Lipids in heart disease Flashcards
Why are lipids needed in the body
- Importatn in constituent of the cell membranes
- helps in the absorption of fat soluble vitamins
- maintains membrane fluidity
- acts as a thermal insulator adn cellular metabolic regulator
- hormone synthesis - steroid synthesis
- organ padding
What are the fat soluble vitamins
A
B
E
K
What enzyme do statins inhibit
- HMG CoA reductase
What do statins lower
- Cholestrol level
What is cholestrol important for
- Vitamin D syntehsis
- steroids
- bile salts
What are modifiable cardiovascualr risk factors
- smoking
- high cholestrol
- hypertension
- high blood glucose
- obesity
What are the unmodifiable risk factros for cardiovascular disease
- Age
- gender
- family history
- ethinicty
The smaller the molecule
the smaller the moelcule the easier it is to penetrate between the endoithelial cells and go into the endothelium
- therefore easy for LDl molecules to get in adn less easy for VLDL adn IDL
Describe how LDLs, HDLs and chylomicrons work together
- Chylomicrons transport fat from the itnestinal mucsoa to the liver
- in the liver some of the chylomicrons release triglycerides and some cholestrol and become low density lipoproteins (LDL)
- LDL then carries fat and cholestrol to the bodys cells
- High density lipoproteins (HDL) Ccarr fat and cholestrol back to the liver for excretion
What is the difference between HDL and LDL
- LDL then carries fat and cholestrol to the bodys cells
- High density lipoproteins (HDL) Ccarr fat and cholestrol back to the liver for excretion
What are the two types of hyperlipidaemias
Primary
Secondary (more common)
What are causes of secondary hyperlipidaemia
∗ Diet ∗ Alcohol ∗ Hypothyroidism ∗ Nephrotic syndrome ∗ Anorexia nervosa ∗ Obstructive liver disease ∗ Obesity ∗ Diabetes mellitus ∗ Pregnancy ∗ Acute hepatitis ∗ Systemic lupus erythematousus ∗ Drugi nduced-Thiazides, B-blockers, anti retroviral drugs, anti-depressants
What do you look for in a fasting lipid profile
∗ Serum total cholesterol ∗ Serum LDL-cholesterol ∗ Serum (fasting) triglyceride ∗ Serum HDL cholesterol ∗ Cholesterol-HDL ratio
What is the friedewald formula
The Friedewald formula (FF) is an estimation of LDL-c level that uses the following levels of
- total cholesterol (TC),
- triglycerides (TG)
- high-density lipoprotein cholesterol (HDL-c):
LDL-c (mg/dL) = TC (mg/dL) − HDL-c (mg/dL) − TG (mg/dL)/5 [6, 11–13].
What levels do you use in the Friedewald formula (FF)
- total cholesterol (TC),
- triglycerides (TG)
- high-density lipoprotein cholesterol (HDL-c):
LDL-c (mg/dL) = TC (mg/dL) − HDL-c (mg/dL) − TG (mg/dL)/5 [6, 11–13].
What does the serum look like if you have high triglyceride
serum looks white
What can happen with high triglyercide
acute pancretitis
What causes primary hyperlipidaemia
genetic
Name a type of primary hyperlipidaemia
- Familial Hypercholesterolemia (FH)
- familial combined hyperlipideaemia
- dysbetalipoproteinemia
What happens in Familial Hypercholesterolemia (FH)
- Codominant genetic disorder, occurs in
heterozygous form - Mutation in LDL receptor, resulting in elevated levels of LDL at birth and throughout life
What are pateints with Familial Hypercholesterolemia (FH) at risk of
- Atheroscloeris
- tendon xanthomas (75% of patients)
- tuberous xanthomas
- xathelasmas of eyes
what is the genetics of familial combined hyperlipidaemia
- Autosomal dominant
What is there increased secretion of in familial combined hyperlipidaemia
- Increased secretions of VLDLs
What happens in dysbetalipoproteinemia
Results in apo E2, a binding-defective form of apoE (which usually plays important role in catabolism of chylomicron and VLDL)
What can dysbetalipoproteinemia cause an increase risk of
- atherosclerosis
- peripheral vascualr disease
- tuberous xanthomas
- striae palmaris
What are the two sources of cholestrol
- diet
- liver synthesises cholestrol
What happens if the body is deficient or resistant in lipoprotein lipase
increases amount of chylomicron leading to increased cholestrol in ciruclation
What is the genetics of Familial Hypercholesterolemia (FH)
- Autosomal dominant
What is a high risk of Familial Hypercholesterolemia (FH)
- high risk of premature CHD - have to identify those with FH
- early treatment leads to a near normal life expectancy
- over 50% risk of CHD in men by age 50 and at least 30 % risk in women by age 60
What criteria can you use to diagnose FH
- Simon Broome criterai
who should you consider FH in
Consider FH in all adults with total cholesterol greater than 7.5 mmol/l
all patients with possible FH should be referred to
A specialist lipid clinic to…
- confirm diagnosis
- intiate cascade testing
- treat
What are the normal cholestrol ranges
- total cholestrol more than 5 is high
- LDL choelstrol more than 3 is high
- HDL high is better
What should definite FH in adults have (Simon broom critera)
Total cholesterol >7.5 and LDL-C > 4.9
AND tendon xanthomata or evidence of these in 1st or 2nd degree relative
OR
An identified genetic mutation for FH
What should you diagnose possible FH in adult with (Simon broom critera)
Total cholesterol > 7.5 and LDL-C > 4.9 and at least one of the following :
1) Family history premature CHD i.e.
MI aged < 60yrs in 1st deg relative or
< 50yrs in 2nd deg relative
2) Family history raised total cholesterol in 1st or 2nd deg relative (> 7.5 in adult OR > 6.7 in child)
What can you see in the patients that shows you have high cholestrol
- Subcutaenous tissue nodules
- athermatous plawues
- fibrous tissue formation
- eruptuive xanthomata = small itchy nodules, VLDL/chylomicron associated
- Tuberous xanthomata - yellow plaques over elbows and knees, IDL induced
- xanthelasma - periorbital skin depositis - LDL assocaition
- tendons - xanthomata
- cornea acrus - under age of 40
what is the Q risk
- it is a cardiovascular risk that is calculated by taking in smoking history, cholestrol level, blood pressure
- more than 10% tend to be started on treatment if lifestyle changes do not help
What is primary prevention for people at risk of developing hyperlipidemia
At risk people
- statin to lower lipids
People without risk factors
- Statins used in asymptomatic men with LDL cholesterol levels persistently above 5 mmol/L despite dietary change
When is statins used for primary prevention for hyperlipidaemia
- Used in asymptomatic individuals with type 2 diabetes
Used in people with two or more of
- positive family history of cardiovascular disease
- albuminuria
- hypertension
- smoking
What is secondary prevention for hyperlipidaemia
- Statins for any patient with macrovascular disease, TIA, or stroke
What drugs can cause hyperlipidaemia
- oral contraceptives
- retinoids, thiazide diuretics, corticosteroids, beta blockers, anti-retrovirals
Who do you screen for hyperlipidaemia
- family history of hyperlipidaemia
- corneal arcus less than 50 years old
- Xanthomata or Xanthelasmata
What are xanthomata
these are yellow lipid deposits that can be eruptive or tuberous plaques on elbows and knees or planar on palmar creases
- these are diagnostic of hyperlipidaemia
- can also be in tendons
What is mixed hyperlipdiameia
- this is an increase in both LDL and triglycerides
What causes mixed hyperlipidaemia
- type 2 diabetes
- metabolic syndrome
- alcohol abuse
- chronic renal failure
What is Xanthelasmata
- these are lipid laden yellow plaques that congregate around the lids or just below the eyes
- these signify hyperlipidaemia
What is the most widely used drug to treat hyperlipidameia
Statins
How does statins work
- Inhibit HMG-CoA reductase
- this decreases cholesterols synthesis in the liver
Name the adverse effects of statins
- Rhabdomyolysis
- muscle aches
- don’t drink grapefruit juice with simvastatin
What lifestyle advice should be given with someone with hyperlipidaemia
- BMI of 20-25
- mediterranean diet - increase fruit, veg, fish, unsaturated fats, decreased red meat
- increase exercise
Name the 1st line therapy for hyperlipdiaemia
- Atrovastatin 20mg at night for primary prevention and 80mg for secondary prevention and primary prevention to those with kidney disease
- Can use simvastatin 40mg as an alternative
What is the 2nd line therapy for hyperlipidaemia
- Ezetimibe - cholesterol absorption inhibitor
- used in statin intolerance or combination with statins to achieve target reduction
Name the 3rd line therapy for hyperlipidemia
- Allirocumab - monoclonal antibody against PCSK9 - reduces hepatocyte LDL receptor expression
- effective in reducing LDL - expensive and needs to be given by injection every 2 weeks
