Can markers predict plaque vulnerability?

The concept of "vulnerable plaque" (VP) has been evolving since its introduction as an atherosclerotic plaque prone to cause cardiovascular events, such as myocardial infarction and stroke. Once defined as a thin-cap fibroatheroma prone to rupture, it now encompasses more atherosclerotic lesion types, including plaque erosion, fissure, and calcified nodules. Along with deeper understanding of plaque biology, many call for identifying the "vulnerable patient" and not just VP, to identify patients at high risk of cardiovascular and cerebrovascular events. Significant research resources have been dedicated to characterizing VP and stratifying vulnerable patients; however, the predictive power of traditional risk factors for clinical complications is limited. As such, there is an unmet need in early identification of VP and patients through plaque vulnerability markers, which when successful, could help healthcare professionals detect subjects at risk and provide the right therapy to the right set of patients. This review presents a summary of the plethora of local and systemic plaque vulnerability markers, those still confined for research use and those in clinical use, and different circulating markers, as well as imaging markers assessed through invasive and noninvasive modalities. The current gaps in marker discovery, development, and implementation are pinpointed, as well as what might be envisioned for the future of plaque vulnerability markers.