Seeing and Sampling the Surface of the Atherosclerotic Plaque

Understanding the mechanisms underlying acute coronary syndromes (ACS) depended for decades on autopsy studies. The limitations of postmortem studies include death as an inclusion criterion, biasing the studies toward events with fatal outcomes. The more numerous nonmortal events comprise a sizable but heretofore largely hidden denominator of uncertain magnitude. To gain insight into the underlying pathophysiologic basis of the ACS, laboratory researchers have conducted innumerable animal studies on atherosclerosis. Advanced genetic manipulations have led to increasingly refined approaches to probe the aspects of experimental atherosclerosis, particularly in mice. Despite their indisputable value for isolating mechanisms, the interpretation and extrapolation of the results of many such mouse studies blithely ignore the yawning gap between the disease in laboratory animals and human patients with atherosclerosis.1,2 Only under extreme circumstances do mouse or rabbit atheromata actually ever cause thrombosis. Experiments in small animals almost never focus on the coronary arteries, structures that differ strikingly in ontogeny from the human aorta or carotid arteries. Experimental studies routinely refer to plaque vulnerability or stable or unstable plaque phenotype without actually assessing stability, instability, or vulnerability. This leap of faith, albeit routinely accepted, represents a striking suspension of intellectual and scientific rigor to which many turn a blind eye.See accompanying article on page 2460 Fortunately, we now possess tools of increasing utility and validation for probing the structure of atherosclerotic plaques in living humans. Traditional contrast arteriography provided silhouettes of the lumen but revealed little of the artery wall or the character of atherosclerotic plaques themselves. Intravascular ultrasound provides an outstanding modality for measuring the volume of atherosclerotic plaques. Use of the radiofrequency backscatter from intravascular ultrasound can furnish some …