The vulnerable plaque "hypothesis": promise, but little progress.

A PubMed search using the terms “vulnerable plaque” or “high-risk” plaque yields 2,000 references to journal articles published over the past 20 years. Indeed, few concepts in cardiovascular medicine have achieved such intense scientific interest over such a long duration. During this 20-year period, many diagnostic techniques designed to “detect” vulnerable plaques have come and gone. In each case, a flurry of promising “findings” has been followed by a sobering reality check. These include thermography, spectroscopy, palpography, virtual histology, optical coherence tomography, and many more (1–5). A large number of startup companies with “breakthrough” approaches have come and gone, nearly all leaving investors with empty pockets, but no progress. What has gone wrong?