Hypercholesterolaemia
🩸 Hypercholesterolaemia is defined as abnormally high cholesterol levels in the blood.
It is a key modifiable risk factor for atherosclerotic cardiovascular disease (ASCVD), including coronary artery disease, stroke, and peripheral arterial disease.
Cholesterol is essential for cell membranes, hormone synthesis, and bile acid production — but excessive levels, particularly of low-density lipoprotein (LDL), drive atherosclerosis and vascular events.
🧬 Types of Cholesterol
- LDL Cholesterol ("bad") 🚫 :
- Main carrier of cholesterol to tissues. Excess LDL → arterial plaque formation.
- HDL Cholesterol ("good") ✅ :
- Protective: transports cholesterol away from arteries to liver for excretion.
- Total Cholesterol 📊 :
- Combined LDL + HDL + VLDL.
- Triglycerides 🍔 :
- Energy storage lipids; high levels → ↑ risk of atherosclerosis & pancreatitis.
⚠️ Causes of Hypercholesterolaemia
- Genetic 🧬 :
- Familial Hypercholesterolaemia (FH): Autosomal dominant; LDL receptor/APOB/PCSK9 mutations. Very high LDL from young age → premature CAD.
- Lifestyle 🍟🚬 :
- Diet high in saturated/trans fats.
- Obesity, sedentary lifestyle.
- Smoking → ↓ HDL, endothelial damage.
- Excess alcohol → ↑ triglycerides.
- Secondary Causes 🩺 :
- Diabetes mellitus.
- Hypothyroidism.
- Nephrotic syndrome, CKD.
- Cholestatic liver disease.
- Drugs: thiazides, ciclosporin, antiretrovirals.
🧑⚕️ Symptoms & Clinical Signs
Hypercholesterolaemia is often silent until vascular complications develop.
- 💔 Angina, MI, stroke, claudication.
- 🟡 Xanthomas (tendinous, tuberous).
- 🟡 Xanthelasma (eyelids).
- 👁️ Corneal arcus (<40 yrs suggests FH).
🔬 Diagnosis
- Lipid Profile 🧪 :
- Total cholesterol, LDL, HDL, triglycerides (fasting or non-fasting depending on guideline).
- Genetic Testing 🧬 :
- If FH suspected (Simon Broome or Dutch Lipid Clinic criteria).
- Risk Assessment 📈 :
- QRISK3 (UK) or ASCVD risk calculator → guides statin initiation in primary prevention.
💊 Treatment
- Lifestyle 🥗🏃♂️ :
- DASH or Mediterranean-style diet (low sat/trans fats, ↑ fibre, ↑ plant sterols).
- 150 minutes/week aerobic exercise.
- Weight optimisation, smoking cessation, alcohol moderation.
- Pharmacological 💉 :
- Statins (first-line): Inhibit HMG-CoA reductase → ↓ LDL, ↓ CV events.
- Ezetimibe: Inhibits intestinal cholesterol absorption; add-on if statins insufficient.
- PCSK9 inhibitors (alirocumab, evolocumab): Powerful LDL reduction; used in FH or statin intolerance.
- Bile acid sequestrants: Rarely used; GI side effects.
- Fibrates: Useful for severe hypertriglyceridaemia (prevent pancreatitis).
- Niacin: Limited use due to flushing, hepatotoxicity.
- Monitoring 📅 :
- Baseline LFTs, CK if myopathy risk.
- Recheck lipids at 3 months → adjust therapy.
- Long-term monitoring annually or per guideline.
🚨 Complications
- Coronary artery disease & MI.
- Ischaemic stroke / TIA.
- Peripheral artery disease (intermittent claudication).
- Aortic aneurysm.
- CKD progression via vascular damage.
💡 Clinical Pearls
- Always exclude secondary causes before diagnosing “primary hypercholesterolaemia.”
- In familial hypercholesterolaemia, start treatment early & offer cascade screening.
- Statins reduce ASCVD events even if baseline cholesterol is normal in high-risk groups (e.g. diabetes).
- Combination therapy (statin + ezetimibe or PCSK9 inhibitor) is increasingly used in refractory cases.
