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Stroke. 2007;38:2123-2126
Published online before print May 24, 2007, doi: 10.1161/STROKEAHA.106.478495
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(Stroke. 2007;38:2123.)
© 2007 American Heart Association, Inc.


Original Contributions

Sex Disparity in the Access of Elderly Patients to Acute Stroke Care

Christian Foerch, MD; Bjoern Misselwitz, PhD; Marek Humpich, MD; Helmuth Steinmetz, MD; Tobias Neumann-Haefelin, MD; Matthias Sitzer, MD for the Arbeitsgruppe Schlaganfall Hessen

From the Department of Neurology (C.F., M.H., H.S., T.N.-H., M.S.), Johann Wolfgang Goethe University, Frankfurt am Main, and Geschaeftsstelle Qualitaetssicherung Hessen (B.M.), Eschborn, Germany.

Correspondence to Christian Foerch, MD, Department of Neurology, Johann Wolfgang Goethe University, Schleusenweg 2-16, 60528 Frankfurt am Main, Germany. E-mail foerch{at}em.uni-frankfurt.de


*    Abstract
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Background and Purpose— Sex differences in the management of acute coronary symptoms are well documented. We sought to determine whether sex disparities exist in acute stroke management, particularly with regard to early hospital admission and thrombolytic therapy.

Methods— We analyzed a prospective, countywide, hospital-based stroke registry. Between 1999 and 2005, all cases with a final diagnosis of cerebral infarction (ICD-10 I63) or intracerebral hemorrhage (ICD-10 I61) were selected. Datasets with missing values for sex and time to admission, as well as datasets of patients transferred between hospitals in the acute phase, were excluded. Main outcome measures were the probability of being admitted within the first 3 hours of stroke onset and being treated with thrombolytic agents for both women and men, after adjustment for age, prestroke disability, severity of clinical symptoms, vascular risk factors, and final diagnosis.

Results— Fifty-three thousand four hundred fourteen patients were included (49.3% female; mean±SD age, 72.1±12.5 years). Women had a 10% lower chance of being admitted within the first 3 hours than men (odds ratio=0.902, 95% CI=0.860 to 0.945, P<0.001). This chance further decreased in elderly women. Similarly, the chance of a female stroke patient being treated with thrombolysis was 13% lower than that of a male patient (odds ratio=0.867, 95% CI=0.782 to 0.960, P=0.006). For patients admitted within the 3-hour time window, the chance of being treated with thrombolysis was similar for women and men (odds ratio=0.915, 95% CI=0.809 to 1.035, P=0.156).

Conclusions— We identified sex disparities in acute stroke management in terms of early hospital admission and thrombolytic treatment. This is best explained by the sociodemographic fact that "surviving spouses" are more likely to be women than men. Attempts to overcome disadvantages in their access to acute stroke care should focus on increased social support.


Key Words: cerebral infarct • intracerebral hemorrhage • acute management • women


*    Introduction
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up arrowAbstract
*Introduction
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Despite the goal that women and men should have equal access to rapid emergency care,1 sex disparities are well documented in the management of myocardial ischemia, with women being diagnosed later and undergoing fewer coronary angiography and revascularization procedures than men.2–4 It is largely unknown whether similar differences exist in the management of acute stroke. Two publications reported that female stroke patients were less likely to undergo standard diagnostic tests than male patients.5,6 Likewise, women underwent carotid surgery and received antithrombotic medication less frequently than did men.5,7 A disproportionate sex ratio was also observed in the large, randomized recombinant tissue-type plasminogen activator stroke trials, in which only 40% to 42% of all patients were women.8–10 Similar findings were reported in several case series of acute stroke patients treated with thrombolysis.11–14 These findings deserve notice because despite a higher annual age-adjusted stroke risk in men, the total number of strokes is higher in women owing to their longer life expectancy.15 However, sex differences in stroke etiology and severity also influence acute treatment. For instance, large-artery atherosclerosis is more frequent in men, whereas cardioembolism is more common in women.15 This may explain why female stroke patients were, on average, more severely affected at the time of hospital admission than male patients.5,16 In addition, uncommon stroke symptoms were more frequently reported in women.17 Taking into account these potential biasing factors, this study attempted to identify and further analyze possible sex differences in acute stroke care, with respect to early hospital admission and thrombolytic therapy, in a prospective, countywide registry that included almost all consecutive stroke patients in the region.


*    Patients and Methods
up arrowTop
up arrowAbstract
up arrowIntroduction
*Patients and Methods
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Our analysis was based on a large, countywide stroke registry in Germany that was provided by the Arbeitsgruppe Schlaganfall Hessen (for details, see www.gqhnet.de).18 At present, >100 hospitals participate in enrolling patients with a final diagnosis of transient ischemic attack, cerebral infarction, or intracerebral hemorrhage into this standardized and computerized registry. All consecutive patients have to be registered, resulting in a proven >90% inclusion rate.

All parameters relevant to this analysis were documented prospectively. The severity of clinical symptoms at the time of hospital admission was assessed by the modified Rankin Scale (mRS). The level of consciousness (alert, somnolent, soporific, or coma), as well as deficits in motor function (no dysfunction; mono-, hemi-, or tetraparesis) and presence or absence of speech disturbances, was also recorded. Vascular risk factors included arterial hypertension and diabetes mellitus. Patients’ prestroke disabilities were determined at the time of hospital admission on the basis of all available information provided by the patient, relatives, or caregivers and were classified according to the mRS. The time from symptom onset to hospital admission was categorized as follows: 0 to 3 hours, 3 to 6 hours, 6 to 24 hours, >24 hours, or unknown. According to the application form, thrombolytic therapy was documented as either intravenous or intra-arterial.

For this analysis, we selected all cases in the entire database with hospital admission dates between January 1, 1999 and December 31, 2005 (n=91 656). Datasets with missing values for sex (n=61) and time to admission (n=3286), as well as datasets of patients transferred between hospitals in the acute phase of stroke (n=13 153), were excluded. Finally, we restricted our analysis to patients with a final diagnosis of cerebral infarction (ICD-10 I63, n=47 841) or intracerebral hemorrhage (ICD-10 I61, n=5573), omitting all remaining datasets (mainly patients with transient ischemic attack).

For the statistical analysis, we used a multivariate logistic-regression model to determine the influence of sex on early hospital admission and thrombolytic therapy. Adjustment was performed for the following variables: age (included continuously), prestroke disability (mRS 0, 1 versus >1), mRS at hospital admission (0 to 3 versus 4, 5), level of consciousness (alert versus somnolent, soporific, or coma), presence of speech disturbances, motor function (no deficit versus mono-, hemi-, or tetraparesis), type of stroke (ischemic versus hemorrhagic), arterial hypertension, or diabetes mellitus. As is to be expected in a prospective database, there were some values missing for each variable (see the Table).


View this table:
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Baseline Characteristics, Clinical Variables, and Vascular Risk Factors of the Study Population by Sex

The registry is a countywide, quality-assurance measure based on state law, for which all inpatients must be documented anonymously. Informed consent was not required before enrollment in the registry. The ethics review committee of the medical faculty of our university reviewed and approved the present analysis.


*    Results
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*Results
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Of the 53 414 patients included in the final analysis, 26 319 patients were female (49.3%). The mean±SD age was 72.1±12.5 years. The baseline variables of the study population by sex are given in the Table. After multivariate adjustment, women were found to have a 10% smaller chance of being admitted within the first 3 hours of symptom onset than men (odds ratio [OR]=0.902, 95% CI=0.860 to 0.945, P<0.001). Compared with men, the probability of women being admitted to hospital within 3 hours of stroke onset decreased further with advancing age (see the Figure).


Figure 1478495
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Forrest plot summarizing the adjusted ORs for early hospital admission (<3 hours after symptom onset) and thrombolytic therapy. An OR >1 indicates a higher chance of female patients reaching the given end point. *Adjustment was performed for age, prestroke disability, severity of clinical symptoms at the time of admission (mRS, level of consciousness, motor function, speech disturbance), vascular risk factors, and type of stroke.

Within the dataset, 2021 ischemic stroke patients were documented as having been treated with thrombolytic agents, and 876 (43.3%) of these were female. One thousand six hundred fifteen patients received intravenous thrombolysis, and 406 received intra-arterial thrombolysis. After adjustment in the multivariate model, the chance of a female stroke patient being treated with either intravenous or intra-arterial thrombolysis was 13% lower than that of a male patient (OR=0.867, 95% CI=0.782 to 0.960, P=0.006). Whereas the sex ratio was balanced for younger stroke patients (in the first and second quartiles of age; OR=1.035, 95% CI=0.911 to 1.175, P=0.600), elderly female patients (in the third and fourth age quartiles) had a 25% smaller chance of receiving thrombolytic treatment (OR=0.753, 95% CI=0.634 to 0.895, P=0.001; see the Figure). For only those patients with ischemic stroke who reached the hospital within the 3-hour time window and who met the approval criteria for recombinant tissue-type plasminogen activator (ie, age between 18 and 80 years, moderate to severe neurological deficit [mRS 3 to 5], and not comatose; n=5088), the multivariate analysis showed that the chance of being treated with intravenous thrombolysis was not significantly different between women and men (OR=1.032, 95% CI=0.887 to 1.201, P=0.681). However, within the same model, a very strong sex disparity to the disadvantage of females was apparent for intra-arterial thrombolysis (OR=0.586, 95% CI=0.362 to 0.951, P=0.030).


*    Discussion
up arrowTop
up arrowAbstract
up arrowIntroduction
up arrowPatients and Methods
up arrowResults
*Discussion
down arrowReferences
 
The main result of our study is that sex disparities indeed exist in acute stroke care, with women having a smaller chance of being admitted to a hospital within the critical first 3 hours after symptom onset and receiving thrombolytic therapy. This result is not entirely explained by age distribution, prestroke disability, severity of clinical symptoms, type of stroke (ischemic versus hemorrhagic), or vascular risk factors. Because we compared proportions within each sex, the total number of women or men cannot have influenced these results.

Our analysis shows that the observed sex disparity appeared only among elderly stroke patients (ie, those in the third and fourth age quartiles, ie, >74 years). No imbalance was found in younger patients (see the Figure). The most plausible explanation for this finding is that elderly women are more likely to live alone. In a study of possible sex differences in stroke care and outcomes, Kapral et al19 reported that 32% of women were living alone compared with only 15% of men. Furthermore, 31% of women were widowed compared with only 7% of men. Consequently, elderly women are more likely to require help from neighbors, caregivers, or their next of kin before they can access emergency stroke care.

Sex disparities in the application of thrombolytic therapy closely mirrored those in early hospital admission. Fewer women received this treatment in our sample. In this context, it is important to note that the attributable effect of thrombolytic treatment was shown to be entirely confined to women, which accentuates the need to aggressively and appropriately treat women for acute stroke.20 It is likely that the delayed admission of female stroke patients constitutes the main cause of the sex disparities in patients treated with thrombolysis. Thus, restricting our analysis to patients admitted within 3 hours after symptom onset revealed no significant sex difference regarding intravenous application. In other words, if stroke patients reach the hospital within the critical time window, emergency physicians do not appear to be biased toward a preferential treatment of one sex. However, we found that more aggressive forms of thrombolysis (ie, intra-arterial application) showed a particularly high sex disparity to the disadvantage of women, even within the 3-hour time window. This finding is apparently similar to studies in the cardiology field that have reported fewer coronary angiographies and interventional procedures in women.

Despite the substantial magnitude of the present study, our analysis is potentially hampered by some limitations: We have no comprehensive information on the comorbidity of the stroke population, which may influence admission latencies and decision making toward thrombolysis in the emergency situation. Furthermore, the proportion of missing values varies between items (see the Table), which may influence multivariate analyses.

In summary, all sex disparities observed in this study are best explained by the sociodemographic fact that "surviving spouses" are more likely to be women than men. Attempts to overcome disadvantages in their access to acute stroke care would have to focus on increased social support.


*    Acknowledgments
 
Disclosures

None.

Received November 21, 2006; revision received January 30, 2007; accepted February 1, 2007.


*    References
up arrowTop
up arrowAbstract
up arrowIntroduction
up arrowPatients and Methods
up arrowResults
up arrowDiscussion
*References
 
1. American Medical Association commission to end health care disparities. Available at http://www.ama-assn.org/ama/pub/category/12809.html. Accessed on May 8, 2007.

2. Gan SC, Beaver SK, Houck PM, MacLehose RF, Lawson HW, Chan L. Treatment of acute myocardial infarction and 30-day mortality among women and men. N Engl J Med. 2000; 343: 8–15.[Abstract/Free Full Text]

3. Anand SS, Xie CC, Mehta S, Franzosi MG, Joyner C, Chrolavicius S, Fox KA, Yusuf S. Differences in the management and prognosis of women and men who suffer from acute coronary syndromes. J Am Coll Cardiol. 2005; 46: 1845–1851.[Abstract/Free Full Text]

4. Redberg RF. Gender, race, and cardiac care: why the differences? J Am Coll Cardiol. 2005; 46: 1852–1854.[Free Full Text]

5. Di Carlo A, Lamassa M, Baldereschi M, Pracucci G, Basile AM, Wolfe CD, Giroud M, Rudd A, Ghetti A, Inzitari D. Sex differences in the clinical presentation, resource use, and 3-month outcome of acute stroke in Europe: data from a multicenter multinational hospital-based registry. Stroke. 2003; 34: 1114–1119.[Abstract/Free Full Text]

6. Smith MA, Lisabeth LD, Brown DL, Morgenstern LB. Gender comparisons of diagnostic evaluation for ischemic stroke patients. Neurology. 2005; 65: 855–858.[Abstract/Free Full Text]

7. Gage BF, Boechler M, Doggette AL, Fortune G, Flaker GC, Rich MW, Radford MJ. Adverse outcomes and predictors of underuse of antithrombotic therapy in Medicare beneficiaries with chronic atrial fibrillation. Stroke. 2000; 31: 822–827.[Abstract/Free Full Text]

8. Tissue plasminogen activator for acute ischemic stroke. The National Institute of Neurological Disorders and Stroke rt-Pa Stroke Study Group. N Engl J Med. 1995; 333: 1581–1587.[Abstract/Free Full Text]

9. Hacke W, Kaste M, Fieschi C, Toni D, Lesaffre E, von Kummer R, Boysen G, Bluhmki E, Hoxter G, Mahagne MH, et al. Intravenous thrombolysis with recombinant tissue plasminogen activator for acute hemispheric stroke. The European Cooperative Acute Stroke Study (ECASS). JAMA. 1995; 274: 1017–1025.[Abstract/Free Full Text]

10. Hacke W, Kaste M, Fieschi C, von Kummer R, Davalos A, Meier D, Larrue V, Bluhmki E, Davis S, Donnan G, Schneider D, Diez-Tejedor E, Trouillas P. Randomised double-blind placebo-controlled trial of thrombolytic therapy with intravenous alteplase in acute ischaemic stroke (ECASS ii). Second European-Australasian Acute Stroke Study Investigators. Lancet. 1998; 352: 1245–1251.[CrossRef][Medline] [Order article via Infotrieve]

11. Grond M, Stenzel C, Schmulling S, Rudolf J, Neveling M, Lechleuthner A, Schneweis S, Heiss WD. Early intravenous thrombolysis for acute ischemic stroke in a community-based approach. Stroke. 1998; 29: 1544–1549.[Abstract/Free Full Text]

12. Tanne D, Bates VE, Verro P, Kasner SE, Binder JR, Patel SC, Mansbach HH, Daley S, Schultz LR, Karanjia PN, Scott P, Dayno JM, Vereczkey-Porter K, Benesch C, Book D, Coplin WM, Dulli D, Levine SR. Initial clinical experience with IV tissue plasminogen activator for acute ischemic stroke: A multicenter survey. The t-PA Stroke Survey Group. Neurology. 1999; 53: 424–427.[Abstract/Free Full Text]

13. Albers GW, Bates VE, Clark WM, Bell R, Verro P, Hamilton SA. Intravenous tissue-type plasminogen activator for treatment of acute stroke: The Standard Treatment with Alteplase to Reverse Stroke (STARS) Study. JAMA. 2000; 283: 1145–1150.[Abstract/Free Full Text]

14. Koennecke HC, Nohr R, Leistner S, Marx P. Intravenous TPA for ischemic stroke team performance over time, safety, and efficacy in a single-center, 2-year experience. Stroke. 2001; 32: 1074–1078.[Abstract/Free Full Text]

15. Kolominsky-Rabas PL, Weber M, Gefeller O, Neundoerfer B, Heuschmann PU. Epidemiology of ischemic stroke subtypes according to TOAST criteria: incidence, recurrence, and long-term survival in ischemic stroke subtypes: a population-based study. Stroke. 2001; 32: 2735–2740.[Abstract/Free Full Text]

16. Roquer J, Campello AR, Gomis M. Sex differences in first-ever acute stroke. Stroke. 2003; 34: 1581–1585.[Abstract/Free Full Text]

17. Labiche LA, Chan W, Saldin KR, Morgenstern LB. Sex and acute stroke presentation. Ann Emerg Med. 2002; 40: 453–460.[CrossRef][Medline] [Order article via Infotrieve]

18. Foerch C, Misselwitz B, Sitzer M, Berger K, Steinmetz H, Neumann-Haefelin T. Difference in recognition of right and left hemispheric stroke. Lancet. 2005; 366: 392–393.[CrossRef][Medline] [Order article via Infotrieve]

19. Kapral MK, Fang J, Hill MD, Silver F, Richards J, Jaigobin C, Cheung AM. Sex differences in stroke care and outcomes: results from the registry of the Canadian Stroke Network. Stroke. 2005; 36: 809–814.[Abstract/Free Full Text]

20. Kent DM, Price LL, Ringleb P, Hill MD, Selker HP. Sex-based differences in response to recombinant tissue plasminogen activator in acute ischemic stroke: a pooled analysis of randomized clinical trials. Stroke. 2005; 36: 62–65.[Abstract/Free Full Text]




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