Definition of dyslipidaemia and familial hypercholesterolaemia

• Dyslipidaemia is defined as abnormal levels of circulating lipids, primarily increased LDL cholesterol (LDLc), increased triglycerides (TG) and/or low HDL cholesterol. At present, LDLc is the major treatment target for reducing cardiovascular disease.
• Most cases of significantly raised LDLc (≥ 5 mmol/L) are due to polygenic risk or secondary causes. However, familial hypercholesterolaemia (FH) should be considered if LDLc ≥ 5 mmol/L and no secondary cause evident, particularly if LDLc > 6.5 mmol/L, xanthomas, or family history of significantly raised LDLc and/or early CVD. If FH suspected, calculate the Dutch Lipid Clinic Network (DLCN) Score. DLCN scores ≥ 6 should be discussed with lipid specialist to proceed with gene testing for FH.
  • Secondary causes of high LDLc include:
    • Ketogenic diet
    • Nephrotic syndrome
    • Chronic kidney disease
    • Cholestatic liver disease
    • Type 2 diabetes
    • Hypothyroidism
    • Obesity
    • Anorexia nervosa
    • Post menopause
    • Pregnancy
    • Medications including corticosteroids, antipsychotics, retinoids, protease inhibitors etc.

• Specialist consultation is recommended if FH is confirmed for genetic counselling and cascade testing, particularly if FH is suspected or confirmed in children.
  • FH should be considered in children if LDLc > 3.5 mmol/L
  • FH should be aggressively managed and lipid lowering therapy is recommended from 8 – 10 years of age.

Treatment approach to dyslipidaemia

• All with dyslipidaemia should have a CKM risk assessment and interventions to optimise healthy living.  Specific advice for dyslipidaemia includes:
  • Avoid trans fats and reduce saturated fats and oils (e.g. coconut, lard, butter).
    • Limit processed and deep-fried foods.
    • Unsaturated fats and oils (e.g. canola, rice bran, avocado, olive, plant-based margarines) may be useful alternatives.
  • Increase intake of fruits, vegetables and wholegrain foods which bind excess cholesterol e.g. oats, barley, quinoa, ground flaxseed and chia seeds
  • Specific dietary interventions to reduce TG levels include:
    • Reduced free sugar intake e.g. avoiding sugary drinks and lollies etc.
    • Reduced alcohol intake
    • Eating foods and/or supplements containing omega-3 fats regularly
  • Physical activity and movement can increase HDLc and reduce LDLc and TG
  • Interventions for weight loss if overweight or obese aiming for > 5% total body weight loss

• Lipid lowering therapy is strongly recommended in addition to healthy living interventions aiming for LDLc < 1.4 mmol/L and > 50% reduction in LDLc from baseline if ANY of the below:
  • LDLc ≥ 4.9 mmol/L and/or known familial hypercholesterolaemia
  • CV disease including asymptomatic coronary or carotid disease (includes CT calcium score > 300)
  • Diabetes with any microvascular or macrovascular complication(s)
  • UACR ≥ 30 mg/mmol
  • eGFR < 45 mL/min
  • UACR 3 – 29 mg/mmol AND eGFR 45 – 59 mL/min
  • 5 year CV risk ≥ 10%

• Lipid lowering therapy is recommended in addition to healthy living interventions  if 5 year CV risk 5 – 9.9% aiming for target LDLc < 1.8 mmol/L and > 50% reduction in LDLc from baseline.
• Lipid lowering therapy should  also be considered if 5 year CV risk 3 – 4.9% and additional risk factors for CVD. Target LDLc is < 1.8 mmol/L.
  • Risk factors to consider lipid lowering therapy include:
    • < 50 years of age
    • Direct family history of CV disease at < 50 years of age
    • Cardiac calcium score 100 - 300
    • Previous gestational diabetes and/or preeclampsia
    • MASLD

Choice of lipid lowering therapy

• First line lipid lowering medications are atorvastatin and rosuvastatin.
  • Rosuvastatin is typically preferred if previous CV event but mismatch with special authority criteria
    • Current special authority requires previous failures of atorvastatin or simvastatin to reach LDLc target unless Māori or Pacific ethnicity
    • Maximise rosuvastatin use in Māori and Pacific peoples given funded and their high CV risk
    • Other ethnicities may choose to self-fund rosuvastatin without trialling atorvastatin as cost is currently around $12 per week

• Usual dose range is atorvastatin is 10 – 80 mg daily and rosuvastatin 5 – 40 mg daily
  • Consider starting rosuvastatin 5 mg daily if South East Asian ancestry due to a common genetic polymorphism that increases rosuvastatin levels
  • Maximum dose of rosuvastatin is 10 mg daily if eGFR < 30 mL/min
  • At least 40 mg atorvastatin or 10 mg rosuvastatin daily is typically required to achieve a 50% reduction in LDLc

• Statins have low and potentially no teratogenicity - so statins can be used in women of child-bearing age without fear.
  • Current advice is to stop statins in pregnancy and breastfeeding, but discuss with secondary care if known cardiovascular disease and/or familial hypercholesterolaemia as it may be safest to continue statin.

• Measure non-fasting LDLc at least 3 monthly and titrate statin to reach LDLc target or maximal tolerated dose
  • 90% of LDLc lowering evident within 2 weeks so do not need to wait 3 months before titrating
  • Repeat testing may be barrier to optimising treatment so consider starting statin at or rapidly titrating statin to estimated dose to reach LDLc target

• Switch atorvastatin to rosuvastatin if LDLc is above target on 80 mg daily or maximal tolerated dose
  • Consider trialling pravastatin if intolerant of low dose atorvastatin and rosuvastatin
• Consider ezetimibe 10 mg daily if LDLc above target despite maximal tolerated dose of statin
  • Ezetimibe no longer requires special authority approval
• Consider evolocumab (Repatha) or inclisiran if LDLc still above target but require SC injection (2-4 weekly or 6 monthly), are not funded and are expensive (particularly evolocumab). They will reduce LDL on average by a further 50% from baseline.
• Measure non-fasting LDLc 6 - 12 monthly once treatment optimised to ensure targets are still met.

Adverse effects of statins

Statins are typically well tolerated with most adverse effects only minor:

• Many reported adverse effects of statins may be due to the nocebo effect, particularly fatigue, muscle aches and memory loss, particularly as statins protect against and do not cause dementia.

• Serious adverse effects such as rhabdomyolysis and hepatotoxicity are extremely rare with statins other than simvastatin. Doses of simvastatin > 40 mg daily are no longer recommended.

• Only 50% of reported mild adverse effects recur on re-trialling the same statin or a different statin. Mild transient elevation of liver enzymes is common and does not require cessation. Exclude other causes.

• Statin-induced myopathy occurs in < 5% of people and predominantly affects the shoulder and hip girdle rather than generalised muscle pain.

• The benefits of statins almost always outweigh the rare deleterious effects on hyperglycaemia in people with prediabetes or diabetes and should not prevent treatment.

Treatment of persistent hypertriglyceridaemia

• Hypertriglyceridaemia is independently associated with increased CV risk but fibrates do not reduce CV events or total mortality in people treated with statins.
• Statins continue to be first line agents to reduce CV risk in hypertriglyceridaemia and healthy living interventions remain important aiming for a TG level < 1.7 mmol/L in secondary prevention and < 5 mmol/L in primary prevention.
  • Avoid trans fats and reduce saturated fats and oils (e.g. coconut, lard, butter).
    • Limit processed and deep-fried foods
    • Unsaturated fats and oils (e.g. canola, rice bran, avocado, olive, plant-based margarines) may be useful alternatives.
  • Increase intake of fruits, vegetables and wholegrain foods which bind excess cholesterol e.g. oats, barley, quinoa, ground flaxseed and chia seeds
  • Specific dietary interventions to reduce TG levels include:
    • Reduced free sugar intake e.g. avoiding sugary drinks and lollies etc.
    • Reduced alcohol intake
    • Eating foods and/or supplements containing omega-3 fats regularly
  • Physical activity and movement  can increase HDLc and reduce LDLc and TG
  • Interventions for weight loss if overweight or obese aiming for > 5% total body weight loss