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(Stroke. 1995;26:577-580.)
© 1995 American Heart Association, Inc.

Articles

Sex Differences in the Management of Patients Hospitalized With Ischemic Cerebrovascular Disease

S. J. Patrick, MD; J. Concato, MD, MS, MPH; C. Viscoli, PhD; D. Chyatte, MD L. M. Brass, MD

From the Departments of Neurology (S.J.P., L.M.B.) and Medicine (J.C., C.V.), Yale University School of Medicine, New Haven, Conn; the Neurosurgery Service, Cleveland Clinic (Ohio) (D.C.); and the Medical Service (J.C.) and the Neurology Service (L.M.B.), Veterans Affairs Medical Center, West Haven, Conn.

	Abstract

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Background and Purpose Previous studies suggest that the management of coronary artery disease differs for women compared with men. We examined this issue for ischemic cerebrovascular disease.

Methods We reviewed the use of angiography and carotid endarterectomy among patients discharged from Connecticut hospitals during 6 years over the past decade. Crude and age-adjusted rates of angiography and endarterectomy were determined for each sex.

Results Among 22 582 female and 19 729 male patients discharged, the rate of cerebral angiography was 11.8% for men and 7.2% for women; the age-adjusted odds ratio was 0.77 (95% confidence interval [CI], 0.72 to 0.82). The rate of endarterectomy was 10.6% for men and 5.7% for women; the age-adjusted odds ratio was 0.67 (95% CI, 0.62 to 0.72). The distribution of cerebrovascular disease type differed by sex, however, with carotid artery disease representing a larger proportion of men (12.2% [2415/19 729]) than women (6.9% [1554/22 582]) (²=355.8, P<.0001). When restricted to this diagnosis, no sex differences exist (odds ratio for angiography, 1.00 [95% CI, 0.87 to 1.14] and for endarterectomy, 0.93 [95% CI, 0.81 to 1.07]).

Conclusions Overall, women hospitalized for ischemic cerebrovascular disease undergo fewer angiograms and are less likely to have carotid endarterectomy than men. These differences are not found when analysis is restricted to subjects with carotid disease and suggest that part of the difference in management may be due to biological differences between men and women.

Key Words: angiography • carotid endarterectomy • cerebral ischemia • gender • women

	Introduction

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Recent reports indicate that women receive fewer invasive cardiac procedures than men.^{1 2 3} Men are twice as likely as women to undergo a coronary bypass or angiography procedure when database information is used to "control" for major arteriosclerotic risk factors.² A recent prospective examination of physicians' decisions to refer patients for cardiac catheterization, however, found no evidence of "sex bias."⁴ Despite possible differences in the management of patients with coronary artery disease by sex, few data are available examining potential differences in the use of carotid endarterectomy among men and women with cerebrovascular disease. Previous hospital and community-based studies assessing the practice and safety of carotid endarterectomy had a male preponderance of patients.^{5 6} Although such studies indirectly suggest that a sex difference exists in the use of carotid endarterectomy, the question of whether the difference in frequency of cerebrovascular procedures among women compared with men is appropriate has not been specifically addressed.

Carotid endarterectomy was recently shown to decrease the risk of stroke and death among patients with high-grade symptomatic carotid stenosis, and both sexes derive benefit.^{7 8} As a result of these findings, surgery is likely to be performed more frequently in the future. The purpose of this research was to investigate sex-related differences in the management of patients with cerebrovascular disease during a period when the indications for carotid endarterectomy were controversial. These circumstances might reveal sex bias in the management of men and women with similar characteristics in that guidelines for appropriate care are uncertain. A statewide (Connecticut) database of hospital discharge information was used to compare rates of cerebral angiography and carotid endarterectomy for men and women hospitalized with stroke or transient cerebral ischemia in selected years during the last decade.

We recognized that databases of hospital discharge information commonly lack sufficient detail to ascertain clinical features of patients and clinical judgment by physicians. These factors ultimately affect the decision to perform diagnostic tests and therapeutic procedures and also influence the outcome of care.^{4 9} As a result, if the distribution of clinical characteristics differs for men and women, sex bias may be inferred even though men and women with similar clinical characteristics are treated similarly. Accordingly, medical record review, or ideally prospective data collection, is desirable to address the question of why diagnostic and therapeutic approaches differ for men and women. If patient characteristics contained in the database account for observed patterns of management, however, concern regarding sex bias can be reduced before conducting more in-depth investigations.

	Subjects and Methods

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Data Sources and Patient Population
Information on all patients aged 50 years or older discharged from the 36 nongovernmental, acute-care hospitals in Connecticut during 1981, 1983, 1985, 1987, 1988, and 1989 were available from the Connecticut Health Information and Exchange (CHIME) database.¹⁰ (These particular years were available from a separate research protocol.) Patient data included age, sex, race, principal diagnosis, the first three secondary diagnoses, major diagnostic and therapeutic procedures, first through third secondary procedures, and patient disposition.

With the use of the International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM) codes 433 through 437.9 inclusive, all patients with principal diagnoses of ischemic stroke or transient cerebral ischemia were identified. The principal diagnosis was the condition determined at discharge to have been chiefly responsible for the patient's admission to the hospital.

Data Analysis
Our hypothesis was that women were less likely than men to undergo cerebral angiography and carotid endarterectomy when hospitalized with ischemic cerebrovascular diseases (ie, an ischemic stroke or transient cerebral ischemia). Rates of carotid endarterectomy (ICD-9-CM code 38.1) among patients hospitalized with ischemic cerebrovascular disease during the selected years were determined, and corresponding age-adjusted female-to-male odds ratios (ORs) (with 95% confidence intervals [CIs]) were calculated. Because carotid endarterectomy is usually preceded by cerebral angiography to assess the degree of carotid stenosis, rates of cerebral angiography (ICD-9-CM code 88.41) and female-to-male ORs were also assessed. Carotid ultrasound was performed infrequently during the index admission and was not considered in this study. Evaluations performed in an outpatient setting were not available for review.

The type of ischemic stroke influences treatment. For example, a stroke associated with carotid stenosis, compared with intracerebral thromboembolism, is more likely to be treated by carotid endarterectomy. If type of stroke is also related to the sex of a patient, an apparent sex difference in therapy may actually represent a biological feature of the disease. Accordingly, rates of endarterectomy and angiography were calculated for patients grouped by type of ischemic cerebrovascular disease with the use of selected ICD-9-CM codes. These included occlusion and stenosis of the carotid artery (ICD-9-CM code 433.1), occlusion of cerebral arteries (ICD-9-CM codes 434.0 through 434.9), transient cerebral ischemia (ICD-9-CM codes 435.0 through 435.8 but excluding 435.0 through 435.2, which are for basilar, vertebral, and subclavian syndromes), and a combined category for all other types of ischemic stroke.

	Results

Top Abstract Introduction Subjects and Methods Results Discussion References

 
A principal diagnosis of ischemic cerebrovascular disease was identified for 22 582 female and 19 729 male patients discharged in Connecticut during the selected years. Demographic and clinical data are shown in Table 1. The age distribution of cerebrovascular disease was younger in men; 26.8% of female compared with 42.8% of male patients discharged with stroke were younger than 70 years of age. (Nonwhite races accounted for 8% of discharged patients and were not analyzed separately.) In addition, the distribution of type of cerebrovascular disease differed between men and women, with occlusion/stenosis of the carotid artery representing a larger proportion of men than women (12.2% [2415/19 729] versus 6.9% [1554/22 582], respectively; ²=355.8, P<.0001).

View this table: [in this window] [in a new window]   Table 1. Demographic and Clinical Characteristics of Patients Hospitalized With Ischemic Stroke or Transient Cerebral Ischemia

Overall rates of cerebral angiography and carotid endarterectomy are shown in Table 2. The age-adjusted female-to-male ORs were 0.77 for angiography (95% CI, 0.72 to 0.82) and 0.67 for endarterectomy (95% CI, 0.62 to 0.72). Thus, both procedures were less common in women, even when adjusting for differences in the age distribution of the population.

View this table: [in this window] [in a new window]   Table 2. Rates and Female-to-Male Odds Ratios for Cerebral Angiography and Carotid Endarterectomy by Age Group

Rates and ORs for carotid endarterectomy and cerebral angiography varied among the different cerebrovascular disease types, however, as shown in Table 3. The highest rates of angiography and endarterectomy were found among patients with a diagnosis of occlusion or stenosis of the carotid artery. The rates of cerebral angiography among patients with carotid artery occlusion or stenosis (ICD-9-CM code 433.1) were 39.3% among women compared with 39.8% among men (age-adjusted OR, 1.00; 95% CI, 0.87 to 1.14). In addition, the rates of surgery in this diagnostic category were similar for both sexes: 63.1% for women compared with 65.5% for men (age-adjusted OR, 0.93; 95% CI, 0.81 to 1.07). Women discharged with a diagnosis of transient cerebral ischemia were less likely than men to receive angiography and surgery (Table 3), although rates of the procedures were too small to provide reliable comparisons. Additional clinical variables to further "adjust" procedure rates, such as severity of cerebrovascular or comorbid disease, are lacking in the current database.

View this table: [in this window] [in a new window]   Table 3. Rates and Female-to-Male Odds Ratios for Cerebral Angiography and Carotid Endarterectomy by Diagnosis

	Discussion

Top Abstract Introduction Subjects and Methods Results Discussion References

 
Despite the apparent (overall) underuse of cerebral angiography and carotid endarterectomy in women, rates of these procedures were similar among men and women with ischemic stroke attributed to carotid disease in our population. The simplest explanation for the observed results is that a higher proportion of men compared with women have carotid occlusion and account for most of the sex-related differences. Previous reports have also documented sex differences in the distribution of cerebrovascular disease. In a review by Caplan et al,¹¹ men had a preponderance of extracranial atherosclerotic disease in both endarterectomy trials and autopsy studies. Among studies that used angiography, Whisnant et al¹² found male sex to be an independent predictor for carotid artery atherosclerosis, and Sinderman et al¹³ described higher rates of internal carotid artery occlusion in men, whereas women had higher rates of middle cerebral artery occlusion. When ultrasound techniques are used to evaluate carotid atherosclerotic disease, men have more plaques than women.^{14 15} Thus, evidence from angiographic, autopsy, and ultrasound studies indicates a male predisposition for carotid atherosclerotic disease, creating an overall excess of surgically treatable cases among men.

Several other explanations are difficult to exclude as potential factors contributing to the overall sex difference in the use of carotid endarterectomy and cerebral angiography (and also apply to reports of sex differences in the management of coronary artery disease). For example, physicians may not refer women for evaluation or therapy as frequently as men. This pattern could be due to a perception that stroke itself is more severe (or has more severe consequences) in men than in women, or to a belief that women have higher operative morbidity or mortality compared with men. Differences in patients' preferences could also explain a sex difference in angiography and endarterectomy. Women may prefer medical therapy compared with surgery and its attendant risks. If such practice patterns or patient preferences were present, however, evidence of their impact would be expected for all categories of type of stroke.

Our study was limited by its reliance on cross-sectional rather than longitudinal data, and unique patient-identifying information was not available. Some patients are therefore included in the study more than once, and procedure rates are based on hospital discharge events rather than individual patients. In addition, changes in practice patterns over time may have occurred. Another limitation involves the classification of stroke types based on the ICD-9-CM system, a taxonomy with limited clinical relevance and accuracy. Although the distribution of types of cerebrovascular disease is consistent with other published data,^{16 17 18 19} diagnoses were coded by nonphysicians reviewing each discharged patient's chart for other purposes. Our results would be threatened, however, only if differential rather than random coding errors occurred for men compared with women.

The high rate of carotid endarterectomy among people with the ICD-9 code of 433.1 suggests that coding for this diagnosis may be influenced by the subsequent management. In addition, only two thirds of these patients had a prior angiogram coded in this data set. This is not the standard of practice in Connecticut and most likely represents angiography on a prior admission or miscoding.

In follow-up of this preliminary report of database information, medical record–based retrospective data or prospective data are needed to obtain more extensive clinical details. Ideally, both inpatient and outpatient data should be included to avoid a potential bias in the use of a hospital evaluation between men and women with transient ischemic attack or stroke. The type and location of vascular lesions should be determined to establish whether sex differences are attributable to provider or patient behavior rather than innate patient characteristics. Other clinical factors influencing the use of endarterectomy should also be measured, including the extent of carotid stenosis as determined by angiography, the presence of symptoms after an initial stroke, the number of prior strokes, functional status, and the severity of comorbid illness. Without additional information, the finding of differential management of patients with known cerebrovascular disease remains unexplained but may be due to biological factors.

	Acknowledgments

 
This study was supported by gifts to the Yale Stroke Program.

	Footnotes

 
Reprint requests to Lawrence M. Brass, MD, Yale Stroke Program, Department of Neurology, LCI-700, Yale University School of Medicine, 333 Cedar St, New Haven, CT 06510.

Received December 8, 1994; revision received January 24, 1995; accepted January 24, 1995.

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