Campaigns in the USA during the past decade by the National Heart, Lung, and Blood Institute (the Heart Truth Campaign) and the American Heart Association (the Red Dress Campaign) have almost doubled the awareness among US women that cardiovascular disease is their leading cause of mortality. The 30 % awareness rate in 1997 increased to 54 % by 2009 (Mosca et al. 2010), but has since remained unchanged. Unfortunately, awareness is lowest for the subsets of women at highest risk, African American and Hispanic women.

Nonetheless, physician assessment of a woman’s cardiovascular risk is characteristically lower than for her male counterparts, which is reflected in the provision of a lesser intensity and quality of cardiovascular preventive therapies for women.

Although obstructive coronary artery disease remains the leading cause of myocardial ischemia in women, complex pathophysiologic mechanisms likely play an important role in myocardial ischemia, myocardial infarction, and ischemic heart disease-related mortality for women. In the Women’s Ischemia Syndrome Evaluation (WISE) study (Von Mering 2000), microvascular disease was considered an important contributor to myocardial ischemia. About half of all women who present with an acute coronary syndrome do not have significant obstructive disease in their epicardial coronary arteries at angiography.

As well, women appear far more likely to have coronary plaque erosion and thrombosis than men, with less plaque rupture compared to men except at elderly age (Anderson et al. 2000). Abnormalities in coronary vasoreactivity appear to contribute to myocardial ischemia in women with nonobstructive coronary disease (Shaw et al. 2009).

Although women have higher rates of myocardial ischemia and ischemic mortality than men, paradoxical is its association with less obstructive disease in the epicardial coronary arteries and more common preservation of left ventricular systolic function. Better understanding of the pathophysiologic mechanisms of myocardial ischemia in women is requisite to guide improved management.

Despite the fact that women and men share the traditional coronary risk factors, these factors impart differential risk by gender. Women smokers have a 25 % greater risk of myocardial infarction than do men who smoke, and smoking is related to almost half of all coronary events in women (Prescott et al. 1998; Huxley and Woodward 2011). The decrease in smoking behavior in the USA has been more prominent for men than for women, with new-onset smoking most common among teenage girls.

Lipid abnormalities also exert a differential risk, with the ratio of total cholesterol: HDL > 3.2 highly predictive of cardiovascular events in women, and an HDL-C level < 30 mg/dL associated with excess cardiovascular mortality. As well, the combination of increased triglycerides and low HDL imparts increased risk, although no interventions to alter triglyceride or HDL levels have been shown to improve outcomes. The new ACC/AHA guidelines for managing elevated cholesterol levels (http://​circ.​ahajournals.​org/​content/​early/​2013/​11/​11/​01.​cir.​0000437738.​63853.​7a.​citation) do not have gender-specific recommendations, thus emphasizing the benefits for women of appropriate intensity statin therapy for both primary and secondary prevention. Lipid-lowering therapy, primarily involving statin drugs to reduce LDL cholesterol levels, has dramatically decreased recurrent cardiovascular events in women and likely decreased incident events as well (Ridker et al. 2008; Kaul et al. 2010). A family history of premature CHD also seems more predictive for women than for men (Gulati et al. 2009).

Unique to women is the risk of hypertensive complications of pregnancy: pregnancy-induced hypertension, preeclampsia, and eclampsia. Pregnancy is probably the first “stress test” a woman incurs, and hypertensive complications predict subsequent increased cardiovascular risks (Mosca et al. 2011). Other pregnancy complications predictive of a woman’s adverse future cardiovascular health include gestational diabetes mellitus, preterm birth, fetal growth restriction, and pregnancy loss (Bonamy and Parikh 2013; Wenger 2014b). As well, women with systemic autoimmune collagen vascular disease have an increased cardiovascular risk, warranting coronary risk factor screening for these women.

The Framingham Risk Score (FRS), traditionally used to calculate a 10-year risk of coronary death or myocardial infarction, is accepted to underestimate risk in women (Pasternak and Abrams 2003). The newly released Pooled Cohort Equations (http://​my.​americanheart.​org/​cvriskcalculator​ and http://​www.​cardiosource.​org/​science-and-quality/​practice-guidelines-and-quality-standards/​2013-prevention-guideline-tools.​aspx for risk equations) in the ACC/AHA Risk Stratification Guidelines will require evaluation with community use for women. In 2011, the American Heart Association updated its Effectiveness-based Guideline for the Prevention of Cardiovascular Disease in Women, highlighting risk assessment and risk-based intervention, with an emphasis on lifetime cardiovascular risk, which is approximately 1 in 3 for US women. It categorized women as at high risk (those with established cardiovascular disease or coronary risk equivalents), at risk (having any of a variety of coronary risk factors or test abnormalities), or at ideal cardiovascular health, based on the absence of multiple risk factors (Mosca et al. 2011). A detailed pregnancy history was recommended as a routine component of cardiovascular risk assessment for women.

Diabetes preferentially disadvantages women, conferring a higher risk of CHD in women than men (Kanaya et al. 2002; Spencer et al. 2010). Although mortality in US diabetic men, nondiabetic men, and nondiabetic women has decreased during the past three decades, women with diabetes have had an increase in mortality in the same time frame (Gregg et al. 2007). The increased cardiovascular risk in diabetic women may reflect risk factor clustering in this population, who are particularly likely to have associated hypertension and an adverse lipid profile. Diabetes essentially negates the premenopausal protective effect of being a woman. As in men, intensive diabetic control failed to prevent coronary events in women (Wassertheil-Smoller et al. 2003).

Although women have lower blood pressures than men at younger age, by age 60 women are more likely to have hypertension than men. Multiple studies have shown cardiovascular benefit in controlling blood pressure in women, with the most dramatic benefit being in stroke reduction (Rashidi et al. 2008). Gender differences may guide the choice of antihypertensive therapy, as women are more likely than men to develop ACE-related cough and are more likely to experience troublesome edema with calcium channel blockers (Engberding and Wenger 2012).

Despite the long-held belief that menopausal hormone therapy improved cardiovascular outcomes, recent large randomized clinical trials in both healthy women and in women with CHD have failed to show cardiovascular benefit. There is documented lack of effectiveness of menopausal hormone therapy in preventing either incident or recurrent cardiovascular disease, but hormone therapy is associated with an increase in stroke risk, myocardial infarction with estrogen plus progestin, invasive breast cancer, venous thromboembolism, gallbladder disease, urinary incontinence, and dementia (Writing Group of Women’s Health Initiative Investigators 2002; Wassertheil-Smoller et al. 2003; Moyer 2013). The recommendations of the U.S. Preventive Services Task Force (Moyer 2013; Wenger 2014a) do not advise menopausal hormone therapy for the primary or secondary prevention of coronary heart disease in women. Based on the results of the randomized hormone clinical trials cited above, according to the U.S. National Health and Nutrition Examination Survey, hormone use by menopausal women decreased from 22 % in 1999–2000 to 4.7 % in 2009–2010. Thirteen-year follow-up data from the WHI hormone trials (Manson et al. 2013) offer some reassurance to younger women who require hormone therapy for the management of moderate-to-severe menopausal symptoms, as their risk–benefit ratio is more favorable than for older women.

Oral contraceptive use has a low cardiovascular risk in women, predominantly because users are young, healthy women with a low baseline coronary risk (Baillargeon et al. 2005). Smoking increases the risk of thrombotic events and women who smoke may be advised to seek alternative forms of contraception.

Supplementation with antioxidant vitamins C, E, and β-carotene; and therapy with folic acid with and without B vitamin supplementation failed to prevent incident or recurrent cardiovascular disease in women (Cook et al. 2007; Albert et al. 2008; Lonn et al. 2006; Clarke et al. 2010). In the Women’s Health Initiative, neither vitamin D nor calcium supplementation decreased cardiovascular events or mortality (Hsai et al. 2007).

Recent studies show that aspirin failed to lessen the risk of myocardial infarction in women younger than 65 years of age, but decreased their stroke risk; this contrasts markedly to the findings in men, where aspirin decreased the risk of myocardial infarction but not of stroke (Ridker et al. 2005; U.S. Preventive Services Task Force 2009).

The choice of diagnostic testing depends on the ability of the woman to exercise, the characteristics of the resting electrocardiogram, and the pretest likelihood of CHD. For women at low risk, testing may not be needed.

In women with a normal resting electrocardiogram who can exercise to adequate intensity, the initial test recommended for low-intermediate risk women is an exercise ECG. In the Women’s Study (Shaw et al. 2011), this was a cost-effective option compared to SPECT imaging.

For women unable to exercise adequately or with an abnormal resting ECG, an imaging study, dobutamine stress echocardiography, or SPECT imaging is appropriate. The diagnostic accuracy of pharmacologic nuclear imaging and dobutamine stress echocardiography is comparable for women, but dobutamine stress echocardiography, in addition to providing data regarding cardiac anatomy, has the advantage of the absence of ionizing radiation exposure. Coronary CT angiography and cardiac magnetic resonance (CMR) imaging are additional options.

Diagnostic procedures are often suboptimally selected for women and are also often deferred inappropriately, likely owing to a misperception of lower coronary risk for women, although women benefit from commonly used noninvasive tests. Test results should guide treatment decisions and/or decisions to pursue invasive testing (Mieres et al. 2005).

Angina is the most common initial and recurrent presentation of CHD in women (Hemingway et al. 2008). Among patients presenting with an initial myocardial infarction, women are more likely than men to have had a history of antecedent stable angina pectoris, raising concern as to whether optimal risk reduction and risk stratification was undertaken in the stable phase of the disease. Women with angina more often than men describe associated symptoms (radiation of pain to the neck, throat, arms, back, or abdomen; dyspnea, weakness, and fatigue); and more often describe palpitations than men (D’Antonio et al. 2006; Milner et al. 1999).

Women, and often young women, are also more likely to present with non-chest pain symptoms of myocardial ischemia (Shaw et al. 2009; Canto et al. 2012a) than are younger men; these non-chest pain presentations are associated with a less favorable outcome (Canto et al. 2012b).

Prevalence of stable angina is comparable for US men and women; paradoxically, women with angina have less obstructive disease at coronary angiography and are less likely to incur myocardial infarction. Compelling arguments have been offered for microvascular disease as etiologic for myocardial ischemia in women (Gulati et al. 2009; Pepine et al. 2010), as well as for intramural coronary atherosclerosis concealed by positive arterial remodeling (Khuddus et al. 2010).

In multiple studies, women with stable ischemic heart disease are less likely to receive evidence-based pharmacologic therapy and are less likely to undergo appropriate diagnostic testing and indicated revascularization procedures (Daly et al. 2006).