Carotid Artery Calcification: Causes, Diagnosis and Treatment

What is carotid artery calcification?

There are two common carotid arteries in the human body. The left common carotid artery is a branch of the aorta, while the right starts at the right subclavian artery. At approximately the height of the 3rd or 4th vertebra, the common carotids split into two vessels, the internal and external carotid arteries. The internal carotid artery is the blood supply for the brain, and the external carotid artery serves the face and scalp.

The carotid arteries supply blood to the whole head and are therefore critical for life. Any significant reduction in the blood flow through them can result in brain ischemia. With time, serious consequences can develop, like stroke.

What is carotid artery calcification?

Carotid artery calcification refers to the buildup of calcium deposits within the walls of the carotid arteries, which are the major blood vessels that supply blood to the brain. Here are some key points about carotid artery calcification:

- It is a marker of atherosclerosis, the buildup of plaque in the arteries [14], [15].
- Calcification can occur in the intimal layer (inner lining) or medial layer (middle layer) of the artery wall [14], [16].
- It is an active, regulated process involving inflammation and mineralization, similar to bone formation [14], [17].
- Carotid calcification is often asymptomatic but increases the risk of stroke and other cardiovascular events [14], [15], [18].
- It can be detected on imaging modalities like computed tomography (CT), ultrasound, and panoramic dental radiographs [14], [19], [20].
- The presence and extent of calcification correlates with advanced age, smoking, diabetes, hypertension and other cardiovascular risk factors [17], [21], [22], [23].

In summary, carotid artery calcification is a manifestation of underlying atherosclerosis and its detection may help identify individuals at increased risk for stroke and other vascular events, allowing for timely preventive interventions.

Carotid artery calcification (CAC) is a condition that affects one or two of the common arteries. It is characterized by the accumulation of calcium deposits [1].

Two types of CAC are known: intimal and medial. They refer to the layers in which the calcification occurs [1].

Carotid artery calcification is linked with increased mortality and morbidity and is a marker of atherosclerosis. It can often lead to strokes, which can cause disabilities or death [1, 2].

What is the etiology of carotid artery calcification?

Intimal carotid artery calcification is primarily associated with atherosclerosis. It is a condition characterized by the buildup of fats, cholesterol, calcium, and other substances in and on the artery walls [3, 4].

The medial CAC is mostly related to aging. Studies have shown that with age, the probability of developing calcification in the carotid arteries increases [5, 6].

Cardiovascular risk factors such as smoking, hypertension, and diabetes mellitus are all linked to CAC. For instance, smoking and hypertension are associated with intimal calcification, while diabetes mellitus is linked to medial calcification [7].

Genetic factors also play a role in the development of CAC. Genes like KLKB1 and ADCC6 have been associated with higher calcifications in the carotid [8].

What are the risk factors for carotid artery calcification?

Several risk factors are associated with carotid artery calcification:

1. **Age**: Older age is consistently associated with an increased risk of carotid calcification [14], [15], [16], [17], [18], [19].
2. **Gender**: Men tend to have a higher calcification volume than women [17].
3. **Smoking**: Current smoking is strongly associated with carotid calcification [18].
4. **Chronic Kidney Disease (CKD)**: CKD is associated with a higher prevalence risk of calcification in different vascular beds, including the carotid artery [20].
5. **Hypertension**: Hypertension is significantly associated with carotid calcification, especially when combined with CKD [16], [20].
6. **Diabetes Mellitus (DM)**: DM is associated with inside-wall calcification at the carotid artery origins [20].
7. **Hypercholesterolemia**: Hypercholesterolemia is independently related to the presence of calcifications [17].
8. **Cardiovascular disease history**: A history of cardiovascular disease is independently related to the volume of calcifications [17].
9. **Use of certain medications**: The use of statins and angiotensin inhibitors is significantly more frequent in patients with calcified carotid plaques [14].

It's important to note that these risk factors can vary across different arteries and between men and women [19].

What is the pathophysiology of carotid artery calcification?

The calcification process of the carotid artery is a complex one. Although it is not completely understood, there are various factors and conditions that influence it.

Depending on the type of CAC, certain locations are more prone to calcification development. The intimal, atherosclerotic CAC tends to develop at the division of the common carotid into the internal and external carotids [9]. The medial CAC can theoretically occur everywhere.

The medial CAC pathophysiology is not clear. However, it involves the transformation of vascular smooth muscle into osteoblast-like cells. This switch in the phenotype leads to the deposition of calcium salts in the vascular wall [10].

In the CAC intima, the most important factor is atherosclerosis. The calcification of carotid plaques is common. It develops in nearly 80% of the cases [11].

What is the pathogenesis of atherosclerosis?

Atherosclerosis is a chronic inflammatory disease that develops over several decades due to multiple factors, including genetic and environmental influences. The pathogenesis of atherosclerosis involves a complex chain of events. It begins with the accumulation of low-density lipoprotein cholesterol within the arterial wall, which stimulates the infiltration of immune cells, leading to the formation of lipid-laden foam cells. The death of these foam cells results in the formation of a lipid-rich necrotic core. Vascular smooth muscle cells migrate into the intima layer, proliferate, and produce extracellular matrix proteins, forming a fibrous cap that stabilizes the atherosclerotic plaque. The plaque can rupture, leading to lumen-occlusive atherothrombosis, which can result in heart attack or stroke. Inflammation plays a pivotal role in this process, with both innate and adaptive immunity involved. Atherogenic lipoproteins, such as oxidized low-density lipoprotein, play a critical role in the pro-inflammatory reaction, whereas high-density lipoproteins exert anti-inflammatory functions [14], [15], [16], [17], [18], [19].

The risk of complications during plaque growth depends on the stability of the buildup mass. The risk of rupture and a potential embolism does not depend on the calcium levels. Instead, it is determined by the type of calcium salts present in the plaques [11].

The two most common types of salts found in plaques are hydroxyapatite (HA) and calcium oxalate. Plaques containing HA have a higher risk of rapture, while those formed with CO are linked to stability [11].

The development of different patterns of calcification also plays a role in the risk of rapture. For example, rim calcification occurs in plaques with intraplaque hemorrhage and active inflammation. The structure of such plaques is at high risk of rapture. Nodular calcifications, on the other hand, are more stable and have a lower risk of rapture and complications [12].

How is the carotid artery calcification diagnosed?

Carotid artery calcification (CAC) is typically diagnosed using various imaging modalities. Computed tomography angiography (CTA) is one of the standard methods. This technique also allows the medical staff to assess the plaque’s composition [1].

Other diagnostic modalities can be used too. Among the techniques used are magnetic resonance angiography (MRA), duplex ultrasound (DUS), positron emission tomography, computed tomography (PET-CT) imaging with 18 F-Sodium Fluoride, and optical coherence tomography (OCT) [1].

Because of the location, the plaque can also be discovered during standard dental panoramic radiographs. Although this method has a relatively low sensitivity of 66%, it can sometimes become handy when no suspicion or symptoms are present [13].

However, a more recent study has shown that an artificial intelligence algorithm using deep learning convolutional neural networks can enhance normal dental radiography. An AI-enhanced program was able to achieve a sensitivity of more than 82% and a specificity of 97% [2].

How is the carotid artery calcification treated?

The best strategy against CAC is prevention, which consists mostly of lifestyle changes. Also, after diagnosis, those adjustments in life can be beneficial by stopping the progression of the inflammatory process.

In severe cases, surgical intervention can be performed. The two most commonly chosen procedures are carotid endarterectomy and carotid stenting. They are chosen based on the anatomy and age of the patient, as well as the surgical risk and the doctor’s skill [1].