Aortic valve sclerosis is more common in men than women. Leaflet thickening and risk of calcific AV damage doubles with every decade of life [4
]. After the age of 65 years the percentage of people with AVS in general population reaches 29% and increases to 40% in people older than 75 years, only to reach 48% to 57% in a population above 80 years [4
Calcific aortic sclerosis coexists with coronary artery disease in about 40% of patients. The risk of myocardial infarction is significantly larger in those patients than in case of coronary artery disease without coexisting AV damage [16
]. In a population-based MESA (Multi-Ethnic Study of Atherosclerosis)
study, which included people between 45 and 84 years old (mean 62 years), aortic valve calcifications (AVC) were found all together in 13% of subjects [17
]. This percentage increased with the severity of coronary artery calcification. In CCS examination, for values ranging: 1–99 Agatston units, 100–399 Agatston units and 400 or more Agatston units the frequency of AVC was 14%, 25% and 38%, respectively [17
]. It means, that the greater the degree of coronary artery calcification, the more likely it is to observe aortic valve calcification in computed tomography (). In other words, identification of calcifications on the aortic valve predicts with large probability the presence of coronary lesions. Aortic valve calcification is rare in the absence of coronary artery calcifications (about 5%) and, in such cases, is a manifestation of pathologies other than atherosclerosis.
Figure 1. Calcification of aortic valve leaflets shown in multi-slice computed tomography imaging. A fragment of coronary stent is visible in the right coronary artery (segment 2). Minute calcifications are also visible in the left anterior descending and circumflex (more ...)
Many observations suggest that aortic valve calcification is not a passive phenomenon. Endothelial cells and myofibroblasts, among other things, actively participate in it and the process itself is very similar to atherosclerotic arterial disease [18
], as evidenced by endothelial dysfunction accompanying AVS and histological picture of degenerated leaflets usually containing signs of chronic inflammation and extracellular matrix calcification [19
As long as 150 years ago Virchof and Rokitansky noted that vascular calcifications exhibit many similarities to osseous tissue. Newest studies corroborate that multipotential cells, such as fibroblasts and smooth muscle cells, participate in formation of calcifications due to the ability to differentiate into osteoblasts, which are involved in extracellular matrix calcification. Osteoblastic transformation of cells from the mesenchymal lineage is initiated by hemodynamic factors (oscillatory shear stress), leading to increased production of, i.a. BMP protein (Bone Morphogenic Protein),
as well as by metabolic disorders accompanying renal failure and diabetes such as: hyperphosphatemia, hypercalcemia and oxidative stress [21
An indirect argument for common pathomechanism of AVS and atherosclerosis is such that sclerosis and subsequent calcification of aortic valve leaflets is promoted by the same classical risk factors that cause endothelial dysfunction, as well as hemodynamic factors involving formation of secondary flows, where the vessel wall is exposed to low/oscillatory shear stress [22
]. Influence of flow-related (hemodynamic) factors on development of calcifications is evidenced by the fact, that they are formed on the aortic side of leaflets, which is exposed to turbulent flows and oscillatory shear stress, while the ventricular surface, subjected to laminar flow and physiological shear stress, is protected from atherosclerotic damage (, ) [24
Figure 2. Distribution of shear stress on aortic valve leaflets. Laminar flow and physiological shear stress on the ventricular surface of AV leaflets constitute a hemodynamic factor facilitating endothelial integrity and promoting production of anti-inflammatory (more ...)
Multi-slice computed tomography imaging. Atherosclerotic aortic wall calcification (right coronary sinus near the site of origin of right coronary artery). Partially calcified atherosclerotic plaque in the proximal right coronary artery.
Another example indicating the influence of hemodynamic factors on valvular damage and calcification is bicuspid valve, which is characterized by disrupted flow [25
]. With time, almost all patients with this congenital anomaly develop more or less severe AS. However, valvular damage occurs two decades earlier in comparison to a normal, tricuspid valve. Altered flow hemodynamics contributes to aortic dilatation, which often accompanies bicuspid aortic valve.
Endothelium exhibits several mechanisms of counteracting the adverse effects of flow (low/oscillatory shear stress). However, these mechanisms become impaired in the presence of numerous risk factors that lead to endothelial dysfunction. In such case, vascular wall becomes susceptible to damage caused by disrupted flow.
Calcific aortic valve damage is an important predictor of coronary artery disease. Cumulative amount of aortic valve and mitral ring calcifications demonstrated in computed tomography or ultrasound examination correlates with CCS [27
]. Pressman et al. [27
] express the view that presence of AVS in echocardiography suggests high likelihood of advanced atherosclerotic lesions in epicardial arteries and should be an indication for coronary artery disease evaluation. Messika-Zeiotum et al. [12
] demonstrated that the extent of coronary artery calcifications in EBCT is more pronounced in people with AVC regardless of sex and age. Respective CCS values in patients with AVC amounted to: 441±802 compared with 256±566 in people without AVC. Moreover, in the discussed study, coronary artery calcifications were more frequent in the presence of AVC.