21. Diet and Cardiovascular Disease Flashcards
What is atherosclerosis?
How were the common factors that contibuted to CVD initially identified?
What are the 4 major risk factors for atherosclerosis? (NB: can see first signs in foetus!)
Give a local and a non-modifiable risk factor.
Focal chronic inflammatory disease of large and medium arteries, induced by lipid products and characterised by intimal thicking and lipid deposition
Framingham Heart study: smoking, cholestrol, hypertension, lack of activity, obersity, menopause, psychosocial factors. High HDL reduced risk of death.
Hyperlioproteinaemia: hypercholesterolaemia/hypertriglyceridaemia (LDL quite big, mainly chol), HDL - good chol, mainly phospholipid), hypertension, smoking, diabetes (T2)
Local: radiotherapy (accelerates atherosclerosis); Non-modifiable: age, gender, family history/genetics/race (S. Asian more likley)
What is the NHS maximum ‘normal’ range for cholestrol in
a) a healthy person
b) a high risk person
Do CVD risk factors have a big effect individually?
Does the diabetes risk with obesity/BMI affect men and women the same?
How is this risk linked to CVD?
a) <5
b) <4
No - they combine to have a multiplicative effect.
No - enormous effect in women and not as big in men
Causes increased risk of hypertension -> risk of CVD
What is the metabolic syndrome?
Explain how increased intracellular fatty acids induce insulin resistance/type 2 diabetes.
A syndrome giving an increased risk of CVD consiting of insulin resistance/type II diabetes, abdominal obesity, hypertension, and dyslipidaemia (abnormal amount of lipid in blood: hypertriglyceridemia and/or low HDL). All can be cosequences of excessive food intake.
1) FA split from circulating triglycerides in blood by glycoprotein lipase. FA transporter CD36 transports excess FA from blood lipids -> cell. If not burnt in mitochondia for metabolic energy, it accumulates.
2) Saturated fatty acids are metabolised to toxic products e.g. ceramide. Signalling from insulin receptor blocked (normally activates GLUT4 glucose transporter) = insulin resistance
What is the most up-to-date conclusion regarding dietry advice and CVD prevention? What are some good foods?
What class of fatty acid is oleic acid and where is it found?
What is a major dietary polyunsaturated fatty acid?
What does the term ‘n-3’ (or omega-3) mean when referring to a polyunstaurated acid?
Moved from ‘sat fat and dietary cholestrol raise blood cholestrol’ to ‘control of total calorie intake more important’. Wholegrains and fibre good.
Monounstaurated, olive oil.
Linoleic (and alpha-linoleic) acid - precursors of many major polyunsaturated FAs
1st double bond exists as 3rd carbon-carbon bond from the terminal (methyl) end of the carbon chain.
What configuration, cis or trans, are most naturally-produced FA in?
Do more saturated fats have a higher or lower melting point?
Describe the trans configuration.
How are trans-fatty acids produced?
Cis
Higher
More stable chains that’re hard to break/transform - form longer chains that aggregate in tissues and lack hydrophilic properties. Increase LDL and decrease HDL.
Hydrogenation of polyunsaturated fatty acids. NOW BANNED IN ENGLAND.
What is arachidonic acid used for?
What can omega 3 FAs be metabolised to?
How do asprin and statins work in respect to polyunsaturated fatty acids?
Incorperated into membrane phospholipids. Released upon inflammation by phospholipase A2 and it synthesises inflammatory mediators (prostaglandins, leuotrienes etc.)
Anti-inflammatory eicosanoids inc. new compounds that inhibit/resolve inflammation. Omega-3 are anti-inflammatory and anti-arthrogenic (inhibits formation of fatty deposits). From fish and nuts
Enhance anti-inflammatory mediators from omega 3 and 6.
What is the conclusion regarding dietary cholesterol and CVD?
What are flavenoids? Give examples.
Why are nitrates from e.g. in beetroot good for the body?
And sulforaphane?
Dietary cholestrol has little importance in regulating serum cholestrol/CDV risk.
Pigmented polyphenol plant compounds involved in photosynthesis and protect from UV light, in tea, chocolate, wine. Beneficial effects on MI and stroke. Inhibitors of multiple enzymes including NADPH oxidase that genretes damaging ROS. Examples: flavonol
Nitric oxide prevents hypertension - made in endothelial cells lining endothelial wall which dilates blood vessels.
Affects cellular metabolism
Flavenoids and the Mediterranean diet have a major effect on preventing CVD
Describe the protective effects of alcohol.
What effect does a chronic/partial deficiency of folate and/or vitamin B<strong>12</strong> have on the body’s amino acid levels?
How is exercise effecive for CVD risk?
Probably though improving blood lipid profile and inhibiting thrombosis. Wine contains multiple flavenoids, and flavenoid-like resveratrol, with anti-CVD and possible life-prolonging effects. But any form of alcohol has hypertensive effect
Low level of methionine and high blood homocysteine level, which is converted to toxic thiolactone, which damages endothelial cells and vessel walls.
Effect mainly through action on other major risk factors e.g. hypertension
When atherosclerosis gets bad, what forms in the artery walls?
What is the most common reason for thrombus formation?
Crystals
Mechanical breakdown in wall -> cracks -> platelets in contact with thrombogenic substances in wall -> thrombus (clot) starts developing -> (MI)
Describe the process of atherosclerosis.
- Damaged endothelium exposes adhesion molecules which capture circulating monocytes.
- Endothelial erosion exposes collagen-rich prothrombotic subendothelium, to which platelets adhere, forming microthrombi.
- Oxidising free radical, superoxide, from NADPH, oxidises in the endothelial membrane.
- Captured monocytes infiltrate through endothelium and differentiate into macrophages in repsonse to growth factors, cytokines generated by infiltrating T-lymphocytes, which go on to generate lots of pro-oxidant spp (superoxide, NO) designed to kill pathogens.
- Adherant platelets degranulate and release inflammatory mediators including PDGF. Neighbouring SM cells proliferate and form neointima, and generate ECM to stabilise the developing plaque (fibrosis)
- Normally circulating lipids in form of LDLs (carrying cholestrol) diffuse in and out of vessel wall, but in this highly oxidising environment, they’re oxidised (ox-LDLs) which are recognised by scavenger receptors on macrophages.
- Ox-LDLs are trapped in vessel wall in macrophages (now foam cells) which die, releasing their contents to form the lipid-rich core of the plaque. Calcification = also feature of mature plaques.
- Most plaques stabilise at this point, as inflammation is resolved, and partially occlude lumen. Plaques that remain inflammed can become unstable and rupture: highly thrombogenic material from core bursts through weakened neointimia and contacts blood -> coagulation cascade -> may completely occlude artery
* NB: LDL takes cholestrol into artery wall and HDL takes it out normally*
Describe the regulation of atherosclerosis at the endothelium-level.
How are birth weight and CVD possibly linked?
Anti inflammatory/atherosclerosis: HDL, exercise (increases blood flow), nitric oxide, nitrates, flanonoids from diet, statins, anti-inflammatory mediators from omega3 FAs
Pro inflammatory/atherosclerosis, endothelial dysfunction: hyperlipidaemia, LDL, smoking, diabetes/hyperglycaemia, homocysteinaemia (elevated homocysteine), atherosclerosis (+ve fb), inflamed endothelium
Low birth weight (due to maternal vascular dysfunction) = increased risk of CVD
What dietary/lifestyle changes could be made to decrease hypertension?
Reduce: obesity, excess Na, alcohol intake, smoking
Start: exercise, K+ (in vegetables, fruit), low fat, low cholestrol, high fruit/vegetable diet
Better population education, food marketing and prophylactic medicine.
