An ETT is usually recommended as the first test for IHD to assessment. The current ACC/AHA guidelines recommend ETT for evaluation of chest symptoms in patients at risk for CAD (Class IIb) and vasospastic angina (Class IIa). However, it can be of a lower utility in women because of its lower specificity and sensitivity in detecting obstructive coronary artery disease (CAD) in women compared to men. This may be due to lower prevalence of obstructive CAD in women, increased frequency of non-specific ST changes in baseline EKGs compared to men (32 % versus 23 %, respectively), and inability to achieve maximal functional capacity secondary to increased prevalence of obesity and osteoarthritis in women [34].

Stress-induced changes in non-invasive cardiac imaging are better markers in assessing for IHD in women. In a study with more than a 1000 women with suspected obstructive CAD, stress echocardiography had a high sensitivity (81–89 %) and high specificity (86 %) in patients with multi-vessel CAD in its ability of predict IHD [35]. In addition, a stress echo can be conducted in various ways, such as a treadmill, bicycle, and pharmacologically. Exercise stress testing is encouraged as it can also assess the patient’s functional capacity and exercise tolerance. The WOMEN (What is the Optimal Method for Ischemia Evaluation in Women?) trial, in which 824 symptomatic women with suspected obstructive CAD were randomized to ETT or exercise myocardial perfusion imaging (MPI), found at 2 years that there was no significant difference in major cardiac events predicted by either modality [36].

Myocardial gated single-photon emission computed tomography (SPECT) is recommended for both men and women with CVD risk factors, and allows for visualization of global or regional perfusion defects. The accuracy of the MPI is comparable between women and men, and is advantageous in patients who have poor exercise tolerance. However, limitations in the MPI include high rate of false positives in global perfusion defects, patients with small hearts, and breast tissue artifact.

Cardiac computed tomography (CT) and magnetic resonance imaging (MRI) are newer imaging modalities that assess cardiac ischemia different from coronary angiography. Cardiac MRI can assess for subendocardial ischemia, one of the initial manifestations of cardiac ischemia, and can explain the etiology of chest pain in the setting of non-obstructive CAD. Coronary computed tomography angiography (CCTA) assesses coronary atherosclerosis, and is often used in the place of invasive coronary angiography. In a large, multicenter prospective international cohort study, the CONFIRM trial demonstrated that CCTA improves the ability to predict mortality and non-fatal MI in symptomatic patients with suspected obstructive CAD [37]. Multiple studies have shown that CCTA can detect significant stenosis in smaller coronary arteries and side branches with 86–94 % sensitivity and 93–97 % specificity, such that it can rule out the presence of hemodynamically significant CAD [38]. However, while the CCTA is an excellent tool to detect anatomic CAD severity, it is unable to assess whether a lesion causes ischemia [31, 32]. To help with risk stratification in primary prevention, very low dose radiation testing with electron beam CT (EBCT) can assess the amount of calcium in coronary arteries, in which a calcium score between 100 and 400 is associated with increased obstructive CAD.

Coronary angiography or cardiac catheterization remains the gold standard in the detection of significant, obstructive CAD. The use of fractional flow reserve (FFR) to determine the hemodynamic significance of a lesion and to guide percutaneous coronary intervention (PCI) with stenting is recommended in both men and women [31, 32]. Although PCI is equally effective in men and women, there is an increased bleeding risk in women, like secondary to the lack of dose adjustment in glycoprotein IIb/IIIa inhibitor according to body size and renal function [39]. Women are treated less aggressively than men are when first presenting with acute coronary syndrome (ACS). Women are also more likely to undergo stress testing than cardiac catheterization in evaluation of their ischemia, and are subsequently likely to experience a delay in cardiac catheterization.

Many women who do have not have obstructive CAD on diagnostic testing are falsely reassured that they do not have IHD. In the WISE (Women’s Ischemia Syndrome Evaluation) study, approximately one-half of symptomatic women without obstructive CAD have coronary microvascular dysfunction (CMD), which is associated with higher CVD risk than asymptomatic women are. In fact, patients with unstable angina in the absence of obstructive CAD have a 2 % risk of CVD and death at 30 days [40]. Furthermore, the 5-year event rates for CVD events in women with persistent chest pain with non-obstructive CAD (i.e., lesions <50 % stenosis in coronary arteries) were 16 % compared to WISE women with normal coronary arteries (i.e., 0 % stenosis in all coronary arteries) at 7.9 % compared to asymptomatic women with normal coronary arteries at 2.4 % [41]. CMD is detected by invasive coronary reactivity testing to assess endothelial and non-endothelial micro and macrovascular responses vasoactive substances, including adenosine, acetylcholine, and nitroglycerin [42].

On arrival to the hospital with stroke symptoms, women have longer door-to-scan times than men. A European study revealed that after age-adjustment, women are less likely than men are to receive imaging of brain, carotid ultrasound, or echocardiograms [43].

Women are less likely to be medically optimized after MI or stroke compared to men. Aspirin use is associated with a reduction in future events in women with a history of CVD, such as unstable angina and acute MI, and stroke. It is recommended for primary prevention for MI in women after age 65 and for stroke prevention after age 50 [44]. However, women are less likely to be discharged on dual antiplatelet therapy, ACE-inhibitor, or statins after an acute event, such as a stroke of MI.

Many CVD medications found to be life-saving have not been adequately tested in women likely due to the under-representation of women in most trials. Beta-blockers have been found to reduce the risk of subsequent MI by 25 % in both women and men (though not statistically significant in women, likely due to the small sample size) [45]. Similarly, the Heart Outcomes Prevention trial demonstrated a reduction in death, MI, and stroke equally in women and men with vascular disease or diabetes with the ACE inhibitor or ARB therapy. If an ACE-inhibitor is used in a woman of child-bearing age, a discussion regarding its teratogenic effects is warranted.

HMG-CoA reductase inhibitors (or statins) are commonly prescribed for dyslipidemia though their pleotropic effects have been found to extend beyond lowering the cholesterol. Statins have been observed to improve endothelial dysfunction and myocardial perfusion, in which treatment for 6–12 weeks of fluvastatin was shown to significantly improve myocardial perfusion in ischemic segments [46]. In addition, long-term therapy with statin in the CARE trial lowered hs-CRP levels in post-infarction patients though the effects have not been shown to correlate with LDL-C levels [34]. The Heart Protection Trial Study (HPS) demonstrated that statins led to a prominent reduction in all-cause mortality in women and a 24 % reduction in vascular events [4].

Advances in coronary revascularization appear to have provided benefit in women and men. Women who receive invasive coronary revascularization are older, have more comorbidities (e.g., diabetes, hypertension, peripheral arterial disease, dyslipidemia), have unstable angina, and more severe angina compared to men. Women make up only one-third of cardiac catheterizations even though there is mortality benefit with intervention in those with obstructive CAD. In addition, physicians are less likely to use heparin, ACE-inhibitors, and glycoprotein IIb/IIIa inhibitors in women, and less likely to discharge them with ACE-inhibitors, statins, beta-blockers and aspirin [28]. A meta-analysis of eight ACS trials revealed that women and men both benefited from an invasive therapy, with a 19–27 % relative risk reduction in death, MI, or repeat ACS. However, biomarker-positive women had a 33 % lower risk reduction than biomarker-negative women, which was not seen in men [47]. In addition, there are more associated complications in women younger than age 55, such as coronary vascular injury likely due to smaller vessels and bleeding complications when compared to men.

Coronary artery bypass graft (CABG) surgery is associated with increased operative mortality in women compared to men (ie., 4.5 % in women versus 1.9 % in men) [48]. This may be because women who undergo CABG have a higher pre-operative risk due to increased comorbidities and smaller anatomy than men. In addition, there is also an increase in complications in women compared to men, including atrial fibrillation, pneumonia, sternal reclosure, leg wounds, and prolonged mechanical ventilation. Women were also found to have fewer internal mammary artery conduits than men, which can be associated with increased incidence of incomplete revascularization in women.

Interestingly, in a study by Patrick et al. of patients hospitalized for ischemic stroke, women underwent fewer cerebral angiography (7.2 %) and carotid endarterectomy (5.7 %) than did men (11.8 % and 10.6 %, respectively), but the differences were not significant after the increased prevalence of carotid disease in men were adjusted [49]. Both men and women benefit equally from carotid endarterectomy. In addition, most studies show that women were less likely to receive alteplase than men. An analysis of a Michigan registry study of ischemic stroke patients revealed that the adjusted odds ratio for alteplase treatment in women was 0.56 (95 % CI 0.4–0.9) compared to men [50].