DIet and CV Disease Flashcards
Define atherosclerosis [2]
A combination of atheromas (fatty deposits in the vascular wall) stiffening of the blood vessel walls
Name 5 modiable risks for atherosclerosis [5]
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.
Name 4 non-modifiable risks for atherosclerosis [3]
- increasing age
- male
- heritability: Fx; South Asians; polygenic influence
What is the most important factor from diet in reducing CVD? [1]
Total calorie intake is most important thing in reducing CVD: particularly saturated fats
What is a refined sugar? [1]
Is it good or bad for CVD? [1]
Refined sugar: extracted from natural sugars like sugar cane; table sugar
Really Bad for CVD !!!
Are polysaccarhides good or bad for CVD? [1]
good
What are the different classes of fatty acids? [3] and their sources [3]
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.
Arachnoid acid:
- omega [] fatty acid [1]
- Where is it found in the body under normal conditions? [1]
Arachnoid acid:
- omega 6 fatty acid [1]
- incorporated into membrane phospholipids
What happens to arachidonic acid during inflammation? [1]
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)
Which enzymes does NSAIDs block? [2]
NSAIDs inhibit cyclooxygenase COX-1 and COX-2
How are omega-3s anti-inflammatory? [3]
Metabolised to anti-inflammatory lipid mediators:
* Resolvins
* protectins
* maresins.
(increasing macrophage phagocytosis of debris and countering proinflammatory molecules)
So overall: omega 6 [] and omega 3 [].
So overall: omega 6 BAD and omega 3 GOOD.
FYI
Aspirin and statins enhance anti-inflammatory mediators from omega 3+6 mediators.
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.
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.
cholesterol
What are flavonoids?
Pigmented compounds found in fruit, veg, tea, chocolates, wine, olive oil
Which pathologies are flavoinoids beneficial with regards too? [2]
Stroke and MI
very significant reductions in risk by up to half.
Why are flavonoids beneficial for stroke and MI? [2]
- Antioxidants
- Inhibit inflam enzymes: e.g NADPH oxidase (which generates ROS)
Important part of Mediter. diet
Alcohol effect and CVD? [2]
Small benefit in small dose
Big risk at big dose
What effect does low and high Folate and B12 levels have on CVD?
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
Chronic deficiency in folate causes low [] and high blood [] levels
Chronic deficiency in folate causes low methionine and high blood homocysteine levels
When chronic folate deficiency: homocysteine is converted to toxic [] which damages endothelium.
When chronic folate deficiency: homocysteine is converted to toxic thiolactone which damages endothelium.
Explain how exercise reduces CVD risk
- 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.
Which layers of blood vessel does atherosclerosis sit in? [1]
Sits in between the intima and the media layers: Primarily a thickening of the intima layer
MoA of atherosclerosis formation?
- 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.
How does inflammation of endothelium drive atherosclerosis? [2]
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
Name 4 things that can trigger endothelium inflammation [4]
Hyperlipidaemia &LDL smoking
Hyperglycaemia & diabetes.
Hypertension and angiotensin II.
Oxidised LDL & atherosclerosis -> positive feedback cycle.
Name 5 things that reduce risk of atherosclerosis
HDL
Increased blood flow (exercise) Nitrites
Nitric oxide
Flavonoids in fruit, veg and wine
Statins
Anti-inflam mediators - eg. Omega 3 fatty acids.
Which weight babies are at risk of CVD later in life? [1]
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’
What effect does Angiotesnin II have on cognitive impairment? [1]
Which drug class impairs onset of dementia? [1]
Angiotensin II shown to directly cause cognitive impairment.
Angiotensin II blockers have been shown to slow the onset of dementia.
Why are statins the OG? [2]
Statins are anti-cholesterol and anti-inflammatory - very good drugs
What is metabolic syndrome a combination of? [4]
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 !
What is a modern viewpoint on EFFECTS OF DIETARY CONSTITUENTS ON CARDIOVASCULAR DISEASE ?
control of total calorie intake most important: though NHS still recommends restricting saturated fat
