Electron Beam Computed Tomography and Coronary Artery Disease: Scanning for Coronary Artery Calcification

Subspecialty Clinics: Cardiology Electron Beam Computed Tomography and Coronary Artery Disease: Scanning for Coronary Artery Calcification JOHN

A. RUMBERGER, PH.D., M.D., PATRICK F. SHEEDY II,

LORRAINE

A. FITZPATRICK, M.D.,

• Objective: To review the association of coronary artery calcification with coronary atherosclerosis and its potential clinical application as detected on electron beam computed tomography (EBCT). • Design: A literature review of coronary artery calcification, coronary artery disease, and EBCT is presented, and clinical applications of EBCT are discussed. • Results: Recent studies have confirmed that arterial calcification is an active process intimately associated with atherosclerotic plaque evolution. Clinical investigations with use of EBCT have shown that a scan "negative" for coronary calcification is common in patients with normal or near-normal findings on coronary angiography, whereas patients with severe obstructive disease most commonly have "positive" scans-greater amounts of coronary artery calcium are associated with more severe luminal disease. Coronary artery calcium as evaluated on EBCT follows patterns that reflect the development of coronary atheromatous disease as a function of age and gender.

Coronary artery calcification is intimately associated with mural atheromatous plaque.':" Recent studies have challenged dogma which implied that coronary artery calcification is merely a marker for passive end-stage plaque "degeneration" by demonstrating that intramural calcium can be observed in all degrees of atherosclerotic involvement, and From the Division of Cardiovascular Diseases and Internal Medicine (JAR., R.S.S.), Department of Diagnostic Radiology (P.F.S., J.F.B.), and Division of Endocrinology/Metabolism and Internal Medicine (L.A.F.), Mayo Clinic Rochester, Rochester, Minnesota. This study was supported in part by Grants HL 46292 and HL 51736 from the National Institutes of Health, Public Health Service, and by Mayo Foundation. Dr. Rumberger is supported in part by an Established Investigator Award from the American Heart Association. Address reprint requests to Dr. J. A. Rumberger, Division of Cardiovascular Diseases, Mayo Clinic Rochester, 200 First Street SW, Rochester, MN 55905. Mayo Clin Proc 1996; 71:369-377

M.D., JEROME F. BREEN, M.D.,

AND ROBERT S. SCHWARTZ, M.D.

Although histologic studies have confirmed that not all atherosclerotic segments have detectable calcification, the area of coronary artery calcification quantified on EBCT has a direct, positive relationship with the histopathologic coronary plaque area. • Conclusion: The long-held notion of "degenerative" calcification of the coronary arteries with aging is incorrect. Although the incidence of coronary artery calcification increases with patient age, this relationship simply parallels the increased incidence of coronary atherosclerosis with advancing age. Data suggest that EBCT is a highly sensitive and specific test for coronary atherosclerosis and provide a basis for clinical applications when EBCT is viewed as a noninvasive method to estimate human coronary atherosclerotic involvement and "plaque burden." (Mayo Clin Proc 1996; 71:369-377) EBCT = electron beam computed tomography; mRNA messenger RNA

=

its presence can denote an active process of plaque development." Electron beam computed tomography (EBCT) has been extensively tested at the Mayo Clinic and elsewhere for noninvasive identification and quantification of discrete coronary artery calcification. Scanning can be completed within minutes, requires minimal patient cooperation, and involves no administration of contrast medium. The absence, presence, and amount of coronary artery calcification determined on EBCT (as a surrogate to localization and quantification of atherosclerotic plaque) may be an effective means to assess and triage patients at risk for premature coronary artery disease or those with nondiagnostic chest pain syndromes. In this report, we review the association of coronary artery calcification with coronary atherosclerosis and its potential clinical application as detected on EBCT. 369

© 1996 Mayo Foundation/or Medical Education and Research

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PATHOPHYSIOLOGIC MECHANISMS OF CALCIFICATION AND ATHEROSCLEROTIC DISEASE Calcification of the coronary arteries is actually calcium phosphate in the form of hydroxyapatite, which also is the major inorganic component of bone. Although the role of calcification in coronary artery disease is unclear, recent data demonstrate its pathophysiologic mechanisms. Fitzpatrick and associates" used special staining techniques to examine coronary artery specimens obtained at autopsy and found that mural mineralization was present to some extent and diffuse in virtually all atherosclerotic plaques. Conversely, hydroxyapatite was not detected in coronary artery sections deemed normal by traditional light microscopy. Furthermore, in calcified atherosclerotic plaques, these investigators identified messenger RNA (mRNA) for a cell attachment protein (osteopontin), a protein associated with calcification (osteonectin), and a "I-carboxylated protein that regulates mineralization (osteocalcin). All three of these proteins are commonly associated with normal calcification and remodeling of bone. Immunohistochemistry demonstrated intense staining for osteopontin in the outer margins of all diseased segments at each calcification front, although staining was often evident throughout an entire plaque. Hirota and colleagues? established that the magnitude of osteopontin expression in situ is related to the severity of atherosclerotic involvement. Conversely, they found osteonectin mRNA to be less prominent in more advanced atherosclerosis than in smaller plaques. These studies and others have established that calcification in coronary artery disease is an active process closely associated with plaque development, which is regulated in a fashion similar to bone mineralization. ELECTRON BEAM COMPUTED TOMOGRAPHY With conventional CT, a single x-ray source mechanically rotates around the patient in concert with a stationary or rotating collimator-detector combination. Scan speeds of 1 to 2 seconds for conventional scanners and even 600 ms for the new spiral technology are still too slow to capture cardiac motion or evaluate fine details of cardiac and coronary anatomy. EBCT (introduced commercially in 1983) employs a stationary source-detector pair coupled to a unique technology whereby x-rays are produced as a rotating electron beam is swept across a series of 1 to 4 semicircular tungsten targets situated beneath the subject. The imaging chain has no moving parts, and scanning through or at preset times during the cardiac cycle and from adjacent cardiac sites is possible in rapid succession. In 1986, a "highresolution" scanning procedure was introduced to facilitate traditional whole body CT examinations of the thorax and abdomen. EBCT currently offers a noninvasive means to

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obtain quantitative information on cardiac anatomy, function, and flow and is a clinical alternative to conventional cardiac imaging. 10 12 For the detection of coronary artery calcium on EBCT, consecutive single-slice, 100-ms scans are performed. Tomographic slice thicknesses are usually 3 mm, although 1.5-mm scans are possible. In this high-resolution volume scanning mode, 20 to 40 sequential scans of the heart with electrocardiographic triggering during late diastole can be completed in about 20 to 40 seconds. Depending on the patient's pulse rate, two serial breath holds may be necessary to obtain tomograms from the root of the aorta and the origin of the left main coronary artery through distal portions of the right coronary artery. During scanning, epicardial coronary artery motion is "frozen"; thus, blurring of vessel borders due to "motion-urisharpness" artifact is minimal. In-plane spatial resolution is about 0.6 mm, and imaged opacities (densities) are accurately localized in three-dimensional space. Three aspects make EBCT ideal for detecting and quantifying coronary artery calcium: rapid, consecutive, thin-slice (1.5 to 3.0 mm) tomographic scanning during a predefined phase of the cardiac cycle within a breath hold; three-dimensional image registration; and no need for intravenous administration of contrast medium. Contrast medium is unnecessary because calcific deposits in arterial walls demonstrate relatively high EBCT densities (measured as Hounsfield units), approximately 2- to lO-fold higher than the surrounding soft tissue. Thus, because of the appearance of highdensity intramural coronary artery calcium deposits adjacent to low-density soft tissue and surrounding fat, visual detection of calcium in the coronary arteries by EBCT is readily apparent, even to untrained observers. An example of a single-level, 100-ms, electrocardiographic-triggered (enddiastolic), 3-mm-thick EBCT scan taken at the base of the left ventricle in a 56-year-old man who underwent coronary angiography is shown in Figure 1 A. Anatomic details of the aorta, pulmonary artery, and proximal portions of the left anterior descending, circumflex, and right coronary arteries are evident. The high-density material surrounding each coronary artery section represents coronary artery calcification. At angiography, the patient was found to have diffuse coronary artery disease with substantial narrowing of the mid-left anterior descending artery and mid-right coronary artery (Fig. 1 B).

CORONARY ARTERY CALCIFICATION, CORONARY ARTERY DISEASE, AND EBCT Tanenbaum and coworkers" described EBCT detection of coronary artery calcium in 54 patients undergoing clinically indicated coronary angiography. In 11 patients with no angiographically detectable coronary artery disease, none

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Fig. 1. A, High-resolution, non-contrast-enhanced electron beam computed tomography (EBCT) of base of heart. Heart is in the middle, sternum is anterior, and spine is posterior. Aorta is near center of scan; pulmonary artery is just anterior and left atrium is just posterior to aorta. High-density areas on periphery of heart are coronary artery calcifications of mid-left anterior descending (right and anterior), mid-left circumflex (right and posterior), and mid-right coronary arteries (left and anterior). B, Single frame from selected coronary angiogram of right coronary artery in same patient in Figure 1 A. Discrete, tubular stenosis of mid-right coronary artery corresponds to area of calcification evident on EBCT scan.

had detectable calcium on EBCT ("negative" test results). Conversely, discrete coronary artery calcium was detected by EBCT in 88% of patients who had at least one hemodynamically significant coronary artery lesion (defined as greater than 70% diameter stenosis). Agatston and associates 14 later developed a calcium scoring algorithm for EBCT images that is now widely used in research and clinical studies. The "calcium score" is a product of the area of calcification per coronary artery segment and a factor rated I through 4 dictated by the maximal calcium CT density within that segment. A calcium score can be calculated for a given coronary segment, a specific coronary artery, or for the entire coronary system; however, most studies have described the use of a composite "score" for the entire epicardial coronary system (left main, left anterior descending, left circumflex, and right coronary arteries). Simons and colleagues" performed EBCT scanning on dissected coronary vessels from hearts obtained at autopsy and compared the extent of coronary artery calcium with paired histologic sections. This study and an independent histologic study by Mautner and coworkers" showed that the correlation of EBCT-quantified coronary artery calcium with the severity of coronary artery luminal narrowing is positive but nonlinear with large confidence limits. Thus, coronary artery calcium cannot be used for absolute quantification of stenosis severity on a segment-by-segment basis. Furthermore, atherosclerosis could be present despite the absence of discrete calcium at the same anatomic site. Simons and associates" indicated, however, that the pres-

ence of "significant" coronary artery disease (that is, 75% or more of an area or approximately 50% or greater diameter stenosis) was present in only 2.5% of individual coronary artery segments with no detectable calcium on EBCT. In a clinical study by Breen and colleagues" of a group of 100 patients younger than 60 years of age who underwent both diagnostic coronary angiography and EBCT, the absence of identifiable coronary artery calcium (that is, a calcium score of zero) had a negative predictive value of 100% for excluding the presence of any lesions with 50% or greater diameter stenosis. A more recent report from the same laboratory showed that the sensitivity of EBCT in detecting coronary artery calcium was between 94 and 97% for the presence of any arteriographic narrowing, and the negative predictive value for significant (50% stenosis or more) disease exceeded 95%.18 Thus, a completely negative EBCT study may have important clinical implications. A study by Fallavollita and coworkers,'? however, suggested that this degree of accuracy in identifying coronary artery disease may not occur in all patient groups. In their study of 106 patients younger than 50 years of age, the negative predictive value for significant angiographic disease overall was only 85%. Furthermore, the sensitivity for detecting 50% or greater stenoses based on coronary artery calcium in 28 patients with single-vessel disease was only 75%. Only twenty 3-mm sections were examined, however, in comparison with 30 to 40 sections in most other studies, and distal calcification, commonly evident in the right coronary artery," may have been overlooked in the analysis. The actual

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negative predictive value for 50% or greater narrowing at angiography or EBCT, which includes the entire epicardial coronary system, probably is closer to 90 to 95%. Despite the excellent sensitivity of coronary artery calcium as detected on EBCT or angiography for luminal disease, the specificity of a "positive" scan (that is, a calcium score above zero) is generally considered poor; it ranges from 35% to 38% for any angiographic narrowing" and from 45%19 to 66%18 for significant disease. This finding suggests restricted clinical application of EBCT-detected calcium to stratify patients in whom a positive test result is specific for variable degrees of coronary artery stenoses. To address these limitations, Kaufmann and associates" performed receiver operating characteristic analysis in 160 patients younger than 60 years of age who had undergone coronary angiography, followed by EBCT. They attempted to determine optimal quantities of calcium ("cutpoints") to distinguish among no (normal), mild (maximal diameter stenosis, 10 to 40%), and significant (50% or greater stenosis) luminal disease. With use of total coronary artery calcium area as defined by EBCT, the best cutpoint for distinguishing between persons without versus those with angiographic disease was the presence of any single calcium area 2 mrrr' or larger (sensitivity, 81%; specificity, 86%; and accuracy, 83%). For persons with no disease in comparison with those who had significant luminal disease, the optimal cutpoint was a calcium area of 18 mm' (sensitivity, 86%; specificity, 81%; and accuracy, 83%). We performed receiver operating characteristic analysis on studies of 251 consecutive patients who underwent EBCT in conjunction with clinically indicated coronary angiography and determined total calcium scores that provided 90 and 95% specificities for variable degrees of angiographically detected disease (Table 1). For example, a calcium score of 36 yields a 95% specificity for at least a 20% or greater coronary artery stenosis, whereas a calcium score of almost 400 is needed to confirm the same specificity for at least a 50% or greater stenosis. Thus, application of selected EBCT-identified coronary calcium areas or calcium score cutpoints have a potential for predicting the likely degree of luminal narrowing that may be found at angiography. Of importance, however, clinical interpretation of the calcium areas or calcium scores (or both) and their relationships to angiographically detected disease should be considered only as guidelines at best because, as previously discussed, a direct one-to-one correlation between coronary artery calcium as detected by EBCT and luminal disease is not possible.

AGE, GENDER, ATHEROSCLEROTIC PLAQUE, AND CORONARY ARTERY CALCIFICATION Janowitz and colleagues" have published the most extensive investigation to date on the prevalence and extent of coro-

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Table I.-Total Electron Beam Computed Tomographic Calcium Score "Cutpoints" for 90% and 95% Specificities in Predicting Angiographic Disease Severity* Angiographic disease severity] ;::20% stenosis ;::30% stenosis ;::40% stenosis ;::50% stenosis ;::70% stenosis

Total EBCn calcium score "cutpoint" 95% specificity 90% specificity 26

75 106 159

284

36

159

175 368

746

*Based on results of 251 patients who underwent EBCT and angiography. tMaximal coronary artery narrowing. tEBCT = electronbeam computedtomography.

nary artery calcium detected by EBCT. This study was conducted in 1,898 men and women, whose ages ranged from 20 to older than 80 years (Fig. 2). The pertinent points about these data are as follows. First, regardless of gender, the prevalence of coronary artery calcium increases with advancing age. Second, the prevalence of coronary calcium is lower in women than in men until about the seventh decade. On the basis of the current information about coronary atherosclerosis, the prevalence of disease in women approaches that of men during the first decade after menopause or about the age of 65 years, as suggested by the EBCT data. Furthermore, in persons younger than 65 years of age, a lO-year lag is noted in the prevalence of coronary artery calcium in women in comparison with that in men. Thus, coronary artery calcium as detected by EBCT follows a pattern similar to that of the epidemiology of human coronary atherosclerosis, both in general and as a function of gender. For a further examination of the issues of coronary disease, age, and coronary artery calcification, some additional analyses were performed on studies previously reported by our Iaboratory.F:" The results of an analysis that examined the total sum of histopathologic coronary artery plaque areas (sum of all three major epicardial vessels) and the total sum of corresponding EBCT-determined coronary artery calcium areas from 13 hearts obtained at autopsy (8 men and 5 women; age range, 17 to 83 years) as a function of age at death are shown in Figure 3. Whole heart coronary plaque area increased progressively with patient age. The corresponding (whole heart) coronary artery calcium area also increased with patient age, in a fashion almost parallel to that of total plaque with advancing age. These data, in conjunction with the data in Figure 2, indicate that the increase in the prevalence and extent of coronary artery calcium with advancing age reflects a parallel increase in the prevalence and

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Percent (%) Incidence

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Age by Decade Fig. 2. Incidence of coronary artery calcification detected by electron beam computed tomography in men and women, as function of age (see text for details). (Data from Janowitz and associates.")

extent of coronary artherosclerotic plaque with advancing age. Two recent reports from the Mayo Clinic, a histopathologic study" and a clinical study," showed that EBCTdetected coronary artery calcium has a similar predictive value in men and women for the evaluation of coronary artery luminal narrowing. A recently published study by Rumberger and coworkers" emphasized that the total area of coronary artery calcification detected by EBCT correlates linearly with the total area of histologic coronary artery plaque on a segmental, individual coronary artery (Fig. 4) and on a whole coronary artery system basis. Nevertheless, the total areas of coronary artery calcification significantly underestimated the total associated coronary artery plaque areas. Thus, identification of calcium by EBCT scanning demonstrates only the "tip of the atherosclerotic iceberg." This study reconfirmed that coronary artery plaque is not always associated with coronary artery calcification as detected on x-ray CT. These data suggest, however, that a specific coronary artery plaque area may be needed for demonstration of coronary artery calcium, and in small plaques, the calcium is either absent or undetectable by this method. This close relationship between calcium and plaque helps to explain why EBCTdetected coronary artery calcium has a limited direct association with luminal narrowing inasmuch as, in independent histologic studies, both coronary artery plaque and its associated coronary artery calcification frequently display a poor

correlation with the extent of histopathologic stenosis.r':" most probably because of vascular remodeling during plaque development.

CLINICAL APPLICAnONS AND INTERPRETAnON A relationship between the fluoroscopic presence of coronary artery calcification and cardiovascular prognosis has been suggested. Detrano and associates" recently described the clinical significance of digital fluoroscopic examination for coronary artery calcium in a prospective assessment of 1,461 asymptomatic adults older than 45 years of age who were at high risk for coronary disease (Framingham risk calculation, 10% or higher over 8 years). At I-year followup, 53 subjects (4%) had at least one cardiac event, which was defined as death due to coronary heart disease, nonfatal infarction, need for coronary revascularization, or development of angina. Fluoroscopically detectable calcium was associated with a relative risk ratio of 2.7 (90% confidence intervals, 1.4 to 4.6) and was an independent predictor of at least one cardiac endpoint when age, gender, and standard risk factors (for example, serum lipids, smoking, and systolic blood pressure) were being controlled. Nevertheless, three deaths due to coronary heart disease and two nonfatal infarctions occurred in subjects without detectable coronary artery calcium. Naito and colleagues" used conventional CT for a mean of 4 years to monitor a group of 241 persons (136 men and 105 women) whose mean age was 61 years. Of 82

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patients with coronary artery calcium, 5.5% had a myocardial infarction, whereas none of the 159 patients without coronary artery calcium experienced infarction. Overall mortality (all causes) did not differ between the two groups; however, for the women, all-cause mortality was 26% (3.7% infarction) in the group with calcification and 9% (0% infarction) in the group without calcification. No data are available on the potential significance of coronary artery calcium detected by conventional CT and prognosis in younger persons. Limited data are available on coronary artery calcium detected by EBCT and prognosis. Preliminary data from an ongoing multicenter trial of 595 patients who were monitored for 1 to 2 years after they underwent clinically indicated angiography and EBCT suggest that the calcium score may be of value in assessing prognosis. In a brief report by Wong and coworkers," the need for revascularization or the occurrence of myocardial infarction (or both) was 0.9% in patients with a calcium score lower than 20 (likely to be associated with no or minimal luminal narrowing) (Table 1), but it increased to 23.3% in patients with a calcium score

greater than 500 (likely to be associated with severe luminal narrowing) (Table 1). Despite the fact that these preliminary data are of interest, they are from patients who underwent clinically indicated coronary angiography and may not necessarily be applicable for determining prognosis in asymptomatic patients with similar calcium scores. Longer follow-up of more subjects is needed to establish the broad application for these provocative data. Information about a negative or positive EBCT examination for coronary artery calcium is summarized in Tables 2 and 3. The most powerful relationships seem to be in identifying persons with minimal or no calcified plaque (calcium score, zero or low [generally less than 20] or total calcium areas, less than 2 mm-) and those with moderate to severe calcified atherosclerotic plaque (calcium score, greater than 400 or total calcium areas, greater than 18 mrrr'). Limited data suggest that the progression of coronary artery plaque development can be monitored by serial EBCT scanning for 3 to 5 years." Until these data are completely scrutinized, however, recommendations for serial testing in a specific person remain moot.

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In our opinion, EBCT has potential in two major patient subgroups; however, as additional data are obtained, these applications are likely to expand. The first group consists of asymptomatic persons at high coronary risk (two or more conventional coronary risk factors). In such persons, scanning may establish the extent, if any, of calcified coronary artery plaque. On the basis of the aforementioned information, persons with minimal or no coronary artery calcium are likely in a group that has a favorable prognosis. In one recent study," a mean of 80% of men and women with a negative EBCT calcium scan were found to have angiographically "normal" coronary arteries. Such persons could

be given general public health guidelines on discontinuation of smoking, adherence to a low-fat diet, regular exercise, and routine medical follow-up. In contrast, asymptomatic persons with at least moderate coronary artery calcium (scores higher than 20 but lower than 300) would likely be candidates for education on angina and coronary artery disease and aggressive risk factor modification, including a strict diet, daily low-dose aspirin, and medications to lower fasting serum cholesterol and low-density lipoprotein levels. Persons with significant coronary artery calcium (calcium score, greater than 400) would likely have advanced plaque disease and should be considered for further assessment, which may

Table 2.-Absence of Detectable Coronary Artery Calcification on Electron Beam Computed Tomography*

Table 3.-Presence of Detectable Coronary Artery Calcification on Electron Beam Computed Tomography*

Does not absolutely exclude the presence of atherosclerotic plaque

The presence of coronary atherosclerotic plaque is confirmed

Is highly unlikely in the presence of severe luminal obstructive disease

The greater the amount of calcification (that is, calcium area or calcium "score"), the higher the likelihood of obstructive disease, but no one-to-one relationship exists, and the findings may not be specific for the site

Is the result in most patients who have had both angiographically normal coronary arteries and normal findings on electron beam computed tomographic scanning Is gender independent

The total amount of calcification correlates best with the total amount of atherosclerotic plaque, although it underestimates the actual "plaque burden"

May be consistent with a low risk of a cardiovascular event during the next 2 to 5 years

A high calcium score may be consistent with a moderate to high risk of a cardiovascular event within 2 to 5 years

*Negative test results.

*Positive test results.

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include formal stress testing or coronary angiography (or both). A second group of patients in whom EBCT scanning may be helpful is those with "atypical" cardiac symptoms in whom the pretest likelihood for ischemic disease is considered low by the clinician. As previously discussed, the negative predictive value of EBCT to detect significant disease (that is, 50% or greater diameter stenosis in any major coronary vessel) is probably close to 95%. This group is likely to have a negative or minimal calcium score. Thus, EBCT may be an appropriate first test in those with symptoms such as "atypical" chest pain syndromes. Persons with a zero or low calcium score could be reassured, and further testing would be directed at noncardiac sources of chest pain. Conversely, if the calcium score is consistent with moderate or severe atherosclerotic plaque development, then additional cardiac testing may be the next appropriate step. These two patient groups, asymptomatic "high-risk" patients and those with no known coronary artery disease and atypical chest pain syndromes, are more commonly examined initially by a primary-care physician than by a cardiologist. Thus, although use of EBCT to detect coronary artery calcium may be valuable to the cardiologist, it may also be useful to the primary-care physician as a screening tool in selected patients who could then be referred to a cardiologist after the findings have been evaluated. EBCT can be done in virtually any subject, is anatomically rather than physiologically based and thus requires no preparation or discontinuation of medications before testing, is completely noninvasive, and involves minimal patient cooperation. Moreover, results are available within minutes for qualitative analysis. Quantitative review of calcium scoring is available within 20 to 30 minutes. The current clinical charge for the examination ("limited CT of the chest") is approximately the same as that for a routine nursemonitored treadmill test. This amount is about one-half the charge for a stress echocardiogram and one-third the charge for a stress radionuclide examination. Use of EBCT, however, involves radiation. At our institution, routine dosimetry studies show that a single "screening" EBCT scan for coronary artery calcium has an "effective" (integrated over thorax) radiation dose of 82 mR for men and approximately 150 mR for women (accounting for breast irradiation). In comparison, a combination posteroanterior and lateral chest roentgenogram involves only 10 mR, and a screening twoview mammogram has about 35 mR. Of course, conventional coronary arteriography would result in radiation doses of an order of magnitude or greater than that with an EBCT scan for coronary artery calcium. Even though the EBCT radiation dose is minimal, indiscriminate use or "mass screening" is not condoned. Currently, we recommend it be

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done only at the request of a physician and for specific clinical indications as previously outlined. In clinical practice, the value of any specific imaging modality depends on its perceived application. The fact that up to 30% of the initial coronary angiograms obtained in the United States reveal normal coronary arteries," a finding that would have been predicted to a high degree of confidence by a negative EBCT examination, may have important implications for cost-containment health-care strategies. Of importance, however, quantification of coronary artery calcium on EBCT cannot define the site and severity of luminal narrowing with absolute certainty. Thus, EBCT will never be a surrogate to direct visualization of the coronary artery lumen with angiography. "Percent stenosis," however, does not disclose the complete "story" for the extent of atherosclerosis. Angiographically detected severe obstructive coronary artery disease clearly correlates with the propensity for the development of angina or acute myocardial infarction (or both), but the presence of severe stenoses may merely be a marker for the presence of angiographically identified modest, noncritical atherosclerotic plaques, which may actually be more prone to rupture and precipitate acute cardiac events. The assessment of "plaque burden" may ultimately be more predictive of cardiac outcomes than is the definition of luminal narrowing. The data presented herein provide a basis to suggest that the application of EBCT to detect coronary artery calcium may have a major clinical and potentially cost-effective role when it is viewed as a direct, noninvasive method to estimate the likelihood of the degree of luminal narrowing or, more importantly and more directly, the likelihood of the coronary atherosclerotic plaque burden in asymptomatic and symptomatic adults suspected of having premature or developing coronary artery disease.

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