Cardiac Risk Factor
EBCT and evaluation of coronary artery calcium
By Patient Care Sept. 2002 : CAROL S. SAUNDERS
Sep 28, 2002, 7:19pm

It is generally accepted that the presence of coronary calcium correlates directly with coronary atherosclerosis. Does the amount, however, as detected by electron-beam CT (EBCT) predict adverse events independently of traditional risk factors such as BP, cholesterol levels, smoking status, plasma glucose level, and age? Furthermore, how well does EBCT predict risk compared with modalities such as magnetic resonance coronary angiography, positron emission tomography, the ankle-brachial index, and B-mode carotid ultrasonography, or the presence of serum markers such as high-sensitivity C-reactive protein (CRP) and homocysteine?

The National Heart, Lung, and Blood Institute of the National Institutes of Health is currently sponsoring the Multi-Ethnic Study of Atherosclerosis (MESA) to answer these questions. This $68 million, 10-year study is evaluating EBCT and other imaging techniques for the prediction of coronary heart disease risk in baseline healthy people. This multicenter study has recruited about 6500 men and women aged 45 to 84; results are expected in a few years.

Until the MESA results are available, the medical community is relying upon a consensus statement published by the American College of Cardiology/American Heart Association (ACC/AHA) in 2000, which concluded that insufficient data exist to recommend EBCT for screening the general population or for routine clinical evaluations.1 In this statement, the ACC/AHA concluded that EBCT has a high sensitivity for coronary artery disease (CAD) but a lower specificity and a total predictive accuracy of 70%. The accuracy of EBCT is similar to, but not superior to, most other current methods for diagnosing CAD.

Thus, because of its low specificity, the group did not recommend EBCT for diagnosing CAD. In addition, the high percentage of false-positive results from EBCT can lead to more testing and increasing expenses without necessarily leading to more or better information. Recent studies completed after the consensus document was published are revealing new aspects of this controversial issue.

POINTS OF CONTENTION
EBCT quantifies arterial calcium area and density with a rapid-scanning electron beam that obtains 30 to 40 serial transaxial images. Because of its ability to detect coronary artery calcification, EBCT is increasingly being used to diagnose CAD in symptomatic patients and to screen people at high risk. Experts are still arguing over the merits and pitfalls of this noninvasive test.

Prediction accuracy
Proponents of EBCT say that the presence of traditional cardiac risk factors does not accurately predict which patients will have an adverse event and that EBCT should be an adjunct to evaluating risk. Opponents say that most patients are well-served by current guidelines and that other tests such as high-sensitivity CRP and carotid ultrasonography provide better validation.

Calcium scoring
Opponents of EBCT say that since the test scores do not predict fragility of arterial plaque, people with negative scans are given false assurances. Since gender differences play a role in the development of coronary artery calcium (CAC)—the prevalence of calcium in women is half that of men until age 60—this aspect needs to be taken into account in testing. The other problem with coronary calcium scoring is that people younger than 50 can have a significant atherosclerotic burden but the deposits may not be calcified.

Proponents of EBCT assert that a useful aspect of a high-positive CAC score is to move an intermediate-risk patient into a high-risk category. In addition, a low or absent CAC score can confer a low likelihood of CAD, especially in older asymptomatic patients.

Age and calcium burden
Whether the CAC score obtained with EBCT can replace age in risk-assessment models is the focus of current research. The newest risk-assessment guidelines for lipid management are contained in the Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults, also known as Adult Treatment Panel (ATP) III.2 ATP III recommends using Framingham risk scoring, in which age becomes the dominant risk factor after age 50.

Age, in general, correlates roughly with coronary atherosclerotic plaque burden. Since individual coronary plaque burden varies greatly at any age, however, measuring plaque levels accurately with noninvasive techniques such as EBCT could replace age as a risk factor in Framingham scoring for risk prediction.3

Bayesian analysis
Bayesian analysis—the application of sequential, individualized decision making, using conditional probabilities—is frequently cited as the preferred approach to EBCT evaluation for stratifying risk of an adverse coronary event.4 The Bayes equation reveals that for any individual, the probability of having an event (in this case, MI or death) can be calculated if certain parameters are known. Opponents assert that because this information is not yet available for EBCT, it cannot be an accepted risk assessor. In addition to the test score, the required parameters are

The pretest probability of CAD of an individual patient
The prevalence of the new test marker (in this case, the CAC score among the general population)
The normal values in an unselected, large group of patients (5000 to 10,000)
The probability of an abnormal EBCT test score in all patients who have had an event (true-positive)
The probability of an abnormal EBCT test score in all patients who have not had an event (false-positive)
Comparative data with standard tests to determine if EBCT better predicts risk.

Cost-effectiveness
Opponents think that the average cost of $300 to $600 per EBCT scan is too expensive, but proponents point out that this argument was also leveled at the cost of mammograms. Proponents assert that if enough EBCT scans are done, the cost will drop significantly. Currently, it is difficult, if not impossible, to get reimbursement for the procedure.



THE NEWEST RESEARCH
Although EBCT has been available for more than a decade, until recently, no studies had followed an unselected group of patients over a period of many years to see whether CAC scores predict future events. Here is a summary of what has been reported in the past 2 years. These studies are small and may be subject to referral bias, but they improve our understanding of EBCT's strengths and weaknesses.

Predicting future events
In a recent study of 288 patients undergoing angiography, researchers found that after a mean of 6.9 years, CAC burden on EBCT predicted future cardiac events.5 The 22 patients who experienced an adverse event during follow-up were older and had more extensive CAC. Only 1 of 87 patients with a low CAC score experienced an event during follow-up. Event-free survival was significantly higher for patients with CAC scores of less than 100 than for those with a score of 100 or higher. When a stepwise multivariable model was used, only age and CAC extent predicted adverse events (risk ratios 1.72 and 1.88, respectively; P<.05).

Accuracy for diagnosing CAD
Another group of investigators concluded from a meta-analysis of 9 studies with 1662 subjects that EBCT is a reasonable diagnostic test for obstructive CAD based on sensitivity and specificity rates.6 Included were studies that used EBCT as a diagnostic test, reported cases in absolute numbers of true and false positive and negative scores, and used coronary angiography as the reference standard for diagnosing obstructive CAD (defined as stenosis with a diameter of 50% or greater). Maximum joint sensitivity and specificity for EBCT was 75%.

EBCT testing as a patient motivator
Will learning the scores of an EBCT test enhance patient motivation to alter cardiovascular risk behaviors? A recent survey of 144 asymptomatic, active smokers who underwent self-referred screening for EBCT found that the presence of CAC did not influence motivation for smoking cessation.7 Patients with CAC (42% of the sample) were more likely to perceive increased cardiovascular risk (42% versus 13%). Overall, most patients (59%) rated themselves as more motivated to quit smoking after EBCT, but there was no relationship between motivational levels or smoking behavior change and the presence of CAC.



PRODUCED BY CAROL S. SAUNDERS


REFERENCES

1. O'Rourke RA, Brundage BH, Froelicher VF, et al. American College of Cardiology/American Heart Association Expert Consensus document on electron-beam computed tomography for the diagnosis and prognosis of coronary artery disease. Circulation. 2000;102:126-140.

2. Executive summary of the Third report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). JAMA. 2001;285:2486-2497.

3. Grundy SM. Coronary plaque as a replacement for age as a risk factor in global risk assessment. Am J Cardiol. 2001;88:8E-11E.

4. Callister T, Raggi P. Electron-beam computed tomography: a Bayesian approach to risk assessment. Am J Cardiol. 2001;88:39E-41E.

5. Keelan PC, Bielak LF, Ashai K, et al. Long-term prognostic value of coronary calcification detected by electron-beam computed tomography in patients undergoing coronary angiography. Circulation. 2001;104:412-417.

6. Nallamothu BK, Saint S, Bielak LF, et al. Electron-beam computed tomography in the diagnosis of coronary artery disease: a meta-analysis. Arch Intern Med. 2001;161:833-838.

7. O'Malley PG, Rupard EJ, Jones DL, et al. Does the diagnosis of coronary calcification with electron beam computed tomography motivate behavioral change in smokers? Mil Med. 2002;167:211-214.



SUGGESTED READING

Conti CR. Clinical usefulness of electron beam computed tomography to detect coronary artery calcification. Clin Cardiol. 2001;24:755-756.

Pearson TA. New tools for coronary risk assessment: what are their advantages and limitations? Circulation. 2002;105:886-892.

Salazar HP, Raggi P. Usefulness of electron-beam computed tomography. Am J Cardiol. 2002;89:17B-22B.

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