What causes calcification of arteries. How is coronary artery calcification diagnosed. What are the treatment options for calcified arteries. How can arterial calcification be prevented.

Understanding Arterial Calcification: Causes and Risk Factors

Arterial calcification refers to the buildup of calcium deposits in the walls of arteries. This process is closely linked to atherosclerosis and vascular damage. While some degree of calcification is common with aging, certain factors can accelerate this process:

• Advanced age (especially over 40)
• Male gender
• Metabolic syndrome
• Dyslipidemia (abnormal cholesterol levels)
• Tobacco use
• Hypertension
• Chronic kidney disease
• Elevated C-reactive protein levels

Are there different types of arterial calcification. Yes, there are two main subtypes:

1. Intimal calcification: Associated with advanced age, smoking, dyslipidemia, and hypertension
2. Medial calcification: Primarily linked to kidney disease

The Pathophysiology of Coronary Artery Calcification

Coronary artery calcification (CAC) is a complex process that begins early in the development of atherosclerosis. While the exact mechanisms are not fully understood, several theories have been proposed:

• Calcium-phosphorus imbalance
• Formation of apoptotic bodies
• Induction of bone formation in vascular tissues
• Role of vascular smooth muscle cells

When does arterial calcification typically begin. Surprisingly, calcium deposits can start forming as early as the second decade of life, immediately following the development of fatty streaks in the arteries. As individuals age, these deposits become more prevalent and complex.

Diagnosing Coronary Artery Calcification: Imaging Techniques

Accurate diagnosis of coronary artery calcification is crucial for assessing cardiovascular risk and guiding treatment decisions. The most common imaging techniques used include:

1. Electron Beam Computed Tomography (EBCT)

EBCT is a specialized type of CT scan that uses an electron beam to produce high-resolution images of the heart and coronary arteries. It is particularly effective at detecting and quantifying calcium deposits.

2. Multidetector Computed Tomography (MDCT)

MDCT is a more widely available technology that can also provide detailed images of coronary calcification. It uses multiple detector rows to capture images from different angles simultaneously.

How is the extent of calcification measured. Both EBCT and MDCT allow for the calculation of a coronary artery calcium score (CACS). This score provides a quantitative assessment of the amount of calcification present in the coronary arteries.

Clinical Implications of Coronary Artery Calcification

While coronary artery calcification itself may not cause specific symptoms, its presence has significant prognostic implications. Understanding these implications is crucial for healthcare providers and patients alike:

• Predictor of future cardiovascular events
• Indicator of overall plaque burden
• Tool for reclassifying patients into more accurate risk categories
• Guide for preventive interventions and treatment strategies

Is a high calcium score always indicative of imminent heart problems. Not necessarily. While a high score does indicate increased risk, it’s important to consider other factors such as age, gender, and overall health status when interpreting results.

Treatment Approaches for Calcified Arteries

Managing arterial calcification often involves a multifaceted approach aimed at slowing progression and reducing cardiovascular risk. Key treatment strategies include:

1. Lifestyle Modifications

• Adopting a heart-healthy diet rich in fruits, vegetables, and whole grains
• Regular physical exercise (at least 150 minutes of moderate-intensity activity per week)
• Smoking cessation
• Stress management techniques

2. Medication Management

Depending on individual risk factors, healthcare providers may prescribe:

• Statins to lower cholesterol levels
• Antihypertensive medications to control blood pressure
• Antiplatelet agents to reduce the risk of blood clots

3. Treatment of Underlying Conditions

Addressing coexisting conditions that contribute to arterial calcification is crucial:

• Management of diabetes through blood sugar control
• Treatment of chronic kidney disease
• Addressing hormonal imbalances

Can arterial calcification be reversed. While complete reversal is challenging, aggressive risk factor modification and appropriate treatment can slow progression and potentially stabilize existing calcifications.

Prevention Strategies: Keeping Your Arteries Healthy

Preventing arterial calcification is an essential aspect of maintaining cardiovascular health. Key preventive measures include:

1. Maintaining a healthy weight through proper diet and exercise
2. Controlling blood pressure (aim for less than 130/80 mmHg)
3. Managing cholesterol levels (target LDL cholesterol below 100 mg/dL)
4. Avoiding tobacco products and limiting alcohol consumption
5. Regular health check-ups and screenings

How often should individuals undergo calcium scoring tests. The frequency of calcium scoring tests depends on individual risk factors. Generally, for those at intermediate risk, a test every 3-5 years may be appropriate. However, it’s essential to consult with a healthcare provider for personalized recommendations.

The Role of Diet in Managing Arterial Calcification

Diet plays a crucial role in both the prevention and management of arterial calcification. A heart-healthy diet can help control risk factors and potentially slow the progression of calcification. Key dietary recommendations include:

1. Calcium and Vitamin K2 Balance

While calcium is essential for bone health, excessive calcium intake without adequate vitamin K2 may contribute to arterial calcification. Vitamin K2 helps direct calcium to the bones and away from the arteries.

2. Omega-3 Fatty Acids

Increasing intake of omega-3 fatty acids, found in fatty fish, flaxseeds, and walnuts, may help reduce inflammation and improve overall cardiovascular health.

3. Antioxidant-Rich Foods

Consuming a variety of colorful fruits and vegetables provides antioxidants that can help protect against oxidative stress and inflammation in the arteries.

4. Limiting Processed Foods

Reducing intake of processed foods, which are often high in unhealthy fats, added sugars, and sodium, can help maintain healthy blood pressure and cholesterol levels.

What specific foods should be emphasized in a diet to prevent arterial calcification. Focus on incorporating the following into your diet:

• Leafy green vegetables (rich in vitamin K)
• Fatty fish like salmon and mackerel (high in omega-3s)
• Nuts and seeds (good sources of healthy fats and minerals)
• Berries and citrus fruits (high in antioxidants)
• Whole grains (provide fiber and essential nutrients)

Emerging Therapies and Research Directions

The field of arterial calcification research is rapidly evolving, with several promising avenues being explored:

1. Targeted Calcium Channel Blockers

Researchers are investigating new calcium channel blockers that specifically target vascular smooth muscle cells to prevent calcium accumulation.

2. MicroRNA Therapies

MicroRNAs play a role in regulating vascular calcification. Therapies targeting specific microRNAs may help prevent or reverse calcification.

3. Nanotechnology-Based Treatments

Nanoparticles designed to target and dissolve calcium deposits in arteries are being developed and tested in preclinical studies.

4. Stem Cell Therapies

The use of stem cells to regenerate damaged vascular tissue and potentially reverse calcification is an area of active research.

When might these new therapies become available. While many of these treatments are still in early stages of research, some may enter clinical trials within the next 5-10 years. However, it’s important to note that the process of developing and approving new therapies is complex and can take many years.

Living with Arterial Calcification: Lifestyle Adjustments and Coping Strategies

For individuals diagnosed with arterial calcification, making appropriate lifestyle adjustments is crucial for managing the condition and maintaining overall health:

1. Regular Exercise Routine

Developing a consistent exercise regimen tailored to individual capabilities can help improve cardiovascular health and manage risk factors.

2. Stress Management

Chronic stress can exacerbate cardiovascular issues. Implementing stress-reduction techniques such as meditation, yoga, or deep breathing exercises can be beneficial.

3. Medication Adherence

Strictly following prescribed medication regimens is essential for managing underlying conditions and reducing cardiovascular risk.

4. Regular Check-ups

Maintaining regular appointments with healthcare providers allows for ongoing monitoring and adjustment of treatment plans as needed.

How can individuals stay motivated in managing their condition long-term. Consider the following strategies:

• Set realistic, achievable health goals
• Join support groups or online communities for individuals with similar conditions
• Keep a health journal to track progress and identify areas for improvement
• Celebrate small victories and milestones in your health journey
• Educate yourself about your condition to stay informed and empowered

By implementing these strategies and working closely with healthcare providers, individuals with arterial calcification can take proactive steps towards managing their condition and improving their overall quality of life.

Coronary Artery Calcification – StatPearls

Jay Mohan; Karan Bhatti; Adam Tawney; Roman Zeltser.

Author Information and Affiliations

Last Update: January 27, 2023.

Continuing Education Activity

Arterial calcium development is closely related to vascular injury, inflammation, and repair. Calcification occurs very early in the process of atherosclerosis; however, The presence of coronary calcification is universal in all patients with documented coronary artery disease. Coronary artery calcium is most commonly evaluated by noncontrast, electrocardiographic (ECG)-gated cardiac electron beam computerized tomography (EBCT) or multidetector computed tomography (MDCT). The presence of coronary calcium score is associated with plaque burden; however, it is not a marker of plaque vulnerability. Nonetheless, it provides insight into the patient’s level of cardiovascular disease risk and is helpful for guiding interventions or preventing coronary artery disease. This activity describes the clinical evaluation of coronary artery calcification and explains the role of the health professional team in coordinating the care of patients with this condition.

Objectives:

• Review the etiology of calcium in the coronary arteries.

• Describe the evaluation of coronary calcification.

• Summarize the treatment and management options for coronary calcification.

• Explain the importance of interprofessional team strategies for improving care coordination and communication to aid in prompt diagnosis of coronary arterial calcification and improving outcomes in patients diagnosed with the condition.

Access free multiple choice questions on this topic.

Introduction

Calcium is the most abundant mineral in the human body. Although the majority of calcium is found in teeth and bone, approximately 1% is dissolved in the bloodstream. As the human body ages, calcium can deposit in various parts of the body. Arterial calcium development is closely related to vascular injury, inflammation, and repair. Calcification occurs very early in the process of atherosclerosis; however, it is only able to be detected when it increases in quantity and using imaging modalities. This accumulation typically occurs after the age of 40 in men and women. The presence of coronary calcification is universal in all patients with documented coronary artery disease. Coronary artery calcium is most commonly evaluated by noncontrast, electrocardiographic (ECG)-gated cardiac electron beam computerized tomography (EBCT) or multidetector computed tomography (MDCT). The presence of coronary calcium score is associated with plaque burden; however, it is not a marker of plaque vulnerability.  Nonetheless, it gives an insight into the patient’s level of cardiovascular disease risk and is helpful for guiding interventions or preventing coronary artery disease.[1][2][3][4]

Etiology

Coronary artery calcification increases with age and is more common in men than women. Furthermore, people with metabolic syndrome, dyslipidemia, tobacco use, hypertension, chronic kidney disease, and a high baseline C-reactive protein level are at an increased risk to develop coronary artery calcification. It is to be noted that coronary artery calcification has 2 main subtypes, intimal and medial. Intimal artery calcification is correlated with advanced age, tobacco use, dyslipidemia, and hypertension. Conversely, medial calcification is associated with kidney disease.

Epidemiology

The presence of coronary artery calcification is age and gender-dependent. It is present in 90% of men and 67% of women older than the age of 70.

Pathophysiology

It is well known that coronary calcification causes reduced myocardial perfusion, abnormal vasomotor response, and overall impaired vascular compliance. Several theories have been proposed about the development of coronary artery calcification. However, the entire mechanism is currently unknown. Mechanisms theorized include calcium-phosphorus imbalance, apoptotic bodies, induction of bone formation, and the role of vascular smooth muscle cells. Nonetheless, it is known that calcification in the coronary arteries can occur as early as the second decade of life, immediately after fatty streak formation. Laboratory analysis of lesions of young adults has demonstrated aggregation of crystalline calcium among lipid particles. Furthermore, calcific deposits are found in greater quantities in older adults and complex lesions.[5][6][7]

History and Physical

Although coronary artery calcification itself has no specific clinical manifestations, it has significant important prognostic implications. It can independently predict future cardiovascular events and reclassify patients into more accurate categories.

Evaluation

Diagnostic Methods

Chest Radiography

Coronary calcification is not easily detected on routine chest radiography. Although chest radiography is inexpensive, it has very poor sensitivity in detecting coronary artery calcification. Chest radiography is not recommended for coronary artery calcification detection. 

Computed Tomography

The detection of coronary artery calcification via CT scan was made possible in the 1980s after the development of the electron-beam CT (EBCT) scanner. This was due to the significantly superior speed of the CT scanner. The superior speed enabled heart motion to be paused long enough to detect calcification in the coronary arteries. Furthermore, the development of the multi-detector CT scan has allowed even faster acquisition of images.

The evaluation of coronary artery calcium scoring via CT offers a fast, reproducible, and relatively cheap modality to determine the extent and presence of coronary calcification. Patients, prior to the test, do not need any specific preparation or intravenous access. Scans are typically obtained with prospective electrocardiogram triggering during diastole. After imaging is acquired, the extent of calcification is quantified using the Agatston score. The Agatston score is obtained by multiplying the area of calcification by the corresponding density.

Currently, the American College of Cardiology/American Heart Association gives class IIa indication for asymptomatic patients with intermediate-risk (10% to 20%) 10-year risk of cardiac events based on the Framingham risk score, as well as for asymptomatic individuals 40 years and older with diabetes mellitus for coronary artery calcium scanning. CAC measurement is generally not recommended for patients at low (less than 10%) or high (greater than 20%) 10-year risk of cardiac events based on the Framingham risk score.

The following definitions have been used to quantify coronary artery calcium score and coronary plaque burden

• 0: No identifiable disease

• 1 to 99: Mild disease 

• 100 to 399: Moderate disease

• Greater than 400: Severe Disease

It is to be noted that although the presence of CAC can help predict the presence of coronary artery stenosis, it is generally a better marker for the extent of coronary atherosclerosis present rather than the degree of stenosis. In early atherosclerosis, there is a compensatory enlargement of the arteries to accommodate the plaque. Therefore, although extensive plaque burden may be present, there may not be any clinically relevant stenosis. Severe coronary calcification (Agatston score greater than 1000) is associated with advanced obstructive coronary disease.

The effective radiation exposure with EBCT is approximately 0.7 to 1.0 mSv in men and 0.9 to 1.3 mSv in women. MDCT has a slightly higher radiation dose of 1.0 to 1.5 mSv in men and 1.1 to 1.9 mSv in women. To place this in context, the average annual background radiation in the United States is 3.0 to 3.6 mSv.

Magnetic Resonance Imaging

MRI has a very limited role due to difficulties in detecting small quantities of calcification. Currently, there is no indication for MRI in the detection of coronary artery calcification.

Treatment / Management

There have been advances in the treatment of coronary artery calcification. Intravascular lithotripsy (IVL) for the modification of severe coronary artery calcification was seen in the Disrupt CAD III study.[8] Risk factor modification is recommended and includes treating hypertension, dyslipidemia, and diabetes mellitus, as well as preventing the development of advanced kidney disease. In addition, the presence of coronary artery calcification makes a percutaneous coronary intervention during cardiac catheterization more challenging. Techniques that can be utilized during cardiac catheterization in addition to drug-eluting or bare metal stent placement include rotational, orbital, or laser atherectomy and cutting balloons.[9][10][11]

Differential Diagnosis

• Acute pericarditis

• Angina pectoris

• Atherosclerosis

• Hypertension

• Kawasaki disease

• Myocarditis

Prognosis

Coronary artery calcification in several large observational studies has been shown to predict future cardiovascular events. Furthermore, when added to commonly used risk prediction models, CAC significantly improves risk prediction and stratification compared to other biomarkers. It can correctly classify patients into low-risk and high-risk categories. Patients have an extremely low risk of cardiovascular disease and events if they have no coronary calcification detected (CAC score of 0). For example, in patients who are classified as low risk due to risk factors present or Framingham risk score, a CAC of 100 indicated an estimated 10-year all-CHD event rate of nearly 10%. However, in patients classified as high risk due to risk factors present, a CAC score of 0 is associated with a 10-year all-CHD event risk of only 3%. Asymptomatic patients who are in the intermediate-risk category most commonly undergo CAC scoring due to guideline recommendations. A CAC score of greater than 400 is associated with worse clinical outcomes. This illustrates the ability of coronary artery calcification scoring to help reclassify the risk of many patients and estimate future cardiovascular events.

Enhancing Healthcare Team Outcomes

Healthcare workers, including the primary caregiver and nurse practitioner, frequently see patients with coronary artery disease. Often these patients are referred to a cardiologist, where imaging studies are done to determine the degree of calcification in the coronary vessels.

Coronary artery calcification in several large observational studies has been shown to predict future cardiovascular events. Furthermore, when added to commonly used risk prediction models, CAC significantly improves risk prediction and stratification compared to other biomarkers. It can correctly classify patients into low-risk and high-risk categories. Patients have an extremely low risk of cardiovascular disease and events if they have no coronary calcification detected (CAC score of 0).

Currently, there is no known specific treatment for coronary artery calcification. Risk factor modification is recommended and includes treating hypertension, dyslipidemia, and diabetes mellitus, as well as preventing the development of advanced kidney disease. In addition, the presence of coronary artery calcification makes a percutaneous coronary intervention during cardiac catheterization more challenging. Techniques that can be utilized during cardiac catheterization in addition to drug-eluting or bare-metal stent placement include rotational, orbital, or laser atherectomy and cutting balloons.

Review Questions

• Access free multiple choice questions on this topic.

• Comment on this article.

References

1.

Reed GW, Rossi JE, Masri A, Griffin BP, Ellis SG, Kapadia SR, Desai MY. Angiographic predictors of adverse outcomes after percutaneous coronary intervention in patients with radiation associated coronary artery disease. Catheter Cardiovasc Interv. 2019 Sep 01;94(3):E104-E110. [PubMed: 30690850]

2.

Chen Y, Hu Z, Li M, Jia Y, He T, Liu Z, Wei D, Yu Y. Comparison of Nongated Chest CT and Dedicated Calcium Scoring CT for Coronary Calcium Quantification Using a 256-Dector Row CT Scanner. Acad Radiol. 2019 Oct;26(10):e267-e274. [PubMed: 30685312]

3.

Sharma SK, Bolduan RW, Patel MR, Martinsen BJ, Azemi T, Giugliano G, Resar JR, Mehran R, Cohen DJ, Popma JJ, Waksman R. Impact of calcification on percutaneous coronary intervention: MACE-Trial 1-year results. Catheter Cardiovasc Interv. 2019 Aug 01;94(2):187-194. [PubMed: 30681262]

4.

Williams MC, Moss AJ, Dweck M, Adamson PD, Alam S, Hunter A, Shah ASV, Pawade T, Weir-McCall JR, Roditi G, van Beek EJR, Newby DE, Nicol ED. Coronary Artery Plaque Characteristics Associated With Adverse Outcomes in the SCOT-HEART Study. J Am Coll Cardiol. 2019 Jan 29;73(3):291-301. [PMC free article: PMC6342893] [PubMed: 30678759]

5.

Lemanowicz A, Białecki M, Leszczyński W, Hawrył M. Coronary age, based on coronary calcium measurement, is increased in patients with morbid obesity. Pol J Radiol. 2018;83:e415-e420. [PMC free article: PMC6334088] [PubMed: 30655919]

6.

Kowall B, Lehmann N, Mahabadi AA, Moebus S, Erbel R, Jöckel KH, Stang A. Associations of metabolically healthy obesity with prevalence and progression of coronary artery calcification: Results from the Heinz Nixdorf Recall Cohort Study. Nutr Metab Cardiovasc Dis. 2019 Mar;29(3):228-235. [PubMed: 30648599]

7.

Gheorghe AG, Jacobsen C, Thomsen R, Linnet K, Lynnerup N, Andersen CB, Fuchs A, Kofoed KF, Banner J. Coronary artery CT calcium score assessed by direct calcium quantification using atomic absorption spectroscopy and compared to macroscopic and histological assessments. Int J Legal Med. 2019 Sep;133(5):1485-1496. [PubMed: 30610447]

8.

Hill JM, Kereiakes DJ, Shlofmitz RA, Klein AJ, Riley RF, Price MJ, Herrmann HC, Bachinsky W, Waksman R, Stone GW., Disrupt CAD III Investigators. Intravascular Lithotripsy for Treatment of Severely Calcified Coronary Artery Disease. J Am Coll Cardiol. 2020 Dec 01;76(22):2635-2646. [PubMed: 33069849]

9.

Shavadia JS, Vo MN, Bainey KR. Challenges With Severe Coronary Artery Calcification in Percutaneous Coronary Intervention: A Narrative Review of Therapeutic Options. Can J Cardiol. 2018 Dec;34(12):1564-1572. [PubMed: 30527144]

10.

Cano-Megías M, Bouarich H, Guisado-Vasco P, Pérez Fernández M, de Arriba-de la Fuente G, Álvarez-Sanz C, Rodríguez-Puyol D. Coronary artery calcification in patients with diabetes mellitus and advanced chronic kidney disease. Endocrinol Diabetes Nutr (Engl Ed). 2019 May;66(5):297-304. [PubMed: 30509882]

11.

Guo J, Nunley KA, Costacou T, Miller RG, Rosano C, Edmundowicz D, Orchard TJ. Greater progression of coronary artery calcification is associated with clinically relevant cognitive impairment in type 1 diabetes. Atherosclerosis. 2019 Jan;280:58-65. [PMC free article: PMC6584032] [PubMed: 30471556]

Disclosure: Jay Mohan declares no relevant financial relationships with ineligible companies.

Disclosure: Karan Bhatti declares no relevant financial relationships with ineligible companies.

Disclosure: Adam Tawney declares no relevant financial relationships with ineligible companies.

Disclosure: Roman Zeltser declares no relevant financial relationships with ineligible companies.

Coronary Artery Calcification – StatPearls

Jay Mohan; Karan Bhatti; Adam Tawney; Roman Zeltser.

Author Information and Affiliations

Last Update: January 27, 2023.

Continuing Education Activity

Arterial calcium development is closely related to vascular injury, inflammation, and repair. Calcification occurs very early in the process of atherosclerosis; however, The presence of coronary calcification is universal in all patients with documented coronary artery disease. Coronary artery calcium is most commonly evaluated by noncontrast, electrocardiographic (ECG)-gated cardiac electron beam computerized tomography (EBCT) or multidetector computed tomography (MDCT). The presence of coronary calcium score is associated with plaque burden; however, it is not a marker of plaque vulnerability. Nonetheless, it provides insight into the patient’s level of cardiovascular disease risk and is helpful for guiding interventions or preventing coronary artery disease. This activity describes the clinical evaluation of coronary artery calcification and explains the role of the health professional team in coordinating the care of patients with this condition.

Objectives:

• Review the etiology of calcium in the coronary arteries.

• Describe the evaluation of coronary calcification.

• Summarize the treatment and management options for coronary calcification.

• Explain the importance of interprofessional team strategies for improving care coordination and communication to aid in prompt diagnosis of coronary arterial calcification and improving outcomes in patients diagnosed with the condition.

Access free multiple choice questions on this topic.

Introduction

Calcium is the most abundant mineral in the human body. Although the majority of calcium is found in teeth and bone, approximately 1% is dissolved in the bloodstream. As the human body ages, calcium can deposit in various parts of the body. Arterial calcium development is closely related to vascular injury, inflammation, and repair. Calcification occurs very early in the process of atherosclerosis; however, it is only able to be detected when it increases in quantity and using imaging modalities. This accumulation typically occurs after the age of 40 in men and women. The presence of coronary calcification is universal in all patients with documented coronary artery disease. Coronary artery calcium is most commonly evaluated by noncontrast, electrocardiographic (ECG)-gated cardiac electron beam computerized tomography (EBCT) or multidetector computed tomography (MDCT). The presence of coronary calcium score is associated with plaque burden; however, it is not a marker of plaque vulnerability.  Nonetheless, it gives an insight into the patient’s level of cardiovascular disease risk and is helpful for guiding interventions or preventing coronary artery disease.[1][2][3][4]

Etiology

Coronary artery calcification increases with age and is more common in men than women. Furthermore, people with metabolic syndrome, dyslipidemia, tobacco use, hypertension, chronic kidney disease, and a high baseline C-reactive protein level are at an increased risk to develop coronary artery calcification. It is to be noted that coronary artery calcification has 2 main subtypes, intimal and medial. Intimal artery calcification is correlated with advanced age, tobacco use, dyslipidemia, and hypertension. Conversely, medial calcification is associated with kidney disease.

Epidemiology

The presence of coronary artery calcification is age and gender-dependent. It is present in 90% of men and 67% of women older than the age of 70.

Pathophysiology

It is well known that coronary calcification causes reduced myocardial perfusion, abnormal vasomotor response, and overall impaired vascular compliance. Several theories have been proposed about the development of coronary artery calcification. However, the entire mechanism is currently unknown. Mechanisms theorized include calcium-phosphorus imbalance, apoptotic bodies, induction of bone formation, and the role of vascular smooth muscle cells. Nonetheless, it is known that calcification in the coronary arteries can occur as early as the second decade of life, immediately after fatty streak formation. Laboratory analysis of lesions of young adults has demonstrated aggregation of crystalline calcium among lipid particles. Furthermore, calcific deposits are found in greater quantities in older adults and complex lesions.[5][6][7]

History and Physical

Although coronary artery calcification itself has no specific clinical manifestations, it has significant important prognostic implications. It can independently predict future cardiovascular events and reclassify patients into more accurate categories.

Evaluation

Diagnostic Methods

Chest Radiography

Coronary calcification is not easily detected on routine chest radiography. Although chest radiography is inexpensive, it has very poor sensitivity in detecting coronary artery calcification. Chest radiography is not recommended for coronary artery calcification detection. 

Computed Tomography

The detection of coronary artery calcification via CT scan was made possible in the 1980s after the development of the electron-beam CT (EBCT) scanner. This was due to the significantly superior speed of the CT scanner. The superior speed enabled heart motion to be paused long enough to detect calcification in the coronary arteries. Furthermore, the development of the multi-detector CT scan has allowed even faster acquisition of images.

The evaluation of coronary artery calcium scoring via CT offers a fast, reproducible, and relatively cheap modality to determine the extent and presence of coronary calcification. Patients, prior to the test, do not need any specific preparation or intravenous access. Scans are typically obtained with prospective electrocardiogram triggering during diastole. After imaging is acquired, the extent of calcification is quantified using the Agatston score. The Agatston score is obtained by multiplying the area of calcification by the corresponding density.

Currently, the American College of Cardiology/American Heart Association gives class IIa indication for asymptomatic patients with intermediate-risk (10% to 20%) 10-year risk of cardiac events based on the Framingham risk score, as well as for asymptomatic individuals 40 years and older with diabetes mellitus for coronary artery calcium scanning. CAC measurement is generally not recommended for patients at low (less than 10%) or high (greater than 20%) 10-year risk of cardiac events based on the Framingham risk score.

The following definitions have been used to quantify coronary artery calcium score and coronary plaque burden

• 0: No identifiable disease

• 1 to 99: Mild disease 

• 100 to 399: Moderate disease

• Greater than 400: Severe Disease

It is to be noted that although the presence of CAC can help predict the presence of coronary artery stenosis, it is generally a better marker for the extent of coronary atherosclerosis present rather than the degree of stenosis. In early atherosclerosis, there is a compensatory enlargement of the arteries to accommodate the plaque. Therefore, although extensive plaque burden may be present, there may not be any clinically relevant stenosis. Severe coronary calcification (Agatston score greater than 1000) is associated with advanced obstructive coronary disease.

The effective radiation exposure with EBCT is approximately 0.7 to 1.0 mSv in men and 0.9 to 1.3 mSv in women. MDCT has a slightly higher radiation dose of 1.0 to 1.5 mSv in men and 1.1 to 1.9 mSv in women. To place this in context, the average annual background radiation in the United States is 3.0 to 3.6 mSv.

Magnetic Resonance Imaging

MRI has a very limited role due to difficulties in detecting small quantities of calcification. Currently, there is no indication for MRI in the detection of coronary artery calcification.

Treatment / Management

There have been advances in the treatment of coronary artery calcification. Intravascular lithotripsy (IVL) for the modification of severe coronary artery calcification was seen in the Disrupt CAD III study.[8] Risk factor modification is recommended and includes treating hypertension, dyslipidemia, and diabetes mellitus, as well as preventing the development of advanced kidney disease. In addition, the presence of coronary artery calcification makes a percutaneous coronary intervention during cardiac catheterization more challenging. Techniques that can be utilized during cardiac catheterization in addition to drug-eluting or bare metal stent placement include rotational, orbital, or laser atherectomy and cutting balloons.[9][10][11]

Differential Diagnosis

• Acute pericarditis

• Angina pectoris

• Atherosclerosis

• Hypertension

• Kawasaki disease

• Myocarditis

Prognosis

Coronary artery calcification in several large observational studies has been shown to predict future cardiovascular events. Furthermore, when added to commonly used risk prediction models, CAC significantly improves risk prediction and stratification compared to other biomarkers. It can correctly classify patients into low-risk and high-risk categories. Patients have an extremely low risk of cardiovascular disease and events if they have no coronary calcification detected (CAC score of 0). For example, in patients who are classified as low risk due to risk factors present or Framingham risk score, a CAC of 100 indicated an estimated 10-year all-CHD event rate of nearly 10%. However, in patients classified as high risk due to risk factors present, a CAC score of 0 is associated with a 10-year all-CHD event risk of only 3%. Asymptomatic patients who are in the intermediate-risk category most commonly undergo CAC scoring due to guideline recommendations. A CAC score of greater than 400 is associated with worse clinical outcomes. This illustrates the ability of coronary artery calcification scoring to help reclassify the risk of many patients and estimate future cardiovascular events.

Enhancing Healthcare Team Outcomes

Healthcare workers, including the primary caregiver and nurse practitioner, frequently see patients with coronary artery disease. Often these patients are referred to a cardiologist, where imaging studies are done to determine the degree of calcification in the coronary vessels.

Coronary artery calcification in several large observational studies has been shown to predict future cardiovascular events. Furthermore, when added to commonly used risk prediction models, CAC significantly improves risk prediction and stratification compared to other biomarkers. It can correctly classify patients into low-risk and high-risk categories. Patients have an extremely low risk of cardiovascular disease and events if they have no coronary calcification detected (CAC score of 0).

Currently, there is no known specific treatment for coronary artery calcification. Risk factor modification is recommended and includes treating hypertension, dyslipidemia, and diabetes mellitus, as well as preventing the development of advanced kidney disease. In addition, the presence of coronary artery calcification makes a percutaneous coronary intervention during cardiac catheterization more challenging. Techniques that can be utilized during cardiac catheterization in addition to drug-eluting or bare-metal stent placement include rotational, orbital, or laser atherectomy and cutting balloons.

Review Questions

• Access free multiple choice questions on this topic.

• Comment on this article.

References

1.

Reed GW, Rossi JE, Masri A, Griffin BP, Ellis SG, Kapadia SR, Desai MY. Angiographic predictors of adverse outcomes after percutaneous coronary intervention in patients with radiation associated coronary artery disease. Catheter Cardiovasc Interv. 2019 Sep 01;94(3):E104-E110. [PubMed: 30690850]

2.

Chen Y, Hu Z, Li M, Jia Y, He T, Liu Z, Wei D, Yu Y. Comparison of Nongated Chest CT and Dedicated Calcium Scoring CT for Coronary Calcium Quantification Using a 256-Dector Row CT Scanner. Acad Radiol. 2019 Oct;26(10):e267-e274. [PubMed: 30685312]

3.

Sharma SK, Bolduan RW, Patel MR, Martinsen BJ, Azemi T, Giugliano G, Resar JR, Mehran R, Cohen DJ, Popma JJ, Waksman R. Impact of calcification on percutaneous coronary intervention: MACE-Trial 1-year results. Catheter Cardiovasc Interv. 2019 Aug 01;94(2):187-194. [PubMed: 30681262]

4.

Williams MC, Moss AJ, Dweck M, Adamson PD, Alam S, Hunter A, Shah ASV, Pawade T, Weir-McCall JR, Roditi G, van Beek EJR, Newby DE, Nicol ED. Coronary Artery Plaque Characteristics Associated With Adverse Outcomes in the SCOT-HEART Study. J Am Coll Cardiol. 2019 Jan 29;73(3):291-301. [PMC free article: PMC6342893] [PubMed: 30678759]

5.

Lemanowicz A, Białecki M, Leszczyński W, Hawrył M. Coronary age, based on coronary calcium measurement, is increased in patients with morbid obesity. Pol J Radiol. 2018;83:e415-e420. [PMC free article: PMC6334088] [PubMed: 30655919]

6.

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Hill JM, Kereiakes DJ, Shlofmitz RA, Klein AJ, Riley RF, Price MJ, Herrmann HC, Bachinsky W, Waksman R, Stone GW., Disrupt CAD III Investigators. Intravascular Lithotripsy for Treatment of Severely Calcified Coronary Artery Disease. J Am Coll Cardiol. 2020 Dec 01;76(22):2635-2646. [PubMed: 33069849]

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Calcification of the coronary arteries – causes, symptoms, who treats

Coronary artery calcification (alternatively called calcification) is a buildup of calcium in the two main arteries of the heart, also called the coronary arteries. Calcification occurs after cholesterol plaques (atherosclerosis) have formed in the arteries for about 5 years. Coronary artery calcification is an indicator of coronary artery disease and can provide your healthcare provider with information to help assess your risk for cardiovascular disease. When plaque builds up in the arteries, it makes it difficult for the blood to circulate. Efficient blood flow is critical to the coronary arteries because they supply the heart muscle with oxygenated blood. If blood cannot pass through the coronary arteries, this can lead to chest pain or a heart attack.

What should be done to diagnose and treat coronary artery calcification ? To solve this problem, the first step for the patient is to make an appointment with a cardiologist or vascular surgeon. After the initial examination, the doctor may prescribe additional tests:

• Laboratory tests
• CT of the heart
• CT coronary angiography
• intravascular ultrasound of the heart
• intravascular optical coherence tomography.

Types of coronary artery calcification

• intimal (in the intimal or inner layer of the artery). This type is more common in the coronary arteries
• medial (in the medial or middle layer of the artery).

Coronary artery calcification and atherosclerosis

The level of calcification is a measure of how severe atherosclerosis can be. Atherosclerosis is the result of plaque buildup in the arteries, causing them to narrow. This makes it difficult for blood to circulate through the arteries.

Risk factors

Patients with ischemic heart disease usually have coronary artery calcification.

Patients older than 70 years (more than 90% of men and 67% of women) develop coronary artery calcification. Before menopause, estrogen protects women from developing atherosclerosis. That is why women develop atherosclerosis 10-15 years later than men.

Other risk factors include:

• chronic kidney disease
• diabetes mellitus
• high bad cholesterol (low density lipoprotein) and too low good cholesterol (high density lipoprotein)
• high body mass index
• family history of coronary artery calcification
• high blood pressure
• heavy smoking
• old age
• parathyroid hormone disorders
• high phosphate
• high calcium levels.

Men also have a higher risk of coronary artery calcification.

Calcification of the coronary arteries makes the arteries stiff and impairs their ability to expand and contract. This increases the risk of cardiovascular disease.

Calcification of the coronary arteries causes less blood to reach the heart muscle. Calcification makes it difficult to perform percutaneous coronary intervention or angioplasty.

Symptoms of calcification

Patients with coronary artery calcification often do not have any symptoms. Over time, symptoms such as:

• stable angina
• shortness of breath
• heart attack.

What causes calcification of the coronary arteries

After 40 years, calcium from the bloodstream can settle in parts of the body. Damaged, inflamed, or repaired arteries are more likely to attract calcium deposits. This process may begin after age 20, but a doctor may not diagnose it until the amount of calcium is large enough to be seen on x-rays.

Calcium deposits start at a small size (0.5 µm) and grow to over 3 mm, while plaque continues to build up continuously.

Researchers believe that microcalcification begins when smooth muscle cells die.

How a doctor diagnoses coronary artery calcification

Diagnostic tests for the disease include:

Computed tomography or multidetector computed tomography of the heart can detect coronary atherosclerosis before it becomes progressive. Computed tomography of the heart may show deposits of calcified plaque in the coronary arteries. This is called a coronary artery calcium test, which looks for:

• amount of deposits
• density
• size.

To get Agatston’s score, the doctor multiplies the area of ​​deposits by their number. The patient scores from 0 to 400 or more, with higher scores indicating a greater risk of heart attack or stroke 10 years later.

Indicators of coronary artery calcification

• 0 points means no disease
• 1 to 99 indicates mild illness
• 100 to 399 indicates moderate illness
• more than 400 shows a severe course of the disease.

More invasive methods for detecting coronary artery calcification:

• intravascular ultrasonography of the heart gives a class I to class IV result, with the fourth class describing the most severe calcification. The procedure uses an ultrasound transducer at the end of the catheter to examine the inside of the coronary arteries
• intravascular optical coherence tomography can reveal the amount and density of calcium deposits. The procedure uses shortwave infrared light to create images from inside the coronary artery.

How a doctor treats coronary artery calcification

Although doctors do not have a standard treatment for coronary artery calcification, some use intravascular lithotripsy to treat severe cases. This newer procedure uses a catheter with a special device on the end that sends out pressure waves to break up calcium deposits. After the procedure, the doctor may place a stent to keep the artery open.

Other treatments to improve arterial blood flow:

• rotational, orbital or laser atherectomy to remove plaque from the artery
• cutting, incision, or high-pressure balloon angioplasty to force calcium plaques against artery walls.

Complications of treatment

Complications of intravascular lithotripsy:

• arrhythmia
• aneurysm or distension of a blood vessel
• stroke
• death.

Complications of rotational atherectomy:

• arterial incision
• heart attack
• death
• the need for emergency coronary bypass surgery.

Complications of coronary angioplasty:

• infarction
• stroke
• arrhythmia
• bleeding
• blood clots.

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Scientific sources:

1. Belkind M.B., Lyakishev A.A., Sinitsin V.E. Calcification of the coronary arteries. Cardiology 1997; 11:75-80.
2. Ternovoy S.K., Sinitsyn V.E., Gagarina N.V. Non-invasive diagnostics of atherosclerosis and calcification of coronary arteries. M., 2003.
3. Dzizinsky AA, Pogodin KV Dopplerographic features of the initial stages of heart failure in elderly and senile patients. Cardiology, 1999, No. 5, p.36-39
4. Kolotaya N.V., Sinitsyn V.E., Ternovoy S.K. Detection of coronary artery calcification using electron beam CT in the diagnosis of coronary artery disease. Angiology and Vascular Surgery, 1999, No. 3, p. 16-24.
5. Gagarina N.V. The use of quantitative assessment of coronary artery calcification using electron beam tomography in the diagnosis of coronary artery disease: Abstract of the thesis. dis. cand. honey. Sciences. M.: RKNPK, 2000. 24 p.

Useful information

Calcification of the coronary arteries

What should be done to diagnose and treat coronary artery calcification? To solve this problem, the first step for the patient is to make an appointment with a cardiologist. After the initial examination, the doctor may prescribe additional studies:

Lab tests
CT coronary angiography.

read more +

Dissection of the coronary artery

What should be done to diagnose and treat coronary artery dissection? To solve this problem, the first step for the patient is to make an appointment with a cardiologist. After the initial examination, the doctor may prescribe additional studies:

Lab tests
CT coronary angiography
Ultrasound of the heart
Electrocardiography.

read more +

What is the difference between CT and MRI

Computed tomography, abbreviated as CT, is a modernized form of the well-known X-ray. CT is performed using a special machine. X-rays are used to obtain an image of the examined part of the body. Unlike conventional X-ray procedures, when the image on the film is obtained as a result of the study, the CT scanner produces three-dimensional images,

read more +

Calcification as a pathogenetic basis of atherosclerosis

Safoshkina E. V.

The process of calcification is characterized by the deposition of calcium phosphates (hydroxyapatites, calcium oxalates and octacalcium phosphates) in soft tissues: in the wall of blood vessels, myocardium, valvular apparatus of the heart, as well as in the renal tissue, skin, tendons [1]. An extremely life-threatening and very common type of calcification is associated with the localization of calcium phosphate deposits in the arteries and heart valves. This type of pathology leads to severe pathology and high mortality [1]. Despite numerous and comprehensive studies of the cellular and biochemical mechanisms of calcification, many problems in this area remain unexplained. Coronary calcification occurs in most patients with coronary artery disease, as well as in patients with ruptures of large vessels. In the arteries, calcification is combined with the formation of atherosclerotic plaques, which increases the risk of heart attacks and the frequency of ischemic episodes. These processes in vessels affected by atherosclerosis lead to even greater damage to their walls, as well as to an increase in the fragility of the vessel wall, which is associated with the risk of atherosclerotic plaque rupture, vascular thrombosis, and stratification of the vascular wall [4]. Calcification of the coronary arteries exacerbates ischemic processes in the myocardium, thereby significantly increasing the risk of adverse cardiovascular events and mortality.

The first attempts at a phenomenological explanation of the observed processes led to the concept that soft tissue calcification is a degenerative process leading to pathological deposition of calcium phosphates in soft tissues [3]. In recent years, general ideas about the process of soft tissue calcification have changed radically. Currently, the concept is accepted, according to which soft tissue calcification is a pathological, regulated process in which cells are involved, as well as a biochemical system that regulates [3]. In other words, ectopic calcification is a complex regulated cellular biochemical process. This concept opens up the prospect of creating prevention methods, and possibly also reversing the calcification process [5].

In later studies, in particular, in the review by L. Demer, the processes of calcification of the vascular wall and valve apparatus are considered in the general vein of the process of atherosclerosis [10]. In particular, in a calcified human aortic valve, elastin movement, lipid accumulation, and inflammatory processes occur, which lead to increased calcification processes. A significant difference between the author’s position and others is the assumption of the presence of osteochondrogenic differentiation of the cells of the valvular apparatus, coupled with a mutual influence on the processes of atherosclerosis.

According to the proposed concept, when the vascular wall is damaged by atherosclerosis, there is a violation of the differentiation of the vascular tissue and, consequently, reparative processes. Differentiation of the cellular elements of the vascular tissue occurs to an incomplete degree, i.e. instead of mature cells, less differentiated progenitors “come” to the damaged vascular tissue, which have the properties of bone tissue cells [2]. In addition, multipotent mesenchymal cells sensitive to growth factors are located both in the sites of angiogenesis and in the sites of atherosclerotic damage to the arteries. Inflammation and macrophage infiltration enhance osteogenic activity in the focus of atherosclerosis. Calcium crystals, interacting with macrophages, increase the production of pro-inflammatory cytokines by the latter, maintaining a positive feedback between calcification and the progression of inflammation. In some cases, “other cells”, in particular, precursors of nervous tissue, are also involved in such areas of vascular tissue formation. Some publications show significant differences in subpopulations of vascular tissue cells (in particular, their response to growth factors and their ability to differentiate) [8,9].

Damage to the vascular wall with subsequent impairment of differentiation of cellular elements is probably an integral component in the calcification of vascular tissue. This is clearly demonstrated in an animal study of ectopic calcification in rats that had atherosclerotic plaques [7].

Many international multicentre clinical trials have shown the effect of lipid-lowering drugs on the suppression of valvular calcification [11]. The anticalcification effect of statins is explained by a decrease in the level of LDL-associated protein (LRP5), an independent activator of the Wnt gene, which includes the accumulation of β-catenin in the nuclear apparatus of the cardiomyocyte, which is a necessary element for the development of osteoblastogenesis. In addition, the embryonic origin of the aortic valve from the neural tube testifies in favor of this mechanism; this process is also controlled by the Wnt gene. L. Demer, Y. Tintut and K. Bostrom in their reviews indicate the possibility of the formation of cells with the characteristics of osteoblasts from mesenchymal tissue under the influence of various growth factors. These processes are more likely to develop in smooth muscle cells of the endothelium damaged by atherosclerosis, as well as in the valvular apparatus of the heart [12]. In addition, ossification processes were detected by histological methods in approximately 60% of patients after balloon angioplasty for restenosis of the aortic orifice; in approximately 15% of cases, atherosclerotic plaques in the carotid arteries and valvular apparatus of the heart had signs of ossification [2]. Histological studies have confirmed that structures similar to bone tissue exist inside atherosclerotic formations, and the processes occurring in them are similar to the processes of remodeling in ordinary trabecular bone [6]. Despite the fact that the mechanisms of calcification and atherosclerosis overlap, calcification does not always occur in the presence of atherosclerotic changes [2]. Metabolic disorders such as diabetes mellitus, uremia, hyperparathyroidism, and arterial hypertension are associated with calcification processes that occur even in the absence of atherosclerosis [13].

An example demonstrating the complexity of the processes of pro- and anti-calcification, the variety of regulatory systems working in balance with each other, can be the following clinical case, which, unfortunately, is not uncommon in the daily practice of a clinician. At the initial visit in December 2009, patient K., born in 1927, about 40 years old, suffering from diabetes mellitus, compensated by diet, coronary heart disease (angina pectoris, FC I), paroxysmal form of atrial fibrillation, hyperglycemia on an empty stomach was noted 10.3 mmol /l, hypercholesterolemia 7.7 mmol/l, echocardiographic signs of atherosclerotic changes in the ascending aorta, calcification of the fibrous ring, left ventricular hypertrophy with the formation of a combined aortic valve disease (moderate stenosis of the aortic orifice, AC insufficiency of I-II degree), calcification of the valves of the AC, MK insufficiency II degree, in the bulb with the transition to the mouth of the right internal carotid artery on the anterior wall, a hyperechoic plaque with a violation of the integrity of the tire, 2 cm long, stenosing the lumen on the left up to 60%, on the right in the common carotid artery – a stable plaque with calcification and stenosis 40-45 %. Taking into account the additional examination, the following treatment was prescribed: concor 5 mg per day, diabeton 60 mg per day, crestor 10 mg per day, followed by dynamic observation for 2 years. During this time, it was possible to stabilize the level of glycemia to 4.8-5.3 mmol/l, the indicators of total cholesterol were reduced to 3.5 mmol/l. Control echocardiography showed no further progression of calcification of the valvular apparatus of the heart. According to ultrasonography with Doppler analysis, the atherosclerotic plaque of the left carotid artery stabilized, in addition, a decrease in stenosis was recorded – up to 40% on the left, up to 25-30% on the right.

Of course, the processes of calcification are not yet fully understood. The mechanisms discussed above may be the key to unraveling this problem. The emergence of the possibility of quantitative determination of some mediators of calcification, obviously, will contribute to a more accurate determination of the time of onset of calcification. This, in turn, will significantly expand the possibilities of preventive therapy, taking into account the necessary needs, review drug therapy in addition to the drugs already used, and create new, more effective ones, taking into account modern ideas about calcification processes in the body.

References:

1. Giachelli C.M. Ectopic calcification: gathering hard facts about soft tissue mineralization. Am J Path., 1999;3;671-675.
2. Abedin M., Tintut Y., Demer L.L. Vascular calcification: mechanisms and clinical ramifications. Arterioscler Thromb Vasc Biol 2004;24;1161-1170.
3. Cotran RS, Kumare V, Robbins SL Cellular injury and cellular death. Pathological Basis of Disease, 5th ed., 1994, 1-35.
4. Stein GS, Lian JB. Molecular mechanisms mediating developmental and hormoneregulated expression of genes in osteoblasts: an integrated relationship of cell growth and differentiation. Cellular and Molecular Biology of Bone, 1993; 48-95.
5. Boström K. Cell differentiation in vascular calcification. Z Cardiol 2000; 89(suppl 2): ​​II-69-II-74.

1. Jeziorska M, McCollum C, Wooley DE. Observations on bone formation and remodeling in advanced atherosclerotic lesions of human carotid arteries. Virchows Arch. 1998;433;559-565.
2. Luo G, Ducy P, McKee MD, Pinero GJ, Loyer E, Behringer RR, Karsenty G. Spontaneous calcification of arteries and cartilages in mice lacking matrix GLA protein. Nature. 1997; 386; 78-81.
3. Hungerford JE, Little CD. Developmental biology of the vascular smooth muscle cell: building a multilayered vessel wall. J Vasc Res 1999;36;2-27.
4. Owens G. Regulation of differention of vascular smooth muscle cells. Phys Rev; 1995; 75; 487-517.
5. Demer LL, Tintut Y. Vascular calcification: pathobiology of a multifaceted disease. circulation. 2008 Jun 3;117(22):2938-48.
6. Rajamannan N.M., Subramaniam M., Stock S.R., Stone N.J., Springett M., Ignatiev K.