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Vol.8, Issue 5; September-October 2023; 

ISSN: 2994-0524 

Impact Factor: 6.14 

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COMPREHENSIVE INSIGHTS INTO MICROVASCULAR ANGINA: A 

COMPARATIVE REVIEW OF PATHOGENESIS, DIAGNOSIS, AND 

TREATMENT" 
 

 
1Dr. Wei Li, Shaanxi and 2Dr. Xin Zhang, 
1University of Chinese Medicine, Xianyang, China 
2Department of Cardiovascular Medicine, Xi'an Traditional Chinese Medicine Hospital, Xi'an, China 

 

Abstract: Microvascular angina (MVA) is a complex syndrome characterized by angina symptoms and objective 

myocardial ischemia without obstructive coronary artery disease. This condition, often overlooked in the past, is 

gaining recognition due to advancements in coronary artery examination methods. MVA is associated with 

structural and functional abnormalities in myocardial coronary arteries with diameters less than 500 microns. This 

review explores the pathogenesis, diagnostic techniques, and Western medicine treatment options for MVA. A 

better understanding of MVA's underlying mechanisms and effective diagnostic and therapeutic approaches is 

essential for managing this condition. 

Keywords: Microvascular angina, myocardial ischemia, diagnostic methods, pathogenesis, treatment options 

 

 

Introduction  

Microvascular angina (hereinafter referred to as MVA) refers to the syndrome with typical or atypical 

symptoms of angina pectoris, accompanied by objective evidence of myocardial ischemia, and excluding 

subepicardial obstructive coronary artery disease and other cardiovascular diseases. From the perspective of 

Pathophysiology, this disease is due to the pathological changes of the structure and function of the inferior 

myocardial coronary artery with a diameter of less than 500 microns [1]. With the continuous optimization of 

modern technology in coronary artery examination methods, the diagnostic rate of microvascular angina is also 

increasing. This article provides a review of the pathogenesis, diagnostic methods, and Western medicine 

treatment of microvascular angina, in order to provide diagnostic and therapeutic ideas for this disease.  

1. Understanding of microvascular angina pectoris  

In 1967, Likoff et al. reported a group of patients with typical labor angina pectoris, positive exercise test and 

normal coronary angiography, which was the first report of such diseases in History of medicine. Subsequently, 

in 1973, Kemp et al. [2] first named this condition X syndrome. In 1985, Cannon renamed this disease 

microvascular angina. In 2013, the European Society of Cardiology Guidelines for the Treatment of Stable 

Coronary artery disease, the disease was named as abnormal microvascular function. The Chinese expert group 

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ISSN: 2994-0524 

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failed to include the structural abnormalities of this disease due to microvascular dysfunction, and therefore 

recommended renaming microvascular dysfunction to coronary microvascular disease (CMVD). In 2020, the 

European Society of Cardiology (ESC) and the European Society for Percutaneous Cardiovascular Intervention 

(EAPCI) jointly issued the "2020 European Expert Consensus on Non Obstructive Coronary Ischemic Disease 

(INOCA)", which refers to myocardial ischemia caused by coronary microcirculation disorders (CMD) as 

microvascular angina.  

Due to limitations in diagnostic and treatment methods in the early stages, positive treadmill exercise tests are 

often used as a diagnostic basis for microvascular angina. With the development of diagnostic and treatment 

technology, people's understanding of such diseases has become clearer. In fact, microvascular angina can only 

be diagnosed if there is a coronary microcirculation disorder. However, microvascular angina is only a subtype 

of non-obstructive coronary ischemic heart disease, and there are many reasons that can cause non obstructive 

coronary myocardial ischemia, such as epicardial vasospasm, myocardial bridge, etc. [3].  

2. The pathogenesis of microvascular angina  

The pathogenesis of microvascular angina can be divided into two types: abnormal coronary microvascular 

function and microvascular structural remodeling [4]. Simply put, one is functional and the other is structural [5], 

and both can exist simultaneously.  

2.1. Functional abnormalities  

Abnormal function refers to abnormal vasomotor function of coronary artery microvessels. The main reasons 

are (1) injury of vascular endothelium: dysfunction of vasomotor function of vascular endothelial factor, which is 

manifested by decreased diastolic function and increased sensitivity to Vasoconstriction stimuli. Mainly due to 

abnormal production and release of endothelial dependent relaxing factor nitric oxide (NO) [6] Smooth muscle 

dysfunction: mainly because endothelial cell independent active factor stimulates receptors on smooth muscle cell 

membrane and intracellular signal pathways, thereby causing abnormal microvascular relaxation [7] Microvascular 

spasm: Some vasoactive substances can cause diffuse microvascular contraction and myocardial ischemia, but 

have no effect on the epicardial coronary artery. For example, the lack of estrogen level will affect the autonomic 

nervous function, and the dysfunction of autonomic nervous function will make the myocardium α abnormal 

activation of Adrenergic receptor causes coronary microvascular contraction, which leads to myocardial ischemia 
[8].  

2.2. Structural abnormalities  

Coronary microvascular remodeling can be divided into three types: centripetal remodeling of Arteriole, 

increase of vascular wall lumen ratio, decrease of myocardial capillary density, etc. [9]. The main reason may be: 

hypertensive ventricular hypertrophy, hypertrophic cardiomyopathy patients usually have the problem of 

hypertrophy of smooth muscle cells and excessive deposition of collagen fiber cells, which is easy to cause the 

thickening of vascular intima [10]. It is worth mentioning that the reconstructed Arteriole will become extremely 

sensitive to the stimuli of Vasoconstriction, which will lead to dysfunction of vasoconstriction. Its response to 

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ISSN: 2994-0524 

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endothelial independent vasodilators (such as adenosine) can be manifested as a decrease in coronary flow reserve 

(CFR) and an increase in microcirculation resistance [11].  

3. Risk factors  

Traditional coronary heart disease risk factors such as hypertension, Dyslipidemia, smoking and diabetes may 

cause coronary microvascular disorders. (1) Hypertension: As mentioned earlier, hypertensive ventricular 

hypertrophy and hypertrophic cardiomyopathy can cause thickening of the intima of blood vessels, leading to the 

occurrence of microvascular structural abnormalities. Studies have shown that patients with microvascular angina 

have a significant increase in interventricular septal thickness compared to normal individuals, and the more 

significant the increase in interventricular septal thickness, the higher the risk of developing coronary 

microvascular angina [12] Dyslipidemia: Lipoprotein a is a risk factor of cardiovascular system. Studies have 

shown that the content of lipoprotein an in patients with microvascular angina is significantly higher than that in 

normal people, while apolipoprotein a is significantly lower. Apolipoprotein a may be a protective factor [13-16]. 

Some studies have also confirmed that lipoprotein associated Phospholipase A2 (Lp PLA 2) can promote the 

release of inflammatory factors, reduce the production of nitric oxide, and lead to dysfunction of coronary 

microvascular endothelial cells. A retrospective study by Zhang Yi and others found that the increase of serum 

Lp-PLA2 and homocysteine (Hcy) is an independent risk factor for coronary micro Vascular disease in middle-

aged and elderly women [17].  

In addition to traditional risk factors, risk variables related to inflammation also play a role in coronary 

microcirculation disorders [18,19]. Interleukin-1 (IL-1), Interleukin 6 (IL-6) tumor necrosis factor produced by 

microvascular smooth muscle cells- α (TNF- α) When inflammatory cells infiltrate, such growth factors and 

cytokines will cause abnormal proliferation and migration of smooth muscle cells [20]. Chen Bin et al. [21] 

monitored the high sensitivity C-reactive protein (hs-CRP) and coronary flow reserve (CFR) of 38 patients with 

microvascular angina using myocardial contrast echocardiography. The analysis results showed that the 

concentration of high sensitivity C-reactive protein was negatively correlated with coronary flow reserve.  

Besides, compared with obstructive Coronary artery disease, social Psychological stress is more involved in 

the occurrence of non obstructive coronary ischemic heart disease. A meta-analysis showed a significant 

correlation between social and psychological factors and ischemic heart disease, including microvascular angina. 

In the female population with ischemic heart disease, patients are often accompanied by psychological disorders 

such as anxiety and depression [22]. Microvascular angina, as a common type of ischemic heart disease, often 

coexists with psychological disorders such as anxiety and depression [23].  

4. Epidemiology  

At present, there is no epidemiological data of coronary micro Vascular disease with large sample data in 

China. The past small sample clinical trials showed that the incidence rate of coronary microvascular disease was 

between 45% and 60% in patients with no obvious obstruction in coronary angiography when there were signs of 

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 American Journal of Medical and Physical Education 
Vol.8, Issue 5; September-October 2023; 

ISSN: 2994-0524 

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myocardial ischemia. The incidence of microvascular angina in women is higher than that in men, especially in 

perimenopausal women [24,25].  

5. Western medicine diagnosis and treatment plan for microvascular angina  

5.1. Diagnostic indicators  

Based on the diagnostic protocols provided in Chinese and foreign guidelines, it is divided into invasive 

assessment and non-invasive assessment. At present, there is no direct method for observing human coronary 

microcirculation, and the existing evaluation indicators mainly rely on functional indicators: (1) CFR Coronary 

Flow Reserve refers to the ratio of the average peak flow rate in the maximum congestive state to the resting 

average peak flow rate under the action of various vasoactive stimuli (such as adenosine). It comprehensively 

reflects the blood flow status of the epicardial coronary artery and coronary artery microcirculation. The normal 

value of CFR is 3-5, and less than 2 indicates insufficient myocardial perfusion. (2) Index of Microcirculatory 

Resistance (IMR) refers to the distal coronary artery pressure under maximum congestion × Average conduction 

time in congested state.  

IMR ≥ 25 indicates microvascular dysfunction. (3) Fractional flow reserve (FFR) is the ratio of distal coronary 

artery mean pressure to aortic pressure in congested state, which can be used to evaluate whether blood flow is 

restricted in patients with obstructive coronary heart disease. FFR ≤ 0.8 indicates abnormalities.  

5.1.1. Invasive assessment  

It includes guide wire direct invasion test and Acetylcholine excitation test. Diagnostic options include 

thermaldilution and Doppler technology based guidewire. There is evidence to suggest that the Doppler may better 

reflect the state of insufficient microvascular perfusion than the thermaldilution [26]. Currently, the intracoronary 

Doppler flow guidewire is the gold standard for measuring CFR in traumatic techniques.The invasive diagnostic 

criteria for microvascular angina given in the guidelines are: diagnostic guide wire and adenosine test: FFR>0.8 

(non-obstructive)+CFR<2.0, IMR ≥ 25 (microcirculation disorders)+Acetylcholine provocation test: no or<90% 

of the internal diameter decreases, angina symptoms, ischemic ECG changes (indicating that there is myocardial 

ischemia without epicardial vasospasm).  

5.1.2. Non invasive assessment  

A variety of non-invasive techniques, including ECG exercise tolerance test, transthoracic Doppler 

echocardiography (TTDE), myocardial contrast echocardiography (MCE), myocardial perfusion imaging, 

Positron emission tomography (PET), and cardiac magnetic resonance imaging (CMR), can be used to detect 

local myocardial ischemia. PET is considered as a non-invasive gold standard for the diagnosis of coronary micro 

Vascular disease due to its high accuracy. Myocardial contrast-enhanced echocardiography (MCE) is widely used 

in clinical practice due to its real-time bedside operation, relatively low cost, and ability to quantitatively and 

qualitatively evaluate myocardial blood flow perfusion. The non-invasive diagnostic criteria provided in the 

guidelines are: objective evidence of myocardial ischemia in resting or under load conditions exists, and CFR 

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values<2.0 are measured and calculated using non-invasive examination equipment to illustrate coronary 

microcirculation disorders;  

If CFR ≥ 2.0, the stimulation test of Acetylcholine is feasible. If there is no spasm of the epicardial coronary artery 

but angina pectoris symptoms and ECG blood deficiency ST-T changes occur, microvascular angina pectoris can 

also be diagnosed.  

5.2. Medicine Treatment  

5.2.1. Traditional treatment:  

(1) Control of risk factors: angiotensin converting enzyme inhibitors (ACEI) and angiotensin receptor blockers 

(ARB) are the first choice for patients with hypertension, statins can be used for patients with 

hypercholesterolemia, active control of blood glucose in patients with diabetes can improve coronary 

microvascular endothelial function, and obesity can improve CFR by weight loss [27];  (2) Improvement of 

myocardial ischemia: drugs for stable microvascular angina are mainly used to reduce myocardial oxygen 

consumption, such as β-blockers. If β-blockers are not tolerated, ivabradine can be used instead [28].Drugs such as 

ACEI, ARB, and ranolazine have the effect of increasing CFR values and improving small vessel remodeling. 

For perimenopausal female patients with stable microvascular angina, estrogen supplementation can be combined. 

At present, studies [29] have reported that endothelial function is impaired in postmenopausal women with 

microvascular angina, and administering exogenous estradiol can increase peripheral blood flow in normal 

postmenopausal women. Calcium antagonists are recommended for angina pectoris, which is mainly caused by 

microvascular spasm. Nicorandil can effectively dilate subepicardial coronary arteries and coronary Arteriole, so 

it should be the first recommended drug for coronary microvascular angina [30].  

5.2.2. New Drug Treatments  

(1) Long term supplementation (6 months) of L-arginine (a precursor of NO) can improve endothelial function, 

coronary blood flow, and symptoms in non-obstructive CAD patients, but does not include CFR Oral 

administration of selective ETA receptor antagonist (Zibotan) can antagonize endothelin-1 induced 

Vasoconstriction, thereby improving vascular endothelial function [31]. (3) Phosphodiesterase is highly expressed 

in vascular smooth muscle cells, and inhibiting its secretion can promote vascular smooth muscle relaxation. Oral 

Phosphodiesterase inhibitor can rapidly increase CFR value of patients, and has anti-inflammatory and antiplatelet 

effects [32].  

6. Etiology, pathogenesis and treatment of traditional Chinese medicine  

There is no name for microvascular angina in traditional Chinese medicine, and there is currently no unified 

classification. According to its clinical symptoms, it should be classified into categories such as "chest pain" and 

"heartache". It shares similarities with traditional chest pain, but also has different characteristics. MVA patients 

are often associated with collateral obstruction. Traditional Chinese medicine believes that the causes of MVA 

related collateral lesions include the following four points: (1) the collateral itself is thin and curved, resulting in 

delayed circulation of qi and blood, which is prone to pathological changes of stasis [33]; (2) The pathogenic factors 

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ISSN: 2994-0524 

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of phlegm and dampness in the blood are often sticky and greasy, which can easily stagnate in the collaterals, 

leading to poor circulation of qi and blood in the veins Due to external cold pathogenic factors, the heart yang is 

insufficient, and the cold pathogenic factors of the six evils have the characteristics of attracting and stagnating. 

Therefore, the two colds interact with each other, causing the collaterals of the heart to be congested and urgent, 

and the qi and blood to be blocked [34] Qi is the leader of blood, and the operation of blood in the collaterals mainly 

depends on the promotion of qi. If Psychological stress is too high, anxiety and gas stagnation may occur, which 

may lead to unfavorable operation of qi, inability to promote blood operation, and blocked collaterals. Wu Yiling, 

an expert in collateral diseases in China, pointed out that according to the "theory of pathological changes in the 

venation vascular system", the concepts of venation, middle and small arteries, and microcirculation are highly 

consistent, so the abnormal function of the collateral homeostasis is similar to the vascular endothelial dysfunction 

called by modern medicine. Collateral deficiency is a state of contraction, contraction, and spasms caused by 

various factors such as external pathogens, excessive emotions, and overwork. It is one of the main pathological 

changes in collateral diseases. Modern medicine believes that a decrease in NO concentration and an increase in 

ET concentration in blood vessels are one of the pathological foundations of coronary artery spasm and endothelial 

dysfunction [35]. The urgency of collaterals is basically similar to the vasospasm in modern medicine, and vascular 

endothelial dysfunction and vasospasm can lead to blood hypercoagulability, microthrombosis formation, and 

even myocardial ischemia and necrosis [36]. This is consistent with the theory of "phlegm stasis obstructing 

collaterals" in traditional Chinese medicine. In summary, phlegm turbidity, qi stagnation, and blood stasis are the 

basic characteristics, so in terms of treatment, the characteristics of traditional Chinese medicine are to regulate 

qi, dissipate phlegm, and promote blood circulation and unblock collaterals.  

7. Summary and Outlook  

In summary, with the development of modern diagnostic and treatment technologies, the relevant pathogenesis 

and diagnosis and treatment plans of microvascular angina have become increasingly perfect, gradually evolving 

from the initial "X syndrome" to the widely recognized "microcirculation function and structural disorders". 

However, many underlying mechanisms have not yet been fully elucidated, and further development and 

popularization of modern diagnostic and treatment technologies are needed. More and more studies show that 

microvascular angina plays an important role in non-obstructive ischemic heart disease, and is closely related to 

cardiovascular diseases such as hypertrophic cardiomyopathy, diabetes heart disease and hypertensive heart 

disease. Therefore, the prevention and treatment of microvascular angina is an important issue that urgently needs 

attention. We hope to raise the attention of clinical colleagues to microvascular angina disease through this 

discussion, update relevant concepts, and conduct large-scale epidemiological investigations if necessary to 

optimize diagnostic plans and form a more standardized and complete diagnosis and treatment system.  

  

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