Atherosclerosis / Dyslipidaemia Flashcards
Atherosclerosis Definition
Atherosclerosis is a lengthy progressive process characterised by the formation of local elevated lesions in the intima of large (aorta) and medium-sized vessels (coronary arteries) - termed atherosclerotic plaques
Atherosclerosis Progression
The development of atherosclerotic plaques requires vessel damage and tissue response. Of note is that LDL migration to the intima is essential for this process.
- Initial lesion
- Histologically normal
- Macrophage infiltrate
- Isolated foam cells
- Fatty streak
- Intracellular lipid accumulation
- Intermediate lesion
- Addition of small extracellular lipid accumulation
- Atheroma
- Core of extracellular lipid
- Fibroatheroma
- Fibrotic/calcific changes
- Complicated lesion
- Surface defect
- Haematoma/haemorrhage
- Thrombosis
Clinical Presentation of Atherosclerosis
- Asymptomatic
- Progressive lumen narrowing due to high grade plaque stenosis
- Acute atherothrombic occlusion (ruptured plaque exposing collagen, lipid debris leading to coagulation)
- Embolisation of distal arterial bed (detachment of small thrombus fragments)
- Ruptured abdominal atherosclerotic aneurysm
Examples of progressive lumen narrowing due to high grade plaque stenosis
- Stable angina pectoris (stenosed coronary artery)
- Intermittent claudication (iliac, femoral or popliteal stenosis)
- Tissue ischaemia (renal atrophy)
Examples of acute atherothrombic occlusion
- MI (coronary arteries)
- Stroke (carotid arteries)
- Lower limb gangrene (iliac, femoral or popliteal arteries)
Lipid Targets
CVD/CHD Prevention (Units in mmol/L) LDL-C < 2.0 (stasis) OR LDL-C < 1.8 (reduce deposits) TC < 4.0 HDL-C > 1.0 TG < 2.0 Non-HDL-C < 2.5
High Risk Dyslipidaemia Populations
- Symptomatic CHD, CVD or PVD
- DM
- Early family history of CHD
- Familial hypercholesterolaemia
- Aboriginal or Torres Straight Islanders
- HTN
- Males
Dyslipidaemia Non-Pharmacological Management
- Dietary modifications
* Reduce fats
* Saturated and trans
* Mono- and polyunsaturated
* Increase soluble fibre
* Introduce plant sterol-enriched milk, margarine or cheese products
* Most effective (approx LDL-C reduction of 10-15%)
* Limit alcohol- Lose weight & increase physical activity
- Most effective in increasing HDL-C
- Lose weight & increase physical activity
Dyslipidaemia Pharmacological Management
- Measure baseline CK and ALT prior to pharmacological management
- Predominant Elevation of LDL-C
- 1st line
- Statin
- 2nd line
- Ezetimibe
- Bile Acid Binding Resins
- Nicotinic acids
- Fibrates
- 1st line
- Predominant Elevation of TG
- Usually associated with low HDL-C
- Increased risk of pancreatitis
- 1st line
- Fibrates and fish oil (omega 3)
- 2nd line
- Add Nicotinic acid
- Predominant Elevation of LDL-C
Statin Overview (incl generic name, mechanism and common side effects)
Generic Name
- Atorvastatin
- Rosuvastatin
Mechanism of Action
* Inhibit HMG CoA reductase
Side Effects
* Myopathy (raised CK)
(increased with nicotinic acid or vibrates)
* Raised ALT/AST
Ezetimibe Overview (incl mechanism and common side effects)
Mechanism of Action
* Inhibits cholesterol absorption
Side Effects
- Myopathy
- Raised ALT/AST
Bile Acid Binding Resins Overview
incl generic name, mechanism and common side effects
Generic Name
- Cholestyramine
- Colestipol
Mechanism of Action
- Increase excretion of bile acids
- Causing more cholesterol to be converted to bile acids.
Side Effects
- Gut related
- Bloating
- Abdominal discomfort
- Diarrhoea
- Constipation
Nicotinic Acids Overview
incl mechanism and common side effects
Mechanism of Action
* Reduce release of VLDL and thus lower TG
Side Effects
- Prostaglandin mediated
- Flushing
- Dizziness
- Palpitations
Fibrates Overview (incl generic name, mechanism and common side effects)
Generic Name
* Fenofibrate
Mechanism of Action
- Promote lipoprotein lipase activity
- Causing increased TG lipolysis
Side Effects
* Myositis-like syndrome
(increased with Statin)
* Gallstones - increased cholesterol in bile
Atherosclerosis Procedural Management
Endarterectomy
- Technique where the atheromatous intima is cored out from the media
Percutaneous Angioplasty
- Balloon open the stenosed vessel and can have a stent placed for long term support
Surgical bypass
- Segments of the saphenous vein or radial artery are used to bypass affected areas
