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Supplement issue

The Pathology of Atherosclerosis: Plaque Development and Plaque Responses to Medical Treatment
William Insull, Jr., MD
Section of Atherosclerosis and Vascular Medicine, Department of Medicine, and Lipid Research Clinic, Baylor College of Medicine, Houston, Texas, USA

ABSTRACT Atherosclerosis develops over the course of 50 years, beginning in the early teenage years. Thecauses of this process appear to be lipid retention, oxidation, and modification, which provoke chronic inflammation at susceptible sites in the walls of all major conduit arteries. Initial fatty streaks evolve into fibrous plaques, some of which develop into forms that are vulnerable to rupture, causing thrombosis or stenosis. Erosion of the surfaces of some plaques and rupture of a plaque’s calcificnodule into the artery lumen also may trigger thrombosis. The process of plaque development is the same regardless of race/ethnicity, sex, or geographic location, apparently worldwide. However, the rate of development is faster in patients with risk factors such as hypertension, tobacco smoking, diabetes mellitus, obesity, and genetic predisposition. Clinical trial data demonstrate that treatmentwith 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) favorably alters plaque size, cellular composition, chemical composition, and biological activities centered on inflammation and cholesterol metabolism, as well as the risk of clinical events due to atherosclerosis. Even with advanced atherosclerosis, statins begin to improve clinical risk within 4 months. During long-termfollow-up in clinical trials for up to 11 years with or without further treatment, clinical benefit remains significant, indicating the durability of treatment-induced changes in the development of plaque. Thus, atherosclerosis, a disease heretofore viewed as inevitably progressive, can be treated to significantly alter arterial lesions and reduce their clinical consequences. © 2009 Published byElsevier Inc. • The American Journal of Medicine (2009) 122, S3–S14 KEYWORDS: Atherosclerosis; Inflammation; Plaque

The clinical practitioner’s goal for atherosclerosis is to treat it effectively. The purpose of this article is to introduce the pathology of atherosclerotic lesions to provide a rational basis for their clinical management. For each human individual, the natural history of the pathologyof arterial lesion development lasts 40 years.1,2 Treatments such as diet modification, exercise, and drugs that affect plasma lipids and hypertension may induce changes in the clinical manifestations and in the natural pathology of plaques and arteries. This review of plaque pathology includes a discussion of both gross pathology and histopathology, along with information on assessment of plaquesby various imaging methStatement of author disclosure: Please see the Author Disclosures section at the end of this article. Requests for reprints should be addressed to William Insull, Jr., MD, Lipid Research Clinic, Baylor Faculty Center, 1709 Dryden Road, Suite 08.08, Houston, Texas 77030-3411. To access a slide kit for this article, please click here. E-mail address: winsull@bcm.edu

ods,because some significant pathology is currently described indirectly only by clinical imaging methods. These imaging methods have been rigorously validated and calibrated against the standard of classic histopathologic methods applied directly to human tissues, and sometimes are referred to as “virtual histology.” Definitions of the terms used in this article are provided in Table 1.

WHAT ISATHEROSCLEROSIS? HOW DO WE STUDY IT?
Atherosclerosis is a disease of the arterial wall that occurs at susceptible sites in the major conduit arteries. It is initiated by lipid retention, oxidation, and modification, which provoke chronic inflammation, ultimately causing thrombosis or stenosis. Atherosclerotic lesions can cause stenosis with potentially lethal distal ischemia or can trigger thrombotic...