s021.jpg (8012 bytes)Coronary artery disease (CAD) is the No. 1 killer in the Western world. Recent developments in surgery, interventional radiology, and pharmacology have begun to reduce the toll, but many times, these treatments are applied late, when they are less likely to produce the maximum benefit. Is earlier diagnosis possible without invasive studies?

Considerable research has been devoted to the potential of coronary calcium measurement as a means of detecting CAD earlier when treatment can be more effective. Although it is clear that calcification can be measured accurately, debate continues over what the measurements imply and which patients should be scanned. This article examines the established technique of electron beam tomography (EBT) and the new use of ultrafast spiral CT scanners for calcium measurement, and present thinking about the role of calcium measurement in screening for CAD, as well as some less controversial roles for the technique.

Looking at EBT
An EBT examination of the heart captures 35 to 40 consecutive 3-mm slices at 100-msec intervals with gating to end-diastole. This speed, which is unmatched by other available equipment, is made possible by the scanner’s absence of moving parts. The output of an electron gun is focused into a minute beam by a series of electromagnets. This beam is swept along one of four fixed tungsten rings underneath the patient, generating a fan-shaped, 30-degree X-ray beam. After passing through the patient, the X-rays are collected by a 210-degree arc of more than 3,000 detectors above the patient. The informational content is digitized and flows to the workstation at the rate of 17 MB/sec.

An EBT scanner can operate in cine, flow, or volume and in single and multislice modes. For calcium scoring, the multislice volume mode is used. The entire examination takes about 10 minutes of the patient’s time and one to two breathholds.

The physician reviews each image slice, circling every calcified site with the mouse and informing the scoring program of its location (e.g., the circumflex artery) by clicking the appropriate button on the workstation screen. Within the marked area, the software identifies each pixel that has a density twice to 10 times that of soft tissue; i.e., 130 HU or greater. The program then rates each pixel’s density on a scale of 1 to 4 that reflects the amount of calcium. Whenever the program finds a dense pixel with three contiguous pixels with densities less than 130 HU, it knows it has reached the edge of the lesion. When the entire series of images has been marked, the computer calculates the Agatston score, which indicates the total size and density of all calcium deposits.

Each report of a calcium scoring scan includes the relevant medical history, a table showing the score by anatomic site, a graph depicting the total score in relation to patient age and sex, and recommendations for further testing and treatment. Representative images can be included.

Ultrafast spiral scanning: A substitute for EBT?
Some makers of ultrafast helical CT scanners are pitching the merits of their systems for calcium scoring.

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GEMS’ HiSpeed CT system

Picker Mx 8000 CT system

In 1988, three manufacturers of ultrafast spiral CT scanners entered the market for calcium scoring. Picker International, now known as Marconi Medical Systems (Highland Heights, Ohio), launched its Mx8000 four-slice scanner, with an acquisition time of 500 msec, and its HeartBeat-CS calcium scoring package. GE Medical Systems (Waukesha, Wis.) also received Food and Drug Administration clearance for its SmartScore software package for use with the HiSpeed CT/i scanner and Advantage workstation. With this technique, the acquisition is not gated to the cardiac cycle. Rather, the software uses the patient’s EKG to select images captured during diastole. The physician defines calcified regions on the axial images or composite maximum intensity projection reconstruction and uses different colors to indicate which artery is affected. The SubSecond Cardio CT software package from Siemens Medical Systems (Iselin, N.J.) is used with the Somatom Plus 4 scanner. To reduce motion artifacts, the program limits the acquisition time to 500 msec, acquiring a partial scan (240 degrees). The acquisition is ECG triggered to every other heartbeat.

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Coronary calcification is identified by the white area in the heart region (left), using Siemens’ Somatom Plus 4 CT scanner (right).

Even when the heart is electrically silent, it is in motion. Thus, the exposure times (e.g., 500 msec) of the spiral scanners can cause blurring of small features such as calcifications. Moreover, because a calcification is spread over more pixels, its density is reduced, and, on occasion, its location in the heart may be unclear. Examples of the need to devise different procedures for scoring on spiral scanners were recently described by Matthew J. Budoff and his colleagues from Harbor-UCLA Medical Center in Torrance, Calif., who studied 31 asymptomatic subjects by both EBT and spiral CT.

“There was a tendency for the spiral scanner scores to be higher than the EBT scores,” Budoff reported this past November at the 1999 Scientific Sessions of the American Heart Association in Atlanta. Three patients with EBT scores of zero had calcification by spiral CT. In two of these subjects, pericardial calcium had been mistaken for disease of the circumflex artery. Significantly, the treatment recommendations would have been different for one third of the subjects depending on whether they were studied by EBT or spiral scanning. The inter-test variability was high – 79 percent – making comparisons of scores obtained by the two methods “impossible.”

Budoff, yet, cautioned against automatically applying protocols and practices from EBT to calcium scoring on spiral scanners.

“The amount of exposure time used with the [spiral] scanner might lead to a need for a different threshold [for identifying calcium],” he noted. Indeed, other investigators have suggested a threshold of 90 HU as appropriate. Budoff also pointed out that 500 msec is “far too slow to eliminate cardiac motion, especially atrial systole,” so there will be some blurring of the CT images. He suggested that lower calcium scores measured on an ultrafast spiral scanner need to be interpreted with caution.

Looking at clinical utility
Two questions have been asked about the utility of calcium scores: Is it helpful in patients with known or suspected CAD? And is it useful in screening asymptomatic patients for CAD? The answer to the first question clearly is “yes.” Some of the present uses of calcium scanning in this population are described in the box.

The answer to the second question is less clear. The atherosclerotic plaques most vulnerable to rupture often are not calcified, a fact that has been one of the chief arguments against using calcium scoring in screening for cardiac event risk. On the other hand, as Alan D. Guerci, M.D., expressed it in arguing the pro-scoring position at the AHA meeting, “EBT cannot identify the plaque of interest, but it can identify the patient of interest.”

The evidence supporting calcium scoring as a predictive technique is derived from histopathologic, angiographic, and clinical studies, as recently reviewed by Rumberger and associates.1

Calcium Scores and Adverse Cardiac Events

Findings of Trials Showing a Positive Correlation between Calcium Scores on EBT and Adverse Cardiac Events in Asymptomatic Patients

The odds ratio of a coronary event during the next 3.6 years was 23:1 in patients with calcium scores of 160 or greater.

Revascularization procedures and coronary events were more likely in men with calcium scores more than 75th percentile for their age.

The odds ratio for the appearance of symptomatic CAD over 36 to 72 months was 6.9 for patients with a calcium score less than 50 vs. 2.7 for those with a score of 1 to 49

Source: Summarized from Rumberger et al. 1

Of particular interest are data from asymptomatic subjects, the conclusions of which are the most relevant to the use of calcium scoring as a screening tool. In a total of 1,866 patients followed for as long as 72 months, there appeared to be a correlation between coronary calcification and the likelihood of a coronary event (see “Calcium Scores and Adverse Cardiac Events” at right). However, in another study, which involved more than 1,300 patients followed for 32 months, there was no correlation between calcium scores and the likelihood of a coronary event.

Do calcium scores tell us anything we don’t already know?
Some observers have charged that although calcium scoring can identify patients at risk of coronary events, it adds nothing to what can be learned from classic risk factors such as diabetes, high blood pressure, and serum lipid profiles. In support of their view, they cite studies such as that of Detrano and associates,2 in which, although patients with higher calcium scores were more likely to have a coronary event, the probability of that event could have been predicted equally well from the traditional risk factors.

Supporters of calcium scoring call attention to reports such as that of Guerci and his colleagues at St. Francis Hospital in Roslyn, N.Y.3 ? In 290 patients with suspected CAD, calcium scores above 80 were associated with a greater likelihood of angiographic coronary disease regardless of the number of risk factors, and if the score was 170 or higher, there was an increased likelihood of obstructive vascular disease, again regardless of the number of risk factors. The applicability of such data to patients without signs and symptoms of CAD, however, is not clear.

The present consensus
Although industry representatives sometimes call calcium scanning a “mammogram of the heart,” practitioners insist that this is not an appropriate analogy. That is, whereas a mammogram is recommended for all women over a certain age, and the proper actions to take for each possible finding are clear, no similar advice can be given for calcium scanning – especially in patients without risk factors for CAD. At the annual meetings of both the American College of Cardiology and the American Heart Association in 1999, there were debates about the appropriateness of calcium use as a screening tool.

Writing Group III of the American Heart Association has just released its Scientific Statement on Noninvasive Tests for Atherosclerotic Burden.4 ? The statement noted that “relatively few prospective data link coronary calcium scores with risk of subsequent [cardiac] events” and that “risk-prediction data in asympomatic persons ? are sparse.” As a result, the Group said it is “reluctant” to advocate the use of calcium scoring for routine risk assessment of asymptomatic persons “despite its promise.” The Group sees considerable potential for scoring to detect advanced CAD in patients at intermediate risk, and many practitioners believe that scanning is appropriate only in patients with known risk factors. (Some make an exception for family history if that is the only risk factor.)

Some Present Uses of Calcium Scoring

Can calcium scores identify asymptomatic individuals at risk of unheralded myocardial infarction? Such patients often have high scores, as reported by Stephan Achenbach, M.D., and his coworkers at the University of Erlangen in Germany. They performed EBT scanning of seven women and 48 men aged 20 to 59 years who suffered unheralded myocardial infarctions. Coronary calcification with a mean Agatston score of 285 (range 1-6315) was found in 47 of these patients, and the culprit vessel was calcified in 43. Significantly, 77 percent of the patients had scores above the 75th percentile for their age, and 62 percent had scores above the 90th percentile. Among the eight patients with calcium scores less than 10, three had normal vessels at angiography, and one had sustained an acute coronary dissection rather than a classic infarction.

“Do not neglect low calcium scores” in the presence of risk factors, Achenbach cautioned. He noted that the Working Group of EBT Centers in Germany recommends the application of secondary prevention guidelines (i.e., treatment for patients who have already had a myocardial infarction) for all patients with significant calcium scores by EBT in the belief that they clearly have CAD.

Some medical centers are using calcium scans as a diagnostic tool. Michael Wright, M.D., of LifeScore in San Diego, has noted that patients who present to the emergency department with chest pain and normal serum concentrations of cardiac enzymes probably are not suffering acute myocardial infarction if an EBT scan shows little coronary calcium. Other centers have found scoring helpful in patients with atypical chest pain. Matthew J. Budoff, M.D., and his colleagues from Harbor-UCLA Medical Center in Torrance, Calif., have used calcium scans to identify patients with false-positive stress tests and to determine whether an episode of heart failure is the result of CAD.

Tracy Q. Callister, M.D., and colleagues from the Electron Beam Tomography Research Foundation and Vanderbilt University in Nashville, have used calcium scores to monitor the response to treatment with HMG-CoA reductase inhibitors, finding that the calcium volume score declined in patients who responded positively to these lipid-lowering drugs. Note, however, that this conclusion applies to groups of patients, not individuals. The applicability of calcium scoring for longitudinal evaluation of individual patients is not clear.

Callister TQ, Paggi P, Cooil B, Lippolis NJ, Russo DJ. Effect of HMG-CoA reductase inhibitors on coronary artery disease as assessed by electron-beam computed tomography. N Engl J Med 1998;339:1972?1978.

The controversy within the medical community over calcium scanning of asymptomatic persons has often been absent from discussions in the popular press, and self-referrals account for a large percentage of the persons being scanned at many centers. In an editorial in the New England Journal of Medicine in 1998, Allen J. Taylor, M.D., and Patrick G. O’Malley, M.D., of Walter Reed Army Medical Center sounded an alarm over the growing number of such persons.5? The commentators point out that indiscriminate use of calcium scoring could lead to unwarranted (and expensive) follow-up testing and even revascularization procedures. At the other extreme, those authors worry about persons who will use a low calcium score as an excuse to pursue a risky lifestyle or will ignore symptoms of cardiac ischemia in the belief that they are free of CAD. From a social perspective, William Stanford, M.D., and Brad H. Thompson, M.D., of the University of Iowa wonder what will happen if insurance companies raise premiums on the basis of calcium scores or police, firefighters, and airline pilots “become unemployable because of extensive calcification.” 6

In conclusion
Several long-term clinical trials have been organized, such as the Multi-Ethnicity Study of Atherosclerosis, which will follow 18,000 persons over 10 years. The hope is that at their conclusion, we will have a better idea of who can benefit from coronary calcium scanning and how calcium scores can best be used in conjunction with traditional risk factors for CAD. Until the data are available, the debate over scanning is likely to continue.

1. Rumberger JA, Brundage BH, Rader DJ, Kondos G. Electron beam computed tomographic coronary calcium scanning: a review and guidelines for use in asymptomatic persons. Mayo Clin Proc 1999;74:243?252.

2. Detrano R. Current perspectives on coronary calcification: the role of electron beam computed tomography. Presented at the Annual Meeting of the American College of Cardiology, 1998.

3. Guerci AD, Spadero LA, Goodman KJ, Lledo-Perez A, Newstein D, Lerner G, Arad Y. Comparison of electron beam computed tomography scanning and conventional risk factor assessment for the prediction of angiographic coronary artery disease. J Am Coll Cardiol 1998;32:673?679.

4. Greenland P, Abrams J, Aurigemma GP, Bond G, Clark LT, Criqui MH, Crouse JR III, Friedman L, Fuster V, Herrington DM, Kuller LH, Ridker PM, Roberts WC, Stanford W, Stone N, Swan HJ, Taubert KA, Wexler L: Beyond secondary prevention: identifying the high-risk patient for primary prevention: noninvasive tests of atherosclerotic burden. Circulation 2000;101:e16.

5. Taylor AJ, O’Malley PG. Self-referral of patients for electron-beam computed tomography to screen for coronary artery disease. N Engl J Med 1998; 339:2018?2020.

6. Stanford W, Thompson BH. Imaging of coronary artery calcification: its importance in assessing atherosclerotic disease. Radiol Clin North Am 1999; 37:257?272.