Although there is no clear evidence of a gender dif- ference in initial stroke severity, there is a growing literature suggesting that women tend to have less favorable outcomes than men after stroke. Examples of unfavorable outcomes include disability (modi- fi ed Rankin Score [mRS] >3) and limitations of activities of daily living (ADLs) (Barthel Index [BI]
<95). The Canadian Stroke Registry reported that a higher percentage of women (30%) had moderate to severe disability (mRS ≥4) compared with men (26%) [14]. A statewide registry in Michigan reported similar results (33% of women vs. 27% of men had mRS ≥4) [63]. In Europe, a multicenter registry reported that women were more likely to be disabled at 3 months (BI <70), even after adjusting for age [6]. The Swedish Riks-Stroke Registry showed that 54% of women were independent in primary ADLs at 3 months post-stroke versus 67% of men [64]. Similarly, in 108 subjects with stroke in the Framingham Study, 34% of women were disabled at 6 months (BI <60) compared with 16% of men [65].
Age and sex are related in complex ways in outcome studies, and cross-sectional studies may not provide the full picture. For example, a longitu-
dinal study of predictors of recovery and a post hoc analysis of the Management of Atherothrombosis with Clopidogrel in High-risk Patients trial showed that women age <65 years (vs. women aged ≥75 years) was independently associated with good recovery, defi ned as mRS <3 [66]. Other factors that were associated with recovery included less disability early post-stroke, no prior history of stroke, the presence of peripheral artery disease, and diabetes [66]. Therefore, this analysis confi rmed the impor- tance of age as a bimodal factor related to outcome, especially related to recovery in women.
One possible reason for women’s poor outcomes could be related to disparities in the access to reha- bilitation services. There do not, however, appear to be any differences in rehabilitation referrals by gender [67,68]. Despite equal access to rehabilita- tion, women have poorer physical functioning than men. In the Kansas Stroke Registry, women were older and had worse pre-stroke physical function than men. In the functional measurements of inter- est, women were less likely to achieve a score of >95 on the BI than men (hazard ratio [HR] 0.68; 95%
CI 0.52–0.90), less likely to perform eight of nine instrumental ADLs without assistance (HR 0.46;
0.30–0.68), and less likely to score >90 on the Short Form 36 (SF-36) Health Survey physical functioning scale (HR 0.54; 0.28–1.01). These poor functional status scores were still present even after adjusting for age, pre-stroke physical function, and depression status at baseline [69]. Poorer pre-stroke disability in women has also been observed in at least two studies [6,64]. One study showed that 32% of women had a pre-stroke mRS of 2–5 versus 23% of men [6]. This is a very important but poorly under- stood factor in the gender differences in outcome.
One possible explanation for the greater pre- stroke disability in women is that this represents the presence of one or more comorbidities. In a study of women admitted with acute stroke, disability (measured with mRS) at 90 days or more was associ- ated with atrial fi brillation, diabetes, history of coro- nary heart disease (CHD), and a higher score on the Charlson Index (a measure of comorbidities that impact 1-year survival), shown in Figure 9.6. In the multivariable analysis adjusted for initial stroke severity, diabetes and CHD were each independently associated with worse disability at 90 days or more after stroke [70]. Although this is one of
the few detailed outcomes studies of women after stroke, there were no men included; so whether these comorbidities are unique to women is unknown.
These data address two major research gaps in outcome studies. First, stroke outcome studies need to take into account comorbidities in their assess- ments of outcomes. In addition, these studies need to include men and women concomitantly, and be inclusive of the age ranges likely to infl uence out- comes in order to determine gender-specifi c pat- terns in these outcomes.
Quality of life (QOL)
QOL has been quantifi ed for stroke with the Stroke Impact Scale (SIS) [71] and the Stroke-Specifi c QOL (SS-QOL) Scale [72], and these scales have been used in various cohorts of stroke subjects. QOL has also been the focus of gender comparison studies. In the Canadian Stroke Registry, women were signifi - cantly more likely to score lower than men on the SIS-16, which represents the physical function domain of the SIS [14]. In addition, the Michigan statewide registry found that women scored lower on the physical domain scores of the SS-QOL than men [63]. More research is needed to better under- stand the gender differences related to QOL and how to improve QOL for stroke subjects in general, and women in particular.
Depression
Women are not only more prone to have depression than men throughout the life, but women are also more likely to experience depressive symptoms fol- lowing stroke. This was shown in 301 consecutive stroke patients admitted to the University of Mary- land Hospital who were evaluated for depression using the Hamilton Rating Scale for Depression and the modifi ed Present State Examination (PSE), in addition to other measures of cognition and ADLs [73]. Women were twice as likely to have major depressive disorder as men (23.6% vs. 12.3% in men; P = 0.01). Depression was also associated with left hemisphere lesion location, but only among women. In addition, the factors associated with major depressive disorder were different for men and women. For example, for women, younger age, personal history of psychiatric disorder, and cogni- tive impairment were associated with major depres- sive disorder, whereas in men, it was younger age and impairment in ADLs and social functioning [73]. Another study from Sweden, the Risk-Stroke Registry, found that 12.4% of men and 16.4% of women reported that they always or often felt depressed [74]. In the multiple regression analysis, women were 30% more likely to have self-reported depression (OR 1.30; 95% CI 1.17–1.44). Other factors included age <65, history of recurrent stroke, and living at home alone, or in an institution. The
4 3 2 1 0
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60%
70%
80%
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DM (+) DM (–) CHD (+)CHD (–) Afib (+) Afib (–)
Charlson >2Charlson0, 1 P = 0.01 P = 0.001 P = 0.03 P = 0.006
mRS
Fig. 9.6 Association between disability measured with the modifi ed Rankin Score (0 = no disability and 4 = moderate to severe disability) and various comorbidities [70]. The Charlson Index is a score based on the presence of one or more comorbidities that impact 1-year mortality. From Bushnell C, et al. Stroke. 2008;39:2138–2140.
Afi b, atrial fi brillation; CHD, coronary heart disease; DM, diabetes mellitus; mRS, modifi ed Rankin Score.
study also assessed reported use of antidepressant drugs, and this was again more common in women than men [74]. The Sunnybrook Stroke Study evalu- ated depression using the objective, observer-rated scale (Montgomery Asberg Depression Rating Scale) and a subjective scale (Zung Self-Rating Depression Scale) in 436 patients with stroke [75]. The preva- lence of self-reported depression at 3 months post- stroke was 21%, whereas the objective measure was 27%, the majority of which was due to mild depres- sion. These rates of depression were similar at 1 year post-stroke. Consistent with other cited studies, female sex was associated with depression measured with both scales. The other important fi nding was that depression was associated with worse functional status, quantifi ed with the Functional Independence Measure, and disability, measured with the Oxford Handicap Scale (same as the mRS) [75]. In summary, these studies have demonstrated that depression is more common in women and is associated with poorer functional status after stroke.
Another important reason to recognize depres- sive symptoms following stroke is because its presence is associated with increased mortality. A randomized trial of treatment strategies for depres- sion post-stroke screened for the presence of self- reported mood symptoms within the PSE and the General Health Questionnaire (GHQ)-28 (a measure of general psychological distress) at 1 month and then followed the cohort for 24 months. The inves- tigators found that subjects in the highest quartile of the GHQ-28 (signifying increased psychological dis- tress) were at a 3-fold risk of death by 12 months (OR 3.1; 95% CI 1.1–8.8; P = 0.037) and 2-fold risk of death by 24 months (OR 2.2; 1.0–4.8; P = 0.048).
Interestingly, an International Classifi cation of Diseases-10 diagnosis of major depression was not associated with mortality.
Depression and psychological stress have also been investigated as risk factors for incident stroke.
In a large study from the United Kingdom, there was no signifi cant relationship between major depressive disorder and incident stroke, but there was a signifi - cant and positive association with psychological stress [76]. Therefore, screening for psychological distress may become an important aspect of risk factor modifi cation.
A major knowledge gap in stroke outcomes is how depression and psychological distress affect
stroke risk. Is this because it leads to reduced physical activity, or weight gain and thus a worsen- ing cardiovascular risk profi le? This is especially important for women because they are at risk of having depression prior to having a stroke, and for having more depressive symptoms following the stroke.
Physical activity
The patient described in the case study had a cere- bellar stroke, which limited her mobility for several months. Patients who have disability from ischemic stroke should be considered for a supervised exercise regimen. Not only have exercise programs been shown to improve outcomes in physical function- ing, but they have also been associated with improved measures of QOL (higher ADL scores, improved social function, and physical role function) [77] and fewer depressive symptoms [78]. Specifi c recom- mendations for physical activity for stroke survivors are summarized in an AHA guidelines statement [79]. These guidelines provide recommendations for aerobic, strength training, fl exibility, and neuro- muscular aspects of potential exercise programs, depending on the goals and needs of the stroke survivor [79].
With regards to sex differences, a recent random- ized controlled trial of supervised versus unsuper- vised exercise program reported that both men and women improved in the 6-minute walking speed and the SF-36 Physical Component summary score, regardless of treatment assignment. However, women made greater gains in the supervised pro- grams, whereas men had greater gains in the unsu- pervised programs (interaction term of gender by treatment P = 0.01) [80]. The reasons for this outcome are unclear but may relate to social interactions.
Measuring exercise capacity is an opportunity to optimize primary and secondary cardiovascular pre- vention. This is important because poor exercise capacity has been associated with cardiac death in women [81]. This was shown in a study in which women with and without coronary disease symp- toms underwent symptom-limited treadmill tests and were followed for cardiac outcomes. The percent of predicted exercise capacity was measured with exercise nomograms developed for women who were active and those who were sedentary (Figure
9.7) [81]. Regardless of the presence of symptoms, women with an exercise capacity less than 85%
of the age-appropriate predicted value had a 2-fold increased risk of death from any cause and a 2.4-fold risk of cardiac death [81]. Although not specifi cally developed for stroke, this type of exercise nomogram is useful for general cardiovas- cular prevention screening and would help identify women who would benefi t from exercise programs.
A major research gap related to physical activity for women is how to motivate women who are at risk for stroke to become active. In addition, given the evidence that women are more likely to have worse functional status and QOL than men post-stroke, various exercise programs could be utilized to improve function and QOL for women after stroke
and concomitantly reduce the risk of recurrent stroke.
In summary, women have a greater lifetime risk of stroke than men, and therefore we have many opportunities and challenges to provide high-quality preventive care. In addition, women may present with unorthodox stroke symptoms, which requires astute history taking to recognize a stroke and direct treatment. During the acute stroke hospitalization, we have an opportunity to improve outcomes by recognizing and treating depression, providing appropriate rehabilitation and exercise programs, and initiating secondary prevention strategies.
References available online at www.wiley.com/go/
strokeguidelines.
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Percentage of predicted exercise capacity for age
Fig. 9.7 Exercise nomogram for determining exercise capacity in active and sedentary women [81]. From Gulati M, et al. N Engl J Med.
2005;353:246–475.
MET, metabolic equivalent.
Fernando D. Testai and Philip B. Gorelick
10
M A J O R P O I N T S
• The incidence and prevalence of stroke in African Americans is signifi cantly higher than in Caucasians;
this disparity is inversely related to age.
• Black patients are about twice as likely to die from stroke than are whites.
• Blacks may have more severe and disabling strokes than whites.
• The reasons for an excess burden of stroke in African Americans have not been clearly defi ned yet;
explanations may include a higher rate of cardiovascular risk factors such as hypertension, diabetes, obesity, smoking, and end stage renal disease, socioeconomic factors, and the infl uence of geography.
• Stroke mechanism may differ among race-ethnic groups; white patients may have a higher proportion of cardioembolic stroke and symptomatic large artery extracranial occlusive disease, and black patients more small-vessel (lacunar) strokes and symptomatic intracranial occlusive disease.
• Age, lower educational level, history of myocardial infarction, recent smoking, and left cortical infarction may be predictors of dementia with stroke in black patients.
• Cardiovascular risk factors may be risk factors for vascular cognitive impairment and also, possibly, for Alzheimer’s disease.
EXAMPLE CASE
A 68-year-old African-American woman with a history of hypertension and hypercholesterolemia awakens in the morning with new onset of slurred speech and right-sided face, arm, and leg weakness.
She had quit smoking cigarettes about 2 months previously. The patient was taken to a local hospital for evaluation. On arrival, her temperature was 36°C, her pulse was 75 bpm, and her blood pressure was 175/105 mm Hg. Her height was 5 feet and her weight was 325 lbs. In the general physical examination, her neck was supple and no carotid bruits were appreciated. The pulmonary exam was normal, and her heart rate was regular with no murmurs or gallops. The peripheral pulses were unremarkable. The fundoscopic exam disclosed
grade II hypertensive changes. Other pertinent neurological fi ndings included slurred speech, fl attening of the right nasolabial fold, and right-sided hemiparesis. Deep tendon refl exes were brisk in the right arm and the right patella; the ankle jerks could not be elicited and the plantar responses were fl exor bilaterally. A metabolic profi le, complete blood count, coagulation studies, and cardiac enzymes were obtained and were remarkable only for a glucose level of 175 mg/dL. Other laboratory tests included erythrosedimentation rate (ESR) (42 mm/h), triglycerides (350 mg/dL), low-density lipoprotein cholesterol (124 mg/dL), and glycosylated hemoglobin A1c (9.2%). The urinalysis showed proteinuria. The electrocardiogram revealed a
A Primer on Stroke Prevention Treatment: An Overview Based on AHA/ASA Guidelines, 1st Edition. Edited by Larry B. Goldstein © 2009 American Heart Association. ISBN: 978-1-405-18651-3
normal sinus rhythm and left ventricular
hypertrophy (LVH) by voltage criteria. The brain CT scan showed old lacunar strokes but no evidence of acute ischemic changes or bleeds. The brain magnetic resonance imaging (MRI) revealed the presence of a small, acute left-sided capsular stroke, chronic ischemic changes, and evidence of prior brain hemorrhage. Whereas echocardiography showed LVH, magnetic resonance angiography (MRA) showed high-grade occlusive disease of the horizontal portion of the middle cerebral artery.
Case vignette discussion
The patient described illustrates key features that may occur in African-Americans with stroke. These include a high prevalence of hypertension and other cardiovascular risk factors, which may include dyslipidemia, obesity, diabetes mellitus, and cigarette smoking; nonoptimally controlled risk factors;
history of cerebral hemorrhage; and lacunar stroke subtype and intracranial occlusive disease. These and other topics germane to stroke in blacks are discussed.
Introduction
Blacks and other racial and ethnic minorities may be disproportionately affected by stroke. Disparities in their level of general health and access to health care in the United States continue to exist [1–6]. African- Americans have approximately two times the stroke risk as compared with their white counterparts, as well as lower life expectancy, poorer health care, and discrimination in the medical care system [3]. Of the three leading causes of mortality, the black-to-white ratio of death is greatest for stroke [1]. The US Insti- tute of Medicine concluded that racial and ethnic minorities receive lower quality of health care than others even after access to healthcare-related factors are taken into account [5]. Furthermore, medical care for minorities may be poorly matched to their needs based on language barriers, geography, cul- tural issues, stereotyping, biases inherent to the healthcare system, and uncertainty on the part of healthcare providers [5]. These gaps may be overcome by comprehensive, multilevel healthcare system strategies.
In this chapter, we discuss the prevention, diagnosis, and treatment of stroke in blacks.
Although blacks traditionally have been underrep- resented in clinical trials, more recent focused trials have helped us to better understand stroke prevention and treatment in this important group.
A theme of barriers to participation in clinical trials and the healthcare system has emerged for blacks, and we recommend means to overcome these challenges.