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This is a clinician-written, evidence-based summary aligned to the 2026 MLA Content Map. It is intended for medical students and junior doctors preparing for the UKMLA. Always cross-reference with NICE guidance, local protocols, and clinical judgement.
The Bottom Line
- Assess CVD risk with QRISK3 in all adults >40 without pre-existing CVD. Offer statin if 10-year risk ≥10%
- Primary prevention: atorvastatin 20 mg OD. Aim for >40% reduction in non-HDL cholesterol at 3 months
- Secondary prevention (established CVD): atorvastatin 80 mg OD
- If statin intolerant or target not met: add ezetimibe 10 mg. Consider PCSK9 inhibitor (evolocumab, alirocumab) via specialist
- Familial hypercholesterolaemia (FH): suspect if total cholesterol >7.5 mmol/L or LDL >4.9 mmol/L, especially with family history of premature CVD
Overview
Hyperlipidaemia refers to elevated levels of lipids (cholesterol and/or triglycerides) in the blood. Elevated LDL cholesterol is the primary driver of atherosclerosis and cardiovascular disease. Hyperlipidaemia may be primary (genetic — including familial hypercholesterolaemia, familial combined hyperlipidaemia) or secondary (diabetes, hypothyroidism, nephrotic syndrome, liver disease, drugs including corticosteroids, thiazides, retinoids). NICE CG181 provides guidance on cardiovascular risk assessment and lipid modification, recommending QRISK3 for risk stratification and statins as the cornerstone of pharmacological management.
Epidemiology
Elevated total cholesterol affects approximately 50% of UK adults. However, cardiovascular risk is determined by the combination of lipid levels with other risk factors (age, sex, BP, smoking, diabetes, ethnicity, deprivation). Familial hypercholesterolaemia (FH) affects approximately 1 in 250 people (heterozygous) and carries a very high risk of premature CVD — approximately 50% of men and 30% of women with untreated FH will develop CHD by age 60. Homozygous FH is rare (1 in 300,000) but causes severe atherosclerosis in childhood.
Clinical Features
Symptoms
Usually asymptomatic — detected on routine blood tests or following CVD event
Symptoms of atherosclerotic disease (angina, claudication, TIA) if longstanding and untreated
Signs
Xanthelasma (yellow deposits around eyelids) — associated with hyperlipidaemia but can occur with normal lipids
Corneal arcus (white/grey ring around cornea) — significant if <50 years old (suggests FH)
Tendon xanthomata (Achilles tendon, extensor tendons of hands) — pathognomonic of FH
Eruptive xanthomata (small yellow papules on buttocks/extensor surfaces) — severe hypertriglyceridaemia
Xanthomata in palmar creases — familial dysbetalipoproteinaemia (Type III)
Signs of peripheral vascular disease or coronary artery disease
Investigations
First-line
Fasting lipid profileTotal cholesterol, LDL, HDL, triglycerides. Non-HDL cholesterol (total minus HDL) is the primary target for treatment monitoring per NICE
QRISK3 assessment10-year CVD risk calculator. Incorporate: age, sex, ethnicity, SBP, TC:HDL ratio, smoking, BMI, deprivation, diabetes, CKD, AF, RA, family history. Offer statin if ≥10%
Baseline bloodsLFTs (baseline before statin), TFTs (exclude secondary cause), HbA1c, U&Es, FBC
Second-line
FH diagnostic criteria (Simon Broome or Dutch Lipid Clinic)Definite FH: tendon xanthomata + cholesterol criteria + family history; or genetic confirmation (LDL receptor, ApoB, PCSK9 mutation)
Repeat lipid profile at 3 months post-statinAssess % reduction in non-HDL cholesterol — aim for >40% reduction from baseline
Specialist
Genetic testingIf FH suspected — enables cascade family screening
Lipoprotein(a)Independent CVD risk factor — measure at least once in lifetime, especially if premature CVD or FH phenotype without genetic confirmation
1
Lifestyle modification (all patients)
- Heart-healthy diet (Mediterranean-style): reduce saturated fat, increase fruits/vegetables/wholegrains, oily fish
- Regular physical activity (≥150 min moderate-intensity per week)
- Smoking cessation
- Alcohol moderation
- Weight management
2
Primary prevention (QRISK3 ≥10%)
- Atorvastatin 20 mg OD (first-line)
- Discuss benefits, risks, and lifestyle modification before starting
- Check non-HDL cholesterol at 3 months — aim for >40% reduction from baseline
- Check LFTs at 3 months, then only if clinically indicated (not routine annual monitoring per NICE)
- If statin intolerant: try lower dose, alternative statin, or non-daily dosing
3
Secondary prevention (established CVD)
- Atorvastatin 80 mg OD (high-intensity)
- Start regardless of baseline cholesterol level
- If target not met or statin intolerant: add ezetimibe 10 mg OD
- If still not at target: consider PCSK9 inhibitor (evolocumab, alirocumab) via lipid clinic — NICE TA394/TA393
- Inclisiran (siRNA targeting PCSK9) — NICE TA733, given as subcutaneous injection twice yearly via secondary care
- Bempedoic acid (ACL inhibitor) — alternative if statin intolerant
4
Familial hypercholesterolaemia
- Do NOT use QRISK3 — FH patients are already at very high risk regardless of score
- Start high-intensity statin from diagnosis (atorvastatin 20–80 mg, titrate to max tolerated)
- Add ezetimibe if target not met. PCSK9 inhibitor if still not at target
- Cascade screening: offer lipid testing + genetic testing to all first-degree relatives
- Refer to specialist lipid clinic
5
Severe hypertriglyceridaemia (>10 mmol/L)
- Risk of acute pancreatitis — urgent treatment needed
- Very low fat diet, stop alcohol, stop exacerbating drugs
- Fibrate (fenofibrate, bezafibrate) — first-line for hypertriglyceridaemia
- Omega-3 fatty acids (icosapent ethyl — NICE TA805) may be considered
Complications
- Atherosclerotic CVD: MI, stroke, PAD — the primary consequence of untreated hyperlipidaemia
- Acute pancreatitis: If triglycerides >10 mmol/L
- Statin side effects: Myalgia (5–10%), rhabdomyolysis (very rare), liver enzyme elevation, new-onset diabetes (small absolute risk)
- Premature death: Untreated FH — 50% of men develop CHD by age 60
UKMLA Exam Tips
- 1QRISK3 ≥10% → offer atorvastatin 20 mg. Established CVD → atorvastatin 80 mg. No QRISK for FH patients
- 2Non-HDL cholesterol is the treatment target (NOT LDL) per NICE — aim for >40% reduction at 3 months
- 3Tendon xanthomata (especially Achilles) are pathognomonic of FH — classic exam image
- 4Statin + ezetimibe + PCSK9 inhibitor is the escalation pathway for refractory hyperlipidaemia
- 5Do NOT routinely monitor LFTs on statins — check at baseline and 3 months only (NICE)
- 6Fibrates are first-line for isolated hypertriglyceridaemia (not statins)
- 7Corneal arcus in a patient <50 years = suspect FH
practicetest your knowledge on hyperlipidaemiaApply what you've learnt with UKMLA-style questions from the iatroX Q-Bank — cardiovascular and beyond.
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