Computed Tomography or Functional Stress Testing for the Prediction of Risk

The clinician now has an overwhelming array of investigations at his or her disposal for patients with suspected coronary heart disease. These tests are used to diagnose or risk-stratify patients and thereby enable the clinician to treat their symptoms and reduce their future risk. Ultimately, these investigations either assess risk factors (eg, lipid, glucose, and C-reactive protein concentrations) and proxies for disease (eg, carotid intima-media thickness and coronary artery calcium score) or are looking to provide circumstantial downstream evidence of disease (eg, markers of ischemia and infarction: Q waves on an ECG, fibrosis on magnetic resonance imaging or functional stress testing). In this issue of Circulation, Budoff and colleagues1 compare 2 of the most widely used approaches, coronary artery calcium scoring and functional stress testing, within the framework of the PROMISE trial (Prospective Multicenter Imaging Study for Evaluation of Chest Pain). Coronary artery calcification is considered pathognomonic of atherosclerosis and has been a marker of coronary artery disease for millennia.2 Its presence is, however, a proxy of disease because it is induced in response to atherosclerosis, and, apart from rare calcific nodules, calcification does not directly cause ischemic heart disease events. Indeed, calcification appears to be an adaptive healing response to the necrotic atheromatous plaque whereby the body attempts to limit and contain the disease, much like the calcification of a caseating granuloma from mycobacterium tuberculosis infection. However, calcification does not directly relate to the degree of luminal or functional stenosis of the coronary artery, nor does it necessarily reflect the current status of the plaque because the calcification may be inactive, ongoing, or incomplete. Indeed, large areas of inert macrocalcification are associated with plaque stability, whereas spotty calcifications or microcalcifications are associated with high-risk plaques, probably because of incomplete calcification.3–5 Consequently, the presence of coronary artery calcification is a surrogate for the extent of coronary atheromatous plaque and, by inference, the risk of future adverse cardiovascular events. Its major strength is its sensitivity and high negative predictive value, with the absence of coronary artery calcification taken to exclude coronary heart disease, the so-called power of zero. Functional stress testing has been at the heart of diagnosing ischemic heart disease for many decades. It has been the investigation of choice for many centers worldwide because it not only greatly assists in the diagnosis of ischemia as the cause of chest pain but also can provide prognostic information and guide coronary revascularization strategies. Of course, functional stress tests principally diagnose the presence of ischemia resulting from flow-limiting obstructive coronary artery disease. Therefore, these tests describe the functional consequences of the disease rather than the disease itself. In this regard, it is important to remember that myocardial ischemia is not necessarily specific for coronary artery disease Computed Tomography or Functional Stress Testing for the Prediction of Risk Can I Have My Cake and Eat It?