Lecture 16: Risk Factors and Lipids

Question 1

What two cell types maintain integrity/elasticity of arterial vasculature?

Answer 1

Endothelial cells and smooth muscle cells

Question 2

Endothelial cells = normal function

Answer 2

Impermeable (to large molecules, like LDL-C), anti-inflammatory, promote vasodilation, resist thrombosis

Question 3

Smooth muscle = normal function

Answer 3

Cause vasoconstriction/dilation, produce extracellular matrix to maintain vascular integrity (collagen and elastin)

Question 4

What is the first step of atherosclerosis

Answer 4

Endothelial cell dysfunction = particles (e.g. LDL) allowed into subendothelial space

Question 5

What is the second step of atherosclerosis

Answer 5

Recruitment of immunologic mediators. This actually causes more LDL to be deposited

Question 6

What happens to the LDL?

Answer 6

Modification –> oxidation/glycation

Question 7

What happens to immune cells?

Answer 7

Uptake of mLDL by monocytes –> “foam cells”

Question 8

All of the above leads to the formation of __________. When does this happen?

Answer 8

Lesions! Late teans

Question 9

What happens to the smooth muscle cells?

Answer 9

Smooth muscle cell migration across the tunica intima into the plaque

Question 10

Three key features of atherosclerotic lesions

Answer 10

1. Fibrous cap; 2. Lipid material (cholesterol); 3. Inflammation

Question 11

Two atherosclerotic categories and features

Answer 11

Vulnerable plaque: large lipid core, thin fibrous cap, many inflammatory cells; Stable plaque: small lipid pool, thick fibrous cap, preserved arterial lumen

Question 12

What happens if a fibrous plaque breaks open?

Answer 12

Released cholesterol can cause blood to clot –> thrombus

Question 13

What is the most common mechanism for an atherosclerotic-induced MI?

Answer 13

Fibrous cap rupture

Question 14

What is another (besides MI) consequence of a ruptured fibrous cap?

Answer 14

Healed rupture = narrow lumen and fibrous intima

Question 15

Traditional risk factors for atherosclerosis (two categories: 3, 4)

Answer 15

Non-modifiable: age, sex, family history; modifiable: dyslipidemia, smoking, DM, physical inactivity

Question 16

Non-traditional risk factors for atherosclerosis (3)

Answer 16

Apoplipoprotein, c-reactive protein, homocysteine

Question 17

Density of lipoprotein increases as the ratio of…

Answer 17

Protein/lipid increases (LDL = more cholesterol)

Question 18

HDL-C (describe)

Answer 18

“Good cholesterol” = reverse cholesterol transport by scavenging for deposited cholesterol from periphery to liver

Question 19

LDL-C (describe)

Answer 19

“Bad cholesterol” = deposits cholesterol into arterial walls, target of pharmacotherapy

Question 20

T/F: Diet and exercise can help lower LDL-C

Answer 20

True

Question 21

Four classes of LDL-C lowering pharm agents

Answer 21

Niacin, bile acid seqestrants, fibric acid, statins

Question 22

What are statins?

Answer 22

HMG-CoA Reductase Inhibitors = increased expression of LDL-C receptor in liver, lowering serum LDL-C

Question 23

Other benefits of statins (4)

Answer 23

Modest raise in HDL-C, favorably modulate vascular tone, stabilize plaque, reduce inflammation

Question 24

Major risk factors for coronary heart disease (5)

Answer 24

Cigarette smoking, HT, low HDL, family history of premature CHD (male relative 45, females >55)

Question 25

If 10-year risk of a heart attack is higher than _____% prescribe…

Answer 25

7.5%; statins

Question 26

Are there current pharm agents to raise HDL-C?

Answer 26

No: due to SEs and toxicity

Question 27

What is one way to raise HDL modestly?

Answer 27

Statins, niacin

Question 28

What is the best way to raise HDL?

Answer 28

Diet and exercise

Question 29

Cardiovascular effects of DM (5) which lead to…(2)

Answer 29

Enhanced inflammation, hypercoagulability, endothelial dysfunction, glycation of lipoproteins, vascular stiffness/calcification –> accelerated atherosclerosis and prothrombotic state

Question 30

By how much does diabetes increase risk for CVD?

Answer 30

Men: 8 –> 17%; Women: 4 –> 17%

Question 31

All diabetic patients should be treated for…why?

Answer 31

Heart disease; patients with diabetes with no prior heart attack are at the same risk for a heart attack as a non-diabetic patient with a prior heart attack

Question 32

How do we treat patients with diabetes to reduce macrovascular risk?

Answer 32

Control: blood pressure, lipids, obesity (controlling glucose does not decrease risk)

Question 33

Describe obesity and vascular effects (4)

Answer 33

1. Inflammation = adipose releases pro-inflammatory cytokines; 2. Hypertension due to increased CO; 3. Endothelial dysfunction; 4. Insulin resistance

Question 34

What are the current physical activity recommendations?

Answer 34

30 minutes or more of moderate activity on most days

Question 35

Smoking related mechanisms of injury (4)

Answer 35

Endothelial damage, prothrombotic effects on platelet function, coronary vasoconstriction, oxidative modification of LDL-C

Question 36

Describe homocysteine’s role in atherogenesis

Answer 36

Elevated homocysteine linked to pathophysiology of atherosclerosis but lowering does not help

Question 37

Describe lipoportein (a)’s role in atherogenesis

Answer 37

Higher levels of lipoprotein (a) associated with higher CV risk but not good therapies

Question 38

Describe c-reative protein’s (CRP) role in atherogenesis

Answer 38

Maker of inflammation, statin therapy might lower CRP (prescribe even if there LDL-C is not high)