Lecture 6 CVD Theme - Ageing Vessels and Ischaemic Heart Disease

Question 1

What can poor cardiovascular health cause?

Answer 1

Heart attacks
Strokes
Heart failure
Chronic kidney disease
Peripheral arterial disease
Onset of vascular dementia

Question 2

What are some modifiable risk factors in CVD?

Answer 2

Smoking
Stress
Drinking
Poor diet

Question 3

What is atherosclerosis?

Answer 3

The hardening and thickening of walls of arteries.

Question 4

Why does atherosclerosis occur?

Answer 4

Fatty deposits in the inner lining of arteries.
Calcification of the wall of the arteries or the thickening of the muscular wall of the arteries from chronically elevated blood pressure.

Question 5

What is the first sign of atherosclerosis?

Answer 5

Aged vessels becoming stiff leading to systolic hypertension.

Question 6

Describe how monocytes transmigrate to the vessel wall.

Answer 6

Endothelial cells become activated and have an additional receptor ICAM1 which recruits monocytes from the blood.
They can then bind to these receptors and trans migrate to the vessel wall.

Question 7

When do arterial endothelial cells capture leukocytes?

Answer 7

When they are subjected to irritative stimuli such as hypertension or pro-inflammatory mediators.

Question 8

What promotes entry and retention of cholesterol-containing low density lipoprotein in the artery walls?

Answer 8

Parallel changes in the endothelial permeability and composition of the ECM.

Question 9

What does retention of cholesterol containing low density lipoproteins in artery walls cause?

Answer 9

Leukocyte adhesion and intact but modified particles undergo endocytosis by monocyte-derived macrophages leading to intracellular cholesterol accumulation.

Question 10

What do chemoattractant mediators do?

Answer 10

Direct the migration of bound leukocytes into the tunica intima.

Question 11

How are foam cells formed?

Answer 11

Once monocytes are in the artery wall, they differentiate into tissue macrophages that engulf lipoprotein particles and become foam cells which proliferate and migrate.

Question 12

How does the lesion progress?

Answer 12

Migration of smooth muscle cells from the tunica media to the tunica intima.
Smooth muscle cells already in the initma are proliferating as well as those derived from the media.
ECM macromolecules such as collagen also increase.
Plaque macrophages and SMCs die in advancing lesions creating an increase in extracellular lipid in the central region of the plaque, this is the lipid (necrotic) core.

Question 13

Describe thrombosis.

Answer 13

The ultimate complication of atherosclerosis.
Physical disruption of the atherosclerosis plaque.
A fracture in the plaques fibrous cap allows blood coagulation components to come into contact with tissue factors, triggering the thrombus to extend into the vessel lumen, impeding blood flow.

Question 14

What are some ways to diagnose atherosclerosis?

Answer 14

Electrocardiogram can find wall motion abnormalities.
Stress test - stress echocardiography, adenosine stress cardiac MRI, myocardial perfusion scan.
Non-invasive imaging - coronary CT, calcium score.
Invasive imaging - coronary angiography.

Question 15

Describe a coronary angiography.

Answer 15

Identifies a coronary stenosis.
A catheter is placed into an artery in the arm or groin and threaded to the heart.
Blood vessels of the heart are then studied by injection of contrast media through the catheter.
A rapid succession of X-Rays is then taken to view blood flow.

Question 16

What complication and treatment would be performed for cerebrovascular disease?

Answer 16

Complication = stroke, vascular dementia?
Treatment = thrombolysis, embolectomy.

Question 17

What complication and treatment would be performed for coronary heart syndrome?

Answer 17

Complication = acute myocardial infarction.
Treatment = revascularisation by stent implantation or bypass-operation.

Question 18

What complication and treatment would be performed for aortic syndrome

Answer 18

Complication = acute aortic dissection.
Treatment = surgery or stent implantation.

Question 19

What complication and treatment would be performed for peripheral artery occlusive disease?

Answer 19

Complication = acute arterial occlusion.
Treatment = anticoagulants, thrombolysis. embolectomy, percutaneous revascularisation, surgery.

Question 20

What drugs can be used to help relieve and manage platelet activation to relieve atherosclerosis?

Answer 20

Aspirin
Clopidogrel
Prasugel
Ticagrelor

Question 21

What drugs can be used to help relieve and manage diabetes to relieve atherosclerosis?

Answer 21

Insuline
Metformin

Question 22

What drugs can be used to help relieve and manage dyslipidaemia to relieve atherosclerosis?

Answer 22

Statins
Fibrates
Ezetimibe

Question 23

What drugs can be used to help relieve and manage hypertension to relieve atherosclerosis?

Answer 23

ACE-inhibitors
AT11-blockers
Calcium blockers
Diuretics

Question 24

What is the Alzheimer’s disease amyloid beta hypothesis in cardiovascular ageing and disease?

Answer 24

2 types of amyloid beta = AB42 and AB40
3 major splice variants of APP produced - APP695 in neurons, APP751 in endothelial cells and APP770 in platelets.
Ageing increases circulating levels and subsequent tissue deposition of AB by augmenting APP production and processing or by decreasing AB clearance and degradation.
Dysregulation of the equilibrium between AB production and removal in compartments inside and outside of the CNS can lead to an accumulation of AB40 in the blood, vascular walls and heart tissue which is associated with CVD.
AB40 found in atherosclerotic plaques.

Question 25

How is AB40 a significant independent predictor for CV death?

Answer 25

AB40 activates a cascade of proinflammatory events in endothelial cells and macrophages involving cytokine secretion and oxidative stress leading to vascular disease.
Incidence of CV death is significantly increased when someone has high AB40.