6 Atherosclerosis RISK factors / Epidemiology Flashcards
Atherosclerosis affects what size arteries ?
large (aorta, carotid, iliac) and medium sized arteries (coronary, renal, cerebral )
atherosclerosis define ?
thickening , narrowing and hardening of the walls of large and medium sized arteries as a consequence of atheroma
atheroma define ?
accumulation of intra- and extracellular lipid in the tunica intima and tunica media of large and medium sized arteries
arteriosclerosis definition ?
thickening and hardening of the walls of arteries and arteriolesfrom any cause (including atherosclerosis)
normal arterial structure
- tunica intima (innermost layer , smooth endothelium, elastic tissue)
- tunica media (smooth muscle, elastic tissue & collagen)
- tunica adventitia (outermost layer)
fundamental lesion in atherosclerosis is called a ….. ?
plaque
3 ish sections: Fat bread of Air
modifiable risk factors of atherosclerosis ?
- carbohydrate excess (western pattern diet)
- sedentary lifestyle
- abdominal obesity
- insulin resistance
- diabetes mellitus
- trans-unsaturated fatty acids
- hypertension
- dyslipidaemia, hyperlipidaemia
- tobacco smoking
Examples of food containing trans-unsaturated FAs ?
- partially hydrogenated oils
- ready-made cookies
- deep-fried foods e.g. elaidic
nonmodifiable risk factors for atherosclerosis ?
- age
- south asian descent
- family history
- genetics
less or uncertain risk factors for atherosclerosis ?
- thrombophilia
- alcohol
- sleep deprivation
- arsenic
- air pollution
- chronic stress
- periodontal disease
- systemic inflammation / infection
Epidemiology of atherosclerosis: AGE (non-modifiable)
throughout adult life it’s …..1… and the risk factors operater over ..2..
- slowly progressive
- years
Epidemiology of atherosclerosis: GENDER (non-modifiable)
1. until when are women relatively protected ?
2. presumed bias …?
3. Incidens in women = that of men by age range ?
- before menopause
- hormonal
- 70s and 80s
Which type of lipoprotein is most significant in contributing to atherosclerosis ?
low-density lipoprotein (LDL) because of it high half-life
what role does HDL play in cardiovascular health ?
HDL is protective as it helps to remove cholesterol from the bloodstream, thereby reducing the risk of plaque formation in the arteries
homozygous familial hypercholesterolaemia
1. type of disorder ?
2. characterised by ?
3. due to ?
- genetic disorder
- extremely high levels of LDL cholesterol
- defects LDL receptor resulting in decreased hepatic uptake of LDL and increased circulating LDL
At what age might individuals with homozygous familial hypercholesterolaemia experience a myocardial infarction ?
before age of 20 years
How are lipids carried in the blood ?
bound to carriers:
* 2% mostly FA bound to albumin (limited capacity to transport FA)
* ~ 98% carried as lipoprotein particles
Lipoprotein particles consist of what ?
- phospholipids
- cholesterols
- cholesterol esters
- proteins
- triacylglycerols
- structure of core of a lipoprotein ?
- what forms outer layer of lipoprotein ?
- hydrophobic lipid core
- hydrophilic outer layer of phospholipid and apolipoprotein (A-E)
How is the prevalence of atherosclerosis distributed among developed and developing nations ?
Atherosclerosis is ubiquitous (present everywhere) among developed nations, with a lower incidence in South America, Africa, and Asia.
Which specific population within Asia is predisposed to atherosclerosis?
south East Asians are predisposed to atherosclerosis.
What factors influence the incidence of atherosclerosis in different regions?
Social circumstances and diet
What happens to migrants who move to high-risk locations and adopt the local lifestyle and diet?
adopt the new lifestyle and diet have the same risk of atherosclerosis as the population in their new location.
What can be inferred about the role of genetics versus lifestyle in the development of atherosclerosis from the information about migrants?
The information about migrants suggests that lifestyle and diet play a significant role in the development of atherosclerosis, as migrants adopt the same risk levels as their new location, regardless of their genetic background.
Associated physical signs of familial hyperlipidaemia ?
- corneal arcus
- tendon xanthomas
- xanthelasma
familial hyperlipidaemia :
1. …….. lipoproteins
2. leads to ….
- genetically determined abnormalities
- early development of atherosclerosis
Smoking is a powerful risk factor for atheroscleorsis and what else ?
ischaemic heart disease
Risk of atheroscleorsis falls after giving up what ?
smoking
Although mode of action is uncertain with smoking and atheroscleorisis . Smoking is a …1… and there is increased …2… because of reduced …3.. (which is a …4… inhbitor)
- procoagulant
- platelet aggregation
- prostacyclin
- platelet activation
With hypertension there is a …1… link between …2… and high …3…. blood pressure.
Mechanism uncertain:
perhaps …4… caused by raised pressure
- strong
- ischaemic heart disease
- systolic and diastolic
- endothelial damage
How does impaired glucose tolerance contribute to the development of atherosclerosis?
formation of advanced glycation end products (AGEs) and the activation of protein kinase C (PKC)
What are advanced glycation end products (AGEs) and how are they formed?
AGEs are formed when glucose derivatives react with amino acids of proteins.
How do AGEs affect collagen in large blood vessels?
AGEs crosslink collagen, reducing the elasticity of large blood vessels and predisposing them to endothelial injury.
What is the impact of AGEs on LDL and cholesterol deposition in blood vessels?
AGEs change protein properties, increasing LDL trapping and enhancing cholesterol deposition in the intima of blood vessels.
How do AGEs influence the procoagulant activity of endothelial cells?
AGEs increase the procoagulant activity of endothelial cells.
What causes the activation of protein kinase C (PKC) in the context of diabetes mellitus?
Intracellular hyperglycaemia causes the activation of protein kinase C (PKC).
What is the effect of PKC activation on fibrinolysis?
PKC activation increases the production of procoagulants (e.g., PAI-1), leading to decreased fibrinolysis.
How does PKC activation contribute to inflammation in blood vessels?
PKC activation results in the production of proinflammatory cytokines by the vascular endothelium.
80% of deaths in DM type 2 happen how ?
cardiovascular deaths
What do DM pateints have at least 3 time greater incidence of death from compared to non-DM ?
CVD (cardiovascular disease)
Protective effect against atherosclerosis for ..1.. women is lost if they are …2…
- premenopausal
- diabetic
Diabetes mellitus is associated with high risk of what 2 diseases ?
- cerebrovascular
- peripheral vascular
Quantity of alcohol that’s associated with increased risk of ischaemic heart disease ?
more than 5 units/ day
Smaller amounts of alcohol may be ..1.. with it ..2.. HDL levels
- protective
- increasing
Genetic variations in which apolipoprotein is associated with changes in LDL levels ?
Apo E
What are polymorphisms in the context of Apo E?
Polymorphisms are genetic variations in the Apo E gene that result in different phenotypes.
How many Apo E phenotypes result from genetic polymorphisms?
at least 6
Can Apo E polymorphisms be used as risk markers for any diseases?
Yes, Apo E polymorphisms can be used as risk markers for atherosclerosis.
Why are Apo E polymorphisms significant in the context of atherosclerosis?
Apo E polymorphisms are significant because they influence LDL levels and can therefore serve as indicators of an individual’s risk for developing atherosclerosis.
