Are There Really Biomarkers of Vulnerable Plaque?

The rationale for the search of biomarkers of vulnerable plaques seems sound. Plaque rupture is a key step in the initiation of an acute coronary syndrome (ACS).4 The atherosclerotic plaque contains large numbers of inflammatory cells that may release hydrolytic enzymes and cytokines, thereby destabilizing the plaque (1). Therefore, many inflammatory biomarkers and enzymes have been suggested as potential biomarkers of vulnerable plaques; however, considerable confusion exists in the literature regarding what is meant by “a biomarker of plaque vulnerability,” and other closely related (but not identical) concepts have emerged as alternatives. These concepts are described briefly below.A biomarker of plaque rupture would show an increasing concentration when a (coronary) atherosclerotic plaque ruptures. A biomarker of plaque rupture would be potentially useful for early diagnosis of acute myocardial infarction (AMI) because plaque rupture precedes myocardial necrosis. Another potential application would be for unstable angina in which plaque rupture, but not myocardial necrosis, occurs. The requirements that a biomarker of plaque rupture must meet to have clinical utility are considerable, however. The biomarker must be abundant in atherosclerotic plaques and be released immediately into the circulation in high concentration after rupture of the plaque. The biomarker concentration must remain increased for quite some time, because plaque rupture might occur up to several days before the patient gets ischemia and thus presents symptoms (2). Biomarker specificity is another demanding requirement. The biomarker should be not only highly specific for atherosclerotic plaques but also, ideally, specific for coronary plaques only. An important limitation on the use of a biomarker of plaque rupture for early diagnosis of AMI is that a large proportion of all infarctions are not caused by plaque rupture. Autopsy studies have shown that approximately 60% of fatal cases are associated with plaque …