Atherosclerosis

Question 1

What are the coronary arteries?

Answer 1

Left and right coronary arteries come off of aorta directly and supply most of the blood to the left and right sides of the heart, respectively.

Question 2

What is atherosclerosis?

Answer 2

Question 3

How does arteriosclerosis differ from atherosclerosis?

Answer 3

Arterosclerosis = small arteries and arterioles

Atherosclerosis = larger arteries (aorta, carotid,iliac) and large and medium sized muscular arteries (coronary and popliteal)

Question 4

What arteries more frequently develope atherosclerosis?

Answer 4

Lower abdominal aorta > coronary > popliteal > internal carotid > circle of Willis

Question 5

What are some other conditions that can result from atherosclerosis?

Answer 5

• Stroke
• TIA
• AAA
• Ischemic colitis
• Aneurysm
• MI
• Stable or unstable angina
• Limb claudication

Question 6

What is the take away from this graph?

Answer 6

Atheroclerotic streaks were visible in large % of young adults –> atherosclerosis is big issue and more prevalent than would imagine

Question 7

Describe the normal anatomy of the lining of arteries.

Answer 7

Tunica intima = single layer of endothelial cells

Tunica media = smooth muscle cells

Tunica adventitia = collagen and connective tissue

Question 8

What is the impact of blood flow on development of atherosclerosis?

Answer 8

Normal, pulsatile, laminar blood flow is protective against athersclerosis because of the force it exerts on the tunica intima. The normal shear stress from blood flow promotes signaling pathways that reduce inflammation, decrease thrombosis, and decrease ROS.

Irregular flow disrupts this shear stress and changs the signaling that occurs in the endothelial cells away from those protective measures. Irregular flow is seen most commonly at arterial branching points.

Question 9

What are the forces that a blood vessel experiences?

Answer 9

Question 11

What are the 3 stages of atherosclerosis?

Answer 11

Question 12

Describe the initiation of atherosclerosis with the formation of the fatty streak.

Answer 12

1. The tunica intima becomes leaky due to irregular flow, high blood glucose, smoking (and other factors I’m sure).
2. LDL enters the space between the tunica intima and the tunica media. This pushes the tunica intima out and can begin the process of occlusion of the vessel.
3. LDL is oxidized in this space, leading to recruitment of monocytes to enter the space. Monocytes then differentiate into macrophages and phagocytize the LDL.
4. The LDL plugs up the macrophage and makes a “foam cell”. The foam cells are “sticky” and can adhere to one another. They also promote the recruitment of other molecules that exacerbate this response.
5. Smooth muscle cells migrate from tunica media to tunica intima and stick to foam cells forming initial plaque.

Question 13

Describe the process of plaque progression.

Answer 13

Smooth muscle cells change genotype when enter tunica intima such that they look more like cancer cells with regards to their ability to proliferate. They also disrupt the ECM by increasing production of enzymes that degrade the ECM, making more space for the plaque to grow. As they do this, they get trapped in the conglomerate of foam cells, LDL and SMCs. The fibrous cap on top of the plaque needs to be intact to prevent rupture of the plaque. A person can have a “stable plaque” (stable angina) and that stability is determined by the integrity of the fibrous cap. If the fibrous cap is ruptured, then the plaque contents are exposed to the blood. There are a lot of pro thrombotic molecules in the plaque so when this happens it promotes rapid thrombosis and complete occlusion of the vessel. Ultimately, parts of this clot can break off and travel through the body causing MI or stroke.

Question 14

What causes angina?

Answer 14

When vessels narrow due to plaque formation, blood flow through these vessels is diminished. This can present as pain in the area where the occlusion is. It can be present all the time or with increasing exertion (increasing blood flow).

Question 15

What factors are seen in a stable plaque vs. unstable plaque?

Answer 15

Stable: thick fibrous cap, small fatty core

Unstable: thin fibrous cap, large fatty core

Question 16

What are some common symptoms of coronary artery disease?

Answer 16

Question 17

What are some non-modifiable and modifiable risk factors for atherosclerosis?

Answer 17

Question 18

What are four key behaviors for ideal CV health?

What are three key health factors for ideal CV health?

Answer 18

Question 19

How do statins work?

Answer 19

Statins are inhibitors of HMG-coA reductase. By lowering the amount of cholesterol that is produced endogenously, they decrease intracellular cholesterol and make cells think they don’t have enough cholesterol. This results in upregulation of the LDL-R which leads to increased removal of LDL from blood and thus increased use of cholesterol from diet.

Question 20

What is PCSK9?

Answer 20

PCSK9 is found in normal human function. It targets the LDL-R for internalization and degradation. Monoclonal antibodies have been developed that inhibit PCSK9 and thus increase the amount of LDL-R that is available on the surface of cells to uptake LDL.

Question 21

If a person has clinical atherosclerotic cardiovascular disease (ASCVD), what is the recommendation for a statin if they are:

• Over 75 years
• Under 75 years

Answer 21

• Moderate intensity
• High intesntiy, unless they are not a candidate for high intensity then moderate intensity

Question 22

• What is the definition of high intensity statin therapy?
• What is the definition of moderate intensity statin therapy?

Answer 22

• Daily dose lowers LDL by 250%
• Daily dose lowers LDL by 30% to 50%

Question 23

If a person does not have ASCVD, but their LDL is > or = to 190mg/dL, what is the recommendation for statin use?

Answer 23

They should start a high intensity statin unless they ar enot a good candidate then they should start moderate intensity

Question 24

If a person has normal LDL and no ASCVD, but they are diabetic and between the ages of 40 - 75, what is the recommendation for statin use?

Answer 24

Moderate intensity statin, unless their estimated 10 year ASCVD risk is >= 7.5%, then start high intensity

Question 25

You have an adult who is over 21 years of age present to your clinic for a physical. They don’t have ASCVD, their LDL is normal and they don’t have diabetes. What is the recommended next step with regards to assessing if they should be on a statin?

Answer 25

Use the ASCVD calculator to esimate their 10 year ASCVD risk.

• If their risk if >=7.5% and their age is between 40 - 75, then you may want to consider starting statin therapy (moderate to high based on risk and family Hx).
• If their risk is < 7.5% and/or if they are < 40 years old, then the prevention benefits of a statin are unclear and treatment may carry more risk than benefit

Question 26

How do you calculate LDL from a blood lipid panel?

What can impact the accuracy of this indirect calculation of LDL?

Answer 26

LDL cholesterol (mg/dL) = total cholesterol – HDL cholesterol – (triglycerides/5)

where “triglycerides/5” is used to represent VLDL. It assumes the patient has fasted for ≥12 hours prior to specimen collection so triglycerides levels are stable and unaffected by a recent meal.