Dyslipidemia Flashcards
What does dyslipidaemia mean?
Disorder of lipid metabolism including lipoprotein overproduction and deficiency.
- Dyslipidaemia is a major risk factor for coronary heart disease, with the risk directly related to cholesterol levels
Dyslipidaemia may be manifested by:
- Increased total cholesterol (TC)
- Increased low density lipoprotein (LDL)
- Increased triglyceride (TG)
- Decreased high density lipoprotein (HDL)
What are the stages of Atherosclerosis?
- There may be some kind of injury in the endothelial cells that line your blood vessels, which can be caused by high blood pressure, smoking, diabetes (high glucose levels) etc.
- This causes adhesion molecules to come in to the surface of the endothelial cells and monocytes also start to bind to the endothelial cells to get into that lower layer of the blood vessel. Your blood vellsels may take up oxidised LDLs, so theres cholesterol that can be deposited which becomes oxidised and combines with these macrophages basically to form foam-cells.
- As these foam cells forms they start to stick down to the blood vessels just underneath the endothelial cell layer and we start to get this plaque formation. So smooth muscle migration occurs, theres adherence and aggregation of platelets that come in, theres extra T-cells that come along which all ultimately causes a massive inflammatory response.
- As this plaque gets bigger and bigger, we have a formation of this necrotic core. Where the blood isn’t reaching those cells anymore, they can’t get the nutrients and oxygen they need, hence we get this necrotic core in the middle of the plaque and we also get this fibrous-cap formation on the top.
- This is a massive inflammatory response, we have cytokines being produced, chemokines coming in and eventually this fibrous cap that started form can eventually rupture (break). This rupture of the plaque can then cause things like heart attack or stroke. If you got high levels of cholesterol circulating, this can develop as the cholesterol can be deposited which eventually can lead to Atherosclerosis.
How is LDL involved in Atherosclerosis?
LDL is oxidised -> cholesterol is deposited in blood vessels -> leads to atherosclerosis
What is the general target advice/levels for cholesterol recommended by experts?
Unless family history or existing heart disease:
- Try keep it as low as possible
- Try keep Total Cholesterol below 5mmol
- Try keep LDL levels below 3mmol
- With treatment and dietary control, aim for at least 40% decrease in non-HDL cholesterol
What is the aetiology of primary dyslipidaemia?
- A lot of dyslipidaemia are inherited diseases - Primary is 60%
- Primary is a combination of diet and genetics
- Diet and lifestyle components include; High saturated fat, Physically inactive, Overweight or obese, smoking and large waist circumference.
What is the aetiology of secondary dyslipidaemia?
Secondary lipidaemia is usually caused by some other underlying cause:
- Disease or certain drugs e.g. diabetes, liver disease, thiazides, GC
- Natural rise as age and after menopause
What inherited conditions increase blood lipids?
- Familial hypercholesterolaemia
- Inherited higher levels from birth - Mutations in LDLR or APOB or PCSK9 (we can’t take up cholesterol the same way we should be able to)
- Homozygous - rare, 1/250000 >20mmol/L
- Heterozygous - 1/250 population, CHD 20 years before general population if untreated - 8mmol/L
- Familial combined hyperlipidaemia
- Raises VLDL and more compact and dense LDL than normal
- High cholesterol and triglyceride - raised by age 20-30 - Type 3 hyperlipidaemia
- High cholesterol and triglyceride levels
- Mutations in ApoE - Polygenic hypercholesterolaemia
- More than 1 gene with changes - Primary hypertriglyceridaemia
- Lipoprotein lipase deficiency
- Very high triglyceride - Lysosomal acid lipase deficiency
- Breaks down fat in lysosomes normally but instead fat builds up in cells
What are the signs of hyperlipidaemia?
- Corneal arcus (eye)
- Tendon xanthomas
- Xanthelesma
What underlying disorders can cause secondary dyslipidaemia?
- Diabetes mellitus
- Hypothyroidism
- Chronic renal failure
- Alcoholism
- Liver disease
Which certain drugs can cause secondary dyslipidaemia?
- Thiazide diuretics
- Loop diuretics
- Beta blockers
- Oral contraceptives
- Ciclosporin
- Glucocorticoids
- Isotretinoin
- Tamoxifen
- Protease inhibitors of HIV
What is lipoprotein(a)?
Another form of lipoprotein that is associated with coronary heart disease.
- It is very strongly associated with atherosclerosis.
- Often located in atherosclerosis lesions
- It is involved in CHD because the structure of Apo(a) is structurally similar to plasminogen
- Lp(a) inhibits binding of plasminogen to receptors on endothelial cells - leads to less plasmin generation and promotion of thrombosis, increased blood clotting.
What non-pharmacological treatment can be done for dyslipisaemia?
- Dietary modification
- Low saturated fat, low trans fat, high mono or polyunsaturated fat - to decrease LDL and increase HDL
- Oily fish twice weekly
- Plant steroid and stanols to decrease cholesterol absorption from gut
- High fibre- soluble fibre (from fruit and veg) may decrease cholesterol absorption from gut - Weight loss - BMI <25
- Smoking
- Physical activity - 30min x 5 times per week
- Reduce alcohol
