02/23g Atherosclerosis

Question 1

What are the progressive steps to forming an atherosclerotic lesion?

Answer 1

1) Begin with fatty streaks (lipid-filled myointimal cells) that start forming within 20 years
2) Progress to fibrous plaques, when a subendothelial cap forms over extracellular lipid
3) Plaques with erosion, intramural hemorrhage, thrombus, and/or calcification qualify as complicated plaques

Question 2

What are common sites of atherosclerotic plaque formation?

Answer 2

*Larger vessels and branch points*
Abdominal aorta and iliac arteries
Proximal coronary arteries
Thoracic aorta
Internal carotid and cerebral artery

Question 3

What are uncommon sites of atherosclerotic plaque formation?

Answer 3

Subclavian arteries
Axillary arteries
Renal arteries
Superior mesenteric and celiac arteries

Question 4

What are the major risk factors for atherosclerosis that cannot be changed?

Answer 4

Genetics
Male
Age (older than 55)

Question 5

What are the major risk factors for atherosclerosis that CAN be changed?

Answer 5

Tobacco use
Hypertension
Lipidemias
Diabetes mellitus

Question 6

What laboratory test result is correlated with a higher risk of adverse coronary events? What does it indicate?

Answer 6

High C-Reactive Protein (CRP), an acute phase reactant

Indicates ongoing inflammation

Question 7

What can you do to reduce your CRP levels and risk of a coronary event?

Answer 7

Adjust lifestyle

Medications (statins)

Question 8

Which is a stronger predictor for coronary artery disease - high CRP or high cholesterol?

Answer 8

High CRP

Question 9

What are three models of the pathogenesis of atherosclerosis?

Answer 9

Intimal injury and repair model - response to injury hypothesis
Mural thrombosis and organization model - thrombogenic or encrustation hypothesis
Monoclonal proliferation model - monoclonal hypothesis

Question 10

What are the possible ‘injuries’ in the Injury and Repair Model?

Answer 10

Hyperlipidemia
Hypertension and shear stress
Tobacco abuse
Inflammatory state
Microorganisms/viruses (CMV, adenovirus)

Question 11

What are the effects of the injury in the Injury and Repair Model?

Answer 11

Accumulation of lipids and free radicals
Release of cytokines and chemokines
Necrosis/apoptosis and thrombosis
Fibrosis

Question 12

What cells are involved in the Injury and Repair Model?

Answer 12

Smooth muscle cells
Macrophages
Endothelial cells
WBCs
Platelets

Question 13

What role to Toll-like receptors play in the progression of atherosclerosis?

Answer 13

TLRs can be stimulated by endogenous ligands
Respond by affecting lipid transport, affecting macrophage uptake and release, interacting with oxidized lipoproteins, and upregulating cytokines
May also stimulate arterial remodeling to accommodate progressing atherosclerosis

Question 14

What conditions are caused by luminal narrowing in clinical atherosclerosis?

Answer 14

Critical stenosis and episodic ischemia

Question 15

What are the symptoms of episodic ischemia?

Answer 15

Angina pectoris
Transient ischemic attacks with possible emboli
Intermittent claudication (cramping while walking)
Renovascular hypertension
Mesenteric ischemia

Question 16

What is acute arterial occlusion? What is the most common cause?

Answer 16

Sudden significant or total obstruction of the lumen of an artery
Most commonly caused by a thrombus superimposed over a plaque rupture/erosion site

Question 17

What is a vulnerable plaque?

Answer 17

A plaque that is more likely to rupture and cause thrombosis

Question 18

What qualities make a plaque vulnerable to rupture?

Answer 18

Large atheromatous core
Thin fibrous cap/increased cap tension
Inflammation or foam cells in fibrous cap
Matrix metalloproteases
Cap fatigue/stress

Question 19

Which type of plaque is more likely to cause clinical effects - an obstructive plaque, or a vulnerable plaque?

Answer 19

A vulnerable plaque

Question 20

What is the purpose of a stress test? What are its limitations?

Answer 20

To demonstrate symptoms of flow restriction when requirements are increased
To demonstrate ischemia due to critical stenosis through exercise or pharmacoloy
Limited because it only predicts severity of stenosis, not plaque vulnerability

Question 21

What are some other complications of atherosclerosis?

Answer 21

Thrombosis
Aneurysms
Aortic dissection

Question 22

What is an aneurysm?

Answer 22

An area of weakness in the wall of a blood vessel that typically results in bulging due to arterial blood pressure

Question 23

What factors can put you at risk for an aneurysm?

Answer 23

Congenital/genetic - polycystic kidney disease, Marfan syndrome
Atherosclerosis
Infectious disease
Autoimmune disorders - lupus, arthritis

Question 24

What factors can put you at risk for aortic dissection?

Answer 24

Cystic medial necrosis - loss of elastin fibers and smooth muscle, and replacement with ground substance
Marfan syndrome
Hypertensive injury (cocaine abuse)