Atherosclerosis

Question 1

What is atherosclerosis?

Answer 1

-a progressive, chronic inflammatory disease of large arteries that starts in childhood and rapidly progresses in the third decade or later

Question 2

Where does atherosclerosis invade?

Answer 2

-med and large arteries - in the artial intima forming plaques

Question 3

Major modifiable risk factors for atherosclerosis;

Answer 3

• *Smoking**
• HTN - esp when get older
• hyperlipidemia
• diabetes
• C-reactive protein

RISK FACTORS ARE ADDITIVE

Question 4

Non modifiable risk factors for atherosclerosis

Answer 4

age
male
-family history

Question 5

What blood component is pro-atherogenic:

Answer 5

• LDL - bad lipoprotein

- Liporotein Lp(a)

Question 6

I Familial lipoprotein lipase deficiency

-increase in what?

Answer 6

-inc chylomicrons - no premature atherosclerosis (AS)

Question 7

IIa Familial hypercholesterolemia

-inc in what?

Answer 7

-Inc LDL - premature AS

Question 8

IIb Familial combined hypercholesterolemia

-inc in what?

Answer 8

• inc LDL
• inc VLDL
• premature AS

Question 9

III familial type III lipoproteinemia

-inc in what?

Answer 9

-inc in IDL - premature AS

Question 10

IV Familial hypertriglycidemia

-inc in what?

Answer 10

-inc in VLDL - premature AS

Question 11

V Only familial AI/CII deficiency

-what problem?

Answer 11

-no HDL - severe AS

Question 12

Unusual associations with AS?

Answer 12

• elevated plasma homocysteine (use folate and Vit B)

- Chlamydia pneumonia in plaques (organisms that induce inflammation)

Question 13

content of atherosclerotic lesions

Answer 13

1) similar to chronic inflammation
- infiltration by macrophages and lymphs
- mesenchymal cell prolif
- fibrosis
- cell necrosis
- neovascularization
2) additional (not in chornic inflam)
- lipid accumulation - esp cholesterol

Question 14

Hypothesis for atherogenesis:

Answer 14

• starts with endothelial cell injury due to hypercholesterolemia, disturbed flow, smoking…etc
• vascular response to injury
• macrophages release agents locally which sustain a chronic inflammatory reaction
• endothelial cells over-express vascular adhesion molecule-1 (VCAM-1)=inc cellular adhesion and inflammatory cells+cytokines (MCP-1- most potent)
• most macrophages accumulate modified lipids = foam cells and fatty streaks

Question 15

role of macrophages:

Answer 15

• plasma LDL gets into the intima = modification or oxidation by free radicals (becomes toxic) –> macrophage takes up = macrophage foam cell
• macrophages, SMCs, and endothelial cells release monocyte chemo-attractant protein 1 (MCP-1) = more monocytes and proliferation of smooth muscle

-smooth muscle can also take up fat but not seen as much as macrophages-macrophages are primary

Question 16

significance of foam cells:

Answer 16

these foam cells start secreting

• growth factors
• hydrolytic enzymes
• active oxygen metabolites (radicals)… etc

Question 17

key features of AS:

Answer 17

• smooth muscle cell proliferation (change from contractile to secretory type)
• accumulation of connective tissue elements –> collagen, elastin, proteoglycans
• lipid deposition –> intra- and extracellular

Question 18

the necrotic core of an AS plaque has:

-what is risk?

Answer 18

a bunch of shit - collagen, fat, foam cells…
one thing being cholesterol cleft (artifact due to slide prep - cholesterol polymerized)

-if this plaque ruptures = instant thrombus

Question 19

Over decades what happens to AS plaques?

Answer 19

they calcify = plasticity of vessel altered

Question 20

role of hemodynamics in atherogenesis

Answer 20

• pressure (HTN)
• regions of low shear and/or disturbed flow
• flow recirculation zones (eddies) - associated with arterial branches and bifurcations

Question 21

Lesion complications:

Answer 21

• calcification
• rupture or ulceration
• hemorrhage
• thrombosis

Question 22

What is a vulnerable plaques?

Answer 22

-one that has a very thin fibrotic cap and is soft = easily rupture especially6 in shoulder region

==> thrombus

Question 23

Late clinical issues of AS?

Answer 23

• aneurysms + rupture
• occlusion by thrombus
• critical stenosis

Question 24

Primary therapies for clinical AS:

Answer 24

• statins
• control BP & DM
• Clotting control
• diet and lifestyle

Question 25

Secondary therapies of clinical AS:

Answer 25

• tissue plasminogen activator
• angioplasty with stent placement (coronary of carotid)
• carotid endarterectomy
• CABG (by-pass)

Question 26

most complex AS lesions where?

Answer 26

superficial femoral artery

Question 27

Ankle brachial pressure index of what is considered abnormal? What does this suggest?

Answer 27

-the lower the number then the more severe the arterial disease

• if >1.3 = calcification of walls of arteries and incompressible vessels ==> severe peripheral vascular disease
• important predictor of mortality

Question 28

Clinical manifestations of AS?

Answer 28

ischemic injury to organs and tissues:

• MI
• ischemic stroke
• peripheral arterial disease (PAD)–> gangrene
• visceral infarction
• atherosclerotic aneurysms

Question 29

Glagov’s coronary remodeling hypothesis:

Answer 29

• basically as you get more AS in the intima the lumen size remains constant.
• the lumen doesnt start to get occluded until late stage disease

Question 30

Diagnostic modality for AS?

Answer 30

• intravascular ultrasound (IVUS)

- cannot predict RUPTURE DURP

Question 31

lumen reduction to what percent of normal yields perfusion issues?

Answer 31

if occluded 70-80% of normal area

Question 32

women vs men risk

Answer 32

men more at risk

-risk becomes approx equal after women pass menopause