Background Information

Definitions

Dyslipidaemia: abnormal concentration of serum lipids (including high total cholesterol, high LDL cholesterol, high triglycerides, and/or low HDL cholesterol)
Hyperlipidaemia: elevated blood lipid levels (including total cholesterol, LDL cholesterol, triglycerides)

Hyperlipidaemia Causes

Primary causes: genetic disorders that affect lipid metabolism

• Familial hypercholesterolaemia – most common (see this article)
• Familial dysbetalipoproteinemia
• Familial hypertriglyceridemia

Secondary causes: ^{[ref, ref]}

Cateogry	Common causes
Lifestyle	High saturated / trans fat diet Weight gain Physical inactivity Excessive alcohol intake
Medical conditions	Metabolic conditions: Cushing’s syndrome Hypothyroidism PCOS Diabetes mellitus Obesity and metabolic syndrome NAFLD Hypoalbuminaemia-related (hypoalbuminaemia triggers the liver to increase lipoprotein synthesis in attempt to increase the plasma oncotic pressure): Nephrotic syndrome Liver disease Malnutrition
Drugs	Thiazide diuretics Systemic glucocorticoids 2nd generation antipsychotics Protease inhibitors (used in HIV) Beta blockers (esp. non-selective ones like propranolol) Oral oestrogen (COCP and hormone replacement therapy), tamoxifen (selective oestrogen receptor modulator)

 

Complications

Direct complications of hyperlipidaemia include: ^[ref]

• Atherosclerotic cardiovascular disease (e.g. coronary artery disease, cerebral vascular disease, peripheral arterial disease)
• Hepatic steatosis and NAFLD
• Hypertriglyceridaemia-induced pancreatitis (usually occurs in severe hypertriglyceridaemia)

Classification of Statins

Common high-intensity statins:

• Atorvastatin 20mg to 80mg
• Rosuvastatin 10mg to 40mg
• Simvastatin 80mg

 

Intensity of a statin is based on the % reduction in LDL cholesterol it can produce.

Statin intensity	% reduction in LDL	Drug and dose
High intensity	>40%	Atorvastatin 20, 40, 80mg
		Rosuvastatin 10, 20, 40mg
		Simvastatin 80mg
Medium intensity	30-40%	Atorvastatin 10mg
		Rosuvastatin 5mg
		Simvastatin 20, 40mg
		Fluvastatin 80mg
Low intensity	<30%	Simvastatin 10mg
		Fluvastatin 20, 40mg
		Pravastatin 10, 20, 40mg

CVD Risk Assessment

Clinical Tools

The QRISK3 risk calculator is recommended to estimate the patient’s 10-year CVD risk

QRISK3 risk calculator should only be used if:

• Patient has NO established CVD (coronary artery disease or stroke / TIA), and
• 25-84 y/o, and
• NOT taking a statin

Click to view factors that can underestimate CVD risk

Lipid Measurement and Assessment

To best estimate CVD risk, measure total cholesterol and HDL cholesterol levels

• The total cholesterol / HDL ratio is a component of the QRISK3 tool
• Although it is not necessary to calculate the 10-year CVD risk, it will improve the accuracy if available

 

Exclude common secondary causes of dyslipidaemia:

• Excess alcohol intake
• Uncontrolled diabetes
• Hypothyroidism
• Liver disease
• Nephrotic syndrome

Management

The rationale for managing hyperlipidaemia is to reduce the risk of atherosclerotic cardiovascular disease.

Referral Criteria

Refer the following patients for specialist assessment (due to possible familial hypercholesterolaemia – see this article)

• Total cholesterol >9.0 mmol/L or non-HDL cholesterol >7.5 mmol/L
• Even in the absence of a family history of premature coronary heart disease

Refer urgently to a specialist if triglycerides are >20 mmol/L and not secondary to excess alcohol intake / poor glycaemic control

• To identify genetic lipid disorders or complex metabolic conditions, and
• Prevent complications like acute pancreatitis

Lifestyle Changes / Conservative Management

• Healthy eating
• Cardioprotective diet
  • Total fat intake ≤30% of total energy intake
  • Saturated fat intake ≤7% of total energy intake
  • ↓ Saturated fat intake
  • Replace saturated fats with monounsaturated and polyunsaturated fats
• Encourage physical activity
• Weight management
• Smoking cessation
• Advice on alcohol consumption

Lipid-Lowering Therapy

Indications

There are 2 main scenarios:

Scenarior	Description
Primary prevention	This applies to those with NO established CVD but at increased risk The purpose of  lipid-lowering therapy in these patients is to prevent the first occurrence of CVD
Secondary prevention	This applies to those who already have established CVD The purpose of lipid-lowering therapy in these patients is to prevent recurrence or worsening of CVD

 

Primary Prevention

Lipid-lowering therapy for CVD primary prevention is indicated if:

• QRISK3 score ≥10%
• CKD
• T1DM with any of the following
  • >40 y/o 
  • Diabetes for >10 years
  • Established nephropathy
  • Presence of other CVD risk factors 

Management:

• 1^st line: atorvastatin 20mg
• Lipid target for primary prevention: >40% reduction in non-HDL cholesterol

Secondary Prevention

All patients with established CVD should receive lipid-lowering therapy for CVD secondary prevention.

1^st line: atorvastatin 80mg (all patients)

• In patients with CKD, atorvastatin 20mg is 1st line (only consider increasing to 80mg if cholesterol target not met, and eGFR >30)
• Another reason to give a lower dose is intolerance / patient’s preference
• NICE recommends considering adding ezetimibe to the maximum tolerated intensity and dose of statin to reduce CVD risk further (even if lipid targets are met)

Lipid target for secondary prevention:

• LDL cholesterol ≤2.0 mmol/L, or
• Non-HDL cholesterol ≤2.6 mmol/L

Statin Therapy

Before starting statins, treat comorbidities and secondary causes of dyslipidaemia

Alternative to Statin

See the following recommendations if statin is contraindicated or not tolerated, and lipid-lowering therapy is indicated.

Indication	Step 1	Step 2 (if ezetimibe alone does not meet lipid target)
Primary prevention	Ezetimibe monotherapy	Ezetimibe + bempedoic acid
Secondary prevention		Consider alternative or additional drugs (i.e. alone or in addition to ezetimibe): Bempedoic acid PCSK9 inhibitors (inclisiran / alirocumab / evolocumab)

 

Safety Information

Information	Description
Important adverse effects	Muscle-related symptoms (muscle pain / weakness / cramp) – most frequently reported side effects Arthralgia GI upset Rare: Myositis Hepatitis Rhabdomyolysis (extremely low risk) Use with caution in those at increased risk of muscle toxicity
Contraindications	Pregnancy (stop statin 3 months before attempting to conceive) Breastfeeding (do not restart until breastfeeding is finished)
Drug interaction	Be aware that combining a statin with liver enzyme inhibitors can increase the risk of muscle toxicity Notable interaction is with grapefruit juice, which is a liver enzyme inhibitor

Treatment Monitoring and Follow-Up

Timing	Tests
Baseline	Full lipid profile LFTs Renal function Diabetes status TSH level (if there are suggestive features of thyroid condition)
At 2-3 months	Full lipid profile LFTs
At 12 months	Full lipid profile LFTs
Beyond 12 months	Annual full lipid profile (but not LFTs, unless clinically indicated)

 

Do NOT routinely measure creatine kinase levels. Only measure if a person on statin develops unexplained muscle pain / tenderness / weakness

• If creatine kinase level <5 times upper limit → unlikely due to statin + investigate for other possible causes
• If creatine kinase level >5 times upper limit → repeat after 7 days
  • If still >5 times upper limit→ discontinue statin
  • If elevated but <5 times upper limit → lower the dose

References