Cardiovascular Dyslipidaemia & Lipid Modification Flashcards
what is Primary hyperlipidaemia
Underlying genetic cause familial hypercholesterolemia (FH), but interacting with environmental factors dietary and other factors such as smoking and physical inactivity (non-familial hypercholesterolemia
what is Secondary hyperlipidaemia
Resulting from another underlying disorder
like Hypothyroidism, nephrotic syndrome, diabetes, liver disease, excess alcohol, diet,
lifestyle, pregnancy, menopause, medications etc.
Hypercholesterolemia
raised levels of one or more of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and triglycerides (TG) in the blood
Atherosclerosis
thickening or hardening of the arteries. It is caused by a buildup of plaque in the inner lining of an artery.
Over time the plaque gets larger and thicker –> this causes arterial narrowing –> leads to poor blood flow
Sometimes atheroma develops a tiny crack (rupture) –> blood clot
what is atheroma
a fatty material that builds up inside your arteries
what causes atherosclerosis? how do plaques/atheroma form?
LDL deposits in tunica intima and becomes oxidised
Oxidised LDLs activate endothelial cells causing them to express receptors for WBCs
Adhesion of white blood cells to activated endothelial cells will allow monocytes and T-helper cells to move into the tunica intima layer
When monocytes move in they become macrophages
Macrophages take up oxidised LDLs and become foam cells
Foam cells are key in atherosclerosis
They promote migration of smooth muscle cells (SMC) from media to intima and SMC proliferation
An increase in SMC proliferation heightens the synthesis of collagen
hardening of atherosclerosis plaque
Foam cells die and release of lipid content
growth of plaque
How do identify/diagnose Hypercholestrolaemia
Health check programme
40-74 invited every 5 years for free health check
Family history
Incidental finding on bloods
Symptoms (angina/claudication)
Risk factors
Comorbidities
QRISK
q risk of less than 10%
Advise on further reduction
Lifestyle
Smoking
Weight loss
Diet
Alcohol
Exercise
Review comorbidities
Review QRISK in 5 years
q risk of more than 10%
Check for familial hypercholesterolemia
Exclude secondary causes (alcohol, diabetes, hypothyroidism, liver disease, etc.)
Discuss lifestyle modifications
Cardioprotective diet (NICE cg 181 – 1.2)
Physical activity, alcohol, smoking
Optimise management of all other modifiable CVD risk factors, including any relevant
comorbidities that may not be optimally treated
Offer opportunity to reassess CVD risk again after they have tried to change lifestyle
Support to change lifestyle? Exercise referral schemes/smoking cessation
Offer statin treatment after risk assessment if lifestyle modification is ineffective
or inappropriate
what are statins used to treat/manage?
Statins are a group of lipid-lowering drugs used to reduce the risk of atherosclerosis and related CVD events.
how do statins work?
Statins work by inhibiting a key enzyme in the liver, HMG-CoA reductase, causing a decrease in hepatic synthesis of cholesterol. This, in turn, increases the expression of hepatic cholesterol receptors, increasing uptake of low-density lipoprotein (LDL) from the blood to the liver, resulting in a fall in plasma cholesterol.
how do statins work?
Statins work by inhibiting a key enzyme in the liver, HMG-CoA reductase, causing a decrease in hepatic synthesis of cholesterol. This, in turn, increases the expression of hepatic cholesterol receptors, increasing uptake of low-density lipoprotein (LDL) from the blood to the liver, resulting in a fall in plasma cholesterol.
when are statins offered?
Offer lipid-modification therapy to:
People aged 84 years and younger if their estimated 10-year risk of developing CVD
using the QRISK assessment tool is 10% or more.
Without the need for a formal risk assessment
T1DM, aged >40/had diabetes for >10 years/other CVD risk factors
CKD
Familial hypercholesterolemia
Consider statin without formal assessment: 85 years of age or older. Think
about the benefits and risks of treatment and comorbidities that make treatment
inappropriate.
people who should NOT be prescribed statins:
- Elderly,
- people with a history of liver disease,
- patients at increased risk of muscle toxicity (personal or family history of muscular disorders, previous history of muscular toxicity, high alcohol intake, renal impairment or hypothyroidism) including myopathy or
rhabdomyolysis - Atorvastatin – haemorrhagic stroke
side effects of statin
- Asthenia (weakness, fatigue),
- constipation,
- diarrhoea,
- dizziness,
- flatulence,
- gastrointestinal discomfort,
- headache,
- myalgia,
- nausea,
- sleep disorders,
- thrombocytopenia
what is flatulence
passing gas from the digestive system out of the back passage
what is myalgia
Myalgia describes muscle aches and pain, which can involve ligaments, tendons and fascia, the soft tissues that connect muscles, bones and organs. Injuries, trauma, overuse, tension, certain drugs and illnesses can all bring about myalgia.
what is thrombocytopenia
a condition that occurs when the platelet count in your blood is too low.
Statin - interventions and tests to be
implemented beforehand
Implement measures to reduce risk of CVD
Address other modifiable CVD risk factors (smoking, BP, obesity, etc.)
Identify and manage secondary causes if hyperlipidemia
Baseline bloods (if not already done)
Lipid measurement
Creatinine kinase (CK) only if they have persistent generalized unexplained muscle pain
CK raised but less than 5 times upper limit of normal, start lipid-lowering treatment
CK 5 or more times upper limit of normal, re-measure after 7 days. Still elevated seek specialist advice (lipid clinic)
Liver function test – MOST IMPORTANT - NICE suggests that liver transaminase enzymes (ALT, AST) should be measured before treatment, and repeated within 3 months and at 12 months of starting treatment
Renal function
HbA1c
Thyroid function tests
Statin – Primary prevention
High-intensity statin with atorvastatin 20mg daily unless contraindicated (if it is
contraindicated consider specialist advice e.g. lipid clinic)
Decline? Advise CVD risk should be reassessed again. DOCUMENT!
Statin – Primary prevention - follow up
Follow up:
Measure lipid profile after 3 months of atorvastatin treatment. The aim is to achieve
a greater than 40% reduction in baseline non-HDL cholesterol level
If not achieved:
Discuss adherence and timing
Reinforce diet and lifestyle measures
Consider increasing the dose of atorvastatin if the person is judged to be at a higher risk
of CVD because of comorbidities or risk score or using clinical judgement
If a greater than 40% reduction in non-HDL cholesterol is still not achieved:
Add ezetimibe
Recheck LFTs within 3 months of starting treatment, and again at 12 months.
Further monitoring not necessary unless clinically indicated
Review statin treatment annually
Routinely monitor for adverse effects of lipid-modification therapy
Unexplained muscle symptoms (pain/tenderness/weakness) check CK
Stop stain if muscle symptoms intolerable of CK is 5 or more times upper limit of
normal
If muscle pain develops but statin was previously tolerated for more than 3 months
explore other causes of myalgia and raised CK (exercise, hypothyroid, infection,
trauma, drug/alcohol misuse)
If statin is suspected to be the cause of muscle pain and CK is elevated stop statin
immediately. Once CK returns to normal, the statin should be reintroduced at a lower dose.
Statin - secondary prevention
Advise lipid modification to adults with established CVD (e.g. past or current
history of MI, angina, stroke, transient ischaemic attack, or peripheral arterial
disease)
High-intensity treatment with atorvastatin 80mg unless contraindicated (seek
specialist advised)
lower dose if drug interactions, increased risk of adverse effects, patient requests to
start lower dose
If already on statin discuss benefits of changing to high-intensity treatment with
atorvastatin 80mg
If unwilling. Reassure them that they will benefit from current treatment
Follow up as per primary prevention
Investigations: Lipid measurements
Total cholesterol >7.5 mmol/L and/or
A family history of premature coronary heart disease (CHD, an event before 60
years in an index person or first-degree relative [parents, siblings, children])
Consider the possibility of familial hypercholesterolemia.
If total cholesterol >9.0 mmol/L, or nin-HDL cholesterol concentration
>7.5 mmol/L arrange for specialist assessment
Triglyceride concentration >20 mmol/L that is not a result of excess alcohol or
poor glycaemic control refer for urgent specialist review
Triglyceride between 10-20 mmol/L:
Repeat triglyceride measurement with a fasting test (after an interval of 5 days, but
within 2 weeks)
Review for potential secondary causes of hyperlipidemia
Seek specialist advice (lipid clinic) if triglyceride concentration remains elevated
Triglyceride between 4.5 and 9.9 mmol/L optimise management of other CVD
risk factors present. Specialist advice if non-HDL concentration is > 7.5 mmol/L
in this group of people
Familial hypercholesterolemia (FH)
Inherited
Present from birth early development of atherosclerosis and CHD
Usually inherited defective gene from one parent (heterozygous FH)
Autosomal dominant pattern of inheritance
Homozygous FH is rare
Suspect FH in adults with:
Total cholesterol level > 7.5 mmol/L and/or
A personal or family history of premature CHD(an event before 60 years in an index
person or first-degree relative [parents, siblings, children])
If suspected, assess the person
Refer children and young people (up to 15 years) for a specialist assessment
Take two measurements of low-density lipoprotein (LDL) cholesterol concentration
Consider clinical diagnosis of homozygous FH in adults with LDL cholesterol concentration > 13 mmol/L
Consider a clinical diagnosis of homozygous FH in a child or young person (up to 15 years of age) with an LDL cholesterol concentration > 11mmol/L
