prepared by Dr. Alan Boyar
The purpose of this guide is to provide information on the background and interpretation of the coronary calcium score in clinical practice. We hope that this will allow you to gain some appreciation of the technology itself, its capabilities and weaknesses, and its role in the milieu of already established cardiac testing modalities (from stress testing to angiography). Coronary artery calcification scanning with the GE-Imatron Electron Beam CT (EBCT) Scanner affords the opportunity to determine very accurately and noninvasively whether or not underlying coronary artery disease is present, early – before the clinical manifestations of coronary artery disease develop so that appropriate interventions can be instituted before irreversible events occur. This information can then be utilized to optimize patient care, helping to determine further evaluation and follow up and to appropriately tailor long term goals.
Coronary Artery Disease (CAD) is currently, and will remain for the foreseeable future, the leading cause of death and disability in the United States. Although effective means are available for treating and delaying CAD progression, treatments are underutilized because at risk individuals are not easily identified. To date, in excess of 300 risk factors for CAD have been identified; however, most of these are not independent of each other and the number of truly independent risk factors remains small. The most famous of these being the ones making up the Framingham score: age, sex, total cholesterol, HDL, smoking, diabetes and hypertension. The problem is that these risk factors fail to explain up to 50% of CAD morbidity and mortality. In addition, these risk factors also sometimes falsely identify individuals without CAD leading to unnecessary and premature intervention. What is needed is a simple and reliable test that will identify individuals with early CAD so that appropriate interventions can be implemented before events occur.
Scan Images: Three Grades of Calcium Plaque Burden
Until recently, it has not been possible to accurately assess the coronary arteries with CT technology. This was related to the fact that the heart is in constant motion within the chest cavity. Conventional helical (spiral) CT scanners operate by having the image gantry rotate about the patient in a continuous loop. Because speed of rotation of the gantry is limited to about two rotations per second, the time required for each tomographic slice to be acquired remains greater than the length of a cardiac cycle, resulting in an image blur. Electron beam CT scanners (EBCT utilize an electron gun (like the cathode ray TV tube with no moving mechanical parts) to acquire the images, taking 10 to 20 images every second, fast enough to “freeze the heart” and therefore making relatively straightforward the assessment of coronary calcification. The introduction of the GE Imatron EBCT scanner enables the detection and quantization of even miniscule coronary calcium deposits. The final product of the this test is the coronary calcium score, an amalgamation of total size and density of the calcium deposits found throughout the coronary tree.
Coronary Calcium and Atherosclerosis
The first take home point is that that the presence of any calcium in the coronary tree is diagnostic of coronary atherosclerosis. Atherosclerosis is the only process that results in the deposition of calcium within the wall of an artery. The deposition of calcium into the walls of the arterial bed is an active process, performed by specialized cells similar to the osteoblasts that build bone. Although it is associated with aging, arterial calcification is NOT due to a degenerative process and is NOT related to the aging process itself. Because atherosclerosis and the associated arterial calcium deposition is extremely rare under the age of 30 and it is not appropriate to look for coronary calcium in young patients without other risk factors. Past 70 years, greater than 95% of men and 75% of women will have detectable coronary calcium.
The second take home point is that while the coronary calcium score provides a quantitative evaluation of extent of the total coronary atherosclerotic plaque burden, it does not tell us anything about the severity of any particular arterial luminal narrowing. That is, the calcium sore does not indicate where or to what degree luminal obstruction is present. However; individuals with large plaque burden, that is individuals with coronary calcium scores greater than 400, have a high likelihood (>90%) of at least one significantly obstructed coronary vessel (>70% stenosis). Therefore; finding an individual with a coronary calcium score greater than 400 does justify further physiologic evaluation such as stress testing. The coronary calcium sore is an anatomical test for total plaque burden that is complementary to the physiologic stress test which tests for functional capacity and adequacy of coronary blood flow.
Coronary Calcium Predicts Cardiac Events
The calcium score directly correlates with the risk of cardiac events. People with higher scores have greater plaque burden and a higher the risk for cardiac events regardless of whether symptoms are present. For asymptomatic individuals, a calcium score of 0 indicates absence of detected calcium and an extremely low likelihood (<1%) of any CAD (negative predictive value 95-100% for stenosis >50%). The odds ratio (ratio of events in an interest group vs. events in a baseline population) of developing symptomatic cardiovascular disease is 3:1 for people with scores of 1 to 80 (where the zero score group is the baseline population), 8:1 for people with scores between 80 and 400 and nearly 25:1 for people with scores above 400. Compare those odds ratios to the odds ratios of the traditional risk factors for coronary heart disease: 1.8:1 for total cholesterol over 240 mg/dl; 1.8:1 for HDL under 35 mg/dl; 5.4:1 for diabetes; 3.6:1 for cigarette smoking; and 2.6:1 for hypertension. The calcium sore alone is a more powerful predictor of future events than all other risk factors combined.
The predictive power of the calcium score continues on after symptomatic coronary heart disease develops. Patients with angina and calcium scores over 400 have cardiac events at rates as high 15% per year.
Some physicians have been questioning us because they are concerned that patients with soft plaque (new atherosclerotic plaque which has not yet calcified) will be missed with EBT. While the presence of a soft coronary plaque can not be excluded by EBT, numerous population studies have demonstrated that having a coronary calcium score of less than 11 is associated with an extremely low rate of cardiac events rate. From these studies we conclude that the clinical importance of soft plaques for the prediction of future events is very low and does not invalidate the use of this technology in everyday clinical practice.
Besides it’s use to stratify middle age patients for the risk of future coronary events, the coronary calcium score is also a strong predictor of mortality in the elderly that is independent of other cardiovascular risk factors. The data shown below was obtained by researchers from University of Groningen Hospital in The Netherlands from 2,032 people ages 55 to 85, with a mean age of 77, who underwent EBCT calcium scoring between 1997 and 2000; 47% of the study patients had calcium scores between 0 and 100, 26% had scores between 100 and 500, and 27% had calcium scores greater than 500. The mean duration of follow-up was 2.7 years, during which time 92 subjects died. After adjusting for age and sex, only an increased calcium score was clearly associated with a decrease in survival. Subjects with calcium scores between 101 and 500 were at a double risk of mortality compared to the reference category, and subjects with calcium scores over 500 were at 2.7 times increased risk of mortality. Over the follow-up period, the increase in mortality between the lowest and the middle category of calcium scores (0-100 and 101-500) was 12.3%; and between the middle and the highest scores (101-500 and >500) was 23.7 per 1,000 person years. This analysis was repeated after excluding those subjects (16%) with a history of cardiovascular disease. Coronary calcification in those with scores over 500 was still associated with 3.1 times the risk of death compared with the lowest-scoring group.
Finally, the presence of detectable coronary calcium is also associated with an increased rate of atherosclerotic events at other locations in the vascular tree. Researchers in Rotterdam in the Netherlands prospectively studied 2013 subjects ages 55 and older (mean age 71 [5.7] years). Subjects with calcium scores between 101 and 500 experienced strokes at twice the rate of the reference group and those with scores above 500 had three times the number of strokes as the reference group.
Rapidly Increasing Coronary Calcium Scores Identify Higher Risk Individuals
Researchers at Tulane studied 495, nonconsecutive, asymptomatic individuals who were referred for screening coronary calcium examination. Individuals with coronary calcium scores above 30 and who were treated with statins as primary prophylaxis by their primary physician were followed with repeat coronary calcium evaluation and for the occurrence of MI. The average age of the cohort was 57, 63% were male, 57% were hypertensive, 15% were diabetic, 40% were smokers and 76% were hyperlipidemic. At initial presentation 31% had coronary calcium scores between 30 and 100, 42% had baseline calcium scores of 101 to 400, 21% had baseline calcium scores between 401 and 1,000 and 7% had scores over 1,000. Follow-up coronary calcium scans were performed at an average of 1.9 years and the occurrences of subsequent MI was determined by phone contact, medical record review or contact with the primary physician. A total of 41 MI’s were documented during the follow-up period. The figure below shows the MI free survival in individuals with stable plaque and in individuals with rapidly increasing calcium scores ( â‰¥ 15% per year). The mean percentage increase in calcium score in individuals experiencing an MI was 42%.
Early detection of CAD can positively impact patient care enormously. After all, what patient’s really want to know is what is their risk of having a heart attack and what they do to lower that risk? Is your patient at high risk or low risk? This is precisely the information that the EBCT heart scan gives you. It is one thing to advise a patient to diet and exercise but do not underestimate the value of seeing that calcified coronary artery on patient moral. This test is an powerful motivational tool that can dramatically improve patient compliance with diet, exercise, smoking cessation and medical therapy.
Indications for Coronary Calcium Scanning:
A coronary calcium scoring evaluation is indicated in those patients for whom the results of this test would be expected to change or influence therapy.
Since over 5% of men over age 45 and women over age 55 have coronary calcium scores above 80 and therefore would be candidates for primary prevention therapies, it is appropriate to begin screening men and women above these ages for coronary artery disease. Screening of younger individuals is appropriate when other risk factors such as a family history of premature coronary disease, diabetes or hypertension are present.
Patients who have a borderline indication for primary cardiac prevention therapy such as elevated lipid levels or mild hypertension and are undecided about taking the necessary medication may use the scan result to decide whether or not to commit themselves to the these therapies.
Patients with a family history of premature coronary disease will benefit from the enhanced risk stratification offered by calcium scoring. If premature CAD is detected, this can lead to a search for less “traditional” risk factors, such as homocysteine levels, Lp(a), and wider screening of family members for these and other treatable cardiac risk factors.
In the setting of dilated cardiomyopathy, coronary calcium scoring can be utilized to noninvasively determine the presence and extent of underlying CAD if any, helping to assess whether the cardiomyopathy is likely or not to be ischemic in etiology. A zero or very low calcium score would imply that the cardiomyopathy is of idiopathic, viral or metabolic origin and not ischemic so that coronary angiography could be avoided.
Coronary calcium scanning should become the initial evaluation for patients who present with chest pain, especially younger persons with atypical symptoms. When no coronary calcium is found, the probability of finding coronary artery stenosis is nearly 0.0% for women and 0.7% for men, and the overall probability of finding an abnormal myocardial perfusion scan is nearly 0.0%. Coronary calcium scoring should become the gatekeeper for costly imaging studies and coronary angiography.
Coronary calcium should be measured annually in all asymptomatic individuals with elevated calcium scores since those with scores that increase more than 15% annually are at increased risk for coronary events and require a change in their treatment plan.
Because scanning involves a minimal X-ray exposure, women who are pregnant or potentially pregnant should not undergo this procedure.
Utilizing the Calcium Score in Asymptomatic Individuals:
When counseling patients about the significance of their particular score, it is important to put their score into the context of normal for their age. The thinking is that plaque that occurs prematurely in younger individuals is more aggressive and hence more unstable than plaque that develops slowly with age. Hence a 70 year old man with score of 150, which is below “average” for that age group, has slower growing, more stable plaque than a 40 year old woman with a score of 150, above the 90th percentile for her age group, who has a more aggressive plaque forming process and needs to be treated accordingly. The correlation between the current calcium score and the overall plaque burden remains a linear one.
Integrating the Calcium Score with the Framingham Risk Score (FRS):
The first step in assessing an individuals 10-year risk for cardiac events begins with determining the Framingham Risk Score (FRS). But the FRS alone won’t identify many individuals who should have a coronary artery scan. When determining the degree of risk, we start with the risk group definitions: Low-risk is defined as a 10 year risk of less than 10%, intermediate-risk is defined as a 10 year risk of 10 to 20% and high-risk is defined as a 10 year risk greater than 20%. In 2004, researchers from Johns Hopkins University in Baltimore calculated the Framingham scores of 5,324 asymptomatic individuals and stratified them into low-risk, intermediate-risk, and high-risk groups. These individuals then underwent EBT coronary artery scanning. Abnormal CAC was then defined as a calcium score greater than the 75th percentile, based on gender and age. Among patients deemed “low-risk” by FRS, 13% exhibited an abnormal coronary artery calcium on EBCT. Abnormal CAC was also found in 21% of the “intermediate-risk” patients and 29% of the “high-risk” groups. This demonstrates that individuals should not be denied a CAC sore because they are “low-risk” by FRS.
The coronary calcium sore is then used to refine the FRS risk using Bayes’s Theorem. Sensitivity and Specificity of CAC sores for predicting all events after 10 years was determined from the published literature and is shown in the table below.
CAC > 0 CAC > 80 CAC > 400 CAC > 600
Sensitivity 98% 81% 35% 25%
Specificity 30% 72% 96% 98%
Once the FRS has been determined, the next table shows how this risk is changed by having a given coronary calcium score. For example: if the FRS 10 yr risk is 6% and the CAC score is 250, then the 10 yr risk of any cardiac event rises to 10%, reclassifying this individual from the “low-risk” group to the “intermediate-risk” group. Note that when the Coronary Calcium Score is below 80, the 10 year risk for any event always in the green zone and conversely, when the Coronary Calcium Score is above 400 the 10 year event risk is in the red zone.
Framingham Score 10 yr. event risk recalculated according to Coronary Calcium Score range:
10 yr risk CAC = 0 CAC 1-80 CAC 81-400 CAC 401-600 CAC > 600
1% 0.3% 0.6% 2% 4% 7%
2% 0.6% 1.1% 4% 7% 13%
3% 0.9% 1.7% 6% 10% 18%
4% 1.2% 2.2% 7% 13% 23%
5% 1.5% 2.8% 9% 16% 27%
6% 1.7% 3.2% 11% 19% 31%
7% 1.9% 3.8% 13% 22% 35%
10% 2.4% 5.4% 16% 25% 36%
15% 3.2% 8.3% 23% 33% 45%
20% 3.8% 9.8% 28% 38% 48%
Low-risk = Green, Intermediate-risk = Yellow and High-risk = Red
Alternatively, the FRS can recalculated by adding the following points for coronary calcium score ranges:
CAC Score Range Adjustment to Framingham Point Score
0 -5 -5
1 to 80 -3 -3
81 to 400 +2 +2
401 to 600 +5 +4
>600 +8 +7
Recommendations for Asymptomatic Individuals:
Recommendations for asymptomatic individuals based on their coronary calcium sore can be summarized as follows. Calcium scores of 0 identify individuals in the “lowest-risk” group with 10 year risk for cardiac events less than 5%. These individuals are to be reassured and CAC scans should be repeated no more often than every 5 years. Calcium scores between 1 and 80 also identify “low-risk” individuals. Consequently; these individuals can be recommended to undergo risk factor modification alone and the CAC scans may be repeated at two to five year intervals to monitor for progression. Calcium scores from 81 to 400 identify individuals at increased risk for cardiac events and many of these individuals will be re-stratified to the “intermediate-risk” or “high-risk groups”. These individuals should be treated according to the secondary prevention guidelines of the American Heart Association with reduction of the LDL cholesterol to less than 100 mg% as specified in the NCEP ATP III guidelines. These individuals should also undergo repeat scans every one to two years to monitor treatment response. Calcium scores above 400 identifies individuals in the “high-risk” group and these individuals also have a high likelihood (>90%) of having at least one significantly obstructed coronary vessel (>70% stenosis). The risk for the development of symptomatic cardiac disease in these patients may be as high as 4.8% per year and additional evaluation for the presence of at risk myocardium should be done in addition following the secondary heart disease prevention guidelines of the American Heart Association. Repeat CAC scans are recommended annually to monitor disease progression and treatment response.
Individuals with super-high CAC scores, CAC scores > 1000, have an annual cardiac event rates in the range of 18% to 24%. These individuals should have urgent cardiology referral for testing for inducible ischemia and be treated very aggressively to lower the risk for cardiac events.
Calcium Score Plaque Burden Probability of CAD Cardiac Event Risk* Relative Risk Recommendations
0 No identifiable plaque Very unlikely, <1% 10 yr risk < 2% Annual risk less than 0.11%. 1 Reassure patient. Discuss risk factors. Repeat scans no more often than every 5 years. 1-80 Small plaque Low probability 50% (2 fold) reduction from FRS predicted risk. Annual event rate 0.2%. 2 Risk factor modification. Repeat scans in 2 to 5 years. 81-400 Moderate atherosclerotic plaque burden Non-obstructive CAD likely, although obstructive disease possible 50% increase in FRS predicted risk. Annual event rate 1%. 10 Secondary prevention guidelines of AHA. Exercise testing if clinically indicated. Daily ASA, Statins. Repeat scans annually. >400 Extensive atherosclerotic plaque burden High likelihood of at least one significant coronary stenosis FRS predicted risk increases 8 fold. 10 year event risk ranges from 20% to 70%. Annual event rate up to 4.8%. 25 Secondary prevention guidelines of AHA. Evaluate for inducible ischemia. Daily ASA, Statins. Repeat scans annually.
* Event risk is for asymptomatic individuals, symptomatic individuals with elevated CAC scores have considerably higher event rates
Application of Coronary Calcium in Symptomatic Individuals
The presence or absence of coronary calcium can significantly alter the posterior probability of CAD for individuals presenting with chest pain. The calculator below shows how these probabilities are affected and computes similar data for exercise treadmill testing. Note that coronary calcium compares favorably with exercise testing for evaluation of chest pain syndromes and often has a higher negative predictive value, especially in women were exercise treadmill testing is known to be weak.
Coronary artery calcification scanning with the electron beam CT scanner is a breakthrough test that affords the opportunity to determine very accurately and noninvasively whether or not coronary artery disease is present in asymptomatic individuals, allowing us to calculate the associated risk of coronary events over time to optimize patient care, helping to appropriately tailor prevention goals and to determine further evaluation and follow up, if needed. A simple to follow treatment recommendation tree has been devised biased solely on absolute calcium score. Repeat coronary artery calcium scoring allows us to monitor changes in the plaque burden and the effects of our treatment. The EBT calcium score is a powerful motivational tool for improving patient compliance with lifestyle changes and medical therapy.
The coronary calcium scoring exam does not define the location or severity of any particular coronary stenosis and is not a substitute for physiological stress testing or angiography. The diagnosis of obstructive coronary disease continues to require stress testing or angiography. Individuals with calcium scores over 10 have coronary heart disease and should receive treatment according to the secondary prevention guidelines of the American Heart Association. Patients with significant coronary calcium deposition, especially those with scores over 400, should be considered for further evaluation to rule out an obstructive lesion with an exercise or pharmacologic stress test. Individuals with symptomatic angina and calcium scores over 600 have an extremely high (~15%/yr) cardiac event rate and should be referred to cardiology for either SPECT or coronary angiography with either the Electron Beam CT or the conventional interventional technique, as clinically indicated.