This document summarizes the pathology of atherosclerosis and plaque development. It discusses how plaque accumulates within arteries over decades from early adulthood. Plaque is made up of cholesterol-rich lipids that cause inflammation. While most plaques are asymptomatic, some advanced plaques can rupture and cause heart attacks or strokes. Lipid-lowering treatment can change the composition of plaques within months and provide long-lasting clinical benefits for over 10 years after treatment ends by altering the arteries.

1. 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
Sponsored by AstraZeneca
Graphical support by Scientific Connexions

2. Atherosclerosis and the Arterial Wall
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.
Lumen
Lipid-Rich
Necrotic
Core
Fibrous Cap
Atheroma
Normal
Media
Adventitia
Intima
Text Figure 1A

3. Developmental Pathology of Arterial Lesions
Thin fibrous cap atheroma.
From Virmani R et al. Arterioscler Thromb Vasc Biol. 2000;20:1262-
1275; used with permission.
Healed plaque rupture.
From Stary HC. Atlas of Atherosclerosis: Progression and
Regression. 2nd ed. New York: Parthenon Publishing; 2003; used
with permission.
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.
Thin fibrous cap
Lipid-rich necrotic core
See Figure 3 for
developmental
flow chart.
Older
fibrous
cap
Newer
fibrous
cap
Insull W Jr. Am J Med. 2009;122:S3S14.
Text Figure 1B-D

4. Increasing Extent of Atherosclerotic
Plaques With Age
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.
0
10
20
30
40
50
60
10-14 15-24 25-34 35-44 45-54 55-65 65-69
Age Group (Years)
Mean
Percent
Intimal
Surface
Involved
With
Lesions
Atherosclerosis in LAD
White Males
New Orleans
High Risk of CVD
0
10
20
30
40
50
60
10-14 15-24 25-34 35-44 45-54 55-65 65-69
Total Lesions
Fibrous Cap (Raised Lesions)
Fatty Streaks
Atherosclerosis in LAD
White Males
Santiago, Chile
Low Risk of CVD
Age Group (Years)
Text Figure 2

5. Developmental Pathology of Atherosclerosis
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.
Text Figure 3

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

7. 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.

8. 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.