The Vulnerable Atherosclerotic Plaque: Strategies for Diagnosis and Management
Renu Virmani, Jagat Narula, Martin B. Leon, James T. Willerson, eds
375 pages. Malden, MA: Blackwell Futura; 2007. $174.95. ISBN 1–40515–859–X
The term “vulnerable plaque” was coined in 1989 by Dr. James E. Muller to describe nonobstructive atherosclerotic plaques that were prone to rupture, leading to acute clinical syndromes. This term has evolved over the ensuing 2 decades and is now often called the “high risk plaque.” Many investigators argue that atherosclerosis is a systemic problem and therefore the proper terminology should be the “vulnerable patient.” Regardless of semantics, identification of the vulnerable plaque has significant implications for clinical care. Novel therapies to pacify plaques, both medical and interventional, are under development and an enhanced understanding both of the risk factors and methodologies used to recognize unstable plaques are poised to advance the field of cardiovascular medicine.
The Vulnerable Atherosclerotic Plaque: Strategies for Diagnosis and Management reviews our understanding of the vulnerable plaque from a broad perspective, including its pathology, potential triggers, diagnostic techniques, and management, in a well-organized manner that progresses from topic to topic quite logically. The book successfully minimizes overlap between chapters. Clinical and basic information is well-integrated and the authors who contributed to the work are outstanding. The length and breadth of the chapters varies, which is somewhat expected in a volume with so many authors. The images, especially the pathological figures, are outstanding and add significantly to the power of the monograph. Most of the illustrative diagrams are likewise excellent, although the unusual colors used in a few tend to distract the reader.
The book opens with an interesting and complete history of the recognition of atherosclerosis and the biology of plaque rupture, and gives the reader a true historical perspective on the field. The following section on pathology is one of the highlights of the book. The section contains chapters on general pathology, especially the thin cap fibroatheroma, as well as individual types of plaque pathology including plaque rupture, erosion, calcification, and periadventitial fat inflammation. The pathological figures are beautiful to behold and augment the reader’s appreciation of the complexity of the biology of atherosclerosis. This portion of the monograph thoroughly reviews the risk factors for the various pathological forms of plaque disruption, eg, the fact that plaque erosion is seen more commonly in younger female smokers. A chapter on murine models of atherosclerosis points out that since mouse atherosclerosis is characterized by fatty streak formation and fibrotic plaque with little thrombosis, they are imperfect models for human vulnerable plaque.
The chapters on various triggers present the limited basic data on what is known in this area, including the role of physical and mechanical stress. The chapter on inflammatory cells (such as macrophages) and molecules (such as matrix metalloproteinases) particularly catches the reader’s eye, as it is presented as a well-written murder mystery with the culprit unfortunately remaining at large in the end. The ying and yang of apoptosis between the good (macrophage apoptosis) and the bad (endothelial and smooth muscle cell apoptosis) is likewise well-presented.
The diagnostic methods section is quite comprehensive and ranges from well-developed techniques such as intravascular ultrasound to those that have only been evaluated ex vivo, such as intravascular palpography. The chapter on biomarkers presents information on a multiplicity of lipid-related markers including oxidized LDL, isoprostanes, myeloperoxidase, Lp(A), LDL particle density, and Lp-PLA2. Interestingly, a discussion of inflammatory markers such as C-reactive protein is not included here, but was discussed in an earlier chapter as a potential marker of plaque rupture. The chapter on magnetic resonance imaging reviews much of the available methodology, including potentially exciting intravascular magnetic resonance techniques, but leaves out any discussion of the evolving role of targeted and non-targeted contrast agents for differentiating plaque components. However, novel radionuclide tracers being developed to target apoptosis and inflammatory markers (including matrix metalloproteinases) are particularly intriguing and are reviewed in a thorough fashion. The figures in the chapters on intravascular ultrasound were particularly excellent and timely, as virtual histology using ultrasound is a rapidly developing application. Innovative measures of plaque vulnerability—including near infrared spectroscopy, intravascular thermography, optical coherence thermography, and intravascular palpography—were all discussed by experts in their respective fields, with technical background that enhances the reader’s understanding of the techniques. In addition, each method was thoroughly evaluated with respect to its individual limitations for clinical application in its present state. One disappointing aspect of the diagnostic methods section was the short shrift given the rapidly expanding role of computed tomography for coronary angiography and plaque characterization.
The final section discusses management of the vulnerable plaque. The opening chapter covers therapies for the vulnerable patient, including established pharmacological therapies; emerging pharmacological therapies, such as Apo A-1 Milano; and other developing interventions, such as drug-eluting stents and gene therapies. The discussion of novel interventional therapies, including photodynamic therapy with porphyrins and thermal stabilization with gentle heating to 42°C, will be particularly interesting to readers without background knowledge in this area. A chapter that discusses the interventionalist’s perspective on therapy for vulnerable plaques is quite realistic with regard to interventional therapy, pointing out that systemic therapies remain the mainstay of treatment. The chapter on the evolving understanding of the role of genetics in plaque vulnerability presents up-to-date information on single nucleotide polymorphisms, epigenetics, and candidate genes.
This book will be useful to a wide audience ranging from the neophyte seeking to get a glimpse of the state-of-the-art in the field to the expert in one particular area who wishes to broaden his or her world view. In addition to a general cardiology audience, pathologists, cardiovascular imagers, and interventionalists will find this book both intriguing and informative. Whoever picks up this book will come away with a much better understanding of what makes both an atherosclerotic plaque and a patient with atherosclerosis vulnerable to acute clinical syndromes.
Dr Kramer reports receiving research support from Siemens Medical Solutions and Merck, a research grant from GE Healthcare, and has served on a speaker’s bureau for GE Healthcare.
Sources of Funding
Dr Kramer is supported in part by NIH R01 HL075792.