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American Journal of Critical Care. 2006;15: 556-566
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CE Article

State of the Heart: Building Science to Improve Women’s Cardiovascular Health

By Anne G. Rosenfeld, RN, PhD, CNS. From Oregon Health & Science University, Portland, Ore.

Corresponding author: Anne G. Rosenfeld, RN, PhD, CNS, Associate Professor, School of Nursing, Oregon Health & Science University, 3455 SW Veterans Hospital Rd, Portland, OR 97239 (e-mail: rosenfea{at}ohsu.edu).


   Abstract
Top
 Abstract
Context
 Gender Bias and Disparities
 Prevention
 Symptoms of CHD in...
 Summary: What Questions Remain?
 Conclusions
 References
 
Cardiovascular disease is the No. 1 killer of women in the United States, and marked disparities in cardiovascular health exist between women and men and among groups of women. Coronary heart disease is underdiagnosed, undertreated, and underresearched in women. Women with suspected heart disease are less likely than men to receive indicated diagnostic tests and procedures; sex-based biases in treatment of myocardial infarction persist; and women continue to be underrepresented in cardiovascular research. An accumulating body of literature points to 3 major explanations: sex-based physiology, provider bias, and psychosocial influences. Women’s acute and prodromal signs and symptoms of myocardial infarction have been described, yet women have difficulty recognizing and acting on these indications. Primary and secondary prevention of heart disease in women is imperative; although the science is lacking in several areas, existing evidence on diet, hormone therapy, aspirin, physical activity and obesity, and diabetes can serve as the basis for interventions. Potentially, large impacts could be made on women’s morbidity and mortality if current scientific knowledge were implemented. The state of the science of women and heart disease is reviewed, with a focus on those areas with the greatest potential to address the needs of women’s cardiovascular status. Key gaps in the science and remaining questions are presented as a research agenda for the coming decade.

Notice to CE enrollees:
A closed-book, multiple-choice examination following this article tests your understanding of the following objectives:
  1. Compare and contrast the prevention, diagnostic, and treatment needs of men and women with or at risk for heart disease.
  2. Describe the limitations associated with generalization and widespread application of cardiovascular research findings to date.
  3. Identify strategies for participation of nursing professionals in promoting primary and secondary prevention of cardiovascular disease in women.

To read this article and take the CE test online, visit www.ajcconline.org and click "CE Articles in This Issue."

Cardiovascular disease is the No. 1 killer of women in the United States and worldwide, and marked disparities in cardiovascular health exist between women and men and among groups of women. Indeed, Mikhail1 recently concluded that coronary heart disease (CHD), the most prevalent form of heart disease, is "underdiagnosed, under-treated, and under researched" in women. In this article, I review the progress of the past decade and a half in building the science that can lead to improving women’s cardiovascular health.


   Context
Top
 Abstract
 Context
Gender Bias and Disparities
 Prevention
 Symptoms of CHD in...
 Summary: What Questions Remain?
 Conclusions
 References
 
During the past 2 decades, cardiovascular disease has become a women’s health issue, as indicated by an increase in funded research and public knowledge. However, the research community and the public have yet to fully translate this growing awareness into action.

Although the National Institutes of Health has promoted the inclusion of women in clinical research,2,3 women continue to be underrepresented in studies that include both men and women. Fewer than half of the trials assessed in a recent evidence review4 of diagnosis and treatment of heart disease in women contained data on women. A review5 of decades of randomized controlled trials of treatment of acute coronary syndrome revealed that although the percentage of women included in trials increased from 20% (1966–1990) to 25% (1991–2000), women are still underrepresented by half, given the prevalence of acute coronary syndrome in the female population. This basic difference between the general population and study populations raises serious questions about the generalizability of research findings in cardiovascular trials.6 Fifty-four percent of subjects enrolled in cardiovascular clinical trials funded by the National Heart, Lung, and Blood Institute between 1965 and 1998 were women, which exceeds the prevalence of cardiovascular disease in women in the general population (49%). However, the enrollment rate was much lower (38%) if single-sex studies are excluded.7 Although single-sex studies are an appropriate way to study outcomes in women, such studies do not eliminate the need to enroll more women in all studies on cardiovascular disease.


Coronary heart disease is underdiagnosed, undertreated, and underresearched in women.

 

Women have become increasingly aware of heart disease. Results from surveys8,9 by the American Heart Association in 2004 and 2005 indicate that women have increased their knowledge of heart disease: in 2005, 57% of the women surveyed correctly identified heart disease as the leading cause of death; in 2004, the majority answered the question incorrectly. However, disparities in awareness among women are striking: although 62% of white women identified heart disease as the leading cause of death, only 42% of Hispanic women and 38% of African American women did so.9 In addition, a much smaller proportion of women perceive heart disease as the greatest threat to their own health, indicating that they have not yet personalized the information. In 2004, the American Heart Association launched the Go Red for Women campaign to raise public awareness of women and heart disease.


Women have higher mortality after a heart attack and poorer outcomes after coronary interventions.

 


   Gender Bias and Disparities
Top
 Abstract
 Context
 Gender Bias and Disparities
Prevention
 Symptoms of CHD in...
 Summary: What Questions Remain?
 Conclusions
 References
 
More than 241 000 women died of CHD in 2002, making it by far the leading cause of death for women in the United States.10 Although numerous studies during the past decades have documented disparities in cardiovascular disease between women and men and among groups of women, a few recent studies are reviewed here to emphasize the persistence of these disparities. Women experience higher mortality after myocardial infarction11 and poorer outcomes after interventions such as percutaneous angioplasty12 and coronary artery bypass graft surgery.13 Furthermore, recent data from the Heart and Estrogen/progestin Replacement Study14 indicated that African American women with heart disease experienced 50% higher risk for myocardial infarction and for death due to CHD than did white women. The differences in outcomes between men and women could occur because women have a heavier burden of risk factors and more comorbid conditions, have a smaller body size, or generally are older at the time of the event associated with CHD. However, evidence is increasing that women’s poor outcomes may also be linked to later diagnosis and suboptimal care.12

Underdiagnosed
Compared with men, women with suspected heart disease are less likely to receive indicated diagnostic tests and procedures. In a recent systematic review, Grady et al4 concluded that women are less likely than men to undergo diagnostic procedures. Anand et al15 analyzed sex-related data from the Clopidogrel in Unstable Angina to Prevent Recurrent Events multicenter, multinational trial. They found that high-risk women had fewer coronary angiography, angioplasty, and coronary artery bypass graft procedures than did men. Anand et al concluded that compared with men, women are referred for diagnostic tests less often, later in the course of the disease, and for reasons unrelated to the risk status. These differences were due to bias rather than health factors.16

Diagnosis of CHD in women can be challenging, perhaps because most of the evidence for the use of diagnostic tests comes from studies of middle-aged men.17 However, a recent consensus statement17 of the American Heart Association concluded that with existing cardiac imaging techniques, CHD can be accurately diagnosed in women. Further, the statement indicated that underdiagnosis of CHD in women contributes to their high mortality rates.

Undertreated
Major disparities exist between men and women in the screening and management of lipid abnormalities even though several trials have indicated the benefit of treatment with statins for women.18 A recent analysis19 of the coronary artery disease registry (N=87730 patients) of Kaiser Permanente of Northern California indicated that women were less likely than men to be treated and treated to therapeutic goal for hyperlipidemia.19 Treatment to lower lipid levels, currently underused in women, could have a great impact on primary and secondary prevention of cardiovascular disease in women.

Sex-based biases in treatment of myocardial infarction persist even in patients considered ideal candidates according to contemporary guidelines.11 Using information from the National Registry of Myocardial Infarction database of 598 911 patients with myocardial infarction between 1994 and 2002 and controlling for confounding variables, Vaccarino et al11 found that women received significantly less reperfusion therapy and angiography than men did. Differences between men and women in use of aspirin and ß-blockers were small and were not clinically significant. African American women had the lowest rate of interventions and the highest mortality. Notably, none of these disparities in treatment changed over time. In addition, percutaneous coronary interventions are performed less often and with greater delays in women than in men.12


Women are less likely than men to be treated and treated to goal for hyperlipidemia.

 

Although women with heart failure are as likely as men to receive smoking cessation counseling, they are less likely than men to have documentation of the 3 other core quality indicators of the Joint Council on Accreditation of Healthcare Organizations: discharge instructions, assessment of left ventricular ejection fraction, and a prescription at the time of discharge for an angiotensin-converting enzyme inhibitor.20

In a study of more than 3500 patients with stable angina, Daly et al21 concluded that women were less likely than men to undergo exercise electrocardiography, to have coronary angiography, to receive antiplatelet and statin therapies, and to have revascularization when they had confirmed coronary artery disease; women were twice as likely as men to die or have a nonfatal myocardial infarction within the first year. The authors21(p497) concluded that these disparities "raise serious concerns about systematic underinvestigation and under-treatment of stable angina in women."


African American women have the lowest intervention rate and the highest mortality following a heart attack.

 

Underresearched
As mentioned earlier, although the proportion of women enrolled in randomized controlled trials of treatment of cardiovascular disease has increased slightly, compared with the prevalence of CHD among the female population, women remain underrepresented in the trials. Women currently account for only 20% to 30% of participants in such trials.4

According to a recent meta-analysis22 of 63 randomized controlled trials of the effectiveness of secondary prevention programs for patients with coronary artery disease, only 1 trial23 was designed specifically for women and only 2 included a majority of female participants. The authors22 concluded that women were underrepresented in the analyzed trials. Although women, particularly African American women, are less likely than men to be referred to and complete secondary prevention programs such as cardiac rehabilitation,24 women do derive benefits from such programs.25 Women’s underrepresentation in clinical trials, however, limits the ability to identify factors that would increase referrals to and participation in such programs. Thus, underprevented can be added to Mikhail’s list1 of disparities between men and women with heart disease.

Grady et al4 conducted a systematic review of research on the diagnosis and treatment of CHD in women and found only 162 articles providing evidence. Although good to fair evidence exists for using ß-blockers, aspirin, and angiotensin-converting enzyme inhibitors to reduce the risk for CHD events in women with heart disease, only weak evidence exists for several important treatments such as coronary angioplasty and stenting.4 Alarmingly, little evidence is available on the key questions about women of different races and ethnicities. This knowledge gap exists even though, compared with white women, African American women are at higher risk, have higher CHD event rates, and are less likely to receive indicated therapies.14

Explanations
Disparities in cardiovascular outcomes between men and women and among groups of women are evident, yet the looming question is why? An accumulating body of literature points to 3 major explanations: sex-based physiology, provider bias, and psychosocial influences. These explanations encompass both gender and sex.26 However, no conclusive evidence currently exists for the contribution of each explanation.

Existing evidence for sex-based differences in physiology includes higher mortality rates after myocardial infarction in younger women, but not older women, compared with their male peers27 and potential sex-based differences in plaque.28 Plaque erosion is more common in younger women, and plaque rupture is more common in men and in older women.29 The Women’s Ischemic Syndrome Evaluation (WISE) study, with its prospective cohort of 936 women referred for diagnostic coronary angiography, is providing an array of new insights and hypotheses for sex-based differences in the pathophysiology of CHD. The WISE study objectives were to improve diagnostic testing for CHD in women, study pathophysiological mechanisms and prognosis, and evaluate the influences of menopausal status and reproductive hormone levels.30 The investigators29 concluded that sex-based differences in coronary endothelial and microvascular dysfunction may explain the differences in outcomes between men and women and pointed out the need for targeted therapeutic strategies based on sex.


There is systematic underinvestigation and undertreatment of stable angina in women.

 

In the WISE cohort, nearly 60% of those evaluated because of chest pain or abnormal results of noninvasive tests did not have angiographic evidence of flow-limiting coronary stenosis; however, these women had disabling signs and symptoms and long-term adverse events.31 Microvascular dysfunction (impaired smooth muscle relaxation and vascular repair processes) played a role in these women’s signs and symptoms of ischemia.31,32

In sum, women have a different form of vascular disease than men do,32 and what works for men may not work for women. Bairey Merz et al29(pS23) propose that sex-based differences in the "process of risk factor injury and atherosclerotic responses may explain the frequency and significance of chest pain symptoms in women." Risk factors that occur with the loss of estrogen in menopause (obesity, hypertension, dyslipidemia) in conjunction with years of relatively higher levels of inflammation lead to endothelial dysfunction, loss of arterial compliance, heterogeneity in myocardial flow, and, finally, ischemia, signs and symptoms, and functional limitations.29


Women have different vascular disease than men, and what works for men may not work for women.

 

Another important physiological difference between men and women is women’s older age and more frequent occurrence of comorbid illnesses at the time women seek medical care.4 Although women’s increased mortality in some studies such as the Global Use of Strategies to Open Occluded Coronary Arteries IIb trial did not differ from that of men after comorbid conditions were controlled for, Redberg33 argues clinical care cannot include controls for these factors.

Several investigators have cited sex and race bias on the part of physicians4; this phenomenon is also termed referral bias34 or physician preferences.28 In several studies with vignettes, investigators35,36 consistently concluded that in men and women with cardiac symptoms, physicians are less likely to diagnose heart disease in women and refer them for treatment. Arber et al35 offered the explanation of "gendered ageism" to explain their finding that compared with men and older women, middle-aged women were asked the fewest questions and prescribed the fewest cardiac medications.

Because of the persistence of the disparities discussed earlier, efforts should focus on reducing the variability in the decision to treat.37 Other authors4 have suggested that the reported disparities between men and women exist because tests and treatments are overused in men. This explanation, however, does not logically lead to the evidence that women have worse outcomes than men do.

Combined with clinician bias, sociocultural factors may have an adverse effect on women’s inclusion in treatment and research. Sociocultural factors include the cultural experiences of members of minority groups and the education available to women. Because of such factors, women may choose not to have certain diagnostic tests or therapies,28,34 yet Grady et al4 cite evidence of the equal willingness of women and men. Because patients rarely refuse to have diagnostic tests or therapies, most likely refusals by patients do not explain the observed differences between men and women.16,38 Variables in healthcare systems include access to care, cost of therapies,28 and structural inequities in the US health-care system.39

What are the perspectives of women on sex-based disparities? The qualitative study of Banks and Malone40 of the experience of African American women seeking care for cardiac signs and symptoms offers insight. Women in this study felt clinicians dismissed or trivialized the women’s signs and symptoms. Such experiences led to delay in accurate diagnosis and influenced women’s care seeking. Most likely a multidimensional approach to reducing the disparities between men and women is indicated, and future research is needed to determine specific points of intervention.


   Prevention
Top
 Abstract
 Context
 Gender Bias and Disparities
 Prevention
Symptoms of CHD in...
 Summary: What Questions Remain?
 Conclusions
 References
 
The epidemic proportions of both cardiovascular disease and cardiovascular risk factors in women highlight the need for primary and secondary prevention. Although evidence is lacking in several areas because of the underrepresentation of women in research on prevention,5,7 the accumulating evidence can serve as the basis for interventions. A synergy of traditional and novel risk factors accounts for a unique risk-factor profile in women. Postmenopausal risk factors (obesity, hypertension, dyslipidemia), levels of C-reactive protein, and metabolic syndrome all appear to be powerful risk factors in women.41


Women are less likely to be identified as high risk, despite risk score evidence.

 

Guidelines
The American Heart Association and the American College of Cardiology published evidence-based guidelines42 for preventing cardiovascular disease in women in 2004, the first such set of guidelines for prevention in women more than 20 years old with all risk profiles. These guidelines were based on available evidence of the effectiveness of risk-reducing interventions and incorporated risk stratification based on the Framingham risk profiles.

One year later, the guidelines were followed up with a study43 of physicians’ awareness of and adherence to the guidelines. The results indicated that although women whom physicians perceived as high risk were as likely as men to receive prevention messages, women were less likely to be identified as high risk, despite calculated Framingham risk scores.

In a systematic review of research on the diagnosis and treatment of CHD in women, Grady et al4 addressed questions related to risk factors for CHD in women and the effectiveness of risk modification in reducing events associated with CHD. The conclusions were limited by the weakness of the evidence and the lack of evidence for women of different races or ethnic backgrounds.4 One exception was the effectiveness of treating hypertension in African American women. Evidence was fair to good for the roles of hyperlipidemia, diabetes, and hyperhomocysteinemia as risk factors but weak for other risk factors. Age, diabetes, and levels of certain lipoproteins were stronger risk factors for women than for men. Evidence was fair to good that smoking cessation and treatment of hypertension and hyperlipidemia can reduce women’s risk of CHD events.4 In women with known CHD, lipid-lowering therapy can reduce mortality due to CHD 26%, nonfatal myocardial infarction 37%, and major CHD events 21%.4 Innovative intervention programs designed for women, such as the Heart-to-Heart exercise intervention of Perry et al44 for rural women, are needed.

Diet
The Nurses’ Health Study (NHS) provided epidemiological evidence for the association between death due to cardiovascular disease in women and diet, exercise, and smoking.45 The NHS cohort also showed a decline in mortality from coronary disease in women during the 3 decades of the study period. This decrease was mostly due to changes in diet and smoking, but the trend is slowed by a concurrent increase in obesity.46

Recent, highly publicized47 findings from the Women’s Health Initiative (WHI) Dietary Modification Trial indicated no significant effect of the study diet on fatal and nonfatal CHD, stroke, and overall cardiovascular disease during 8.1 years of follow-up.48 The dietary intervention was a low-fat (<20% of energy intake) diet high in fruits, vegetables, and grains.

These results must be interpreted with caution because of several crucial limitations of the trial.49 First, heart disease was a secondary outcome of the study, which was designed to test effects on breast and colorectal cancer. Second, the study had only 40% power to detect a 14% difference in CHD outcomes; despite this low power to detect differences, the results indicated a trend toward lower rates of fatal and nonfatal CHD in women who followed the study diet. Third, the low-fat diet did not conform to current dietary guidelines to reduce saturated and trans fats and thus was not designed specifically to reduce CHD risk. Finally, most of the intervention group did not achieve reduction of total fat to 20% of total energy intake.


Low trans fat diets reduce coronary heart disease in women, especially younger women.

 

Because of these limitations, previous evidence for primary and secondary prevention continues to be important. Observational data from 20 years of follow-up in the NHS reveal that a diet low in trans fat is associated with a reduction in CHD in women and that this association is especially true for younger women,50 a crucial prevention message. Data from clinical trials on the use of diet to prevent CHD events in women are sparse. In trials51,52 that included women, weight and other risk factors were used as proxies for cardiovascular outcomes. Evidence from diet trials that included women and men indicated that a Mediterranean-style diet prevented recurrent CHD events.52

Physical Inactivity and Obesity
Additional NHS data53 on more than 88000 participants indicated that physical inactivity and obesity are independent risk factors for CHD and that even modest weight gain (4–10 kg) during a 20-year period increases the risk for CHD. In the NHS cohort, physical inactivity and obesity accounted for 32% of CHD. The investigators53 concluded that lean women need to be active and that obese women can benefit from physical activity.

Diabetes
Cardiovascular disease is the most common complication of diabetes in women,54 and diabetes is the only condition that causes women to have rates of CHD similar to those of men.55 Women with diabetes are 2 to 4 times more likely than women without diabetes to be hospitalized for cardiovascular disease. Mortality trends reveal that although mortality due to heart disease has declined 27% in women without diabetes, it has increased 23% in women with diabetes.56 Experts agree that diabetes abolishes the advantage women have over men in surviving cardiovascular disease, although the extent of the interaction between diabetes and sex is not fully understood.57–60 Importantly, women should receive aggressive interventions to prevent CHD. The Collaborative Atorvastatin Diabetes Study61 showed the benefit of statin therapy in primary prevention in both women and men with diabetes but no known cardiovascular disease; patients treated with statins had a 36% reduction in cardiovascular events.

Aspirin
The Women’s Health Study investigated the role of aspirin in the primary prevention of CHD in healthy women 45 years and older.62 Aspirin is known to reduce the risk for CHD in men, but its effects in women were unclear.62 Results indicate that use of low-dose aspirin by healthy women lowered the risk of stroke but not of myocardial infarction, the primary end point in the trial.62 A recent meta-analysis63 supports these findings.

Hormone Therapy
On the basis of initial observational data indicating that hormone therapy helped prevent CHD,46 such therapy has been investigated in several clinical trials. The Heart and Estrogen Replacement Study and the WHI were designed to evaluate the effect of hormone therapy on CHD events. The Women’s Angiographic Vitamin and Estrogen Trial, the Women’s Estrogen /progestin and Lipid-Lowering Hormone Atherosclerosis Regression Trial, and the Estrogen Replacement and Atherosclerosis Trial were designed to determine the long-term effects of hormone therapy on progression of atherosclerosis, as indicated by angiograms. The evidence from the studies and trials was overwhelming: hormone therapy does not reduce the risk of primary or secondary CHD events or progression of atherosclerosis and may in fact increase the risk for CHD.64–68


Diabetes eliminates the cardiovascular survival advantage among women.

 

However, new evidence from the NHS suggests that the question is not yet settled. Grodstein et al69 reanalyzed the NHS data, using a subsample of women who resembled the WHI participants (older, later start of hormone therapy, some with established CHD), and found no effect, as the investigators in the WHI had. In a subsample of women without diagnosed CHD who started hormone therapy soon after menopause, however, estrogen alone and estrogen plus progestin appeared to have cardioprotective effects.69 The time that hormone therapy is started may be the key to CHD prevention, because the effects of estrogen on coronary arteries varies with reproductive stage, time since menopause, and stage of atherosclerosis.70 The timing hypothesis is being investigated in current hormone therapy trials.70

Secondary Prevention
Although secondary prevention programs are effective for women,22 women are less likely than men to enroll in and complete such programs. This difference may be due to referral bias71 as well as to women’s unique barriers to participation. The primary barriers identified by women are lack of time and family obligations.72 The evidence from studies of exercise and health promotion for women can be applied to secondary prevention,73–75 though such studies do not necessarily include measures of cardiovascular outcomes.


Hormone therapy does not reduce coronary events or atherosclerosis progression.

 


   Symptoms of CHD in Women
Top
 Abstract
 Context
 Gender Bias and Disparities
 Prevention
 Symptoms of CHD in...
Summary: What Questions Remain?
 Conclusions
 References
 
Symptoms of CHD in women are more "complex and multifactorial" than those of men29(pS26); a possible explanation for the poor outcomes of women with cardiovascular disease is the women’s difficulty in recognizing and then acting on cardiac symptoms.76,77 A similar point can be made for clinicians’ inabilities to recognize the symptoms of CHD in women. Although much has been written about the similarities and differences in the symptoms between women and men,78 many researchers and clinicians continue to label women’s symptoms as "atypical."79

Myocardial Infarction
The seminal description by McSweeney et al80 of women’s prodromal and acute symptoms of myocardial infarction serves as the standard for evaluating women’s indications of myocardial infarction. McSweeney et al found that only 57% of women with myocardial infarction had acute chest pain and that women were likely to describe this chest pain as "tightness," "heaviness," and "aching" rather than as pain. The most frequent acute symptoms of myocardial infarction were shortness of breath, weakness, and fatigue—symptoms that women do not recognize as cardiac related.81 A total of 95% of the women experienced prodromal symptoms, including unusual fatigue, sleep disturbances, shortness of breath, indigestion, and anxiety, before the development of symptoms of acute myocardial infarction.80 Most African American women experienced shortness of breath, weakness, and dizziness and did not frequently report chest pain.82 The most common prodromal symptoms of African American women were unusual fatigue, anxiety, and sleep disturbances.

Delay in Seeking Treatment
Sex plays a role in how quickly a patient decides to seek treatment. Failure to recognize the symptoms of acute myocardial infarction contributes to a delay in seeking treatment,83–86 and prompt recognition of the symptoms is important because early entry into the healthcare system reduces mortality due to cardiovascular disease. Women who access emergency medical services at the onset of symptoms are more likely than women who do not to receive time-sensitive reperfusion medications and other life-saving therapies. Symptoms viewed as "atypical" and/or the lack of chest pain, both more common in women than in men, result in longer delays in seeking care, failure to diagnose myocardial infarction at the time of admission, and the withholding of evidenced-based cardiac therapies.87 In most studies,88–91 women delayed longer than men in seeking help for the symptoms of acute myocardial infarction; in none of the studies did men delay longer than women.

The decision trajectories (ie, patterns of decisions and actions) used by women with acute symptoms of myocardial infarction have been described.76,77 The women in the sample used 1 of 2 types of trajectories: knowing (defined as knowing almost immediately that they would seek help) and managing (defined as treating an alternative hypothesis or minimizing their symptoms). Four subgroups of knowing were identified: knowing and going immediately; knowing and going on the woman’s own terms; knowing and letting someone take over; and knowing and waiting (until morning or Monday).


Women with heart failure have lower quality of life than do men with heart failure.

 

Variables predictive of which trajectory a woman would follow were social support, personal control, perceived threat of heart disease, and neuroticism. The knowing group was characterized by lower social support and higher neuroticism and perceived threat of heart disease. The managing group was associated with the opposite pattern for these 3 variables. The knowing and managing groups did not differ in the frequencies of symptoms.

Heart Failure
Heart failure is a significant illness in older women, yet as Sweitzer and Douglas92(p1961) observed, "There is a disturbing uncertainty about the efficacy of many established therapies in women." Women with heart failure report lower quality of life than do men with heart failure,93 but research on heart failure has included predominantly men. This disparity is largely due to the exclusion of patients who have diastolic heart failure, which is more prevalent in women, especially in older women.94

However, studies of fatigue, a major symptom of heart failure, have tended to include more women than men.95 Friedman96 explored the differences between men and women in symptoms before hospitalization and found that shortness of breath was the leading symptom in both men and women. The prevalence of fatigue, the second most common symptom, was similar in men and women. Ekman and Ehrenberg97 compared fatigue in men and women who had heart failure and found that the women reported more severe fatigue than did the men, consistent with the higher prevalence of fatigue in women in the general population.

In other studies,96,98 women with heart failure reported lower activity levels than men did; this difference has been detected for all cardiovascular disorders.99 Daily activities are limited by symptoms of heart failure,100 and older women with heart failure have reductions in aerobic power associated with functional disability that limits their ability to live independently.101 Women therefore stand to benefit more than men from cardiac rehabilitation and exercise interventions, but women remain underrepresented in research on interventions to prevent heart failure.


   Summary: What Questions Remain?
Top
 Abstract
 Context
 Gender Bias and Disparities
 Prevention
 Symptoms of CHD in...
 Summary: What Questions Remain?
Conclusions
 References
 
Emerging science is addressing women’s unique cardiovascular status, but many crucial questions remain about the prevention, diagnostic, and treatment needs of women with or at risk for CHD. The TableGo presents key gaps in the science as a research agenda for the coming decade.


View this table:
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  		What questions remain? A research agenda

 
It is time to move beyond studies that document disparities between men and women and conduct studies to evaluate the effectiveness of interventions tailored for women, particularly women of diverse races and ethnicities. The evidence base for prevention, symptoms, and treatment of CHD in nonwhite women,4 especially Latinas,109 is weak. Current efforts to reduce racial and ethnic disparities in healthcare110 that include key elements of systems analysis, systems change, and community involvement can be applied to efforts to eliminate sex bias.

Studies should be designed to allow analysis by sex, and all outcomes data either should be reported by sex and race/ethnicity or be available for systematic reviews. The types of outcomes studied should include not only morbidity and mortality but also important elements of the quality of care such as patients’ symptoms, functioning, and quality of life.111

Community-based participatory research methods are needed to address many of the important remaining questions. According to Satcher et al,39(p463) "Eliminating disparities will require large-scale, multidimensional, community-participatory interventions focused explicitly on health disparities for specific population groups." Such efforts will require adequate funding to support sex-based research.


   Conclusions
Top
 Abstract
 Context
 Gender Bias and Disparities
 Prevention
 Symptoms of CHD in...
 Summary: What Questions Remain?
 Conclusions
References
 
Women are living longer than ever before, and thanks to lifestyle changes and the scientific evidence for primary and secondary prevention, mortality due to heart disease is declining. Implementation of current scientific knowledge could have great effects on women’s morbidity and mortality. However, women with heart disease remain underdiagnosed, undertreated, and underresearched. Little evidence is available to answer important questions for women of different races or ethnicities, yet these women bear substantial burdens because of cardiovascular disease. Likewise, older women are underrepresented in existing research, though heart disease is largely a disease of older women. We’ve come a long way, but we have much left to do to build the science that can alleviate the No. 1 health threat to women: cardiovascular disease.


   ACKNOWLEDGMENT
 
I acknowledge the assistance of Blair G. Darney, MPH, in the preparation of this manuscript.

To purchase electronic or print reprints, contact The InnoVision Group, 101 Columbia, Aliso Viejo, CA 92656. Phone, (800) 809-2273 or (949) 362-2050 (ext 532); fax, (949) 362-2049; e-mail, reprints{at}aacn.org.


   REFERENCES
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 Abstract
 Context
 Gender Bias and Disparities
 Prevention
 Symptoms of CHD in...
 Summary: What Questions Remain?
 Conclusions
 References
 

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