Cardiovascular disease (CVD) is the leading cause of death in the United States (Figure 1-1).¹ The burden of CVD is shared by men and women alike (Figures 1-2 and 1-3), although CVD’s impact on women has been traditionally underappreciated. For far too long, women were not represented in major cardiovascular trials (Figure 1-4 and Table 1-1).² In addition, both patients and physicians have displayed a lack of awareness regarding CVD’s prevalence in women, although this scenario is changing now (Figure 1-5).^3,4 The pathophysiology of CVD has unique characteristics in women. Furthermore, as women are increasingly being included in cardiovascular trials, management strategies specific to women are being defined.^5,6,7,8,9 In this Atlas and Synopsis of Women’s Cardiovascular Health, we hope to highlight the impact of CVD on women, its unique characteristics in women, and important topics in CVD that have female-specific management strategies.

In the United States more women than men die of CVD (Figure 1-6).¹ Moreover, more women have died of CVD than cancer (including breast cancer), chronic lower respiratory disease, Alzheimer disease, and accidents combined (Figure 1-7).¹ From 1998 to 2008, though the overall death rates attributable to CVD declined to 30.6%, these have shown an increasing trend among young women (<55 years).^1,10 Of particular concern is the rise in obese American population, with its subsequent impact on diabetes and development of CVD in future. According to NHANES 2007-2008, 34% of men and women in the United States are obese.¹¹ However, the impact of obesity on the development of CVD appears to be greater on women than men. Among individuals in the Framingham Heart Study, obesity increased the relative risk of CVD by 64% in women, as opposed to 46% in men.¹²

The average age of first myocardial infarction (MI) is 64.5 years for men and 70.3 years for women.¹ The onset of CVD in women is on average 10 years later than men and incidence serious clinical events such as MI and sudden death usually lag behind by 20 years.¹³ The consequences of CVD are worse in women than in men. Women with premature MI (<50), experience a 2-fold increase in mortality after acute MI (Figure 1-8);¹⁴ however among older individuals (>65), women are more likely to die within the first year after MI.¹ In individuals ages 45 to 64 years, women are more likely than men to have heart failure within 5 years of MI.¹

The burden of CVD is high among women. However, it appears that the pathophysiology of CVD varies between women and men. On cardiovascular computed tomography (CT), women have been shown to have smaller coronary artery diameters.¹⁵ They are less likely to have obstructive coronary artery disease at time of coronary angiography.^16,17 Despite the lack of obstructive disease visualized on cardiac catheterization at time of acute coronary syndrome (ACS), the prognosis of these women is not benign. Over half of symptomatic women without obstructive coronary artery disease continue to have signs and symptoms of ischemia, undergo repeat hospitalization, and coronary angiography.^18,19

Recently, disorders of the coronary microvasculature and endothelial dysfunction have been implicated in the occurrence of CVD without obstructive coronary artery disease in women. Han et al²⁰ studied men and women with early coronary artery disease and found that men have higher degrees of atheroma and epicardial endothelial dysfunction, whereas women have more incidence of the microvasculature. Retinal artery narrowing has been shown to be a marker for microvascular disease, and in the population covered under the Atherosclerosis Risk in Communities (ARIC) study, a decrease in retinal artery diameter as assessed on retinal photographs corresponded to an increase in CVD incidence in women. This relationship was not seen in men, supporting a more prominent role of microvascular disease in CVD pathophysiology in women as opposed to men.²¹ In addition, autopsy data have shown that women have a greater frequency of coronary plaque erosion and distal embolization (Figure 1-9).²² In the WISE study, approximately half of women with chest pain without obstructive coronary artery disease had microvascular dysfunction.²³ In a study of postmenopausal women, impairment of flow-mediated dilation of the brachial artery predicted the development of cardiovascular events.²⁴ Hypertensive postmenopausal women were treated with antihypertensive therapy, which resulted in an improvement in flow-mediated vasodilation and an associated improvement in cardiovascular events.²⁵ Given the occurrence of CVD in women without obstructive coronary artery disease, the term female-specific ischemic heart disease has been recommended when discussing disease of the coronary arteries in women.²⁶

An exercise stress test is used commonly in the evaluation of suspected coronary artery disease. In women, the ST-segment depression noted on exercise stress testing is felt to be less accurate than in men. Also, the sensitivity and specificity of ST-segment depression is lower in women than in men.²⁷ However, the negative predictive value is high in both.²⁸ A negative exercise stress test, therefore, can effectively rule out the diagnosis of CAD in women. The Duke Treadmill score, which incorporates exercise time, ST deviation, and an anginal score, is particularly useful in women, and performs better in women than men in predicting significant CVD.²⁹ Exercise is a powerful predictor of CVD. Importantly, a nomogram has been established defining age-predicted exercise capacity in women.³⁰ As mentioned earlier, women who are unable to reach 5 metabolic equivalents (METs) or perform <85% of age-predicted fitness level on an exercise stress test have a higher risk of MI and all-cause mortality.^30,31

Stress echocardiography has similar high levels of sensitivity and specificity in women and men.^32,33 Its lack of radiation is particularly attractive in younger women. Myocardial perfusion imaging utilizing single-photon emission computed tomography (SPECT) has been well studied in women. The incorporation of technetium-99 sestamibi radiotracer and the use of gating technology have improved the sensitivity and specificity of SPECT imaging in women to nearly 90% (Table 1-2).^34,35 SPECT stress imaging effectively risk-stratifies women.^36,37,38 In a study including women with a normal myocardial perfusion using SPECT imaging, the annual CVD death rate was very low (0.6% per year) in contrast to a much higher event rate (5% per year) in those with abnormal myocardial perfusion.³⁸