Myocardial Ischemia in Women – Lessons from the NHLBI WISE Study [Pubmed Abstract] [Full Text HTML] [Full Text PDF]. Clin Cardiol. 2012 Mar;35(3):141-8. doi: 10.1002/clc.21966.
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Symptoms and Prevalence of Myocardial ischemia in Women
The evaluation of women with IHD is influenced by the definition of angina, given that “typical” symptoms have been established from largely male populations and reflect a
pattern that is more typical in men.52 Nonetheless, from a meta-analysis of 74 studies, it appears that women have a similar or even higher prevalence of angina compared with
men.53 In an analysis of 69 studies of symptoms with acute coronary syndromes (ACS), women did appear to have less “typical” symptoms compared with men, but the majority of women still had typical symptoms with their presentation.54 Women with any symptoms suggestive of myocardial ischemia still have a probability of CAD that is lower than that for men,55 and as the WISE study has demonstrated, 57% of women will not have obstructive
CAD when coronary angiography is performed.56 Indeed, these findings have been confirmed in larger data registries.57 In those women without obstructive CAD, more than half will continue to have signs and symptoms of myocardial ischemia, be repeatedly hospitalized, and undergo repeat coronary angiography, all of which impacts healthcare resources.19 From the WISE data, such women with chest pain and no obstructive CAD have a higher mortality and adverse cardiovascular events when compared with asymptomatic women, underscoring that the prognosis in women with symptoms and signs of ischemia is not benign, even when they have no obstructive CAD or “normal” coronary arteries.58 [Emphasis added]In women who present with ACS, it is not infrequent for the angiogram to be “normal” or demonstrate no obstructive CAD.
DIAGNOSIS OF MYOCARDIAL ISCHEMIA IN WOMEN
Exercise Stress Testing for Myocardial Ischemia in Women
An exercise stress test is often used to diagnose CAD. In women, the sensitivity of
specificity of ST-segment depression is lower in women than in men,66 but these values are influenced by the lower prevalence of obstructive CAD.67 ST-segment depression is only one variable from exercise stress testing that has important diagnostic and prognostic value in women.67 However, ST-segment depression can be combined with additional exercise stress testing variables, including exercise duration and symptoms, to determine the Duke
Treadmill Score, which more accurately predicts both the presence of CAD and IHD mortality in women.68,69 In addition to other important prognostic markers, exercise
capacity (fitness level) can be estimated using an exercise stress test, and an exercise capacity of <5 METs or the inability to achieve ≥ 85% of age-predicted fitness level has
been shown to be predictor of MI, IHD death and all-cause mortality in women.67,70,71Noninvasive Imaging for Myocardial Ischemia in Women
Imaging modalities can also be used to assess IHD risk in women either in addition to exercise stress testing or with pharmacologic agents when exercise is not possible. . . . Myocardial perfusion can be evaluated in women using single photon emission computed tomography (SPECT) imaging, positron emission tomography (PET) or cardiac magnetic resonance (CMR).
Stress CMR imaging is unique compared with other stress imaging modalities, as it allows assessment of subendocardial perfusion. In a small study of 20 patients (80% female) with abnormal stress tests and normal coronary arteries, subendocardial ischemia was frequently
present when compared with controls when adenosine CMR was performed.76 This has been confirmed in another study,77 while further publications have demonstrated both
subendocardial and subepicadial ischemia in these patients.78 In women with ACS and normal coronary arteries, subendocardial ischemia on CMR was the most common finding.13 Newer techniques using CMR with exercise testing are being evaluated to assess IHD in women.79 There is limited information regarding prognosis related to stress-induced CMR perfusion abnormalities in women with no obstructive CAD, but in a small sub-study
from WISE, women with nonobstructive CAD with an abnormal stress-induced CMR had an increase in adverse cardiovascular events.75 Further investigations evaluating the prognostic value of subendocardial ischemia in women are needed.Coronary Reactivity Testing for Myocardial Ischemia in Women
Vascular reactivity disproportionately affects women in a variety of other diseases, such as migraine headaches, Raynaud’s phenomenon, and autoimmune arteritis.14 It is not surprising that there would be an increased rate of vascular reactivity in the coronary circulation of women, as well. In the past, coronary reactivity in women was thought to be due to vasospasm of the epicardial arteries, known as Prinzemetal’s angina.80 More recent research has revealed that microvascular coronary dysfunction (MCD) involving endothelial and nonendothelial pathways can be responsible for IHD in women, particularly in women with “normal” coronary arteries and those with nonobstructive CAD.81
Microvascular Coronary Dysfunction—There is emerging data supporting a gender-specific role of MCD, as an early stage of IHD. . . . In the WISE study, almost half the women who had measures of coronary flow reserve had
abnormal responses consistent with MCD.83 In another study that examined intravascular ultrasound and coronary reactivity testing in men and women, women had far less obstructive CAD and more MCD than men.84 This evidence of MCD appears to be part of the IHD pathophysiology, and may explain the higher rates of angina in women, in addition to the ischemia and ACS in absence of obstructive CAD that occurs so frequently in women.Endothelial Dysfunction—Endothelial response is adversely affected by traditional cardiac risk factors, including tobacco abuse, hyperlipidemia, diabetes and hypertension,85 and worsens after menopause.86 Endothelial dysfunction can contribute to IHD in women.
Both peripheral assessment of endothelial response and direct assessment of endothelial function in the coronary circulation have been shown to be associated with IHD risk.5 Restoration of endothelial function has been demonstrated to improved outcomes in women,
as seen in a group of postmenopausal, hypertensive women who were treated for hypertension, who also had an improvement in their endothelial response.87Both MCD (non-endothelial dependent) and endothelial dysfunction (endothelial-dependent) predict adverse cardiovascular events.88 The role of MCD in IHD among women without obstructive CAD has only recently been recognized and more complete assessment of coronary reactivity in such a setting has been suggested.58,89
Treatment and Outcomes of Obstructive CAD in Women
Optimal medical therapy for women with IHD is no different than for men, but women often receive less intensive medical therapy or lifestyle counseling, which ultimately influences outcomes.16,90–93 There are also sex differences in treatment for ACS that also influence
outcomes. In addition to the difference in medical therapy, there are sex differences in use of cardiac catheterization and revascularization use and timing, which are associated with poorer outcomes in women after ACS or MI.91,9
