CRC - Cardiovascular Plaque Rupture
|Publication Date:||25 February 2002|
Plaque rupture is the common pathophysiology of the acute ischemic syndromes of sudden cardiac death, acute myocardial infarction, and unstable angina. As such it is responsible for 700,000 deaths per year and approximately $50 billion in costs in the United States alone. Although the mortality from these diseases is decreasing in the United States, in many parts of the world it is rapidly increasing. Thus, plaque rupture represents one of the major public health hazards of the new millennium.
Until recently very little was known about plaque rupture. In the past decade its relationship to the acute ischemic coronary syndromes has been established by careful pathological studies by many investigators. In addition, through study of human tissue and cultured cells much has been learned about the mechanisms of plaque rupture. The distribution and effect of physical stresses on plaque have been elucidated, as have a number of proteolytic processes that cause degradation of the collagenous and non-collagenous components of plaque. Inflammation has been identified as playing an important role in the pathogenesis of plaque rupture. However, the triggers of the inflammatory response are not well understood. Infectious agents have been identified in atherosclerotic plaque and are proposed as one possible initiator of the inflammatory response.
In addition, relatively little is known regarding the ability to detect and treat plaque at risk of rupture. Intensive efforts are underway to characterize and identify vulnerable plaque using invasive and noninvasive approaches. Methods being investigated include both new imaging modalities and modifications of existing technology for use in the coronary arteries.
Treatment to prevent plaque rupture by stabilizing the vulnerable plaque is in its infancy. Dramatic success has been achieved with the use of HMG-CoA reductase inhibitors to lower cholesterol. However, these powerful agents reduce the risk of plaque rupture by only about 30%. Additional therapeutic strategies are therefore urgently needed. Because of the possible link to infection, antibiotics for prevention of plaque rupture are under intense investigation. Other drugs are being developed that may prevent plaque rupture by inhibition of the inflammatory reaction or the enzymes responsible for plaque degradation.
It is the goal of Cardiovascular Plaque Rupture to present a timely review of these findings and to stimulate further research into this important topic. Many of the leading investigators in this emerging new field of investigation have contributed to this project. I am deeply grateful to them for their time and expertise. I would also like to acknowledge the critical contribution of the professionals at Marcel Dekker, Inc., in particular Sandra Beberman and Barbara Mathieu. They have kept this project moving despite the untimely death of their colleague Graham Garratt (who immediately grasped the importance of a book on this subject when I presented it to him) and the birth of my twins and the resultant inertia caused by a year of sleep deprivation. It is my hope that this text will serve to stimulate interest in this field, present the fundamentals, and lay the groundwork for understanding and contributing to the many important advances that are yet to come.