Hyperlipidaemia Flashcards
What is hyperlipidaemia?
high blood levels of cholesterol, triglycerides or both
what can hyperlipidaemia lead to?
cardiovascular disease
hyperlipidaemia causes atherosclerosis and in turn:
- coronary heart disease (angina, myocardial infarctions)
- strokes and transient ischaemic attacks (TIA)
- peripheral arterial disease
What is the difference between primary and secondary prevention of cardiovascular event?
In summary, primary prevention aims to prevent the initial occurrence of cardiovascular disease, while secondary prevention focuses on preventing recurrent events and managing established heart disease.
Who needs primary prevention of cardiovascular disease?
- type 1 diabetes mellitus
- type 2 diabetes mellitus only if CVD risk > 10%
- if risk calculators e.g. QRISK 2: 10 year CVD risk > 10%
- chronic kidney disease or albuminuria
- familial hypercholesterolaemia
- 85 years and above (reduce risk of non- fatal myocardial infarction)
who needs secondary prevention of cardiovascular disease?
those with established CVD
coronary heart disease (angina, MI)
cerebrovascular disease (stroke/ transient ischaemic attack)
peripheral arterial disease
who can we NOT use the QRISK2 tool for?
patients at high cardiovascular risk as their score will be underestimated
this includes:
- type 1 diabetes mellitus
- established cardiovascular disease
- over 85 years
- chronic kidney disease (eGFR <60mL/min/1.73m2)
- familial hypercholesterolemia
how is hyperlipidaemia diagnosed?
6mmol/L total cholestrol
What are TOTAL cholesterol targets for HEALTHY ADULTS?
≤ 5mmol/ L
What are TOTAL cholesterol targets for HIGH RISK ADULTS?
≤ 4 mmol/L
what are LDL cholesterol targets for HEALTHY ADULTS?
≤ 3 mmol/L
What are LDL cholesterol targets for HGIH RISK ADULTS?
≤ 2 mmol/L
What should HDL levels be?
> 1 mmol/L
(‘good’ cholesterol- higher the better!)
What should Triglycerides levels be?
<1.7 mmol/L
What are causes of hyperlipidaemia?
DRUGS and CONDITIONS
What drugs can cause hyperlipidaemia?
- antipsychotics
- immunosuppressants
- corticosteroids
- antiretrovirals (HIV drugs)
What conditions can cause hyperlipidaemia?
- hypOthyroidism
- liver or kidney disease
- diabetes mellitus
- family history of high cholesterol
- lifestyle factors: smoking, excess alcohol consumption, obesity and a poor fatty diet
What are examples of hyperlipidaemia drugs?
statins
bile acid sequestrants
fibrates
nicotinic acid group
ezetimibe
lomitapide
alirocumab
What are examples of statins?
atorvastatin
fluvastatin
pravastatin
rosuvastatin
simvastatin
What are examples of bile acid sequestrants?
colesevelam
colestipol
colestyramine
What are examples of fibrates?
bezafibrates
ciprofibrate
fenofibrate
gemfibrozil
What are examples of nicotinic acid group?
acipimox
nicotinic acid
omega- 3 fatty acid
what is the mechanism of action of statins?
Statins work by inhibiting an enzyme called HMG-CoA reductase. This enzyme is involved in the liver’s production of cholesterol, a key component of lipoproteins (such as LDL, low-density lipoprotein) in the blood.
Lowers LDL cholesterol synthesis by the liver via inhibition of HMG- CoA reductase
By inhibiting HMG-CoA reductase, statins reduce the production of cholesterol within liver cells. This leads to a decrease in the intracellular levels of cholesterol.
Also, As a response to reduced intracellular cholesterol levels, liver cells increase the number of LDL receptors on their surface. These receptors are responsible for capturing LDL cholesterol particles circulating in the blood.
This process helps lower the levels of LDL cholesterol circulating in the blood.
Which statins must be taken at night?
All of them except Atorvastatin
(cholesterol synthesis greater at night; more effective)
What are examples of high- intensity statins?
- atorvastatin 20mg- 80mg
- rosuvastatin 10mg
-simvastatin 80mg
What statin is high intensity statin choice for prevention of cardiovascular prevention?
atorvastatin
what is atorvastatin dose for PRIMARY PREVENTION?
20mg OD
what is atorvastatin dose for SECONDAY PREVENTION?
80mg OD
What is MHRA warning for simvastatin 80mg?
high risk of myopathy
give only if high risk of cardiovascular complications or severe hypercholesterolaemia and treatment goals not achieved at lower dose
which high- intensity statins are used to prevent cardiovascular disease?
atorvastatin
rosuvastatin
simvastatin
how is hyperlipidaemia treated?
statin first choice
how is primary hypercholesterolaemia and familial hypercholesterolaemia treated?
high intensity statin
If statin not tolerated or contra- indicated= ezetimibe
how is moderate hypertriglyceridemia treated?
high intensity statin
if statin not tolerated or contra- indicated
= fibrate
how is severe hyperlipidaemia treated?
add on ezetimibe
(under specialist supervision)
if a persons triglycerides are still high after LDL reduced?
add fibrate or nicotinic acid (also lowers LDL)
Before starting statins, we MUST address any secondary causes of dyslipidaemia. What may these be?
- hypothyroidism
- uncontrolled diabetes mellitus
- nephrotic syndrome (albuminuria)
- liver disease e.g. alcoholic cirrhosis
What are side effects of statins?
myopathy
myositis
rhabdomyolysis
patient counselling: report tender, weak and painful muscles
Who has a higher risk of muscle toxicity?
- personal or family history of muscle disorder
- high alcohol intake
- renal impairment
- hypothyroidism (treat before starting statin)
When is there an increased risk of myopathy?
- concomitant ezetimibe or fibrates, especially gemfibrozil
- concomitant fusidic acid: restart statin 7 days after last dose (increased risk of rhabdomyolysis)
How should we counsel patients who have interstitial lung disease and are taking statins?
report short breath, cough, weight loss
why should we take caution when giving statins to diabetics or those at high risk of diabetes?
statins can raise HbA1c or blood glucose levels
How can we monitor those on statins?
baseline lipid profile
renal function
thyroid function
HbA1c if high risk of developing diabetes
When should we discontinue statins for a patient?
If
- severe muscle symptoms
- if creatinine kinase levels are 5 x normal*
- if liver transaminases 3x normal (liver function)
*if level returns to normal and muscle symptoms resolve a statin can be reintroduced at a lower dose and monitor)
What drugs interact with statins?
drugs that increase statin levels as = increased myopathy risk
macrolide antibiotic e.g. clarithromycin
(patient counselling: stop taking statin until antibiotic course completed. There is no need to contact the prescriber)
ezetimibe/ fibrates especially gemfibrozil : AVOID!
fusidic acid
(restart statin 7 days after last ORAL fusidic acid dose)
What are statin dose adjustment’s due to interactions for: SIMVASTATIN
Max. 10mg with fibrate
Max. 20mg with amiodarone, amlodipine, diltiazem, verapamil
What are statin dose adjustment’s due to interactions for: ATORVASTATIN
Max. 10mg with ciclosporin
What are statin dose adjustment’s due to interactions for: ROSUVASTATIN
Initially 5mg
Max. 20mg with clopidogrel
Can you take statins whilst being pregnant?
NO as TERATOGENIC
Effective contraception must be used DURING AND 1 month after stopping
Stop taking the statin 3 months before conceiving and restart after breastfeeding finished
What is the mechanism of action of ezitimibe?
TO DO WITH CHOLESTROL ABSORPTION!
Cholesterol absorption occurs through specialized transporters in the intestinal cells, including the NPC1L1 (Niemann-Pick C1-Like 1) protein.
Ezetimibe acts as a cholesterol absorption inhibitor by selectively blocking the NPC1L1 protein in the small intestine. This protein plays a key role in cholesterol uptake from the digestive tract.
Ezetimibe inhibits NPC1L1, reducing the absorption of cholesterol from the diet. As a result, less dietary cholesterol enters the bloodstream.
leads to a decrease in the concentration of LDL cholesterol in the bloodstream over time, as the liver compensates by removing LDL cholesterol from circulation.
What is an alternative to statin in familial and primary hypercholesterolaemia?
ezitimibe
what are interactions of ezitimibe?
statins
as can cause myopathy= rhabdomyolysis
what is the mechanism of action of fibrates
fibrates lower blood triglyceride levels
by reducing the livers production of VLDL (the triglyceride- carrying particle that circulates in the blood)
and by speeding up the removal of triglycerides from the blood
how can we treat those with severe hypertriglyceridaemia > 10mmol/L or in those who cannot tolerate a statin (specialist)
- bezafibrate
- fenofibrate
- ciprofibrate
- gemfibrozil (do not use with statin as high risk of myopathy - rhabdomyolysis)
What are interactions of fibrates?
statins
(myopathy, renal impairment)
What is the mechanism of action of bile acid sequestrants?
they bind and sequesters bile acids
the liver then produces more bile acids to replace those that have been lost
The body uses cholestrol to make bile acids
This reduces the amount of LDL cholestrol ciruclating in the blood
what are examples of bile acid sequestrants?
colesevelam
colestipol
colesytramine
what are interactions of bile acid sequestrants?
impair absorption of fat- souble vitamins ADEK and other drugs
pt counselling: take other drugs 1 hour BEFORE (4 hours for colevesalm) OR 4 hours AFTER bile acid sequestrant
when are omega- 3 fatty acids used in hyperlipidaemia?
no evidence for use
used an adjunct to statins and diet to lower triglycerides
when are nicotinic acid groups used in hyperlipidaemia?
specialist use
use limited by flushing (prostaglandin- mediated)
