Vascular Endothelial Fxn, Risk Factors For Cad

Front 1

single largest killer of men and women in US

Back 1

coronary artery disease (CAD)

Front 2

3 layers of arteries, from innermost to outermost

Back 2

Intima, Media, Adventitia

Front 3

What's the anatomy of an atherosclerotic plaque?

Back 3

1) fibrous cap : consists of activated smooth muscle cells and T cells

2)lipid-filled core : with macrophage foam cells

Front 4

What effect does NO have on growht of endothelial cells?

Back 4

It inhibits growth

Front 5

Endothelial Derived Relaxing Factor (EDRF) is also known as:

Back 5

NO

Front 6

What does EDRF/NO do in the endothelium?

Back 6

It causes vasodilation, inhibition of growth, is antithrombotic, and anti-inflammatory

Front 7

What causes EDRF/NO to be released?

Back 7

Biochemical mediators: Ach, ADP, bradykinin, histamine
Biomechanical forces: shear stress

Also released tonically.

Front 8

Ach, ADP, bradykinin, histamine: how are these related to NO release?

Back 8

They all cause NO release from endothelium

Front 9

What does ACh normally do to arteries? How is this changed in conditions that are risk factors for CAD (hi cholesterol, smoking, etc)?

Back 9

Normally promotes release of NO, which causes an increase in blood flow thru vasodilation. This is decreased with risk factors.

Front 10

T/F Endothelial dysfunction and decreased NO availability is one of the first events in atherogenesis

Back 10

T

Front 11

What is the effect of free radicals like superoxide on NO?

Back 11

Breaks it down

Front 12

What is the effect of shear stress on NO?

Back 12

Increases release. This is why plaques tend to accumulate in bifurcations which are areas of low shear stress.

Front 13

NO effect on Monocytes

Back 13

Inhibits chemotaxis and activation (antiinflammatory)

Front 14

T/F One of the earliest changes associated with these risk factors is an increase in oxidative stress in the vessel wall.

Back 14

T

Front 15

What does the increase in oxidative stress do to the vessel wall?

Back 15

Causes decreased production of NO.

Causes increased production of vasoconstrictive substances, such as endothelin and angiotensin II.

Front 16

T/F Most of the ACE in the body is circulating.

Back 16

F. Only 10% is circulating. The remainder is in the tissues.

Front 17

T/F Increased AII leads to increased production of superoxide ion.

Back 17

T. This results in Reduced NO availability.

Front 18

What "activates" the SM cells of the vessel intima and causes them to grow?

Back 18

angiotensin II

Front 19

What happens in LDL infiltration to the intima?

Back 19

LDL gets oxidized and is taken up by macrophages which become foam cells and form early plaques.

Front 20

OX-LDL- leads to expression of what adhesion molecules on endothelial surface?

Back 20

(ICAM-1, VCAM-1, P-selectin)

Front 21

What happens when the adhesion molecules on the endothelial surface are upregulated by OX-LDL?

Back 21

Adhesion of monocytes and T-lymphocytes to endothelium

Front 22

MCP-1 (monocyte chemoattractant protein-1): role in atherogenesis

Back 22

Endothelial-derived cytokine that facilitates movement of monocytes & certain T-lymphocytes into the intima (transmigration)

Front 23

M-CSF (monocyte colony stimulating factor): role in atherogenesis

Back 23

Endothelial-derived cytokine that promotes activation and maturation of monocytes & macrophages in the intima
expression of scavenger receptors allows uptake of ox-LDL by macrophages

Front 24

T/F A low shear state is prothrombotic

Back 24

T

Front 25

a one cell thick layer that lines the intima

Back 25

endothelium

Front 26

T/F Enhanced permeability to lipoproteins is an important and possibly first step in the development of atherogenesis

Back 26

T

Front 27

How does NO cause dilation of arteries?

Back 27

Stimulates guanylate cyclase to produce gGMP. This causes SM relaxation and dilation of the artery.

Front 28

NO effect on platelets

Back 28

Inhibitions aggregation and adhesion (antithrombotic)

Front 29

What two systems generate angiotensin II (AII?)

Back 29

1) Renin-angiotensin (tissue)

2) Circulating

Front 30

T/F The renin-angiotensin system contributes to a reduction in NO and therefore anti-atherosclerotic effects

Back 30

F. These are pro-atherosclerotic.

Front 31

earliest lesion in atherosclerosis

Back 31

foam cell (lipid laden macrophage)

Front 32

accumulation of foam cells in the intima is known as ______

Back 32

fatty streaks

Front 33

T/F in an MI, the culprit lesion is usually large and focal

Back 33

F. Size of lesion isn't necessarily related to risk of causing MI.

Front 34

What % of patients with an MI have at least one risk factor of HTN, hyperlipidemia, diabetes, or current smoking?

Back 34

80%

Front 35

T/F Risk modification is important because it reduces development and progression of atherosclerosis.

Back 35

Kinda T, Kinda F.

Risk mgmt also reduces the conversion of stable plaques to unstable plaques that have a tendency to rupture.

Front 36

Non-modifiable risk factors for CV risk

Back 36

Male gender
Age
Family history

Front 37

Primary prevention : defn

Back 37

preventive tx before recognized CV events

Front 38

Secondary prevention: defn

Back 38

tx focused on patients with existing CVD or diabetes

Front 39

A ratio of total cholesterol:HDL <___ is associated with a reduced risk of coronary events

Back 39

4.0

Front 40

LDL should be lowered to ____ for primary prevention and ____ for secondary prevention

Back 40

less than 100, <70mg/dl

Front 41

T/F Effective therapies to raise HDL don't yet exist

Back 41

T

Front 42

What are some lifestyle factors that raise HDL?

Back 42

Exercise and moderate alcohol intake.

Front 43

How does risk for atherosclerosis and MI change when one quits using tobacco?

Back 43

Stopping smoking for one year reduces the risk of having an MI in the next year to nearly that of a nonsmoker.

Front 44

What type of exercise is best for reducing CV risk?

Back 44

Regular (3x/week) and aerobic. Weights are acceptable if done in rhythmic reps and without breath-holding.

Front 45

T/F Diabetics without recognized CAD have an equally increased risk of events compared to patients who've had a recent MI

Back 45

T

Front 46

T/F benefits of tight BP control and tight glucose control are equal in diabetes

Back 46

F. BP control is more important, but both are very important.

Front 47

Obesity, in particular truncal obesity, increases CV mortality risk by _______ over normal weight

Back 47

50-100%

Front 48

T/F Young age obesity appears to have a greater CV risk than older persons

Back 48

T

Front 49

What do the Framingham point score quantify?

Back 49

10 year risk for developing CHD

Front 50

What are the 6 risk factors accounted for in the Framingham point score?

Back 50

1) Smoking
2) Age
3) HDL level
4) Systolic BP
5)Total cholesterol
6) Sum of the points

Front 51

What are the additional benefits beyond blood pressure lowering effects of ACE inhibitors?

Back 51

Improves vascular function.

Reduces risk of CVD death, nonfatal MI, Stroke, and new onset diabetes.

Front 52

T/F Systemic measures fo inflammation correlate with risk of coronary events

Back 52

T

Front 53

How does CRP level affect mortality risk?

Back 53

they're positively correlated

Front 54

What is the role of statins in CV risk reduction?

Back 54

They reduce the acute and chronic risk of coronary events.

They lower LDL predominantly, but also lower triglycerides and slightly increase HDL.

They also reduce CRP (ie, reduce inflammation).

Front 55

Can cholesterol treatment cause a regression in plaques?

Back 55

There is an arresting of plaque progression at LDL levels <70, but not a regression.

Front 56

Risk factors adversely affect endothelial function resulting in paradoxical ____ mediated vasoconstriction.

Back 56

acetylcholine

Front 57

T/F primary proinflammatory risk factors result in hepatic production of acute-phase reactants, such as CRP.

Back 57

T