26 HOW TO TREAT: ISCHAEMIC HEART DISEASE IN WOMEN
26 HOW TO TREAT: ISCHAEMIC HEART DISEASE IN WOMEN
20 JUNE 2025 ausdoc. com. au flow-limiting stenoses; ie, the underlying cause of angina and ischaemia was not attributed to epicardial stenoses. 26 A large 2010 observational study of 400,000 patients with angina who had coronary angiograms reported that only 41 % of those with a positive non-invasive stress test had obstructive CAD. 27 In patients aged 50-59 with typical angina, 68 % of men and 87 % of women did not have obstructive CAD. 28 Other non-obstructive causes of angina and ischaemia include epicardial or microvascular coronary vasospasm, coronary microvascular dysfunction( CMD) and derangements of myocardial energy or metabolism. 29
The CorMicA trial found 45 % of patients presenting with angina or ischaemia did not have obstructive CAD at angiography, but nearly 90 % of this 45 % demonstrated objective evidence of coronary vasomotor dysfunction, including 81 % with CMD. 30
Thus, in a significant proportion of patients with suspected CAD, CMD or epicardial vasospasm contributes to angina. These functional mechanisms can also coexist with obstructive CAD. 31 INOCA / ANOCA is more frequent in women; about 50-70 % of women compared with 30-50 % of men undergoing coronary angiograms lack angiographic evidence of obstructive CAD. 32-34
Risk factors for IHD in women
Risk factors are divided into the traditional and non-traditional, including‘ sex specific’, and other under-recognised risk factors that affect women more( see figure 4). 30
UNIQUENESS OF CHEST PAIN IN WOMEN
CHEST pain is the most common symptom in women with ACS, with a prevalence similar to that of men. 36-38 Historically, women were thought to present with‘ atypical’ chest pain. 39 However, the 2021 chest pain guidelines discourage the use of‘ atypical’, as this can be angina without typical chest symptoms, and may imply that the chest pain is non-cardiac, and be misinterpreted as benign in nature. 40 The terms‘ cardiac,’‘ possibly cardiac’ and‘ non-cardiac’ are encouraged.
While chest pain is the most common symptom, women with MI are more likely to present with associated symptoms of shortness of breath, palpitations, fatigue, epigastric symptoms, and pain in the jaw, neck, arms or shoulders. 41, 42 Women were more likely to perceive their symptoms as due to stress or anxiety, with their healthcare professional concluding the symptoms were not heart related. 42
In stable patients with suspected CAD, chest pain was the primary symptom; women had a higher prevalence of associated symptoms, but healthcare professionals were more likely to characterise women as having a lower pretest probability of CAD when compared with men. 43
It is thus important to increase awareness of symptom recognition in both women and healthcare professionals. Some key recommendations from the 2021 chest pain guidelines on the uniqueness of chest pain in women appear in box 1. 40
ISCHAEMIA WITH NO OBSTRUCTIVE CAD
ABOUT 50 % of patients with chest pain and objective evidence of
Figure 1. Mechanisms of ischaemia.
Coronary microvascular dysfunction( CMD)
Impairs coronary physiology and myocardial blood flow in patients with risk factors
Causes microvascular angina and contributes to myocardial ischaemia in CAD
Platelets and coagulation
Systemic inflammatory and autoimmune diseases
Ischaemia with non-obstructive coronary artery disease( INCOA)
myocardial ischaemia( such as abnormal stress ECG, or an abnormal cardiac stress imaging test) have no
44, 45 obstructive CAD on angiography. This chest pain / chronic coronary syndrome is termed ischaemia with non-obstructive coronary arteries( INOCA). ANOCA is angina with non-obstructive coronary arteries, without demonstrable ischaemia.
ANOCA and INOCA are more common in women( 50-70 % compared with 30-50 % of men) undergoing coronary angiography for angina. 46 The mismatch between blood supply and myocardial oxygen demands leading to angina and ischaemia in ANOCA / INOCA are due to CMD or coronary vasospasm, or a combination.
The diagnosis of INOCA and stratification into‘ endotypes’ is made with invasive studies( coronary functional testing or functional coronary angiogram) or non-invasive( PET / MRI) methods.
ANOCA / INOCA is rarely correctly diagnosed and is associated with recurrent angina, decrease in quality of life( QoL), repeated
Inflammation
Transient vasospasm
Prinzmetal angina
Coronary artery stenosis
Myocardial ischaemia
Vasospastic angina( VSA)
• Non-obstructive coronary atherosclerosis is frequently present in INOCA.
• These mechanisms can overlap.
Myocardial bridge
Persistent vasospasm
Myocardial infarction
hospitalisations, unnecessary repeat coronary angiography and an increased risk of major adverse cardiovascular events( MACE) both shortand long-term. 24 Current treatment is tailored towards the specific endotype, but treatment remains elusive.
Microvascular angina( MVA) is the clinical manifestation of myocardial ischaemia caused by CMD. This may result from structural remodelling of the microvasculature or vasomotor disorders affecting the coronary arterioles, or both mechanisms. 47 Suspect CMD when exertional or rest angina is present in the absence of obstructive CAD and in association with myocardial ischaemia. 47
The diagnostic criteria for MVA appear in table 1. All four criteria must be present to diagnose MVA. Smoking, age, diabetes, hypertension and dyslipidaemia are associated with CMD. 48 Inflammatory diseases such as systemic lupus erythematosus( SLE) and rheumatoid arthritis( RA), which occur more often in women, are also associated with MVA, and there is evidence
Coronary microvascular dysfunction
Vascular spasm
Stable plaque
Reduction in fractional flow reserve
Demand ischaemia and angina
Adapted from Kunadian V et al 2020 24
Ischaemia with obstructive coronary artery disease
Atherosclerotic cardiovascular disease( ASCVD)
that psychosocial stress is also
49, 50 involved.
Epicardial vasospastic angina( VSA) is the clinical manifestation of myocardial ischaemia caused by abnormal vasoconstriction of one or more epicardial arteries, leading to a dynamic epicardial coronary artery obstruction. The diagnosis of VSA requires nitrate-responsive angina, transient ischaemic ECG changes( ST elevation 0.1mV or greater or ST depression 0.1mV or greater or new negative U waves) during the episodes, and demonstration of coronary artery spasm. 51 Coronary artery spasm is defined as transient total or subtotal coronary artery occlusion( more than 90 % constriction) with angina and ischaemic ECG changes either spontaneously or in response to a provocative stimulus( typically acetylcholine or hyperventilation). 52
Vasospastic angina is associated with recurrent disabling chest pain, AMI or sudden cardiac death. 53
MVA and VSA can coexist, and this is associated with a worse prognosis. 54
Vulnerable plaque
Plaque rupture thrombosis
Acute coronary syndromes / infarction
Box 1. Key recommendations on uniqueness of chest pain in women
• Women who present with chest pain are at risk of underdiagnosis; always consider potential cardiac causes.
• In a woman presenting with chest pain, obtain a history that emphasises accompanying symptoms that are more common in women with ACS.
• Do not describe chest pain as atypical; this is not helpful in determining the cause, and pain can be misinterpreted as benign in nature.
• Describe chest pain as cardiac, possibly cardiac or non-cardiac, because these terms are more specific to the potential underlying diagnosis.
Source: Gulati M at al 2021 40
Adapted from Kunadian V et al 2020 24
Figure 2. Mechanisms of myocardial ischaemia in INOCA and obstructive CAD.
Prevalence
In the absence of obstructive CAD, CMD has an estimated prevalence of up to 53 % in those undergoing non-invasive stress tests.
55, 56
In patients with suspected INOCA undergoing invasive evaluation, CMD and coronary vasospasm are diagnosed in up to four in five patients, with 50-80 % of these being female. 57-60 There is a higher prevalence of coronary vasospasm in Japanese and Taiwanese populations compared with western populations. 61, 62 Prevalence estimates will change as more centres evaluate for INOCA.
Clinical presentation
Patients with INOCA present with symptoms similar to angina with obstructive CAD( ie, chest pain), but may also present with breathlessness, pain between the shoulder blades, indigestion, nausea, extreme fatigue, weakness, vomiting and / or sleep disturbances. 63
Young and middle-aged women often do not present with classical