Cardiovascular Dyslipidaemia & Lipid Modification

Question 1

what is Primary hyperlipidaemia

Answer 1

Underlying genetic cause familial hypercholesterolemia (FH), but interacting with environmental factors dietary and other factors such as smoking and physical inactivity (non-familial hypercholesterolemia

Question 2

what is Secondary hyperlipidaemia

Answer 2

Resulting from another underlying disorder
like Hypothyroidism, nephrotic syndrome, diabetes, liver disease, excess alcohol, diet,
lifestyle, pregnancy, menopause, medications etc.

Question 3

Hypercholesterolemia

Answer 3

raised levels of one or more of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and triglycerides (TG) in the blood

Question 4

Atherosclerosis

Answer 4

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

Question 5

what is atheroma

Answer 5

a fatty material that builds up inside your arteries

Question 6

what causes atherosclerosis? how do plaques/atheroma form?

Answer 6

 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

Question 7

How do identify/diagnose Hypercholestrolaemia

Answer 7

 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

Question 8

q risk of less than 10%

Answer 8

 Advise on further reduction
 Lifestyle
 Smoking
 Weight loss
 Diet
 Alcohol
 Exercise
 Review comorbidities
 Review QRISK in 5 years

Question 9

q risk of more than 10%

Answer 9

 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

Question 10

what are statins used to treat/manage?

Answer 10

Statins are a group of lipid-lowering drugs used to reduce the risk of atherosclerosis and related CVD events.

Question 11

how do statins work?

Answer 11

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.

Question 12

how do statins work?

Answer 12

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.

Question 13

when are statins offered?

Answer 13

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.

Question 14

people who should NOT be prescribed statins:

Answer 14

• 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

Question 15

side effects of statin

Answer 15

• Asthenia (weakness, fatigue),
• constipation,
• diarrhoea,
• dizziness,
• flatulence,
• gastrointestinal discomfort,
• headache,
• myalgia,
• nausea,
• sleep disorders,
• thrombocytopenia

Question 16

what is flatulence

Answer 16

passing gas from the digestive system out of the back passage

Question 17

what is myalgia

Answer 17

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.

Question 18

what is thrombocytopenia

Answer 18

a condition that occurs when the platelet count in your blood is too low.

Question 19

Statin - interventions and tests to be
implemented beforehand

Answer 19

 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

Question 20

Statin – Primary prevention

Answer 20

 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!

Question 21

Statin – Primary prevention - follow up

Answer 21

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.

Question 22

Statin - secondary prevention

Answer 22

 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

Question 23

Investigations: Lipid measurements

Answer 23

 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

Question 24

Familial hypercholesterolemia (FH)

Answer 24

 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

Question 25

tendon xanthomata

Answer 25

cholesterol deposits in tendons. They commonly affect the tendons of the dorsal surface of the hands and the achilles tendon.

Question 26

Clinical signs of FH

Answer 26

• tendon xanthomata,
• xanthelasma
• premature corneal arcus.

Question 27

History to consider

Answer 27

• Personal history of cardiovascular diseases and secondary causes of hyperlipidaemia
• Family history of cardiovascular diseases, particularly at a young age (<50 years old)
• Smoking
• Excess alcohol consumption
• Obesity

Question 28

Xanthelasma

Answer 28

are lipid-laden nodules on the eyelids

Question 29

premature corneal arcus

Answer 29

bluish rims surrounding the irises of the eyes

Question 30

what does a lipid profile tell us?

Answer 30

A lipid profile is a blood test that shows the serum levels of TC, non-HDL cholesterol, LDL-C, HDL-C and TG.

The TC/HDL ratio provides the best estimate of cardiovascular risk in a patient and is specifically used in the QRISK2 score to calculate the 10-year risk of developing myocardial infarction or stroke in a patient.

Question 31

What assessment can be carried out to confirm a clinical diagnosis of FH in primary care

Answer 31

Use the Simon Broome criteria or the Dutch Lipid Clinic Network (DLCN) criteria.

 Make a clinical diagnosis of FH in people who meet the Simon Broome criteria for
‘possible’ or ‘definite’ FH, or have a DLCN score greater than 5.
 Be aware that the Simon Broome criteria has different lipid concentration levels for
adults and children.

Question 32

FH – Management

Answer 32

 Do not use CHD risk assessment tools such as QRISK to guide management
 People with FH are already at high risk of premature CHD
 Refer people at high risk to a specialist with expertise in FH
 High risk: established CHD, family history of premature CHD, 2 or more CVD risk
factors (male gender, smoking, hypertension, or diabetes)
 Consider routine referral to a cardiologist for possible CHD if the person has a
family history of CHD in early adulthood
 For all other adults with confirmed heterozygous FH:
 ECG
 Baseline bloods to determine suitability for lipid-modifying drugs
 Implement measures to reduce risk of CVD:
 Address modifiable CVD risk factors
 Individualized nutritional advice from a dietician
 Identify and manage secondary causes of hyperlipidemia
 Optimise treatment for conditions associated with an increased risk of CVD (AF, RA, SLE, and other systemic
inflammatory disorders; and serious mental health problems)
 Provide written information on FH
 Advice on support groups

 High-intensity statin, aim to achieve at least a 50% reduction in LDL
 Baseline bloods before initiating statin
 Atorvastatin 20mg or rosuvastatin 10mg daily
 Advise that this is lifelong treatment
 Follow up person to assess efficacy and tolerability

 If statin contraindicated:
 Ezetimibe 10mg once daily
 Refer to specialist with expertise in FH

 If both statin and ezetimibe contraindicated:
 Refer to specialist
 Secondary care treatment include: bile acid sequestrant (resin) or a fibrate. A proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor (aclirocumab and evolocumab)

 Lipid levels after 3 months of statin treatment. Aim for >50% reduction in LDL
 If not reached discuss adherence and timing of dose.
 Titrate dose of statin to mac licensed or tolerated dose

 If statin monotherapy fails. Consider on for the following 2 options
 Add ezetimibe 10mg once daily
 Consider prescribing simvastatin 80 mg for people with severe hypercholesterolemia and high risk of cardiovascular complications

 If combined treatment with statin and ezetimibe fails to achieve the target, or simvastatin
80mg is not indicated
 Refer to specialist with expertise in FH

 Recheck LFTs within 3 months of starting treatment and again at 12 months.
Further monitoring not necessary
 Offer regular structured review annually
 Medication adherence and adverse effects. Symptoms of CHD. ECG if this was not
carried out at diagnosis. Fasting lipids and blood pressure, HbA1c and renal function.
Smoking cessation, weight loss, lifestyle advice, change to meds,
pregnancy/contraception.