The Pathology of Atherosclerosis: Plaque Development and Plaque Responses to Medical Treatment William Insull, Jr, MD Professor of Medicine and Pediatrics, Director, Lipid Research Clinic, Baylor College of Medicine, Houston, TX Graphical support by Scientific Connexions Sponsored by AstraZeneca

Atherosclerosis and the Arterial Wall Text Figure 1A Fibrous Cap Atheroma Normal Intima Media Lumen Adventitia Lipid-Rich Necrotic Core Figure 1A Coronary fibrous cap atheroma in a 24-year-old man. (From Stary HC. Atlas of Atherosclerosis: Progression and Regression. 2nd ed. New York: Parthenon Publishing; 2003.) From Stary HC. Atlas of Atherosclerosis: Progression and Regression. 2nd ed. New York: Parthenon Publishing; 2003, used with permission. Insull W Jr. Am J Med. 2009;122:S3S14.

Developmental Pathology of Arterial Lesions Text Figure 1B-D Lipid-rich necrotic core Thin fibrous cap atheroma. From Virmani R et al. Arterioscler Thromb Vasc Biol. 2000;20:1262-1275; used with permission. See Figure 3 for developmental flow chart. Thin fibrous cap Older fibrous cap Healed plaque rupture. From Stary HC. Atlas of Atherosclerosis: Progression and Regression. 2nd ed. New York: Parthenon Publishing; 2003; used with permission. Newer fibrous cap Figures 1B-D (B adapted from Virmani R, Kolodgie FD, Burke AP, et al. Lessons from sudden coronary death: a comprehensive morphological classification scheme for atherosclerotic lesions. Arterioscler Thromb Vasc Biol. 2000;20:1262–1275; used with permission; C and D from Stary HC. Atlas of Atherosclerosis: Progression and Regression. 2nd ed. New York: Parthenon Publishing; 2003.) Stenosis (cross section of anterior descending coronary artery). From Stary HC. Atlas of Atherosclerosis: Progression and Regression. 2nd ed. New York: Parthenon Publishing; 2003; used with permission. Insull W Jr. Am J Med. 2009;122:S3S14.

Increasing Extent of Atherosclerotic Plaques With Age Text Figure 2 Atherosclerosis in LAD White Males New Orleans High Risk of CVD Atherosclerosis in LAD White Males Santiago, Chile Low Risk of CVD Mean Percent Intimal Surface Involved With Lesions Figure 2 Increasing extent of atherosclerotic plaques with age. CVD = cardiovascular disease; LAD, left anterior descending. (Adapted from McGill HC Jr [ed]. The geographic pathology of atherosclerosis. Lab Invest. 1968;18:465–653, Reference Table 19; with permission.) Age Group (Years) Age Group (Years) CVD = cardiovascular disease; LAD = left anterior descending coronary artery. Adapted with permission from McGill HC Jr (ed). Lab Invest. 1968;18:465–653. Insull W Jr. Am J Med. 2009;122:S3S14.

Developmental Pathology of Atherosclerosis Text Figure 3 Figure 3 Flow chart of the general concepts of the development of atherosclerosis. (Adapted from Virmani R, Kolodgie FD, Burke AP, et al. Lessons from sudden coronary death: a comprehensive morphological classification scheme for atherosclerotic lesions. Arterioscler Thromb Vasc Biol. 2000;20:1262–1275; used with permission.) ACS = acute coronary syndromes. Adapted with permission from Virmani R et al. Arterioscler Thromb Vasc Biol. 2000;20:1262–1275. Insull W Jr. Am J Med. 2009;122:S3S14.

Influence of Therapeutic Intervention on the Atherosclerotic Process Text Figure 4 Figure 4 Influence of therapeutic intervention on the atherosclerotic process. Insull W Jr. Am J Med. 2009;122:S3S14.

Pearls for Clinical Guidance Atherosclerosis develops over 50 years, from early teenage years to death Atherosclerotic plaques develop as accumulations of cholesterol-rich lipids that incite inflammatory responses Atherosclerosis affects all major conduit arteries, largely in their proximal portions A small proportion of the most advanced plaques in the coronary arteries or the cerebrovascular arteries can cause sudden death due to thrombotic occlusion or ischemic stenosis Insull W Jr. Am J Med. 2009;122:S3S14.

Pearls for Clinical Guidance continued Each person’s extent of atherosclerosis depends on his or her risk factors and arterial susceptibility Lipid treatment can produce favorable major changes in the composition of advanced plaques within 4 months, resulting in clinical benefit Clinical benefit that continues after lipid treatment for atherosclerosis has ceased may be fully durable for at least 10 years, indicating the durability of histologic alterations of the artery Insull W Jr. Am J Med. 2009;122:S3S14.