B4.021 Atherosclerosis

Question 1

what is atherosclerosis

Answer 1

lipid laden deposits in the intima of large and medium sized arteries

Question 2

what is the “response to injury” hypothesis surrounding the formation of atherosclerosis

Answer 2

1. chronic endothelial cell injury (nicotine, lipids, HTN)
2. accumulation of lipoproteins, mainly LDL
3. modification of lesional lipoproteins by oxidation
4. adhesion and migration of blood monocytes into the lesion, and transformation into foam cells
5. adhesion of platelets
6. release of cytokines and growth factors, causing migration of SM cells from media to intima
7. smooth muscle cells proliferate and produce ECM
8. enhances accumulation of lipids

Question 3

risk factors for atherosclerosis

Answer 3

age
gender (females protected by estrogen)
genetic influences
hyperlipidemia
hypertension
cigarette smoking
DM

Question 4

discuss the structure of a lipoprotein

Answer 4

small ball of lipids
cholesterol and triglyceride core
phospholipid, cholesterol, and protein shell

Question 5

what are the 2 major goals of lipoproteins?

Answer 5

1. transport of triglycerides from intestines and liver to sites of utilization
2. transport of cholesterol to peripheral tissues for membrane synthesis and steroid production or to liver for bile acid synthesis

Question 6

what is reverse cholesterol transport?

Answer 6

uptake of cholesterol from extrahepatic sources, esterification by LCAT and transport by large HDL particles

Question 7

what are the 4 ways by which cells regulate cholesterol content?

Answer 7

1. synthesis of cholesterol in SER
2. receptor mediated endocytosis of LDL
3. efflux of cholesterol from plasma membranes to apo-A1/HDL
4. intracellular cholesterol esterification via acetyl-CoA acetyltransferase

Question 8

what are the 5 classes of lipid lowering drugs?

Answer 8

1. bile acid binding resins (cholestyramine)
2. cholesterol absorption inhibitors (ezetimibe)
3. HMG-CaA inhibitors (statins)
4. Fibrates
5. Niacin

Question 9

how do statins work

Answer 9

decrease LDL
well tolerated
risks for myositis, hepatic toxicity, diabetes

Question 10

when are statins indicated?

Answer 10

for those with 10 yr cardiac risk >7.5%

Question 11

what do fibrates do?

Answer 11

inhibit PPAR-alpha

Question 12

what does niacin do?

Answer 12

decreases hepatic VLDL secretion

Question 13

how does aspirin work as an antiplatelet?

Answer 13

inhibits TXA2 by irreversibly acetylating COX1

reduced TXA2 attenuates platelet activity

Question 14

why is ADP a target for antiplatelet agents?

Answer 14

it is a key receptor on the platelet surface that enhances recruitment and activation

Question 15

how does vorapaxar work?

Answer 15

blocks PAR-1

Question 16

how do IIb/IIIa antiplatelet drugs work?

Answer 16

block binding of platelets to fibrinogen

Question 17

discuss the primary prevention function of aspirin

Answer 17

doses >75 mg/day show clear reduction in mortality and cardiovascular events
underprescribed
not uniformly tolerated (mainly GI issues)

Question 18

discuss the secondary prevention function of aspirin

Answer 18

greater effects

indicated in almost all pts with atherosclerosis except in those with allergies or bleeding risk

Question 19

what is a good marker of inflammatory state?

Answer 19

CRP
generated by liver in response to IL-1/IL-6 pathways
direct role in disease not yet proven, but proven to be a good biomarker

Question 20

what makes a good biomarker

Answer 20

varies with disease
can be detected
sensitive/specific
cheap to detect

Question 21

what are the 3 primary manifestations of clinically significant atherosclerosis

Answer 21

1. aneurysm and rupture
2. occlusion by thrombus
3. critical stenosis (>70%)

Question 22

which areas are particularly susceptible to atherosclerosis?

Answer 22

thoracic and abdominal aorta
coronary arteries
peripheral arteries
carotid arteries

Question 23

which areas are protected from atherosclerosis

Answer 23

internal mammary arteries

Question 24

what makes an atheroprone site prone?

Answer 24

turbulence creates low shear stress

Question 25

coronary artery clinical presentations of atherosclerosis

Answer 25

aneurysm- rare
plaque rupture- frequent
occlusion- common
embolism- uncommon
dissection- rare (nonathero in females)

Question 26

aortic clinical presentations of atherosclerosis

Answer 26

aneurysm- common
occlusion- rare
embolism- common
dissection- common (aneurysm)

Question 27

peripheral artery clinical presentations of atherosclerosis

Answer 27

aneurysm- uncommon
occlusion- common
embolism- common
dissection- rare

Question 28

carotid clinical presentations of atherosclerosis

Answer 28

aneurysm- uncommon
occlusion- uncommon
embolism- common
dissection- rare (nonathero)

Question 29

discuss glagovs coronary remodeling hypothesis

Answer 29

compensatory expansion maintains constant lumen size up to 40% occlusion
above 40%, expansion is overcome and the lumen truly narrows

Question 30

why does coronary angiography often underestimate plaque burden?

Answer 30

can’t distinguish stable from unstable plaque due to imaging angles

Question 31

what are the 3 primary outcomes of plaque erosion/rupture?

Answer 31

healing
embolism
thrombosis

Question 32

are plaques that rupture leading to MI usually the most stenotic by angiography?

Answer 32

no

Question 33

what diameter stenosis % is responsible for the majority of MI?

Answer 33

<50%

Question 34

what are the 3 ways by which inflammation can lead to plaque disruption?

Answer 34

plaque rupture
superficial erosion
thrombosis

Question 35

plaque rupture

Answer 35

decreased collagen synthesis
increased collagen degradation
VSMC apoptosis

Question 36

superficial erosion

Answer 36

increased EC apoptosis

increased BM collagen degradation

Question 37

thrombosis

Answer 37

increased expression of TF, fibrinogen, and PAI-1

Question 38

what si Virchow’s triad?

Answer 38

3 primary factors in the pathogenesis of thrombosis

1. injury to epithelium
2. alterations in blood flow
3. increased coagulability of blood

Question 39

what causes lines of Zahn?

Answer 39

plaque rupture > thrombosis > healing

Question 40

describe the features of an abdominal aortic aneurysm

Answer 40

presents as abdominal mass, may pulsate
risk of rupture is directly related to the size of the aneurysm (5 cm good cutoff)
operative risk is low prior to rupture, and high in the event of a rupture
embolism is a constant risk

Question 41

optimal medical therapy for chronic atherosclerosis

Answer 41

aspirin
statins
risk factor modification

Question 42

treatment of persistent angina

Answer 42

beta blockers
ACE inhib
Ca channel blockers

Question 43

surgical options for chronic atherosclerosis

Answer 43

bypass surgery

endarterectomy: removal of atheroma (usually carotids)