The identification of potential triggers of acute coronary syndromes (ACS) represented by unstable angina (UA), myocardial infarction (MI) (preceded or not by UA), and sudden coronary death (SCD) is a rapidly growing area of research. Coronary plaque disruption and subsequent thrombosis is the major recognized pathogenetic component of “unstable plaques,” which characterize the transition from stable coronary artery disease (CAD) to ACS. However, in the presence of unstable or even stable plaques, a thrombogenic state or “high-risk blood” may contribute, at least in some cases, to the development of ACS.1 Furthermore, thrombosis is also an integral component of the chronic atherothrombotic progression of atherosclerosis. Although the observation that plaque disruption leads to ACS goes back a number of decades, the notion of “vulnerable plaques” was first developed a little over a decade ago on the basis of post-mortem observations in patients with ACS.2 At the site of culprit coronary lesions, a rupture was often found at the shoulder of atheromatous plaques with a large pultaceous lipid core and a thin fibrous cap. Such rupture was originally thought to be the result of localized mechanical shear stress forces.3 However, on the basis of emerging evidence of a prevalent inflammatory component in ACS, inflammatory mechanisms of plaque instability began to receive considerable attention.4 The acquisition of knowledge does not necessarily makes things more comprehensible, but rather often adds novel complexities. Yet, when confronted with a pressing issue, such as predicting major future adverse events, there is a natural inclination to accept generalizations not yet justified by available data. The intriguing concept of a vulnerable plaque, as a potential short-term precursor of unstable plaques, derives from the theoretical possibility of identifying those coronary atherosclerotic plaques that might become unstable and thus trigger ACS. The notion of vulnerable plaques is …