Civil de Guadalajara ‘‘Fray Antonio Alcalde’’, †Department of Neuro-
                                                                        accepted September 11, 2008.
sciences, Centro Universitario de Ciencias de la Salud, Universidad                                      ´
                                                                          Address correspondence to Jose L. Ruiz-Sandoval, MD, Servicio de
de Guadalajara, ‡Department of Neurology, Instituto Nacional de                   ´               ´
                                                                        Neurologıa y Neurocirugıa, Hospital Civil de Guadalajara ‘‘Fray An-
             ´                 ´                    ´
Ciencias Medicas y Nutricion ‘‘Salvador Zubiran,’’ Mexico City,
                                                                        tonio Alcalde,’’ Hospital 278, Guadalajara, Jalisco, Mexico 44280.
                                                  ´        ´
xDepartment of Neurology, Hospital Regional Gomez Farıas, Zapo-
                                                                        E-mail: jorulej-1nj@prodigy.net.mx.
                                                     ´            ´
pan, kStroke Clinic, Instituto Nacional de Neurologıa y Neurocirugıa,
                                                                          1052-3057/$—see front matter
Mexico City, {Department of Neurology, Instituto Panvascular de Oc-
                                                                          Ó 2009 by National Stroke Association
cidente, Guadalajara, #Department of Neurology, Hospital General
                                                                          doi:10.1016/j.jstrokecerebrovasdis.2008.09.019
           ´                                            ´
de Culiacan; and **Department of Neurology, Hospital Angeles Quer-
´        ´
etaro, Mexico.


48                                  Journal of Stroke and Cerebrovascular Diseases, Vol. 18, No. 1 (January-February), 2009: pp 48-55
ANEURYSMAL SUBARACHNOID HEMORRHAGE IN MEXICAN HOSPITALS                                                                    49

   Depending on the population and study design, it is es-       nonneurologic clinics or services (e.g., internal medicine,
timated that subarachnoid hemorrhage (SAH) accounts              gastroenterology, and endocrinology facilities); (2) medical
for less than 10% of the clinical forms of acute cerebrovas-     students and their families; and (3) volunteers from out-
cular disease.1,2 On the other hand, SAH as a result of rup-     side the hospitals. The internal committee of ethics of every
ture of intracranial aneurysms accounts for approximately        participating center approved the study and the inclusion
3% of all strokes2 and for 85% of all SAH cases.3 Its clinical   of control subjects. Informed consent was obtained from
impact is greater than it appears considering only the fre-      the patient, control subject, or the patient’s legal proxy.
quency of this condition as it affects otherwise healthy            Mean arterial pressure (MAP) was calculated from the
young adults.                                                    systolic blood pressure (SBP) and diastolic blood pressure
   Information regarding frequency, associated risk factors,     (DBP) measurements at admittance to the emergency de-
and outcome of persons with SAH in Mexico is unknown.            partment as follows: MAP 5 DBP 1 0.412 (SBP – DBP).8,9
                                     ´
To address this issue, the Asociacion Mexicana de Enfer-         This formula corrects for the spurious variation of MAP
medad Vascular Cerebral created the Registro Nacional            in hypertensive persons; therefore, it is best suited for co-
Mexicano de Enfermedad Vascular Cerebral (RENAME-                horts with a high frequency of high blood pressure.8 Hy-
VASC),4 which is a nationwide, nongovernmental, nonin-           pertension and diabetes mellitus were defined as
dustry-sponsored, multicentric register of consecutive           established by standard guidelines.10,11 For the purpose
patients with acute cerebrovascular disease hospitalized         of the current report, smoking was defined as the con-
in Mexico. The initial purpose of this national registry         sumption (either past or current) of 5 or more cigarettes
was to conduct a first-step stroke surveillance system,           for at least 2 days per week during 12 months or more,
which implies the systematic registering of patients with        and alcoholism as more than two alcoholic drinks per
acute cerebrovascular disease admitted to a hospital or          day (on average). Vasospasm was defined by means of
clinic-based facility and following up of the patients until     a single angiography of 4 vessels during the diagnostic
discharge from hospital or death.5 The aim of this RENA-         work-up, at any time of the hospital stay.
MEVASC report on SAH was to describe the clinical and               Parametric continuous variables are expressed as geo-
demographic characteristics, risk factors, and outcome at        metric means and SD, or minimum and maximum. Non-
discharge of Mexican patients hospitalized for aneurysmal        parametric continuous variables are expressed as
SAH, with a nationwide representation.                           medians. As the median age of the study group was 51
                                                                 years, we divided the cohort into people aged 49 years
  Methods                                                        or younger and 50 years or older to analyze the associa-
                                                                 tion of age with risk factors, clinical characteristics, and
  Patients
                                                                 outcome. To compare quantitative variables distributed
   This prospective hospital-based multicentric registry         between two groups, Student t test and Mann-Whitney
was conducted from November 2002 to October 2004 in              U test were performed in distributions of parametric
25 tertiary referral centers from 14 Mexican states.4 Consec-    and nonparametric variables, respectively. Chi-square
utive patients were registered if a suspected acute ischemic     statistics (i.e., Pearson Chi-square or Fisher exact test, as
or hemorrhagic stroke was confirmed by head computed              corresponded) were used to compare nominal variables
tomography scan or magnetic resonance imaging. A stan-           in bivariate analyses. To find independent risk factors
dardized, structured questionnaire was used to collect           for aneurysmal SAH (as compared with control subjects)
clinical and demographic data from the patient or primary        a multivariate analysis was constructed by a binary logis-
guardian and medical records by the local investigator.          tic regression model. Independent variables were chosen
Other data registered included in-hospital management            if P was less than .1 in bivariate analyses, but relevant
and outcome at discharge and at 3 months follow-up.              nonsignificant variables remained in the model for adjust-
The patient’s functional status was classified by the modi-       ment. Subsequently a forward-stepwise method was per-
fied Rankin scale.4 All data were sent to a reference center      formed. Adjusted odds ratios with 95% confidence
in hard version and electronically captured by two investi-      intervals that resulted in final step of the model are pro-
gators, after completion of the registering deadline. For the    vided. The fitness of the model was evaluated by using
purpose of this report, patients with SAH due to ruptured        the Hosmer-Lemeshow goodness-of-fit test, which was
intracranial aneurysms confirmed by 4-vessel angio-               considered as reliable if P was greater than .20. All P
graphic techniques were included.6,7 To compare the fre-         values reported are 2-sided and regarded as significant
quency of putative risk factors between patients with            when P was less than .05. Software (SPSS v 13.0) was
aneurysmal SAH and the general population, 231 age-              used for all calculations.
and sex-matched ambulatory persons without history of
SAH were included as control subjects. These people
                                                                   Results
were registered explicitly for the purpose of this study
and consisted of persons without any known neurologic              A total of 2000 patients with acute cerebrovascular dis-
disease: (1) relatives of patients who attend to                 ease were included in the registry: 1092 ischemic stroke
50                                                                                                      J.L. RUIZ-SANDOVAL ET AL.

(either infarct or transient ischemic attack), 580 intracere-           in patients 50 years or older than in younger persons;
bral hemorrhage, 59 cerebral venous thrombosis, and 269                 nonetheless, more seizures were reported in the latter
nontraumatic SAH. All patients included pertained to the                group. Single aneurysms occurred in 85% cases (Table
Latin American bioethnic group. In all, 38 patients were                4). In 92% patients the lesions were located at the anterior
excluded because they had a cause of SAH other than                     circulation. There were no differences in vascular topog-
ruptured aneurysms, or because they lacked angiogra-                    raphy according to age or sex (Table 4). Other anatomic
phy. Therefore, after applying selection criteria, 231 pa-              characteristics of the aneurysms, such as size, neck, and
tients were analyzed. There were 153 (66%) women and                    dome, were not registered.
78 (34%) men, with a mean age of 51.8 years (median 51                     Duration of the hospital stay had a median of 23 days
years, range 16-90). In all, 55 (24%) patients were younger             (range 2-98 days) (Table 5). In all, 157 (68%) patients re-
than 40 years and 49 (21%) were 65 years or older. Hyper-               quired entering the intensive care department at any
tension was more frequent among patients than control                   time of their hospitalization, whereas 74 (32%) patients
subjects, whereas few cases of diabetes mellitus were ob-               were treated completely in general wards. The need for
served in the SAH group (Table 1). After multivariate                   mechanical ventilation occurred in 91 (39%) cases. We
analysis controlled for potential confounders, hyperten-                lacked information regarding the time to angiography
sion remained a significant risk and diabetes an inversely               or time to surgery or endovascular intervention after hos-
associated factor for aneurysmal SAH. Table 2 shows the                 pital arrival. Invasive treatment of the aneurysms was
distribution of risk factors among patients, stratified by               performed in 159 (69%) patients by using the following
sex and age. Alcohol consumption and smoking were                       techniques: clipping of ruptured aneurysm in 126 (79%
more common in men than in women. Hypertension                          of those surgically treated), endovascular coiling in 29
and diabetes mellitus were more frequent in patients 50                 (18%, all of them performed in a single center), and aneu-
years or older than in younger persons.                                 rysm wrapping in 4 (2%) patients. The type of manage-
   The onset of the clinical manifestations was registered              ment (any invasive intervention v only medical
in 184 cases; of these, 69 (37.5%) occurred during the first             treatment) did not differ with age (P 5 .31, for persons
12 hours of the day (at awakening in 8%, n 5 19) and in                 aged $ 50 v younger individuals), sex (P 5 .45, for men
115 (62.5%) during the afternoon or night. No monthly                   v women), or aneurysm topography (P 5 .20, for anterior
or seasonal patterns in hospitalization for aneurysmal                  v posterior circulation); however, aneurysm wrapping
SAH were identified. The hemorrhage was preceded by                      was performed only for aneurysms of the anterior circula-
a physical effort in 29 (12%) cases and by emotional stress             tion (P , .001). Hydrocephalus was observed in 22%
in 11 (5%) (without differences according to age or sex).               cases; of them, 72% received a shunting procedure. Pneu-
Table 3 shows the clinical manifestations and laboratory                monia was the most frequent systemic complication (87/
work-up at hospital arrival. The main features were head-               231, 38%), followed by urinary tract infections (47/231,
ache, vomiting, and impaired consciousness. More men                    20%), cardiac arrhythmia (17/231, 7%), and lower-limb
than women presented to hospital with a Glasgow                         deep-vein thrombosis (4/231, 2%). In all, 46 (20%) pa-
Coma Scale score greater than 13 (80% v 59%, respec-                    tients died in the hospital; 25 (54%) with a neurologic
tively; P 5 .002). Impaired consciousness at event onset                cause, 13 (28%) with a systemic nonneurologic complica-
and higher blood pressure measures were more frequent                   tion, 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             Patients (n 5 231)      Control subjects (n 5 231)       P value*       Multivariate OR (95% CI)y

     Age, y, mean (range)            51.6 (16-90)                51.6 (16-90)                .99                      NS
     Female, n (%)                    156 (66)                   156 (66)                    .99                      NS
     Hypertension, n (%)               96 (42)                    67 (29)                    .005              2.46 (1.59-3.81)
     Diabetes mellitus, n (%)          16 (7)                     35 (15)                    .005              0.34 (0.17-0.68)
     Alcoholism, n (%)                 30 (13)                    35 (15)                    .50                      NS
     Current smoker, n (%)             68 (29)                    61 (26)                    .47                      NS
     Former smoker, n (%)              15 (6)                     12 (5)                     .55                      NS

  Abbreviations: CI, confidence interval; NS, not significant; 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-fit 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                                                                                           51

                       Table 2. Risk factors for aneurysmal subarachnoid hemorrhage stratified by sex and age

                                                                 Sex                                            Age, y

           Variable                  Total              Male            Female         P value*         #49                 $50        P valuey

   Age, y, mean (range)          51.6 (16-90)        49.1 (16-90)     52.8 (17-90)       .89        38.1 (16-49)      63.0 (50-90)      ,.001
   Hypertension, n (%)            96 (42)              29 (37)          67 (44)          .33         26 (24)           70 (56)          ,.001
   Diabetes mellitus, n (%)       16 (7)                6 (8)           10 (6)           .74           2 (2)            14 (11)          .005
   Alcoholism, n (%)              30 (13)              21 (27)           9 (6)          ,.001        13 (12)            17 (14)          .76
   Current smoker, n (%)          68 (29)              30 (38)          38 (25)          .03         35 (33)           33 (26)           .27
   Former smoker, n (%)           43 (19)              19 (24)          24 (16)          .11         18 (17)           25 (20)           .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 depen-                        SAH among forms of stroke has been reported to be
dence on others for activities of daily living, 33 (14%)                       around 15%.13-15
with partial dependence and walking impairment, 43                                We found that the main risk factor for aneurysmal SAH
(19%) with disabilities but able to walk without assis-                        was hypertension, whereas diabetes mellitus was in-
tance, 30 (13%) with mild disabilities, 30 (13%) with min-                     versely related with this condition; which is consistent
imal impairment, and 23 (10%) completely asymptomatic                          with previous studies.16 According to other reports,17-20
(Table 5). Table 6 shows the analyses on in-hospital mor-                      we found that the female:male ratio is 2:1. A high number
tality according to different clinical scales. Of note, the                    of persons younger than 40 years was observed, contrast-
presence of radiographic findings typical of cerebral vaso-                     ing with the respective frequency reported for other coun-
spasm was not associated with in-hospital mortality.                           tries, including those with a very high incidence of
                                                                               SAH.17,21 This phenomenon could be due at least in part
  Discussion
                                                                               to the high proportion of young Mexican inhabitants.
  Cerebrovascular disease is the fourth cause of death in                      Other possible explanations could be that congenital vas-
the general population of Mexico, accounting for more                          cular abnormalities and other conditions associated with
than 27,000 (5.5% of total) deaths by 2006.12 In previous                      the aneurysm formation or rupture has a high representa-
hospital series from Mexico, the proportion of cases of                        tion in our young population, or that the young have



                Table 3. Clinical manifestations and laboratory analysis at hospital arrival, stratified by sex and age

                                                                      Sex                                          Age, y

               Variable                      Total          Male             Female      P value*         #49                $50       P valuey

   Headache, n (%)                       209 (90)          67 (89)          142 (94)         .21         99 (94)         110 (91)        .34
   Vomiting, n (%)                       152 (66)          48 (61)          104 (68)         .33         72 (68)          80 (64)        .53
   Probable seizures, n (%)               49 (21)          17 (22)           32 (21)         .87         31 (29)          18 (14)        .006
   Impaired consciousness at             130 (56)          32 (41)           98 (64)         .001        50 (47)          80 (64)        .01
      event onset, n (%)
   Systolic blood pressure, mm           142 (28)         137 (21)          145 (30)         .09       134 (24)          149 (29)        .01
      Hg, mean (SD)z
   Mean arterial pressure, mm            110 (18)         107 (15)          111 (20)         .10       105 (17)          113 (19)        .004
      Hg, mean (SD)z
   Pulse pressure, mm Hg, mean            55 (21)          51 (16)           57 (22)         .07         50 (16)            60 (23)      .002
      (SD)z
   Glucose, mg/dL, mean (SD)             136 (63)        136 (68)         136 (60)           .98       130 (58)         142 (67)         .17
   International normalized ratio,      1.11 (0.17)      1.10 (0.15)     1.13 (0.18)         .54       1.13 (0.17)     1.09 (0.17)       .40
      mean (SD)
   Hematocrit, %, mean (SD)               40 (6)           43 (7)          39 (5)         ,.001         40 (7)           41 (6)          .28
   Platelets, 310-4, mean (SD)          24.6 (8.4)       22.3 (7.6)      25.8 (8.6)        .003        25.0 (9.4)      24.2 (7.4)        .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.
52                                                                                                                J.L. RUIZ-SANDOVAL ET AL.

             Table 4. Number and vascular topography of the intracranial aneurysms as assessed by angiographic studies

                                                                                             Sex                                   Age, y

                     Variable                              Total                 Male              Female                 #49                $50

     No. of aneurysms*
       1, n (%)                                        197 (85)                 67 (86)            130 (85)             91 (86)             106 (85)
       .1, n (%)                                        34 (15)                 11 (14)             23 (15)             15 (14)              19 (15)
     Anterior circulation (n 5 213, 92%)y
       Posterior communicating artery, n (%)            64 (28)                 20 (26)             44 (29)             28 (26)              36 (29)
       Anterior communicating artery, n (%)             61 (26)                 22 (28)             39 (26)             25 (24)              36 (29)
       Middle cerebral artery, n (%)                    46 (20)                 16 (21)             30 (20)             23 (22)              23 (18)
       Internal carotid artery (supraclinoid),          27 (12)                  8 (10)             19 (12)             16 (15)              11 (9)
       n (%)
       Internal carotid artery (opthalmic), n           15 (6)                   4 (5)              11 (7)                7 (6)               8 (6)
       (%)
     Posterior circulation (n 5 18, 8%)z
       Posterior cerebral artery, n (%)                     5 (2)                 0 (0)              5 (3)                2 (2)               3 (2)
       Basilar artery, n (%)                                7 (3)                4 (5)               3 (2)                1 (1)               6 (5)
       Vertebral artery, n (%)                              6 (3)                4 (5)               2 (1)                4 (4)               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                         to the patient and possibly a high chance of being surgi-
frequently than do older persons.                                               cally treated.24
   The rate of microsurgical intervention or endovascular                         We observed a lower mortality than that previously re-
therapy was higher in our study, as compared with other                         ported.19,23-27 Our explanation to this finding is that RE-
reports.19,22,23 Indeed, this is possibly due to the fact that                  NAMEVASC is a hospital-based study on persons who
our cohort corresponds to patients hospitalized in urban                        reached medical assistance in urban teaching hospitals,
teaching hospitals, where the patients are treated almost                       and who had a diagnosis based on 4-vessel angiography.
entirely with microsurgical clipping.24 In the United                           Many patients with the extreme medical conditions after
States, higher rates of any invasive procedure in the urban                     SAH could be lost in the prehospital part of their disease
setting were observed, when compared with rural facili-                         evolution, due to a wrong diagnosis or death. Also, some
ties.23 In Mexico most of the invasive procedures are                           patients who arrived at our centers may not have been
performed in governmental teaching hospitals or in                              correctly diagnosed as having SAH, or may not have
public-insurance settings, which implies a minimal cost                         been documented by angiography and thus, were not


                   Table 5. Events during hospitalization and clinical outcome at discharge stratified by sex and age

                                                                              Sex                                       Age, y

                     Variable                      Total              Male          Female     P value*         #49               $50       P valuey

     Days of hospitalization, median              23 (2-98)         24 (3-92)     23 (2-98)        .81        19 (2-98)     28 (2-82)         .24
        (minimum and maximum)
     In-hospital systemic complications, n       107 (46)           34 (44)       73 (48)          .55        43 (41)       64 (51)           .11
        (%)
     Modified Rankin score at discharge                                                             .77                                        .03
        0-2, n (%)                                83 (36)           29 (37)       54 (35)                     46 (43)       37 (30)
        3-6, n (%)                               148 (64)           49 (63)       99 (65)                     60 (57)       88 (70)

  *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.
ANEURYSMAL SUBARACHNOID HEMORRHAGE IN MEXICAN HOSPITALS                                                                                   53

              Table 6. In-hospital mortality according to clinical and brain imaging characteristics at hospital arrival

                                                 Sex                          Age, y                      In-hospital death

           Variable            Total      Male     Female P value*        #49       $50      P valuey    Present    Absent     P valuez

   Hunt-Hess scalex                                            .09                              .04                               .001
     Grade I-II, n (%)        133 (66) 51 (74) 82 (62)                   72 (73) 61 (59)                14 (40)     119 (71)
     Grade III-V, n (%)        69 (34) 51 (38) 18 (26)                   26 (27) 43 (41)                21 (60)      48 (29)
   Fisher scale//                                              .86                              .34                             ,.001
     Grade I-II, n (%)         52 (26) 17 (25) 35 (26)                   28 (29) 24 (23)                  0 (0)   52 (31)
     Grade III-IV, n (%)      149 (74) 52 (75) 97 (74)                   68 (71) 81 (77)                34 (100) 115 (69)
   Glasgow Coma Scale{                                         .007                             .01                             ,.001
     Points 13-15, n (%)      149 (67) 61 (80) 88 (59)                   78 (76) 71 (59)                17 (39)     132 (73)
     Points 9-12, n (%)        43 (19) 9 (12) 34 (23)                    12 (11) 31 (25)                14 (33)      29 (16)
     Points 3-8, n (%)         32 (14) 6 (8) 26 (18)                     13 (13) 19 (16)                12 (28)      20 (11)
   Cerebral vasospasm#                                         .36                              .67                               .99
     Present, n (%)            88 (44) 26 (39) 62 (47)                   41 (43) 47 (46)                15 (44)      73 (45)
     Absent, n (%)            110 (56) 40 (61) 70 (53)                   55 (57) 55 (54)                19 (56)      91 (55)

  *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               compared with non-Hispanic whites,1,30,31 population-
they reach medical attention or diagnosis, and a consider-               based studies on stroke incidence have shown that the
able proportion of patients are missed during an emer-                   proportion of aneurysmal SAH among subtypes of
gency department visit, mainly due to a wrong                            cerebrovascular disease is less than 10%, which includes
diagnostic impression.28                                                 populations with Mexican ancestry.30,31 A long-term
   As expected,7 the global neurologic impairment and                    follow-up was not possible for all patients of our registry,
SAH grade at hospital arrival were associated with in-                   and only 35% persons of our sample were followed up for
hospital mortality, and notably, the vasospasm did not ex-               3 months or more (data not shown). A population-based
plain any effect on short-term outcome. However, our                     study on incidence, conditioning factors, and long-term
definition of vasospasm was limited, based on a single an-                outcome of persons with aneurysmal SAH in Mexico is
giography performed at any time during hospitalization,                  urgently needed. This issue will be certainly solved by
which is not a standard procedure to define this very dy-                 the US National Institutes of Health–sponsored Brain
namic phenomenon. Therefore, the consequences and                        Attack Surveillance in Durango City (BASID) Study. The
magnitude of clinically significant vasospasm could not                   RENAMEVASC prospective study is the first attempt in
be described with precision. This problem represents                     describing the general characteristics of aneurysmal
a limitation of our study. Nevertheless, vasospasm is                    SAH in Mexico with a nonsponsored and completely
not the only factor associated with neurologic worsening                 voluntary multicentric organization. Person-oriented
after SAH and its contribution on outcome may be small,                  data were registered with clinical and radiologic informa-
as could be inferred from clinical trials aimed to prevent               tion on aneurysmal topography and short-term outcome,
or reverse vasospasm to change the fate of SAH.29                        information that could be hardly provided in prospective
   Indeed, our study has other limitations. This is a hospi-             nonsponsored studies.
tal-based registry with a rather small sample size on pa-                   In conclusion, hypertension is the main risk factor for
tients admitted to referral centers with neurosurgical                   aneurysmal SAH in Mexico; however, other contributing
departments, which may favor hospitalization of patients                 risk factors could not be completely excluded with the
suitable for a surgical intervention, with the correspond-               methodology of this study.6,15 The female:male ratio of
ing high recording of the hemorrhagic forms of cerebro-                  hospitalized patients with aneurysmal SAH is 2:1, and
vascular disease (i.e., intracerebral hemorrhage and                     a considerably high proportion of patients are young.
SAH).13-15 Although it has been recognized that hemor-                   Most aneurysms are solitary and located at the anterior
rhagic stroke is more frequent among Hispanics, when                     circulation. We observed a high rate of invasive therapy,
54                                                                                                J.L. RUIZ-SANDOVAL ET AL.

owing to the characteristics of our study design and the            3. van Gijn J, Kerr RS, Rinkel GJE. Subarachnoid hemor-
Mexican health care system. A low in-hospital mortality                rhage. Lancet 2007;369:306-318.
was observed, possibly due to a low registering of fatal                                ´
                                                                    4. Arauz A, Cantu C, Ruiz-Sandoval JL, et al. Short-term
                                                                       prognosis of transient ischemic attacks: Mexican multi-
cases that occurred before aneurysm documentation.
                                                                       center stroke registry [in Spanish]. Rev Invest Clin 2006;
However, a high proportion of patients are discharged                  58:530-539.
with important neurologic impairment.                               5. Bonita R, Mendis S, Truelsen T, et al. The global stroke ini-
                                                                       tiative. Lancet Neurol 2004;3:391-393.
   The RENAMEVASC Investigators: Steering Committee                 6. Matsuda M, Watanabe K, Saito A, et al. Circumstances,
            ´                         ´
   C. Cantu-Brito, A. Arauz-Gongora, J. L. Ruiz-Sandoval, J.           activities, and events precipitating aneurysmal subarach-
Villarreal-Careaga, L. Murillo-Bonilla, R. Rangel-Guerra,              noid hemorrhage. J Stroke Cerebrovasc Dis 2007;16:25-29.
                                                                    7. Kazumata K, Kamiyama H, Ishikawa T. Reference table
F. Barinagarrementeria
                                                                       predicting the outcome of subarachnoid hemorrhage in
   Coordinating Office                                                  the elderly, stratified by age. J Stroke Cerebrovasc Dis
            ´
   C. Cantu-Brito, L. Murillo-Bonilla                                  2006;15:14-17.
   Participants                                                     8. Meaney E, Alva F, Moguel R, et al. Formula and nomo-
   The following centers and investigators participated in the         gram for the sphygmomanometric calculation of the
                                        ´
RENAMEVASC study: C. Cantu-Brito (Instituto Nacional de                mean arterial pressure. Heart 2000;84:64.
                                                                    9. Chiquete E, Ruiz-Sandoval MC, Alvarez-Palazuelos LE,
Ciencias Me   ´ dicas y Nutricion Salvador Zubiran, Ciudad de
                                  ´                 ´
                                                                       et al. Hypertensive intracerebral hemorrhage in the
Me ´ xico); A. Arauz-Gongora, L. Murillo-Bonilla, and L.
                              ´
                                                                       very elderly. Cerebrovasc Dis 2007;24:196-201.
                                              ´
Hoyos (Instituto Nacional de Neurologıa y Neurocirugıa,        ´   10. Chobanian AV, Bakris GL, Black HR, et al. The seventh re-
Ciudad de Me       ´ xico); J. L. Ruiz-Sandoval and E. Chiquete        port of the joint national committee on prevention, detec-
(Hospital Civil de Guadalajara, Jalisco); J. Villarreal-Careaga        tion, evaluation, and treatment of high blood pressure:
                     ´
and F. Guzman-Reyes (Hospital General de Culiacan,            ´        The JNC 7 report. JAMA 2003;289:2560-2572.
                                                                   11. American Diabetes Association. Diagnosis and classifica-
Sinaloa); F. Barinagarrementeria (Hospital Angeles de Quer-
                                                                       tion of diabetes mellitus. Diabetes Care 2006;28:S37-S42.
´             ´                     ´                  ´
etaro, Queretaro); J. A. Fernandez (Hospital Juarez, Ciudad                                                          ´
                                                                   12. Statistics on general mortality. Secretarıa de Salud,
        ´
de Mexico); B. Torres (Hospital General de Leon, Guana-  ´                ´
                                                                       Mexico, 2006. Available from: URL:http://www.salud.
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juato); C. Leon-Jimenez (Hospital Regional ISSSTE, Zapopan,            gob.mx/. Accessed April 2, 2008.
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Jalisco); I. Rodrıguez-Leyva (Hospital General de San Luis         13. Chiquete E, Ruiz-Sandoval JL. Prehospital events and in-
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Potosı, San Luis Potosi); R. Rangel-Guerra (Hospital Univer-           hospital mortality after acute stroke in a Mexican cohort
                            ´                        ´                 [in Spanish]. Rev Mex Neuroci 2007;8:41-48.
sitario de Nuevo Leon, Monterrey, Nuevo Leon); M. Banos      ˜
                                                                   14. Gardeal G, Segura MA, Ramos F, et al. Intracranial aneu-
(Hospital General de Balbuena, Ciudad de Mexico); L.       ´
                                                                       rysms: Review of 100 cases in a period of 12 years at the
                                                  ´
Espinosa and M. de la Maza (Hospital San Jose de Monterrey,            General Hospital of Mexico [in Spanish]. Arch Neurocien
            ´
Nuevo Leon); H. Colorado (Hospital General ISSSTE, Vera-               (Mex) 1996;1:288-291.
cruz, Veracruz); M. C. Loy-Gerala (Hospital General de Pue-        15. Connolly ES Jr, Poisik A, Winfree CJ, et al. Cigarette
bla, Puebla); J. Huebe-Rafool (Hospital General de Pachuca,            smoking and the development and rupture of cerebral
                                                                       aneurysms in a mixed race population: Implications for
Hidalgo); G. Aguayo Leytte (Hospital General de Aguasca-
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lientes, Aguascalientes); G. Tavera-Guittings (Hospital
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General ISSSTE, Campeche, Campeche); V. Garcia-Talavera            16. Feigin VL, Rinkel GJ, Lawes CM, et al. Risk factors for
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M. Segura (Hospital General de Morelia, Morelia); J. L.                review of epidemiological studies. Stroke 2005;
Sosa (Hospital General de Villahermosa, Tabasco); O. Tala-             36:2773-2780.
   ´                                                ´
mas-Murra (Hospital General ISSSTE, Torreon, Coahuila);            17. Rooij NK, Linn FH, van der Plas JA, et al. Incidence of
                                                                       subarachnoid hemorrhage: A systematic review with em-
                        ´
M. Alanis-Quiroga (Hospital Universitario de Torreon,        ´
                                                                       phasis on region, age, gender and time trends. J Neurol
Coahuila); J. M. Escamilla (Hospital de la Marina Nacional,            Neurosurg Psychiatry 2007;78:1365-1372.
                 ´                        ´
Ciudad de Mexico); M. A. Alegrıa (Hospital Central Militar,        18. Wermer MJH, van der Schaaf IC, Algra A, et al. Risk of
                   ´
Ciudad de Mexico); and J. C. Angulo (Hospital General,                 rupture of unruptured intracranial aneurysms in relation
Veracruz, Veracruz).                                                   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 hospitaliza-
                                                                       tion and mortality for subarachnoid hemorrhage and un-
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  • 1. Aneurysmal Subarachnoid Hemorrhage in a Mexican Multicenter Registry of Cerebrovascular Disease: The RENAMEVASC Study ´ ´ Jose L. Ruiz-Sandoval, MD,*† Carlos Cantu, MD, PhD,‡ Erwin Chiquete, MD, PhD,*† ´ ´ Carolina Leon-Jimenez, MD,x Antonio Arauz, MD, PhD,k Luis M. Murillo-Bonilla, MD, MSc,{ Jorge Villarreal-Careaga, MD,# ´ Fernando Barinagarrementerıa, MD,** and The RENAMEVASC Investigators 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 pa- tients with aneurysmal SAH. Methods: A first-step surveillance system was con- ducted on consecutive cases confirmed 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 fac- tors. 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% confidence interval 1.59-3.81) and diabetes mellitus (odds ratio 0.34, 95% confi- dence 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%), en- dovascular 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 dis- charged with a modified Rankin score of 4 or 5. Conclusions: Hypertension is the main risk factor for aneurysmal SAH in hospitalized patients from Mexico. The fe- male: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 dis- charged with important neurologic impairment. Key Words: Cerebral aneurysm— epidemiology—outcome—risk factors—subarachnoid hemorrhage. Ó 2009 by National Stroke Association From the *Department of Neurology and Neurosurgery, Hospital Received May 22, 2008; revision received September 1, 2008; Civil de Guadalajara ‘‘Fray Antonio Alcalde’’, †Department of Neuro- accepted September 11, 2008. sciences, Centro Universitario de Ciencias de la Salud, Universidad ´ Address correspondence to Jose L. Ruiz-Sandoval, MD, Servicio de de Guadalajara, ‡Department of Neurology, Instituto Nacional de ´ ´ Neurologıa y Neurocirugıa, Hospital Civil de Guadalajara ‘‘Fray An- ´ ´ ´ Ciencias Medicas y Nutricion ‘‘Salvador Zubiran,’’ Mexico City, tonio Alcalde,’’ Hospital 278, Guadalajara, Jalisco, Mexico 44280. ´ ´ xDepartment of Neurology, Hospital Regional Gomez Farıas, Zapo- E-mail: jorulej-1nj@prodigy.net.mx. ´ ´ pan, kStroke Clinic, Instituto Nacional de Neurologıa y Neurocirugıa, 1052-3057/$—see front matter Mexico City, {Department of Neurology, Instituto Panvascular de Oc- Ó 2009 by National Stroke Association cidente, Guadalajara, #Department of Neurology, Hospital General doi:10.1016/j.jstrokecerebrovasdis.2008.09.019 ´ ´ de Culiacan; and **Department of Neurology, Hospital Angeles Quer- ´ ´ etaro, Mexico. 48 Journal of Stroke and Cerebrovascular Diseases, Vol. 18, No. 1 (January-February), 2009: pp 48-55
  • 2. ANEURYSMAL SUBARACHNOID HEMORRHAGE IN MEXICAN HOSPITALS 49 Depending on the population and study design, it is es- nonneurologic clinics or services (e.g., internal medicine, timated that subarachnoid hemorrhage (SAH) accounts gastroenterology, and endocrinology facilities); (2) medical for less than 10% of the clinical forms of acute cerebrovas- students and their families; and (3) volunteers from out- cular disease.1,2 On the other hand, SAH as a result of rup- side the hospitals. The internal committee of ethics of every ture of intracranial aneurysms accounts for approximately participating center approved the study and the inclusion 3% of all strokes2 and for 85% of all SAH cases.3 Its clinical of control subjects. Informed consent was obtained from impact is greater than it appears considering only the fre- the patient, control subject, or the patient’s legal proxy. quency of this condition as it affects otherwise healthy Mean arterial pressure (MAP) was calculated from the young adults. systolic blood pressure (SBP) and diastolic blood pressure Information regarding frequency, associated risk factors, (DBP) measurements at admittance to the emergency de- and outcome of persons with SAH in Mexico is unknown. partment as follows: MAP 5 DBP 1 0.412 (SBP – DBP).8,9 ´ To address this issue, the Asociacion Mexicana de Enfer- This formula corrects for the spurious variation of MAP medad Vascular Cerebral created the Registro Nacional in hypertensive persons; therefore, it is best suited for co- Mexicano de Enfermedad Vascular Cerebral (RENAME- horts with a high frequency of high blood pressure.8 Hy- VASC),4 which is a nationwide, nongovernmental, nonin- pertension and diabetes mellitus were defined as dustry-sponsored, multicentric register of consecutive established by standard guidelines.10,11 For the purpose patients with acute cerebrovascular disease hospitalized of the current report, smoking was defined as the con- in Mexico. The initial purpose of this national registry sumption (either past or current) of 5 or more cigarettes was to conduct a first-step stroke surveillance system, for at least 2 days per week during 12 months or more, which implies the systematic registering of patients with and alcoholism as more than two alcoholic drinks per acute cerebrovascular disease admitted to a hospital or day (on average). Vasospasm was defined by means of clinic-based facility and following up of the patients until a single angiography of 4 vessels during the diagnostic discharge from hospital or death.5 The aim of this RENA- work-up, at any time of the hospital stay. MEVASC report on SAH was to describe the clinical and Parametric continuous variables are expressed as geo- demographic characteristics, risk factors, and outcome at metric means and SD, or minimum and maximum. Non- discharge of Mexican patients hospitalized for aneurysmal parametric continuous variables are expressed as SAH, with a nationwide representation. medians. As the median age of the study group was 51 years, we divided the cohort into people aged 49 years Methods or younger and 50 years or older to analyze the associa- tion of age with risk factors, clinical characteristics, and Patients outcome. To compare quantitative variables distributed This prospective hospital-based multicentric registry between two groups, Student t test and Mann-Whitney was conducted from November 2002 to October 2004 in U test were performed in distributions of parametric 25 tertiary referral centers from 14 Mexican states.4 Consec- and nonparametric variables, respectively. Chi-square utive patients were registered if a suspected acute ischemic statistics (i.e., Pearson Chi-square or Fisher exact test, as or hemorrhagic stroke was confirmed by head computed corresponded) were used to compare nominal variables tomography scan or magnetic resonance imaging. A stan- in bivariate analyses. To find independent risk factors dardized, structured questionnaire was used to collect for aneurysmal SAH (as compared with control subjects) clinical and demographic data from the patient or primary a multivariate analysis was constructed by a binary logis- guardian and medical records by the local investigator. tic regression model. Independent variables were chosen Other data registered included in-hospital management if P was less than .1 in bivariate analyses, but relevant and outcome at discharge and at 3 months follow-up. nonsignificant variables remained in the model for adjust- The patient’s functional status was classified by the modi- ment. Subsequently a forward-stepwise method was per- fied Rankin scale.4 All data were sent to a reference center formed. Adjusted odds ratios with 95% confidence in hard version and electronically captured by two investi- intervals that resulted in final step of the model are pro- gators, after completion of the registering deadline. For the vided. The fitness of the model was evaluated by using purpose of this report, patients with SAH due to ruptured the Hosmer-Lemeshow goodness-of-fit test, which was intracranial aneurysms confirmed by 4-vessel angio- considered as reliable if P was greater than .20. All P graphic techniques were included.6,7 To compare the fre- values reported are 2-sided and regarded as significant quency of putative risk factors between patients with when P was less than .05. Software (SPSS v 13.0) was aneurysmal SAH and the general population, 231 age- used for all calculations. and sex-matched ambulatory persons without history of SAH were included as control subjects. These people Results were registered explicitly for the purpose of this study and consisted of persons without any known neurologic A total of 2000 patients with acute cerebrovascular dis- disease: (1) relatives of patients who attend to ease were included in the registry: 1092 ischemic stroke
  • 3. 50 J.L. RUIZ-SANDOVAL ET AL. (either infarct or transient ischemic attack), 580 intracere- in patients 50 years or older than in younger persons; bral hemorrhage, 59 cerebral venous thrombosis, and 269 nonetheless, more seizures were reported in the latter nontraumatic SAH. All patients included pertained to the group. Single aneurysms occurred in 85% cases (Table Latin American bioethnic group. In all, 38 patients were 4). In 92% patients the lesions were located at the anterior excluded because they had a cause of SAH other than circulation. There were no differences in vascular topog- ruptured aneurysms, or because they lacked angiogra- raphy according to age or sex (Table 4). Other anatomic phy. Therefore, after applying selection criteria, 231 pa- characteristics of the aneurysms, such as size, neck, and tients were analyzed. There were 153 (66%) women and dome, were not registered. 78 (34%) men, with a mean age of 51.8 years (median 51 Duration of the hospital stay had a median of 23 days years, range 16-90). In all, 55 (24%) patients were younger (range 2-98 days) (Table 5). In all, 157 (68%) patients re- than 40 years and 49 (21%) were 65 years or older. Hyper- quired entering the intensive care department at any tension was more frequent among patients than control time of their hospitalization, whereas 74 (32%) patients subjects, whereas few cases of diabetes mellitus were ob- were treated completely in general wards. The need for served in the SAH group (Table 1). After multivariate mechanical ventilation occurred in 91 (39%) cases. We analysis controlled for potential confounders, hyperten- lacked information regarding the time to angiography sion remained a significant risk and diabetes an inversely or time to surgery or endovascular intervention after hos- associated factor for aneurysmal SAH. Table 2 shows the pital arrival. Invasive treatment of the aneurysms was distribution of risk factors among patients, stratified by performed in 159 (69%) patients by using the following sex and age. Alcohol consumption and smoking were techniques: clipping of ruptured aneurysm in 126 (79% more common in men than in women. Hypertension of those surgically treated), endovascular coiling in 29 and diabetes mellitus were more frequent in patients 50 (18%, all of them performed in a single center), and aneu- years or older than in younger persons. rysm wrapping in 4 (2%) patients. The type of manage- The onset of the clinical manifestations was registered ment (any invasive intervention v only medical in 184 cases; of these, 69 (37.5%) occurred during the first treatment) did not differ with age (P 5 .31, for persons 12 hours of the day (at awakening in 8%, n 5 19) and in aged $ 50 v younger individuals), sex (P 5 .45, for men 115 (62.5%) during the afternoon or night. No monthly v women), or aneurysm topography (P 5 .20, for anterior or seasonal patterns in hospitalization for aneurysmal v posterior circulation); however, aneurysm wrapping SAH were identified. The hemorrhage was preceded by was performed only for aneurysms of the anterior circula- a physical effort in 29 (12%) cases and by emotional stress tion (P , .001). Hydrocephalus was observed in 22% in 11 (5%) (without differences according to age or sex). cases; of them, 72% received a shunting procedure. Pneu- Table 3 shows the clinical manifestations and laboratory monia was the most frequent systemic complication (87/ work-up at hospital arrival. The main features were head- 231, 38%), followed by urinary tract infections (47/231, ache, vomiting, and impaired consciousness. More men 20%), cardiac arrhythmia (17/231, 7%), and lower-limb than women presented to hospital with a Glasgow deep-vein thrombosis (4/231, 2%). In all, 46 (20%) pa- Coma Scale score greater than 13 (80% v 59%, respec- tients died in the hospital; 25 (54%) with a neurologic tively; P 5 .002). Impaired consciousness at event onset cause, 13 (28%) with a systemic nonneurologic complica- and higher blood pressure measures were more frequent tion, 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 Patients (n 5 231) Control subjects (n 5 231) P value* Multivariate OR (95% CI)y Age, y, mean (range) 51.6 (16-90) 51.6 (16-90) .99 NS Female, n (%) 156 (66) 156 (66) .99 NS Hypertension, n (%) 96 (42) 67 (29) .005 2.46 (1.59-3.81) Diabetes mellitus, n (%) 16 (7) 35 (15) .005 0.34 (0.17-0.68) Alcoholism, n (%) 30 (13) 35 (15) .50 NS Current smoker, n (%) 68 (29) 61 (26) .47 NS Former smoker, n (%) 15 (6) 12 (5) .55 NS Abbreviations: CI, confidence interval; NS, not significant; 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-fit 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.
  • 4. ANEURYSMAL SUBARACHNOID HEMORRHAGE IN MEXICAN HOSPITALS 51 Table 2. Risk factors for aneurysmal subarachnoid hemorrhage stratified by sex and age Sex Age, y Variable Total Male Female P value* #49 $50 P valuey Age, y, mean (range) 51.6 (16-90) 49.1 (16-90) 52.8 (17-90) .89 38.1 (16-49) 63.0 (50-90) ,.001 Hypertension, n (%) 96 (42) 29 (37) 67 (44) .33 26 (24) 70 (56) ,.001 Diabetes mellitus, n (%) 16 (7) 6 (8) 10 (6) .74 2 (2) 14 (11) .005 Alcoholism, n (%) 30 (13) 21 (27) 9 (6) ,.001 13 (12) 17 (14) .76 Current smoker, n (%) 68 (29) 30 (38) 38 (25) .03 35 (33) 33 (26) .27 Former smoker, n (%) 43 (19) 19 (24) 24 (16) .11 18 (17) 25 (20) .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 depen- SAH among forms of stroke has been reported to be dence on others for activities of daily living, 33 (14%) around 15%.13-15 with partial dependence and walking impairment, 43 We found that the main risk factor for aneurysmal SAH (19%) with disabilities but able to walk without assis- was hypertension, whereas diabetes mellitus was in- tance, 30 (13%) with mild disabilities, 30 (13%) with min- versely related with this condition; which is consistent imal impairment, and 23 (10%) completely asymptomatic with previous studies.16 According to other reports,17-20 (Table 5). Table 6 shows the analyses on in-hospital mor- we found that the female:male ratio is 2:1. A high number tality according to different clinical scales. Of note, the of persons younger than 40 years was observed, contrast- presence of radiographic findings typical of cerebral vaso- ing with the respective frequency reported for other coun- spasm was not associated with in-hospital mortality. tries, including those with a very high incidence of SAH.17,21 This phenomenon could be due at least in part Discussion to the high proportion of young Mexican inhabitants. Cerebrovascular disease is the fourth cause of death in Other possible explanations could be that congenital vas- the general population of Mexico, accounting for more cular abnormalities and other conditions associated with than 27,000 (5.5% of total) deaths by 2006.12 In previous the aneurysm formation or rupture has a high representa- hospital series from Mexico, the proportion of cases of tion in our young population, or that the young have Table 3. Clinical manifestations and laboratory analysis at hospital arrival, stratified by sex and age Sex Age, y Variable Total Male Female P value* #49 $50 P valuey Headache, n (%) 209 (90) 67 (89) 142 (94) .21 99 (94) 110 (91) .34 Vomiting, n (%) 152 (66) 48 (61) 104 (68) .33 72 (68) 80 (64) .53 Probable seizures, n (%) 49 (21) 17 (22) 32 (21) .87 31 (29) 18 (14) .006 Impaired consciousness at 130 (56) 32 (41) 98 (64) .001 50 (47) 80 (64) .01 event onset, n (%) Systolic blood pressure, mm 142 (28) 137 (21) 145 (30) .09 134 (24) 149 (29) .01 Hg, mean (SD)z Mean arterial pressure, mm 110 (18) 107 (15) 111 (20) .10 105 (17) 113 (19) .004 Hg, mean (SD)z Pulse pressure, mm Hg, mean 55 (21) 51 (16) 57 (22) .07 50 (16) 60 (23) .002 (SD)z Glucose, mg/dL, mean (SD) 136 (63) 136 (68) 136 (60) .98 130 (58) 142 (67) .17 International normalized ratio, 1.11 (0.17) 1.10 (0.15) 1.13 (0.18) .54 1.13 (0.17) 1.09 (0.17) .40 mean (SD) Hematocrit, %, mean (SD) 40 (6) 43 (7) 39 (5) ,.001 40 (7) 41 (6) .28 Platelets, 310-4, mean (SD) 24.6 (8.4) 22.3 (7.6) 25.8 (8.6) .003 25.0 (9.4) 24.2 (7.4) .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.
  • 5. 52 J.L. RUIZ-SANDOVAL ET AL. Table 4. Number and vascular topography of the intracranial aneurysms as assessed by angiographic studies Sex Age, y Variable Total Male Female #49 $50 No. of aneurysms* 1, n (%) 197 (85) 67 (86) 130 (85) 91 (86) 106 (85) .1, n (%) 34 (15) 11 (14) 23 (15) 15 (14) 19 (15) Anterior circulation (n 5 213, 92%)y Posterior communicating artery, n (%) 64 (28) 20 (26) 44 (29) 28 (26) 36 (29) Anterior communicating artery, n (%) 61 (26) 22 (28) 39 (26) 25 (24) 36 (29) Middle cerebral artery, n (%) 46 (20) 16 (21) 30 (20) 23 (22) 23 (18) Internal carotid artery (supraclinoid), 27 (12) 8 (10) 19 (12) 16 (15) 11 (9) n (%) Internal carotid artery (opthalmic), n 15 (6) 4 (5) 11 (7) 7 (6) 8 (6) (%) Posterior circulation (n 5 18, 8%)z Posterior cerebral artery, n (%) 5 (2) 0 (0) 5 (3) 2 (2) 3 (2) Basilar artery, n (%) 7 (3) 4 (5) 3 (2) 1 (1) 6 (5) Vertebral artery, n (%) 6 (3) 4 (5) 2 (1) 4 (4) 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 to the patient and possibly a high chance of being surgi- frequently than do older persons. cally treated.24 The rate of microsurgical intervention or endovascular We observed a lower mortality than that previously re- therapy was higher in our study, as compared with other ported.19,23-27 Our explanation to this finding is that RE- reports.19,22,23 Indeed, this is possibly due to the fact that NAMEVASC is a hospital-based study on persons who our cohort corresponds to patients hospitalized in urban reached medical assistance in urban teaching hospitals, teaching hospitals, where the patients are treated almost and who had a diagnosis based on 4-vessel angiography. entirely with microsurgical clipping.24 In the United Many patients with the extreme medical conditions after States, higher rates of any invasive procedure in the urban SAH could be lost in the prehospital part of their disease setting were observed, when compared with rural facili- evolution, due to a wrong diagnosis or death. Also, some ties.23 In Mexico most of the invasive procedures are patients who arrived at our centers may not have been performed in governmental teaching hospitals or in correctly diagnosed as having SAH, or may not have public-insurance settings, which implies a minimal cost been documented by angiography and thus, were not Table 5. Events during hospitalization and clinical outcome at discharge stratified by sex and age Sex Age, y Variable Total Male Female P value* #49 $50 P valuey Days of hospitalization, median 23 (2-98) 24 (3-92) 23 (2-98) .81 19 (2-98) 28 (2-82) .24 (minimum and maximum) In-hospital systemic complications, n 107 (46) 34 (44) 73 (48) .55 43 (41) 64 (51) .11 (%) Modified Rankin score at discharge .77 .03 0-2, n (%) 83 (36) 29 (37) 54 (35) 46 (43) 37 (30) 3-6, n (%) 148 (64) 49 (63) 99 (65) 60 (57) 88 (70) *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.
  • 6. ANEURYSMAL SUBARACHNOID HEMORRHAGE IN MEXICAN HOSPITALS 53 Table 6. In-hospital mortality according to clinical and brain imaging characteristics at hospital arrival Sex Age, y In-hospital death Variable Total Male Female P value* #49 $50 P valuey Present Absent P valuez Hunt-Hess scalex .09 .04 .001 Grade I-II, n (%) 133 (66) 51 (74) 82 (62) 72 (73) 61 (59) 14 (40) 119 (71) Grade III-V, n (%) 69 (34) 51 (38) 18 (26) 26 (27) 43 (41) 21 (60) 48 (29) Fisher scale// .86 .34 ,.001 Grade I-II, n (%) 52 (26) 17 (25) 35 (26) 28 (29) 24 (23) 0 (0) 52 (31) Grade III-IV, n (%) 149 (74) 52 (75) 97 (74) 68 (71) 81 (77) 34 (100) 115 (69) Glasgow Coma Scale{ .007 .01 ,.001 Points 13-15, n (%) 149 (67) 61 (80) 88 (59) 78 (76) 71 (59) 17 (39) 132 (73) Points 9-12, n (%) 43 (19) 9 (12) 34 (23) 12 (11) 31 (25) 14 (33) 29 (16) Points 3-8, n (%) 32 (14) 6 (8) 26 (18) 13 (13) 19 (16) 12 (28) 20 (11) Cerebral vasospasm# .36 .67 .99 Present, n (%) 88 (44) 26 (39) 62 (47) 41 (43) 47 (46) 15 (44) 73 (45) Absent, n (%) 110 (56) 40 (61) 70 (53) 55 (57) 55 (54) 19 (56) 91 (55) *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 compared with non-Hispanic whites,1,30,31 population- they reach medical attention or diagnosis, and a consider- based studies on stroke incidence have shown that the able proportion of patients are missed during an emer- proportion of aneurysmal SAH among subtypes of gency department visit, mainly due to a wrong cerebrovascular disease is less than 10%, which includes diagnostic impression.28 populations with Mexican ancestry.30,31 A long-term As expected,7 the global neurologic impairment and follow-up was not possible for all patients of our registry, SAH grade at hospital arrival were associated with in- and only 35% persons of our sample were followed up for hospital mortality, and notably, the vasospasm did not ex- 3 months or more (data not shown). A population-based plain any effect on short-term outcome. However, our study on incidence, conditioning factors, and long-term definition of vasospasm was limited, based on a single an- outcome of persons with aneurysmal SAH in Mexico is giography performed at any time during hospitalization, urgently needed. This issue will be certainly solved by which is not a standard procedure to define this very dy- the US National Institutes of Health–sponsored Brain namic phenomenon. Therefore, the consequences and Attack Surveillance in Durango City (BASID) Study. The magnitude of clinically significant vasospasm could not RENAMEVASC prospective study is the first attempt in be described with precision. This problem represents describing the general characteristics of aneurysmal a limitation of our study. Nevertheless, vasospasm is SAH in Mexico with a nonsponsored and completely not the only factor associated with neurologic worsening voluntary multicentric organization. Person-oriented after SAH and its contribution on outcome may be small, data were registered with clinical and radiologic informa- as could be inferred from clinical trials aimed to prevent tion on aneurysmal topography and short-term outcome, or reverse vasospasm to change the fate of SAH.29 information that could be hardly provided in prospective Indeed, our study has other limitations. This is a hospi- nonsponsored studies. tal-based registry with a rather small sample size on pa- In conclusion, hypertension is the main risk factor for tients admitted to referral centers with neurosurgical aneurysmal SAH in Mexico; however, other contributing departments, which may favor hospitalization of patients risk factors could not be completely excluded with the suitable for a surgical intervention, with the correspond- methodology of this study.6,15 The female:male ratio of ing high recording of the hemorrhagic forms of cerebro- hospitalized patients with aneurysmal SAH is 2:1, and vascular disease (i.e., intracerebral hemorrhage and a considerably high proportion of patients are young. SAH).13-15 Although it has been recognized that hemor- Most aneurysms are solitary and located at the anterior rhagic stroke is more frequent among Hispanics, when circulation. We observed a high rate of invasive therapy,
  • 7. 54 J.L. RUIZ-SANDOVAL ET AL. owing to the characteristics of our study design and the 3. van Gijn J, Kerr RS, Rinkel GJE. Subarachnoid hemor- Mexican health care system. A low in-hospital mortality rhage. Lancet 2007;369:306-318. was observed, possibly due to a low registering of fatal ´ 4. Arauz A, Cantu C, Ruiz-Sandoval JL, et al. Short-term prognosis of transient ischemic attacks: Mexican multi- cases that occurred before aneurysm documentation. center stroke registry [in Spanish]. Rev Invest Clin 2006; However, a high proportion of patients are discharged 58:530-539. with important neurologic impairment. 5. Bonita R, Mendis S, Truelsen T, et al. The global stroke ini- tiative. Lancet Neurol 2004;3:391-393. The RENAMEVASC Investigators: Steering Committee 6. Matsuda M, Watanabe K, Saito A, et al. Circumstances, ´ ´ C. Cantu-Brito, A. Arauz-Gongora, J. L. Ruiz-Sandoval, J. activities, and events precipitating aneurysmal subarach- Villarreal-Careaga, L. Murillo-Bonilla, R. Rangel-Guerra, noid hemorrhage. J Stroke Cerebrovasc Dis 2007;16:25-29. 7. Kazumata K, Kamiyama H, Ishikawa T. Reference table F. Barinagarrementeria predicting the outcome of subarachnoid hemorrhage in Coordinating Office the elderly, stratified by age. J Stroke Cerebrovasc Dis ´ C. Cantu-Brito, L. Murillo-Bonilla 2006;15:14-17. Participants 8. Meaney E, Alva F, Moguel R, et al. Formula and nomo- The following centers and investigators participated in the gram for the sphygmomanometric calculation of the ´ RENAMEVASC study: C. Cantu-Brito (Instituto Nacional de mean arterial pressure. Heart 2000;84:64. 9. Chiquete E, Ruiz-Sandoval MC, Alvarez-Palazuelos LE, Ciencias Me ´ dicas y Nutricion Salvador Zubiran, Ciudad de ´ ´ et al. Hypertensive intracerebral hemorrhage in the Me ´ xico); A. Arauz-Gongora, L. Murillo-Bonilla, and L. ´ very elderly. Cerebrovasc Dis 2007;24:196-201. ´ Hoyos (Instituto Nacional de Neurologıa y Neurocirugıa, ´ 10. Chobanian AV, Bakris GL, Black HR, et al. The seventh re- Ciudad de Me ´ xico); J. L. Ruiz-Sandoval and E. Chiquete port of the joint national committee on prevention, detec- (Hospital Civil de Guadalajara, Jalisco); J. Villarreal-Careaga tion, evaluation, and treatment of high blood pressure: ´ and F. Guzman-Reyes (Hospital General de Culiacan, ´ The JNC 7 report. JAMA 2003;289:2560-2572. 11. American Diabetes Association. Diagnosis and classifica- Sinaloa); F. Barinagarrementeria (Hospital Angeles de Quer- tion of diabetes mellitus. Diabetes Care 2006;28:S37-S42. ´ ´ ´ ´ etaro, Queretaro); J. A. Fernandez (Hospital Juarez, Ciudad ´ 12. Statistics on general mortality. Secretarıa de Salud, ´ de Mexico); B. Torres (Hospital General de Leon, Guana- ´ ´ Mexico, 2006. Available from: URL:http://www.salud. ´ ´ juato); C. Leon-Jimenez (Hospital Regional ISSSTE, Zapopan, gob.mx/. Accessed April 2, 2008. ´ Jalisco); I. Rodrıguez-Leyva (Hospital General de San Luis 13. Chiquete E, Ruiz-Sandoval JL. Prehospital events and in- ´ Potosı, San Luis Potosi); R. Rangel-Guerra (Hospital Univer- hospital mortality after acute stroke in a Mexican cohort ´ ´ [in Spanish]. Rev Mex Neuroci 2007;8:41-48. sitario de Nuevo Leon, Monterrey, Nuevo Leon); M. Banos ˜ 14. Gardeal G, Segura MA, Ramos F, et al. Intracranial aneu- (Hospital General de Balbuena, Ciudad de Mexico); L. ´ rysms: Review of 100 cases in a period of 12 years at the ´ Espinosa and M. de la Maza (Hospital San Jose de Monterrey, General Hospital of Mexico [in Spanish]. Arch Neurocien ´ Nuevo Leon); H. Colorado (Hospital General ISSSTE, Vera- (Mex) 1996;1:288-291. cruz, Veracruz); M. C. Loy-Gerala (Hospital General de Pue- 15. Connolly ES Jr, Poisik A, Winfree CJ, et al. Cigarette bla, Puebla); J. Huebe-Rafool (Hospital General de Pachuca, smoking and the development and rupture of cerebral aneurysms in a mixed race population: Implications for Hidalgo); G. 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