Clinical aspects of CV risk Flashcards
what is atherosclerosis?
a progressive disease that is characterised by a build-up of plaque within the arteries
how can plaque be formed?
- fatty substances
- cholesterol
- cellular waste
- calcium
- fibrin
what are the 2 ways that plaques can block blood flow through artery?
1) PARTIALLY BLOCK blood flow through an artery
1) TOTALLY BLOCK blood flow through an artery
what 2 things can happen to the plaque?
1) bleeding into the plaque
2) formation of a clot on the surface of the plaque
= blocking the artery
what 2 things can happen as a result from atherosclerosis?
1) heart attack
2) stroke
in the pathogenesis of atherosclerotic plaques, what happens after endothelial damage?
- give examples.
= protective response results in production of cellular adhesion molecules such as cytokines (e.g. interleukin 1, TNF-alpha), chemokines (IL8) and growth factors.
in pathogenesis of atherosclerotic plaques, what happens after the protective response resulting in production of cellular adhesion molecules?
= monocytes and T lymphocytes (inflammatory cells) attach to ‘sticky’ surfaces of endothelial cells
in pathogenesis of atherosclerotic plaques, what happens after monocytes and T lymphocytes attach to sticky surfaces of endothelial cells?
= inflammatory cells migrate through arterial wall to sub-endothelial space
in pathogenesis of atherosclerotic plaques, what happens after migrate through arterial wall to sub-endothelial space?
= monocytes differentiate into macrophages where they take up oxidised LDL-C
in pathogenesis of atherosclerotic plaques, what happens after macrophages are up oxidised LDL-C?
= oxidised LDL promotes death of endothelial cells & inflammatory response causing
= LIPID RICH FOAM CELLS
n pathogenesis of atherosclerotic plaques, what happens after lipid rich foam cells?
= fatty streak & plaques
what is the primary event in atherosclerosis thought to be and what causes this primary event?
thought to be damage to the endothelium of arterial walls, causing endothelial dysfunction
Caused by;
- haemo-dynamic factors (shear stress causing by hypertension)
- vasoactive substances
- mediators (cytokines) from blood cells
- smoke
- bad diet
- elevated glucose levels
- oxidised LDL-C
what is athero-thrombosis?
= formation of acute thrombus (blood clot) in a vessel affected by atherosclerosis
how is athero-thrombosis initially initiated?
then what happens?
Initiated by;
= changes in vessel wall resulting from plaque disruption
= atheroscloritc plaques becomes unstable & rupture, exposing components like collagen…allowing platelets to adhere to the damaged area & initiate thrombus formation
what can a thrombus do?
= extend or occlude the vessel, causing acute ischema & tissue injury.
- fatal or non-fatal CV events e.g. stroke, MI, peripheral artery occlusion which could lead to ischemia
what are some MODIFIABLE risk factors of developing atherosclerotic plaques?
1) smoking
2) dyslipidaemia
- raised LDL cholesterol
- raised triglycerides
- low HDL cholesterol
3) raised blood pressure
4) diabetes mellitus
5) obesity
6) dietary factors
7) thrombogenic factors
8) lack of exercise
9) excessive alcohol consumption
10) deprivation
11) inactivity
what are NON-MODIFIABLE risk factors of developing atherosclerotic plaques?
1) age
2) gender
3) family history of coronary heart disease
4) person history of coronary heart disease
what are the 5 classifications of lipoproteins in order from lowest density to highest?
1) chylomicrons
2) VLDL (very low density lipoproteins)
3) IDL (intermediate density lipoproteins)
4) LDL (low density lipoproteins)
5) HDL (high density lipoproteins)
Yes or No.
Are chylomicrons associated with atherosclerosis?
- where are chylomicrons synthesised?
- what do they transport?
No.
Synthesised;
= in gut after a fatty meal
Transport;
= they transport dietary triglyceride from gut to sites of use & storage, & are cleared rapidly from bloodstream
Where are VLDL lipoproteins produced and what do they do?
Why are VLDL implicated in atherosclerosis?
Synthesised
= in the liver
Function;
= main carriers of endogenous triglycerides & cholesterol to sites for use or storage
Atherosclerosis;
= as VLDL are involved in the synthesis of LDL & HDL
when are IDL lipoproteins formed?
formed;
= formed during the breakdown of VLDL & chylomicrons
In comparison to VLDL, do IDL contain more or less triglyceride & cholesterol?
IDL = contain less triglyceride & more cholesterol than VLDL
Yes or No.
Are ILD lipoproteins involved in atherosclerosis?
Yes - they are involved.
what are LDL generated from?
Generated;
= from IDL in circulation
what lipoprotein is the principle lipoprotein involved in arteriosclerosis and why?
LDL
= because they are the main carriers of cholesterol
what is the most atherogenic form LDL?
oxidised LDL
does HDL cause atherosclerosis?
no
- they protect against is development
What 2 diseases is LDL cholesterol strongly associated to?
1) atherosclerosis
2) coronary heart events
what 4 factors modify LDL cholesterol?
1) low HDL cholesterol
2) smoking
3) hypertension
4) diabetes
what diseases are associated with triglycerides?
- whats its relationship to HDL and LDL levels?
increased risk of CHD events
- related to LOW HDL levels & HIGHLY ATHEROGENIC forms of LDL cholesterol
what is normal triglyceride levels and what are high triglyceride levels?
normal = 2.3mmol/l
high = 11.3mmol/l
= increased pancreatitis risk
what role does HDL cholesterol do?
= protective effect for risk of atherosclerosis and CHD
what is the relationship between HDL levels and risk for atherosclerosis and CHD?
- lower the HDL cholesterol level, the higher the risk for atherosclerosis and CHD
= low level, increases risk
when does HDL cholesterol trend to be low?
when triglycerides are high
when is the level of HDL lowered?
- smoking
- obesity
- physical inactivity
in the endogenous pathway of lipid metabolism, what particles transports tri-glycerides and cholesterol from liver to rest of the body?
VLDL
what happens to VLDL?
- it undergoes dilapidation with the enzyme lipoprotein lipase
in the endogenous pathway, what happens to the triglycerides?
- they are removed from the core & exchanged for cholesterol esters, principally HDL.
in the endogenous pathway, what is most of VLDL transformed into?
- what enzyme facilities this transfer in large VLDL particles and small VLDL particles?
= LDL
Large VLDL particles = lipoprotein lipase
Small VLDL = hepatic lipase
In the exogenous pathway, what happens to the dietary fats?
- they are broken down in GI tract into cholesterol & fatty acids and tri-glyerides
in the exogenous pathway, what happens to most of the triglycerides?
what happens after this absorption?
- virtually all triglycerides are absorbed to form CHYLOMICRONS which enter bloodstream to be transported to liver.
in the exogenous pathway, what happens to he chylomicrons formed?
- chylomicrons are hydrolysed by enzyme lipoprotein lipase releasing energy production or storage
- chylomicrons undergo further dilapidation, resulting in formation of chylomicrons remnants.
what is the primary target to prevent CHD?
LDL-C
what do statins do?
= always reduce coronary heart disease end points
= reduces total cholesterol & LDL cholesterol
what other effects does statin cause?
- improvement of endothelial dysfunction
- increased nitric oxide bioavailability
- antioxidant properties
- inhibition of inflammatory response
- stabilisation of atherosclerotic plaques
what are xanthelasma’s?
= xanthomas of eyelids that may or may not be associated with hyper-lipidemia
where are tendon xanthomas found?
= extensor tendons of;
- fingers
- patella
- elbows
- achilles tendon (common)
what infiltrates the tendon in tendon xanthomas?
= lipids;
- hypercholestterolemia; types I & II
- normal lipids; cerebrotendinous xanthomatosis; plant sterols
what is tuberous xanthomas?
= lipid deposits in; - dermis & sub-cutis - papular - nodular or plaques - extensor surfaces of large joints - hands - buttock - heels - flexures = familial or acquired hyper-tri-glycereidemias; biliary cirrhosis
what is eruptive xanthomas?
= small reddish yellow papules; buttocks, posterior things or body folds
what causes eruptive xanthomas?
usually abrupt increase in serum triglyceride levels
what are possible diseases attributed to hypertension?
- heart failure
- left ventricular hypertrophy
- MI
- coronary heart disease
- stroke
- hypersensitive encephalopathy
- cerebral haemorrhage
what are the 2 types of hypertension and wha causes them?
1) essential hypertension
= no underlying cause
2) secondary hypertension
= underlying cause
what 3 things does hypertension treatment?
1) reduces ischaemic heart disease
2) reduces stroke
3) redues mortality
what lifestyles medication can be made to lower hypertension?
- lose weight
- limit alcohol intake
- increase physical activity
- reduce salts intake
- stop smoking
- limit intake of foods rich in fats & cholesterol
for microvascular complications, when does the clock start ticking?
= at onset of hyperglycaemia
for macro-vascular complications, when does the clock start ticking?
= before diagnosis of hyperglycaemia
what 5 things should a healthy diet contain?
- micronutrients
- antioxidants
- omega 3 & 6
- polyunsaturates
- mono-saturates
what is metabolic syndrome?
= cluster of biochemical and physiological abnormalities associated with the development of CV disease and type 2 diabetes.
what are the 5 risk factors for metabolic syndrome?
- and what are the defining levels for each.
1) abdominal obesity
- waste circumference
2) triglycerides
- > 1.7mmol/l
3) HDL-C
- < 1mmol/l in men
- < 1.3mmol/l in women
4) Blood pressure
- > 130/>85mmHg
5) fasting glucose
- > 5.6mmol/l
what ethnic group has a higher & lower death rate for CHD?
South asians = higher death rate
Black Caribbean & black africans = lower death rate
how do you treat ischaemia?
1) anti-anginal medications
- calcium blokers
- beta blockers
- nitrates
2) re-vascularization
- angioplasty
- CAGB
how do you treat atherothtrombosis?
- statins
- aspirin
- beta blockers
- ACE inhibitors
- exercise
- smoking cessation
