DIet and CV Disease

Question 1

Define atherosclerosis [2]

Answer 1

A combination of atheromas (fatty deposits in the vascular wall) stiffening of the blood vessel walls

Question 2

Name 5 modiable risks for atherosclerosis [5]

Answer 2

hyperlipoproteinemia:
* Smoking Diabetes Hypertension Obesity
* Can lead to hypercholesterolaemia, this mostly contains LDL (but also VLDL and HDL). Measure total cholesterol to establish if hypercholesterolaemia is present.
Smoking
obestity
Physical inactivity
Ethanol intake
Psychosocial.
Lipoprotein (a)
* major prothrombotic LDL lipoprotein, which carries pathologically oxidised lipids.

Question 3

Name 4 non-modifiable risks for atherosclerosis [3]

Answer 3

• increasing age
• male
• heritability: Fx; South Asians; polygenic influence

Question 4

What is the most important factor from diet in reducing CVD? [1]

Answer 4

Total calorie intake is most important thing in reducing CVD: particularly saturated fats

Question 5

What is a refined sugar? [1]
Is it good or bad for CVD? [1]

Answer 5

Refined sugar: extracted from natural sugars like sugar cane; table sugar

Really Bad for CVD !!!

Question 6

Are polysaccarhides good or bad for CVD? [1]

Answer 6

good

Question 7

What are the different classes of fatty acids? [3] and their sources [3]

Answer 7

Saturated
* From traditional dietary sources. Eg. Animal and vegetable fat.

Monounsaturated
* From olive oil, sardines, tuna, rape seed oil.

Polyunsaturated
* Omega - no. of carbons from the free end. Eg. Omega 3 oils.

Question 8

Arachnoid acid:
- omega [] fatty acid [1]
- Where is it found in the body under normal conditions? [1]

Answer 8

Arachnoid acid:
- omega 6 fatty acid [1]
- incorporated into membrane phospholipids

Question 9

What happens to arachidonic acid during inflammation? [1]

Answer 9

Escapes from membrane: metabolised to potent inflammatory mediators by phospholipase A2 (PLA2) eg. Prostaglandins

(which is in turn further metabolized by cyclooxygenases (COXs) and lipoxygenases (LOXs) and cytochrome P450 (CYP) enzymes)

Question 10

Which enzymes does NSAIDs block? [2]

Answer 10

NSAIDs inhibit cyclooxygenase COX-1 and COX-2

Question 11

How are omega-3s anti-inflammatory? [3]

Answer 11

Metabolised to anti-inflammatory lipid mediators:
* Resolvins
* protectins
* maresins.
(increasing macrophage phagocytosis of debris and countering proinflammatory molecules)

Question 12

So overall: omega 6 [] and omega 3 [].

Answer 12

So overall: omega 6 BAD and omega 3 GOOD.

Question 13

FYI

Answer 13

Aspirin and statins enhance anti-inflammatory mediators from omega 3+6 mediators.

Question 14

Overall conclusions about fatty acids in diet in relation to CVD:

Effects of fat composition of the diet on CVD are [] There Is [] evidence forthe beneficial effect of PUFAs and omega 3 fatty acids.

Answer 14

Overall conclusions about fatty acids in diet in relation to CVD:

Effects of fat composition of the diet on CVD are not large There Is weak evidence forthe beneficial effect of PUFAs and omega 3 fatty acids.

Question 15

cholesterol

Question 16

What are flavonoids?

Answer 16

Pigmented compounds found in fruit, veg, tea, chocolates, wine, olive oil

Question 17

Which pathologies are flavoinoids beneficial with regards too? [2]

Answer 17

Stroke and MI
very significant reductions in risk by up to half.

Question 18

Why are flavonoids beneficial for stroke and MI? [2]

Answer 18

• Antioxidants
• Inhibit inflam enzymes: e.g NADPH oxidase (which generates ROS)

Important part of Mediter. diet

Question 19

Alcohol effect and CVD? [2]

Answer 19

Small benefit in small dose
Big risk at big dose

Question 20

What effect does low and high Folate and B12 levels have on CVD?

Answer 20

When the body has Folate and vit B12 (necessary co factors for)
* methionine synthase enzyme: converts homocysteine –> methionine.

BUT: without Folate and B12:
* homocysteine -> homocysteine thiolactone (damages endothelium
= ATHEROSCLEROSIS

Question 21

Chronic deficiency in folate causes low [] and high blood [] levels

Answer 21

Chronic deficiency in folate causes low methionine and high blood homocysteine levels

Question 22

When chronic folate deficiency: homocysteine is converted to toxic [] which damages endothelium.

Answer 22

When chronic folate deficiency: homocysteine is converted to toxic thiolactone which damages endothelium.

Question 23

Explain how exercise reduces CVD risk

Answer 23

• Increased exercise stimulates blood flow -> increases NO in blood vessels
• NO is anti-atherosclerotic because it is anti-inflammatory -> reduced CVD risk
• NO also reduces hypertension through dilation/reduction of peripheral resistance.

Question 24

Which layers of blood vessel does atherosclerosis sit in? [1]

Answer 24

Sits in between the intima and the media layers: Primarily a thickening of the intima layer

Question 25

MoA of atherosclerosis formation?

Answer 25

* **Leukocytes** migrate from blood **into the arterial wall** when it is damaged. * Process driven by **oxidised LDL** which aggregates in the wall between the intima and the media: oxidised LDL is a **DAMP** which means it is treated as though it is a **pathogen**. * Macrophages take up the oxidised LDL which makes them turn into **foamy cells** * **HDL** reduces this process, that is why it is good - it takes cholesterol out of the artery wall.

Question 26

How does inflammation of endothelium drive atherosclerosis? [2]

Answer 26

Inflamed/damaged endothelium cells make **adhesion molecules with chemoattractants** which recruit more **leukocytes** **LDL** will accumulate at the point of **inflammation** and will **oxidise** to **foam cells**

Question 27

Name 4 things that can trigger endothelium inflammation [4]

Answer 27

Hyperlipidaemia &LDL smoking Hyperglycaemia & diabetes. Hypertension and angiotensin II. Oxidised LDL & atherosclerosis -> positive feedback cycle.

Question 28

Name 5 things that reduce risk of atherosclerosis

Answer 28

HDL Increased blood flow (exercise) Nitrites Nitric oxide Flavonoids in fruit, veg and wine Statins Anti-inflam mediators - eg. Omega 3 fatty acids.

Question 29

Which weight babies are at risk of CVD later in life? [1]

Answer 29

**Low weight babies** associated with **CVD** and **diabetes** later in life. Restriction of foetal growth by poor maternal nutrition or maternal endothelial dysfunction. Caused by reprogramming of neurohormonal regulation by epigenetic mechanisms - 'foetal reprogramming'

Question 30

What effect does Angiotesnin II have on cognitive impairment? [1] Which drug class impairs onset of dementia? [1]

Answer 30

**Angiotensin II** shown to directly cause **cognitive impairment**. **Angiotensin II blockers** have been shown to slow the onset of dementia.

Question 31

Why are statins the OG? [2]

Answer 31

Statins are **anti-cholesterol** and **anti-inflammatory** - very good drugs

Question 32

What is metabolic syndrome a combination of? [4]

Answer 32

Syndrome of increased CVD risk because of: * Insulin resistance/ Type II diabetes * Abdominal obesity * Dyslipidaemia (particularly hypertriglyceridaemia) * Hypertension These factors cluster together more frequently than expected by chance !

Question 33

What is a modern viewpoint on EFFECTS OF DIETARY CONSTITUENTS ON CARDIOVASCULAR DISEASE ?

Answer 33

**control of total calorie intake most important**: though NHS still recommends restricting saturated fat