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Cardiopatia isquemica en la mujer. Med Clin N Am, 2024

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Is chem ic H ea r t D i s ea s e i n

Wo m en
a b,
Eleonore Grant, MD , Monika Sanghavi, MD *

KEYWORDS
 Ischemic heart disease  women’s cardiovascular health
 MI with no obstructive coronary arteries  Spontaneous coronary artery dissection
 acute coronary syndrome

KEY POINTS
 Women have a unique clinical phenotype of ischemic heart disease with higher prevalence
of non-occlusive disease, and decreased burden of obstructive atherosclerosis.
 Women share a disproportionate burden of traditional risk-factors for heart disease and
have sex-specific risk-factors that are not incorporated into commonly used risk scores.
 Ischemia with non-Obstructive Coronary Arteries (INOCA) is a clinical entity grouping
several endotypes including microvascular disease, vasospasm, and myocardial bridging
and is more common in women.
 There is a burgeoning understanding of the discordance between angina and ischemia in
women, especially in INOCA and this should be carefully considered in treatment
strategies.

INTRODUCTION

The landscape of ischemic heart disease in women has expanded significantly with
attention to sex-specific differences. The focus has shifted from obstructive epicardial
atherosclerosis to a spectrum of ischemic heart disease including nonobstructive eti-
ologies. Better appreciation of the different phenotypes of ischemic heart disease may
help reduce disparities between the sexes. Women with ischemic heart disease are
reported to have a higher prevalence of angina,1 lower health-related quality of life,2
higher emergency room visits,3 and increased short- and long-term mortality than
men.4 This article reviews the current understanding of ischemic heart disease high-
lighting sex-specific differences.

a
Department of Internal Medicine, University of Pennsylvania, 3400 Civic Center Boulevard,
Philadelphia, PA 19104, USA; b Division of Cardiology, University of Pennsylvania, 3400 Civic
Center Boulevard, Philadelphia, PA 19104, USA
* Corresponding author.
E-mail address: Monika.Sanghavi@pennmedicine.upenn.edu

Med Clin N Am 108 (2024) 567–579


https://doi.org/10.1016/j.mcna.2023.11.001 medical.theclinics.com
0025-7125/24/ª 2023 Elsevier Inc. All rights reserved.

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568 Grant & Sanghavi

BIOLOGIC DIFFERENCES

In addition to differences in hormonal milieu, several sex differences in cardiovascular


anatomy and function have been reported, which may contribute to the differences in
clinical phenotypes and presentation.5,6 Women are known to have smaller epicardial
arteries compared with men even when matched for body mass index (BMI) and left
ventricular mass.7 They have higher resting blood flow per gram of myocardial
mass,8 which may be due to differences in autonomic function.9

RISK FACTORS
Traditional Risk Factors, Differing Burden of Disease
Women share many of the same traditional cardiovascular risk factors as men (hyper-
lipidemia, hypertension [HTN], diabetes mellitus [DM], abdominal obesity, smoking,
and physical inactivity).10 However, HTN, DM, and smoking are more potent risk fac-
tors in women than men (odds ratio of 1.5, 1.6, and 2.0, respectively).10 Possible rea-
sons for this have been theorized: (1) HTN is often undertreated in women as
compared with men;11 (2) DM may cause heightened impairment of endothelium-
dependent vasodilation which may disproportionally affect women11; and (3) smoking
risk is potentiated by use of combined oral contraceptive pills (tenfold increase in
myocardial infarction (MI) and threefold increase in stroke).12 This underscores the
need to target these modifiable risk factors in primary and secondary prevention of
Ischemic Heart Disease (IHD) in women.

Sex-Specific Risk Factors


Several sex-specific risk factors have also been reported.11–16 These include (1) hor-
monal risk factors, (2) adverse pregnancy outcomes,17 and (3) inflammation and rheu-
matologic conditions.14,18

Hormonal factors
Endogenous estrogen is cardioprotective due to a myriad of positive effects on the
metabolic and vascular system19 and is theorized to be the reason for the 10-year
delay in atherosclerotic events in women compared with men. The loss of endogenous
estrogen production during menopause has been associated with increased cardio-
vascular risk, redistribution of body fat, reduced glucose tolerance, abnormal lipids,
and increased blood pressure and arterial stiffening.19–21 Still, exogenous estrogen
replacement has not been proven as a reliable mechanism to reduce cardiovascular
risk.20
Polycystic ovarian syndrome (PCOS) is associated with adverse cardio-metabolic
health and higher incidence of IHD. Although the association is well-established, it
is still debated whether PCOS is an independent a risk factor for IHD or if it is due
to the adverse metabolic effects (dyslipidemia, insulin resistance, weight gain).17

Hypertensive and metabolic disorders of pregnancy


Adverse pregnancy outcomes including hypertensive disorders of pregnancy, gesta-
tional diabetes, preterm birth, and small for gestational age infant have all been shown
to increase the risk of IHD.17 This is true for the peripartum period, but also confers a
twofold life-time risk of cardiovascular disease (CVD).17 Preeclampsia is an athero-
sclerotic CVD (ASCVD) risk enhancer, similar to family history, and should be consid-
ered when assessing the risk of ischemic heart disease in women. Timing, severity,
and recurrence of preeclampsia are all correlated with future cardiovascular risk
and can be gleaned when obtaining a pregnancy history.

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Ischemic Heart Disease in Women 569

Rheumatologic conditions
Women are also disproportionately affected by inflammatory and autoimmune condi-
tions which confer a higher lifetime risk of IHD and are also considered ASCVD risk
enhancers. Patients with lupus have a three- to fourfold increased risk of CV events
and death.22 Inflammation is important in the pathogenesis of atherosclerosis and
may explain the increased risk in these patients.
Other risk factors affecting women disproportionately include chest wall radiation in
patients with breast cancer, psychosocial risk factors,23 including poor mental
health24 and low socioeconomic status.25

PRESENTATION

Ischemic heart disease can present as acute coronary syndrome (ACS) or as chronic
disease with stable symptoms of angina pectoris. The definition of “typical” angina
pectoris is based on the traditional paradigm of obstructive coronary artery disease
that was commonly noted in men. Although chest pain is the most common presen-
tation for both sexes, there are important differences that need to be considered.
Highlighted in the following sections are sex differences in the presentation of acute
coronary syndrome and chronic ischemic heart disease.

Acute Presentations
The most common symptom of acute ischemic heart disease is chest discomfort; how-
ever, women are known to have a broader range of symptoms on presentation. Young
women (aged 35–54 years) are 50% more likely than similarly aged men to present
without chest pain when they have an ST elevation MI (STEMI).26,27 Although many
women with acute myocardial infarction (AMI) have nonobstructive disease (as dis-
cussed below), women with obstructive epicardial disease are more likely to suffer
from plaque erosion and embolization compared with plaque rupture in men.27 Of
note, women presenting with AMI are much less likely to receive guideline-
recommended therapies than men (lipid-lowering medications, dual antiplatelet ther-
apy, beta-blockers, angiotensin-converting enzyme [ACE]/angiogensin receptor
block [ARB]), and less likely to achieve door to balloon time of less than 90 minutes.2
This discrepancy is likely multifactorial from delayed diagnosis and incomplete under-
standing of the spectrum of ischemic disease, these discrepancies are even more sig-
nificant in young women.

MI with no obstructive coronary arteries


Women presenting with ACS are more likely than men to have no evidence of
obstructive disease on coronary angiography.27 MI with no obstructive coronary ar-
teries (MINOCA) is a working diagnosis. It encompasses many possible underlying
diagnoses and requires further investigation.28 In one international, multicenter
study, the use of optical coherence tomography and cardiac magnetic resonance
(CMR) identified a potential mechanism in 84.5% of women with a diagnosis of
MINOCA. Approximately three of four were determined to be of an ischemic cause
and the remainder of non-ischemic cause.29 Ischemic causes of MINOCA can
involve the epicardial and/or microvascular circulation. Epicardial causes of
MINOCA include plaque disruption, epicardial spasm, spontaneous coronary artery
dissection (SCAD), embolism, whereas microvascular causes include microvas-
cular spasm and supply demand mismatch secondary to microvascular disease.
Given the heterogeneity of the clinical entity, its treatment is largely dependent
on the underlying etiology.

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570 Grant & Sanghavi

Spontaneous coronary artery dissection


SCAD is defined as a non-iatrogenic and non-atherosclerotic separation of the layers of
an epicardial coronary wall by intramural hemorrhage with or without intimal tear. SCAD
likely represents less than 4% of all AMIs in women, but up to one-third of MIs in women
younger than 50 years. More than 90% of SCAD events occur in women.30 Diagnosis is
made by coronary angiography showing abrupt smooth tapering of the vessel due to
intramural hematoma or presence of an intimal flap.31 Accurate diagnosis is key
because management differs significantly from atherosclerotic disease with a prefer-
ence for conservative management in stable patients.31 Optimal medical treatment is
unknown. The use of antiplatelets is extrapolated from atherosclerotic disease man-
agement despite different pathophysiology. Management should target symptom
reduction because chest pain is common after the initial event and prevention of recur-
rence. The use of beta-blockade has been associated with reduced risk of recurrent
SCAD in one observational study.32 Statins are recommended based on atherosclerotic
risk.33 Head-to-pelvis cross-sectional imaging is recommended to evaluate for extra-
coronary vascular anomalies due to the high prevalence of arteriopathies in this popu-
lation. In addition, referral to cardiac rehab is recommended for all patients with SCAD.
Stress cardiomyopathy/Takotsubo
Stress cardiomyopathy, an ACS mimicker, presents as sudden and transient left ven-
tricular dysfunction, typically associated with left ventricular apical ballooning and aki-
nesis. Most cases (60%–90%) present after an emotional or physiologic trigger with a
predilection for the postmenopausal, elderly female.34,35 It is thought that microvas-
cular dysfunction may be the pathologic mechanism in Takotsubo, though there is
also an overlapping association reported with SCAD and myocardial bridging.36–39

Chronic Presentations
Chronic IHD in women most commonly presents as stable angina, independent of un-
derlying etiology.40 However, compared with men, women report broader symptomol-
ogy (ie, shortness of breath, nausea, epigastric pain) and are more likely to report
atypical symptoms such as fatigue, jaw pain, or dyspnea. Women present later into
their symptom onset or will have repeated visits with the medical system before diag-
nosis. Women with nonobstructive disease will have had a myriad of tests (stress test,
invasive angiography, computed tomography angiography [CTA]) and may be falsely
reassured or dismissed if they are negative.41

PATHOPHYSIOLOGY
Differences in Types of Disease
Although chronic IHD from obstructive epicardial disease is common, women with
angina disproportionally suffer from nonobstructive etiologies of ischemic heart
disease.3,18,40,42–44
Under the umbrella term of open artery ischemia (OAI),45 several stable clinical phe-
notypes have emerged.45
1. ANOCA (angina with non-obstructive coronary arteries)
2. INOCA (ischemia with non-obstructive coronary arteries)46
These clinical phenotypes are manifestations of several endotypes of disease (cor-
onary spasm, myocardial bridge, endothelial dysfunction, coronary microvascular
dysfunction [CMD], and microvascular spasm). These endotypes can be divided
anatomically into disease of the epicardial and microvascular circulation as discussed
below (Fig. 1).

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Ischemic Heart Disease in Women 571

Fig. 1. Etiologies of chronic IHD categorized anatomically.

Epicardial Circulation
Atherosclerosis
Women are more likely to have diffuse and nonobstructive atherosclerosis noted on cor-
onary angiogram. Although focally nonobstructive, diffuse disease can be functionally
significant. The WISE study, in women with stable symptomatic CAD, demonstrated
that 57% of women with symptoms and signs of ischemia had nonobstructive CAD
on angiography.47 Nonobstructive CAD is defined as less than 50% diameter stenosis
of all major epicardial vessels and is at least twice as prevalent in women compared
with men.15 The sex-specific difference in incidence of obstructive atherosclerosis is
most notable earlier in life and becomes less significant with age (and menopause).5
Epicardial artery vasospasm and endothelial dysfunction
Prinzmetal angina is a clinical syndrome of recurrent angina associated with myocardial
ischemia from coronary spasm. Chest pain often occurs at rest or at night; however, ex-
ertional symptoms in the morning have also been reported.46 Smoking is an established
risk factor where diabetes and HTN are not. On invasive testing, coronary spasm is
defined as severe (>90%) constriction of the coronary artery after administration of
acetylcholine with ECG changes indicative of ischemia and associated angina.
Endothelial dysfunction is also diagnosed on invasive testing with administration of
acetylcholine and is diagnosed in the setting of constriction of the epicardial vessel
(>0% to <90%) with acetylcholine instead of the expected vasodilation in normal
vasculature.
Myocardial bridge
This is a congenital anomaly where a segment of epicardial vessel traverses through
the myocardium and is thus compressed during systole. The degree of compression is
not predictable of the hemodynamic effects. Most commonly, the bridge overlies the
left anterior descending artery. Myocardial bridges are common and are reported in
25% of autopsies and CT angiograms. Although most are not hemodynamically or
clinically significant, they can been associated with acute and chronic IHD.37

Microcirculation
Microvascular spasm
Vasospastic angina can also be due to microvascular spasm. Challenging to diag-
nose, microvascular spasm is diagnosed by ECG changes and angina in the absence
of epicardial constriction with administration of acetylcholine invasively; however,
functionally should show decreased coronary blood flow and increased sinus lactate
accumulation after administration of acetylcholine.

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572 Grant & Sanghavi

Coronary microvascular dysfunction


The coronary microcirculation (arterioles and pre-arterioles) represents 90% of the
coronary circulating blood volume and is the primary regulator of coronary blood
flow. CMD can be defined as abnormal microvascular flow responses or abnormal
microvascular resistance45,48,49 and has multiple underlying etiologies. These include
structural and functional abnormalities as well as external causes (myocardial and sys-
temic).45 Structural etiologies include microvascular luminal obstruction (ie, microem-
bolization during ACS), vascular wall infiltration, vascular remodeling (ie, hypertrophic
cardiomyopathy), perivascular fibrosis, or rarefaction, whereas functional etiologies
include endothelial, smooth muscle, or autonomic dysfunction.5 CMD can be diag-
nosed in the noninvasively with decreased coronary flow reserve (coronary flow
reserve [CFR] <2.0–2.5) on PET imaging or invasively with abnormal microvascular
resistance (index of microvascualr resistance [IMR] <25 or hyperemic microvascular
resistance [hMR]<2.0) on coronary function testing.40

Diagnostic Testing in Stable IHD


Evaluation of obstructive disease
Risk stratification of chest pain before test selection helps determine pretest probabil-
ity of disease. Traditional risk scores (ie, Framingham and Diamond and Forrester)
tend to overestimate women’s risk for obstructive coronary disease. Young age signif-
icantly lowers pretest probability of detecting IHD. Thus, young women with multiple
risk factors or risk enhancers (ie, hypertensive disorders of pregnancy, early meno-
pause, diabetes)50 should have more nuanced risk assessment. Newer risk scores
should be considered for more accurate contemporary risk assessment of ischemic
heart disease.51–54 Current risk assessment can help identify low-risk patients not
requiring additional diagnostic testing for obstructive CAD.53

Choice of initial diagnostic testing


Choosing the appropriate diagnostic test for evaluation of ischemic heart disease in
women depends on several factors such as test availability, local expertise, patient’s
body habitus, and ability to exercise.
The 2021 chest pain guidelines give coronary CTA (CCTA) and stress testing both
class I indications in patients with intermediate or high pretest probability and no
established coronary disease. Both should be considered and have intrinsic advan-
tages and disadvantages; however, there are some sex differences in noninvasive
stress testing that should be considered.
In a sub-study of PROMISE evaluating the association between sex and noninvasive
testing results and adverse events (composite of death, myocardial infarction, and un-
stable angina), women were significantly less likely to have an abnormal CCTA (>70%
stenosis) compared with a positive stress test. CCTA was less likely to be positive
compared with exercise ECG and nuclear stress (OR: 0.66, P < .001) but not
compared with stress echocardiography.55 Women with a positive CCTA were more
strongly associated with clinical events than a positive stress test suggesting it is a
better predictor of adverse events.56
In addition, CCTA can help detect nonobstructive atherosclerotic plaque, which is
associated with increased mortality compared with those without CAD. Data from
the CAC consortium showed that women with larger and more numerous calcified le-
sions on CCTA had a 2.2-fold higher CVD mortality compared with men suggesting a
higher relative risk in women compared with men.55,56
Future guidelines may provide sex-specific recommendations for stress testing as
the nuanced differences between men and women are better understood.

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Ischemic Heart Disease in Women 573

Functional coronary assessment


For patients with persistent symptoms, evidence of ischemia, and no obstructive dis-
ease on imaging, PET stress testing and stress CMR may provide additional noninva-
sive imaging options for the evaluation of persistent chest pain symptoms and
nonobstructive disease to evaluate for microvascular dysfunction. These are both
given a 2a recommendation in the 2021 Chest Pain guidelines.
Coronary function testing is an invasive option to evaluate for microvascular
dysfunction but provides the additional opportunity to assess for endothelial depen-
dent dysfunction with the administration of acetylcholine.

Management
Historically, ischemic burden on testing and angina symptoms have thought to be
closely linked and targeting ischemia would also treat angina.
However, recent studies have shown that angina symptoms/severity are not directly
associated with the presence of ischemia: a discordance not well understood. In the
CIAO-ISCHEMIA trial, it was found that among women with INOCA, improvement in
ischemia (23%) and angina (43%) were common at 1 year but were not correlated.57
This highlights the importance of considering both ischemia and angina when manag-
ing a patient with ischemic heart disease.

Pharmacotherapy
For traditional atherosclerotic disease, women should be treated aggressively with
secondary prevention interventions such aspirin, statins, cardiac rehabilitation.
Pharmacotherapy for OAI should target the underlying endotype (Fig. 2). The Cor-
MICA trial tested the use of an invasive diagnostic strategy in angina and nonobstruc-
tive coronary artery disease and was able to show an improvement in Seattle Angina
Questionnaire and Quality of life.58

Fig. 2. Treatment pathways for patients with ANOCA. This figure includes therapies for pa-
tients with ANOCA based on endotype. ACE, angiotensin-converting enzyme; ANOCA,
angina with nonobstructive coronary arteries; CCBs, calcium channel blockers; EECP,
enhanced external counterpulsation; GLP-1, glucagon-like peptide-1; PDE-5, phosphodies-
terase 5 inhibitors; SLNTG, sublingual nitroglycerin; TCA/SSRI, tricyclic antidepressants/selec-
tive serotonin reuptake inhibitors. (Adapted from Smilowitz NR, Prasad M, Widmer RJ, et al.
Comprehensive Management of ANOCA, Part 2—Program Development, Treatment, and
Research Initiatives. J Am Coll Cardiol. 2023;82(12):1264-1279. https://doi.org/10.1016/j.
jacc.2023.06.044)

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574 Grant & Sanghavi

The recent JACC State of the Art Review of ANOCA outlines treatment strategies for
individual endotypes (see Fig. 2). Lifestyle changes and statins are the cornerstone
therapy for all endotypes, but additional treatment needs to be individualized.59
For coronary microvascular dysfunction, first-line therapy includes nonselective
beta blockade, angiotensin converting enzyme inhibitor (ACE-I), and sublingual nitro-
glycerin. Ranolazine, calcium channel blockers, and ivabradine can also be consid-
ered. The second line includes ranolazine, calcium channel blockers, and nitrates.59
For vasospasm (both epicardial and microvascular), the mainstay of therapy in-
cludes calcium channel blockers and short-acting nitrates.59 For microvascular
spasm, ACE-inhibitors should also be considered.
For myocardial bridging, beta blockade or calcium channel blockers are the treat-
ment of choice and nitrates should be avoided as it is thought to dilate the proximal
and distal segments of the compressed artery and can worsen the resulting systolic
stenosis. Percutaneous coronary intervention (PCI) or surgical myotomy is the surgical
intervention of choice and should be considered on a case-by-case basis.36,37
For endothelial dysfunction, nitrates and calcium channel blockers should be
considered.

Considerations in Pregnancy
Acute presentation in pregnancy
AMI is uncommon in women of reproductive age. However, pregnancy increases the
risk three- to fourfold and is associated with significant morbidity and mortality.60–62
The recent reported case fatality rate is approximately 5%.60 There is a higher inci-
dence of myocardial infarction with increasing maternal age.60 Acute MIs are most
common in the third trimester or postpartum period. Approximately 25% of women
present with an STEMI and 75% with an non-ST elevation MI (NSTEMI). The anterior
wall is most commonly involved (69% of cases). The mechanism of injury is most
commonly due to coronary dissection (43%), followed by atherosclerosis (27%) and
thrombosis (17%).63

Chronic ischemic heart disease


Established coronary disease is not an absolute contraindication to pregnancy. How-
ever, it is a risk predictor for maternal cardiac complications in the CARPREG II risk
index.64 The associated risk depends on several factors including residual left ventric-
ular function and ongoing myocardial ischemia. It has been recommended that
women wait at least 1-year post-revascularization or postinfarction before preg-
nancy65,66 and should undergoing cardiac testing for risk stratification prior as part
of preconception counseling.

SUMMARY

Over the last decade, we have gained a better understanding of sex-based differences
in ischemic heart disease but application in clinical practice is still limited. With
increased testing availability, improved insurance coverage for testing, and develop-
ment of more targeted treatment options, there is hope that the entire spectrum of
ischemic heart disease will be better understood and optimally treated.

CLINICS CARE POINTS

 Review sex-specific risk factors when evaluating a woman’s risk for ischemic heart disease.

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Ischemic Heart Disease in Women 575

 Consider the entire spectrum of ischemic heart disease in patients presenting with angina.
 MINOCA is a working diagnosis requiring further investigation.

REFERENCES

1. Hemingway H, Langenberg C, Damant J, et al. Prevalence of Angina in Women


Versus Men. Circulation 2008;117(12). https://doi.org/10.1161/circulationaha.
107.720953.
2. Gijsberts CM, Agostoni P, Hoefer IE, et al. Gender differences in health-related
quality of life in patients undergoing coronary angiography. Open Heart 2015;
2(1). https://doi.org/10.1136/openhrt-2014-000231.
3. Schmidt KMT, Nan J, Scantlebury DC, et al. Stable Ischemic Heart Disease in
Women. Curr Treat Options Cardiovasc Med 2018;20(9). https://doi.org/10.
1007/s11936-018-0665-4.
4. Mehilli J, Presbitero P. Coronary artery disease and acute coronary syndrome in
women. Heart 2020;106(7). https://doi.org/10.1136/heartjnl-2019-315555.
5. Reynolds HR, Bairey Merz CN, Berry C, et al. Coronary arterial function and dis-
ease in women with no obstructive coronary arteries. Circ Res 2022;130(4).
https://doi.org/10.1161/CIRCRESAHA.121.319892.
6. Sanghavi M, Gulati M. Sex differences in the pathophysiology, treatment, and out-
comes in IHD. Curr Atheroscler Rep 2015;17(6). https://doi.org/10.1007/s11883-
015-0511-z.
7. Hiteshi AK, Li D, Gao Y, et al. Gender differences in coronary artery diameter are
not related to body habitus or left ventricular mass. Clin Cardiol 2014;37(10).
https://doi.org/10.1002/clc.22310.
8. Taqueti VR. Sex differences in the coronary system. Adv Exp Med Biol 2018;1065.
https://doi.org/10.1007/978-3-319-77932-4_17.
9. Aggarwal NR, Patel HN, Mehta LS, et al. Sex differences in ischemic heart dis-
ease: advances, obstacles, and next steps. Circ Cardiovasc Qual Outcomes
2018;11(2). https://doi.org/10.1161/CIRCOUTCOMES.117.004437.
10. Yusuf PS, Hawken S, Ôunpuu S, et al. Effect of potentially modifiable risk factors
associated with myocardial infarction in 52 countries (the INTERHEART study):
Case-control study. Lancet 2004;364(9438). https://doi.org/10.1016/S0140-
6736(04)17018-9.
11. Geraghty L, Figtree GA, Schutte AE, et al. Cardiovascular disease in women:
from pathophysiology to novel and emerging risk factors. Heart Lung Circ
2021;30(1). https://doi.org/10.1016/j.hlc.2020.05.108.
12. Kaminski P, Szpotanska-Sikorska M, Wielgos M. Cardiovascular risk and the use
of oral contraceptives. Neuroendocrinol Lett 2013;34(7).
13. Garovic VD, Dechend R, Easterling T, et al. Hypertension in pregnancy: diag-
nosis, blood pressure goals, and pharmacotherapy: a scientific statement from
the American heart association. Hypertension 2022;79(2). https://doi.org/10.
1161/HYP.0000000000000208.
14. Mulvagh SL, Mullen KA, Nerenberg KA, et al. The Canadian Women’s Heart
Health Alliance Atlas on the epidemiology, diagnosis, and management of cardio-
vascular disease in women — chapter 4: sex- and gender-unique disparities:
CVD across the lifespan of a woman. CJC Open 2022;4(2). https://doi.org/10.
1016/j.cjco.2021.09.013.

Downloaded for Anonymous User (n/a) at MARA University of Technology from ClinicalKey.com by Elsevier on April 08,
2024. For personal use only. No other uses without permission. Copyright ©2024. Elsevier Inc. All rights reserved.
576 Grant & Sanghavi

15. Pravda NS, Karny-Rahkovich O, Shiyovich A, et al. Coronary artery disease in


women: A comprehensive appraisal. J Clin Med 2021;10(20). https://doi.org/10.
3390/jcm10204664.
16. Young L, Cho L. Unique cardiovascular risk factors in women. Heart 2019;
105(21). https://doi.org/10.1136/heartjnl-2018-314268.
17. O’Kelly AC, Michos ED, Shufelt CL, et al. Pregnancy and reproductive risk factors
for cardiovascular disease in women. Circ Res 2022;130(4). https://doi.org/10.
1161/CIRCRESAHA.121.319895.
18. Samad F, Agarwal A, Samad Z. Stable ischemic heart disease in women: Current
perspectives. Int J Womens Health 2017;9. https://doi.org/10.2147/IJWH.S107372.
19. Naftolin F, Friedenthal J, Nachtigall R, et al. Cardiovascular health and the meno-
pausal woman: The role of estrogen and when to begin and end hormone treat-
ment [version 1; peer review: 3 approved]. F1000Res 2019;8. https://doi.org/10.
12688/f1000research.15548.1.
20. Cho L, Davis M, Elgendy I, et al. Summary of updated recommendations for pri-
mary prevention of cardiovascular disease in women: JACC state-of-the-art re-
view. J Am Coll Cardiol 2020;75(20). https://doi.org/10.1016/j.jacc.2020.03.060.
21. Nappi RE, Chedraui P, Lambrinoudaki I, et al. Menopause: a cardiometabolic
transition. Lancet Diabetes Endocrinol 2022;10(6). https://doi.org/10.1016/
S2213-8587(22)00076-6.
22. Ajeganova S, Hafström I, Frostegård J. Patients with SLE have higher risk of car-
diovascular events and mortality in comparison with controls with the same levels
of traditional risk factors and intima-media measures, which is related to accumu-
lated disease damage and antiphospholipid syndrome: A case-control study
over 10 years. Lupus Sci Med 2021;8(1). https://doi.org/10.1136/lupus-2020-
000454.
23. Vogel B, Acevedo M, Appelman Y, et al. The Lancet women and cardiovascular
disease Commission: reducing the global burden by 2030. Lancet 2021;397:
10292. https://doi.org/10.1016/S0140-6736(21)00684-X.
24. Jespersen L, Abildstrøm SZ, Hvelplund A, et al. Persistent angina: Highly preva-
lent and associated with long-term anxiety, depression, low physical functioning,
and quality of life in stable angina pectoris. Clin Res Cardiol 2013;102(8). https://
doi.org/10.1007/s00392-013-0568-z.
25. Hamad R, Penko J, Kazi DS, et al. Association of low socioeconomic status with
premature coronary heart disease in US adults. JAMA Cardiol 2020;5(8). https://
doi.org/10.1001/jamacardio.2020.1458.
26. Minissian MB, Mehta PK, Hayes SN, et al. Ischemic heart disease in young
women: JACC review topic of the week. J Am Coll Cardiol 2022;80(10). https://
doi.org/10.1016/j.jacc.2022.01.057.
27. Mehta LS, Beckie TM, DeVon HA, et al. Acute myocardial infarction in women : a
scientific statement from the american heart association. Circulation 2016;133(9).
https://doi.org/10.1161/CIR.0000000000000351.
28. Tamis-Holland JE, Jneid H, Reynolds HR, et al. Contemporary diagnosis and
management of patients with myocardial infarction in the absence of obstructive
coronary artery disease: a scientific statement from the american heart associa-
tion. Circulation 2019;139(18). https://doi.org/10.1161/CIR.0000000000000670.
29. Maehara A, Kwong RY, et al. Coronary optical coherence tomography and car-
diac magnetic resonance imaging to determine underlying causes of myocardial
infarction with nonobstructive coronary arteries in women. Circulation 2021;143:
624–40. Circulation. 2023;147(8). doi:10.1161/CIR.0000000000001132.

Downloaded for Anonymous User (n/a) at MARA University of Technology from ClinicalKey.com by Elsevier on April 08,
2024. For personal use only. No other uses without permission. Copyright ©2024. Elsevier Inc. All rights reserved.
Ischemic Heart Disease in Women 577

30. Mahmoud AN, Taduru SS, Mentias A, et al. Trends of incidence, clinical presen-
tation, and in-hospital mortality among women with acute myocardial infarction
with or without spontaneous coronary artery dissection: a population-based anal-
ysis. JACC Cardiovasc Interv 2018;11(1). https://doi.org/10.1016/j.jcin.2017.
08.016.
31. Kim ESH. Spontaneous coronary-artery dissection. N Engl J Med 2020;383(24):
2358–70.
32. Saw J, Humphries K, Aymong E, et al. Spontaneous coronary artery dissection:
clinical outcomes and risk of recurrence. J Am Coll Cardiol 2017;70(9). https://
doi.org/10.1016/j.jacc.2017.06.053.
33. Hayes SN, Kim CESH, Saw J, et al. Spontaneous coronary artery dissection: cur-
rent state of the science: a scientific statement from the american heart associa-
tion. Circulation 2018;137(19). https://doi.org/10.1161/CIR.0000000000000564.
34. Cheema AN, Yanagawa B, Verma S, et al. Myocardial infarction with nonobstruc-
tive coronary artery disease (MINOCA): A review of pathophysiology and man-
agement. Curr Opin Cardiol 2021;36(5):589–96.
35. Lyon AR, Citro R, Schneider B, et al. Pathophysiology of Takotsubo syndrome:
JACC State-of-the-art review. J Am Coll Cardiol 2021;77(7). https://doi.org/10.
1016/j.jacc.2020.10.060.
36. Corban MT, Hung OY, Eshtehardi P, et al. Myocardial bridging: Contemporary un-
derstanding of pathophysiology with implications for diagnostic and therapeutic
strategies. J Am Coll Cardiol 2014;63(22). https://doi.org/10.1016/j.jacc.2014.
01.049.
37. Sternheim D, Power DA, Samtani R, et al. Myocardial bridging: diagnosis, func-
tional assessment, and management: JACC state-of-the-art review. J Am Coll
Cardiol 2021;78(22). https://doi.org/10.1016/j.jacc.2021.09.859.
38. Kegai S, Sato K, Goto K, et al. Coexistence of spontaneous coronary artery
dissection, takotsubo cardiomyopathy, and myocardial bridge. JACC Case Rep
2021;3(2). https://doi.org/10.1016/j.jaccas.2020.11.042.
39. Hausvater A, Smilowitz NR, Saw J, et al. Spontaneous coronary artery dissection
in patients with a provisional diagnosis of takotsubo syndrome. J Am Heart Assoc
2019;8(22). https://doi.org/10.1161/JAHA.119.013581.
40. Samuels BA, Shah SM, Widmer RJ, et al. Comprehensive management of
ANOCA, part 1—definition, patient population, and diagnosis: JACC state-of-
the-art review. J Am Coll Cardiol 2023;82(12):1245–63.
41. Dean J, Cruz SD, Mehta PK, et al. Coronary microvascular dysfunction: Sex-
specific risk, diagnosis, and therapy. Nat Rev Cardiol 2015;12(7). https://doi.
org/10.1038/nrcardio.2015.72.
42. Kunadian V, Chieffo A, Camici PG, et al. An EAPCI expert consensus document
on ischaemia with non-obstructive coronary arteries in collaboration with Euro-
pean society of cardiology working group on coronary pathophysiology & micro-
circulation endorsed by coronary vasomotor disorders international study group.
Eur Heart J 2020;41(37):3504–20.
43. Reeh J, Therming CB, Heitmann M, et al. Prediction of obstructive coronary artery
disease and prognosis in patients with suspected stable angina. Eur Heart J
2019;40(18). https://doi.org/10.1093/eurheartj/ehy806.
44. Ford TJ, Corcoran D, Berry C. Stable coronary syndromes: Pathophysiology,
diagnostic advances and therapeutic need. Heart 2018;104(4):284–92.
45. Pepine CJ. ANOCA/INOCA/MINOCA: Open artery ischemia. Am Heart J: Cardiol
Res Pract 2023;26. https://doi.org/10.1016/j.ahjo.2023.100260.

Downloaded for Anonymous User (n/a) at MARA University of Technology from ClinicalKey.com by Elsevier on April 08,
2024. For personal use only. No other uses without permission. Copyright ©2024. Elsevier Inc. All rights reserved.
578 Grant & Sanghavi

46. Kenkre TS, Malhotra P, Johnson BD, et al. Ten-year mortality in the wise study
(women’s ischemia syndrome evaluation). Circ Cardiovasc Qual Outcomes
2017;10(12). https://doi.org/10.1161/CIRCOUTCOMES.116.003863.
47. Beltrame JF, Crea F, Kaski JC, et al. International standardization of diagnostic
criteria for vasospastic angina. Eur Heart J 2017;38(33). https://doi.org/10.
1093/eurheartj/ehv351.
48. Camici PG, Crea F. Coronary microvascular dysfunction. N Engl J Med 2007;
356(8). https://doi.org/10.1056/nejmra061889.
49. Ford TJ, Ong P, Sechtem U, et al. Assessment of vascular dysfunction in patients
without obstructive coronary artery disease: why, how, and when. JACC Cardio-
vasc Interv 2020;13(16). https://doi.org/10.1016/j.jcin.2020.05.052.
50. Juarez-Orozco LE, Saraste A, Capodanno D, et al. Impact of a decreasing pre-
test probability on the performance of diagnostic tests for coronary artery dis-
ease. Eur Heart J Cardiovasc Imaging 2019;20(11). https://doi.org/10.1093/
ehjci/jez054.
51. Winther S, Schmidt SE, Mayrhofer T, et al. Incorporating coronary calcification
into pre-test assessment of the likelihood of coronary artery disease. J Am Coll
Cardiol 2020;76(21). https://doi.org/10.1016/j.jacc.2020.09.585.
52. Gulati M, Levy PD, Mukherjee D, et al. 2021 AHA/ACC/ASE/CHEST/SAEM/SCCT/
SCMR guideline for the evaluation and diagnosis of chest pain. J Cardiovasc
Comput Tomogr 2022;16(1). https://doi.org/10.1016/j.jcct.2021.11.009.
53. Sanghavi M, Parikh NI. Harnessing the power of pregnancy and pregnancy-
related events to predict cardiovascular disease in women. Circulation 2017;
135(6). https://doi.org/10.1161/CIRCULATIONAHA.117.026890.
54. Reynolds HR, Hausvater A, Carney K. Test selection for women with suspected
stable ischemic heart disease. J Womens Health 2018;27(7). https://doi.org/10.
1089/jwh.2017.6587.
55. Pagidipati NJ, Hemal K, Coles A, et al. Sex differences in functional and CT angi-
ography testing in patients with suspected coronary artery disease. J Am Coll
Cardiol 2016;67(22). https://doi.org/10.1016/j.jacc.2016.03.523.
56. Rodriguez Lozano PF, Rrapo Kaso E, Bourque JM, et al. Cardiovascular imaging
for ischemic heart disease in women: time for a paradigm shift. JACC Cardiovasc
Imaging 2022;15(8). https://doi.org/10.1016/j.jcmg.2022.01.006.
57. Reynolds HR, Picard MH, Spertus JA, et al. Natural history of patients with
ischemia and no obstructive coronary artery disease: The CIAO-ISCHEMIA
study. Circulation 2021;144(13). https://doi.org/10.1161/CIRCULATIONAHA.120.
046791.
58. Ford TJ, Stanley B, Good R, et al. Stratified medical therapy using invasive cor-
onary function testing in angina: the CorMicA trial. J Am Coll Cardiol 2018;
72(23). https://doi.org/10.1016/j.jacc.2018.09.006.
59. Smilowitz NR, Prasad M, Widmer RJ, et al. Comprehensive management of
ANOCA, part 2—program development, treatment, and research initiatives.
J Am Coll Cardiol 2023;82(12):1264–79.
60. James AH, Jamison MG, Biswas MS, et al. Acute myocardial infarction in preg-
nancy: A United States population-based study. Circulation 2006;113(12).
https://doi.org/10.1161/CIRCULATIONAHA.105.576751.
61. Pacheco LD, Saade GR, Hankins GDV. Acute myocardial infarction during preg-
nancy. Clin Obstet Gynecol 2014;57(4). https://doi.org/10.1097/GRF.0000000000
000065.
62. Roth A, Elkayam U. Acute myocardial infarction associated with pregnancy. J Am
Coll Cardiol 2008;52(3). https://doi.org/10.1016/j.jacc.2008.03.049.

Downloaded for Anonymous User (n/a) at MARA University of Technology from ClinicalKey.com by Elsevier on April 08,
2024. For personal use only. No other uses without permission. Copyright ©2024. Elsevier Inc. All rights reserved.
Ischemic Heart Disease in Women 579

63. Elkayam U, Jalnapurkar S, Barakkat MN, et al. Pregnancy-associated acute myocar-


dial infarction: a review of contemporary experience in 150 cases between 2006 and
2011. Circulation 2014;129(16). https://doi.org/10.1161/CIRCULATIONAHA.113.
002054.
64. Silversides CK, Grewal J, Mason J, et al. Pregnancy outcomes in women with
heart disease: the CARPREG II study. J Am Coll Cardiol 2018;71(21). https://
doi.org/10.1016/j.jacc.2018.02.076.
65. Regitz-Zagrosek V, Roos-Hesselink JW, Bauersachs J, et al. 2018 ESC Guidelines
for the management of cardiovascular diseases during pregnancy. Eur Heart J
2018;39(34). https://doi.org/10.1093/eurheartj/ehy340.
66. Wilson AM, Boyle AJ, Fox P. Management of ischaemic heart disease in women of
child-bearing age. Intern Med J 2004;34(12). https://doi.org/10.1111/j.1445-
5994.2004.00698.x.

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