A potential protective element of myocardial bridge against severe obstructive atherosclerosis in the whole coronary system

Myocardial bridge (MB) is referred to muscle overlying intramyocardial segment of an epicardial coronary artery, usually in the middle segment of the left anterior descending coronary artery (LAD) [1, 2]. Some studies reported anatomical properties of MB on atherosclerosis evolution in LAD. Location, length, and thickness are closely interrelated, and longer or thicker MBs are located significantly proximally in LAD [3]. Its characteristic compression of the tunneled coronary segment is clinically silent in many cases but is of interesting to clinical researchers due to its association with myocardial ischemia [4, 5].

The golden standard of MB diagnosis in angiography is defined as systolic milking effect produced by systolic compression by the intramyocardial segment [6]. MB is the most common congenital coronary variation, and the prevalence of MB varies from less than 5% [1, 6] under angiography, to 23% with intravascular ultrasound (IVUS) [6], to 55.6% under autopsy [7] due to the reason that short and thin bridges causing little systolic compression are easy to be ignored [8].

The presence of MB can be associated with various complications such as angina, acute myocardial infarction, arrhythmias, and even sudden death [4, 9–18]. MB can also be considered a benign variation of coronary arteries [19], or a double-edged sword [5]. The cause of angina is generally thought to be a distinct reduction of coronary artery flow due to muscular compression during systole [5, 20, 21]. Previous studies have suggested that in the intramyocardial segments, the vessel is protected from obstructive atherosclerosis, however, it is not clear whether MB has positive or negative effects on obstructive atherosclerosis in the whole coronary artery system. In the present study, we aimed at exploring a clinical relationship between MB and severe obstructive atherosclerosis requiring treatment with percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG) in the whole coronary artery system.

Currently, many studies consider MB as a contributing factor in myocardial ischemia, angina, myocardial infarction and arrhythmia [4, 9–17]. However, less atherosclerotic lesions are found in bridge segments in contrast to non-bridged coronary arteries [18, 23–27]. Limited proof indicates that compression by contracting myocardial muscles may provide some potential anti-atherosclerotic mechanisms linked with the release of anticoagulant and growth factors [18]. However, the overall protective or detrimental role of MB in the whole coronary system and knowledge on the mechanisms are still desired.

According to previous studies, formation of atherosclerotic plaque can frequently be found at segment proximal to the bridge, while the intramural segment is typically absent [18, 23], but not in all cases [26]. As supported by a morphological observation of cholesterol-fed rabbits, foam cells and modified smooth muscle cells have the same distribution on a cellar level with atheromatous plaques at proximal segments but not at intramural segments [25]. Also, endothelial cells proximal to MB were arranged in a pavement-like, polygonal and flat appearance because of a high sheer stress [27]. These pathologic changes in proximal segment may be due to the accumulation of ApoB, proliferating cell nuclear antigens (PCNA) in smooth muscle cells and increased endothelial cell permeability [25].

Diagnosis of MB under coronary angiography is based on the typical “milking effect” and a “step down-step up” phenomenon induced by muscle compression during systole [6]. Though coronary angiography is now the gold standard and is most widely used in diagnosing MB, it has some technical restrictions compared with other new imaging techniques, such as intravenous ultrasound (IVUS), intracoronary Doppler ultrasound, multi-detector computed tomography, and intracoronary pressure devices [1, 3, 7]. In other words, the percentage of MB varies with different diagnostic method and equipment. In this retrospective study, the overall incidence of MB was 8.53%, but the female had higher morbidity of MB than the male (10.75% vs. 7.31%, P <  0.0001). In the non-SOCAD group, the rate of MB was much higher than that in the SOCAD group (16.05% vs. 1.84%, P <  0.0001); whereas, in patients with MB, the rate of SOCAD requiring treatment with PCI or CABG was much lower than that in patients without MB (11.42% vs 56.76%, P <  0.0001). Take this in account, we speculated that MB might produce a potential positive role against severe obstructive atherosclerosis in the whole coronary artery system. Accordingly, we analyzed the relationship between MB and severe obstructive atherosclerosis by adjusting for age, sex, hypertension, impaired glucose metabolism, hyperlipidemia, ischemic cerebrovascular diseases, and chronic kidney diseases. Based on our results, there seemed to be a clue that MB might produce a potential protective element against severe obstructive atherosclerosis in the whole coronary artery system (log-OR = − 2.134; P <  0.0001).

Hyperlipidemia is a significant risk factor of CAD, which is a wide-accepted truth [28]. In the present study, however, we observed that the rate of hyperlipidemia in SOCAD group was lower than that in non-SOCAD group. We must mention that, it is not interpreted from our result that hyperlipidemia is negatively associated with severe obstructive CAD because of the reasons that patients without SOCAD didn’t receive intensive lipid-lowering management, whereas patients with SOCAD (some of them had a long history of coronary heart disease) received an intensive lipid-lowering therapy even before admission according to the current guidelines.

Although the possible mechanisms of atherogenic protection of MB is unknown, there is still some supported evidence. Loukas et al. [18] found that the bridged segments demonstrated weaker proliferative activities of Ki-67 (a cellular marker for proliferation), and a decreased count of smooth muscle cells and macrophages. This phenomenon might be explained with that the MB-related contracting myocardium compression stimulates the release of anticoagulant and growth factors, which could produce a synergistic effect in preventing the endothelium from denudation, inflammation, and resultant atherosclerosis in vessels with MB and possibly in the whole coronary system. In addition, multi-slice CT scanning showed that the presence of MB was associated with a lower Agatston Calcium Score in the bridged segments [29]. The presence of an MB may also influence arterial tissue through the alteration of hemodynamic forces. According to previous study [24], any atherosclerosis in the MB-segment is suppressed histopathologically and ultrastructurally. Abrupt changes of endothelial cell morphology in the intima beneath the bridge were observed with scanning electron microscopy, which indicates that the arterial tissue beneath the bridge is protected by hemodynamic factors. In cholesterol-fed rabbits, the intima in the MB segment covered by myocardial tissue was free of atherosclerotic lesions, and the endothelial cells were spindle-shaped and engorged [25], which also indicates that the protective element of MB against atherosclerosis might be linked with an alteration of endothelial permeability due to hemodynamic force changes tending towards a higher shear stress. Based on the documented studies as above, the role of myocardial bridges to suppress coronary atherosclerosis might be potential, but it still deserves further scientific research in biochemical and pathophysiological fronts.

Despite the presence of MB can be associated with various complications such as angina, acute myocardial infarction, arrhythmias, and even sudden death [4, 9–17], it can also be considered a benign variation of coronary arteries [19]. So, the treatment of MB is still uncertain due to the lack of convincing evidence. In clinical practice, beta-blockers are usually the first choice of treatment in symptomatic patients [30], other treatments including coronary stents and surgical interventions such as myotomy or bypass are also considered a second-line option. According to a recent systematic review and pooled analysis raised by Enrico Cerrato and colleagues [31], patients with symptomatic isolated MB generally have a good long-term prognosis; pharmacological treatment alone, especially with beta-blockers, can improve angina in most cases. In other words, their study clearly supports that MB is a benign variation of coronary arteries.

In conclusion, our results provided a clue that MB might be acted as a potential protective element against severe obstructive atherosclerosis in the whole coronary artery system by adjusting for sex, age, diabetes mellitus, hypertension, and other risk factors, but it still needs further scientific research due to lack of convincing evidence.