O'Rourke, RA; Brundage, BH; Froelicher, VF; Greenland, P; Grundy, SM; Hachamovitch, R; Pohost, GM; Shaw, LJ; Weintraub, WS; Winters, WL; Forrester, JS; Douglas, PS; Faxon, DP; Fisher, JD; Gregoratos, G; Hochman, JS; Hutter, AM; Kaul, S; Wolk, MJ
Coronary artery calcification is part of the development of atherosclerosis; it occurs exclusively in atherosclerotic arteries and is absent in the normal vessel wall. Electron-beam computed tomography (EBCT), the focus of this document, is a highly sensitive technique for detecting coronary artery calcium and is being used with increasing frequency for the screening of asymptomatic people to assess those at high risk for developing coronary heart disease (CHD) and cardiac events, as well as for the diagnosis of obstructive coronary artery disease (CAD) in symptomatic patients. The use of EBCT has the greatest potential for further determination of risk, particularly in elderly asymptomatic patients and others at intermediate risk. The calcium score has been advocated by some as a potential surrogate for age in risk-assessment models. EBCT has also been proposed as a useful technique for assessing the progression or regression of coronary artery stenosis in response to treatment of risk factors such as hypercholesterolemia.
EBCT uses an electron beam in stationary tungsten targets, which permits very rapid scanning times. Serial transaxial images are obtained in 100 ms with a thickness of 3 to 6 mm for purposes of detecting coronary artery calcium. Thirty to 40 adjacent axial scans are obtained during 1 to 2 breath-holding sequences. Current EBCT software permits quantification of calcium area and density. Histological studies support the association of tissue densities of 130 Hounsfield units (HU) with calcified plaque. However, a plaque vulnerable to fissure or erosion can be present in the absence of calcium. Also, sex differences play a role in the development of coronary calcium, the prevalence of calcium in women being half that of men until age 60 years. EBCT calcium scores have correlated with pathological examination of the atherosclerotic plaque.
This American College of Cardiology (ACC)/American Heart Association (AHA) Writing Group reviewed the literature on EBCT published between 1988 and 1999 and also used information obtained when possible from articles in press and data sets from EBCT research centers. We also reviewed the Blue Cross/Blue Shield (BC/BS) Technology Evaluation Center (TEC) assessment of EBCT for screening asymptomatic patients for CAD and for diagnosing CHD in symptomatic patients. Three members of this Writing Group attended the recent AHA Prevention V Conference on “Identification of the High-Risk Patient for Primary Prevention,” and one of our members is also a participant in the design of the National Institutes of Health/National Heart, Lung, and Blood Institute (NIH/NHLBI) forthcoming Multiethnic Study of Atherosclerosis (MESA), which will include a prospective assessment of EBCT in asymptomatic people.
We performed meta-analysis on the relationship between CHD and calcium prevalence in patients undergoing EBCT and cardiac catheterization to determine the diagnostic accuracy of EBCT in catheterized patients. We also performed a meta-analysis of published data in order to compare the diagnostic characteristics of the available alternative tests for detecting angiographic obstructive CAD. The studies demonstrate a high sensitivity of EBCT for CAD, a much lower specificity, and an overall predictive accuracy of ≈70% in typical CAD patient populations. The test has proven to have a predictive accuracy approximately equivalent to alternative methods for diagnosing CAD but has not been found to be superior to alternative noninvasive methods (eg, SPECT [single photon emission computed tomography] imaging). The majority of the members of the Writing Group would not recommend EBCT for diagnosing obstructive CAD because of its low specificity (high percentage of false-positive results), which can result in additional expensive and unnecessary testing to rule out a diagnosis of CAD. The 1999 ACC/AHA Coronary Angiography Guideline Committee reached a similar conclusion [1].
Because the severity of coronary atherosclerosis is known to be associated with risk of coronary events, coronary calcium scores should likewise correlate with risk for coronary events. However, for a test to be most valuable when asymptomatic patients are screened, it should increase the likelihood of CHD above the probability determined by standard and readily available assessments, such as the Framingham risk model based on levels of blood pressure, cholesterol, high-density lipoprotein (HDL) cholesterol, cigarette smoking, plasma glucose, and age. The published literature does not completely answer the question of whether the EBCT calcium score is additive to the Framingham score for defining CHD risk in asymptomatic patients. In one recent large study [2], the addition of EBCT data provided no incremental value to the risk determined by the Framingham and National Cholesterol Education Program risk factors in a direct comparison. There have been other studies that examine this point [2, 3 and 4], but those reports did not adequately test whether EBCT scores were incremental to the other risk factor data. This is an area of important current investigation, including the NIH/NHLBI’s MESA study. It is possible that a positive calcium score might be valuable in determining whether a patient who appears to be at intermediate CHD risk is actually at high risk. Conversely, a low or absent EBCT calcium score may also prove useful in determining a low likelihood of developing CHD. This may be particularly beneficial in elderly asymptomatic patients in whom the management of other risk factors may be modified according to the calcium score. Selected use of coronary calcium scores when a physician is faced with the patient with intermediate coronary disease risk may be appropriate. However, the published literature does not clearly define which asymptomatic people require or will benefit from EBCT. Additional appropriately designed studies of EBCT for this purpose are strongly encouraged. In the setting of this degree of uncertainty, EBCT screening should not be made available to the general public without a physician’s request.
The usefulness of EBCT in determination of changing calcium scores that correlate with regression or progression of CHD is currently being studied intensively. However, the test-to-test variability and the interrater reliability of the calcium score measurement in the same individual studied at close intervals in time have been deterrents to the recommendation of serial EBCT scans for determining the response of coronary artery stenosis lesions to medical interventions designed to cause regression of disease. The Writing Group concluded that this is a promising use of EBCT, but the small number of published studies require corroboration before EBCT can be widely recommended for this purpose.
Our conclusions are consistent with the recommendation of the Agency for Health Care Policy and Research–funded BC/BS TEC, the Prevention V Conference report of the AHA (Dr Philip Greenland), and the MESA project currently being planned by the NIH/NHLBI. The latter study will evaluate EBCT and other techniques in the long-term assessment of CHD risk in 6500 apparently healthy people. As additional data are obtained, our conclusion might require revision.
This Writing Group encourages further properly designed outcomes research using EBCT and additional studies of the role of EBCT and patient follow-up for assessing progression or regression of CHD.