Makindo Medical Notes

🩸 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.