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 to the patient’s level of cardiovascular disease risk and is helpful for guiding interventions or prevent coronary artery disease.
Coronary artery calcification increases with age and is more common in men than woman. 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.
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.
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.
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.
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.
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 Agaston 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
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 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.
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.
Currently, there is no known specific treatment for coronary artery calcification. Risk factor modification is recommended and includes treating hypertension, dyslipidemia, 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.
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.